NOTE: This video is ONLY available to watch in selected countries and geographies
NOTE: This video is ONLY available to watch in selected countries and geographies
“I took a giant leap of faith and applied for a radiology residency with the sole intention of doing interventional radiology (IR). I was lucky—it turned out to be the perfect specialty for me,” Karim Valji, professor of radiology at the University of Washington (Seattle, USA) and professor Emeritus at the University of California, San Diego (USA) tells Interventional News. Valji is also the former editor-in-chief of the Journal of Vascular and Interventional Radiology (JVIR).
What attracted you to a career in IR?
In medical school, I was drawn more towards the doctors who were ‘thinkers’ rather than ‘doers’. I started an internal medicine residency at UCSF [University of California, San Francisco], but by the end of my internship I realised that I really wanted to work in a procedure-driven field. Ernie Ring and Bob Kerlan were there running one of the premier IR sections in the country, and I watched them do several cases on my patients. Having spent no time whatsoever on an IR service, I took a giant leap of faith and applied for a radiology residency with the sole intention of doing IR. I was lucky–it turned out to be the perfect specialty for me.
Your 2020 Dotter Lecture focused on a fundamental question—why are we doing this procedure? Could you outline recurring scenarios in which this question should be at the forefront of a proceduralist’s mind?
In the busyness of our hectic workday, it is so easy just to do the cases listed on the board without stepping back to consider what we are really doing for every patient. We really need to have a different mindset. Like a surgeon, we must always start by looking at a patient’s clinical problem and consider how IR might benefit him or her. Sometimes it is as simple as deciding that a tunnelled catheter is more appropriate for this person than the port that was requested.
On one end of the spectrum are the referrals that require help with a complex situation. In that scenario, there may be a tendency to get swept up in the details of a proposed procedure—or a desperate patient or provider can make us feel compelled to do something. But we need to stop and ask these questions: Is the procedure likely to help the clinical situation? Are the potential benefits worth the risks? Is there a better option, perhaps even doing no intervention at all? And will it help the patient in the long run?
The polar opposite is the routine elective tube change. The case is totally mundane and so easy to do, but frankly, our responsibility goes beyond just changing out the catheter. We need to advocate for the patient and make sure there is a long-term plan that will, if possible and desired, allow the external catheter to come out. If that is not the case, we need to help the patient and family understand why the device may be in place for the long run. So, we must work with referring providers to advance treatment that will optimise the patient’s ultimate quality of life.
Having been the editor-in-chief of JVIR and having written three textbooks for IR, in 2022, what are ways to best educate the IR community?
Of course, when I started in IR over 30 years ago, the resources for learning the substance of IR were limited. To pick up the basics of interventional radiology, many current residents tell me that they still prefer print textbooks and ‘linear reading’ to study a particular topic or learn the fundamentals of our field more broadly. But frankly, I think many also rely more on various online sites for ‘bites’ of information that are short and well illustrated, and preferably interactive. While those sources are usually more enticing and up-to-date than print books, I do wonder about the accuracy of some of that material.
The quality of research being published in JVIR has never been higher. There is no better authority for learning about the newest advances in our field. However, I think we should always have a healthy dose of scepticism about any new technique or concept that we read about, even in venerated journals. In that same vein, I have found that many interventional radiologists (especially very experienced ones) can get dogmatic about the procedures they do and how they do them. It brings to mind the warning that a former dean at Harvard Medical School gave to an incoming class: “Half of what we are going to teach you is wrong and half of it is right. The problem is we do not know which half.”
What is your advice to a young trainee or interventional radiologist with an interest in academic medicine?
First, find a mentor—a person who can inspire you and guide you as you start doing research or getting involved in some other academic pursuit. It is not necessary to find someone with an international reputation or a CV a mile long. It is much more important to choose a person whom you respect and enjoy working with.
Second, if you have no experience with research, try your hand at a simple case report or short review article. Unfortunately, the sheer act of writing seems to turn off many aspiring young interventional radiologists. But, please believe that with some effort almost anyone can learn to write reasonably well.
Finally, do not reject the idea of academics simply because you think it means years of churning out papers. In many institutions, an interventional radiologist with an aptitude for teaching or an interest in leadership can have a rewarding and successful career as an educator or an administrator with minimal requirements for publication.
In the last few years, what research paper has particularly caught your attention?
In a JVIR article several years ago, my colleague Jeff Chick reported results of a national survey that he conducted to assess burnout among interventional radiologists. The findings were sobering. Burnout is a serious and growing concern for healthcare providers of every sort. Lack of energy, disengagement from colleagues, loss of satisfaction with work, a short temper with staff or even patients—these are some of the signs.
There certainly are a number of strategies for helping prevent or deal with burnout. But the first step is admitting to yourself that there may be a serious problem brewing, and that it should not be taken as a personal failure. Unfortunately, the ‘superman’ ethos that is common among interventional radiologists can make it hard to accept that reality.
At the very least, interventional radiologists concerned about their negativity towards work need to share these feelings with family or with close, trusted peers. And, just as important, all IR groups should confront this issue openly and directly, and make a real effort to identify and support colleagues who seem to be at risk.
What is one important way interventional radiologists can improve the quality of patient care they deliver?
Better communication. Not just with patients and families, but also with other providers who make up the medical team. Many surveys show that poor communication is one of the biggest complaints by the public about the modern healthcare system. We sometimes fail to be explicit about what a patient should expect during and after a procedure. Or, we do not provide clear and thorough information about how to manage a catheter, for example, when the patient is recovering. Or, we do not make it easy to reach us when a patient or family has concerns.
But on a broader level, the many individuals and teams caring for a patient sometimes give mixed or confusing messages about care plans and expectations for the future. The IR doctor gives the patient instructions about nephrostomy catheter management, and the IR nurse tells the family member something different. We do a complex venous reconstruction, but the procedure fails when another provider stops anticoagulation prematurely because the long-term plan was not well communicated. The problem is daunting. But we need to do our best to make the system work for each of our patients.
What gives you the most pleasure from travelling and teaching in different countries?
My most satisfying teaching experiences overseas have involved showing unknown cases to IR residents and fellows. These young trainees are so eager and grateful for teaching from someone from the USA who works in a leading centre for IR. And, any preconceived notions about the quality of training in some less-advantaged countries are quickly dispelled after a short time spent with some of their smart and enthusiastic interventional radiologists-to-be.
What are your interests outside medicine?
I am a voracious reader, gym junkie, and avid theatre-goer. My husband Jon and I spend as much time as we can visiting San Diego to see our two children and grandkids (now aged six, three, and one). And we are both lifelong travel fanatics. We spend hours and hours on Kayak putting together our own trips. We know exotic airport codes like sports fans know players’ stats. And our interests complement one another’s really well. I have made him appreciate all that world cities have to offer, and he entices me to places I could once barely find on a map…The Gambia, anyone?
The March top 10 features news that the US trial of the LimFlow system designed to prevent amputations has completed enrolment. Other highlights include two video interviews addressing the treatment of the superficial femoral artery (SFA), as well as a report of an ECR 2022 session, in which Thomas Helmberger called for a “shift [in] treatment focus from volume to value”.
Enrolment has been completed in the PROMISE II pivotal trial of the LimFlow deep vein arterialisation system designed to prevent amputations in so-called “no-option” chronic limb-threatening ischaemia (CLTI) patients, the eponymous device maker announced today.
2) Evidence in the SFA: What kind of stent should we use?
Antonio Micari (interventional cardiologist, Italy) gives his thoughts on the EMINENT RCT and whether it may have influenced his decision to use drug-eluting stents and drug coated balloons after a percutaneous transluminal angioplasty.
3) ECR 2022: Interventional oncology is the fourth pillar of oncology—a shift is needed
With cancer cases growing worldwide and an increased number of late-stage diseases in elderly patients, there is an increasing need for an integrated approach. “Through evidence, cost, and acceptance of interventional oncology (IO), we can create value-based care and shift the treatment focus from volume to value”.
4) Merit Medical wins FDA breakthrough nod for microspheres for treating knee osteoarthritis
Merit Medical announced that it has received US Food and Drug Administration (FDA) breakthrough device designation for its Embosphere microspheres.
Johns Hopkins Medicine researchers have developed and tested a new imaging approach they say will accelerate imaging-based research in the lab by allowing investigators to capture images of blood vessels at different spatial scales.
6) Evidence in the SFA: Considering the data when making decisions for patients
Koen Deloose (vascular surgeon, Belgium) looks at the evidence needed in order to make the best decisions for his patients when treating the superficial femoral artery (SFA). Deloose dives into the implications on daily practice of the EMINENT RCT results, as well as stenting strategy and the use of paclitaxel in the future.
The VasQ external support device (Laminate Medical) has demonstrated long-term benefits for radiocephalic (forearm) arteriovenous fistula (AVF) creation in a retrospective analysis of 150 consecutive procedures. Robert Shahverdyan (Asklepios Klinik Barmbek, Hamburg, Germany) and Dirk Hentschel (Brigham and Women’s Hospital, Boston, USA) have published these data in Seminars in Dialysis.
Six-month outcomes from the ongoing CLOUT registry demonstrate the “safety and efficacy” of the ClotTriever thrombectomy system (Inari Medical) in a real-world deep vein thrombosis (DVT) population regardless of clot chronicity level, the 2022 annual meeting of the American Venous Forum (AVF; 23–26, Orlando, USA) heard.
9) Instylla first-in-human clinical trial published results demonstrate success
A prospective multicentre study has evaluated the safety and efficacy of a polyethylene glycol (PEG)-based liquid embolic in treating hypervascular tumours, according to an Instylla press release.
10) S.M.A.R.T. Radianz vascular stent system approved for transradial use in the USA
Cordis recently announced that the US Food and Drug Administration (FDA) has approved the S.M.A.R.T. Radianz vascular stent system, a self-expanding stent purposefully engineered for radial peripheral procedures.
One of the sessions at this year’s Society of Interventional Oncology (SIO) meeting (24–28 March, San Francisco, USA) comprised four debates moderated by David Breen (University Hospital Southampton, Southampton, UK) and William Rilling (Medical College of Wisconsin, Milwaukee, USA). One of the key takeaways from the session was that radiation oncology has seen much innovation, and that this must continue in order to provide the best outcomes for patients into the future. Another was that “response assessment [can be] challenging”.
Peripheral colorectal lung metastases: SBRT vs. ablation
Abraham Wu (Memorial Sloan Kettering Cancer Center, New York, USA) and Thierry de Baere (Institut Gustav Roussy, Villejuif, France) took to the podium in turn—Wu as a proponent of stereotactic body radiation therapy (SBRT), and de Baere of thermal ablation, as a means of treating peripheral colorectal lung metastases.
“SBRT has really ushered in a revolution in radiation oncology.” Wu began his side of the argument by dubbing SBRT a “new standard for early-stage inoperable lung cancer”, citing the therapy as particularly successful in metastatic tumours.
Wu proceeded to highlight the non-invasive benefit of SBRT—there is “no cutting, needles, pain, nor a need for anaesthesia.” Furthermore, there are no medical contraindications, with patients free to continue on anticoagulant drugs alongside receiving SBRT. The toxicity profile, Wu assured, is also “favourable”, with “essentially no mortality risk” associated with using the therapy to treat peripheral lesions, including when treating multiple lesions, and retreating the same one.
It is also easily adaptable to large tumour sizes, and complicated tumour shapes and locations, Wu emphasised. The convenience of the therapy is also a draw when it comes to SBRT, now that it is available relatively widely in “most modern radiation facilities”.
Wu’s bottom line is that “high-level control is achievable with a sufficient dose”, which is safe for peripheral lesions. He contended that “SBRT is the preferred treatment” for peripheral colorectal lung metastases, stating that there is a larger and longer-term evidence base when compared to ablation.
De Baere began his counterargument by explaining that he “fully [agreed] with the previous speaker in that what matters is local tumour control”. However, defining local tumour control is another matter entirely. He argued that ablation sees total control in the longer term, when compared to SBRT, which, de Baere suggested “puts some smoke around the tumour”, then making it difficult to have local response criteria. Where it may be tempting to look at imaging for two years post-SBRT and declare a complete response, he underlined the need to “look past two years”, and once one does that, in the case of SBRT, he believes that it is “always the same story”—the tumour is still growing, just very slowly.
One can get a more reliable picture of the ongoing success of treating via ablation, de Baere highlighted, as it can be obtained with pathology, as opposed to the imaging that indicates in SBRT cases whether it is working.
De Baere brought nuance to his side of the debate, acknowledging that different types of cancer, for example, primary vs. metastatic, warranted different treatment approaches. Likewise, the observed success of a particular approach depends on the dosage given. It is perfectly possible, de Baere admitted, that a tumour can continue to grow after ablation, if you “mistarget with cryotherapy” or give “too low a dose”. However, he maintained that while SBRT may seem low-toxicity in the short term, in the middle or long term, “it is a different story” and one starts to see a decrease in lung function.
Given the opportunity to answer his opponent’s comment, Wu thanked de Baere for a “strong and thoughtful response”, agreeing that “response assessment with SBRT is challenging” and that it is a “limitation” of the treatment when compared to other modalities. Wu went on to outline that administering a sufficient radiation dose can resolve the issues with SBRT that de Baere pointed to, but, given his chance for rebuttal, de Baere doubled down on his preference for ablation—that a high enough dose may well “kill the tumour [with SBRT], but maybe you will also kill the patient or the lung.”
Alucent Biomedical announced in a press release that it has enrolled the first patient in ACTIVATE II, an Australia-based first-in-human clinical trial to evaluate the safety and efficacy of its natural vascular scaffolding (AlucentNVS) technology. The therapy is designed to open vessels and maintain patency without the use of permanent implants for the treatment of peripheral artery disease (PAD) of the lower extremities.
The AlucentNVS vessel restoration system with photoactivated linking combines standard angioplasty with linking of the structural proteins in the wall of a blood vessel. The intervention is designed to deliver restoration of the vessel’s lumen and sustained improvement of blood flow, without the introduction of a foreign implant, such as a metallic stent. AlucentNVS photoactivated linking is also designed to mitigate the well-known adverse effects of angioplasty, such as vessel recoil. Sustained, improved blood flow is expected to result in pain relief, limb preservation, and an improved quality of life for patients.
The first patient in the ACTIVATE II study was enrolled by Chris Delaney at Flinders Medical Centre in Adelaide, Australia. In total, the trial will enrol up to 50 subjects at up to 12 research sites, which will include Prince of Wales Hospital in Sydney, The Alfred Hospital in Melbourne, Royal Perth Hospital, and Sir Charles Gairdner Hospital in Perth. The primary endpoints of the study are freedom from composite investigational-device, procedure-related major adverse events, primary patency as assessed by Doppler ultrasound, and freedom from clinically driven target lesion revascularisation (CD-TLR) at one year.
ACTIVATE II follows the completion of enrolment for ACTIVATE I safety study of AlucentNVS in the USA. Pre-clinical testing of AlucentNVS in animal studies has shown acute and long-term safety and patency without the pro-inflammatory and mechanical risks of placing a rigid foreign implant into the blood vessel.
“PAD is a difficult condition affecting so many people worldwide, and its current treatments have significant shortcomings,” said Myles Greenberg, Alucent Biomedical’s CEO. “We want to change that by offering a whole new way to treat these patients with AlucentNVS. Alucent’s novel approach has the potential to change the way PAD is managed in the future.”
Interventional News 85 Highlights:
Interventional News 85 Highlights:
Truvic Medical, a subsidiary of Imperative Care, announced in a press release that it has received 510(k) clearance from the US Food and Drug Administration (FDA) for the Prodigy thrombectomy system, designed for the treatment of peripheral vascular thrombus.
“We are excited to receive FDA clearance for our first thrombectomy system. We look forward to working with experts in the field to translate Prodigy’s novel design elements and features into superb clinical outcomes,” said Mike Buck, CEO of Truvic. “This represents our first regulatory milestone as part of our strategy to advance multiple programmes designed to meet patients’ needs and bring more innovative technologies to the market, faster.”
“Imperative Care and Truvic share a culture of innovation and intense commitment to the needs of patients. I am pleased that these common values continue to help propel our development programmes towards elevation of patient care,” Fred Khosravi, chairman and CEO of Imperative Care, added
Truvic is based in Campbell, California, USA and its technology is designed to redefine peripheral vascular thrombus management by enabling single-session thrombus removal without the use of thrombolytics.
Imperative Care is a medical technology company focused on developing the next generation of solutions to address the vast and urgent needs in stroke intervention and peripheral thrombectomy. The company has two FDA 510(k) cleared product platforms, as well as an expansive stroke technology development pipeline.
A study from Sweden published by The BMJ recently finds an increased risk of deep vein thrombosis (DVT) up to three months after COVID-19 infection, pulmonary embolism (PE) up to six months, and a bleeding event up to two months.
The findings also show a higher risk of events in patients with underlying conditions (comorbidities), patients with more severe COVID-19, and during the first pandemic wave compared with the second and third waves.
The researchers say these results support measures to prevent thrombotic events (thromboprophylaxis), especially for high-risk patients, and strengthen the importance of vaccination against COVID-19.
It is well known that COVID-19 increases the risk of venous thromboembolism (VTE), the authors write. However, they note that less evidence exists on the length of time this risk is increased, if risk changed during the pandemic waves, and whether COVID-19 also increases the risk of major bleeding.
To address these uncertainties, the researchers set out to measure the risk of DVT, PE, and bleeding after COVID-19.
Using national registries in Sweden, they identified more than one million people with confirmed SARSCoV-2 infection between 1 February 2020 and 25 May 2021, matched by age, sex, and county of residence to more than four million people who had not had a positive SARS-CoV-2 test result.
They then performed two analyses: in the first, they calculated the rates of DVT, PE, and bleeding in COVID-19 individuals during a control period (before and long after COVID-19 diagnosis) and compared it to the rates in different time intervals after COVID-19 diagnosis (days 1–7, 8–14, 15–30, 31–60, 61–90, and 91–180).
In the second analysis, they calculated the rates of DVT, PE, and bleeding during the period 1–30 days after COVID-19 diagnosis in the COVID-19 group and compared them to the corresponding rates in the control group.
The results show that compared with the control period, risks were significantly increased 90 days after COVID-19 for DVT, 180 days for PE, and 60 days for bleeding.
After taking account of a range of potentially influential factors, the researchers found a fivefold increase in risk of DVT, a 33-fold increase in risk of PE, and an almost twofold increase in risk of bleeding in the 30 days after infection.
In absolute terms, this means that a first DVT occurred in 401 patients with COVID-19 (absolute risk 0.04%) and 267 control patients (absolute risk 0.01%). A first PE event occurred in 1,761 patients with COVID-19 (absolute risk 0.17%) and 171 control patients (absolute risk 0.004%), and a first bleeding event occurred in 1,002 patients with COVID-19 (absolute risk 0.10%) and 1,292 control patients (absolute risk 0.04%).
Risks were highest in patients with more severe COVID-19 and during the first pandemic wave compared with the second and third waves, which the researchers say could be explained by improvements in treatment and vaccine coverage in older patients after the first wave.
Even among mild, non-hospitalised COVID-19 patients, the researchers found increased risks of DVT and PE. No increased risk of bleeding was found in mild cases, but a noticeable increase was observed in more severe cases.
This is an observational study, so the researchers cannot establish cause, and they acknowledge several limitations which might have affected their findings. For example, VTE may have been underdiagnosed in patients with COVID-19, testing for COVID-19 was limited, especially during the first pandemic wave, and information on vaccination was not available.
However, results were largely consistent after further analyses, and are in line with similar studies on the association between COVID-19 and thromboembolic events, suggesting that they withstand scrutiny.
As such, the researchers say their findings suggest that COVID-19 is an independent risk factor for DVT, PE, and bleeding, and that the risk of these outcomes is increased for three, six, and two months after COVID-19, respectively.
“Our findings arguably support thromboprophylaxis to avoid thrombotic events, especially for high-risk patients, and strengthen the importance of vaccination against COVID-19,” they conclude.
In a linked editorial, researchers at the University of Glasgow (Glasgow, UK) point out that despite the potential for new variants of concern, most governments are removing restrictions and shifting their focus to determining how best to “live with COVID-19.”
However, they say this study “reminds us of the need to remain vigilant to the complications associated with even mild SARS-CoV-2 infection, including thromboembolism.”
NOTE: This video is ONLY available to watch in selected countries and geographies
LimFlow recently announced it has closed a US$40 million (€36 million) oversubscribed Series D financing round.
A press release reports that new investors Longitude Capital, Soleus Capital Management, and an undisclosed strategic investor joined the round along with current major shareholders of the company: Sofinnova Partners, through its Crossover Strategy fund; Bpifrance, the French sovereign investment bank; and Balestier, a Singaporean family fund.
The LimFlow system, designated by the US Food and Drug Administration (FDA) as a Breakthrough technology, uses a minimally invasive family of transcatheter products designed to optimise perfusion of the critically ischaemic foot, potentially avoiding major amputation, resolving pain, and promoting wound healing. Proceeds from the Series D financing will fund follow-up for the PROMISE II US pivotal trial necessary to obtain FDA approval and will support the commercialisation of the LimFlow system for deep vein arterialisation, the press release details.
The company recently completed enrolment in PROMISE II, the US pivotal trial of the LimFlow system. It also completed enrolment in CLariTI, a natural history study of high-risk and no-option chronic limb-threatening ischaemia (CLTI) patients, intended to shed light on outcomes from patients treated with the current standard of care. Over the last year, the company also integrated the second-generation of its LimFlow system into its clinical programme and reported positive two-year data from its PROMISE I US feasibility study.
“We are thankful for the support of so many industry-leading investors, both new and existing, who recognise the potential of the LimFlow system to address a major clinical need in saving patients from amputation,” said LimFlow CEO Dan Rose. “We look forward to sharing results from our pivotal trial later this year, and to the prospect of being able to make the LimFlow system commercially available as early as next year to the patients in the USA and Europe who desperately need it.”
“We are truly impressed by the clinical results LimFlow has delivered for patients who have exhausted all other treatment options. We are excited about the technology’s potential to transform the way CLTI patients are treated, and in turn, transform the quality of their lives,” said Maxwell Bikoff, principal at Longitude Capital.
“The LimFlow management team has achieved key milestones and financing needed to successfully bring the LimFlow system to market. We are enthusiastic about continuing to work with the company to help make this game-changing technology accessible to patients in the near future,” said Kinam Hong, partner at Sofinnova Partners.
Cordis has announced a strategic investment venture that will expand the scope of the global cardiovascular technology company into the venous thromboembolism (VTE) market with a strategic investment in Endovascular Engineering (E2), a developer of next-generation thrombectomy devices to treat patients with deep vein thrombosis (DVT) and pulmonary embolism (PE).
Cordis is partnering with Santé Ventures and another strategic investor in the E2 transaction, a press release reports.
According to Cordis CEO Shar Matin, “Our investment in E2 meets all the criteria in our strategy to fuel differentiated technology development, expanding our portfolio with innovative and clinically compelling solutions that respond to unmet needs in cardiovascular health. Growing our venous offerings expands our capacity to improve outcomes and deliver better quality of life to more patients around the world.”
“Our new business model leverages the robust global corporate infrastructure and sales capacity of Cordis, and the speed, creativity, and agility of the Cordis-X growth engine,” Matin continued. “DVT and PE affect patients young and old. The investment in E2 supports Cordis’ legacy as a leader in creating lifesaving cardiovascular technologies.”
E2, based in Menlo Park, USA, was founded in 2019 to focus on development of advanced mechanical thrombectomy solutions. CEO Mike Rosenthal said, “The E2 team is thrilled to welcome Cordis and our other investment partners as we join together to help us further the pursuit of developing healthcare solutions that matter. We share a pioneering spirit dedicated to serving patients and physicians in the underserved peripheral indications.”
Shockwave Medical has announced the global commercial availability of the Shockwave M5+ peripheral intravascular lithotripsy (IVL) catheter after receiving both CE mark and US Food and Drug Administration (FDA) clearance.
A company press release details that the Shockwave M5+ catheter is specifically designed to decrease IVL treatment time, provide alternative access options, and expand IVL therapy to patients with larger vessel sizes.
“Shockwave’s new peripheral catheter offers remarkable improvements that enable efficient and effective treatment for some of our most difficult-to-treat patients, some of whom previously could not have been treated with IVL,” said Peter Soukas (Miriam and Rhode Island Hospitals, Providence, USA), one of the first physicians to use the new catheter. “While treating patients with long, severely calcified lesions will always be challenging, the new Shockwave catheter is appropriately sized for larger vessels and has been optimised to expand options for facilitating vessel access, all while decreasing the amount of time needed to perform IVL in the procedure.”
Shockwave M5+ incorporates valued customer feedback to improve IVL efficiency in tackling complex calcified lesions, including quicker cycle time that delivers two pulses per second, an increased catheter length of 135cm, and a new, larger 8mm size, the company communicates. The catheter is specifically designed to treat otherwise difficult-to-treat calcified lesions in the peripheral arterial system of the lower extremities, including the iliac, femoral, iliofemoral, popliteal, infrapopliteal, and renal arteries.
“The launch of Shockwave M5+ is the latest step in our commitment to expanding the applicability of our technology for more diverse patient populations and anatomies,” said Doug Godshall, chief executive officer of Shockwave Medical. “After a very successful limited launch, we are enthusiastic about the global rollout of Shockwave M5+ and the ability to provide our customers with a new tool to advance treatment options—with the consistent reliability and simplicity of IVL that physicians have come to expect when treating patients with Shockwave IVL.”
Shockwave Medical advises that the M5+ catheter is now commercially available in Europe and the USA.
Synchron has announced the results from a study in which four people with amyotrophic lateral sclerosis (ALS) received an implant of the company’s Stentrode device—a small, mesh-like material inserted within a patient’s blood vessel that does not require invasive, open brain surgery. The results were presented on 29 March as part of an exclusive press briefing highlighting breakthrough science at the American Academy of Neurology’s 74th annual meeting (AAN 2022; 2–7 April, Seattle, USA).
Researchers monitored participants for one year and found the device to be safe, with no serious adverse events that led to disability or death, according to Synchron. The Stentrode device also stayed in place for all four patients and the blood vessel in which the device was implanted remained open. Receiving the implant allowed participants to use a computer to communicate by text, and perform daily tasks, such as online shopping and banking, a company press release states.
“People with ALS eventually lose their ability to move their limbs, making them unable to operate devices like a phone or computer,” said study author Bruce Campbell (University of Melbourne, Melbourne, Australia). “Our research is exciting because while other devices require surgery that involves opening the skull, this brain-computer interface [BCI] device is much less invasive. It receives electrical signals from the brain, allowing people to control a computer by thought.”
Rather than drilling through the skull, the Stentrode is fed through a patient’s vein until it reaches the brain. The device, comprised of a net-like material with 16 sensors attached, expands to line the vessel wall. That device is connected to an electronic device in the chest that then relays the brain signals from the motor cortex—the part of the brain that generates signals for movement—into commands for a laptop computer.
“These results are a huge advancement for the field of BCI. We have shown that our endovascular BCI approach is safe, and allows patients to accomplish daily online tasks without invasive brain surgery,” said Thomas Oxley, CEO and co-founder of Synchron. “Years of research and technological development culminated in this moment and, as we continue to develop our technology, it has the potential to change the lives of millions of patients globally who suffer from paralysis, and other debilitating neurological and brain-related diseases.”
An analysis showed benefit of XARELTO plus aspirin in reducing thrombotic hospitalisations for peripheral arterial disease (PAD) patients with and without chronic kidney disease (CKD). A separate analysis demonstrated PAD patients who received XARELTO plus aspirin in addition to statin therapy had the lowest risk of the composite of major adverse cardiovascular events (MACE) or major adverse limb events (MALE) compared to all other treatment groups in the study.
The Janssen Pharmaceutical Companies of Johnson & Johnson recently announced data from new analyses from the Phase 3 VOYAGER PAD clinical trial reinforcing the benefit of the XARELTO (rivaroxaban) vascular dose (2.5mg twice daily plus aspirin 100mg once daily) in reducing severe vascular events in patients with PAD after lower-extremity revascularisation (LER), a procedure that restores blood flow to the legs.
Data from the two analyses demonstrate the role that the XARELTO vascular dose plays in PAD patients with and without CKD and in PAD patients with and without a history of statin therapy. Results will be featured at the American College of Cardiology’s 71st Annual Scientific Session (ACC) 2022 (Washington D.C., USA, 2–4 April).
One lesser known but serious cardiovascular condition is PAD, a common, chronic circulatory condition that causes blood vessels to narrow, thereby reducing blood flow to the limbs, and most often the legs. It is a disease that often goes undiagnosed and undertreated.
While it usually starts asymptomatically, PAD can progress to severe symptoms and require revascularisation—a surgical procedure that restores blood flow after arteries have been clogged—to avoid amputation.
“At Janssen, we are continuing to invest in clinical research to help evolve the standard of care for people living with serious cardiovascular diseases, like PAD, an area of critical unmet need,” said James F. List, Global Therapeutic Area Head, Cardiovascular, Metabolism, and Retina at Janssen Research & Development. “Our research continues to support the use of the XARELTO vascular dose and is a treatment option physicians should consider for patients with PAD or coronary artery disease.”
Nipro Medical Corporation is set to introduce its second-generation Cronus high-pressure (HP) percutaneous transluminal angioplasty (PTA) balloon catheter to the US market.
Cronus HP is indicated for use in popliteal, femoral, iliac, and renal arteries, and in the treatment of arteriovenous fistulas (AVFs), with Cronus HP serving as Nipro’s “go-to choice” for vascular surgeons and interventional nephrologists in the repair and restoration of AVFs in haemodialysis patients—according to a press release from the company.
“Vascular access complications happen, even with the greatest of care,” said John O’Connor, director of Vascular Sales at Nipro. “So, we are here to ensure failed fistulas are transformed into functional fistulas.”
The release adds that the characteristics that are foundational to the Cronus HP include strength, flexibility and durability at high pressures, the ability to aid in using only one balloon during a procedure, facilitating entry across the lesion, and helping to minimise ‘balloon dog-boning’ and address difficult stenoses.
“Cronus HP signifies a unique bridge of two worlds within the Nipro product portfolio—renal and vascular,” said Joe Dawson, executive vice president of Nipro. The release also notes that the company’s vascular division, newly established in April 2021, already features nine products across three categories, including intravascular imaging.
Janssen has announced the launch of ‘Save Legs. Change Lives. Spot Peripheral Artery Disease Now‘, a multi-year initiative aimed at creating urgency and action to address the hidden threat of peripheral arterial disease (PAD)-related amputation, with an initial focus on reaching Black Americans.
Janssen details in a press release that it has joined forces with leading professional associations, healthcare systems, and community organisations to advance equitable care for individuals and communities placed at an increased risk for cardiovascular disease in the USA.
The company states that Black Americans experience disproportionate rates of cardiovascular disease, and—as a result of higher rates of asymptomatic PAD, less access to quality vascular care, and greater risk for delays in care—are up to four times more likely than white Americans to have a PAD-related amputation.
“While health inequities have long existed, the last several years have brought them to the forefront of our collective consciousness. Black Americans are placed at disproportionate risk of losing legs and lives—a reality we all must actively address,” said Pernessa Seele, founder and CEO, The Balm in Gilead, a faith-based organisation engaged in eliminating health disparities. “We believe the most effective way to eliminate the alarming health disparities within Black populations is for intentional, sustained and compassionate action by the healthcare industry, public health and faith communities.”
‘Save Legs. Change Lives.’ has three main areas of focus: driving research, collaborating with powerful partners, and empowering individuals and communities, Janssen states.
Research to break down barriers to PAD screening and increase equitable care
As part of the initiative, Janssen is supporting, sponsoring, and promoting research to uncover systemic bias, identify unmet patient needs, and propel healthcare systems toward change. The company details that research already underway includes a data-based tool to help health systems identify groups of patients with inadequate PAD care and better direct efforts toward those placed at the highest risk of amputation, as well as a series of white papers that highlight best practices of leading limb salvage programmes for people at risk for amputation.
“Everyone deserves a chance to avoid an amputation. I grew up in my dad’s podiatry practice and I saw from a young age what a difference you can make in simply helping people move through the world,” said David G Armstrong, professor of Surgery and director of the Southwestern Academic Limb Salvage Alliance (SALSA), at Keck School of Medicine, University of Southern California (Los Angeles, USA), and president of the American Limb Preservation Society (ALPS). “Limb preservation is of paramount importance, and I believe in the big idea that, together, we can eliminate limb amputations over the next generation. The inspiring thing is that—even with so many factors collectively stacked against our patients, ongoing research, awareness and sharing of best practices is vital to ensure we help people with PAD protect their legs and avoid the devastating consequences of amputation.”
Collaboration to unlock better PAD care and improve outcomes
Janssen notes that it is collaborating with various partners, including universities, health systems, non-governmental organisations, and change makers to break down barriers to equitable and inclusive care, ranging from access and health literacy to healthcare provider diversity.
The company states that it is proud to help support the American Heart Association’s PAD National Action Plan, which aims to reduce PAD-related amputation. Additionally, Janssen is sponsoring the American College of Cardiology Foundation’s ‘Change the FIELD’ initiative, a major multi-year effort to foster inclusivity, equity, leadership, and diversity in the field of cardiology.
Education, awareness and screening to reach individuals placed at greatest risk
Janssen is supporting grassroots PAD awareness, education and screening that empowers individuals and communities to change the trajectory of their health, the company adds in their press release. These efforts include:
“‘Save Legs. Change Lives.’ sets in motion a vision for more relevant, trusted and inclusive care for everyone affected by PAD,” said Avery Ince, vice president, Medical Affairs, Janssen Cardiovascular & Metabolism, Janssen Scientific Affairs. “As part of Johnson & Johnson, Janssen believes that major corporations have the power—and therefore the responsibility—to tackle pressing health challenges and make good health a reality for all people. We hope our efforts will inspire action to reduce amputations among people living with PAD.”
‘Save Legs. Change Lives.’ is part of Johnson & Johnson’s broader initiative, Our Race to Health Equity (ORTHE)—a US$100 million commitment to help eradicate racial and social injustice as a public health threat.
Venous stenting was a hot topic on the agenda of the recent American Venous Forum (AVF) annual meeting (23–26 February, Orlando, USA). Catching the audience’s attention, one presenter highlighted a head-to-head study of dedicated versus non-dedicated stents.
“Iliofemoral venous obstruction when not adequately treated results in chronic debilitating disease and poor quality of life,” said Lillian Tran (University of Pittsburgh Medical Center, Pittsburgh, USA), who noted that deep venous stenting is “increasingly preferred” as the mainstay treatment over medical therapy alone.
According to Tran, this move towards stenting necessitates studies comparing the performance of novel, dedicated venous stents with the more traditional, non-dedicated stents. At AVF, Tran reported the findings of such a head-to-head study at a single centre, detailing that the use of dedicated venous stents was associated with a significant reduction in extension into the inferior vena cava (IVC) without reduced early patency rates compared to non-dedicated stents.
The presenter stressed that outcomes after iliac vein stenting rely on multiple technical considerations and stent attributes. “In addition to adequate sizing and consistency in deployment, […] venous stents must establish a balance between radial force, flexibility and crush resistance,” she informed the audience. Tran detailed that dedicated, nitinol-based stents have been developed to meet these requirements and are now on the market in the USA and Europe. Four of these stents have been approved by the US Food and Drug Administration (FDA) for venous indications, the presenter relayed, noting, however, the fact that the Vici (Boston Scientific) and Venovo (BD) stents were recalled last year.
Outcomes data from investigational device exemption (IDE) trials of the four dedicated venous stents have demonstrated excellent patency rates, Tran communicated. However, she highlighted that head-to-head, comparative performance data against the more traditional Wallstent (Boston Scientific) and other non-dedicated stents are limited.
Tran et al therefore performed a retrospective review of all patients who underwent iliofemoral venous stenting for acute thrombotic, post-thrombotic and non-thrombotic indications at their institution between 2014 and 2021, grouping patients based on the use of novel, dedicated venous stents versus non-dedicated stents during their treatment.
The team measured 30-day stent failure and one-year patency rates as primary outcomes, Tran detailed, adding that secondary outcomes included stent sizing and extension.
A total of 135 patients (186 limbs) were treated in the study, Tran told AVF attendees, specifying that 63 limbs were treated using novel dedicated stents, while 123 were treated using the traditional Wallstent or another non-dedicated stent.
The team noted no preference in stent type in treating acute thrombotic or post-thrombotic lesions at their institution, but they did observe that dedicated venous stents were more likely to be used in non-thrombotic lesions.
Addressing the AVF audience, Tran reported that fewer stents were deployed per limb with the use of novel dedicated venous stents. In addition, she revealed that one patient had a stent fracture without thrombosis, and that there were no cases of deployment failure or stent migration in either group.
Additionally, larger size was observed in limbs using the Wallstent alone compared to dedicated venous stents and proximal stent extension into the IVC greater than 50% was significantly reduced with the use of novel venous stents compared to the non-dedicated devices, Tran detailed.
The presenter relayed some further key outcomes from the study: “Overall, dedicated venous stent use was not significantly associated with differences in early stent patency rates, nor was it a predictor of 30-day stent failure using a logistic regression analysis.”
In addition, she reported that primary patency rates remain comparable between novel venous stents and non-dedicated stents at one year. On subgroup analysis, the researchers did not see any differences between the non-dedicated and dedicated stents in either 30-day or one-year stent patency rates.
Tran acknowledged some limitations of the group’s study, including its retrospective nature, small sample size, short follow-up and no concurrent measurement of clinical improvement.
“In our experience, we found a significant reduction in extension into the IVC, total number of stents deployed and mean stent diameter with the use of novel, dedicated venous stents compared to Wallstents alone,” Tran concluded. In addition, she recapped that there were no significant differences in early outcomes between the two stent types.
Robert Hinchliffe (University of Bristol, Bristol, UK) shares his excitement to attend the upcoming CX Symposium (26–28 April, London, UK). “CX has always represented an unprecedented opportunity to share new techniques and to analyse the latest and best clinical trials across vascular interventions,” the CX 2022 executive board member tells Vascular News. This year, a highlight for Hinchliffe will be a session on the “hurting leg,” which is due to take place on the final day of the in-person and virtual meeting.
“We would all agree that a large component of our practice is patients who present with lower limb problems,” says Hinchliffe, emphasising the significance of the topic. He also highlights the fact that patients are presenting late in many cases—which could well explain high amputation rates. In light of this, he believes that CX 2022 “will be a really fantastic opportunity to assess these really troublesome patients”.
“Hurting legs are a very emotive issue for patients,” Hinchliffe relays, adding that they are a “common problem” for vascular specialists. Unfortunately, however, he highlights that “these problems are not managed particularly well within vascular centres, and it is unclear why this is the case”. Hinchliffe hopes that “CX 2022 will really shine a spotlight on the need to improve evidence in this area, and give an opportunity to share the latest ideas and cutting-edge research”.
In his own practice, Hinchliffe recognises outcome variation between regions and within regions. He points out that while this is “complex problem,” patient engagement is “really quite key”.
Another issue lies in the interdisciplinary nature of patient management, Hinchliffe tells Vascular News. He elaborates that patient management spans primary care, all the way through to more specialist interventions by other vascular surgeons, interventional radiologists, or cardiologists. “We really have not fostered good relationships between professionals,” he says, underlining the problem. Hinchliffe believes that CX 2022 “presents an opportunity to deal with, and shine a light on these problems, providing the opportunity to improve communication and pathways between groups of professionals”.
Finally, Hinchliffe highlights an ongoing need to raise awareness of the hurting leg. He notes that, in other cardiovascular arenas in the UK, a number of campaigns to raise the awareness of stroke, and the timely treatment of stroke, appeared to be “very effective”. “Clearly, there needs to be research to understand how to make the biggest difference and how to reach those hard-to-reach groups,” he urges. “Fundamentally, I think it is a question of raising the awareness both to patients and healthcare professionals and usually in primary care.”
This year, the CX Symposium will be held in person for the first time since 2019. After a two-year COVID-19-induced hiatus, Hinchliffe is keen to get back to face-to-face meetings. “It will be really fantastic to be back at the CX Symposium,” he says, describing it as “an opportunity to meet old friends and hopefully meet some new ones” in addition to its educational offerings.
Researchers at the Wyss Center for Bio and Neuroengineering (Geneva, Switzerland), in collaboration with the University of Tübingen (Tübingen, Germany), have enabled a person with complete paralysis, who cannot speak, to communicate via an implanted brain-computer interface (BCI).
This breakthrough came as part of a clinical case study that has been ongoing for more than two years with the participant—who has advanced amyotrophic lateral sclerosis (ALS)—and the results show that communication is possible with people who are completely ‘locked-in’ because of ALS, according to a Wyss Center press release. Details of the study are published in Nature Communications.
“This study answers a long-standing question about whether people with complete locked-in syndrome, who have lost all voluntary muscle control including movement of the eyes or mouth, also lose the ability of their brain to generate commands for communication,” said Wyss Center senior neuroscientist Jonas Zimmermann. “Successful communication has previously been demonstrated with BCIs in individuals with paralysis. But, to our knowledge, ours is the first study to achieve communication by someone who has no remaining voluntary movement and, hence, for whom the BCI is now the sole means of communication.”
The study participant is a man in his thirties who has been diagnosed with a fast-progressing form of ALS. He has two intracortical microelectrode arrays surgically implanted in his motor cortex. The release details that two microelectrode arrays, each 3.2mm2, were inserted into the surface of his motor cortex. Each array has 64 needle-like electrodes that record neural signals.
The participant, who lives at home with his family, has learned to generate brain activity by attempting different movements. These brain signals are picked up by the implanted microelectrodes and are decoded by a machine learning model in real-time. The model then maps the signals to mean either ‘yes’ or ‘no’. And, to reveal what the participant wants to communicate, a speller programme reads the letters of the alphabet aloud. Using auditory neurofeedback, the participant is able to choose ‘yes’ or ‘no’ to confirm or reject the letter, ultimately forming whole words and sentences.
“This study has also demonstrated that, with the involvement of family or caregivers, the system can, in principle, be used at home,” said Wyss Center chief technology officer George Kouvas. “This is an important step for people living with ALS who are being cared for outside the hospital environment. This technology, benefiting a patient and his family in their own environment, is a great example of how technological advances in the BCI field can be translated to create direct impact.”
Medtronic recently voluntarily recalled a subset of its IN.PACT Admiral and IN.PACT AV paclitaxel-coated percutaneous transluminal angioplasty (PTA) balloon catheters due to the potential for pouch damage resulting in a loss of sterility. This is according to a news alert from the company dated 31 March.
Medtronic communicates that approximately 6,000 IN.PACT Admiral catheters and three IN.PACT AV catheters distributed to customers globally are impacted by this recall. “Medtronic is communicating to customers with affected product on hand to immediately quarantine and return the product to Medtronic, as well as send back a signed confirmation form,” the company details.
The news alert continues: “The pouch damage was discovered during a routine inspection. Upon investigation, a change implemented to one manufacturing line was determined to be the cause. All batches manufactured on this line after that change are being retrieved. The problem on that line was fixed. Additionally, to ensure that no further issues, production on all lines was paused until a follow up packaging inspection was completed. No further errors were discovered.”
According to Medtronic, the company has received zero complaints involving this issue. In addition, they report that there have been zero reports of injury or death related to this issue. “There are no actions required for patients where the affected IN.PACT Admiral and IN.PACT AV catheters were used during a procedure. Patients should continue to be monitored in accordance with the medical facility’s standard care protocols,” the release reads.
The company stresses that, for most regions, there is little or no impact for customers to order replacement product. It advises that customers may reach out to Medtronic Customer service (800-551-5544, selection option “Vascular”) for any questions regarding their return or ordering replacement product.
The company notes that no other Medtronic products are affected by this issue, and that all appropriate regulatory bodies have been notified.
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Ra Medical Systems has announced the achievement of a milestone with the enrollment of 100 subjects in the pivotal clinical study, according to a press release. The study is to evaluate the safety and effectiveness of the DABRA excimer laser system as an atherectomy device for the treatment of peripheral arterial disease (PAD). This pivotal atherectomy study is cleared to enroll up to 125 subjects.
“I want to recognize the support from our Ra Medical team and our physician-investigators and staff for their diligence in reaching this significant enrollment milestone, particularly given the daunting challenges that arose from the COVID-19 pandemic,” said Will McGuire, Ra Medical Systems CEO. “Securing clearance for the atherectomy indication is a top priority for Ra Medical as we believe it will expand our addressable market beyond the existing clearance for crossing chronic total occlusions (CTO). Third-party research estimates that the combined CTO and atherectomy markets in the US will approximate $900 million this year.
“Due to the unpredictable nature of the pandemic, we are unable to accurately predict when we will complete study enrollment. However, our goal is to reach full enrollment during the third quarter of this year and to complete a six-month follow-up in early 2023,” he added.
The open-label pivotal atherectomy clinical trial can enroll subjects with symptoms of PAD (Rutherford Class 2-5) at up to 10 sites. Seven sites have been cleared for enrollment and one additional site is in the final phase of qualification. Outcome measures include safety, acute technical success, and clinical success. The trial’s primary efficacy endpoint is the mean reduction in percent diameter stenosis in each patient’s primary lesion as measured by angiography immediately following treatment with DABRA and before any adjunctive treatment. The trial’s safety and clinical success endpoints are major adverse events at 30 days post-procedure and incidence of primary target lesion revascularisation at six months.
Tractus Vascular recently announced the first-in-man use of the Tractus Crossing Support Catheter (Tractus CSC). The Tractus CSC represents a highly novel approach to treating vascular disease, the company states.
Chronic total occlusion (CTO) remains one of the most challenging pathologies encountered by surgeons and interventionalists in performing endovascular interventions. John H. Rundback and Kevin Herman of American Endovascular and Amputation Prevention in West Orange, New Jersey, USA both used the Tractus CSC to treat several patients with challenging cases of critical limb ischaemia, including CTO. Rundback noted, “the Tractus catheter tracked like ice and performed exceptionally well; the cases were all extremely successful.”
The Tractus CSC is US Food and Drug Administration (FDA) 510(k) cleared with 0.014inch, 0.018inch and 0.035inch guidewire compatibility and lengths of 90, 135, 155 and 170cm. While most crossing support catheters are constructed with a braided sheath, Tractus offers its Jigsaw Technology laser cut stainless steel shaft consisting of a continuous helical cut pattern forming interlocking teeth. Distal “gusset cuts” offer a continuous stainless steel tip which extends the attributes of this novel catheter shaft.
In future peripheral arterial disease (PAD) research, clinicians should not consider men and women as a single population and should instead report their data separately. This is the main conclusion of a systematic review and meta-analysis recently published in the European Journal of Vascular and Endovascular Surgery (EJVES), which found that symptoms of lower leg PAD present differently between men and women.
Authors Cindy P Porras (Utrecht University, Utrecht, The Netherlands) and colleagues write that while PAD has traditionally been labelled as a predominantly male disease, recent studies suggest that women are affected at least as often as men. Some of these studies also describe differences in the clinical presentation of lower extremity PAD between the sexes, however the authors note that there has been no systematic review collating this information. Therefore, the present study aimed to collate and pool the available evidence in order to evaluate differences in symptoms between men and women who present with lower limb PAD.
Using PubMed, EMBASE, and the Cochrane Library, Porras et al identified all relevant studies, collecting data on study design, source of data, population characteristics, and the outcome of interest using the Newcastle–Ottawa scale and Cochrane risk of bias tool. The authors note that, using the GRADE methodology, the evidence quality was rated as high, moderate, low, or very low based on the risk of bias, inconsistency, indirectness, and imprecision. In addition, the authors detail that estimates of relative effects were pooled to generate pooled odds ratios (ORs) and the 95% confidence interval (CI) using a random-effects model.
Porras et al relay that only studies reporting on symptomatic PAD were included in their analysis. They specify that studies were eligible if they included patients over the age of 18 with a diagnosis of PAD— established either by questionnaire, ankle-brachial index at rest, treadmill, or duplex—reported symptom prevalence, and presented outcomes. The authors note that review articles and case studies were excluded from their analysis.
Out of the 2,186 studies identified, a total of 21 and 20 studies were deemed eligible for qualitative and quantitative analysis, respectively. The investigators report that, of the qualitative studies, 13 were cross-sectional, six were cohorts, one was a case-control study, and one was a randomised controlled trial. Among the eligible study populations with diagnosed PAD, women represented 43.9%.
The 21 studies eligible for qualitative analysis reported on 1,929,966 patients with diagnosed PAD. According to the authors, the data from these studies show that women presented with intermittent claudication less often than men (25.9 vs. 30.2% with OR 0.78 [95% CI 0.72–0.84]; p<0.001; very low quality of evidence). In contrast, Porras et al communicate that rest pain and atypical leg symptoms were more prevalent in women (12.8% vs. 9.2%; OR 1.4 [95% CI 1.22–1.6]; very low quality of evidence, and 22.8% vs. 19.8%; OR 1.18 [95% CI 0.96–1.45]; very low quality of evidence, respectively).
The authors acknowledge some limitations of the present study. They recognise a “substantial heterogeneity” between the studies, the fact that only studies written in English were analysed, and that not all studies reported outcomes of interest. However, Porras and colleagues express their confidence that these limitations “are unlikely to influence the results significantly” as the lower prevalence of intermittent claudication in women was consistent over several subgroups and in sensitivity analyses.
Looking ahead, Porras et al suggest that future studies are needed to understand the possible reasons for differences in clinical presentation in women and men with PAD, and how this influences diagnosis, treatment, and outcomes.
Artio Medical, a medical device company developing innovative products for the peripheral vascular, neurovascular, and cardiology markets, today announced it received US Food and Drug Administration (FDA) clearance for its Solus Gold embolization device, a next-generation product for peripheral vascular occlusion.
“Current occlusion devices can be difficult to position in challenging anatomy, often require multiple implants, and usually take time to completely occlude the target vessel. This can be a problem when physicians need to control or prevent bleeding and reduce the risk of further complications,” commented Blaise Baxter, the vice president of Neurovascular and Peripheral Vascular Interventions for Artio Medical. “The Solus Gold device aims to overcome these limitations with a single implant designed for precision placement and immediate occlusion, even in high-flow vessels and short landing zones.”
The Solus Gold embolization device is indicated to obstruct or reduce the rate of blood flow in the peripheral vasculature. The delivery system balances flexibility, enabling physicians to navigate tortuous vasculature. Following a controlled expansion and simple mechanical detachment, the non-porous, balloon-like gold implant provides 360° vessel apposition for immediate and complete occlusion, and resists migration and recanalisation, providing physicians with a “one-and-done” solution for peripheral vascular occlusion. As demonstrated in a pre-clinical study, the Solus Gold device achieved immediate occlusion in >90% of cases, including in large and high flow vessels, and demonstrated 0% migration and 0% recanalisation in testing out to 3 months.
“We would like to thank the FDA for providing helpful input to the Artio team through the Q-Submission process, and for the careful and thoughtful review of our 510(k) application. I would also like to thank the talented and dedicated Solus Gold product development team at Artio, our many partners in the industry, and our supportive investors for helping Artio reach this important milestone,” said Nicholas Franano, president and CEO of Artio Medical. “When I first learned to embolize vessels using small metal coils more than 20 years ago, I thought surely someone will come up with a better device for doing that. As we prepare for the market release of the Solus Gold device later this year, I am excited to have the opportunity to provide physicians and patients with an improved peripheral vascular embolization experience.
Malignant ureteric obstruction (MUO) poses several tangible threats to cancer patients—and these threats translate, in turn, to challenges for the interventional radiologist and other treating physicians. Here, Conrad von Stempel and Tim Fotheringham (University College LondoN Hospitals and Barts NHS Foundation Trusts, London, UK) describe a number of alternative techniques to common approaches via percutaneous nephrostomy (PCN) or with polymeric JJ stents, while also assessing currently available evidence in this space.
Ureteric obstruction is a common sequela of genitourinary and other malignancies. Obstruction occurs from direct tumour infiltration, extrinsic compression from lymphadenopathy or tumour mass, and can occur because of malignant fibrosis or surgery. Patients with MUO have a poor overall prognosis with the median life expectancy of less than 12 months.1,2 MUO is a feature of advanced cancer and progressive bilateral obstruction leads to irreversible deterioration of renal function. The development of MUO may also preclude chemotherapy and other cancer therapies.
A multidisciplinary approach in the management of patients with MUO is required, as treatment selection is dependent on the prognosis of the patient, and the patient’s performance status combined with available cancer treatment options. Although some MUO can be treated with a retrograde approach, many patients require an antegrade approach by an interventional radiologist. MUO is commonly treated with PCN or with polymeric JJ stents—however, there are other management options available.
Permanent PCN may be required when there is extensive tumour infiltration in the bladder or when the ureteric obstruction cannot be crossed. PCN drainage is a relative contraindication for chemotherapy, requires regular exchanges, and is an undesirable outcome for most patients. Frequent tube dislodgement can occur with PCN, even when using larger-diameter nephrostomy tubes, placing the nephrostomy in a tunnel, or attempting to secure the tube with sutures and dedicated drain-fixation devices. The loop or circle nephrostomy is an alternative in such patients, using a double calyceal puncture. The loop nephrostomy has greater security with less chance of accidental displacement and requires less frequent routine tube changes than standard PCN.3,4
If the bladder still functions, extra-anatomical stenting can be considered through a subcutaneous tunnel and suprapubic access. Extra-anatomic stenting was first described in the 1990s but is seldom offered in PCN-dependent patients with MUO.5 A dedicated device, such as the Paterson-Forrester subcutaneous urinary diversion stent (Cook Medical; 8.5Fr, 65cm) can be placed and exchanged at three monthly intervals under local anaesthetic.
While it is difficult to draw too many conclusions from a limited number of studies, the self-expanding, covered ureteric stents do appear to be more effective in treating MUO, and with better long-term outcomes, compared with JJ stents.
JJ stenting with 6–8Fr polyurethane devices fail to relieve MUO at three months in up to 51% of patients and require regular routine exchange via the retrograde route at three-to-six-month intervals. Stent primary patency is between 40% and 60% at one year.6 An alternative to a polyurethane JJ stent is the Resonance stent (Cook Medical), which is a metal JJ stent made from a cobalt-chromium-nickel-molybdenum alloy and has a maximum indwell time of 12 months before exchange is required. The Resonance has improved primary patency to polymeric stents in some studies with >90% patency at one year, owing to less risk of extrinsic compression and encrustation. In a systemic review, the reported migration is low, at 1%—however, stent obstruction at 17% was seen and patients are prone to the same symptoms of bladder irritation seen with JJ stents.7
Dedicated covered, self-expanding ureteric stents have become available, which can be inserted either retrogradely or antegradely, and offer alternatives to JJ stents requiring fewer exchanges. Devices currently available include Uventa (Taewoong Medical), which is a double-layered, coated, self-expandable metallic mesh stent. The Allium (Allium Medical Solutions) is a fully covered, self-expanding nitinol stent. The entire stent is covered with a biocompatible, biostable polymer, making it a nonpermeable tube, to prevent tissue ingrowth and early encrustation stent. The Hilzo stent (BCM) has a polytetrafluoroethylene (PTFE) cover in spiral configuration—intended to help prevent stent migration. It is designed with soft and smooth ends to minimise hyperplasia.
All of these devices have a delivery size that is suitable for antegrade insertion—10Fr or less—and when deployed the diameter ranges from 7–10mm. The stents can be overlapped at points of tight narrowing, or in very long stricture, and offer focal distension of the diseased portion of ureter and require less frequent reintervention than JJ stents. Removal and replacement of these devices requires endoscopic intervention with graspers to either unwind or collapse the device.
While it is difficult to draw too many conclusions from a limited number of studies, the self-expanding, covered ureteric stents do appear to be more effective in treating MUO, and with better long-term outcomes, compared with JJ stents. Complications seen include occlusion from hyperplasia, encrustation, migration and fistulation. The cost of the devices is offset by the reduced need for reintervention as compared with JJ stents.7–10
In conclusion, there are more options for treating patients with MUO other than PCN and JJ stents. Avoiding permanent PCN is advantageous to the patient, and significantly reduces readmission for either exchanges or managing the arising complications. Interventional radiologists should consider alternatives such as extra-anatomical stents and self-expanding covered stents when dealing with MUO.
References:
Conrad von Stempel is a consultant interventional radiologist at the University College London (UCL) Hospitals NHS Foundation Trust in London, UK.
Tim Fotheringham is a consultant interventional radiologist at Barts Health NHS Trust in London, UK.
The authors declared no relevant disclosures pertaining to this article.
The February top 10 features news of the recent Japanese randomised control trial results, which support the use of mechanical thrombectomy in ischaemic stroke patients. Other highlights include an exploration of innovations in treating and diagnosing small renal masses by Vinson Wai-Shun Chan and Tze Min Wah, as well as Fluidx Medical’s announcement of “very promising” results from the company’s GPX-Clear embolic device in-vivo research.
1) Mechanical thrombectomy shown to restore more function than medication alone following severe stroke
A new study from Japan has become the first randomised controlled trial to demonstrate the effectiveness of endovascular mechanical thrombectomy procedures in patients who have severe strokes involving clots in one or more large brain arteries.
2) Percutaneous melphalan perfusion can induce significant responses in uveal liver metastases
A recent retrospective analysis published in Melanoma Research has found that percutaneous hepatic perfusion with melphalan for the treatment of metastatic uveal melanoma offers a hepatic response rate of 66.7% and good progression-free survival.
3) Fluidx Medical’s embolic device demonstrates promising visibility
Fluidx Medical Technology has announced the results of the GPX-Clear embolic device in-vivo research which uses the base GPX technology and incorporates an intermediate-term radiopacity agent, as described by the company.
4) SIRONA head-to-head randomised trial achieves 50% enrolment
Concept Medical has announced that the SIRONA randomised controlled trial (head-to-head comparison of sirolimus versus paclitaxel drug-eluting balloon angioplasty in the femoropopliteal artery) has completed half the targeted enrolment.
5) Shifting paradigms in diagnosing and treating small renal masses
In light of recent and upcoming developments, Vinson Wai-Shun Chan and Tze Min Wah (Leeds, UK) explore the evidence and latest progress in renal tumour biopsy and discuss the treatment of small renal masses more broadly.
An associate professor of Radiology at the Division of Interventional Radiology, Nuovo Santa Chiara University Hospital, Pisa, Italy, Laura Crocetti is also an internationally recognised ablation expert. Here she answers questions posed by Interventional News.
7) Cerenovus launches Emboguard balloon guide catheter for acute ischaemic stroke
Cerenovus—a neurovascular firm that forms part of Johnson & Johnson Medical Devices Companies—has announced the launch of Emboguard, the next-generation balloon guide catheter to be used in endovascular procedures, including those for patients with acute ischaemic stroke.
8) Global EXCELLENT study “shows how much stroke thrombectomy has advanced”
Preliminary late-breaking research presented at this year’s International Stroke Conference (9–11 February, New Orleans, USA) shows that mechanical removal of blood clots reduced post-stroke disability in nearly half of “all-comer” real-world stroke patients.
9) MedAlliance acquires Japanese partner MDK Medical
MedAlliance has acquired its partner MDK Medical, a Japanese vascular specialist company. MDK Medical has previously worked closely with MedAlliance in developing Japanese clinical studies for the novel sirolimus drug-eluting balloon—the Selution SLR— for the treatment of peripheral arterial disease.
10) First patient enrolled in PEERLESS study of FlowTriever system
Inari Medical has announced that the first patient has been enrolled in PEERLESS prospective, randomised controlled trial comparing the outcomes of patients with intermediate-high risk pulmonary embolism treated with the FlowTriever system versus catheter-directed thrombolysis.
With cancer cases growing worldwide and an increased number of late-stage diseases in elderly patients, there is an increasing need for an integrated approach. “Through evidence, cost, and acceptance of interventional oncology (IO), we can create value-based care and shift the treatment focus from volume to value”. This was the main take-home message presented by Thomas Helmberger (Public Hospital, Munich, Germany) at the European Conference of Radiology (ECR) 2022 (2–6 March, virtual).
Starting off the presentation, Helmberger provided some background on the future of patients with malignant diseases, with more patient cases currently in more and in less developed countries. He explained that “this growing number of patients translates to increasing cost and this demographic impact will challenge our healthcare systems”. He went on to explain that for example in colorectal malignomas 20–25% of patients exhibit stage four cancer, with the majority being elderly patients. He pointed out that this, therefore, means that we have to “deal with not only cancer but also comorbidities”. Discussing the “wave” of elderly patients, he explained the “Sisyphus effect”—more elderly expect to be fit and independent into older age, requiring more medical resources, creating more elderly patients.
Discussing the current developments in IO, Helmberger explained that IO techniques are resembling already known techniques, for example, radio-embolic techniques are resembling radiotherapy.
He drew attention to current issues in IO by making reference to an early closed randomised controlled trial (RCT) comparing surgery and percutaneous thermal ablation for hepatic metastases which had just recently illustrated drawbacks such as misconceptions about the eligibility criteria, unconscious bias towards surgery, and a lack of dedicated research nurses to name a few. The currently ongoing COLLISION RCT is dealing with the same comparison, however, it can be questioned to what extent artificial RCTs are still necessary for comparison to real-life data. Numerous studies over the past 15 years pointed to no difference in the overall survival in percutaneous thermal ablation compared to surgery in primary and secondary liver malignancies with diameters up to 3 cm (Otto et al, 2010; Lee et al, 2016). He also explained that combining transarterial therapies such as chemo- and radioembolisation can even enhance the therapeutical benefit of surgical and percutaneous ablative therapies (Hholami et al, 2020).
Helmberger raised the important factor of cost, with healthcare costs presenting differently in each country and between interventional approaches, with local ablation therapies usually costing less. However, in the sense of cost-effectiveness, Helmberger explained it is of limited use to only analyse a single procedure cost, as this does not provide sufficient information on the overall process costs. According to Helmberger, the effectiveness of IO is proven through evidence, cost, but still less acceptance, since “many guidelines and recommendations from professional societies are reluctant to implement interventional radiology techniques”. However, he stressed that IO embedded into interdisciplinary therapy concepts will optimise treatments to be given at the right time during a disease continuum. In doing so, he claims we can create more and more “value-based care”, which remains a central challenge in times of increasingly limited resources.
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Fist Assist Devices has announced a three-year affiliation with Regional Health Care Group to commercialise and launch sales of the Fist Assist Model FA-1 device in Australia and New Zealand.
The FA-1 device is a wearable, patent-protected, intermittent compression device that has European CE-mark clearance for use in conditions where vein dilation is desired in patients that will require or have already undergone arteriovenous fistula placement for eventual haemodialysis.
In addition, it is intended to help with infusion arm vein access for chemotherapy, radiology or phlebotomy access support. FA-1 also recently received US Food and Drug Administration (FDA) Breakthrough Device designation for presurgical vein dilation in patients with end-stage kidney disease.
“We are thrilled to combine forces with Regional Health Care Group for the official launch of the Fist Assist Model FA-1 device in Australia and New Zealand,” said Tej Singh, chief executive officer and founder of Fist Assist. “This is a huge milestone, as we now have a committed, dedicated, and exceptional commercialisation arm that is poised to deeply penetrate the Oceania market.”
“We are excited to distribute and commercialise the innovative FA-1 device,” said Scott Clissold, national business development manager of Regional Health Care Group. “We have been watching the Fist Assist technology and patiently awaiting the right time to commercialise a ground-breaking, market-changing and innovative device that will improve the patient journey with renal and cancer care in Australia.”
Enrolment has been completed in the PROMISE II pivotal trial of the LimFlow deep vein arterialisation system designed to prevent amputations in so-called “no-option” chronic limb-threatening ischaemia (CLTI) patients, the eponymous device maker announced today.
“The PROMISE II investigators are very encouraged by our experience using the LimFlow system to treat CLTI patients with no other options. These are likely the sickest patients ever to have been enrolled in a limb salvage trial,” said Daniel Clair, PROMISE II principal investigator, and professor and chair of the department of vascular surgery at Vanderbilt University Medical Center Section of Surgical Sciences in Nashville, Tennessee. “Major amputations have a devastating effect on the lives of patients and their families. We are excited about the prospect of helping improve the lives of more of these patients once this novel technology becomes broadly available.”
PROMISE II is a multicentre, prospective, single-arm study being conducted at sites in the USA of 105 no-option CLTI patients. Endpoints include amputation-free survival at six months, limb salvage and wound healing, with subjects followed out to three years. The no-option patients treated in PROMISE II were determined by an independent physician committee to be no longer eligible for conventional endovascular or surgical therapy to treat CLTI, according to LimFlow.
The company also announced completion of enrolment in the CLariTI study of approximately 200 high-risk and no-option CLTI patients. The prospective, observational, multicentre CLariTI study will track the clinical progression of CLTI and incidence of death, amputation, and revascularisation attempts in patients undergoing standard medical management for the disease over a one-year period.
“Despite suffering from the most advanced form of CLTI, these no-option and high risk patients have been excluded from other trials,” said Anahita Dua, CLariTI principal investigator and assistant professor of surgery at Harvard Medical School in Boston. “Our hope is that the CLariTI study gives us better insights into the reintervention, amputation and death rates in no-option and high-risk patients treated with the current standard of care.”
A prospective multicentre study has evaluated the safety and efficacy of a polyethylene glycol (PEG)-based liquid embolic in treating hypervascular tumours, according to an Instylla press release.
Instylla recently announced the publication of results from the first-in-human (FIH) clinical trial of the Embrace hydrogel embolic system (HES) for the treatment of hypervascular tumours, in the Journal of Vascular and Interventional Radiology (JVIR). This prospective, single-arm multicentre study demonstrated that Embrace HES effectively embolized malignant and benign hypervascular tumours by blocking tumour blood supply with technical success and persistent embolization, as noted in imaging follow-up at 30-days, in all eight patients treated on this study.
“This phase I first-in-human study of Embrace HES in the embolization of a range of hypervascular tumours has shown promising results,” commented Gerard Goh (The Alfred Hospital and Monash University, Melbourne, Australia), lead author on the study. “Embrace HES holds great potential with its ease of use, technical success in all patients, and no tumour revascularisation in the 30-day follow-up imaging.”
Ten embolizations were performed in eight patients with a range of tumour types, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and angiomyolipoma (AML). Tumour sizes ranged from 2.1–7.5cm and were treated with Embrace HES volumes from 0.4 to 4.0ml, with an average delivery time of 15 minutes.
Jee-Fu Huang (Kaohsiung Medical University Hospital, Kaohsiung, Taiwan) added, “Taiwan has one of the highest age-adjusted incident rates of HCC in East Asia, which is also the second leading cause of cancer-related deaths. This novel liquid embolic, designed to achieve capillary-level embolization, had favourable patient outcomes in the FIH trial, including HCC tumours. We are encouraged by these results. Our centre is currently enrolling in the Instylla HES HVT pivotal study, so I look forward to continuing to assess Embrace HES in treating hypervascular tumours.”
Cordis recently announced that the US Food and Drug Administration (FDA) has approved the S.M.A.R.T. Radianz vascular stent system, a self-expanding stent purposefully engineered for radial peripheral procedures.
The newly approved vascular stent system joins the Brite Tip Radianz guiding sheath and Saberx Radianz percutaneous transluminal angioplasty (PTA) catheter to complete the Radianz radial peripheral system, a company press release notes.
According to Cordis, the safety and efficacy profile of S.M.A.R.T. vascular stents is validated with a solid foundation of clinical evidence and real-world experience. It claims that the S.M.A.R.T. vascular stents are the only SE lower extremity stents with 10-year follow-up, proven to provide reliable outcomes in over 3,000 patients, and that they have shown comparable one-year revascularisation rates and a significantly lower cost of hospitalisation versus drug-coated stents.
“I am excited that Cordis has committed to delivering new interventional tools that can be utilised in treating patients with cardiac or vascular disorders via a transradial access,” said Craig M Walker, president and founder of the Cardiovascular Institute of the South (Houma, USA). “We have been constrained in the greater utilisation of this important access site associated with greater patient comfort and less major bleeding as our diagnostic and interventional tools that can be delivered via this access have been limited. These lower profile devices should expand the utilisation of radial access in treating patients.”
Cordis advises that the S.M.A.R.T. Radianz vascular stent system features improved ergonomics and advanced one-handed deployment capability, offering excellent placement accuracy and up to 300% greater stability. The product is available in a broad size matrix to support iliac and superficial femoral artery (SFA) lesion treatment, and the rapid exchange delivery system offers more convenient wire management and device exchange compared with over-the-wire (OTW) catheter systems, the company adds.
“At Cordis, we see the Radianz radial peripheral system as a best-in-class option for treating peripheral lesions with the added benefit of reducing the cost of care,” said Matt Muscari, Cordis president, Americas. “Empowered by our legacy, we are now focused on investing in a future of innovation. We are committed to leading the way in radial access to enable the less-invasive procedures that patients prefer.”
The VasQ external support device (Laminate Medical) has demonstrated long-term benefits for radiocephalic (forearm) arteriovenous fistula (AVF) creation in a retrospective analysis of 150 consecutive procedures. Robert Shahverdyan (Asklepios Klinik Barmbek, Hamburg, Germany) and Dirk Hentschel (Brigham and Women’s Hospital, Boston, USA) have published these data in Seminars in Dialysis.
The VasQ device is implanted around the connection between the vein and artery of an AVF to promote maturation into a functional access for haemodialysis. Standard fistulas have reported failure rates to become functional for haemodialysis as high as 60% within the first year, as per a press release from Laminate.
However, the newly published data demonstrate that implanting VasQ resulted in 90% of fistulas being used for dialysis within a median of 41 days, and 84% maintaining secondary patency out to 36 months. The results suggest, according to Laminate, that the addition of VasQ to Shahverdyan and colleagues’ standard of care has helped haemodialysis patients receive more functional fistulas that are durable over the long term.
“I am excited to share these data, which build on my previous publication that demonstrated the short-term benefit of VasQ to reduce my primary failure rate,” Shahverdyan said. “Now, we see the early success with VasQ translated to the long-term benefit of more patients retaining a functional fistula out to three years.”
“I was excited to partner with Robert on this publication,” Hentschel added. “The data supporting VasQ’s use in creating usable fistulas continue to build. I am looking forward to having this technology available for use in US patients.”
Laminate is currently completing a US pivotal study and preparing its submission for market clearance to the US Food and Drug Administration (FDA) for review.
Cardiovascular Systems Inc (CSI) has announced the start of enrolment in a first in-human trial of the peripheral everolimus drug-coated balloon (DCB) being developed by Chansu Vascular Technologies (CVT).
DCBs are a widely accepted percutaneous interventional treatment option for femoropopliteal lesions in patients with peripheral arterial disease. Everolimus, the active drug in CVT’s DCB formulation, acts as a cytostatic agent to reduce tissue hyperplasia and associated restenosis and has a long history of safety and efficacy in coronary drug-eluting stent applications.
The first patient was treated by Benjamin Honton, principal investigator at the Clinique Pasteur, Toulouse, France. The peripheral DCB was used to successfully treat a 69-year-old male with a 7.5cm lesion in his superficial femoral artery (SFA).
“We are honoured to enrol the first patient in the CVT-SFA trial,” said Honton. “We believe this promising new generation of everolimus DCBs could improve patient outcomes for those suffering from peripheral arterial disease.”
CVT intends to enrol 75 patients at a minimum of four sites in France and Germany to support an investigational device exemption (IDE) submission to the US Food and Drug Administration (FDA) and a subsequent US pivotal clinical study.
Jeffery Chambers, CSI’s chief medical officer, said: “Following the announcement of the first in-human experience with CVT’s coronary everolimus DCB in November 2021, we are thrilled to announce the first in-human experience with the peripheral everolimus DCB. We believe these products could become important new therapies in the treatment of peripheral and coronary artery disease.”
Under the terms of the agreements signed with CVT, CSI advises that it is providing milestone-based financing to CVT for the development of coronary and peripheral DCBs. Under an acquisition option agreement, upon CVT’s completion of key technical and clinical milestones in the development programme, CSI will have exclusive rights and obligations to acquire CVT, subject to the satisfaction of closing conditions set forth in the agreement.
Merit Medical announced today that it has received US Food and Drug Administration (FDA) breakthrough device designation for its Embosphere microspheres.
Utah-based Merit Medical’s breakthrough nod covers the Embosphere microspheres for the genicular artery embolization (GAE) indication for reducing blood flow to the knee to reduce pain and disability caused by knee osteoarthritis.
Merit Medical said in a news release that Embosphere microspheres are the most clinically utilised and clinically studied spherical embolic, having been used in more than 250,000 procedures.
“We are pleased with the recognition and partnership of the FDA, making it possible for new and innovative products to reach the market faster,” Merit Medical chairperson and chief executive officer Fred P. Lampropoulos said in the release. “Merit’s embolotherapy platform of products has provided consistent and predictable results for effective embolization. We believe this breakthrough designation allows us to accelerate our programmes to study and obtain FDA clearance for the GAE indication for Embosphere microspheres, ultimately expanding treatment options for patients.”
In October 2021, Varian received an FDA breakthrough device designation for microspheres under the same indication for GAE in treating knee osteoarthritis.
An embolic device by Fluidx Medical has been used successfully in a variety of complex cancer cases, according to a company press release.
As part of an ongoing multicentre study, Fluidx Medical has released additional information on treating tumours, including a highly vascularised metastatic renal cell carcinoma, with the GPX embolic device.
“We were very pleased with the outcome and the resulting occlusion created by GPX,” said Martin Krauss, head of interventional radiology at Christchurch Hospital (Christchurch, New Zealand.) “In one procedure, the renal cell carcinoma had metastasised to the upper femur/pelvic region. We used a combination of GPX and coils during the case. We treated five different tumour vessel segments with GPX.”
“GPX successfully occluded a variety of vessel presentations from smaller low-flow vessels to larger higher-flowing feeding vessels,” said Christopher Phillips, director of clinical affairs at Fluidx. “GPX was delivered using a range of microcatheters and showed versatility in treating small and large metastatic tumour vessel beds. GPX was delivered through standard microcatheters that were appropriate for each targeted vessel’s size and blood flow.”
The GPX embolic device is designed for simple preparation and controlled delivery. The company advises that the device is packaged ready to use in a syringe, can be prepped tableside by the clinician in about 30 seconds, and may be delivered through standard microcatheters.
Fluidx Medical describes its GPX technology as a low-viscosity, aqueous-based solution in a syringe that solidifies into a durable embolus upon delivery, without polymerisation or dimethyl-sulfoxide (DMSO) precipitation. GPX is designed to occlude blood vessels independent of a patient’s coagulation situation.
Guerbet
announces it will more than double its line of microcatheters and launch a new line of guidewires, resulting in a broad range of interventional imaging and embolization solutions becoming available.
The company obtained its original offering of 18 references of SeQure and DraKon microcatheters as part of their acquisition of Accurate Medical Therapeutics in 2018. It received the CE mark in April 2019, and was US Food and Drug Administration (FDA) cleared in 2018.
Guerbet now expands the portfolio, adding 20 versions for a total of 38, and launching a new line of Axessio guidewires with two diameters. A limited market evaluation began in the United States during the fourth quarter of 2021, paving the way for a commercial launch rollout in the second quarter in select markets.
“The positive feedback we have received during the limited market release of our line extension has reinforced Guerbet’s decision to expand available tools to the healthcare professionals for various embolization procedures,” affirms David Hale, chief executive officer. “This year marks our 40th anniversary in interventional radiology. We are proud of that, but we consider it just the beginning. We have never been more dedicated to continuous growth and innovation to help interventional radiology physicians to meet an even greater number of patient needs.”
Both the SeQure and DraKon technologies offer interventional radiologists optimised navigation capabilities which is expected to enable access to difficult anatomies and reach further. Additionally, SeQure is the only reflux control microcatheter enabling a fluid barrier technology for flow-directed embolization. The new models are designed to deliver more targeted treatment and use a wider range of beads, from extra-small to large.
“Innovation means everything to us, because it means everything to our physician partners and to their patients,” explains Jean-François Blanc, Guerbet’s senior VP, for interventional imaging. “The more we see the results, the more we see opportunity to improve lives, and we just want to keep pushing forward. With strategic acquisitions that helped create a unique toolkit of microcatheters and this latest portfolio extension, we are advancing options for the interventional radiology community.”
InspireMD has announced that its CGuard embolic prevention stent system (EPS) will be included as a device option for stenting in CREST-2 (Carotid revascularisation endarterectomy or stenting trial). Following the recent approval of the CREST-2 investigational device exemption (IDE) supplement application from the US Food and Drug Administration (FDA), the company states that it will be evaluating strategic sites to enable expediated access.
Marvin Slosman, chief executive officer of InspireMD, commented: “This approval for use of CGuard EPS in a trial as significant as CREST-2 is proxy to the validation of our technology platform, contributing to this important work. The CREST-2 trial is widely acknowledged as the most significant ongoing trial to scientifically investigate the optimal course of treatment to prevent strokes for asymptomatic patients with significant carotid disease. The opportunity to be a part of CREST-2 is a tremendous milestone for our company, and we look forward to CGuard playing an important role in the stenting results”.
The study first enrolled patients in 2014, as two parallel multicentre randomised, observer-blinded endpoint clinical trials with the purpose of being to determine the best way to prevent strokes in patients with high-grade carotid stenosis but no stroke symptoms related to that blockage. According to an InspireMD press release, the trial will enrol an estimated 2,480 participants who will remain in the study for four years following the start of intervention.
“The CREST-2 executive committee is keenly focused on positioning the results of the trial to be relevant, actionable, and informative to contemporary practices,” said Thomas Brott (Mayo Clinic, Jacksonville, USA), principal investigator of the National Institute of Neurological Disorders and Stroke (NINDS)-sponsored trial. “Over the course of the trial we have continually introduced state of the art medical, pharmacological therapies to reduce the risk of stroke in our randomised patient population. It is critical of any long-term study to remain aligned with evolving technology and relevant devices. After examining the extensive clinical experience with the CGuard stent and the large body of evidence to its effectiveness, the study executive committee felt it appropriate to include this stent as a treatment option. Patients that agree to participate in the CREST-2 trial, depending on accessibility and operator training and discretion, will now have access to this state of the art, carotid stent device.”
Cardiovascular Systems Inc (CSI) recently announced it has partnered with Innova Vascular (Innova) to develop a full line of novel thrombectomy devices.
According to a press release, CSI intends to acquire and commercialise novel thrombectomy devices from Innova targeting peripheral vascular disease, including deep vein thrombosis (DVT) and pulmonary embolism (PE).
Sanjay Shrivastava, CEO of Innova said: “We strive to bring solutions that are easy to use, safe, and highly effective in treating potentially devastating diseases. We are excited to partner with CSI, which has been serving the interventional cardiology, interventional radiology, and vascular surgery communities that will be the primary users of Innova products. CSI’s commercial presence in this space makes it an excellent fit for accelerating the commercialisation of Innova’s products post regulatory clearances.”
CSI claims that, pending regulatory clearance in the USA, the company could begin to commercialise a portfolio of manual aspiration and clot retrieval devices for the treatment of peripheral vascular disease in 2023. The portfolio and corresponding indications for use are expected to be expanded to include treatment of DVT and PE following the completion of subsequent clinical trials.
Scott Ward, chairman, president and CEO, said: “The commercialisation of these thrombectomy devices will be an important addition to our growing pipeline of products. In total, developing novel drug-coated balloons, intravascular lithotripsy, mechanical circulatory support, and thrombectomy devices target some of the fastest-growing segments within interventional cardiology. Supplementing our core orbital atherectomy devices with these technologies will greatly increase the number of patients we will reach while simultaneously expanding our total addressable market to over US$18 billion in the coming years.”
Under the terms of the agreements signed with Innova, CSI has provided financing to Innova for the development of thrombectomy devices. Under an acquisition option agreement, upon Innova’s completion of key technical, regulatory, and clinical milestones in the development programme, CSI will have exclusive rights to acquire the thrombectomy devices, subject to the satisfaction of closing conditions set forth in the agreement.
Six-month outcomes from the ongoing CLOUT registry demonstrate the “safety and efficacy” of the ClotTriever thrombectomy system (Inari Medical) in a real-world deep vein thrombosis (DVT) population regardless of clot chronicity level, the 2022 annual meeting of the American Venous Forum (AVF; 23–26, Orlando, USA) heard.
David Dexter (Eastern Virginia Medical School and Sentara Vascular Specialists, Norfolk, USA) was delivering the latest subgroup analysis update from the prospective, multicentre study on behalf of the CLOUT registry investigators based on the first 250 patients enrolled at 24 sites. “We were able to meet the performance goal of greater than 75% in all three [chronicity] groups,” Dexter told attendees. “We had remarkably low device-related serious adverse events at one month. And our rates of post-thrombotic syndrome [PTS]—including moderate to severe—at six months were similarly low.”
The data from the registry show 33% of the 250 patients with acute thrombus, 35% with subacute and 32% with chronic.
Almost all procedures were single session, with an average of four passes using the ClotTriever device for all chronicity subgroups, Dexter said. No patients required adjunctive thrombolytics. Adjuvant angioplasty was used in 73% (acute: 70%; subacute: 68%; chronic: 84%) and stents in 47% (acute: 46%; subacute: 42%; chronic: 50%) of cases.
Complete or near-complete thrombus removal was achieved in 85% (acute: 90%; subacute 81%; chronic: 84%) of limbs, including 51% (acute: 54%; subacute: 49%; chronic: 49%) with 100% thrombus removal. The post-thrombectomy median hospital stay was one day for all subgroups.
At six months, 90% (acute: 86%; subacute: 89%; chronic: 96%) of the treated limbs had flow present, and 90% (acute: 84%; subacute: 90%; chronic: 91%) were compressible. Any PTS at six months was about 20% in the acute, 25% in the subacute and 30% in the chronic arms. “Statistically, this has a p value of 0.5—we will see how that holds out in another two years when we have finished enrolment of 500 patients,” Dexter said. On the other hand, moderate-to-severe PTS, “was remarkably low at 5% in the acute arm, and about 10% in the subacute and chronic arms.”
Major adverse events and serious adverse “were similar and also rare,” Dexter added. “All-cause mortality was three patients throughout the first 250.”
Furthermore, in terms of venous clinical severity score (VCSS) scores, at 30 days and six months numbers were “nicely low” at 3 and 2 for the acute group, 4 and 3 among subacute patients, and 4 and 4 in the chronic subset, Dexter pointed out. Pain score numbers were “essentially zero across the board.” The same was true when measuring quality of life, he said. “The average quality of life went back to the patient’s baseline regardless of the chronicity believed to be in the clot for acute, subacute and chronic.”
The CLOUT registry’s follow-up out to two years is ongoing. Total enrolment of 500 patients at up to 50 sites has the intention of probing all-comers—across acute, subacute and chronic clot subgroups.
An emerging endovenous valve formation system designed to treat patients with chronic venous insufficiency (CVI) with evidence of deep venous reflux has demonstrated continual improvement since US investigators started performing clinical cases with the device 18 months ago, according to recently presented early data.
The BlueLeaf procedure, currently undergoing clinical research worldwide, has shown a rate of 90% technical success among the first 10 patients treated in the USA, William Marston (University of North Carolina at Chapel Hill, Chapel Hill, USA), one of the INFINITE-US early feasibility study investigators, told the 2022 annual meeting of the American Venous Forum (AVF; 23–26 February, Orlando, USA).
These data are part of a total of 30 patients treated at sites worldwide, demonstrating a 93% technical success rate of forming at least one valve, said Marston, who disclosed a consultancy relationship with InterVene, the company behind the BlueLeaf device.
Enrolled patients, classed as C5–6 on the CEAP (Clinical-Etiological-Anatomical-Pathophysiological) classification of disease severity, all had significant deep vein reflux in two main segments between the knee and the common femoral vein, adequate inflow and no acute deep vein thrombosis (DVT), Marston explained.
Thus far, all subjects in the study have had a maximum of two valves formed using the device—most performed on the right leg and all monocuspid valves (US Food and Drug Administration [FDA] approval has now been granted to form bicuspid valves). The patient pool has a mean age of 59, presented with a venous clinical severity score (VCSS) of 15, and 70% had a previous history of DVT (six on the ipsilateral limb).
Marston told AVF attendees how the US investigators had achieved success in nine out of the 10 patients, with the mean number of leaflets formed standing at 1.7. He further noted how procedure time was currently decreasing, explaining how the system requires a period of adjustment as physicians adapt to patient and equipment positioning. Marston pointed out two minor device deficiencies that did not lead to any complications.
In terms of VCSS among the first six subjects with follow-up out to 12 weeks, investigators saw a mean decrease of 2.3, he said, though he cautioned the early-stage nature of the data. Marston reported no major adverse events, one partial valve pocket thrombosis at one day and one partial distal intraluminal thrombosis. Both were asymptomatic and no longer seen after 30 day duplex follow-up, he added.
The process behind the development of the BlueLeaf system—which gained FDA Breakthrough Device designation late last year—”has been under evolution such that we are just starting to do bicuspid valves and, in fact, we are scheduled to do the first one in the USA next week,” Marston said. “The device we are using today is quite different from the one we used 18 months ago.”
The system involves retrograde access; a high-pressure balloon expanded to force the deck of the device up against the vein wall; an advanced needle that enters the vein wall and hydrodissects a flap; and then a nitinol dissector advanced into the flap, expanding and deepening the formation to create a valve cusp.
Improvements made to the latest generation of the device means the valve cusp formed has more depth and a deeper capture of blood after creation, Marston elaborated. Additionally, “the device balloon has been strengthened to help puncture post-thrombotic veins, as most of the patients enrolled are post-thrombotic.”
Marston drew attention to one of the study cases with one year of follow-up to demonstrate the BlueLeaf system’s evolution. The 53-year-old male patient, who had two monocuspid valves created, showed no DVT through 365 days follow up and a VCSS improvement from a baseline of 9 to 6. Marston noted how the valve cusp still showed some motion at one year compared to initial formation. “We would like to see more but this was with a very early version of the device,” he said. “The cusps are now deeper and wider and hopefully will move better at 365 days than we see here. But this patient did have a well-preserved improvement in VCSS.”
Concluding, Marston told the AVF meeting the BlueLeaf procedure “is technically feasible,” capable of forming valve cusps and under “continual improvement.” “The cusps we are forming today are much better than they were a year ago,” he said, pointing to an “exciting” future as study investigators progress into bicuspid valve formation and the hope of greater luminal coverage.
Recently released clinical data has outlined the benefits of the RenovaRP paracentesis management system (GI Supply) for patients with ascites. The study, which was published in the Diagnostic and Interventional Radiology journal by Shane Weber (Dearborn, USA) et al, found that there was a substantially higher fluid flow rate during paracentesis using the RenovaRP system as compared to wall suction.1
The purpose of the study was to investigate if the use of RenovaRP as a treatment for ascites would reduce procedure time compared to standard wall suction without increasing adverse effects, such as hypotension or abdominal pain.2
Procedure room time decreased from 53 minutes with wall suction to 31 minutes with RenovaRP (p<0.001).3 The paper’s authors noted that the RenovaRP pump is portable, simple to use, requires little staff training, and can be used to perform paracentesis outside of interventional radiology. The authors also highlighted that, as a self-contained system, it avoids exposing medical team members to patients’ body fluids, which may occur during exchange of wall-suction canisters.4
Karen Brown (Salt Lake City, USA), a co-author of the research paper, said: “Exposure to a patient’s body fluids is a risk faced by healthcare professionals that must change cannisters or open cannisters to pour in the material that solidifies the removed fluid.”
Brown added that the patient experience “was comparable to conventional wall suction. Patients said they liked Renova better, which might have been due in part to it being a faster procedure”
The study authors also noted that on certain high-volume centres where paracentesis procedures are performed frequently, the RenovaRP pump can be expected to provide superior through-put with relatively minimal added procedural costs. In addition, the pump offers providers and patients substantially faster procedure times without adverse outcomes.5
Rhett Klein, vice president of sales and marketing at GI Supply, commented: “While we anticipated positive outcomes from this clinical study, our team was gratified that the results clearly support the benefits of the RenovaRP system. We are dedicated to enhancing patient safety and satisfaction in a cost-effective system that also supports the needs of medical staff.”
References:
1: Weber S, Al-Dulaimi R, Quencer K, et al. Paracentesis: faster and easier using the RenovaRP® pump. Diagnostic and Interventional Radiology 2022
2: Ibid.
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Aidoc, a technology company that provides artificial intelligence (AI) solutions for medical imaging, including in the cardiovascular space, is extending its services beyond the radiologist’s workstation. This is according to the company’s vice president of Innovation, Demetri Giannikopoulos, who spoke to Interventional News at this year’s International Symposium on Endovascular Therapy (ISET 2022; 16–19 January, Hollywood, USA) about the company’s journey and its place in a growing market.
With seven US Food and Drug Administration (FDA) clearances for a variety of pathologies, Aidoc states that its AI algorithms deliver a cross-specialty AI experience for physicians in nearly 600 medical centres across the globe.
Specifically, the company’s suite of solutions includes providing thoracic radiologists triage and notification tools to help identify positive cases of pulmonary embolism (PE). This identification by Aidoc’s AI process is combined with automated right ventricle/left ventricle (RV/LV) ratio calculations, provided by partner company Imbio’s software, to improve patient severity assessment and expedite treatment.
“AI is everywhere,” says Giannikopoulos, who notes that what makes it “transformational” in medicine is its ability to help to shape patient care plans and pathways. The technology can be leveraged to identify the appropriate patients for treatment and bring those patients to the care team in a timely manner, he explains.
Aidoc started in diagnostic radiology. The company’s solutions would automatically flag any positive cases of acute pathologies on the scans, and then prioritise the patients with those positive cases on radiologists’ worklists. “The radiologists would have earlier awareness of the patients with positive acute findings,” Giannikopoulos tells Interventional News.
The company has been extending its AI solutions beyond the radiologist’s work station and connecting radiologists’ findings with the multidisciplinary teams (MDTs) that directly care for the patients, Giannikopoulos reveals. He elaborates: “The focus now is on driving awareness from the radiologist directly to the emergency care physician, directly to the interventionalist, so they know that there is a patient that is worth evaluating immediately.”
“The opportunity for PE patients to fall through the cracks is significant,” says Giannikopoulos, alluding to one of the key reasons why the company endeavours to become more involved in direct patient care. “A lot of times PE is managed by the bedside physician without consulting with the interventional team,” he adds. “We are alerting the team based on the PE identification in the image plus the RV/LV analysis.”
While AI has the potential to improve patient care, Giannikopoulos acknowledges the importance of “pulling the signal from the noise” amidst a growing pool of evidence in the field and fragmented care pathways, and underlines various challenges associated with standing out in a crowded market. He believes that the level of integration Aidoc currently has with the clinical care team sets the company apart, referencing in particular Aidoc’s immediate access to both imaging results and patient information, which can be quickly transferred to team members by their mobile devices.
Johns Hopkins Medicine researchers have developed and tested a new imaging approach they say will accelerate imaging-based research in the lab by allowing investigators to capture images of blood vessels at different spatial scales.
Tested in mouse tissues, the method, dubbed “VascuViz,” includes a quick-setting polymer mixture to fill blood vessels and make them visible in multiple imaging techniques. The approach enables researchers to visualise the structure of a tissue’s vasculature, which in conjunction with detailed mathematical models or complementary images of other tissue elements can clarify the complex role of blood flow in health and disease, say the researchers. The combined images of the blood vessels should not only enhance the study of the biology of diseases that involve abnormalities in blood flow, such as cancer and stroke, but also advance our understanding of the structures and functions of tissues throughout the body, they say.
The report was published on 10 February in Nature Methods.
“Usually, if you want to gather data on blood vessels in a given tissue and combine it with all of its surrounding context like the structure and the types of cells growing there, you have to relabel the tissue several times, acquire multiple images and piece together the complementary information,” says Arvind Pathak (Johns Hopkins University School of Medicine, Baltimore, USA), senior author of the study. “This can be an expensive and time-consuming process that risks destroying the tissue’s architecture, precluding our ability to use the combined information in novel ways.”
Researchers use many different imaging methods, such as magnetic resonance imaging (MRI), computed tomography (CT) and microscopy to study the role of blood vessels in the lab. These images are useful for understanding the dynamics of how tissues develop disease or respond to treatment. However, integrating the data available in these images has remained a challenge because agents used to make a blood vessel visible to one imaging method can make it invisible on other tools. This limits the amount of data researchers can gather from a single sample.
VascuViz overcomes this problem by making the structure of the largest arteries to the smallest microvasculature visible to a variety of imaging tools, which allows researchers to develop a multilayered understanding of blood vessels and related tissue components with less time and effort.
The development of VascuViz is particularly useful in creating computerised visualisations of how complex biological systems such as the circulatory system work, and is a hallmark of the growing field of “image-based” vascular systems biology.
“Now, rather than using an approximation, we can more precisely estimate features like blood flow in actual blood vessels and combine it with complementary information, such as cell density,” says lead author Akanksha Bhargava (Johns Hopkins University School of Medicine). To do this, VascuViz-based measurements are entered into computer simulations of blood flow, such as the cancer models Bhargava studies.
To create VascuViz, Bhargava tested several combinations of existing imaging agents and their suitability for different imaging methods. After multiple iterations, she found that a CT contrast agent named BriteVu and a fluorescently labelled MRI contrast agent called Galbumin-Rhodamine could be combined to create a compound that makes the macro- and microvasculature simultaneously visible when imaging with MRI, CT and optical imaging techniques without interference.
With the compound working in test tubes, the researchers then tested it in a variety of mouse tissues, perfusing it through the vascular system of breast cancer models, leg muscles, the brain and kidney tissues. The resulting images of the tissues acquired with MRI, CT and optical microscopy were then combined to create stunning 3D visualisations of the vasculature and associated components comprising these disease model and organ systems.
Due to VascuViz’s affordability and commercially available components, Pathak and his team hope it is globally adopted by scientists to help shed new light on different diseases involving the vasculature.
Other researchers involved in this study include Benjamin Monteagudo, Priyanka Kushwaha, Janaka Senarathna, Yunke Ren, Ryan Riddle and Manisha Aggarwal of the Johns Hopkins University School of Medicine.
This work was supported by the National Cancer Institute, the National Institute of Dental & Craniofacial Research and NIH Instrumentation grant and the Sidney Kimmel Comprehensive Cancer Center, Quantitative Sciences Pilot Project Grant.
Ra Medical Systems a medical device company focused on developing the excimer laser system to treat vascular diseases, has announced that enrollment has reached 95 subjects in the pivotal clinical trial to evaluate the safety and effectiveness of the DABRA excimer laser system as an atherectomy device for the treatment of peripheral arterial disease (PAD). The company also announces approval from the US Food and Drug Administration (FDA) to increase subject enrollment from 100 subjects to 125 subjects.
DABRA has been cleared by the FDA for crossing chronic total occlusion (CTOs) in patients with symptomatic infrainguinal lower extremity vascular disease and has an intended use for ablating a channel in occlusive peripheral vascular disease. The FDA defines atherectomy to include a prespecified improvement in luminal patency.
The open-label pivotal atherectomy clinical trial can enroll subjects with symptoms of PAD (Rutherford Class 2-5) at up to 10 sites. Outcome measures include safety, acute technical success and clinical success. The trial’s primary efficacy endpoint is the mean reduction in percent diameter stenosis in each patient’s primary lesion as measured by angiography immediately following treatment with DABRA and before any adjunctive treatment. The trial’s safety and clinical success endpoints are major adverse events at 30 days post-procedure and incidence of primary target lesion revascularization at six months.
Perfuze announced today that it has closed a €22.5 million Series A investment round—the proceeds from which will be used to drive the next stage of a US clinical study and regulatory clearance of its Millipede system. The funds will also be used to support ongoing development of new products and to initiate commercialisation of its technology.
The Series A funding was led by new investors LSP, investing from its LSP Health Economics Fund 2, and Seroba Life Sciences. The round was also supported by new investor SV Health Investors, investing from its Medtech Convergence Fund, and existing investors Earlybird, the HBM-MedFocus Fund, Enterprise Ireland and a syndicate of Irish business veterans and stroke physicians, according to a Perfuze press release.
With the closing of this Series A financing round, Anne Portwich, partner at LSP, and Daniel O’Mahony, partner at Seroba Life Sciences, will join the Perfuze board of directors, while Megan MacDonagh, senior associate at SV Health investors, will join as a board observer.
Wayne Allen, CEO of Perfuze, said: “We are delighted to have completed our Series A financing with such experienced investors, and this capital facilitates our continued growth and development. We believe that the Perfuze Millipede system is the next wave of thrombectomy technology in the rapidly growing stroke market and has the potential to positively impact the lives of thousands of stroke patients.”
According to the World Health Organization (WHO), stroke is the second leading global cause of death and a leading cause of disability, the release adds. Perfuze’s next-generation, catheter-based aspiration technology for the treatment of large vessel occlusion (LVO) acute ischaemic stroke aims to provide superior clinical outcomes in shorter procedural times, resulting in safe, cost-effective therapy.
In a press release by Front Line Medical Technologies, the company have announced the expanded availability and distribution of their COBRA-OS (control of bleeding, resuscitation, arterial occlusion system), as more physicians, including interventional radiologists, continue to implement the life-saving aortic occlusion device for various applications.
The COBRA-OS, which is approved by Health Canada and cleared by the U.S. Food and Drug Administration (FDA), is the first 4 French REBOA (Resuscitative Endovascular Balloon Occlusion of the Aorta) device and has the lowest profile on the market, according to the company. The device is guidewire-free and has a 25mm diameter compliant balloon with a uniquely designed Safety Shoulder Reservoir incorporated into the device to help prevent aortic rupture during inflation. Despite being so small, the device is also strong enough to hold back aortic pressure and allows for permissive hypotension in bleeding areas below the balloon. The device can be deployed quickly, in just over a minute, which is key in emergency situations.
In addition to permitting interventional radiologists the time to perform internal iliac artery embolization in hypotensive patients with unstable traumatic pelvic fractures, the COBRA-OS has been recently used prophylactically to treat a pregnant patient with placenta accreta, significantly reducing the risk to both mother and child.
Adam Power (Victoria Hospital in London, Ontario, Canada), vascular surgeon and co-inventor of the COBRA-OS, has successfully utilized the device with his interventional radiology colleagues in traumatic bleeding cases to help stabilise patients. As the device is so low profile, he has even been contacted to help with pediatric patients with uncontrolled bleeding.
“The COBRA-OS is a versatile tool that can be a swiss army knife for interventionalists. There is no other compliant balloon medical device in the world that goes through a 4 French sheath and can expand to 25mm diameter. I’ve even seen it be used coaxially in larger sheaths to occlude the aorta and allow interventions through the same single sheath which was pretty impressive,” said Power. “Access site complications are the bane of my existence as a vascular surgeon and I want to help lower their incidence, especially in extremely sick patients.”
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In light of recent and upcoming developments in the space, Vinson Wai-Shun Chan and Tze Min Wah (Leeds, UK) explore the evidence and latest progress in renal tumour biopsy (RTB), and discuss the treatment of small renal masses (SRMs) more broadly.
The optimal diagnostic pathway and treatments for small renal masses (T1N0M0) is controversial. Due to the lack of tumour markers and inability to determine malignancy from benign pathologies, SRMs are often over-treated. Yet, RTB has not been widely implemented into the diagnostic pathway of SRMs. In terms of treatment, partial nephrectomy remains the gold standard for curative surgery but is associated with significantly reduced renal function and high complication rates. Although high-quality evidence is lacking, percutaneous image-guided ablation (IGA) provides excellent oncological, perioperative, and renal function outcomes.
As a result of increased used of abdominal imaging, the rates of incidentally discovered SRMs have increased over the past decade. However, there is no reliable imaging or tumour markers to determine the lesion’s malignant potential. Further, it was shown that over 20% of these treated masses are benign in histology, suggesting significant overtreatment of patients without malignant disease. A systematic review and meta-analysis have reported that diagnostic core biopsies have a sensitivity and specificity of 99.1% and 99.7%, respectively, for malignancy. Despite the proven accuracy and safety profile of RTB, there is reluctance to implement RTB within the urological community.
The benefits of performing RTB before treatment is at least twofold. First, this can guide patient decision-making on whether to receive treatment. More than 90% of interviewed patients with SRMs have expressed that they believe knowing the mass’ histology status will aid decision-making for the optimal treatment. Secondly, given a malignant result for RTB, an RTB can guide the best treatment for the patient, where low-grade SRMs could opt for active surveillance or IGA; and high-grade SRMs could opt for partial or radical nephrectomy. In fact, the latest study of the EuRECA registry1 showed that, amongst patients undergoing ablation, the pre-cryoablation biopsy rate rose from 42% in 2015 to 72% in 2019 (p<0.001). Subsequently, patients are less likely to be overtreated for benign disease when more biopsies are performed (odds ratio [OR]=0.64, p<0.001).
This has shown promising potential in extending the use of preoperative RTB to other forms of SRM treatment—especially partial nephrectomy—avoiding the significant decline in renal function and high complication rates post-nephrectomy. However, it is important to stratify patients who will benefit the most from biopsies. For example, patients over the age of 70 or who are unfit to undergo definitive treatment for SRM may not benefit from RTB; while those with complex tumours or comorbidities may benefit from RTB to prevent complex, high-risk treatments in these patients.1
Since the introduction of image-guided radiofrequency ablation (RFA) in 1998, the technology of IGA has developed significantly to include multiple different energy sources including cryoablation, microwave, and irreversible electroporation (IRE).2 The advantages of IGA compared to partial nephrectomy are at least twofold. Firstly, IGA is significantly less invasive compared to partial nephrectomy, with significantly reduced complication rates.3 Secondly, IGA is associated with a significantly lesser drop in renal function, which is crucial in patients with bilateral (synchronous or asynchronous) disease, or those who require repeat treatments—such as Von-Hippel Lindau syndrome (VHL) patients.
However, there is a lack of high-quality evidence to support the oncological non-inferiority of IGA compared to partial nephrectomy. This could be due to a few reasons. Firstly, previous recruitment of various trials involving IGA has failed, notably in the SURAB and the CONSERVE studies, which could be a result of patient preferences and lack of evidence at the time to support the recruitment process. Secondly, as pointed out by a review performed by the European Association of Urology (EAU) Renal Cancer working group, the quality of observational studies and systematic reviews on the area is poor, notably affected by severe selection bias whereby younger and fitter patients tend to receive partial nephrectomy, compared to old and frail patients receiving IGA. Similarly, the latest systematic review and meta-analysis, published in the International Journal of Surgery, has suggested the same.3
Based on the limited quality of evidence on T1a SRMs, ablation is associated with similar cancer-specific survival, metastasis-free survival and disease-free survival compared to partial nephrectomy. Local recurrence-free survival is similar to partial nephrectomy patients with a follow-up of more than five years.3 Patients undergoing ablation also experience significantly less postoperative complications (risk ratio [RR]=0.72, p=0.02) and significantly smaller decline in renal function postoperatively (mean difference [MD]= -7.42, p<0.01).
Similarly, the long-term outcomes at our centre from 2003 to 2020 have shown similar outcomes, with overall survival, cancer-specific survival, local-recurrence free survival and metastasis-free survival in IGA at least as good as partial nephrectomy, with significantly better renal function preservation.4 Specifically, IGA is of use in patients with Von-Hippel Lindau syndrome—shown in the 17 patients who underwent IGA for VHL-associated renal cell carcinoma (RCC) and experienced excellent oncological outcome without the need for renal dialysis over 10 years of follow-up.5
The role of RTB and IGA has developed significantly throughout the last two decades; however, further research is required to consolidate the role of RTB and IGA in the treatment of SRMs. Firstly, RTB needs to be implemented in both research and clinical pathways. RTB can act as index tests for future diagnostic studies to facilitate development of new imaging modalities. For future interventional studies of new treatments, RTB will also allow focused research on RCC, rather than undifferentiated SRMs alone to improve the quality of evidence. Secondly, studies reporting outcomes from interventional oncology studies must conform to the CONSORT guidelines to allow for meta-analysis and further discussion of the data. Finally, urologists and interventional radiologists should work closely together to embrace and produce optimal outcomes for patients presenting with RCCs. Upcoming results from the NEST trial comparing the effectiveness of nephron-sparing surgeries and future research studies are highly anticipated.
References:
Vinson Wai-Shun Chan is a final year medical student in the School of Medicine in the Faculty of Medicine and Health at the University of Leeds in Leeds, UK.
Tze Min Wah is a professor, and senior consultant diagnostic and interventional radiologist, in the Department of Diagnostic and Interventional Radiology in the Institute of Oncology at St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, in Leeds, UK.
The authors declared no relevant disclosures pertaining to this article.
Inari Medical has announced that the first patient has been enrolled in PEERLESS prospective, randomised controlled trial (RCT) comparing the outcomes of patients with intermediate-high risk pulmonary embolism (PE) treated with the FlowTriever system versus catheter-directed thrombolysis (CDT).
The first PEERLESS patient was enrolled by Amir Kaki, interventional cardiologist, Ascension St John Hospital, Dearborn, USA. PEERLESS will randomise 550 patients and will also enrol up to 150 patients in a registry cohort for patients who cannot be randomised due to an absolute contraindication to thrombolytics. The trial will include up to 60 centres in the USA and Europe.
“We are excited and honoured to enrol the first patient in this landmark clinical trial,” said Kaki. “From our own experience, the FlowTriever system has the potential to change the way we treat PE patients, safely removing significant clot burden while avoiding thrombolytics and procedure-related ICU stay. Ascension St John’s research team continues to be on the cutting-edge of medical device research and we look forward to contributing and developing the evidence base for the treatment of pulmonary embolism.”
“The start of PEERLESS represents an exciting milestone in the advancement of PE treatment, where randomised clinical data evaluating relevant patient outcomes has been limited,” said global co-principal investigator, Carin Gonsalves, professor of radiology and co-director of the Division of Interventional Radiology at Thomas Jefferson University in Philadelphia, USA. “PEERLESS marks an opportunity to directly compare FlowTriever outcomes to CDT outcomes, addressing current gaps in our understanding of PE and providing critical information to clinicians on the optimal treatment for these patients.”
“The treatment of PE is undergoing a transformation. We have been thrilled by the desire of physicians to move this field forward and generate high-quality data through PEERLESS,” said Thomas Tu, Inari’s chief medical officer. “We are grateful for the collaboration and dedication of our clinical trial investigators on this first of many PE studies to come.”
A new study from Japan has become the first randomised controlled trial (RCT) to demonstrate the effectiveness of endovascular mechanical thrombectomy procedures in patients who have severe strokes involving clots in one or more large brain arteries. This preliminary, late-breaking research, which was presented at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA), found that patients who suffer a severe ischaemic stroke may regain far more function if their clots are mechanically removed in addition to standard medical therapy. An increased occurrence of intracranial haemorrhage was, however, also observed in patients who underwent a thrombectomy in the study.
“Our findings confirm that anyone who suffers from stroke should be transferred to a medical facility capable of endovascular therapy as soon as possible,” said senior author of the study Takeshi Morimoto (Hyogo College of Medicine, Nishinomiya, Japan)—who also presented these data at ISC 2022. “The benefit of endovascular therapy is not limited by the severity or region of a stroke. These patients may have the chance to more fully recover from stroke and go back to their previous lives and activity levels.”
In 2018, the American Heart Association (AHA) updated its stroke treatment guidelines to recommend endovascular therapy—which involves clot removal via mechanical thrombectomy—for select stroke patients, with a view to improving their odds of functional recovery. As per an AHA press release, effectiveness of the approach had previously been established for patients whose large-vessel clots disrupted blood flow to fewer areas of the brain. However, clinical experience was mixed for patients with more severe strokes whereby a clot interrupts blood flow to a large area of the brain.
“I have often encountered a dramatic improvement in a patient just after the mechanical clot removal procedure, even when the infarction area was large,” said Shinichi Yoshimura (Hyogo College of Medicine, Nishinomiya, Japan), lead author of the study. “Yet, patients sometimes also experienced severe haemorrhagic transformation [a life-threatening complication that occurs when blood from outside the brain crosses the blood-brain barrier and worsens stroke outcome] after the artery was reopened. So, in Japan, our stroke physicians are always cautious about endovascular therapy when the infarction area is large.”
In this randomised study, which has now also been published in the New England Journal of Medicine, 203 stroke patients (average age of 76 years; 44% women) were treated at 45 hospitals in Japan. Most of these patients (71%) were examined and had magnetic resonance imaging (MRI) or a CT scan of the brain within six hours after stroke symptoms were first noticed—the timeframe that patients are generally considered eligible for endovascular therapy. The other patients were seen between six and 24 hours after symptoms were noticed, and additional imaging showed areas of the brain that might benefit from prompt treatment.
On imaging, all patients were found to have clots blocking a large artery in the brain—either the internal carotid artery, the proximal middle cerebral artery, or both. The strokes were rated as severe (median score of 22 on the National Institutes of Health Stroke Scale [NIHSS], which assesses a patient’s ability to perform normal functions such as speaking and moving) and involved disrupted blood flow to large areas of the brain (about seven out of 10 regions).
After imaging, the patients were randomly selected to receive either standard medical care for stroke—consisting of providing intravenous fluids, controlling blood pressure and other risk factors, and administering clot-busting medications for select patients at lower risk of bleeding—or standard medical care plus endovascular therapy performed within an hour after imaging. Due to bleeding concerns, intravenous clot-busting medications were sparingly administered to select patients in a similar proportion in both treatment groups (27 of those who received endovascular therapy and 29 who received standard care).
Comparing the 100 patients who received endovascular therapy plus standard care with 102 on standard therapy alone, the analysis found:
In addition, several outcomes were compared to evaluate the safety of adding endovascular therapy to medical treatment, with researchers reporting:
“The finding of more intracranial bleeding in the patients who received endovascular therapy is very important,” Morimoto added. “However, there were haemorrhages with symptoms and some that caused no symptoms. The haemorrhages with no symptoms were detected on imaging conducted for this study in the endovascular treatment group, not in the standard practice group. Symptomatic intracranial haemorrhage still occurred more commonly among patients in the endovascular group, however, it was not a statistically significant difference from the standard care group.”
The results of this study may not be generalisable to the USA or western countries—because it was conducted in Japan, where there is less use of intravenous thrombolysis than in the USA and other western countries, and where more strokes are imaged with MRI compared to CT, perhaps leading to different estimates of how many brain regions are affected by the stroke, the AHA release states. Due to these differences in treatment protocols, this study’s results may over- or underestimate the effectiveness of endovascular therapy.
The researchers are currently performing sub-analyses to help identify factors that might signal which patients are more likely to have a greater return of function after the treatment. “In addition, tools, devices or rehabilitation methods that could potentially improve the likelihood for similar patients to recover with less disability should be investigated,” Morimoto said.
Cerenovus—a neurovascular firm that forms part of Johnson & Johnson Medical Devices Companies—has announced the launch of Emboguard, its next-generation balloon guide catheter to be used in endovascular procedures, including those for patients with acute ischaemic stroke.
Emboguard is designed to optimise removal of blood clots by controlling blood flow locally during mechanical thrombectomy procedures. Balloon guide catheters increase first pass recanalisation, reduce procedure time, and reduce the odds of clot fragments breaking off and causing distal emboli, according to a Cerenovus press release, which also details that distal emboli in an endovascular procedure can result in new ischaemic events.
“Without timely and effective treatment of stroke, patients can suffer from lifelong disability or dependency,” said David Fiorella (Stony Brook University Hospital, New York, USA). “The benefits of balloon guide catheters are becoming increasingly recognised for their ability to maximise patient outcomes. By adding this innovation to their stroke solutions portfolio, Cerenovus will be arming physicians with the tools they need to better serve our patients, potentially increasing the chances to live a functional and fulfilling life post-stroke.”
Emboguard is the latest addition to Cerenovus Stroke Solutions—a suite of technologies designed with compatibility in mind to assist physicians in performing mechanical thrombectomy procedures. Launched in 2020, it now includes the Embotrap III revascularisation device, the Prowler Ex microcatheter, and the Cerenovus large bore catheter as well as both the Emboguard balloon guide catheter and the Cerebase guide sheath.
The Emboguard balloon guide catheter is set to debut for the first time at the ongoing International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA).
NovaSignal Corporation has announced the results of a multicentre, prospective, single-arm study indicating that the company’s autonomous NovaGuide intelligent ultrasound is three times more likely to detect right-to-left shunt (RLS)—a recognised risk factor for stroke—than standard of care transthoracic echocardiography (TTE). These results were presented in a late-breaking science session at the International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA).
“In the stroke population, RLS detection—especially due to a patent foramen ovale (PFO)—is important to reduce the risk of future stroke,” said the study’s principal investigator Mark Rubin (University of Tennessee Health Science Center, Memphis, USA). “We have known for decades that transcranial Doppler (TCD) is exquisitely sensitive for RLS detection, but expertise is scarce. NovaGuide broadens the availability of TCD, allowing any provider to help their patients benefit from the sensitivity of TCD for RLS detection. The BUBL study results underscore the potential for using this diagnostic capability to improve the management of ischaemic stroke patients.”
The BUBL clinical trial assessed use of NovaGuide compared to TTE for RLS diagnosis. The study enrolled adults (≥18 years) who presented with neurological signs and symptoms, which included embolic stroke or transient ischaemic attack, on the differential diagnosis. The primary outcome was the percent shunt detection rate of NovaGuide relative to standard of care TTE.
Among the 129 evaluable participants, RLS detection rate was 63.6% with NovaGuide (82 patients) and 20.9% by TTE (27 patients) for a difference of 42.6% (95% confidence interval [CI]=28.6%–56.7%, p<0.001). Additionally, NovaGuide accurately identified 35 patients (27%) with intervenable shunts (Spencer Logarithmic Scale ≥3), while TTE identified 13 (10%) of these cases for a difference of 17.1% (95% CI=6.9%–27.2%, p=0.002). The primary safety endpoint of adverse events with NovaGuide was 0% (95% CI=0%–2.8%).
“Stroke care has advanced significantly in recent years, but those who have suffered a stroke have a high risk of recurrence,” said Robert Hamilton, chief scientific officer and co-founder of NovaSignal. “RLS is a known risk factor for stroke and these study findings underscore the importance of utilising NovaGuide as a diagnostic technology. It substantially improves detection of RLS compared to current standard of care. The results of this study suggest there may be many undiagnosed patients with RLS who are not receiving appropriate medical management with today’s diagnostic standards.”
Imperative Care has announced the launch of its Zoom POD aspiration tubing—the company’s latest innovation in elevating stroke care.
This is the newest addition to Imperative’s Zoom stroke solution, which is an ischaemic stroke product portfolio also including the Zoom 88 large distal platform for neurovascular access, four Zoom aspiration catheters in various sizes, and the Zoom pump with accessories.
The Zoom POD is the first and only sterile field clot filter device, according to Imperative, enabling faster time to clot capture during critical mechanical thrombectomy procedures for ischaemic stroke patients.
It is integrated into the aspiration tubing, shortening the distance from aspiration to filtration while maintaining full aspiration power. And, because it is positioned within the sterile field, the physician can immediately see the clot as it is extracted from the patient, quickly confirming clot capture and giving them more control over the thrombectomy procedure.
“Stroke care is all about speed. In order to achieve the best possible outcomes for patients, it is imperative to retrieve the clot from the brain quickly,” said Shahid Nimjee (The Ohio State University Wexner Medical Center, Columbus, USA).
“The Zoom POD will allow physicians like myself to visually confirm immediately, right within the sterile field, that the clot has been captured. Additionally, the ability to capture the clot in the Zoom POD allows me to easily take the clot back to the pathology lab, break it down, and analyse it.”
Mechanical removal of blood clots reduced post-stroke disability in nearly half of “all-comer” real-world stroke patients in a global study, according to preliminary late-breaking research presented at this year’s International Stroke Conference (ISC 2022; 9–11 February, New Orleans, USA).
“This study shows how much stroke thrombectomy has advanced,” said lead study author Raul Nogueira (University of Pittsburgh School of Medicine, Pittsburgh, USA). “We saw a wide range of cases, including patients who, not too long ago, would not be considered good candidates for thrombectomy based on older age, pre-existing disability or large size of the stroke on presentation. Our findings in this study expand thrombectomy to be considered for more stroke patients.”
Previous studies have found that stroke patients who received mechanical clot removal had less disability after three months than those who did not. However, according to an American Heart Association (AHA) press release, these studies were performed in carefully selected centres and employed strict clinical and imaging inclusion criteria—which decreases the generalisability of their findings.
To examine the effectiveness of blood-clot removal across a wide range of stroke patients seen in routine daily care, i.e., outside of a clinical trial, the EXCELLENT (Embotrap extraction and clot evaluation and lesion evaluation for neurothrombectomy) trial enrolled 1,000 adult ischaemic stroke patients (average age=70, 52% female) at 36 sites worldwide, from September 2018 to March 2021. The sites were a mix of thrombectomy-capable and comprehensive stroke centres. Patients were treated with a specific mechanical thrombectomy device called Embotrap (Cerenovus) in an unlimited time frame in the trial.
The study was designed to collect real-world treatment and did not exclude patients based on pre-stroke independence level, severity of stroke, location of the occlusion, or time between onset of stroke and treatment, researchers said. As per current guidelines, mechanical thrombectomy treatment can be used within 24 hours of symptom onset in select patients. In addition, the study analysed the characteristics of the removed blood clots and how that impacted stroke recovery.
The EXCELLENT trial found that most of the patients required only one attempt to remove the blood clot. However, it is common to require multiple attempts to completely remove the clot. In nearly half of all patients, clot removal resulted in slight/minimal disability (able to look after own affairs without assistance or no worsening from their pre-stroke condition), as gauged by a standard scale measuring level of disability 90 days after stroke.
The study also found blood clots that were rich in red blood cells and low in platelets resulted in less disability than blood clots composed of less red blood cells, or those rich in red blood cells and high in platelet content. In this study, only 10% of patients whose clots had a higher composition of red blood cell count and a lower composition of platelets died within 90 days, compared to 24% of patients whose clots had a lower composition of red blood cells and platelets. Among patients with higher red blood cell content, 63% with lower platelet content had either slight or no disability, compared to 51% with higher platelet content.
“We knew that fibrin was associated with more difficult clot removal. However, this novel observation that platelets may modify clot properties is very intriguing,” Nogueira added. “The results may have potential implications for technique and device selection when removing clots and the development of better blood-clot removal strategies.”
“I think the future success of ablation was truly unforeseeable, in 1986, when Tito Livraghi published his first paper about ethanol injection in a liver tumour. If we accurately match the energy source, the route of energy delivery, and imaging with the specifics of the lesion, we can treat lesions in almost every organ and anatomical space. Sometimes, it is necessary to enter the operating room together with the surgeon in order to get the best treatment results for the patient, but this should be seen as another opportunity—not an event to escape from,” says Laura Crocetti, associate professor of Radiology, Division of Interventional Radiology, Nuovo Santa Chiara University Hospital, Pisa, Italy. An internationally recognised ablation expert, she is also deputy chairperson of the European Conference on Interventional Oncology (ECIO) for 2022 and 2023.
What attracted you to a career in interventional radiology?
When I was in medical school, I was attracted by minimally-invasive treatments that enabled the possibility of curing patients with minimal damage and discomfort. The other passion I had was for technology and the latest developments on the horizon. So, when I heard of interventional radiology, I immediately realised that represented my future.
Could you share a positive and negative experience you have had as a woman in the interventional field?
I will start with a negative experience: I am a small-framed woman (my son says I am “short”) typically dressed in a non-slim-fit green working uniform and perhaps looking a few years younger than her age. Unfortunately, that is not what most patients expect when told they are scheduled to meet “professor” Crocetti, a “well-known” expert in the field of ablation who will perform the procedure. Still, an empathetic bond is almost always immediately formed, and they feel reassured and protected “in my hands”. Patients often witness their appreciation with very kind messages and emails afterwards.
The first surprise is unfortunately also sometimes observed in older, male leaders and colleagues who do not know you. Interestingly, you can seem transparent or invisible to their eyes. The important thing is that in the long term, I have always been able to convince my colleagues about my professional capacity and am very proud of this.
The positive experience as a woman physician often comes from everyday interactions with my female colleagues: the positive and supportive feeling is immediate and the desire to cooperate and work together is very strong. As female physicians, we are thorough, efficient, and well organised, and our results are usually very good!
What are the most important cancer imaging techniques that you see on the horizon?
I am extremely optimistic about the future of magnetic resonance (MR) and would like to emphasise its as-yet insufficiently explored aspects. Function, metabolism, and vascularisation can all be investigated with this technique. The vast amount of information that magnetic fields can provide is almost infinite. I am fortunate to have a very interesting opportunity to cooperate with the 7T consortium in Pisa (IMAGO 7) and the team really conveys that we are only at the beginning with MR. The application of MR in cancer imaging, for example before and after chemoradiotherapy or interventional radiology procedures, will remain a hot topic in the future.
Where do you see the greatest potential for ablative therapy?
I think the future success of ablation was truly unforeseeable, in 1986, when Tito Livraghi published his first paper about ethanol injection in a liver tumour. The potential of ablative treatments stem from their ductility combined with efficacy. If we accurately match the energy source, the route of energy delivery, and imaging with the specifics of the lesion (its size and location, roughly speaking), we can treat lesions in every organ and anatomical space. Sometimes, it is necessary to enter the operating room together with the surgeon in order to get the best treatment results for the patient, but this should be seen as another opportunity—not an event to escape from.
Do you see different niches for radiofrequency, microwave, and cryoablation?
Each ablative modality has its specificity. Generally speaking, at the moment my workhorse for the liver is microwave ablation, but for kidney, soft tissue, and prostate, I prefer cryoablation. I can see a future of selected microwave devices in thyroid and lung as well, but at the moment I still prefer radiofrequency here. A personalised approach for patient care includes not only choosing an interventional treatment and selecting the correct timing for it, but also picking from all the different energy sources and imaging approaches available to optimise treatment success.
What evidence would you like to see generated in your field of special interest–liver ablation?
Liver ablation is an area where we actually have quite a lot of evidence, especially when compared with other organs. Its efficacy and cost-effectiveness, for example, has been well established in hepatocellular carcinoma (HCC) and it is recognised in the major guidelines. I am very much looking forward to the results of the COLLISION trial, the noninferiority randomised study comparing ablation and resection in ablatable and resectable colorectal liver metastases of less than 3cm.
In the near future, I think we should produce evidence about the role of combination therapies including ablation and immunotherapy.
You have declared the International Accreditation System for Interventional Oncology Services (IASIOS) accreditation to be an important milestone for your hospital. Why?
IASIOS accreditation is a way of demonstrating first to us and then to the global community that the interventional oncology service we provide is of high quality and meets rigorous international standards. It helps to improve the whole process of patient care and treatment and is specifically designed for medical facilities offering interventional oncology. Accreditation already exists for other specialties or services, and it is extremely important to have it already up and running for interventional oncology.
As deputy chairperson for ECIO 2022 (24–27 April, Vienna, Austria), what would you like the programme to reflect?
ECIO is by definition a multidisciplinary meeting and the programme will reflect this special attitude of the congress. All topics will be addressed from multiple points of view and there will also be lots of opportunities to speak about ongoing research and new technologies. It is really a privilege for me to work with Philippe Pereira, the chairperson of ECIO 2022, to prepare the programme (www.ecio.org).
Could you describe a memorable case that has stayed with you?
It is the first liver radiofrequency ablation I performed many years ago, for sure. My heart was beating very fast…but everything went smoothly. I also recall all the difficult cases, those in which I had complications; I remember them all very well. Many of my patients have, fortunately, been able to live with a very long disease history and two of them, in particular, have become family friends. It has been very difficult to say to them that there was nothing further I could offer them and their families from an interventional treatment perspective.
What are your interests outside of medicine?
I love the sea, and particularly enjoy fishing and have a licence for a boat. My other passion is music and I am a conservatory graduate in piano. Hiking with my husband, Francesco, and son, Aurelio, is a family activity we enjoy together.
Percutaneous hepatic perfusion with melphalan for the treatment of metastatic uveal melanoma (mUM) offers a hepatic response rate of 66.7% and good progression-free survival (PFS). This is the main concluding finding of a recent retrospective analysis published in Melanoma Research—which the authors claim includes the largest number of mUM patients treated in a single centre with melphalan percutaneous hepatic perfusion (M-PHP) to date worldwide.
Carrying a poor prognosis, uveal melanoma (UM) is the most common primary ocular malignancy in adults, according to Sachin Modi and Brian Stedman (University Hospital Southampton NHS Foundation Trust, Southampton, UK) et al. 50% of patients with UM develop metastatic disease, which has a 10‒25% one-year survival rate with no standard established treatment. According to the authors, previous studies have demonstrated M-PHP to be effective for mUM for liver predominant disease, however, it is highlighted that existing research is limited by small sample populations. Modi et al specify that their analysis, therefore, illustrates findings on the safety and efficacy of M-PHP in a sample population of 83 patients, which is the largest number of mUM patients treated in a single centre with M-PHP to date worldwide.
All patients with diagnosed mUM who received M-PHP between August 2012 and September 2020 at the University Hospital Southampton NHS Foundation Trust were included in this retrospective study.
Patients with the non-progressive single-site extrahepatic disease were also included. All patients received 3mg/kg of melphalan, which was delivered with the Hepatic CHEMOSAT Delivery System (Delcath Systems) with the GEN 2 filter (see Figure 1). The authors note that liver function and full blood count were monitored in all patients’ weekly following treatment, with repeat computerised tomography (CT) and magnetic resonance imaging (MRI) every six to 12 weeks to monitor the tumour and overall response, as per RECIST guidelines. The disease control rate (DCR) was calculated as the proportion of patients with complete response (CR) to treatment, partial response (PR), or stable disease (SD) for at least nine weeks. Further M-PHP sessions were planned at six to 10-week intervals, on the presentation of no disease progression.
A total of 252 treatments with M-PHP were performed across 83 patients (aged 18 to 80), with a median of three M-PHP cycles per patient—two patients experienced a single incomplete treatment, resulting in a total patient number of 81. The median patient age was 59.3 years old (±12.2 years), consisting of 36 (44.4%) males. It is noted that 69 (85.2%) patients presented only intrahepatic disease at the time of workup, however, 12 (14.8%) patients had both intrahepatic and single organ extrahepatic disease.
Modi et al report a median follow-up time of 12.9 months across all patients, with a median time of 13.9 months follow-up time for patients still alive. At the data collection cut-off date (1 January 2021), a total of 15 (18.5%) patients were still alive, three were still continuing M-PHP treatment, with 66 (81.5%) deaths. The overall survival (OS) median was 14.9 months from the first treatment—and OS rates were 62% and 27% at one and two years, respectively.
The authors note that the OS was significantly different (p<0.0001) across hepatic responses, with the overall response rate at 49/81 (60.5%) patients. For CR, the response time was 34.7 months, compared to 16.9 months for PR, 10.6 months for SD, and 7.7 months for progressive disease (PD). A total of 7/81 (8.6%) patients presented the best overall response—CR. A total patient number of 42/81 (51.9%) demonstrated PR, 16/81 (19.8%) for both SD and PD. Hepatic only CR was seen in 10/81 (12.3%) patients and PR was present in 9/81 (11.1%) patients.
In conclusion, the analysis presents an overall response rate of 60.5% (49/81), hepatic disease control rate of 88.9% (72/81), and hepatic response rate of 66.7% (54/81) with M-PHP. The median overall PFS and OS were 8.4 and 14.9 months respectively. The authors report no fatal treatment-related adverse effects (TRAE), however, 43 grade three (n=29) or four (n=14) TRAE occurred in 23 (27.7%) patients, presenting a significant reduction in these events in procedures performed between 2016–2020 vs. 2012–2016 (0.17 vs. 0.90 per patient, p<0.0001). Modi et al suggest M-PHP for mUM exhibits “excellent response rates” and PFS, compared to available treatments.
Stedman said “with such a large series the Southampton team have now demonstrated this treatment can be delivered safely with very few side effects. Patients tolerate the procedure with no impact on performance or quality of life. Having proved the technology works on one of the most chemo-resistant cancers, the team is keen to demonstrate its efficacy in other tumour types.”
“We are happy to report these findings which show impressive response rates with improvement in safety and complications with experience. We hope with this new data and the upcoming data from the international FOCUS study (due to be reported Q4 2022) will lead to better access for this treatment for patients on the NHS and worldwide” added Modi.
From an oncologist’s perspective, co-author Matthew Wheater (University Hospital Southampton NHS Foundation Trust, Southampton, UK) commented that “metastatic uveal melanoma has been a real challenge to treat, with little response to the agents that have shown such promise in cutaneous melanoma. The randomised data showing a survival benefit for tebentafusp is a significant step forward, however radiological responses to treatment are rare. Our paper shows that melphalan-PHP can induce significant responses in liver metastases, is safe to deliver and well tolerated by patients, providing meaningful quality of life. We eagerly await the final survival results of the Focus trial and hope that if this confirms our findings then melphalan PHP will become a mainstay of treatment for ocular melanoma with wider availability of treatment to benefit more patients.”
Concept Medical recently announced that the SIRONA randomised controlled trial (RCT; Head-to-head comparison of sirolimus versus paclitaxel drug-eluting balloon angioplasty in the femoropopliteal artery) has completed half the targeted enrolment.
According to a company press release, SIRONA is the world’s first and largest head-to-head RCT investigating the use of a sirolimus drug-coated balloon (DCB; Magic Touch PTA, Concept Medical) vs. a paclitaxel DCB (CE-certified devices) for the treatment of femoropopliteal occlusive artery disease.
The investigator-initiated and -driven trial, led by Ulf Teichgräber (Jena University Hospital, Jena, Germany) aims to evaluate the safety and efficacy of a sirolimus DCB against a paclitaxel DCB in stenosed or occluded lesions in the superficial femoral artery (SFA) and/or popliteal artery in peripheral arterial disease (PAD) patients with Rutherford class 2–4.
Marianne Brodmann (University of Graz, Graz, Austria) enrolled the 239th patient on 23 November 2021, making the trial halfway towards its target of enrolling 478 patients set to be randomised in 1:1 fashion across 30 sites in Germany and Austria.
Thomas Zeller, site investigator of Universitäts-Herzzentrum Freiburg in Bad Krozingen, Germany, expresses his thoughts on the importance of the trial: “The SIRONA trial substantially contributes to evaluating the effectiveness of an alternative antiproliferative coating (sirolimus) for balloon catheters to treat femoropopliteal stenoses and occlusions compared to the current gold standard of a paclitaxel coating. Especially with regard to the still ongoing safety discussion, SIRONA represents the first head-to-head comparison and therefore is of high scientific and clinical relevance, and is fortunately widely accepted by study patients as the recruitment status demonstrates.”
Teichgräber adds: “I am convinced that SIRONA represents a game-changing trial for PAD.”
Sirtex Medical has announced with Grand Pharmaceutical Group Limited, that SIR-Spheres Y-90 resin microspheres have been approved by the national medical products administration (NMPA) for the treatment of patients with colorectal cancer liver metastases.
According to a recent press release, the NDA approval of SIR-Spheres for the Chinese market is the first therapeutic radiopharmaceutical approved by the NMPA in 2022 and is the only radioactive microsphere product approved by the NMPA based on clinical trial data obtained outside of China. The first procedure of selective internal radiation therapy (SIRT) using SIR-Spheres in China was successfully performed in September 2021, which at that time utilised the pilot implementation policy for commercialised medical devices in Hainan.
According to GLOBOCAN 2020, there were 410,000 new cases of liver cancer with 390,000 deaths in China. Additionally, in 2020, there were over 550,000 new cases of colorectal cancer with more than 280,000 deaths in China. Those morbidity and mortality rates are about twice as high as average global rates.
“The prognosis for patients suffering from liver cancer in China is poor, with the five-year survival rate being roughly 12%,” notes Dr. Tang Weikun, Chairman of the Board at Grand Pharmaceutical Group Limited. “The use of SIR-Spheres to downstage liver tumors to the point where they can be surgically removed has been well documented in other countries. Our hope is that by expanding the reach of SIR-Spheres to China, we will have a similar impact, with improved treatment outcomes and survival rates among patients diagnosed with liver tumors.”
Royal Philips has announced an update to its handheld ultrasound platform—Lumify—adding Pulse Wave Doppler technology to expand the haemodynamic assessment and measurement capabilities of the system.
In a press release, Philips said that the new functionality would enable clinicians to quantify blood flow in a wide range of point-of-care diagnostic applications including cardiology, vascular, abdominal, urology, obstetrics and gynecology.
Pulse Wave Doppler ultrasound provides clinicians with more information, in addition to 2D and colour imaging, to assess haemodynamic patterns to differentiate between arterial and venous blood flow and quantify haemodynamic function, Philips detailed in a press release. An additional update to the system includes obstetric measurements to help in early assessment of gestational age and the identification of high-risk pregnancies.
“By applying Philips’ expertise in cardiovascular care, imaging and patient monitoring to Philips Handheld Ultrasound—Lumify—we are committed to deliver a dedicated, innovative point-of-care portfolio, enabling clinicians to quickly assess haemodynamics—including cardiovascular function, organ perfusion and fetal assessment—in a daily routine, to identify abnormalities and intervene quickly,” said Matthijs Groot Wassink, general manager of Point of Care Ultrasound at Philips. “With the addition of Pulse Wave Doppler and enhanced obstetrics measurements, we have increased the number of markers on which diagnoses can be made, to deliver high quality imaging and enhance the evaluation and effectiveness of treatment in real-time.”
“Having Colour Flow Doppler (CFD) and Pulse Wave Doppler on a handheld device is game changing, allowing clinicians to take point-of-care ultrasound examinations to the next level,” said Robert Jones, professor of Emergency Medicine at the MetroHealth System, Cleveland, USA.
Regio Biosciences, a Hibiscus BioVentures company, recently announced it has entered into an exclusive license agreement with AstraZeneca to further develop REG-101, a novel therapeutic acting on reverse cholesterol transport. Regio expects to initiate a Phase 2a clinical programme evaluating REG-101 in peripheral arterial disease (PAD) during the second half of 2022.
Under the terms of the agreement, AstraZeneca will provide an exclusive license to Regio for further development of REG-101, previously known as MEDI5884, to address patients with high unmet medical needs, including PAD and cardiovascular disease. Regio will be solely responsible for all research, development, and commercial activities of REG-101. Initial financing for Regio’s development activities is being provided via investment by Hibiscus Capital Management (HCM Fund II) and Innoforce.
“The Regio team is thrilled to announce the signing of this license agreement with AstraZeneca to further develop REG-101,” said Chris Jeffers, chairman of Regio Biosciences and CEO of Hibiscus BioTechnology. “We believe that REG-101 could complement the current standard of care as a patient-centric, once-monthly injection for peripheral artery disease.”
“PAD currently has few pharmaceutical options, and without appropriate treatment, symptoms of PAD can progress from pain while walking to gangrene and limb loss,” said Rakesh Dixit, president and CSO of Regio Biosciences. “We believe reducing the size of cholesterol-rich plaque within peripheral arteries using REG-101 has the potential to directly and positively address the underlying pathophysiology of PAD.”
Regio has partnered with CPC Clinical Research (CPC) and multiple clinical sites in the USA to conduct a phase 2a clinical trial in patients with PAD. “Despite current standard of care therapies that address control of blood pressure, LDL [low-density lipoprotein] cholesterol levels, and clotting risks, there are currently no available pharmacological treatments targeting reverse cholesterol transport to target the plaque that underlies the adverse effects negatively impacting millions of patients,” said cardiologist and vascular medicine specialist Marc P Bonaca (University of Colorado Anschutz Medical Campus, Aurora, USA), who serves as the executive director of CPC Clinical Research and CPC Community Health. “As a clinician, I believe a therapeutic that improves function, reduces the need for recurrent limb interventions as well as other adverse cardiovascular outcomes could provide meaningful improvements for patient quality of life.”
Humacyte today announced results from the first series of compassionate use cases of the company’s investigational Human Acellular Vessel (HAV) for the treatment of chronic limb-threatening ischaemia (CLTI) and vascular trauma.
The HAVs were observed to remain patent and infection free in patients requiring vascular reconstruction, thereby highlighting the potential of the HAV to expand limb salvage options for patients who have exhausted current revascularisation conduit options, a company press release communicates. These results were presented at the 46th Annual Winter Meeting of the Vascular and Endovascular Surgery Society (VESS; 27–30 January, Snowmass, USA).
Humacyte details that their HAVs are engineered replacement vessels being designed to be durable, infection-resistant and off-the-shelf to address long-standing limitations in vessel tissue repair and replacement. The company reports that, under the US Food and Drug Administration’s (FDA) expanded access programme (EAP), the HAV has been implanted in more than 20 patients to address multiple severe vascular repair, reconstruction and replacement conditions when there is not a suitable conduit available for treatment.
The results of eight of these EAP patients were reported at the VESS meeting by Alexander Kersey (Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, USA), in a presentation, titled, “Real-world experience with the Human Acellular Vessel: A bioengineered implant for arterial repair that expands limb salvage options.”
Each of the patients had severe peripheral arterial disease (PAD) or vascular injury requiring vascular reconstruction but lacked other treatment options and were at risk for limb loss. In this high-risk group of patients, five of the bypasses performed with the HAV currently remain patent (with follow-up times ranging from four to 20 months after surgery), and no incidences of infection of the HAV were noted. Researchers treating these patients concluded that the HAV may greatly expand opportunities for limb salvage in trauma and urgent vascular reconstruction when patients lack suitable alternative conduits.
“Many patients who require urgent vascular reconstruction due to vascular injury or severe PAD are not candidates for synthetic vascular grafts or autologous vein grafts, and those who have exhausted other treatment methods are at high risk of amputation,” said Kersey. “There is considerable need for a new treatment option to avoid resorting to amputation, and results from these compassionate use cases merit additional research into the role the HAV may play in the future of limb-sparing surgery.”
In addition to infection resistance and durable patency, the presentation highlighted the potential clinical utility of the HAV that can be implanted using normal surgical procedures as a readily available, biological alternative for patients at high risk for amputation.
The HAV is currently being evaluated in late-stage clinical trials in vascular trauma repair, arteriovenous access for haemodialysis, and PAD. Humacyte advises that the HAV is an investigational product candidate and is not currently approved for sale by the FDA or any international regulatory authority.
January’s top 10 features technological advancements, with Cook Medical receiving US Food and Drug Administration (FDA) approval for new drug-eluting stents and Adept Medical launching Lower Leg Support for patients with peripheral artery disease. In addition, Inari Medical announced positive six-month FLASH registry patient outcome data following treatment of pulmonary embolism with FlowTriever, and Ajax Health has appointed two leading cardiovascular professionals to Cordis-X.
1) Cook Medical receives FDA breakthrough designation for new drug-eluting stent
Cook Medical has received breakthrough device designation from the US Food and Drug Administration (FDA) on a new drug-eluting stent for below the knee. This new stent is designed to treat patients suffering from chronic limb-threatening ischaemia.
2) Fundamental IR techniques help provide invaluable treatment options for animals
Peter Littler (Newcastle, UK) talks to Gerard McLauchlan (Surrey, UK) and Alex Horton (Surrey, UK) regarding veterinary interventional radiology (IR) following a special session titled “All Creatures Great and Small: IR for animals” at the British Society of Interventional Radiology annual scientific meeting (8–10 December, Glasgow, UK).
3) Adept Medical launches Lower Leg Support for PAD patients
Adept Medical has unveiled the Lower Leg Support solution, which is designed to assist with peripheral artery disease (PAD) interventions.
4) ISET 2022 audience hears latest data on endovascular therapies
At this year’s International Symposium on Endovascular Therapy (ISET 2022; 16–19 January, Hollywood, USA), experts presented an array of late-breaking trial results on topics ranging from venous stenting to abdominal aortic aneurysm sac sealing.
5) Improving interdepartmental communication to avoid forgotten ureteric stents
There are some very serious risks associated with forgotten ureteric JJ stents. David Maudgil, a consultant interventional radiologist at Wexham Park Hospital, Frimley Health Foundation Trust (Slough, UK), outlines why and when these devices are used, explains the risks a forgotten stent might pose, and provides some guidance on how to mitigate such risks.
6) Embolization comes knocking on knee pain’s door
A wealth of data emerging in the last 18 months, including from a small multicentre, randomised study of genicular artery embolization for knee pain secondary to osteoarthritis, brings a glimpse of other similar minimally invasive options to treat disability in the entire musculoskeletal system. Embolization, which is rapidly surfacing as a safe and effective procedure for the treatment of patients with osteoarthritis of the knee, has been shown to be technically achievable, with very promising outcomes at early follow-up.
7) Philips integrates cloud-based AI and 3D mapping into its mobile C-arm system series
Royal Philips has announced physicians will now have access to advanced new 3D image guidance capabilities through the image-guided therapy mobile C-arm system—Zenition, aiming to improve the outcomes for patients undergoing endovascular treatment. The company has signed a strategic partnership agreement with Cydar, a provider of cloud-based procedure maps software to plan and guide surgery in real-time.
8) BD launches Crosser iQ CTO recanalisation system
BD (Becton, Dickinson, and Company) has announced the launch and 510(k) clearance from the US Food and Drug Administration (FDA) of the Crosser iQ chronic total occlusion (CTO) recanalisation system, which is designed to cross peripheral artery CTOs intraluminally.
9) Six-month registry interim data flash early thrombectomy safety in pulmonary embolism patients
Inari Medical has announced positive acute and long-term interim results from the first 500 pulmonary embolism patients enrolled in the FlowTriever outcomes registry (FLASH).
10) Jeremy Durack and John Simpson to join Cordis-X innovation accelerator
Ajax Health has announced the appointments of two cardiovascular professionals to Cordis-X, an independent accelerator created to drive innovation and growth to Cordis.
Fluidx Medical Technology has announced the results of the GPX-Clear embolic device in-vivo research which uses the base GPX technology and incorporates an intermediate-term radiopacity agent, as described by the company.
“Our initial in-vivo work with GPX-Clear looks very promising. It has the advantages of the baseline GPX product around ease of use, minimal preparation, and compatibility with standard microcatheters, with the added benefit of radiopacity that dissipates within the first 24 hours,” said Ryan O’Hara, an interventional oncologist at the University of Utah (Salt Lake City, Utah).
According to O’Hara, “There are many instances, particularly in oncology, in which clear visibility of the treated region post-embolisation is critical and can be obscured by radiopacity agents. This is an exciting future product in the GPX line-up and the first product of it’s kind.”
The GPX-Clear embolic device leverages the core GPX technology as well as incorporates a non-artifact-inducing radiopacity agent. The radiopacity agent is trapped within the polymer matrix, providing excellent visibility of the embolic device during and post-embolic delivery—the radiopacity agent then dissipates within 24 hours post-delivery, enabling unobstructed visibility of the treated area.
According to the company, the GPX embolic device is an innovative embolic designed for simple preparation and controlled delivery. The company describes that the device is packaged ready-to-use in a syringe, can be prepped tableside by the clinician in about 30 seconds, does not require dimethyl sulfoxide (DMSO) precipitation, and may be delivered through standard microcatheters. The company note, GPX is therefore designed to occlude blood vessels independent of a patient’s coagulation status.
The GPX embolic device is under development and does not have marketing clearance or approval in any market at this time.
January’s top 10 features technological advancements, with Cook Medical receiving US Food and Drug Administration (FDA) approval for new drug-eluting stents and Adept Medical launching Lower Leg Support for patients with peripheral artery disease. In addition, Inari Medical announced positive six-month FLASH registry patient outcome data following treatment of pulmonary embolism with FlowTriever, and Ajax Health has appointed two leading cardiovascular professionals to Cordis-X.
1) Cook Medical receives FDA breakthrough designation for new drug-eluting stent
Cook Medical has received breakthrough device designation from the US Food and Drug Administration (FDA) on a new drug-eluting stent for below the knee. This new stent is designed to treat patients suffering from chronic limb-threatening ischaemia.
2) Fundamental IR techniques help provide invaluable treatment options for animals
Peter Littler (Newcastle, UK) talks to Gerard McLauchlan (Surrey, UK) and Alex Horton (Surrey, UK) regarding veterinary interventional radiology (IR) following a special session titled “All Creatures Great and Small: IR for animals” at the British Society of Interventional Radiology annual scientific meeting (8–10 December, Glasgow, UK).
3) Adept Medical launches Lower Leg Support for PAD patients
Adept Medical has unveiled the Lower Leg Support solution, which is designed to assist with peripheral artery disease (PAD) interventions.
4) ISET 2022 audience hears latest data on endovascular therapies
At this year’s International Symposium on Endovascular Therapy (ISET 2022; 16–19 January, Hollywood, USA), experts presented an array of late-breaking trial results on topics ranging from venous stenting to abdominal aortic aneurysm sac sealing.
5) Improving interdepartmental communication to avoid forgotten ureteric stents
There are some very serious risks associated with forgotten ureteric JJ stents. David Maudgil, a consultant interventional radiologist at Wexham Park Hospital, Frimley Health Foundation Trust (Slough, UK), outlines why and when these devices are used, explains the risks a forgotten stent might pose, and provides some guidance on how to mitigate such risks.
6) Embolization comes knocking on knee pain’s door
A wealth of data emerging in the last 18 months, including from a small multicentre, randomised study of genicular artery embolization for knee pain secondary to osteoarthritis, brings a glimpse of other similar minimally invasive options to treat disability in the entire musculoskeletal system. Embolization, which is rapidly surfacing as a safe and effective procedure for the treatment of patients with osteoarthritis of the knee, has been shown to be technically achievable, with very promising outcomes at early follow-up.
7) Philips integrates cloud-based AI and 3D mapping into its mobile C-arm system series
Royal Philips has announced physicians will now have access to advanced new 3D image guidance capabilities through the image-guided therapy mobile C-arm system—Zenition, aiming to improve the outcomes for patients undergoing endovascular treatment. The company has signed a strategic partnership agreement with Cydar, a provider of cloud-based procedure maps software to plan and guide surgery in real-time.
8) BD launches Crosser iQ CTO recanalisation system
BD (Becton, Dickinson, and Company) has announced the launch and 510(k) clearance from the US Food and Drug Administration (FDA) of the Crosser iQ chronic total occlusion (CTO) recanalisation system, which is designed to cross peripheral artery CTOs intraluminally.
9) Six-month registry interim data flash early thrombectomy safety in pulmonary embolism patients
Inari Medical has announced positive acute and long-term interim results from the first 500 pulmonary embolism patients enrolled in the FlowTriever outcomes registry (FLASH).
10) Jeremy Durack and John Simpson to join Cordis-X innovation accelerator
Ajax Health has announced the appointments of two cardiovascular professionals to Cordis-X, an independent accelerator created to drive innovation and growth to Cordis.
MedAlliance has acquired its partner MDK Medical, a Japanese vascular specialist company. MDK Medical has previously worked closely with MedAlliance in developing Japanese clinical studies for its novel sirolimus drug-eluting balloon (DEB) Selution SLR in the treatment of peripheral arterial disease (PAD).
The first Selution SLR study was initiated in July 2020 and involved 134 patients. Enrolment was completed in September 2021. Its objective is to assess the safety and efficacy of Selution SLR in the treatment of lesions of superficial femoral arteries and/or popliteal arteries. The acquisition will facilitate expansion of the Japanese clinical trial programme, which will include diseases of the inferior femoral artery, arteriovenous (AV) fistula access used for kidney dialysis and a drug eluting balloon for the treatment of erectile dysfunction.
“We are very excited to have acquired MDK Medical, as we now have direct access to the Japanese market”, said MedAlliance chairman and CEO Jeffrey B Jump. “We will be focusing on gaining approval for Selution SLR in Japan, one of the world’s most important markets”.
Selution SLR was awarded CE mark approval for the treatment of PAD in February 2020 and for the treatment of coronary arterial disease in May 2020. The US Food and Drug Administration (FDA) has awarded Selution SLR with four breakthrough designations: for the treatment of atherosclerotic lesions in native coronary arteries; coronary in-stent restenosis; peripheral below-the-knee and AV fistula indications.
In August 2021, the first of over 3,000 patients was enrolled in a coronary randomised controlled study comparing Selution SLR with limus drug-eluting stents (DESs). According to MedAlliance, this is the largest DEB study ever initiated and has the potential to change medical practice.
The US Food and Drug Administration (FDA) has issued two final guidances providing recommendations for including patient perspectives in medical device clinical studies.
As per an FDA press release, the finalised version of the first of these two guidance documents, entitled “Patient Engagement in the Design and Conduct of Medical Device Clinical Studies”, features key points including:
The second of these two newly issued guidances, entitled “Principles for selecting, developing, modifying, and adapting patient-reported outcome instruments for use in medical device evaluation”, intends to:
According to a press release, Texray radiation protection equipment reduces radiation dose by up to 97% during clinical interventions. This was the main concluding finding of a study led by Felix Bärenfänger (Klinikum Dortmund, Dortmund and University of Witten/Herdecke, Witten, Germany) and colleagues and published in the European Journal of Radiology.
The Texray headband (HeadPeace), and an extended thyroid collar (MindPeace), were evaluated during 20 general radiological and 32 neuroradiological interventions. The clinical evaluation concluded a significant dose reduction of 80–90%, with an average of 81.2±11.1% (general radiology) and 92.1±4.2% (neuroradiology).
It is reported the study revealed a radiation exposure of the head and neck area with cumulative local dose values up to 4.4mSv, in a relatively small sample of procedures. According to the press release, this value is surprisingly high, given that experienced operators performed the interventions, and lead protection shields were used in all procedures.
“We believe that an additional device for the head area is reasonable because usage of the devices yielded effective protection. I was really surprised to see how much scatter radiation is still arriving on the performing physician, although we are already using all these different lead shields and radiation protection devices,” concludes senior author Stefan Rohde (Klinikum Dortmund, Dortmund and University of Witten/Herdecke, Witten, Germany).
We are facing several problems in the field of clinical oncology research, by which I mean that study results are being collected, analysed and reported in many different ways, and we tend not to speak the same language within our discipline, writes Robbert S. Puijk (Amsterdam University Medical Centers and OLVG Hospital, Amsterdam, The Netherlands). These shortcomings are the reason we took the initiative to develop new guidelines regarding preferred clinical outcome measures following image-guided tumour ablation.
Image-guided thermal and non-thermal tumour ablation techniques have become indispensable therapeutic options for a variety of cancer types. For smaller-size malignant tumours, international guidelines have already adopted thermal ablation as a first-line treatment option1-7. The continuing emergence of novel treatment options and growing demand for minimally invasive image-guided tumour ablation techniques have raised the need for evidence-based IO, and with that comes the need for clear documentation of oncologic outcome parameters.
Shortcomings in how to collect, analyse and report data were the motive for our team to develop a modified Delphi consensus project8 in order to provide a framework of key opinion leader recommendations on patient-, procedure-, and tumour-related definitions, starting and ending time definitions, survival time definitions, time-to-event end points, and patient-reported outcome measures. The team consisted of members of the Society of Interventional Oncology (SIO), two independent epidemiologists and Carine Bellera, biostatistician from the French-based Definition for the Assessment of Time-to-Event End Points in Cancer Trials (DATECAN) group.
A total of 62 IO experts from Europe, the United States and Asia, working in 48 centres, eventually joined the evaluating committee. The panellists were asked to rate multiple statements and to provide additional comments whenever desirable. The article can be found online as open access publication in the Radiology journal.
To make the purpose and final results of this project clear, I can provide a few common practical examples which we hope to have solved by now. One of the most straightforward, but misleading, situations is when overall survival, for example for locally advanced pancreatic cancer, is analysed using the date of diagnosis to the date of death in one study and the date of the interventional procedure to the date of death in the other study. In order to compare survival probabilities in terms of Kaplan-Meier estimates and avoid misinterpretations as mentioned earlier, the experts reached consensus on starting and ending time definitions by documenting the time from the date of detection of disease (diagnosis), the date of the start of neo-adjuvant or induction therapy, and the date of the first intervention.
Another confusing situation might occur when different outcome measures are misused or used interchangeably, such as local tumour progression-free survival (LTPFS), primary- or secondary technique efficacy and local control. LTPFS is intended to reflect the effectiveness of the first local treatment, while local control should be used to reflect the final success after additional overlapping (completion) procedures (+/- alternative treatment methods). Furthermore, we tend to merely analyse and report a variety of outcome measures and procedure- or tumour-related outcomes per patient only while results of this article show that this is strictly speaking incorrect. To overcome this issue the experts reached consensus on whether to address outcomes per patient, per session or per tumour. As previously published by Muneeb Ahmed and colleagues, efficacy of a certain ablation device or image-guiding technique to eradicate tumours can best be illustrated by comparing the time to local tumour progression.9 Suppose a situation where a patient has been locally treated for three liver metastases and local tumour progression is being analysed and reported on a per patient basis. In this case, progression of one of the three tumours already counts as an event while the other two tumours where treated successfully, leading to an impractical LTPFS curve while comparing data analysed and reported on a per tumour basis. Therefore, and for the fact that multiple index tumours in one patient cannot be regarded as independent as these tumours are potentially correlated, the experts agreed that one should address and report several parameters both on a per patient and per tumour basis.
Another common issue is related to the fact that, prior to our article, no clear agreements have been made concerning the documentation of complications in the field of IO, as opposed to surgical series where the Clavien-Dindo classification is established to be used.10 Although consensus was not reached for the preferred validated classification system to document, analyse, and report complications and adverse events, the experts have agreed that one should indicate the most recent version of a certain validated classification system so that complications and adverse events can be categorised consistently according to severity, time of occurrence, and likelihood of the event being related to the procedure.
We believe that the clear definitions in these comprehensive guidelines will undoubtedly provide a necessary foundation for scientific reproducibility between randomised and retrospective studies as they will ensure an objective and reliable interpretation of results, allow for accurate comparison of outcomes, and avoid misinterpretations among physicians and researchers. The interchangeable setup of this current consensus document allows us to follow up this project regularly and, hopefully in the near future, helps us to extend these guidelines to regional and systemic cancer treatments to eventually attract the participation of other (inter)national medical societies. Therefore, we encourage all of our colleagues to adopt the recommendations outlined in this proposal in order to facilitate universal communication of scientific advances in the field of clinical oncology research.
Robbert S Puijk is an interventional radiology resident at the OLVG Hospital, (Amsterdam, The Netherlands) and researcher at the Amsterdam University Medical Centers, location VUmc (Amsterdam, The Netherlands)
References:
Concept Medical has shared the latest update from its IMPRESSION (Sirolimus-coated balloon angioplasty versus plain balloon angioplasty in the treatment of dialysis access dysfunction) randomised controlled trial (RCT), as it crosses the 50% enrolment mark.
The IMPRESSION trial enrolled its index patient on 11 January 2021 to assess the efficacy of the MagicTouch sirolimus-coated balloon (Concept Medical) against a placebo plain balloon in dysfunctional arteriovenous fistulas (AVFs). Since then, the prospective, multicentre, two-arm parallel group RCT has continued enrolling rapidly and has already crossed the 50% enrolment mark in just over 10 months.
The trial—under lead principal investigator (PI) Suai Chieh Tan, head and senior consultant, Department of Renal Medicine, Singapore General Hospital, Singapore, along with site PIs Edward Choke (Sengkang General Hospital, Singapore) and Jackie Ho Pei (National University Heart Centre, Singapore)—targets enrolment of 170 patients with end-stage kidney disease (ESKD) and a matured dysfunctional AVF across these three sites.
The primary aim of the trial is to evaluate primary circuit patency improvement at six months while comparing the MagicTouch AVF and placebo plain balloon in 1:1 randomised fashion.
According to a Concept Medical press release, the trial is doing “exceedingly well”, with 90 patients successfully enrolled so far. And, although the past year was shrouded by COVID-19, and impacted many healthcare institutions, the rate of enrolment has not slowed down.
“I would like to thank all the patients who have participated in the study. I hope that, together, we can find a better treatment to improve your health and many others who are experiencing the same recurring problem of a dysfunctional fistula,” said Tan.
Plain balloon angioplasty has historically been the “go-to” procedure in this area, the release adds. However, its long-term patency is poor, as ESKD patients often experience re-narrowing of their AVF or arteriovenous graft (AVG) due to stenosis. Paclitaxel-coated balloons are also being used to treat dysfunctional AVF—but mixed results have been coupled with safety concerns raised by the US Food and Drug Administration (FDA) regarding paclitaxel, Concept Medical claims.
The sirolimus-coated balloon thus “seems to be a promising option”, the release concludes, as the MagicTouch AVF was granted Breakthrough Device designation by the FDA in 2019, and the IMPRESSION RCT “will provide much-needed data” to reinforce this.
Veryan Medical has confirmed the release of MIMICS-3D EU three-year results by the study principal investigator Michael Lichtenberg (Vascular Center Arnsberg, Klinikum Hochsauerland, Arnsberg, Germany) at this year’s International Symposium on Endovascular Therapy (ISET 2022; 16–19 January, Hollywood, USA).
MIMICS-3D EU is a prospective, multicentre, observational registry to evaluate the BioMimics 3D vascular stent system. The study evaluated safety, effectiveness and device performance within a real-world clinical population of 507 patients enrolled in 23 pan-European sites.
The mean age of enrolled patients was 70 years; 66% were male and 37% were diabetic. Rutherford 0–1, 2–4 and 5–6 were 1%, 82% and 17%, respectively. Mean lesion length was 126mm and 57% of lesions were occlusions. Lesion calcification according to PACSS (Rocha-Singh KJ et al, 2014) was Grade #0—18%; #1—30%; #2—24%; #3—15%; #4—14%. BioMimics 3D placement followed atherectomy in 8% of lesions. Drug-coated balloons (DCB) were combined with BioMimics 3D in 50% of lesions treated.
Technical success for the BioMimics 3D implant procedure as assessed by the operator was 99%, Veryan Medical reports. An independent clinical events committee adjudicated major adverse events (MAE) including death and potential device-related events. The primary safety endpoint was a composite of MAE, comprising death, major index-limb amputation or clinically-driven target lesion revascularisation (CD-TLR) through 30 days. The primary outcome measure for effectiveness is freedom from CD-TLR through 12 months.
A press release details that the Kaplan Meier (KM) estimate of freedom from CD-TLR at one year, two years and three years in the intention-to-treat (ITT) population was 90%, 82% and 78%, respectively. The KM estimate of freedom from loss of primary stent patency (PSVR >2.4) through three years in the ITT population was 71%. There were 4/676 (0.6%) site-reported stent fractures
Lichtenberg commented: “I have been using BioMimics in my daily clinical practice for seven years and it is my ‘go to’ stent for a number of different indications, including long lesions, calcified lesions and lesions located in the distal SFA [superficial femoral artery] and proximal popliteal. I was delighted to be the principal investigator for the MIMICS-3D study and am pleased that the results further validate earlier results from the MIMICS clinical programme, the combined database of which provides significant validation of the clinical benefits of swirling flow.”
Nick Yeo, Veryan’s CEO noted: “I would like to thank Dr Lichtenberg for his significant contribution to the successful running of the MIMICS-3D study, providing invaluable leadership and guidance throughout. I would also like to thank all the other investigators and study coordinators who contributed to the success of the study, and particularly for being so rigorous about the quality of data collected, which is unusual for a typical registry of this type. CD-TLR and patency outcomes in the MIMICS-3D EU study are consistent with those of earlier MIMICS studies and are achieved in longer, more complex lesions. We are excited that these investigations into the postmarket performance of BioMimics 3D support the hypothesis that imparting non-planar curvature onto the femoropopliteal arteries to promote swirling blood flow and increase wall shear stress, results in clinical outcomes that are comparable to those of drug-coated and drug-eluting devices.”
Cook Medical has received Breakthrough Device designation from the US Food and Drug Administration (FDA) on a new drug-eluting stent for below the knee (BTK). This new stent is designed to treat patients suffering from chronic limb-threatening ischemia (CLTI).
“CLTI is a debilitating disease of growing prevalence around the globe and this is Cook Medical’s latest innovation within our peripheral arterial disease (PAD) programme,” said Mark Breedlove, vice president of Cook Medical’s Vascular division.
He continued: “This new product leverages our deep understanding of stent design and drug elution for lower limb anatomies, and it complements our dedicated portfolio of BTK products for limb preservation. Our goal is to improve the long-term clinical outcomes for CLTI patients.”
The Breakthrough Device designation is granted for devices that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions.
While the product is not commercially available yet, the benefits of the designation include priority review and interactive and timely communication with FDA during the clinical trial and premarket review phases in order to help get lifesaving devices to patients more quickly, a Cook Medical press release details.
According to the US Food and Drug Administration (FDA), Medtronic is recalling its HawkOne directional atherectomy system.
The FDA has identified the recall as a Class I—the most serious type in that “use of these devices may cause serious injuries or death.” So far, there have been 163 complaints, 55 injuries and no deaths reported in relation to the device issue, the FDA reported.
HawkOne consists of a catheter and cutter driver, and is used during procedures intended to remove blockage from peripheral arteries. The recall was made “due to the risk of the guidewire within the [system’s] catheter moving downward or prolapsing when force is applied during use,” according to the FDA.
The company distributed an urgent medical device notice to customers on 6 December 2021, requesting they share reports of the defect with all relevant parties, and review both HawkOne’s instructions for use (IFU), and the warnings and precautions listed in the urgent notice letter, before using the product.
“In accordance with our commitment to patient safety, Medtronic recently initiated a voluntary recall to customers related to the risk associated with tip damage caused by guidewire prolapse in its 6 French (6Fr) HawkOne directional atherectomy system,” Medtronic said in a statement. “In our letter to customers, Medtronic noted that a small number of customer reports of tip damage (at a rate of 0.168% when compared to quantity of devices distributed) during the use of the 6FR HawkOne devices. While most of these instances were resolved without patient issue, a small number required endovascular retrieval (0.033%) or open surgical retrieval (0.028%).”
The statement added that there are no product retrievals or disposals requested associated with the recall and no actions required for patients treated with HawkOne.
Should the catheter function as outlined, the FDA reported in a medical device recall advisory, “the catheter tip may break off or separate and this could lead to serious adverse events, including a tear along the inside wall of an artery (arterial dissection), a rupture or breakage of an artery (arterial rupture), decrease in blood flow to a part of the body because of a blocked artery (ischaemia), and/or blood vessel complications that could require surgical repair and additional procedures to capture and remove the detached and/or migrated (embolised) tip.”
Medtronic asked customers to complete a confirmation form enclosed in the urgent notice letter and email them to [email protected].
Peter Littler (Newcastle, UK) talks to Gerard McLauchlan (Surrey, UK) and Alex Horton (Surrey, UK) about veterinary interventional radiology following a special session titled All Creatures Great and Small: IR for animals at the British Society of Interventional Radiology annual scientific meeting (8–10 December, Glasgow, UK).
McLauchlan and Horton discuss some of their most recent interesting cases, with Horton noting that they treat oncological and other conditions such as large arteriovenous malformations in the liver with intrahepatic shunts and other therapies such as prostate embolization and intra-arterial chemotherapy.
He notes that although the “fundamental IR techniques are identical” when it comes to treating humans and animals, there are still some “adjustments” needed and a learning curve with dealing with animals.
McLauchlan says his work with Horton means they can now “offer the animals and their owners a lifeline that they previously would not have had”. He goes on to state that “around 80% of our caseload is oncological so what we now see more than anything is prostate cancer in dogs. It is really uncommon, making up 0.6% of all dog cancers, but we are seeing at least one case a week come to us because we now offer embolization as a treatment.”
They identify some of the interesting and unique problems that arise when working with animals and pinpoint the biggest hurdles as being equipment cost (“four nurses worth of equipment in a cupboard”) and room set-up, particularly in regard to imaging that this available.
Fluidx Medical recently announced that its GPX embolic device was used to effectively devascularise a large tumour with multiple feeding vessels as part of a multicentre clinical trial.
“This could have been a challenging case since it involved a large renal tumour fed by small, low flow, tortuous vessels. We were able to use our standard embolic microcatheter to deliver GPX in a highly controlled fashion. Since we were not worried about catheter entrapment, we could take our time and ensure that we occluded all targeted vessels completely. GPX flowed distally very well, completely filling the targeted region,” said Martin Krauss, head of Interventional Radiology, Christchurch Hospital, Christchurch, New Zealand. “Based on our case experiences, GPX is a great product for effectively filling distal vasculature.”
Fluidx Medical states that the GPX embolic device is an innovative embolic designed for simple preparation and controlled delivery. The device is packaged ready to use in a syringe, can be prepped tableside by the clinician in about 30 seconds, and may be delivered through standard microcatheters (no complex mixing systems or special delivery catheters are necessary), the company adds.
A press release details that GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolus upon delivery without polymerisation or dimethyl-sulfoxide (DMSO) precipitation, a press release explains. According to Fluidx Medical, GPX is designed to occlude blood vessels independent of a patient’s coagulation situation.
“Treating a tumour with multiple feeding vessels in a controlled, thorough manner without risk of catheter entrapment can improve patient care and minimise the need for follow-on procedures,” said Libble Ginster, CEO of Fluidx Medical Technology. “GPX demonstrates improved control and precision. GPX does not require 20+ minutes of preparation time or the clinician to use a special catheter system. The simplicity of GPX preparation makes real-time clinical decision-making possible. We continue to be excited about the GPX portfolio and its future in advancing cancer care.”
The GPX embolic device is under development and does not have marketing clearance or approval in any market at this time, the company advises. It is for investigational use (in New Zealand) only.
BD (Becton, Dickinson and Company) has announced the launch and 510(k) clearance from the US Food and Drug Administration (FDA) of the Crosser iQ chronic total occlusion (CTO) recanalisation system, which is designed to cross peripheral artery CTOs intraluminally.
The Crosser iQ ultrasonic CTO device was developed to help improve CTO crossing predictability to aid clinicians treating these challenging lesions—the CTO crossing device also pairs the Crosser iQ ultrasonic CTO device with the BD recanalization system and the Recon support catheter. The new system utilizes proprietary technology that automatically adjusts the crossing power output to help stabilize the distal tip of the device to assist in crossing through the entire length of the CTO intraluminally.
The BD recanalization system and Crosser iQ ultrasonic CTO device is indicated to facilitate the intraluminal placement of conventional guidewires beyond peripheral artery CTOs, the company claims. The Crosser iQ ultrasonic CTO device is contraindicated for use in carotid arteries.
According to the company, the device utilizes a unique mechanism of action that is specifically designed to vibrate against peripheral arterial CTOs creating an intraluminal channel to facilitate the placement of conventional guidewires.
During the procedure, power from the BD recanalization system is converted into ultrasonic vibrational energy causing microbubbles to expand and implode at the tip of the Crosser iQ ultrasonic CTO device. This breaks the internal structure of the plaque and erodes the solid surface of the CTO, allowing the physician to automatically and selectively ablate plaque, while remaining atraumatic to elastic tissue, advised BD.
A new study reports that watching TV for four hours a day or more is associated with a 35% higher risk of venous thromboembolism (VTE) compared with less than 2.5 hours. The research is published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).
“Our study findings also suggested that being physically active does not eliminate the increased risk of blood clots associated with prolonged TV watching,” said lead author Setor Kunutsor of the University of Bristol (Bristol, UK). “If you are going to binge on TV you need to take breaks. You can stand and stretch every 30 minutes or use a stationary bike. And avoid combining television with unhealthy snacking.”
he researchers conducted a systematic review and meta-analysis. The analysis included three studies with a total of 131,421 participants aged 40 years and older without pre-existing VTE. The amount of time spent watching TV was assessed by questionnaire and participants were categorised as prolonged viewers (watching TV at least four hours per day) and never/seldom viewers (watching TV less than 2.5 hours per day).
The average duration of follow-up in the three studies ranged from 5.1 to 19.8 years. During this period, 964 participants developed VTE. The researchers analysed the relative risk of developing VTE in prolonged versus never/seldom TV watchers. They found that prolonged viewers were 1.35 times more likely to develop VTE compared to never/seldom viewers.
The association was independent of age, sex, body mass index (BMI) and physical activity. “All three studies adjusted for these factors since they are strongly related to the risk of VTE; for instance, older age, higher BMI and physical inactivity are linked with an increased risk of VTE,” said Kunutsor. “The findings indicate that regardless of physical activity, your BMI, how old you are and your gender, watching many hours of television is a risky activity with regards to developing blood clots.”
Kunutsor noted that the findings are based on observational studies and do not prove that extended TV watching causes blood clots.
Regarding the possible reasons for the observed relationship, he said: “Prolonged TV viewing involves immobilisation which is a risk factor for VTE. This is why people are encouraged to move around after surgery or during a long-haul flight. In addition, when you sit in a cramped position for long periods, blood pools in your extremities rather than circulating and this can cause blood clots. Finally, binge-watchers tend to eat unhealthy snacks which may lead to obesity and high blood pressure which both raise the likelihood of blood clots.”
Kunutsor concluded: “Our results suggest that we should limit the time we spend in front of the television. Long periods of TV watching should be interspersed with movement to keep the circulation going. Generally speaking, if you sit a lot in your daily life—for example your work involves sitting for hours at a computer—be sure to get up and move around from time to time.”
Findings from a first-of-its-kind study conducted at University Hospitals (UH) Harrington Heart & Vascular Institute (Cleveland, USA) showed a novel system-wide interdisciplinary team assembled to evaluate alternative treatments to major amputation improved outcomes for patients with chronic limb-threatening ischaemia (CLTI). The findings were recently published in Circulation: Cardiovascular Interventions from the American Heart Association.
Clinical decisions approving amputation are frequently made in isolation by a patient’s individual caregivers, a UH press release states. To address this problem, UH Harrington Heart & Vascular Institute created a novel system-wide interdisciplinary team called the Limb Salvage Advisory Council (LSAC) and evaluated its impact on a specific population of patients who were already scheduled for amputation. According to UH, only one quarter (excluding those who died or were lost to follow-up) of the patients formerly scheduled for a major amputation actually lost a limb at 180 days after being managed by LSAC.
“Circulation issues often cause painful cramping, numbness and wounds which can greatly decrease a person’s quality of life. When a doctor suggests amputation to address the pain, patients usually follow that recommendation, yet nearly half of all people with vascular disease will die within five years of an amputation. This is higher than the five-year mortality rates for breast cancer, colon cancer and prostate cancer,” said Mehdi Shishehbor, president of UH Harrington Heart & Vascular Institute, and Angela and James Hambrick chair in Innovation.
Shishehbor leads UH’s limb salvage programme, which uses minimally invasive approaches to restore blood flow to dying limbs and prevent amputation.
The LSAC at UH includes vascular surgeons, endovascular interventionalists, vascular medicine specialists, podiatrists, and wound care experts. Once a patient who is scheduled for a major amputation is identified, the treating physician may elect to notify a designated coordinator who arranges for an urgent virtual LSAC meeting. LSAC members review and discuss available data including comorbidities, functional status, extent of tissue loss, relevant imaging studies and prior interventions with the goal of providing diversified thoughtful inputs. Eventually, the LSAC reaches one of two conclusions: the limb is salvageable and a plan is created to save it, or the patient is approved to proceed with the originally scheduled amputation.
The press release details that, statistically, amputees are disproportionately of lower socioeconomic status, and that African Americans are up to four times more likely to have an amputation than white Americans.
“UH is committed to improving the health of all people by advancing science and human health. All people should have the opportunity to receive the necessary medical resources and support to have a healthier life, regardless of their status in the community or their race,” said Shishehbor. “We believe that broad implementation of this policy nationwide could really help people and significantly reduce amputation rates across the USA.”
A total of 19 patients who were scheduled for major amputation underwent LSAC evaluation between January and September 2019. The patients had a mean age of 63. Three patients were deemed unsalvageable due to extensive tissue loss and proceeded with their originally scheduled amputation, while the other 16 patients were considered for limb salvage. Fifteen patients had successful revascularisation. Nine of them had not undergone major amputation at 180 days and six of them had complete healing or significant reduction in wound size in that time.
UH claims that this is the first study investigating the impact of a novel and proactive interdisciplinary intervention on patients already planned for a major amputation due to CLTI. Two studies have reported on the adoption of multidisciplinary care in CLTI and improved outcomes; however, both were retrospective and had revascularisation proceduralists from a single specialty.
“Our interdisciplinary LSAC is unique because it involves not just multiple teams including endovascular interventionalists and vascular surgeons, but often multiple physicians within the same specialty. This ensures different points of view and more potential options to avoid amputation,” said Tarek Hammad, interventional cardiologist at UH Harrington Heart & Vascular Institute. “It is important to foster a culture of mutual respect and trust within the team and among various specialties to avoid judgement and competition.”
These findings may have significant policy implications if all patients scheduled for major amputation were mandated to receive an evaluation with an interdisciplinary team such as LSAC, UH asserts, adding that widespread implementation of this policy could greatly reduce scheduled amputations. This cause could be further helped by future research exploring how to move the referral to LSAC further upstream allowing for early intervention, the press release concludes.
Ajax Health has announced the appointments of two cardiovascular professionals to Cordis-X, an independent accelerator created to drive innovation and growth to Cordis.
“Since the acquisition of Cordis almost a year ago, we have made substantial investments in R&D, M&A, and strategic partnerships,” said Duke Rohlen, executive chairman of Cordis and CEO of Ajax Health and Cordis-X. “Recruiting Dr John Simpson and Dr Jeremy Durack, two of the greatest minds in cardiovascular science, will help us forge a bold new vision for Cordis.”
Simpson, a cardiologist, is credited with inventing and commercialising the first over-the-wire balloon catheter used for percutaneous transluminal coronary angioplasty (PTCA) and is known for pioneering interventional cardiology as it exists today, an Ajax Health press release details. As senior advisor to Cordis-X, Simpson brings decades of scientific and commercial experience. He has founded and successfully transacted multiple MedTech companies, including ACS and DVI (both acquired by Eli Lilly), CVIS (acquired by Boston Scientific), Perclose (acquired by Abbott), Lumend (acquired by Cordis), and Fox Hollow (acquired by ev3, which is now part of Medtronic).
Simpson received his PhD in biomedical sciences from the University of Texas, his MD from Duke University, and completed his fellowship in interventional cardiology at Stanford University. A member of the American College of Physicians and fellow of the American College of Cardiology, Simpson has published on a wide variety of medical subjects and lectured extensively throughout the world.
Jeremy Durack, an interventional radiologist and former vice-chair of Radiology at Memorial Sloan Kettering Cancer Center, will serve as chief clinical officer for Cordis-X. He is renowned for his work in vascular and interventional radiology, with expertise in a wide range of minimally invasive procedures and particular interest in the treatment of genitourinary cancers and venous thrombosis, the press release communicates.
Durack received his MD from Stanford University School of Medicine and completed his residency and fellowship at UCSF School of Medicine. He has been a leader in the Society of Interventional Radiology and brings a wealth of international research experience to the team.
“The collective capabilities of Ajax Health, Cordis-X, and Cordis are creating a tractor beam for the best and brightest,” said Durack. “It is not just recruiting engineers and physicians motivated to improve how we prevent and treat cardiovascular disease, but also to develop new ways of thinking about fields such as interventional oncology as well as how we can address global health disparities.”
The appointments of Simpson and Durack signal an aggressive effort by Cordis-X to recruit some of the most successful industry innovators to its team.
“I have great admiration for Cordis,” said Simpson. “They created the first catheter I ever used for diagnostic angiography in humans. Cordis products were state of the art, ahead of everyone else. I look forward to helping the organisation push the edges of innovation and create new products we will be talking about decades from now.”
Royal Philips today announced physicians will now have access to advanced new 3D image guidance capabilities through the image-guided therapy mobile C-arm system—Zenition, aiming to improve the outcomes for patients undergoing endovascular treatment. The company has signed a strategic partnership agreement with Cydar, a UK based provider of cloud-based procedure maps software to plan and guide surgery in real time.
As patient numbers rise and procedures become more complex and time-consuming, patient-specific real-time procedure planning and guidance, optimisation of equipment utilisation, and usability have become ever more important. To help overcome these challenges, Philips claims that the image-guided therapy mobile C-arm system—Zenition—brings together innovations in image capture and processing, ease-of-use, and versatility, many of which were pioneered on Philips’ image-guided therapy platform Azurion. Like Azurion, the Zenition mobile C-arm system allows hospitals to maximise operating room performance, enhance their clinical capabilities, and provide staff with a seamless user experience, a press release details.
The integration of Cydar EV Maps software into the Zenition platform now adds extended procedure planning and real-time 3D guidance capabilities.
Cloud-based AI and computer vision
Cydar EV Maps assists in the planning, real-time guidance, and postprocedure review of the endovascular surgery. It brings cloud-based AI and computer vision to mobile surgery, enabling reductions in radiation exposure, fluoroscopy time, and procedure time together with improved ease of use, Philips states. It enables surgeons to create a detailed patient-specific 3D map of the target vasculature to help plan surgery, and then uses these maps to augment intraoperative live image guidance, updating the maps in real time to account for deformations during surgery, such as guidewires and instruments deforming the patient’s blood vessels.
Cydar EV also facilitates post procedure outcome analysis. The combined result of this integration of procedure planning, guidance and review is that surgeons can work more accurately and efficiently—enabling an approximate 50% reduction in radiation exposure, a significant reduction in fluoroscopy time and a reduction of procedure times by more than 20%, according to Philips, all while helping achieve better outcomes for patients.
“With Philips’ integrated portfolio, using validated AI and cloud technologies, we can facilitate collaborative care to optimise surgical pathways,” said Karim Boussebaa, general manager Image Guided Therapy Systems at Philips. “Philips has a strong global network of mobile surgery systems and recognises that Cydar’s EV Maps solution can play a key role in further improving our integrated offering for endovascular procedures.”
“By partnering with Philips to bring our Cydar EV Map solution to Philips’ user-friendly Zenition platform of mobile C-arms, we are a step closer to achieving our mission to ensure every image-guided minimally-invasive surgical procedure goes exactly as planned,” said Paul Mussenden, CEO of Cydar. “The benefits of this combined solution, with integrated and enhanced procedure planning and visualisation, include shorter and more predictable procedure times, reduced X-ray exposure to patients and staff, and fewer injections of iodine dye—the leading cause of in-hospital kidney failure.”
Cydar EV Maps is currently in use across the EU, UK and USA. It is certified Software-as-a-Medical Device with EU CE mark and US Food and Drug Administration (FDA) 510(k) clearances.
Royal Philips today announced physicians will now have access to advanced new 3D image guidance capabilities through its image-guided therapy mobile C-arm system—Zenition, aiming to improve the outcomes for patients undergoing endovascular treatment. The company has signed a strategic partnership agreement with Cydar, a UK based provider of cloud-based procedure maps software to plan and guide surgery in real time.
As patient numbers rise and procedures become more complex and time-consuming, patient-specific real-time procedure planning and guidance, optimisation of equipment utilisation, and usability have become ever more important. To help overcome these challenges, Philips claims that its image-guided therapy mobile C-arm system—Zenition—brings together innovations in image capture and processing, ease-of-use, and versatility, many of which were pioneered on Philips’ image-guided therapy platform Azurion. Like Azurion, the Zenition mobile C-arm system allows hospitals to maximise operating room performance, enhance their clinical capabilities, and provide staff with a seamless user experience, a press release details. The integration of Cydar EV Maps software into the Zenition platform now adds extended procedure planning and real-time 3D guidance capabilities.
Cloud-based AI and computer vision
Cydar EV Maps assists in the planning, real-time guidance, and postprocedure review of the endovascular surgery. It brings cloud-based AI and computer vision to mobile surgery, enabling reductions in radiation exposure, fluoroscopy time, and procedure time together with improved ease of use, Philips states. It enables surgeons to create a detailed patient-specific 3D map of the target vasculature to help plan surgery, and then uses these maps to augment intraoperative live image guidance, updating the maps in real time to account for deformations during surgery, such as guidewires and instruments deforming the patient’s blood vessels. Cydar EV also facilitates post procedure outcome analysis. The combined result of this integration of procedure planning, guidance and review is that surgeons can work more accurately and efficiently—enabling an approximate 50% reduction in radiation exposure, a significant reduction in fluoroscopy time and a reduction of procedure times by more than 20%, according to Philips, all while helping achieve better outcomes for patients.
“With Philips’ integrated portfolio, using validated AI and cloud technologies, we can facilitate collaborative care to optimise surgical pathways,” said Karim Boussebaa, general manager Image Guided Therapy Systems at Philips. “Philips has a strong global network of mobile surgery systems and recognises that Cydar’s EV Maps solution can play a key role in further improving our integrated offering for endovascular procedures.”
“By partnering with Philips to bring our Cydar EV Map solution to Philips’ user-friendly Zenition platform of mobile C-arms, we are a step closer to achieving our mission to ensure every image-guided minimally-invasive surgical procedure goes exactly as planned,” said Paul Mussenden, CEO of Cydar. “The benefits of this combined solution, with integrated and enhanced procedure planning and visualisation, include shorter and more predictable procedure times, reduced X-ray exposure to patients and staff, and fewer injections of iodine dye—the leading cause of in-hospital kidney failure.”
Cydar EV Maps is currently in use across the EU, UK and USA. It is certified Software-as-a-Medical Device with EU CE mark and US Food and Drug Administration (FDA) 510(k) clearances.
There are some very serious risks associated with forgotten ureteric JJ stents. David Maudgil, a consultant interventional radiologist at Wexham Park Hospital, Frimley Health Foundation Trust (Slough, UK), outlines why and when these devices are used, explains the risks a forgotten stent might pose and provides some guidance on how to mitigate such risks.
Interventional radiologists routinely place large numbers of ureteric JJ stents, for a number of different indications including ureteric blockage or ureteric injury. This is often when retrograde attempts have failed or when there is no available retrograde route from the bladder. The patients who require this come from a wide range of non-urological or nephrological specialties, particularly general surgery, gynaecology and medicine, but will usually require follow up and change of the stent by urologists within three to six months.
If the stent is not removed or changed in a timely fashion, there is a high risk of encrustation of stone material around the stent which may not only block the stent but also make it extremely difficult to remove without damaging the kidney, ureter and bladder. There is also a small risk of the stent fracturing within the ureter, causing acute blockage with probable added infection. For these reasons, a forgotten ureteric stent constitutes a “never” event and a serious untoward incident (SUI).
Although guidelines and procedures exist for routine monitoring and change of stents placed retrogradely (by urologists), we did not have a robust system for handing these patients promptly to urology for follow up of their stent (see Box 1 for Healthcare Safety Investigation Branch [HSIB] guidelines).
Box 1 – The UK HSIB published its report: Unplanned delayed removal of ureteric stents in October 2020. They made the following safety recommendations:
| Safety recommendation R/2020/091:
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Relevant specialties to develop national standards which support electronic and paper-based systems for stent logging/ tracking. These standards should include guidance on monitoring and human oversight.
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| Safety recommendation R/2020/092:
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Review stent patient information leaflets. This should include accessibility and clinical considerations, especially with regards to side effects and complications, and advice on the action to take should concerns arise.
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| Safety recommendation R/2020/093:
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Provide guidance for staff working within the stone care pathway to promote consistent advice to patients as part of discharge planning.
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| Safety recommendation R/2020/094:
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Include information in discharge letters and other communication sent to GPs and patients regarding patients’ stent status, potential complications and the possibility of a retained stent.
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We performed an audit showing that of 50 patients in 2019 who had antegrade stents inserted (67% as emergency admissions), 40% subsequently had stents replaced retrogradely, 45% removed, and 15% had extra-anatomical stenting or died before readmission. The mean time from stent insertion to planning removal was 13 days, which appeared unacceptably long and increased the risk of the patient being lost to urological follow up.
These findings were discussed at a joint interdepartmental meeting and we agreed that a logbook should be kept where all antegrade stents would be recorded. Moreover, a standing item at the weekly uroradiological meeting was discussion of every antegrade stent insertion and formulation of an agreed plan for urology to follow up the patient.
Subsequent re-audit three months later showed that all patients had been discussed in a timely manner with mean interval from stent insertion to planning removal reduced to 3.3 days. It was clear that interdepartmental communication regarding these patients was much improved, and that a safe system of working had been developed. This audit, with subsequent significant improvement after discussion, was presented at the the BSIR Annual Scientific Meeting 2021 (8–10 December, Glasgow, UK).
David Maudgil is a consultant interventional radiologist at Wexham Park Hospital, Frimley Health Foundation Trust (Slough, UK).
Relevant disclosures:
None
References:
https://www.hsib.org.uk/investigations-and-reports
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Adept Medical has today unveiled its Lower Leg Support solution, which is designed to assist with peripheral artery disease (PAD) interventions.
The Lower Leg Support aims to gently immobilise the patient’s leg during fluoroscopy-guided treatment of critical limb ischaemia. The device holds the foot in a slightly plantar flexed position and is endorotation and exorotation capable, providing multiple positioning options to facilitate imaging.
Adept Medical say that the clinician-led, ergonomic design optimally positions the leg to suit the procedural requirements desired during lower limb interventions.
Matt Lazenby, medical product design manager at Adept Medical, said: “Peripheral artery disease is becoming more and more common with over 200 million cases worldwide. We were approached by a number of imaging equipment suppliers, interventional radiologists and vascular specialists requesting a method to keep the leg immobilised whilst treating critical limb ischemia, reducing the requirement for repeat imaging and associated risks.
“This is why we developed the Adept Medical Lower Leg Support. Working with clinicians in the field, we worked hard to provide a solution to comfortably immobilise the leg, aiming to reduce some of the procedural risks for the patient and clinical team. We’re very proud of the result.”
The reversible footplate allows the product to be used on both the left and right foot. The footplate can be removed entirely to enable distal artery access, ultrasound imaging and manipulation of the foot, should it be required during the procedure.
The Lower Leg Support is fitted with a soft foam Leg Pad, providing pressure management for patients who often suffer from painful ulcerations, and soft foam straps to gently immobilise patients under conscious sedation.
Adept Medical say that the Lower Leg Support is compatible with most common table models and is suitable for use with C-arm imaging systems. Resting on top of the table mattress, it can be secured with two table straps equipped with buckles for tensioning and quick release. The Table Straps wrap around the cantilevered table and mattress.
Thrombolex recently announced the results of the RESCUE trial’s prespecified interim analysis, of the first 62 evaluable patients, in a late-breaking clinical trials session at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
This PIVOTAL trial is scheduled to enrol at least 100 evaluable patients with acute intermediate-risk pulmonary embolism. This trial is evaluating the efficacy and safety of the Bashir and Bashir S-B endovascular catheters (BECs) in the treatment of acute PE under an investigational device exemption (IDE) from the US Food and Drug Administration (FDA). The Bashir endovascular catheter is intended for the controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature. It is also now intended for the controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature, enabling the restoration of blood flow in patients with venous thrombus.
The goal of RESCUE is to achieve an additional indication for use of these devices in the treatment of acute pulmonary embolism.
This prespecified interim analysis was presented by Akhilesh Sista, chief of Interventional Radiology, NYU Langone Health, New York, USA. The analysis included 44 males and 18 females with an average age of 58.5 years; 90.3% had high intermediate-risk pulmonary embolism with both right ventricular dysfunction and elevated biomarkers. Each patient was treated with 7mgs of r-tPA into each pulmonary artery over five hours (a total of 14 mg r-tPA in 58 patients with bilateral pulmonary embolism and 7mg in four patients with unilateral pulmonary embolism) at 18 participating centres in the USA.
Computed tomography (CT) scan at 48 hours after infusion showed that the right ventricular to left ventricular (RV/LV) diameter ratio decreased by 32.1% (0.52±0.38: 95% confidence interval [CI] 0.42–0.62, p<0.0001), and the pulmonary clot burden by Refined Modified Miller Index had decreased by 36.3% (8.4±4.3: 95% CI 7.34–9.5, p<0.0001). The successful device placement rate was 100%, there were no device-related complications and the major bleed rate at 72 hours was zero.
“These interim results from the RESCUE trial are very exciting,” said Sista. “The most notable finding is the core lab-assessed reduction in pulmonary thrombus burden at 48 hours, which may translate to better short- and long-term outcomes pending further research. The reduction in RV/LV ratio and the absence of device- or drug-related adverse events are also salutary outcomes. The expandable infusion basket of the device, with the pharmacomechanical mode of action, appears to restore blood flow promptly. I look forward to the final results of RESCUE and subsequent investigations that will determine the role of this promising novel technology in the treatment of acute pulmonary embolism.” Brian Firth, chief scientific officer of Thrombolex and principal investigator on the Small Business Innovation Research grant from the National Heart Lung and Blood Institute (NHLBI) stated: “The strong support and encouragement that we have received from the NHLBI as we have conducted this trial, especially in the midst of the COVID-19 epidemic, has really made this trial possible.”
Inari Medical has announced positive acute and long-term interim results from the first 500 pulmonary embolism patients enrolled in the FlowTriever outcomes registry (FLASH).
A press release reports that at 48 hours post-procedure, the major adverse event rate and mortality rate were low, at 1.4% and 0.2%, respectively. None of the deaths or major adverse events were device related. Collectively, these pulmonary embolism patients experienced substantial on-table improvements in haemodynamics and symptoms, which translated to six-month improvements in cardiac function, functional status, and quality of life measures. The outcomes were achieved while limiting utilisation of hospital resources, the release adds, with less than 4% of patients receiving adjunctive therapy and a median of zero days in the intensive care unit (ICU) post procedure.
Speaking to Interventional News regarding the growing interest in mechanical thromboaspiration in the treatment of pulmonary embolism patients, Narayan Karunanithy, a consultant interventional radiologist, at Guy’s & St Thomas’ NHS Foundation Trust, London, UK said: “The catheter-based interventional treatments available to treat acute pulmonary embolism have expanded beyond catheter-directed thrombolysis recently to include several percutaneous mechanical thromboaspiration devices. Potential benefits of the latter include the use of the devices in patients with high bleeding risk, when rapid restoration of perfusion to offload the right ventricle is required in high-risk pulmonary embolism and as an alternative to surgical embolectomy in patients with multiple comorbidities. This potentially allows a larger cohort of patients with severe pulmonary embolism to be safely treated. However, at present, there is a lack of robust evidence for these devices demonstrating benefit over standard care. The big research questions are whether high- and intermediate-risk pulmonary embolism patients treated with mechanical thromboaspiration achieve better immediate and long-term outcomes than those managed with standard care anticoagulation and whether the use of the devices is safe. The field is evolving rapidly and in the next few years we are likely to see large-scale studies answer these questions.”
FLASH is a prospective, multicentre, single-arm registry evaluating real-world patient outcomes after treatment of pulmonary embolism with FlowTriever. The 500-patient interim results were presented on 27 October via webcast at Transcatheter Cardiovascular Therapeutics (TCT) 2021 by principal investigator Catalin Toma (University of Pittsburgh Medical Center in Pittsburgh, USA.
“These interim results reinforce the strong safety profile of the FlowTriever system in real-world pulmonary embolism patients, with substantial on-table clinical improvements and immediate symptom relief,” said Toma, who added: “We believe these six-month follow-up data suggest that removal of clot burden without the risks of lytics has potential positive long-term implications for pulmonary embolism patients, including strikingly low rates of hospital readmissions, dyspnoea, CTED (chronic thromboembolic disease), and CTEPH (chronic thromboembolic pulmonary hypertension). These data suggest that treatment with FlowTriever may fundamentally improve the natural course of the disease, and that is tremendously exciting.”
In October, Inari Medical also announced planned enrolment in the PEERLESS trial, a new randomised controlled trial comparing the clinical outcomes of patients with intermediate-high risk pulmonary embolism treated with the FlowTriever System versus catheter-directed thrombolysis. PEERLESS is a prospective, multicentre trial that will include up to 700 patients enrolled in 60 centres in the USA and Europe. The study consists of a primary randomisation cohort of 550 patients, and for patients who cannot be randomised due to an absolute contraindication to thrombolytics, a secondary non-randomised cohort of up to 150 patients. The primary outcome for the trial is a hierarchical composite of outcomes including all-cause mortality, major bleeding events, clinical deterioration and/or bailout, and length of stay in the intensive care unit.
“Historically, due to the major bleeding associated with lytic therapy, physicians needed to carefully weigh a patient’s risk of death against the risk of intervention, reserving advanced treatment for only the sickest of pulmonary embolism patients,” said global co-principal investigator, Carin Gonsalves (Division of Interventional Radiology, University Philadelphia, USA). “By offering patients immediate symptom relief upon removal of significant clot burden without the risks of lytics, the potential for bloodless thrombectomy with the FlowTriever System has fundamentally altered the pulmonary embolism treatment landscape, challenging physicians to rethink risk stratification and the goals of intervention.”
In the trial, radioembolization (also called selective internal radiation therapy [SIRT) or sometimes transarterial radioembolization [TARE]) using glass beads (Therasphere; Boston Scientific) containing radioactive yttrium (Y-90) was used as a second-line treatment in combination with standard of care systemic chemotherapy for patients who had disease progression during or after first-line chemotherapy.
The EPOCH trialists, set their sights on determining the impact of radioembolization and second-line chemotherapy in patients with colorectal liver metastases who progressed on oxaliplatin- or irinotecan-based first-line therapy. The international, prospective phase 3 EPOCHpivotal clinical trial randomised 428 patients.
Findings from the trial, which were presented at the European Society for Medical Oncology (ESMO) Congress 2021 in the Autumn and published in theJournal of Clinical Oncology, showed that the addition of SIRT met both its primary endpoints, including progression-free survival (PFS) and hepatic progression-free survival (hPFS) of patients with metastatic colorectal cancer (mCRC) of the liver. The trial did not show significant improvement in overall survival of the patients in the SIRT arm.
The addition of TheraSphere treatment significantly increased both PFS (p=0.0013) and hPFS (p<0.0001). Patients receiving SIRT with second-line chemotherapy were 31% less likely to show disease progression or death (HR= 0.69) and 41% less likely to show hepatic disease progression or death vs. with chemotherapy alone (HR= 0.59). Median overall survival was 14 and 14.4 months (p=0.7229). There were 68.4% grade 3 adverse events reported radioembolization as compared with 49.3% in those who received chemotherapy alone. Both groups received full chemotherapy dose intensity.
Riad Salem (Northwestern Memorial Hospital, Chicago, USA) and co-principal investigator of the trial, said: “TheEPOCHtrial not only demonstrated positive safety and efficacy data for the patients treated in this study, but underscores the success of integrating a device-based therapy like TheraSphere treatment in the continuum of care with systemic chemotherapy and biologic regimens, thereby providing the rationale and setting the stage for future investigation in other cancer types.
”EPOCH is being hailed as the first positive phase 3 SIRT trial in any disease setting. The data is expected to support Boston Scientific’s regulatory submission to the US Food and Drug Administration (FDA). In the conclusion of the published article, the authors, write: “Further subset analyses are needed to better define the ideal patient population that would benefit from radioembolization.”
A previous phase 3 trial, SIRFLOX, that used a different resin yttrium-90 microsphere platform (SIR-Spheres; Sirtex/China Grand Pharmaceutical and Healthcare Holdings) failed to show significant additive benefits to chemotherapy as measured by progression-free survival at any site (but significantly delayed disease progression in the liver). The trial also did not find additive SIRT when it came to overall survival in a first-line setting. These results and subsequent analyses including a pooled analysis of SIRFLOX-FOXFIRE-FOXFIRE global, which reported some encouraging data for patients with respect to progression in the liver still did not reveal significant benefits with respect to overall survival.
Commenting on the EPOCH trial results, Mary Mulcahy, medical oncologist at Northwestern Memorial Hospital and co-principal investigator of the trial, noted: “In the second line of therapy for metastatic colorectal cancer, with disease isolated to the liver, the addition of TheraSphere with chemotherapy resulted in a significant delay in overall tumour progression. Additionally, chemotherapy-related adverse events were comparable between the trial arms.”Peter Littler (Freeman Hospital, Newcastle, UK) is the 2021 British Society of Interventional Radiology (BSIR) Scientific Programme Committee chair and has a specialist interest in interventional oncology. Speaking broadly on the availability of SIRT in the UK for this patient group, he says: “This study adds important information to existing literature in the area. SIRT availability in the UK for patients with colorectal metastases is limited to small numbers in the palliative setting in relatively few commissioned NHS (National Health Service) centres. Positive phase 3 data in this patient group should inform further evaluation of the technology, enabling greater access to SIRT for more of our patients.”
Mercator MedSystems has recently announced that the DEXTERITY trials research has begun under a technology transfer grant for approximately $300,000 funded by the National Institutes of Health (NIH). Preclinical research performed using the grant resources aims to demonstrate mechanistic effects of local delivery of anti-inflammatory drugs to treat deep vein thrombosis (DVT).
“The formation of DVT appears to begin due to vein wall inflammation, and then as the body’s natural processes work to remove the obstruction, the vein becomes further inflamed,” stated Kirk Seward (president and chief science and technology officer of Mercator, California, USA) “Current treatments to remove the thrombus do not treat this underlying inflammation, which has been tied to the development of new clotting events or dysfunction of the vein and valves. Ultimately, in up to half of DVT patients treated with clot-removing drugs or devices, the damage from the thrombus and the residual inflammation can lead to chronic pain and other symptoms known as post-thrombotic syndrome.”
The NIH grant is being conducted in concert with a team at Massachusetts General Hospital, Harvard Medical School in Boston, Massachusetts, led by Farouc Jaffer (associate professor of medicine at Harvard Medical School and an attending interventional cardiologist at Massachusetts General, Massachusetts, USA), another co-principal investigator for the grant research.
Jaffer commented, “Our team at Massachusetts General Hospital has extensive experience with the development of preclinical models to demonstrate the mechanisms of DVT and restoration of blood flow. In this project, we are measuring molecular, physiologic, and biologic outcomes that will be key to understanding how anti-inflammatory drugs, when delivered locally and precisely to the area around the vein, may work to counteract vein wall injury arising from this disease. We hope that our joint research will help reduce the incidence of the post-thrombotic syndrome, a consequence of DVT that has overburdened the healthcare system for years.”
According to the company, the research covered by this grant is part of a broad effort to treat inflammation related to DVT. In addition to this mechanistic research, Mercator is conducting human clinical trials with the company’s Bullfrog micro-infusion device to deliver the anti-inflammatory drug dexamethasone specifically to areas around affected veins after thrombus removal. The Bullfrog has received US Food and Drug Administration (FDA) clearance and CE Mark approval. Enrollment in the DEXTERITY clinical trials is ongoing.
Akura Medical has announced the closing of its $25M Series A1 financing, which will be used to support the development of its next-generation thrombectomy device.
The financing was led by Cormorant Asset Management, with participation from The Capital Partnership (TCP), PA MedTech VC Fund and Shifamed angel investors.
Amr Salahieh, founder of Shifamed and chairman of the board of Akura Medical, said: “Akura Medical’s mechanical thrombectomy device is designed to simplify the procedure and integrate various mechanisms to efficiently and effectively remove blood clots.
“We are extremely pleased to close this oversubscribed round of financing. The strong interest from investors validates the clear unmet need in this space and we look forward to expanding our world-class team as we drive towards the next development milestones.”
Bihua Chen, founder and managing member of Cormorant Asset Management, added: “Venous thromboembolism (VTE) is a large market that is currently underserved due to limitations of existing treatment options.
“We are excited to lead this round and believe there is ample room for improvement over existing treatments. Akura Medical’s differentiated technology has the potential to overcome these shortcomings with its elegant mechanical thrombectomy solution.”
A wealth of data emerging in the last 18 months, including from a small multicentre, randomised, sham-controlled study of genicular artery embolization for knee pain secondary to osteoarthritis, brings in its slipstream a glimpse of other similar minimally invasive options to treat disability in the entire musculoskeletal system. Embolization, which is rapidly surfacing as a safe and effective procedure for the treatment of patients with osteoarthritis of the knee, has been shown to be technically achievable, with very promising outcomes at early follow-up. It is thought to bring down pain by reducing synovial arterial hypervascularity.
A multicentre, randomised, single-blinded, sham-controlled study published online ahead of print in October 2021 in the Journal of Vascular and Interventional Radiology (JVIR) showed that, in patients with mild-to-moderate knee osteoarthritis, embolization results in symptomatic improvement greater than the sham procedure did, with clinically significant reduction in pain and disability (as measured by the Visual Analogue Score [VAS] and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]). In the 21-patient study, all those assigned to the sham group failed to show significant improvements at one month and crossed over to the treatment arm.
“Genicular artery embolization has the potential to be one of the most commonly performed embolization procedures for interventional radiologists in the near future and make a substantial impact in the lives of millions of patients. The data from our study demonstrate that the effect of embolization in reducing pain and improving function is far greater than the effect of a sham procedure or placebo. This study will be useful in convincing potential referrers as well as insurance companies that this procedure should be part of the osteoarthritic knee pain treatment algorithm. What is most exciting is that this procedure may just be the first of many different embolization procedures that will be utilised to treat pain throughout the musculoskeletal system,” Ari J Isaacson, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA, and one of the researchers on the sham trial, tells Interventional News.
These investigators further reported statistically significantly greater pain reduction captured by VAS in the treatment group when compared to those undergoing the sham treatment at one month (p<0.01). Disability improvement was also significantly greater in the treatment group (p=0.02).
“Genicular artery embolization has given many of my patients, some of whom have previously given up trying to control their pain, new opportunities to live more fulfilling lives. Often, these patients do not respond to conservative management, but are precluded by their comorbidities from having a knee replacement. Embolization can be performed with permanent particles, which have been shown to be safe, or temporary agents such as an imipenem/cilastatin slurry. The embolization technique itself is also constantly evolving to become safer and more effective. Examples include using ice packs on the skin, which have significantly decreased the rates of cutaneous non-target embolization that results in skin ulcerations. Of course, more knowledge is necessary, and important studies are on the horizon. Nevertheless, we should recognise that we do not yet fully understand the mechanism of action of this treatment. With careful due diligence, however, I think we can help many patients. For instance, I treat with temporary embolics rather than permanent embolics, and tend to treat patients who also have more severe disease and more pain,” says Yilun Koethe, Oregon Health and Science University, Oregon, USA.
Another recent publication that set out to evaluate the safety and efficacy of embolization for the treatment of symptomatic knee osteoarthritis found the procedure to be “effective and durable in reducing pain symptoms from moderate or severe knee osteoarthritis that is refractory to other conservative therapy, with an acceptable safety profile.
”Siddarth A Padia (Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, USA) and colleagues write that in their 40-patients study, the WOMAC total and VAS pain scores decreased by 61% and 67% at 12 months from a median baseline of 52 (of 96) and 8 (of 10), respectively. Sixty-eight percent of patients had a reduction of ≥50% in both WOMAC total and VAS pain scores.
The prospective, single-centre, open-label US Food and Drug Administration-approved investigational device exemption study was published in October 2021 in the Journal of Bone & Joint Surgery.
Padia and colleagues pointed to transient skin discolouration and transient mild knee pain after the procedure being “common and expected”. Treatment-related adverse events included a groin haematoma requiring overnight observation, self-resolving focal skin ulceration, and an asymptomatic small bone infarct on magnetic resonance imaging (MRI) at three months.
“Other than total knee arthroplasty, treatments for knee osteoarthritis have been limited in effect and duration. Research over the past several decades has failed to improve treatment options for this common ailment. Genicular artery embolization looks to be a promising breakthrough therapy for symptomatic knee osteoarthritis. Our trial showed that embolization demonstrated a marked reduction in pain and improvement in function in 68% of study participants, with minimal adverse events. Moreover, the duration of effect was seen to at least one year. These results will serve as a platform for a large-scale randomised trial, which will hopefully begin in 2022,” Padia told this newspaper.
If the evidence-base carries on being augmented for genicular artery embolization, experts believe that its impact can be widespread. “Knee pain from arthritis affects many people of different backgrounds, genders, ethnicities, and ages. Embolization has the potential to improve the lives of different kinds of patients all over the world,” Theresa Caridi, University of Alabama at Birmingham, Birmingham, USA, contends.
Mark Little, University Department of Radiology, Royal Berkshire NHS Foundation Trust, Reading, UK, commented: “Over the last 18 months, there has been increasing amounts of data within the literature.All studies have reported consistent results; embolization is a safe and potentially effective treatment for patients with osteoarthritis of the knee. The recent study that randomised 21 patients to receive genicular artery embolization or a sham procedure was the first paper to address the placebo effect. Our own interim data from the GENESIS study, which was published in CardioVascular and Interventional Radiology in January 2021, revealed a significant improvement in pain and function at one-year follow-up, in addition to an improvement in synovitis on contrast-enhanced MRI. Embolization for this indication clearly has the potential to offer a unique, minimally invasive treatment to the millions of patients with symptomatic knee osteoarthritis, which could change the way in which we treat the disease! More data are needed to study the long-term outcomes of the procedure, the health economics associated with it, and the ideal embolic agent. Further randomised controlled studies are warranted comparing it to a sham procedure, and best medical therapy, in order to improve data generalisability. My group is extremely excited to commence recruitment for GENESIS II, a large randomised, sham-controlled trial for genicular artery embolization at the beginning of 2022. The future seems vibrant for this procedure.”
Transit Scientific recently announced that its XO Cross platform has been successfully used in challenging peripheral vascular procedures.
A press release details that Jihad Mustapha, interventional cardiologist at Advanced Cardiac & Vascular Center in Grand Rapids, USA, has performed several procedures using 2F XO Cross 14 microcatheters in 90cm and 175cm lengths, designed to facilitate guidewire support, guidewire exchange, and contrast media injection during complex peripheral vascular interventions.
“The 1:1 torque of the XO Cross 14 provided new levels of trackability during the procedures,” Mustapha states. “The XO Cross 14 performed well when treating anterior tibial artery (AT) to posterior tibial artery (TA) pedal loop chronic total occlusions (CTOs), showing uniquely impressive navigation throughout the pedals, saving time and elevating treatment capabilities.”
He adds: “The XO Cross 14 enabled me to effectively cross four chronic CTOs in the pedal loop and then push up into the proximal posterior tibial to treat an additional CTO during a limb-salvage procedure. I would not have been able to access this CTO without the XO Cross 14 catheter.”
AT to PT pedal loop procedures typically involve crossing narrow, tortuous, stenosed, and potentially calcified and/or occluded distal vasculature to facilitate treatment. Penetrating certain narrow lesions can cause guidewires and catheters to buckle, increasing procedure time, requiring device escalation, increasing X-ray exposure, increasing costs, and increasing risk of procedural complications.
“XO Cross technology continues to perform well in difficult anatomy,” says Greg Method, president and CEO of Transit Scientific. “Successfully performing in AT to PT pedal loop procedures further demonstrates how XO Cross technology can help physicians treat diverse disease with better tools.”
Transit Scientific’s XO Cross platform features 24 US Food and Drug Administration (FDA)-cleared devices including 2Fr XO Cross 14 microcatheters, 2.6Fr XO Cross 18 microcatheters, and the 3.8F XO Cross 35 support catheters for use with standard 0.014″, 0.018″, and 0.035″ guidewires in 90cm, 135cm, 150cm, and 175cm lengths.
Interventional News’ top 10 most popular stories of 2021
The top 10 stories of 2021 feature advances in ablation precision, as well as a multicentre, first-in-human prospective study exploring the safety and efficacy of combined renal and common hepatic artery denervation in patients with type 2 diabetes and hypertension. The CAVA trial, which delivered evidence supporting the use of totally implanted ports to supply systemic chemotherapy, also attracted many readers.
1) Ablation 2.0: Improved precision as interventionalists approach A0
Ablation is entering a new era of increased precision and quantification, the interventional radiology community argues. Several clinical trials—including the ACCLAIM, COLLISION, and COVER-ALL trials—are currently underway, and aim to bolster the evidence-base demonstrating favourable patient outcomes from thermal ablation.
2)Multi-organ denervation to combat cardiometabolic disease: A novel concept put to the test
Following a successful proof-of-concept study, researchers have embarked upon a first-in-human study to explore the safety and efficacy of combined renal and common hepatic artery denervation in patients with type 2 diabetes and hypertension. Co-principal investigators Gerard S Goh and Markus P Schlaich explain the rationale behind this single-blinded, multicentre, prospective feasibility study—named the MODUS trial—and explore the “pandemic” of cardiometabolic disease.
Trisacryl gelatin microspheres 100–300μm in size can be considered for genicular artery embolization (GAE), a study presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online) reported. The presentation covered two-year outcomes of a study comparing Embosphere microspheres (Merit Medical), with imipenem cilastatin for GAE in patients with moderate-to-severe knee osteoarthritis. The particles are comparable in terms of pain reduction and there is a sustained effect out to two-years of follow-up, Shivank Bhatia (University of Miami Miller School of Medicine, Miami, USA) informed delegates.
Despite lower mortality and shorter hospital stays, uterine artery embolization (UAE) is used far less commonly than hysterectomy in the management of clinically significant postpartum haemorrhage. This conclusion, presented at the Society of Interventional Radiology (SIR) annual meeting (20–26 March, online) by Janice Newsome (Emory University Hospital, Atlanta, USA), has led investigators to call for a postpartum haemorrhage response team, akin to a trauma response team. MD candidate Linzi Ardnt, also at Emory University Hospital, is the lead researcher for this work.
5) Parag Patel
From an early understanding in medical school that interventional radiology was “the future”, Parag Patel has dedicated his career to the discipline, notably as a primary investigator of the BEST-CLI and ATTRACT trials, and now as the incoming president-elect of the Society of Interventional Radiology (SIR). He has also been integral to the design and implementation of a universal interventional radiology education curriculum in the USA. In so doing, he has played a large part in shaping that future he once envisioned.
6) Coding changes will impact reimbursement for US interventional radiologists in 2021
Revisions to current procedural terminology codes in the USA for 2021 overhaul the evaluation and management section, reducing documentation requirements and introducing new rules determining the level of coding. These changes will affect interventional radiologists and radiation oncologists more than they will impact the day-to-day work of diagnostic radiologists, according to Erin Stephens, a senior client manager in education at Healthcare Administrative Partners.
Siemens Healthineers has launched the Somatom X.ceed, a new high-resolution, high-speed computed tomography (CT) scanner. The fastest single-source CT scanner from Siemens Healthineers can assist healthcare providers with their clinical decisions in areas like emergency imaging, cardiac CT, and CT-guided interventions.
Constantinos Sofocleous (Memorial Sloan-Kettering Cancer Center, New York, USA) sat down with Interventional News to discuss how image-guided thermal ablation, when it is deployed with an intent to cure small colorectal liver metastases, can be fine-tuned so that its outcomes match those achieved by open surgery.
9) Ablation-confirmation software must become the new normal for IRs to be competitive with surgeons
“If interventional radiologists wish to become competitive with surgeons, the availability of software enabling the accurate comparison of pre- and post-interventional computed tomography or magnetic resonance imaging scans must become mandatory and routinely employed,” Luigi Solbiati (professor of Radiology at Humanitas University, Milan, Italy) argues.
For most patients receiving systemic anticancer treatment, totally implanted ports (PORTs) are more effective and safer than both Hickman-type tunnelled catheters (Hickman) and peripherally inserted central catheters (PICCs). The CAVA trial’s results, published online in The Lancet, recommended reshaping current guidelines and practice, so that most patients requiring chemotherapy for solid tumours receive a PORT within the UK National Health Service, foreshadowing a pivot in practice that might be “slow to start with”.
December’s top 10 features findings of a retrospective cost-utility analysis published in BMJ Surgery Interventions & Health Technologies. In addition, highlights from the 2021 British Society of Interventional Radiology (BSIR) Annual Scientific Meeting (8–10 December, Glasgow, UK) attracted many readers, alongside an interview with the BSIR former president, Trevor Cleveland (Sheffield, UK).
This advertorial is sponsored by Sirtex Medical.
Two experts in the field of interventional radiology, Bernhard Gebauer (head of interventional radiology at Charité – Universitätsmedizin Berlin in Berlin, Germany) and Ahmed Kamel Abdel Aal (professor of interventional radiology at the University of Texas Health Science Centre in Houston, USA) talk to Interventional News about their experience with SIR-Spheres Y-90 resin microspheres (Sirtex Medical).
2) One-year snapshot shows cost benefits for prostate artery embolization over gold standard surgery
A retrospective cost-utility analysis from a UK National Health Service (NHS) perspective finds prostate artery embolization is more cost-effective than transurethral resection of the prostate, the gold standard for the management of patients with benign prostate hyperplasia at one-year follow-up.
3) BSIR expands focus on diversity, equity and inclusion
Elika Kashef (interventional radiologist at Imperial College NHS Trust, London, UK) addresses the implications of interventional radiology not being equally accessible to people from all walks of life. This has triggered a re-think in the aspirations and nomenclature of the British Society of Interventional Radiology (BSIR) Women and Diversity Committee so that its broader agenda is reflected in its new name: Diversity, Equity and Inclusion Committee.
4) BSIR 2021: Interventional radiologists rev up on IR registry and build strong case for day-case units
The British Society for Interventional Radiology (BSIR) has set up an interventional radiology (IR) registry to capture a glimpse of the scope, breadth, and immediate complication rate provided by the service in the UK. In parallel, UK interventional radiologists are bent on building a strong case for IR units to have their own day-case facilities, as these enabled the subspecialty to take pole position during the pandemic as a great resource for image-guided interventions and activity in a COVID-19-secure environment.
5) Expert raises red flags over forgotten stents and how they fail
“In the last few years, we have seen quite a dramatic increase in patients who present with a structural failure of their stent in the upper gastrointestinal tract, notably the oesophagus, stomach, and duodenum, which has been brought on by the dramatic increase in survival of patients, even with disseminated cancer, Hans-Ulrich Laasch (Christie NHS Foundation Trust, Manchester, UK) tells Interventional News.
Nicholas Inston (consultant vascular access and renal transplant surgeon, Birmingham, UK) discusses the crucial care interventional radiologists provide for renal patients with Ian Mcafferty (consultant interventional radiologist, Birmingham, UK, and immediate past president of the British Society of Interventional Radiology [BSIR]).
7) Philips acquires Vesper Medical
Royal Philips has announced that it has signed an agreement to acquire Vesper Medical, a US-based medical technology company that develops minimally-invasive peripheral vascular devices.
8) Fluidx Medical Technology announces Series A led by multinational strategic investor
Fluidx Medical Technology recently announced the oversubscribed closing of the first tranche of its Series A financing round. The Series A was led by a large multinational strategic investor and joined by the existing investor base as well as several new investors. A press release details that the funding will be used to support prospective clinical trials, including the pivotal trial, as well as preparation for market entry.
9) Personalised dosimetry and inclusion in guidelines redraw SIRT use for HCC
Jon Bell (Manchester, UK) outlines the importance of standardisation of selective internal radiation therapy (SIRT) and how this rests on an advanced understanding of personalised dosimetry to achieve optimal outcomes for hepatocellular carcinoma (HCC) patients. “So interventional radiologists, wherever they work, will be treating the same patients in the same way. […] The standardisation is crucial,” he says.
“Young interventional radiologists have got a very exciting future,” Trevor Cleveland (Sheffield, UK, and a former president of the British Society of Interventional Radiology [BSIR]), tells Interventional News. In 2021, Cleveland delivered the Wattie Fletcher lecture at the BSIR Annual Scientific Meeting (8–10 December, Glasgow, UK).
Upstream Peripheral Technologies announced today that its GoBack catheter for crossing and re-entry was proven very effective for patients undergoing complex revascularisations in lower limb arteries. The findings are based on a peer-reviewed study published in the Journal of Endovascular Therapy.
In a single-centre retrospective study led by Andrej Schmidt (University Hospital Leipzig, Leipzig, Germany), researchers reviewed outcomes of 100 consecutive patients who underwent treatment with the GoBack catheter after failed crossing attempts using standard guidewire and support catheter techniques. All lesions were confirmed as either de novo or reoccluded chronic total occlusions (CTOs). The overall technical success rate was 92%.
According to Upstream, the study highlights the versatility and effectiveness of the GoBack catheter as both a crossing and re-entry tool when compared to alternative products, and further outlines the clinical benefits of the GoBack catheter with its robust, retractable needle at its tip.
Dani Rottenberg, founder and CEO of Upstream, remarked, “All patients should have access to the most effective endovascular revascularisation technologies to avoid unnecessary bypass surgeries and amputations. The GoBack helps clinicians achieve such a goal, especially in more complex lesions.”
With these positive results, Upstream plans to make the GoBack available to hospitals and peripheral vascular catheterisation labs throughout the world. Rottenberg explains, “The GoBack helps facilities manage their costs and maximise their lab optimisation by reducing procedure time and using less consumables per procedure.”
A press release details that the GoBack catheter is a single-lumen crossing catheter which features a curved nitinol needle that serves as an effective crossing tool. The needle can be extended straight or to a curved position beyond the GoBack catheter’s tip. The protrusion length is determined by the clinician with a thumb selector on the device’s handle. The GoBack comes in two configurations of 4 French and 2.9 French for above- and below-the-knee procedures. The GoBack has regulatory approval in 30 countries.
Royal Philips has announced US Food and Drug Administration (FDA) de novo clearance for the Philips inferior vena cava (IVC) filter removal laser sheath—CavaClear—to remove an IVC filter when previous methods of removal have failed.
Philips CavaClear IVC filter removal laser sheath is the first and only FDA-cleared solution for advanced IVC filter removal, the company said in a press release. Earlier in 2021, the FDA granted the device Breakthrough Device Designation. Laser has been clinically proven to provide a success rate over 99%, with low complication rates, the press release adds.
IVC filters are used to treat patients with venous thromboembolism, in which blood clots form in the deep veins of the leg and groin, and can travel through the circulatory system. They are placed in the inferior vena cava to capture blood clots from moving to the lungs.
Research has shown that IVC filters may have long-term complications, as the filters can fracture and travel through the bloodstream to other parts of the body. Other identified long-term risks associated with IVC filters include lower limb deep vein thrombosis and IVC occlusion. The FDA recommends that implanting physicians consider removing retrievable IVC filters as soon as they are no longer indicated.
Prior to CavaClear, limited options for removal existed if the filter became difficult to remove, according to Philips. Advanced retrieval tools and techniques are required if the IVC filter becomes embedded in the vasculature. Physicians previously had very few tools to remove the filter when complications occurred and until now there were no FDA-approved devices for this type of advanced removal.
“Today is a historic day. With the approval of CavaClear, physicians now have a device specifically geared remove chronically embedded IVC filters,” said Kush R Desai MD, associate professor of Radiology, Surgery, and Medicine, and director of deep venous interventions at Northwestern University Feinberg School of Medicine (Chicago, USA). “Backed by evidence, this technology can be applied to retrieve IVC filters that are no longer indicated, reducing potential clinical risk for patients and satisfying the FDA’s guidance to retrieve filters when they are no longer indicated.”
“With the FDA’s clearance of CavaClear more than one million patients and their physicians now have access to a safe, effective and efficient option for advanced IVC filter removal,” said Chris Landon, senior vice president and General Manager Image Guided Therapy Devices at Philips. “This clearance demonstrates the commitment of Philips to innovating procedures with physician collaboration to meet unmet needs that can have a critical impact on the lives of patients and their families.”
Fist Assist Devices has announced that it recently received Breakthrough Device designation from the US Food and Drug Administration (FDA) for its Fist Assist Model FA-1 device.
According to the company, the FA-1 is the world’s first wearable device for presurgical vein dilation that promotes arteriovenous fistula (AVF) creation in adult patients diagnosed with chronic renal failure whose preoperative assessment of the venous anatomy suggests that superficial arm vein or perforator vein size is inadequate for the creation of an AVF for haemodialysis access.
Access to the FA-1 device by patients with an end-stage renal disease (ESRD) vein dilation indication is now expedited through the FDA Breakthrough Device programme—which is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions, such as ESRD.
The programme provides Fist Assist with priority FDA review and interactive communication regarding device development, clinical data, and future indication applications, during the premarket review process, according to a press release from the company.
“As this is a first-of-its-kind wearable device for haemodialysis patients focused on presurgery vein dilation, we are ecstatic to have the FDA recognise this innovative approach to vein dilation and the potential of this therapeutic wearable device that supports the patient’s journey through ESRD,” said Hrishikesh Gadagkar, Fist Assist regulatory advisor and CEO of Idonea Solutions. “We appreciate the FDA’s thorough review of Fist Assist’s Breakthrough Device designation request and look forward to a collaborative relationship as the company develops its FDA de novo classification application.”
The FA-1 device is a wearable, intermittent pneumatic compression device that is worn on the arm to promote vein dilation. The device compresses the outflow vein, which has both biological and physiological benefits, and—because it is automated—the FA-1 device significantly improves patients’ compliance compared to other vein dilation alternatives.
“This designation is another major milestone for Fist Assist Devices. We expect it to change the algorithm for patient care,” said Tej Singh, founder and CEO of Fist Assist. “The recently published data from the FACT trial on stage 4 vein dilation and pFACT trial on perforator vein dilation confirms the value of intermittent vein compression to CKD [chronic kidney disease] patients.
“The FA-1 device benefits patients, physicians and healthcare delivery systems because larger veins give patients more treatment options regarding surgical or endoAVF procedures. Ultimately, our goals are to help patients achieve better outcomes and have more hope. This designation gets us one step closer to accomplishing our goals.”
“Young interventional radiologists have got a very exciting future,” Trevor Cleveland (Sheffield, UK, and a former president of the British Society of Interventional Radiology [BSIR]), tells Interventional News. In 2021, Cleveland delivered the Wattie Fletcher lecture at the BSIR Annual Scientific Meeting (8–10 December, Glasgow, UK).
In discussing the rapid transformation seen in interventional radiology (IR) during his career, Cleveland draws out the revolutions in treatment for gastrointestinal (GI) bleeding, oncology, and trauma that have all been marked by a shift to more minimally-invasive treatments. In his view, the ability for IR to provide a 24-hour service, generate evidence for good patient care, and grasp technological advances have been central to underpin success and “embrace the change”.
“We are very dependent on, and use a lot of high-tech devices. […] One of the reasons we did not treat GI bleeds was because the coils were big, cumbersome, and difficult to deliver. Nowadays, we have got microcatheters and microcoils and we can really get right to work to where the bleeding is a problem,” he explains.
And, on the subject of evidence, Cleveland says, “evidence is king, really, isn’t it?”
Nicholas Inston (consultant vascular access and renal transplant surgeon, Birmingham, UK) discusses the crucial care interventional radiologists provide for renal patients with Ian Mcafferty (consultant interventional radiologist, Birmingham, UK, and immediate past president of the British Society of Interventional Radiology [BSIR]).
Mcafferty asserts that there has been “an evolution” that has seen interventional radiologists poised on the brink of “a primary care role” to deliver therapies such as renal ablation, tumour embolization, and prostatic artery embolization. This shift might provoke the need for a specialised renal or broader, genitourinary, interventionalist. “[These minimally invasive procedures are being] driven by the patients wanting them, rather than traditional surgery,” Mcafferty insists.
Dialysis interventions come in for particular scrutiny with interventional radiologists adding percutaneous arteriovenous fistula creation (EndoAVF) to an armamentarium that has, in the main, consisted of maturation, maintenance and salvage interventions.
The sweeping advances in technology will see interventional radiologists, who tend to be early adopters, really push the field forward, “and this will benefit renal patients”, says Inston, who is also on the executive board of the Charing Cross (CX) Vascular Access Masterclass and editor-in-chief of Renal Interventions.
This interview was filmed at the BSIR Annual Scientific Meeting 2021 (8–10 December, Glasgow, UK).
Jon Bell (Manchester, UK) outlines the importance of standardisation of selective internal radiation therapy (SIRT) and how this rests on an advanced understanding of personalised dosimetry to achieve optimal outcomes for hepatocellular carcinoma (HCC) patients. “So interventional radiologists, wherever they work, will be treating the same patients in the same way. […] The standardisation is crucial,” he says.
“The biggest thing we have seen in the past few weeks is the new Barcelona Clinic Liver Cancer (BCLC) classification, and the importance of seeing radioembolization there for the very first time, and it is there because of LEGACY data,” he says, noting that the dosimetry is a core component of this. It is only when the whole team is familiar with dosimetry that “we going to get the best outcomes for our patients and it is all about patient care at the end of the day,” comments Bell. In parallel, in the UK, the National Institute of Health and Care Excellence (NICE) multiple technology appraisal guidance has granted SIRT reimbursement leading to the treatment gaining ground and a changed landscape.
“We now have great opportunity where we can educate, influence interventional radiologists to go out and promote the therapy and really embed it in the patient pathway,” he says at the British Society of Interventional Radiology (BSIR) Annual Scientific Meeting 2021 (8–10 December, Glasgow, UK).
Janice Newsome (Emory University Hospital, Atlanta, USA), tells Interventional News that she considers herself “a little bit of a global citizen”. “As interventional radiologists, we believe deeply in what we do, every single day—fundamentally, that it improves the health of the patients we treat. And if I believe that, it is only one step further away to see that good healthcare should be available to everyone, everywhere. So, health equity is crucial, both where high-quality healthcare is already being provided, and even more so in places where it is not available, or accessible,” she says.
Newsome is also categorical that while she is a strong believer in “interventional radiology”, the desire to take these image-guided procedures to benefit patients in need of them, across the world, means that she is open to looking beyond traditional silos and groups to the broad church of available specialists on the ground. Her sights are set on training really anyone in the healthcare team who can be trained to deliver image-guided procedures, well. “As interventional radiologists, we could never put in all the nephrostomy tubes or all the dialysis catheters that are needed for the population in Tanzania or Rwanda. We really need to be able to partner with the nephrologists seeing these patients; we need to be able to partner with the surgeons that may be already placing subclavian catheters with less-than-optimal outcomes, right? Because again, what we want to do is to advance minimally-invasive procedures. Yes, ideally via interventional radiologists, but really at the end, it is to help with the health of that population and not to really dissect the human body in the way that we have in other parts of the Western world to say that only this specialty can do this here, or only that specialty can do that there. Our goal is to train these skills broadly. And yes, we prefer that these procedures are done by interventional radiologists, but I find that the best way is to find out who else is on this journey.”
Minimally-invasive procedures for maximum impact
Newsome points to one of the smallest procedures performed by interventional radiologists—percutaneous abscess drainage—as having a colossal impact. “People in every country need to be able to have percutaneous abscess drainage. We can actually get a needle into any cavity, or any place in the body and try to drain infected fluid from that body cavity. That simple procedure has done so much to change outcomes. It should be available to any doctor who can use simple imaging to put a tube in the body to prevent the patient from needing another operation, needing anaesthesia, or long hospital stays, or even potentially, dying.” Maternal mortality, especially when related to clinically significant postpartum haemorrhage, is another area in which Newsome seeks to move the needle with interventional solutions. “A more advanced procedure that I do think should be available to every woman, everywhere, and will change the percentages of women that die during childbirth, in large part due to bleeding [complications], is embolization. I believe that any doctor, and I hope it is an interventional radiologist, who can safely perform embolization procedures to stop bleeding can help to save a woman’s life during childbirth. I am really passionate about this, because I believe that giving birth should be something that is quite joyous and no one should die while they are trying to bring a life into the world.” Pain palliation procedures are also singled out as being transformative to populations, be they nerve blocks, or ablation procedures to treat pain. Because pain, in some communities, can change the entire livelihood of a family.
For instance, in farming communities, farmers with degenerative conditions such as arthritis may not be able to provide for their families due to pain. “Pain has a huge impact on lives. Procedures that can alleviate pain and help with degenerative changes in the body should be provided around the world,” she says.
A local and global need
It is generally accepted that lower- and middle-income countries would be able to improve the health of their populations with the wider deployment of image-guided procedures. Newsome contends: “I would say that the need is great locally. And the need is great globally. Low- and middle-income countries tend to be where we focus on when we talk about global health. I have decided myself to concentrate my efforts in Sub-Saharan Africa and to concentrate that effort into training programmes where sustainability is more important. So medical tourism is not the name of the game and medical missions are not the name of the game. Instead, how we assess what is going on locally in that area and provide the care that that population needs [is the real focus].”
Outreach efforts and training
There have been several organisations over the years that have recognised this deficit of minimally invasive procedures in several countries in the world. “Organisations such as Rad-Aid, Partners Health, Doctors Without Borders, have all done incredible work. I can talk specifically about a programme called Road to IR. This organisation decided to take a different approach to set up curriculum training programmes in partnership with universities to provide in-depth training for interventional radiology. It was birthed in Tanzania, and although this programme began many years ago, three years ago we graduated our first fellowship-trained interventional radiologist from Tanzania who eventually moved back to Rwanda, where he originally came from. We are replicating the same programme Road to IR Rwanda through the generosity of one of our industry partners, and the Memorandum of Understanding signed between Emory University and the Ministry of Health in Rwanda. Our goal there is to continue to provide minimally-invasive procedures through an educational programme knowing very well that you can give a person a fish and they will eat fish on that day, but if you teach a person to fish, they will eat fish every day.”
Elaborating, she adds: “If we are able to get in at the university level and start training interventional radiologists, then we are going to be able to blanket whole regions and through societies be able to provide examinations to be able to validate this training, so that people can move freely from one country in Africa to the other and still be able to continue their training and then be able to be in practice.”
Newsome acknowledges that the barriers to widespread adoption of image-guided procedures rests in large part on the high cost of disposables, the time of experts, and language and translation barriers. Of course, COVID-19 was particularly disruptive for training programmes abroad. Still, she remains upbeat. “Even with that disruption, I will tell you that we have still survived and even thrived during COVID-19. One of the things it taught all of us is really how connected our world is; it also forced us to embrace other technologies in medicine. Besides the platforms that allow us to speak to each other, procedural telemedicine was birthed during COVID-19. Even in our lab, we were able to broadcast cases initially through what my partners here call ‘ghetto technology’—having one camera look at another camera or my laptop and five iPads in a room, trying to make sure that our learners are still learning, whether these are learners from right here at Emory or learners that are across the pond or ocean. There has also been an acceleration in the industry development of these technologies. We are going to be way better off in terms of procedural telemedicine or procedural education using these platforms going forward. I am excited about it and there are several of them that are already on the horizons being tested right here,” she says.
Smiling at the margins of progress
What encouraging health equity milestones would bring a smile to Newsome’s face? “I believe that in terms of global health equity, I am going to dance when we are able to have interventional procedure lists deployed in low- and middle-income countries in numbers that are suitable for their populations; I am going to dance when maternal mortality is really changed in the USA, considering that I am also right here in Georgia, a state where this is a huge medical issue. And one single thing that I know from a health equity standpoint that will continue to make me smile is when I see women interventionalists/ women proceduralists taking their rightful role in healthcare. When we are able to break down all those barriers in places in the world where medicine and medical care in the form of minimally-invasive procedures are so male-dominated, I will truly laugh. So, when more women are involved in that space, I believe that we are going to see a lot of change—and I will dance long and hard when those numbers start becoming more equal.”
Emma Hardy, UK Member of Parliament (MP) for Hull West and Hessle and chair of the All-Party Parliamentary Group on Vascular and Venous Disease, outlines pilot efforts steered by National Health Service (NHS) England and the National Wound Care Strategy Programme to improve the care landscape for people afflicted with lower limb wounds in the UK.
This country is facing a crisis in vascular disease made worse by the effects of the COVID-19 pandemic. However, there is a potential answer in the recommendations of the National Wound Care Strategy Programme, being implemented in places like Hull University Teaching Hospitals Trust, but for it to succeed it needs the full commitment and backing of government.
When I was younger my neighbour suffered from vascular disease, although I did not understand at the time. The course of their disease meant an amputation and a life curtailed by pain and disability. I grew up as witness not only to their suffering, but to that of the loved ones and family around them. These memories came rushing back two years ago when I was visiting Hull Royal Infirmary and meeting the vascular service staff, patients, and their families. Suddenly I was reliving this experience through their eyes, and through the eyes of the medical staff who treat this awful disease. The effect on me was immediate and profound.
I learnt that the the most severe form of the disease comes after the tissues have died resulting in foot and leg ulceration, threatening the life of the sufferer. If they do not receive successful treatment to restore blood flow and save their leg, they not only lose it, but face worse survival rates than people with heart failure, stroke, and most cancers.
I was completely unprepared for the scale and the severity of the disease in the UK. Nor was I expecting to hear of the lack of investment in treatment alongside the huge disparities in outcomes depending on where you lived. The General Election was announced shortly after my visit, but the experiences of that day haunted me. Particularly the words of a surgeon, as he showed me images of foot ulcers, that “time is tissue”; that the development of a foot ulcer from something that appears to be small and trivial into something that requires amputation, can be as short as 48 hours.
Many who are not at risk of an amputation must still live with wounds that struggle to heal on their own. Research suggests that around 730,000 wounds of the leg and feet occur each year in the UK. These wounds can be incredibly painful and debilitating, to the point that the person is unable to walk properly and struggles to cope with everyday activities, such as going to the shop or meeting with friends.
Once Parliament reconvened after the election, I joined the All-Party Parliamentary Group on Vascular and Venous Disease and was appointed Chair. As a result, I have had the privilege to meet some of the brightest clinicians and researchers working to revolutionise the way we care for people with these health conditions. Some of this innovative work is taking place right here in Hull.
The National Wound Care Strategy Programme is an initiative to improve the care of wounds, including those on legs and feet. I recently met with the passionate Hull Royal Infirmary and City Health Care Partnership teams who were awarded the opportunity to lead the development of this innovative programme with a national pilot site in Hull. They described the work required to reorganise and integrate the care system to deliver better outcomes for patients. The aim is to make it as easy as possible for people with these health issues to access the right care as soon as possible and the results have been extremely encouraging.
Nurses report that patients’ wounds are healing much better than they did before, and 100% of those treated have rated the new service as “good” or “very good”. I am heartened both by the positive impact this programme has had on patients, and by the fact that Hull is at the epicentre of this national revolution in healthcare.
Although the new systems are having positive effects, the teams are battling with a severe staffing crisis, particularly in community nursing. The Government needs to develop a comprehensive workforce plan to ensure our local NHS services in Hull can meet people’s needs.
Vascular disease is a prime example of how investing in prevention and prompt treatment prevents chronic long-term conditions that ultimately cost far more, both in monetary terms and in human suffering. The cost of wound management in the NHS currently stands at a staggering £8.3 billion a year and the government must understand that if they provide the necessary resources now, our hard-working health professionals can make a real and profound difference to the futures of tens of thousands of people and reduce long-term financial pressures.
Disclaimer
All-Party Parliamentary Group on Vascular and Venous Disease communications are not to be considered official activity from either the House of Commons or the House of Lords. It has not been approved by either House or its committees. All-Party Parliamentary Groups are informal groups of Members of both Houses with a common interest in particular issues. The views expressed in these pages are those of the group.
Elika Kashef (London, UK) addresses the implications of interventional radiology not being equally accessible to people from all walks of life. This has triggered a re-think in the aspirations and nomenclature of the British Society of Interventional Radiology (BSIR) Women and Diversity Committee so that its broader agenda is reflected in its new name: Diversity, Equity and Inclusion Committee.
She talks about the multiple outreach efforts and challenges to ensure that medical students, irrespective of their background, race or gender, are exposed to interventional radiology—an essential requirement to deal with the huge workforce issue that is looming for the subspecialty, simultaneously making certain that the life-saving benefits of interventional radiology are available to all. The new committee will also maintain its focus on retaining women in interventional radiology to up their number from the current 12%, Kashef tells Interventional News at the BSIR Annual Scientific Meeting 2021 (8–10 December, Glasgow, UK).
Alexandros Mallios (Paris, France) and Robert Shahverdyan (Hamburg, Germany) talk to Vascular News about some of the benefits of the Ellipsys™ Vascular Access System (Medtronic), how it compares to more traditional fistula creation techniques, and the key steps for achieving EndoAVF success with the system.
“What I love about Ellipsys is that the procedure is very easy and you can create a very durable arteriovenous (AV) fistula in a short time and with good results,” says Shahverdyan. Mallios outlines that the device is “very simple [to use] and efficacious”. The steps taken when using Ellipsys are “very repetitive” and thus provide a greater consistency in outcomes than those seen with surgically created fistulas, states Mallios, adding that surgery leads to “fairly variable results”. Using Ellipsys can help “minimise these differences so that you get very similar results each time”. Another major advantage of the procedure is that it is “almost painless for patients” and is associated with “better long-term flow results”, he adds.
Shahverdyan and Mallios further compare EndoAVF procedures with traditional surgical techniques, with Shahverdyan noting that the former offers “significantly shorter procedure time with practically no adverse events”. Understanding the anatomy of the patient is “crucial” in order to plan the procedure as well as how to cannulate the fistula, he adds. He also discusses the fistula flow rates obtained with the Ellipsys system and how best to optimise the procedure so that other physicians can “get the great results that we have had”.
This video is sponsored by Medtronic.
Principal investigator of the VOYAGER PAD trial, Marc Bonaca (University of Colorado Anschutz Medical Campus, Aurora, USA) speaks to Vascular News about the latest data from the study, which indicate that patients with claudication are at high risk for adverse limb events and cardiovascular events after undergoing revascularisation. Bonaca highlights the significance of the findings—which he presented the findings at the American Heart Association (AHA) Scientific Sessions (13–15 November, virtual)—and, speaking on what is next for VOAYGER PAD, relays that “there is a lot yet to come”.
What are the key takeaway message from this new subanalysis?
We learned that patients who underwent revascularisation for claudication were severely disabled, with 62% unable to or able to with much difficulty for walking two blocks. We also found that revascularisation was effective in the short term in terms of haemodynamics (ankle-brachial index), patient-reported outcomes (the 62% with disability was reduced to 18%), and in terms of physician assessment (61% with moderate or severe symptoms were asymptomatic or with mild symptoms after the procedure). The benefit on patient-reported outcomes appeared durable out to about two years. With these benefits, however, we saw that the risk of major adverse limb events like amputation and acute limb ischaemia were frequent and increased fourfold on what we see for patients with claudication who have not progressed to needing revascularisation. Finally, we saw a significant benefit of rivaroxaban with regard to irreversible harm events of the heart, limb and brain, with a number needed to treat less than 50, and while there was more bleeding with rivaroxaban, there was a net benefit in this population when looking at events prevented/caused or the net outcome of event-free survival.
Why was it important to carry out a subanalysis of patients with chronic peripheral arterial disease (PAD) who have claudication?
Many clinicians may consider patients with claudication at lower risk of adverse limb events and therefore question the risk/benefit of intensive antithrombotic therapy. It was important to understand the risks in the population and the risk/benefit of therapy.
Are there any findings of the that surprised you?
The data on the durability of benefit for symptoms was surprising and encouraging. The data showing the very high risk of adverse limb events was concerning and surprising.
VOYAGER PAD updates always interest our readers—why do think that might be?
VOYAGER PAD was a unique trial. There are very few trials in PAD and this is the largest post revascularisation trial. Beyond the efficacy and safety of rivaroxaban, it serves as an important dataset to learn about PAD as a disease state and how we can better risk stratify and treat this extremely high-risk population.
What is next for VOYAGER PAD?
There is a lot yet to come and in some ways we have just started. We have extensive data on patient-reported outcomes to understand disability in this population. We have analyses understanding how optimal medical therapy (e.g. statin use) impacts the risk benefit of rivaroxaban and overall risk. We have subgroup analyses exploring high risk subgroups like those with chronic kidney disease. We also have limb specific analyses such as validation of the Wound, Ischemia and food Infection (WIfI) classification, and data to come from an angiographic core lab of over 2000 images. Like all trials, VOYAGER PAD was a collaborative effort and many are participating and leading these important analyses.
A large-scale analysis of the use of Philips’ intravascular ultrasound (IVUS) in lower extremity peripheral vascular interventions adds “meaningful data” to a growing pool of evidence advocating the continued use of the imaging methodology, Eric A Secemsky (Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA) tells Vascular News. The focus now, he believes, should be on understanding and addressing barriers to widespread adoption of the technology.
What are the key takeaways from this study?
In our analysis—which I presented for the first time at Transcatheter Cardiovascular Therapeutics (TCT) 2021 (4–6 November, Orlando, USA)—IVUS use made up about 11% of lower extremity arterial interventions, and when used as part of those procedures, was associated with improved outcomes, including decreased risks of amputation and thrombosis. So, although causality is hard to prove in an observational study, that association seems robust when IVUS was used during the peripheral vascular procedures.
Another take-home message is that IVUS use during iliofemoral venous stenting was actually quite high—it was used in over 50% of procedures. I think what this shows is that if you are not using IVUS, you are going to be in the minority when you are performing iliofemoral venous stenting. We have to restrain causal interpretation here, but when IVUS was used as part of a venous procedure, there were fewer hospitalisations for stent embolisation or stent thrombosis, and so we have to assume that IVUS played at least a partial role in those outcomes.
What are the benefits and drawbacks of real-world data?
The strengths of real-world data are that they represent the patients we take care of in clinical practice and the large sample size allows us to look at important subgroups while still analysing a meaningful number of procedures. They also allow us to collect important information on use patterns—so, in this case, how IVUS is being used over time and how it is being used by different providers.
There are limitations as well, and we conduct observational analyses like this one with caution in terms of causal inference. You can gain a good understanding of what outcomes look like between patients who are treated with IVUS versus those not treated with IVUS, but there are certainly important characteristics that we are not able to capture in a claims-based analysis such as anatomical considerations and the reasons why IVUS was used.
With this analysis, we have been able to provide some real-world evidence that IVUS appears to be associated with a beneficial outcome as part of a procedure, and, overall, I think that these are meaningful data to help guide us forward in terms of the continued use of IVUS. However, we must be mindful of some of the limitations associated with real-world data.
This has proven to be a popular story on the Vascular News website—do you have any views on why that might be?
We have increasingly been performing endovascular procedures in the peripheral vascular space, yet our patients are still having adverse events such as venous stent embolisation. I think we understand that we can do something better here, and I think everyone in the field is looking to see how we can improve our outcomes. We have learned a lot from the coronary space where IVUS has been an important adjunctive therapy to improve outcomes, and so I think with that type of experience behind us, as well as some (albeit limited) data out there to support IVUS use in peripheral interventions, and then also our anecdotal experience, more and more people are understanding the value of what IVUS adds to optimise the procedure and achieve better outcomes for our patients.
How does your data compare to previous studies of IVUS in the peripheral space?
We have performed a pretty exhaustive systematic review summarising all the data on IVUS that hopefully will be in press in the near future. There are actually limited data in the arterial sphere, and most are from either from single-centre or small, multicentre, retrospective studies. That being said, the data that are available have primarily shown that IVUS can be beneficial in multiple phases during peripheral arterial intervention. On the venous sides, there are stronger data thanks to the VIDIO study, which was a prospective study evaluating the benefits of IVUS during peripheral venous intervention. Those data are probably the highest-level data we have in the peripheral IVUS space. Overall, I think that all the data out there, including from this latest analysis, are showing consistent findings of benefit.
You announced a new global consensus for the appropriate use of IVUS at Vascular Interventional Advances (VIVA) 2021 (5 – 7 October, Las Vegas, USA)—do these new real-world data inform the recommendations at all?
The consensus document really helps harmonise where experts in the field feel IVUS is beneficial during peripheral interventions. I think it also demonstrates that there is a lot of support for incorporating IVUS routinely into practice and that this is not dependent on the need for more prospective data. These sentiments are already set without the availability of a large-scale randomised trial—ongoing, resulting, or otherwise. I think the take-home message from the global consensus document is that IVUS is an important adjunct to peripheral procedures and this mirrors the growth in IVUS use we observed in the Medicare studies.
What is next for IVUS in peripheral vascular interventions?
Our focus now is on trying to understand other barriers to adoption outside of generating more prospective data. I think that with the results of the consensus document, there is a clear and strong endorsement for using IVUS during peripheral interventions and now we need to understand why people are not using it. One of the reasons will be reimbursement, and that is hard to control, but a lot of it relates to educating practitioners to readily interpret IVUS images and understanding how to build the technology into their workflow without creating delays or extending the length of the procedure.
Do you think it is time for guidelines to advocate the use of IVUS in peripheral interventions, or is there still a way to go in terms of having enough data to back that up?
Based on the consensus of operators and the already increasing use of IVUS—especially in the iliofemoral venous system—I think it should be given a high level of recommendation in any upcoming guidelines. Obviously, there are economic considerations, but from a safety standpoint there is really no harm with these devices. IVUS is meant to improve outcomes, which we and others have shown, and so I think that it definitely deserves inclusion in the guidelines with high support.
Royal Philips today announced that it has signed an agreement to acquire Vesper Medical, a US-based medical technology company that develops minimally-invasive peripheral vascular devices.
Vesper Medical will further expand Philips’ portfolio of diagnostic and therapeutic devices with an advanced venous stent portfolio for the treatment of deep venous disease, the company notes. The transaction, which is subject to customary closing conditions, is expected to be completed in the first quarter of 2022. Financial details of the transaction were not disclosed.
A press release details that Vesper Medical will complement Philips’ current intravascular ultrasound (IVUS) offering in venous imaging by adding a venous stenting solution to address the root cause of chronic deep venous disease. The Vesper Duo venous stent system consists of venous stents intended to treat deep venous obstruction.
“The acquisition of Vesper Medical is another step in our objective to innovate patient treatment with more sophisticated technology and expand our growth in the vascular therapy space,” said Chris Landon, senior vice president and general manager Image Guided Therapy Devices at Philips. “Leveraging our significant procedural expertise, we see strong clinical synergies between Vesper Medical’s innovative stenting solution and our existing peripheral vascular offering. This combined offering will help to better support clinicians to decide, guide, treat and confirm during the procedure, thereby enhancing patient care.”
“I am proud that Philips will become the home for our innovations and our people, joining forces to shape the future of treating deep venous disease,” said Bruce Shook, president and CEO of Vesper Medical. “I look forward to further advance our next generation venous technology and bring it to patients and clinicians globally, together with Philips.”
Vesper Medical was founded in 2016 and is headquartered in Wayne, USA. Upon completion of the transaction, Vesper Medical and approximately 20 of its employees will become part of Philips’ Image-Guided Therapy business.
Many patients are outliving their gastrointestinal (GI) stents, and this can pose particular problems. “In the last few years, we have seen quite a dramatic increase in patients who present with a structural failure of their stent in the upper GI tract, notably the oesophagus, stomach and duodenum, which has been brought on by the dramatic increase in survival of patients, even with disseminated cancer, Hans-Ulrich Laasch (Christie NHS Foundation Trust, Manchester, UK) tells Interventional News.
While much further research is needed, the superalloy, nitinol, that the stents are made of undergoes corrosive failure when exposed to stomach acid so the stents break and fall apart. “We probably have at least one or two stent procedures a week where we have to revise a stent, exchange it and replace it, because the old one is no longer functional,” notes Laasch, who adds that interventional radiologists should be integral to tracking these devices as they have the requisite understanding of the clinical problem, are familiar with how the stents should look, and access to the imaging that shows the changes the earliest.
This interview was filmed at the British Society of Interventional Radiology (BSIR) Annual Scientific Meeting 2021 (8–10 December, Glasgow, UK).
Cleaning and low-level disinfection (LLD) effective against bloodborne pathogens are safe and sufficient procedures for disinfecting ultrasound transducers used in percutaneous procedures—this is according to an intersocietal position statement recently issued by the American Institute of Ultrasound in Medicine (AIUM).
Appearing in the peer-reviewed Journal of Ultrasound Medicine, the statement was issued in an effort to clear up confusion over disinfection practices and ensure that ultrasound equipment remains both safe and available.
Originally published in February 2021, the statement was recently republished with the support of 20 healthcare organisations, together representing more than 790,000 physicians, nurses, infection control professionals, and other healthcare professionals.
Glynis Harvey, CEO of the AIUM, said: “Our hope is that having the support of so many organisations will encourage the widespread adoption of appropriate disinfection practices in clinical and professional settings, bringing significant benefits to patients.”
The position statement was developed to address a growing debate over disinfection practices among practitioners in a wide range of medical specialties, explains Oliver Kripfgans, a medical ultrasound physicist and research associate professor at the University of Michigan (Ann Arbor, USA) who spearheaded development of the statement.
In many advanced medical procedures, ultrasound is used for guiding needles, catheters, and other devices that are inserted through the skin. Such percutaneous procedures include vascular access, arthrocentesis, paracentesis, pericardiocentesis, thoracentesis, lumbar puncture, and the delivery of regional anaesthesia.
The current debate stems from confusion over how ultrasound transducers should be disinfected between such procedures. Some practitioners have supported the use of high-level disinfection (HLD) techniques, which typically involve placing transducers in an apparatus that exposes them to specialised disinfecting chemicals such as glutaraldehyde or a mist of hydrogen peroxide.
Meanwhile, others have maintained that adequate protection is provided by use of a disposable transducer cover followed by cleaning and LLD, which involves wiping the equipment thoroughly with standard disinfectants.
In order to clarify these issues, the AIUM organised an intersocietal taskforce to examine the evidence available in published studies. The taskforce concluded that ultrasound-guided percutaneous procedures can be safely performed in conjunction with cleaning and LLD techniques, noting that transducer covers or other approved mechanical barriers protect the sterility of the procedure. Moreover, evidence showed that rare cases of infection are typically linked to the use of nonsterile or contaminated coupling gels, failure to use a transducer cover, or improper cleaning—but not to the use of LLD techniques.
The taskforce also found that recommendations for HLD are “not evidence-based and will result in unwarranted and unnecessary use of resources”.
Kripfgans said: “There was great concern that we were actually harming patients by requiring high-level disinfection.
With the support of the 20 signatory organisations, the AIUM is now launching an educational campaign to publicise the position statement and encourage the adoption of LLD techniques “to ensure that this invaluable tool remains available to every patient who can benefit from it,” says Harvey.
To read the full statement and view the complete list of signatories, visit https://onlinelibrary.wiley.com/doi/10.1002/jum.15653
Teleflex Incorporated have announced that the company has received reimbursement approval from the Central Social Insurance Medical Council of Japan (Chuikyo) for the UroLift System for patients who require treatment for benign prostatic hyperplasia (BPH).
The UroLift System treatment is a minimally invasive approach to treating BPH, commonly known as an enlarged prostate, a condition that causes bothersome urinary symptoms in men. Performed as a same-day outpatient procedure, the UroLift System can help improve quality of life, and offers lasting relief from symptoms with minimal downtime for patients, according to the company.
“The UroLift System is a major advancement in the treatment of BPH and can positively impact patients’ quality of life. We are very excited to have this technology available soon in Japan and look forward to its use in treating our patients,” said Satoru Takahashi, the professor and chairman in the Department of Urology, Nihon University School of Medicine, Tokyo, Japan.
The newly approved reimbursement for the UroLift System in Japan goes into effect 1 April 2022. Teleflex currently plans to enroll Japan’s Pharmaceuticals and Medical Devices Agency (PMDA-mandated), post-market clinical study to expand its already robust clinical data on the efficacy of the UroLift System and support widespread adoption of the UroLift System in Japan.
Cordis has announced George Adams as chief medical officer.
“We are delighted to have Dr Adams join our team as we continue to build the new Cordis,” said CEO Shar Matin. “His depth of expertise in the treatment of both complex coronary and peripheral vascular disease will play a vital role in furthering our mission to improve patient care at pace with cost-effective, differentiated solutions that build on our legacy of innovation.”
Adams is globally recognised for his expertise in the treatment of peripheral vascular disease in patients with chronic limb-threatening ischaemia (CLTI) and treatment of coronary artery disease in patients with acute coronary syndromes, a Cordis press release details. He is involved in the development of regional and national systems of care for the treatment of CLTI, ST-elevation myocardial infarction (STEMI), and management of complex coronary and peripheral vascular disease. He has a well-established network of peers and associates who are viewed as key opinion leaders within the global cardiovascular community.
“It is with great honour and excitement that I join the Cordis team as chief medical officer,” said Adams. “I look forward to playing a role in reinvigorating an incredible 62-year legacy. I am grateful to be a part of the future that Cordis is building with integrity and a vision for innovation.”
November’s top 10 features a pilot study regarding cryoablation for the treatment of early-stage, low-risk breast tumours, as well as data indicating that the Ellipsys vascular access system (Avenu Medical/Medtronic) offers an “excellent alternative” to arteriovenous fistula creation via surgical procedures in end-stage renal disease patients. In addition, the declaration of UK interventional radiologists of why to attend British Society of Interventional Radiology (BSIR) (8—10 December, Glasgow, United Kingdom) also attracted many readers.
1)Cryoablation could freeze out lumpectomy in early-stage, low-risk breast tumours
A pilot study, published in the Journal of Cancer Therapy, reveals that percutaneous cryoablation of early-stage, low-risk breast cancer tumours smaller than 15mm presents a potential substitute for lumpectomy.
2)Benefits of percutaneous fistula creation further bolstered by five-year Ellipsys data
The Ellipsys vascular access system (Avenu Medical/Medtronic) can be used to easily and safely create durable percutaneous arteriovenous fistulas (AVFs) for haemodialysis—with new, long-term data suggesting it offers an “excellent alternative” to AVF creation via surgical procedures in end-stage renal disease patients. That is according to Jeffrey Hull, an interventional radiologist and director of the Richmond Vascular Institute in Richmond, USA, who presented five-year results from the Ellipsys US pivotal trial at this year’s American Society of Nephrology (ASN) Kidney Week (2–7 November 2021, virtual).
3)UK interventional radiologists declare top reasons to attend BSIR 2021 in Glasgow
Hear from Alex Barnacle (London; British Society for Interventional Radiology [BSIR] communications chair), Peter Littler (Newcastle; the 2021 Scientific Programme Committee chair), Ian McCafferty (Birmingham; current BSIR president) and Phil Haslam (Newcastle; incoming BSIR president) about what they are most looking forward to at this year’s meeting.
4)TCT 2021: Six-month RADIANCE-HTN TRIO results “open a window” for renal denervation
Six-month outcomes from the randomised RADIANCE-HTN TRIO trial, comparing endovascular ultrasound renal denervation to a sham procedure for treatment-resistant hypertension, demonstrate the additional effects of pharmacologic intervention with maintenance of a blood pressure-lowering effect of renal denervation at six months, according to investigators.
5)TCT 2021: Randomised trials show “consistent” reduction in blood pressure through renal denervation
Randomised placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure, the findings of a systematic review and meta-analysis suggest.
6)Sarasota team completes “world first” procedure with ACE Xtend robotic system
XACT Robotics recently announced what it describes as the world’s first remote-controlled robotic instrument insertion and non-linear steering during an interventional oncology percutaneous procedure with ACE Xtend.
7)Innovative embolic device shows promise for interventional oncology drug delivery
Fluidx Medical’s GPX embolic device has released initial results for Oncology Drug Delivery. Fluidx Medical Technology announced that a next-generation, doxorubicin-loaded GPX embolic device was featured at the recent symposium on clinical interventional oncology (CIO) conference highlighting the technology’s potential for oncology drug delivery.
8)SIO announces ACCLAIM clinical trial with support from industry partners
The Society of Interventional Oncology (SIO) has announced the launch of the society’s first clinical trial—Ablation with confirmation of colorectal liver metastases (ACCLAIM) prospective trial for microwave ablation as a local cure. An SIO press release details that this multi-million-dollar trial is funded collectively through grants from Boston Scientific Corporation, NeuWave Medical (part of Ethicon), and Varian, a Siemens Healthineers company.
9)Philips announces large-scale study outcomes on use of IVUS in peripheral interventions
Royal Philips announced the results of a new large-scale real-world analysis of Centers for Medicare & Medicaid Services (CMS) data on the health outcomes of peripheral vascular interventions guided by intravascular ultrasound (IVUS).
10) Medtronic unveils data on hypertension treatment preferences, launches SPYRAL AFFIRM study
Medtronic today announced findings from a new study of patient preferences for the treatment of hypertension. The findings are set to be presented during the “What’s Novel in Interventional Hypertension” session at the 33rd Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando, USA and virtual)—the yearly scientific symposium of the Cardiovascular Research Foundation.
Interventional News 84 Highlights:
Interventional News 84 Highlights:
Arrow International has recalled its Arrow-Trerotola over-the-wire 7Fr percutaneous thrombolytic device (PTD) kits, which are used to remove clots in adult patients who have arteriovenous fistulas (AVFs) and synthetic dialysis grafts.
The recall has been attributed to the risk of the orange inner lumen of the Arrow-Trerotola PTD catheter’s tip component separating from the device’s self-expanding basket. A statement from the US Food and Drug Administration (FDA) adds that, if this occurs, the lumen may fracture and detach, and block the blood vessel(s) it is being used in.
Resulting health consequences depend upon where the fractured tip component embolises, the FDA statement continues. If the embolisation is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy. In some cases, the embolisation could be central, or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events, such as vessel damage, need for additional medical procedures, or possibly death, the statement adds.
The FDA has identified this as a Class I recall—the most serious type of recall—meaning use of these devices may cause serious injuries or death. To date, there have been seven complaints and no injuries or deaths reported for the Arrow-Trerotola PTD kits.
Arrow, which is a subsidiary of Teleflex, has recalled 3,241 of these devices in the USA following initiation of the recall in August 2021.
More information for healthcare providers or patients who may be affected by the recall can be found here.
Fluidx Medical Technology, has recently announced the oversubscribed closing of the first tranche of the Series A financing round. The Series A was led by a large multinational strategic investor and joined by the existing investor base as well as several new investors. The funding will be used to support prospective clinical trials, including the pivotal trial, as well as preparation for market entry.
“GPX has been quite simple to prepare, deliver and control,” said Andrew Holden (director of Interventional Radiology, Auckland City Hospital, Auckland, New Zealand). “The material is very radiopaque during delivery and has demonstrated excellent distal penetration, particularly important in our tumor embolization cases.”
Embolic devices are widely used to stop blood flow for targeted treatment of hypervascular tumors, vessel malformations, internal bleeds, and other cancer-related uses. Challenges with embolic devices today can include complicated preparation processes, issues with visibility during device delivery, reliance on the body’s coagulation situation, and lack of complete penetration of vessel beds and tumor feeding vessels.
The GPX Embolic Device is an innovative embolic designed for simple preparation and quick material delivery. GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolus upon delivery without polymerization or dimethyl-sulfoxide (DMSO) precipitation. GPX is designed to occlude blood vessels independent of a patient’s coagulation situation. Unlike competitive technologies that require special preparation materials and time, the GPX device is packaged ready-to-use in a syringe, requires less than 30 seconds of tableside preparation by the clinician, and may be delivered through standard catheters or small microcatheters (no complex mixing systems or special delivery catheters are necessary).
The British Society for Interventional Radiology (BSIR) has set up an interventional radiology (IR) registry to capture a glimpse of the scope, breadth and immediate complication rate provided by the service in the UK. In parallel, UK interventional radiologists are bent on building a strong case for IR units to have their own day-case facilities, as these enabled the subspecialty to take pole position during the pandemic as a great resource for image-guided interventions and activity in a COVID-19- secure environment.
Other milestones to mark and challenges to navigate include interventional oncology advances such as the final draft National Institute of Health and Care Excellence (NICE) guidance recommending the use of selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), supporting interventional radiologists who are not formally recognised as paediatric specialists but performing paediatric interventions in “bits and pieces” and getting direct preferencing for radiology registrars into interventional radiology, so that from 2022, they will be “badged as an interventional radiologist, all the way through their training”.
Alex Barnacle (London; BSIR communications chair), Peter Littler (Newcastle; the 2021 Scientific Programme Committee chair), Ian McCafferty (Birmingham; current BSIR president) and Phil Haslam (Newcastle; incoming BSIR president) discuss these developments ahead of this year’s BSIR annual scientific meeting in Glasgow next week (8–10 December, Glasgow, UK).
This advertorial is sponsored by Sirtex Medical.
Two experts in the field of interventional radiology, Bernhard Gebauer (head of interventional radiology at Charité – Universitätsmedizin Berlin in Berlin, Germany) and Ahmed Kamel Abdel Aal (professor of interventional radiology at The University of Texas Health Science Centre in Houston, USA) talk to Interventional News about their experience with SIR-Spheres Y-90 resin microspheres (Sirtex Medical)—which are used in selective internal radiation therapy (SIRT) for certain liver tumours*—and discuss how this advanced technology can help improve survival, boost patient quality of life (QoL) and enable greater flexibility, customisation and speed of treatment.
Real-world data
Real-world data from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Registry for SIR-Spheres Therapy (CIRT)—which was presented at the CIRSE 2020 Summit (12–15 September, virtual)—showed that SIR-Spheres Y-90 resin microspheres were associated with low 30-day mortality (1%) as well as a low incidence (2.5%) of serious adverse events (grade ≥3) within 30 days of treatment. Serious adverse events such as gastritis, gastrointestinal ulcerations, radiation cholecystitis and radioembolization-induced liver disease occurred in less than 0.3% of the total patient cohort.
This large European registry, which included 1,027 patients, was designed to observe the real-life clinical application of SIRT with SIR-Spheres Y-90 resin microspheres and the impact of the treatment in clinical practice. “The strength of CIRT registry data is that they reflect patient and tumour treatment in a real-world scenario, including large treatment centres and smaller hospitals from different countries and healthcare systems,” says Gebauer.
In addition to highlighting low mortality and low serious adverse events, the data also found that median overall survival was 9.8 months (95% CI: 8.3–12.9) in 237 patients with metastatic colorectal cancer (mCRC). These figures from CIRT are “a great result for patients with certain types of cancer who have limited options”, adds Kamel.
Similar findings were reported in the CIRSE Registry for SIR-Spheres Therapy in France (CIRT-FR), the interim analysis of which revealed some interesting data in relation to safety and patient QoL. There were a total of 200 patients (median age 66; 70% male) including 38 mCRC patients in the CIRT-FR registry. As was the case in CIRT, 30-day mortality was 1%. A total of 12% of patients experienced at least one adverse event within 30 days following treatment. In relation to health-related QoL, which was assessed using the EORTC QLQ-C30 questionnaire, the overall global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%)
“For heavily pretreated patients, the toxicity of a treatment and QoL are very important”, says Gebauer, adding that “the data show that SIR-Spheres Y-90 resin microspheres are well tolerated and maintain patients’ QoL.” He also explains that, with this technology, patients can be offered a chemo-free interval in order to have the liver treated but without the side effects of a systemic therapy.
Patient selection
Gebauer further discusses which patients can benefit most from this treatment, noting that, in general “SIR-Spheres Y-90 resin microspheres are an option for a broad range of patients.” He also outlines that oncological factors such as tumour size and number of tumours, as well as the functional capacity of the liver “play a great role” in determining the use of SIR-Spheres Y-90 resin microspheres.
“Usually Y-90 treatment using SIR-Spheres is used in patients where the tumours are not resectable or ablatable, either because of tumour factors (tumour too large, adherent to critical organs or structures or invading vascular structures), remaining hepatic reserve limitations (especially if large hepatic resections are planned) or other patient factors or comorbidities that limit larger resections. Specifically, in the first group (tumour factors) Y-90 SIRT could reduce the tumour volume and transfer the patient in a secondary resectable or ablatable state.
“In selected cases, patients might benefit from an earlier treatment with SIRT. SIR-Spheres Y-90 resin microspheres show good response rates in localised liver tumours and offer patients surgical options that were unavailable before SIRT.
“So patients could be transferred into a suitable stage for resection or ablation and transferred into a potentially curative stage. Depending on the location of liver tumours SIRT allows various treatment strategies including segmentectomy, lobectomy and hemiablation with contralateral hypertrophy for resection”, he adds.
“Preinterventional state-of-the-art imaging is essential for therapy planning”, says Gebauer, who adds that “personalised medicine is nowadays the standard of cancer care and therefore the dosimetry should also be so in order to improve the results of SIRT.”
Kamel outlines how it is “important to realise that each disease and each patient is different”. He agrees with Gebauer that, as a result, “treatment should be based on the goal of the therapy, the patient’s liver function, the number and location of the lesions and the prior, concurrent and future treatment(s). Personalised dosimetry is always recommended for all patients receiving Y-90 SIR-Spheres”, he concludes.
Utilisation and customisation
SIR-Spheres Y-90 resin microspheres therapy is a minimally invasive procedure that sees patients usually return home shortly after the procedure is completed. It is currently the only fully US Food and Drug Administration (FDA)-approved Y-90 radiation therapy in the USA for the treatment of colorectal cancer that has spread to the liver. The Y-90 resin microspheres can be delivered in a slow, deliberate manner, thereby helping to achieve an even distribution, thus maximising the number of microspheres delivered and optimising tumour coverage.
Discussing some of the challenges associated with many Y-90 programmes, Kamel states that “outcomes are often variable and not consistent. It can also take some time between the decision for treatment and treatment with Y-90. This can delay other treatments and adds a lot of stress to the patient,” he continues.
However, there is a solution. Helping to address these challenges is Sirtex’s FLEXdose Delivery Programme, which Kamel says has helped optimise his practice. He explains that the FLEXdose Delivery Programme provides physicians with the opportunity to have one-, two- or three-day pre-calibrated vials which contain exactly the same number of microspheres, with different activity per sphere.
“This offers you the flexibility to give the same activity but with either more or fewer microspheres, allowing you the ability to customise treatment based on the tumour burden, lobes and segments of the liver involved, and how selective you are with your catheter,” says Kamel.
“Another advantage is the activity draw, which is really very important in our programme and is very unique to SIR-Spheres. It allows you to administer a tailored and personalised activity for the patient’s specific needs. Imagine that on the day of treatment you wanted a smaller dose or another dose. You can draw the exact dose that you desire from the vial. Being able to change the dose on the day of the treatment means you do not have to keep bringing the patient back again because you do not have the right dose.”
“Previously, the usual sequence of events was to map, do the dose calculation, order the dose and then treat,” notes Kamel. “However, utilising Sirtex’s Order-Map-Treat programme, you get a much faster patient treatment.”
“We know that we can always draw the exact dose we want and that is the beauty of this. It has also really changed the mindset of our referring physicians because we can provide an accelerated treatment timeline that enables patients to be quickly returned to their medical oncologists for further systemic treatment(s)”, concludes Kamel.
*For full indication and prescribing information, please refer to the IFU at www.sirtex.com.
Bernhard Gebauer is head of interventional radiology at Charité – Universitätsmedizin Berlin in Berlin, Germany. He is German board certified in radiology and interventional radiology and specialised in IR cancer treatment.
Ahmed Kamel Abdel Aal is a professor of interventional radiology and the chief of vascular and interventional radiology and the vice chair of radiology at The University of Texas Health Science Center at Houston (UTHealth) in Houston, USA. He is American board certified in radiology and interventional radiology and received his fellowship training in vascular and interventional radiology as well as neuroradiology at the University of Alabama in Birmingham, USA.
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Artio Medical has announced that full results from its first-in-human clinical study of the Amplifi vein dilation system were presented at the 2021 VEITHSymposium (16–20 November, Orlando, USA and virtual) by Surendra Shenoy, associate professor of surgery in the Washington University School of Medicine at Barnes-Jewish Hospital (St Louis, USA).
“Data from the first five patients treated with the Amplifi system demonstrated more than a doubling of forearm and upper arm cephalic vein diameters following a mean treatment period of 8.6 days,” said Shenoy. “We were able to successfully create an arteriovenous fistula (AVF) using treated veins in all patients and observed rapid and robust AVF maturation. These data are very encouraging, and I believe this technology has the potential to offer a much-needed solution for increasing AVF suitability and reducing maturation failure.”
The Amplifi vein dilation system is designed to stimulate arm vein enlargement prior to AVF creation to make more patients requiring vascular access for haemodialysis eligible for AVF surgery, reduce the time required for AVF maturation, and increase successful maturation rates, an Artio press release states.
“When physicians create AVFs today, we know there are often vein segments with pre-existing problems, but we do not currently have adequate tools to identify these segments—which contributes to the high rate of AVF maturation failure,” Shenoy added. “The Amplifi system could allow physicians to better identify these segments and either treat them at the time of AVF creation or exclude them from the AVF circuit.
“In this study, three of the five patients had pre-existing problems in the cephalic vein, which were made more apparent by Amplifi system treatment. In one patient, an AVF was made more proximally and, in another, angioplasty was performed, and both patients went on to have successful AVF maturation and use.”
Erdie De Peralta, vice president of clinical and regulatory affairs at Artio, said: “We are pleased to have the data from the Amplifi system FIH [first-in-human] presented at the VEITH conference and look forward to building upon this initial clinical experience with our US IDE [investigational device exemption] trial, which is projected to begin enrolment in 2023.”
Prostate artery embolization (PAE) is more cost-effective than transurethral resection of the prostate (TURP), the gold standard for the management of patients with benign prostate hyperplasia (BPH) at one-year follow-up. However, embolization exhibits a higher reintervention rate, which may reduce the cost-effectiveness in subsequent years following intervention.
There were the concluding findings of a retrospective cost-utility analysis from a UK National Health Service (NHS) perspective, published in October 2021 in BMJ Surgery Interventions & Health Technologies, Sachin Modi, University Hospital Southampton NHS Foundation Trust, Southampton, UK (senior author) and colleagues.
The prevalence of BPH increases with age, which, combined with an ageing population in the UK, will create a financial burden on the NHS. With PAE offering a minimally invasive alternative, Modi and colleagues set out to investigate the cost-effectiveness of PAE vs. TURP, in the management of BPH after one-year follow-up. This comparison study, therefore, collected patient data from the UK Register of Prostate Embolization (UK-ROPE) study at one, three, six and 12 months. UK-ROPE holds data on patients treated with embolization or surgical interventions from across 20 U.K centres, and was funded by the UK National Institute for Health and Care Excellence (NICE). In the UK-ROPE study, male patients received either embolization (PAE) (n=133), surgery (TURP) (n=31), open prostatectomy or holmium laser enucleation of the prostate (HoLEP) between July 2014 and January 2016. Patient outcome data was collected on the International Prostate Symptom Score (IPSS), quality of life (QoL) and International Index of Erectile Function (IIEF).
Within the cost analysis, effectiveness was measured as quality-adjusted life years (QALYs) and the costs for both embolization and surgery were taken from University Hospital Southampton data, using 2016 as a reference year. An incremental cost-effectiveness ratio (ICER) was then derived from cost, IPSS values and QALY values associated with both interventions at 12 months.
The original UK-ROPE study outcomes showed no significant differences in patient baseline IIEF, prostate volume or maximum urinary flow rate, however, and it demonstrated that embolization showed a significant statistically improvement in IPSS and QoL post-procedure. However, the improvement in IPSS following surgery was greater.
Within the embolization group, the QALY value was 0.96 (SD=0.03), compared to a surgery QALY score of 0.98 (SD=0.03). The average cost per patient of embolization and surgery was £2,000 and £3,028, respectively. Therefore, the ICER was £64,798.10 saved per QALY lost, making embolization more cost-effective. Within the patient cohort, 36% of those who received embolization reported complications at 12 months, with 84% of surgery patients also reporting complications in the same timeframe.
In conclusion, embolization was deemed to be a more cost-effective intervention in the management of BPH compared to TURP. Shorter patient stays and the lack of necessity for an operating theatre/anaesthesia were major contributing factors to this, however, due to a higher reintervention rate in the embolization group, the authors suggest that this benefit may not be maintained in subsequent years and longer term comparison studies are required to fully evaluate this.
Aopeng Medical’s Allvas endovascular intervention surgical robot has successfully completed a first-in-human clinical evaluation of robot-assisted peripheral artery intervention of an iliac artery in the Department of Vascular Surgery at Shanghai Changhai Hospital.
The procedure was performed by Qing-Sheng Lu and colleagues in the Department of Vascular Surgery at Shanghai Changhai Hospital in Shanghai, China. The endovascular intervention surgical robot, combined with digital subtraction angiography (DSA), precisely evaluated the target lesion and location, and completed a refined operation process to better ensure the safety of the procedure, reduce iatrogenic injury, and reduce the incidence of complications and postoperative reintervention rate, a press release from Aopeng Medical reports.
According to Aopeng Medical, the Allvas endovascular intervention surgical robot is the first platform-robot in peripheral artery intervention with independent intellectual property rights in China. Its core technology covers robot architecture design, robotic arm and actuator process design, force feedback mechanism, software algorithm and automated surgery, and system integration. Aopeng Medical claims that the Allvas is the world’s first universal peripheral artery interventional robot. Early this year, the company completed what it asserts to be world’s first in-human clinical trial of robot-assisted endovascular aortic repair of thoracic aortic aneurysm and abdominal aortic aneurysm.
The traditional surgical treatment has numerous side effects, such as high trauma, high risk, difficulty and multiple complications. In comparison, Aopeng Medical alleges that its endovascular intervention surgical robot, Allvas, can achieve precise positioning through digital technology, which meets specific needs from the individual patient. The company adds that Allvas is also expected to reduce the radiation dose received by the operator by more than 90% and improve the precision of surgical manipulation, thus helping physicians to achieve higher efficiency and more satisfactory effects in clinical practice.
Canon Medical Systems is introducing an all-new size for its high-definition flat panel detector for vascular and interventional radiology (IR) procedures, a press release from the company reports. Canon Medical claims that the 12”×16” high-definition detector provides more than twice the spatial resolution of conventional flat panel detectors, helping clinicians see fine details in complex interventional procedures. The new 12”×16” detector joins the existing 12”×12” high-definition detector to provide clinicians with the ideal size for their unique procedural needs.
“All those things which the device does that were impossible to see with conventional flat panel detectors become overly abundant with high-definition detector technology,” said Adnan Siddiqui, director of neurological stroke services, Kaleida Health; CEO of The Jacobs Institute; and professor of neurosurgery at the University at Buffalo, New York, USA).
Now available on Canon Alphenix interventional systems, the 12”×16” high-definition flat panel detector offers the highest resolution in the market, according to Canon Medical. Made up of what the company asserts to be the world’s first true high-definition detector—with 76-micron resolution—for resolving fine details, the hybrid 12″x16″ panel is combined with high-definition flat panel technology that results in resolutions of 2.6lp/mm (standard) and 6.6lp/mm (high-definition detector).
Canon Medical is showcasing Alphenix high-definition detector technology at this year’s virtual Radiological Society of North America (RSNA) annual meeting (28 November–2 December, Illinois, United States). Learn more about the Alphenix’s full suite of technology here.
Cardiovascular Systems has initiated a voluntary recall of unused Wirion embolic protection systems due to complaints of filter breakage during retrieval.
Wirion is a distal embolic protection filter used to capture thrombus and debris that can be associated with all types of peripheral vascular intervention procedures, including atherectomy.
CSI has informed all affected healthcare facilities to discontinue use of Wirion immediately and return unused product to CSI. The US Food and Drug Administration (FDA) has also been notified. To date, CSI has received nine complaints of filter breakage during retrieval. Filter breakage may result in device embolism and possible additional intervention.
The company plans to voluntarily recall all Wirion units currently in customer inventory. In total, 697 devices were distributed in the USA between 22 March and 15 November 2021.
Interventional radiology is regularly characterised as being “a hotbed of innovation”, but the first study to directly evaluate the level of agreement between disclosed financial relationships and open payment data for top-cited image-guided procedures in the USA lays bare that 97% of the studied authors failed to disclose at least one active financial relationship. Importantly, declaring an interest does not equate to resolving potential bias, note authors Lee J Hsieh (University of California San Diego, San Diego, USA) and Mina S Makary (The Ohio State University Medical Center, Columbus, USA). Their research, published online ahead of print in October 2021 in the Journal of Vascular and Interventional Radiology also reignites the debate around how to weed out bias without bedevilling and stifling innovation. Interventional News speaks to the authors of the study to drill down on its findings and implications.
How should the findings of this study influence interventional radiologists to scrutinise published data?
The significance of this work is that it is the first study which directly evaluates the prevalence of conflict of interest (COI) disclosures in US-based interventional radiology (IR) research while evaluating the level of agreement between disclosed financial relationships and open payment data for top-cited image-guided procedure research. Findings from this work should raise the attention of interventional radiologists evaluating published data to this often invisible factor that creates a risk of bias. For example, studies have shown that those with industry sponsorships are more likely to have pro-industry conclusions, and others may publish conclusions inconsistent with the study results. Industry sponsorships may also erode academic freedom and influence research agendas, inadvertently suppressing research that does not further industry’s objectives in science or policy. This potential for bias is the reason expert consensus has emphasised the importance of COI disclosure to help mitigate any potential bias and support data integrity.
What were the leading results from your data?
One of the most interesting findings was that among the 396 authors of 100 US-based, top-cited image-guided procedure publications, 97% failed to disclose at least one active financial relationship, with an average of US$57,937 in undisclosed payments per publication. For comparison, previous studies in other areas of healthcare have found discrepancies in 43–69% of publications, while still others have reported a median rate as high as 81%. Together these trends suggest that conflicts of interest are prevalent in IR, like other areas of healthcare research, and conflicts of interest in top-cited image-guided procedure research are often underreported.
A 30% positive COI rate that climbs to 50% in standards of practice and device-related publications—what needs to be done to help recast these numbers?
To improve disclosure, authors and organisations have advocated for further development and use of open disclosure databases, building upon the successful implementation of ClinicalTrials.gov. Many have noted that relying primarily on self-disclosure is limited and that people may overlook potential biases in themselves that they would otherwise perceive in others. Even authors who are transparent with their COIs may falsely equate disclosure with resolution, assuming that once a potential bias is disclosed, no further action is required. As such, the Committee on Publication Ethics described the importance of a shared responsibility between authors to disclose as well as journal editors to screen for and minimise potential bias. Accurate and complete disclosures may improve author transparency and public trust, but a more comprehensive approach involving public effort, policy change, and institutional support may be needed to address the underlying issues of COIs.
What are the limitations of this dataset? How globally applicable is it?
This work had several limitations. The prevalence of positive COIs in IR was estimated from a single volume of a single IR journal, which reflects only a fraction of a broader body of IR literature. COI disclosures may vary over time and across different journals. The assessment of agreement between disclosed financial relationships and open payment data was limited to studies published after the enactment of the Sunshine Act in August 2013. Since non-domestic financial data are difficult to obtain, only those of US authors were analysed. These all limit the generalisability and external validity of the results, particularly in the global arena.
How do you propose preparing a change?
While relationships between clinicians and industry can have many positive effects, these relationships nevertheless do create a risk of bias that must be mitigated to support the integrity of research. Our collective efforts are necessary to better understand how best to encourage disclosure and reduce bias without stifling innovation, a hallmark of our specialty.
Endologix has completed enrolment in the TORUS 2 investigational device exemption (IDE) clinical study in the USA, a press release reports.
The TORUS 2 study is a prospective, single-arm trial of 188 patients to evaluate safety and effectiveness of the Torus stent graft system in the treatment of peripheral arterial disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal arteries.
The study is led by national co-principal investigators Peter Schneider, professor of surgery, Division of Vascular and Endovascular Surgery at University of California San Francisco (San Francisco, USA), and Ehrin Armstrong, medical director, Adventist Heart and Vascular Institute at Adventist Health St Helena (St Helena, USA). “The development of a new self-expanding covered stent for treatment of the SFA and proximal popliteal arteries represents an important advancement in optimal endovascular therapy of complex lesions,” said Armstrong.
“We especially appreciate the strong efforts of our clinical trial sites to enrol this trial efficiently and with high quality. This is the first time in years that a new and specifically designed stent graft for the femoral-popliteal segment is being evaluated for clinical utility,” said Schneider.
“The completion of enrolment for TORUS 2 is a significant milestone in a clinically challenging area of vascular disease,” said Matt Thompson, president and CEO of Endologix. “The TORUS stent graft is also a pivotal component of the Detour procedure, a totally percutaneous femoropopliteal bypass, currently under clinical investigation. Both systems continue our commitment to expanding the Endologix portfolio of innovative devices and supporting clinical evidence.”
Shockwave Medical has announced the start of the Disrupt BTK II postmarket study to assess the safety, effectiveness and optimal clinical use of the Shockwave peripheral intravascular lithotripsy (IVL) system for the treatment of calcified peripheral lesions below the knee (BTK), including some of the most challenging patients with chronic limb-threatening ischaemia (CLTI).
Disrupt BTK II is a postmarket, prospective, multicentre, single-arm study led by Ehrin Armstrong, medical director and interventional cardiologist, Adventist Heart & Vascular Institute (St Helena, USA), and Venita Chandra, vascular surgeon and clinical associate professor, Division of Vascular Surgery, Stanford Health Care (Stanford, USA). The study is expected to enrol 250 patients across 40 sites globally that will be followed for two years to assess the long-term durability of IVL in this difficult-to-treat patient population. The first Disrupt BTK II patient was enrolled at Midwest Cardiovascular Research Foundation (Davenport, USA) by Nicolas Shammas.
“Patients with severely calcified, diffuse below-the-knee disease, and especially those with CLTI, are often in severe pain with limited treatment options to achieve adequate arterial revascularisation. The unmet clinical need for this population is extremely high,” said Armstrong. “Disrupt BTK II will further evaluate how IVL may be optimally used to treat patients who have historically been excluded from most endovascular treatment trials.”
The primary effectiveness endpoint of Disrupt BTK II is procedural success, defined as ≤50% residual stenosis for all treated target lesions without serious angiographic complications (flow-limiting dissection, perforation, distal embolisation, or acute vessel closure), as assessed by an independent angiographic core lab. The study will assess the absence of major adverse limb events (MALE) within 30 days of the index procedure as a primary safety endpoint.
“More and more patients with CLTI also present with end-stage renal disease, advanced diabetes, or other comorbidities that impact their overall health and our ability to effectively treat their CLTI,” said Chandra. “We already know that IVL can reduce significant dissection as well as reduce the need for provisional stenting over conventional PTA [percutaneous transluminal angioplasty] in peripheral vessel beds, but what makes Disrupt BTK II even more exciting is that we are now isolating the treatment effect to get a clearer picture about what role IVL can offer as a definitive therapy for these very complex patients.”
October’s top 10 features an interview with Maureen Kohi (Chapel Hill, USA), the chair and professor of Radiology (University of North Carolina), and the chief of Interventional Radiology (University of California, San Francisco, USA). The US Food and Drug Administration (FDA) granted Varian breakthrough device designation for its Embozene microspheres for genicular artery embolization (GAE), which has attracted many readers, as has issue 83 of Interventional News.
1) Maureen Kohi
“I strongly believe that you cannot be what you cannot see. If you want more women or under-represented minorities (URMs) to enter the field and be at the table, then we need more women and URM leaders in the field,” Maureen Kohi (Chapel Hill, USA).
2) Varian receives FDA breakthrough device designation for its Embozene microspheres
Varian, a Siemens Healthineers company, announced that the US Food and Drug Administration (FDA) has granted the company breakthrough device designation for its Embozene microspheres for genicular artery embolization (GAE) for symptomatic knee osteoarthritis.
3) Head-to-head trial shows superiority of FemoSeal over ProGlide for peripheral interventions
Results of the randomised, prospective, multicentre STEP trial show that the FemoSeal vascular closure system (Terumo) is superior to the Perclose ProGlide suture-mediated closure system (Abbott) in peripheral arterial disease (PAD) patients in terms of technical success using a retrograde femoral puncture. Bahaa Nasr (Brest University Hospital, Brest, France) presented the late-breaking data at Paris Vascular Insights (PVI) 2021 (21–23 October, Paris, France), concluding that FemoSeal should be used in PAD patients undergoing lower limb arterial endovascular treatment, especially if they are discharged on the same day as their surgery.
One-year results presented at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA) from the EMINENT trial demonstrated the superiority of the Eluvia drug-eluting stent (DES) system (Boston Scientific) compared to self-expanding bare metal stents for the treatment of patients with peripheral arterial disease (PAD) with superficial femoral artery (SFA) or popliteal artery lesions up to 210mm in length, the principal investigator (PI) said. The study enrolled 775 patients, making it the largest randomised trial of a DES for the treatment of PAD to date, Boston Scientific said in a press release.
Rethink fistula creation and maintenance with Tobias Steinke, Ounali Jaffer, Panagiotis Kitrou and Robert Jones in this four-page advertorial.
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6)The future of procedural training is virtual
In the wake of the COVID-19 pandemic, the world of education went virtual. John Rundback (Advanced Interventional & Vascular Services LLP and American Endovascular & Amputation Prevention PC in Clifton, USA), who has been involved in interventional device education for more than 25 years, believes virtual procedural training is here to stay. In this interview, Rundback details how procedural training has adapted and is thriving in its new digital setting, with available systems offering increasingly immersive learning environments available to an international cohort of students. He also predicts an 80:20 split between virtual and in-person training in the future.
7)Target lesion revascularisation in the firing line
Is target lesion revascularisation (TLR) a meaningful clinical endpoint for research or should it be “tossed as a legitimate endpoint for peripheral vascular disease treatment success in US FDA [Food and Drug Administration] approval trials?” Recent keynote presentations and conference debate on appropriate care for peripheral vascular disease leave overuse of interventional therapy, particularly for claudication, staring down the end of a barrel. They also trigger a conversation around TLR becoming a target in and of itself.
8)Interventional News issue 83—September 2021 Edition
Interventional News 83 highlights:
9) Sirtex Medical and China Grand Pharmaceutical announce successful first administration of SIR-Spheres Y-90 resin microspheres in China
Sirtex Medical (Sirtex) has announced that the first procedure of selective internal radiation therapy (SIRT) using SIRSpheres Y-90 resin microspheres in China was successfully performed for a patient with hepatocellular carcinoma (HCC) on 28 September 2021. The milestone was reached with the support of Sirtex shareholder China Grand Pharmaceutical and Healthcare Holdings Limited.
10)ECLIPSE shows cryoablation effective for local control of pulmonary long-term metastatic tumours
Cryoablation is effective for local tumour control in patients with pulmonary metastatic disease. Within the ECLIPSE study, cryoablation had no significant impact on the patient’s quality of life (QoL), with the patient disease-specific survival rate remaining higher than the overall survival rate at both three and five years of follow-up.
Avinger recently announced that it has received 510(k) clearance from the US Food and Drug Administration (FDA) for a new clinical indication for the Pantheris image-guided atherectomy system. This clearance allows the company to directly market Pantheris for the treatment of in-stent restenosis (ISR) in the lower extremity arteries.
“We are excited to receive FDA clearance for the ISR indication, which expands our addressable market for Pantheris to include a high-incidence disease state for which there are few available indicated treatment options,” commented Jeff Soinski, Avinger’s president and CEO. “Pantheris is now the only directional atherectomy device to have a clinical indication for the treatment of in-stent restenosis, providing a compelling new point of differentiation for the device. By combining real-time intravascular imaging with the precise control and large luminal gain of directional atherectomy, Pantheris enables physicians to visualise stent struts and safely target ISR lesions to restore blood flow to occluded vessels, while avoiding the structure of the previously implanted stent.”
To support the 510(k) submission with the FDA, Avinger provided data generated from the INSIGHT trial, a prospective, global, single-arm, multicentre study to evaluate the safety and effectiveness of Pantheris for treating in-stent restenosis in lower extremity arteries. Sean Janzer, an interventional cardiologist at Albert Einstein Medical Center in Philadelphia, USA, and Glen Schwartzberg, a vascular surgeon in Baton Rouge, USA, served as co-principal investigators of the study. The clinical data from INSIGHT was presented at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA) by Jon George, an interventional cardiologist at University of Pennsylvania Health System in Philadelphia, USA, and were also presented at the 2021 VEITH Symposium (16–20 November, Orlando, USA) by Todd Vogel, chief of cardiovascular surgery at University of Missouri Health in Columbia, USA.
“The Pantheris system’s combination of onboard image guidance and a directional excision mechanism provides significant clinical advantages in treating in-stent restenosis not available with any other therapy,” noted Schwartzberg. “This technology allows the operator to target only the blockage and maximise the channel for restored blood flow while avoiding negative interactions with clearly delineated stent struts. Based on the results of the INSIGHT study and my personal experience with the device, I believe that Pantheris can help physicians safely and effectively treat many ISR patients that previously may not have had other options available and reduce the need for repeat interventions and more invasive surgeries.”
According to a press release, Avinger’s proprietary Lumivascular technology allows physicians, for the first time ever, to see from inside the artery during an atherectomy or chronic total occlusion (CTO) crossing procedure by using optical coherence tomography (OCT) that is displayed on Avinger’s Lightbox console.
Physicians performing atherectomy or crossing CTOs with other devices must rely solely on X-ray and tactile feedback to guide their interventions while treating complicated arterial disease. With the Lumivascular approach, the press release continues, physicians can more accurately navigate their devices and treat peripheral arterial disease (PAD) lesions, due to real-time OCT images generated from inside the artery, without exposing healthcare workers and patients to the negative effects of ionising radiation.
After COP26, it is time for the interventional radiology world to congregate in Glasgow, UK. Diversity, veterinary interventions, sun tan, or single malt–everyone has their own reasons to head there.
Hear from Alex Barnacle (London; British Society for Interventional Radiology [BSIR] communications chair), Peter Littler (Newcastle; the 2021 Scientific Programme Committee chair), Ian McCafferty (Birmingham; current BSIR president) and Phil Haslam (Newcastle; incoming BSIR president) about what they are most looking forward to at this year’s meeting.
Register here for BSIR 2021
The confirmatory EVAS2 clinical study to evaluate the safety and effectiveness of Endologix‘s Nellix endovascular aneurysm sealing system (EVAS) for the treatment of infrarenal abdominal aortic aneurysms (AAAs) contains positive two-year follow-up data, the leading investigator has revealed.
A first study update was presented by principal investigator Jeffrey Carpenter, chairman and chief of the Department of Surgery at Cooper University Health Care in Camden, USA, at the 2021 VEITHsymposium (16–20 November, Orlando, USA).
Carpenter told delegates data from two years of follow-up of patients treated with the EVAS device demonstrate 92% freedom from all-cause mortality, 100% freedom from migration, 100% freedom from saccular enlargement, 98% freedom from type Ia endoleaks, and 98% freedom from type II endoleaks. “We are only at two years of good follow-up,” Carpenter said, explaining that this was the point at which “the signal of problems” emerged in EVAS1. However, he said the study investigators were hopeful of success in the current study as they continue to follow study participants, with data “holding up.”
Carpenter explained that at two years of follow-up in the device’s pivotal investigational device exemption (IDE) trial, “there was a signal of migration and a signal of aneurysm enlargement development.” A root-cause analysis found that thrombus “was playing a big role” in the case of migration, he told VEITH 2021 attendees. Regarding aneurysm enlargement, Carpenter continued, “we were originally employing what turns out to be a plug,” under an understanding that they only needed to fill the aneurysmal portion of the aorta with polymer—but not the seal zones, or “firewalls.” Adjustments were made, resulting in “a revision of the instructions for use (IFU) to make sure that there was able to be sufficient polymer placed into the aneurysm sac to stabilise the stents and that we had good seal zones proximally and distally,” he said.
In 2019, Endologix issued a voluntary recall for the EVAS system in order to ensure optimal patient outcomes through the most appropriate use of the device, with the company noting that it had determined off-label use was occurring at “an unacceptable level, with the consequence of suboptimal results.”
The 333 patients in EVAS1 retrospectively yielded the device IFU, Carpenter explained. Those in this group treated on-label experienced 97% freedom from migration, he added. EVAS2 consists of 92 patients and is an IDE prospective, multicentre, single-arm study with consecutive, eligible subject enrolment at each site. Participants are being followed at 30 days (primary safety endpoint), six months, one year (primary effectiveness endpoint) and annually thereafter out to five years (total follow-up commitment).
Summarising the EVAS2 data delivered at VEITH 2021, Carpenter concluded: “Active sac management of EVAS has shown good freedom from type II endoleak and freedom from all-cause and cardiovascular mortality in all quartiles. Clearly, a second-generation Nellix device is necessary if this is going to be an everyday infrarenal aneurysm repair device.” Data regarding five-year freedom from major adverse events are “encouraging,” he added.
The Society of Interventional Oncology (SIO) has announced the launch of the society’s first clinical trial—Ablation with confirmation of colorectal liver metastases (ACCLAIM) prospective trial for microwave ablation as a local cure. An SIO press release details that this multi-million-dollar trial is funded collectively through grants from Boston Scientific Corporation, NeuWave Medical (part of Ethicon), and Varian, a Siemens Healthineers company.
In this prospective, multicentre, international trial SIO proposes to establish microwave ablation as the preferred treatment option for selected colorectal liver metastases that can be ablated with sufficient margins. The study will be the first global, prospective trial to use an objective and reproducible technical outcome in its study design, which SIO believes will drive important changes to future treatment guidelines. The study will incorporate software to assess the ablation zone and margins and determine if achieving complete margins during an ablation equates to procedural success, where the primary outcome is local disease progression at two-years post-ablation.
Constantinos T Sofocleous (Memorial Sloan Kettering Cancer Center, New York, USA) is the principal investigator for the study. “The ACCLAIM trial could impact patient guidelines with regards to the role of ablation as a treatment option for CRC [colorectal cancer] liver metastases. The study is expected to raise the bar for the standard of care, establishing a reproducible method of achieving tumour ablation with local control,” said Sofocleous. “Clinical research is essential for the continued progress of interventional oncology and SIO will continue to drive such important and focused research efforts.”
Despite a favourable safety profile, historically, the inconsistent local tumour progression (LTP) rates after thermal ablation when compared to surgery have limited the widespread adoption of this treatment option in patients with metastatic colorectal cancer to the liver. Suboptimal outcomes and LTP have been attributed to insufficient coverage of the tumour by the ablation zone (tumour and margins). The ACCLAIM study will estimate disease-free survival of colorectal liver metastases treated with MWA incorporating 3D ablation margin confirmation intraoperatively and through a subsequent independent review centralised validation process.
Matthew Callstrom, professor and department chair of radiology at Mayo Clinic (Rochester, USA) is president of the SIO. “It is important to drive what we do as a field forward together, and it takes collaboration and long-term relationships with our industry partners to enable the right studies to be successful,” said Callstrom. “The ACCLAIM industry partners are raising the bar for research investment by making an important commitment to support societies like SIO. Together, we are advancing our vision to establish interventional oncology as the fourth pillar of cancer therapy.”
Participants of the ACCLAIM trial will be patients with a diagnosis of colorectal cancer liver metastases. MWA will be performed using a US Food and Drug Administration (FDA)-cleared, commercially available MWA system and using margin confirmation (visualisation) software. The ACCLAIM study is set to launch in 2022 with an expected three-year enrolment period of 275 participants across sites in the USA and Europe.
XACT Robotics has announced plans to present oral and virtual presentations at the Radiology Society of North America (RSNA 2021, 28 November–2 December, Chicago, USA and virtual) that showcase clinical findings and case studies from leading radiology centres.
Sebastian Flacke (Lahey Hospital and Medical Center, Burlington, USA) will present new data from a multicentre study using the XACT ACE robotic system during percutaneous procedures. His presentation, “Feasibility and accuracy of a hands-free robotic system for CT [computed tomography]-guided percutaneous needle insertion and steering,” will be held on 29 November at 3pm CST.
In a second poster presentation, Gerald Grubbs (Sarasota Interventional Radiology (SIR), Sarasota, USA) will highlight recent clinical experience with the XACT ACE robotic system. His presentation, “Real world use of a hands-free robotic system for percutaneous procedures,” will be held virtually. On-demand access can be obtained by registering through the virtual meeting with RSNA.
RSNA 2021 will also serve as the venue where, for the first time, the company will introduce ACE Xtend, which enables remote activation of the XACT ACE robotic system for CT-guided percutaneous procedures. According to a press release from XACT Robotics, the system’s new capabilities will allow providers to enable precise robotic insertion and non-linear steering of various instruments from outside the procedure room. This, the company claims, will make the procedure more efficient and improve overall safety by reducing the risk of exposure to radiation and other harmful pathogens.
The XACT ACE robotic system features non-linear steering to combine advanced image-based planning and real-time, the company said.
The system received US Food and Drug Administration (FDA) clearance for use during CT-guided percutaneous procedures, as well as CE mark, and commenced commercialisation in October 2020.
The company will showcase the XACT ACE robotic system, including its new ACE Xtend, at the booth (#1557) throughout the RSNA meeting, and at a virtual product theatre on Monday 29 November at 4pm CST.
The UNC Department of Radiology (Chapel Hill, USA) recently named Gloria Salazar, as the department’s next division chief of vascular and interventional radiology (VIR).
Following selection from a competitive pool of candidates nationwide, Salazar began leading the VIR division as an associate professor of radiology in October 2021.
Salazar was recruited to Massachusetts General Hospital (MGH)’s Department of Radiology (Boston, USA) in 2008 as an assistant radiologist, following three years of clinical research and advanced clinical interventional radiology (IR) fellowship training at Beth Israel Deaconess Medical Center in Boston, USA. With over twelve years at MGH, she has built an institutional leadership record, major roles including outpatient IR medical director, Waltham Vein Center (Boston, USA) medical director, fibroids programme co-director, simulation and patient experience officer, and Department of Radiology quality and safety chair.
Salazar is established as a women’s health advocate, subspecialty expert, and practitioner volunteer to the underserved. In collaboration with MGH’s Obstetrics and Gynaecology Department, she co-developed the institution’s programme for fibroids to create a multidisciplinary clinic that improves patient-centred care and informed decision-making for women seeking treatment for fibroids. Her strong belief in outreach to underserved populations led Salazar to join MGH’s Spanish language care medical group during the 2020 COVID-19 pandemic surge to deliver volunteer care to COVID-19 non-English speaking patients. She also served as a faculty proctor and invited speaker at the inaugural Society of Interventional Radiology (SIR) Giveback Program (2019, El Salvador). This programme aims to expand options in minimally invasive procedures in Latin American countries to help underserved women avoid hysterectomies.
As a scholar, Salazar is routinely invited to speak worldwide at conferences and symposia on wide-ranging topics in IR, including quality assurance, procedural treatment, practice quality improvement (IR/general radiology), the value of simulation, and women’s health. She has co-authored multiple publications and book chapters and served as principal investigator (PI) or co-PI of multiple clinical trials and has a strong collaborative record with industry partners in her subspecialty. She is additionally an active SIR member, having served in major leadership roles including:
1) SIR Women’s Health Service line chair
2) SIR Diversity and Inclusion (D&I) advisory board member
3) SIR International Exchange committee member.
Maureen Kohi, UNC Radiology Department chair, noted: “I am confident that Salazar’s exceptional clinical acumen, her national and international reputation as a VIR leader, and her commitment to research and education will continue to elevate our outstanding VIR Division.”
UNC Department of Radiology thanks interim Charles Burke, VIR division chief, UNC Radiology Department, for his dedication and service within the VIR Division and across the department.
Viz.ai has announced the US commercial launch of its AI-powered modules for pulmonary embolism and aortic disease. Debuting at VEITHsymposium 2021 (16–20 November, Orlando, USA), the new modules allow for faster clinical decision making and improved care coordination for patients suffering from these two life-threatening conditions, a press release details.
The new modules leverage advanced deep learning to communicate time-sensitive information, including advanced imaging studies and real time clinical information, to specialists who can more quickly and easily make treatment decisions for the patient, the press release continues. Users can access all aortic and pulmonary imaging from the cloud.
“This technology has changed the way we triage and treat stroke patients, dramatically improving their care,” said Richard Saxon, interventional radiologist at Tri-City and Palomar Health, San Marcos, USA. “In a similar fashion, I believe the Viz.ai PE and Aortic modules will enhance image interpretation with AI [artificial intelligence], dramatically improve the quality and speed of mobile image viewing, and improve caregiver communication. This is truly the care coordination of the future.”
According to Viz.ai, the company has accelerated the time-to-notification of the treatment team by 73% and time-to-treatment by 24%.
“The launch of these two new modules brings the power of the Viz platform to a vast new faction of medical professionals and patients battling life-threatening conditions,” said Chris Mansi, Viz.ai CEO and cofounder. “This is a significant milestone in our mission to fundamentally improve how healthcare is delivered in the world.”
Viz.ai will be showcasing the new AI-powered PE and aortic disease modules at VEITHsymposium Booth #317.
In a pooled analysis of the predictors of drug-coated balloon (DCB) effectiveness, the IN.PACT Admiral DCB (Medtronic) performed well across a broad range of clinical, anatomical, and procedural scenarios. This is according to Prakash Krishnan (Mount Sinai Hospital, New York, USA), who presented key findings of the investigation in a featured clinical research session at Transcatheter Cardiovascular Therapeutics (TCT) 2021 (4–6 November, Orlando, USA).
The analysis combined data from 557 patients treated with DCBs in the IN.PACT superficial femoral artery (SFA) randomised controlled trial (RCT), the IN.PACT Japan RCT and the prespecified long lesion and chronic total occlusion imaging cohorts of the IN.PACT Global study.
The objective of this pooled IN.PACT analysis was to examine the factors contributing to 12-month effectiveness outcomes when DCBs are used for the treatment of femoropopliteal disease. While several studies have evaluated the predictors of DCB efficacy in smaller populations, Medtronic claims that the IN.PACT analysis is the first large-scale collaborative effort to evaluate a broad set of clinical, anatomical and procedural factors using rigorous, core-laboratory-adjudicated data.
Krishnan informed the TCT audience that only residual stenosis >30%, Rutherford category >3, and smaller preprocedure reference vessel diameter were significant multivariable predictors of decreased DCB effectiveness.
He also stressed the importance of vessel preparation, noting that patients with postprocedure residual stenosis <30% had a 4.7-fold higher risk of clinically-driven target lesion revascularisation (CD-TLR; hazard ratio [HR], 5.67; 95% confidence interval [CI], 2.32–13.85) and a 1.7-fold higher risk of binary restenosis (HR, 2.73; 95% CI, 1.6–4.65 through 12-month follow-up compared to patients who had residual stenosis ≤30%.
Other key findings included the following:
In his presentation, Krishnan concluded that DCBs work well across a wide range of clinical and anatomical scenarios, adding that patency can be optimised by procedural factors under the operators control, specifically, achieving a postprocedural residual stenosis <30%.
A pilot study, published in the Journal of Cancer Therapy, reveals that percutaneous cryoablation of early-stage, low-risk breast cancer tumours smaller than 15mm presents a potential substitute for lumpectomy.
Investigators, Hinsanoro Kawamoto (Department of Breast Surgery, Breast and Imaging Center, StMarianna) and colleagues report “encouraging short- to mid-term oncology results with good cosmesis outcomes” for the procedure.
They highlight that patients would be able to benefit from local anaesthesia in an outpatient setting and a shorter recovery period.
The pilot study enrolled eight patients and set out to evaluate the feasibility, safety, and cosmetic outcomes of percutaneous cryoablation of breast intraductal carcinoma lesions, as well as post-cryoablation magnetic resonance imaging (MRI) as a follow-up tool for detection of residual malignancies and local recurrences.
“We are excited to see the publication of these data from an independent study which further supports the use of our ProSense cryoablation system to eliminate small malignant lesions in the breast instead of performing breast surgery under general anaesthesia,” commented Eyal Shamir, chief executive officer of IceCure.
A press release from the company states: “The independent study conducted at the St Marianna University Breast and Imaging Center enrolled eight women, 53–72 years of age. Percutaneous ultrasound-guided cryoablation of the breast tumour was performed using IceCure’s ProSense, under local anaesthesia without the need for subsequent resection. The procedure lasted for 40 minutes on average. All patients received radiation and endocrine therapies. The patients were followed using vacuum-assisted biopsy (VAB), mammography (MG), MRI, and Moiré Topography for cosmetic outcomes.”
In September 2021, IceCure announced an Annals of Surgical Oncology publication authored by Richard Fine (West Comprehensive Breast Center, Germantown, USA) and colleagues. The article reported results previously announced at the American Society of Breast Surgeons Annual Meeting, that at a mean of 34.83 months following treatment with the ProSense cryoablation system, only 2.06% (four of 194 patients) experienced cancer recurrence.
The ICE3 trial commenced in 2014 and was conducted at 19 US hospitals, including Columbia University Medical Center and Mount Sinai Beth, Isarel. The trial enrolled and treated 194 patients (average age of 75) with low-risk, early-stage breast cancer tumours measuring up to 1.5cm.
Fine and colleagues conclude: “Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally-invasive procedure with minimal risks.” Fine stated that “the three-year ICE3 trial results highlighting the efficacy and safety of the procedure in this patient group are extremely promising for breast cryoablation. Being able to provide a minimally-invasive option for treating appropriate low-risk patients represents a dramatic improvement in care. The procedure is quick, painless and can be delivered with local anaesthesia in doctors’ offices, with minimal recovery time and excellent cosmetic outcomes.”
Rapid Medical today announced US Food and Drug Administration (FDA) investigational device exemption (IDE) approval for what it claims is the first-ever trial to expand interventional stroke treatment to distal regions of the brain.
The DISTALS study is a pivotal, international, multicentre, randomised controlled trial (RCT) to evaluate the safety and effectiveness of distal thrombectomy. This new frontier for ischaemic stroke has been created by Rapid Medical’s development of TIGERTRIEVER 13—the smallest available thrombectomy device—according to a company press release.
“We are especially pleased to receive unprecedented FDA IDE approval for a study with DISTALS focus,” said Jeffrey Saver, professor of neurology and director of the Comprehensive Stroke and Vascular Neurology Program at the University of California Los Angeles (UCLA) in Los Angeles, USA, and the study’s principal investigator. “With the ever-growing benefits of mechanical thrombectomy, we hope to offer better recoveries to a much broader patient population. Rapid Medical has been at the forefront of enabling that progress.”
Currently, less than 10% of ischaemic stroke patients receive mechanical thrombectomy, a well-proven treatment that significantly improves patient outcomes, the release continues. While Rapid Medical’s TIGERTRIEVER 13 has already been used to treat nearly 1,500 patients in Europe and the Middle East, the DISTALS study aims to extend these benefits to an additional 25–40% of stroke patients. It focuses on far territories in the brain, such as M3 blood vessels, and allows intervention within 24 hours from symptoms onset.
“The DISTALS trial is critical for the field of interventional stroke therapy,” said David Fiorella, director of the Cerebrovascular Center at Stony Brook University Medical Center in Stony Brook, USA, and co-coordinating investigator. “It potentially allows us to offer thrombectomy to an additional large group of stroke patients who may benefit substantially.”
The leading investigators of the DISTALS study also include René Chapot, professor and department head of neuroradiology and radiology at Alfried Krupp Krankenhaus in Essen, Germany and Rishi Gupta, director of Neurocritical Care at Wellstar Health System in Marietta, USA. Rapid Medical plans to start the study in Q4 2021 or early in Q1 2022—according to the company’s co-founder and CEO Ronen Eckhouse.
Endologix has announced the appointment of Matthew Thompson as president and chief executive officer. Thompson will also join Endologix’s board of directors. Richard Mott, who previously held the CEO position on an interim basis, will return to his role as executive chairman of the board of directors.
Thompson has been serving as Endologix’s chief medical officer since 2016, and, in that capacity, had oversight of the company’s business development, medical affairs, regulatory, clinical and R&D departments. Thompson also led the April 2021 acquisition and subsequent integration of PQ Bypass. He is a contract staff surgeon in the Department of Vascular Surgery, Heart, Vascular and Thoracic Institute at the Cleveland Clinic Foundation Ohio and visiting professor at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, USA. Previously he was the professor of vascular surgery at St George’s, University of London and a consultant vascular Surgeon at St George’s Vascular Institute in London, UK.
“I have had the pleasure of working side by side with Matt over the past year and have the utmost confidence in his ability to lead Endologix through this transformative period. Matt embodies the fusion of the entrepreneurial vision and subject matter expertise that we need to successfully accelerate Endologix as a leader in the development and commercialisation of the most innovative devices for the treatment of vascular disease,” said Mott.
“I have been extremely impressed with Matt’s leadership of major company initiatives, including the PQ Bypass acquisition and integration, and the AFX FDA [US Food and Drug Administration] advisory panel meeting, as well as his leadership of major functions within the company,” noted Andrew El Bardissi, Deerfield partner and member of the Endologix board of directors. “I am confident in Matt’s ability to step into the CEO role and guide the company during this important period of growth.”
“I am excited about the opportunity to lead such a dynamic and innovative organisation. I look forward to continuing my close relationship with Rich, the board, and the talented and dedicated team of employees that I have worked so closely with over the past several years,” said Thompson. “I will be completely committed to our physician customers and to the safety and health of their patients, as we continue to work collaboratively with the FDA and other global regulatory agencies to ensure we maintain the highest standards possible. In the next year, we will continue to drive market share gains with our family of AAA [abdominal aortic aneurysm] products and prepare our regulatory submissions for our innovative long-lesion PAD [peripheral arterial disease] products being developed after our acquisition of PQ Bypass earlier this year.”
XACT Robotics today announced what it describes as the world’s first remote-controlled robotic instrument insertion and non-linear steering during an interventional oncology percutaneous procedure with ACE Xtend.
ACE Xtend is the remote-control feature of the XACT ACE robotic system, which the company claims is the “world’s first and only” comprehensive robotic system that integrates image-guided planning and real-time monitoring with precise robotic insertion and non-linear steering to deliver various instruments to a desired target in the body. The procedure using the XACT ACE robotic system with ACE Xtend was successfully completed by the interventional radiology team at Sarasota Interventional Radiology in Sarasota, USA.
“We are very excited about the addition of remote capabilities with ACE Xtend, that can improve workflows, allow us to perform more procedures, and better support our patients and staff,” said Gerald Grubbs (Sarasota Interventional Radiology, Sarasota, USA). “The ability for our interventional radiology team to perform procedures without having to enter the procedure room also increases overall safety by reducing the risk of exposure to radiation and other harmful pathogens.”
In a press release, XACT Robotics said that the XACT ACE system’s features have been proven in over 200 clinical and pre-clinical cases to improve tip-to-target accuracy, efficiency, and consistency in interventional percutaneous procedures. With the addition of ACE Xtend, users can now reduce their exposure to harmful radiation and pathogens by controlling the XACT ACE robotic system from the control room, the company said.
“We are proud to announce this historic event as it shows our commitment to advancing care in interventional percutaneous procedures, and to deliver better outcomes to patients across the world,” said Harel Gadot (founder, executive chairman, and president of XACT Robotics). “With the ability to control the XACT ACE robotic system from outside the imaging suite, we make the procedure more efficient and as such allow more patients to be treated.”
The upcoming Controversies in Dialysis Access (CiDA) meeting in Dallas, Texas is stepping up the scrutiny on the controversies and questions currently igniting the dialysis community, Bart Dolmatch (Portola Valley, USA) tells Renal Interventions at the Paris Vascular Insights meeting.
Topping the agenda are the use of drug-coated balloon technology to maintain and treat stenosis in the dialysis access circuit (“the results of at least four large, randomised trials are phenomenally different”); the place for percutaneous arteriovenous fistula creation (“is it ready for prime time?”) and safety and quality in the provision of dialysis access (“who is watching?”). And, they will all come under the scanner at CiDA.
The Ellipsys vascular access system (Avenu Medical/Medtronic) can be used to easily and safely create durable percutaneous arteriovenous fistulas (pAVFs) for haemodialysis—with new, long-term data suggesting it offers an “excellent alternative” to AVF creation via surgical procedures in end-stage renal disease (ESRD) patients. That is according to Jeffrey Hull, an interventional radiologist and director of the Richmond Vascular Institute in Richmond, USA, who presented five-year results from the Ellipsys US pivotal trial at this year’s American Society of Nephrology (ASN) Kidney Week (2–7 November 2021, virtual).
And, speaking to Renal Interventions shortly after this event regarding the role endovascular AVFs now play within access creation strategies, Hull stated: “Once you get past the wrist issue, I would say it could be percutaneous fistula first. If you are a candidate for a fistula, but not a great wrist fistula candidate, then maybe the first possible fistula that should be considered for you is a percutaneous fistula—and I think the data are promising enough to support this.”
Hull began his ASN Kidney Week presentation by briefly demonstrating the procedure through which a proximal radial artery fistula is created using the Ellipsys system—noting the application of pressure and heat to “weld” the target vein and proximal radial artery together. This differs from more traditional, surgical procedures in which suturing is used to create the anastomosis between these vessels, he added. Hull also noted that balloon dilatation is commonly used to relieve spasm in the anastomosis shortly after the procedure.
He went on to provide the audience with an overview of the Ellipsys US pivotal trial, a prospective, multicentre, single-arm study intended to evaluate the safety and effectiveness of AVF creation using the Ellipsys device. It involved a total of 107 patients treated across five outpatient, office-based labs, he reported, adding that—aside from the fact 76 (71%) of these patients were male—the baseline characteristics of these patients were “typical of those seen in dialysis patient populations”, with a mean age of 56.6 years and an obesity prevalence of 50%.
Moving on to discuss one-year data from this trial, Hull reported a technical success rate of 95% (102/107 patients) and a clinical success rate of 95% (98/103 patients), with an average procedure time of 24 minutes also being observed. He added that the target vein was the cephalic vein in the majority of cases (74%), followed by the basilic (24%) and brachial (2%) veins. Discussing methods used to increase blood flow through the anastomoses created in the trial—referred to as maturation procedures—Hull noted that percutaneous transluminal angioplasty (PTA) proximal to the fistula was used in 72% of cases, while branch (35%) and deep (32%) embolisation, cubital vein ligation (31%) and transposition (26%) were also deployed.
Hull then noted that, at one-year follow-up, fistula-related events including thrombosis, stenosis, cannulation-related injuries or difficulties, and steal syndrome, generally looked “very similar” to those seen in surgically created fistulas—something that he stated was “a little disappointing” at that stage. He did add, however, that the Ellipsys US pivotal trial met its primary efficacy endpoint, as 86% (92/107) of fistulas were mature at 90 days, and met its primary safety endpoint, due to there being no serious, device-related adverse events.
Discussing the crux of his ASN Kidney Week presentation, Hull reported that a total of 85 patients were eligible for further follow-up at one year and the trial’s investigators continued to follow up these patients out to five years. Regarding the first of several long-term endpoints—fistula use, assessed by two-needle cannulation—Hull told the audience that 92% (83/90) of these fistulas were used in patients requiring dialysis, describing this as “an excellent outcome” that compares favourably to the 63% rate of two-needle cannulation observed in US patients with surgically created fistulas. He further noted that fistula non-use was low, with 11 of the 24 patients whose percutaneous fistula was unused ultimately not requiring haemodialysis.
Outlining access complications through five years, Hull said 27 patients experienced complications including fistula dysfunction (21.2%), cannulation injury (12.9%), thrombosis (5.9%) and arm swelling (4.7%)—with these being typical of those seen in dialysis patient populations. A total of 91 additional procedures were performed to rectify these issues, he stated, with the most commonly observed types being balloon dilatation (n=71) and thrombectomy (n=12), followed by stent grafting (n=6) and surgical repair (n=4).
Hull also noted, regarding additional procedures per patient per year in the US pivotal trial, that this figure (2.66) was similar to those associated with surgically created fistulas at one year, but that in years two through five a “drastic reduction” in additional procedures per patient per year—ranging from 0.18 to 0.57—was observed. “We attribute that to the low-to-moderate flow in these [percutaneously created] fistulas, averaging 1,000ml per minute, and also the multi-outflow feature of these fistulas whereby, if an injury occurs, the blood will flow around it and keep the fistula operational until it can be repaired,” he reported.
Touching on the final long-term endpoint from the trial, Hull relayed “excellent” primary assisted and secondary patency rates of 74% and 82%, respectively, at five years as per Kaplan Meier estimates, while the functional patency rate was found to be 91.8% through the follow-up period as well. “In summary, this follow-up study has shown us several important things—the first being that high-quality fistulas can be performed by interventional nephrologists,” he concluded. “Secondly, we have expanded the places in which these fistulas can be created, not just in the hospital but now in office-based labs and ambulatory surgery centres too.”
In addition to reiterating the high fistula usage, positive long-term patency outcomes, and low complication rates and subsequent maintenance procedures, seen through five years in the study, Hull ended his presentation by noting that, moving forward, the goal is to reduce the time to two-needle cannulation for the Ellipsys system, with cannulation- and cost-related issues also continuing to be evaluated further.
Royal Philips today announced the results of a new large-scale real-world analysis of Centers for Medicare & Medicaid Services (CMS) data on the health outcomes of peripheral vascular interventions guided by intravascular ultrasound (IVUS).
The study was conducted independently by the Smith Center for Outcomes Research at Beth Israel Deaconess Medical Center (Boston, USA), with the results presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021 (4–6 November, Orlando, USA) by Eric A Secemsky, director of Vascular Intervention and interventional cardiologist at Beth Israel Deaconess Medical Center and assistant professor of Medicine at Harvard Medical School in Boston, USA. The study was supported by Philips.
A press release details that numerous prospective studies have already shown the benefit of IVUS guidance in peripheral vascular interventions, making it a gold-standard imaging modality for this application. The new study results now show that the outcome observations from these prior studies apply directly to a broader patient population and across vascular beds, demonstrating strong support for the use of IVUS during peripheral interventions, the release continues.
“The results of this large-scale study demonstrate favourable long-term outcomes in peripheral vascular interventions when IVUS is used,” said Secemsky. “This analysis, combined with the recent appropriate use consensus on IVUS that was presented at VIVA [Vascular Interventional Advances; 5–7 October, Las Vegas, USA], highlights a clear opportunity to improve health outcomes for millions of patients by broader and more routine implementation of the technology in clinical practice. This is a moment for us to further our efforts in saving lives and saving limbs.”
Peripheral arterial disease (PAD): A 32% reduction in major adverse limb events, including amputations, during lower extremity arterial interventions
The study looked at Medicare beneficiaries aged 65 years or older who underwent lower extremity arterial interventions between 1 January 2016 and 31 December 2019. Among 697,794 interventions, the investigators found a 32% reduction in major adverse limb events, such as amputations, over a median 425 days of follow-up. These findings were consistent across disease states, including chronic limb-threatening ischaemia (CLTI) and non-CLTI, as well as arterial segments such as iliac, femoropopliteal and tibial.
Chronic venous disease (CVD): A 31% reduction in repeat intervention, hospitalisation or death during iliofemoral venous stenting
Separately, the investigators examined Medicare beneficiary data for patients treated between 1 January 2017 and 31 December 2019 in multiple clinical settings, including hospital in-patient settings, hospital outpatient centres and private office-based clinics, involving 20,984 individual patients. Of these, 72% underwent stenting guided by IVUS. When IVUS was used, there was a 31% reduction in the composite outcome of repeat intervention, hospitalisation or death. In addition, IVUS use reduced the risk of stent thrombosis, embolisation and stenosis.
“We commend Dr Secemsky and the Smith Center for Outcomes Research for this ongoing study to simplify clinical procedures and improve clinical, economic and patient outcomes,” said Chris Landon, senior vice president and general manager Image Guided Therapy Devices at Philips. “We are committed to supporting evidence-based medical guidelines in pursuit of better patient outcomes. We believe that the ability of IVUS to deliver procedure optimisation and confidence enhances patient and staff experiences and lowers cost of care.”
First-ever global consensus for the appropriate use of IVUS in peripheral vascular disease interventions
In October 2021, a team of clinical experts led by Secemsky established the first-ever global, cross-specialty expert consensus for the appropriate use of IVUS in peripheral vascular disease interventions. This initiative was jointly supported by Philips and Boston Scientific. Today, healthcare providers’ use of IVUS in peripheral vascular disease interventions is not standardised and is therefore inconsistent. The new appropriate-use expert consensus may help establish global standards of care to adopt into guidelines and improve quality of care in peripheral vascular disease, a Philips press release states.
Hispanic adults hospitalised for treatment of symptoms of peripheral arterial disease (PAD) were more likely to access this care by going to the emergency room (ER), and they experienced longer and more expensive hospitalisations than non-Hispanic white patients with PAD, according to preliminary research to be presented at the American Heart Association (AHA) Quality of Care and Outcomes (QCOR) Research Scientific Sessions 2021. The meeting will be held virtually on Monday 15 November 2021 in conjunction with the Association’s Scientific Sessions 2021.
“The Hispanic population is one of the fastest growing ethnic groups in the USA, and prior studies have shown worse outcomes among Hispanic adults with PAD, including higher rates of amputation and fewer revascularisation procedures compared to non-Hispanic white adults with PAD,” said lead study author Kristie Harris, an instructor of Medicine at Yale School of Medicine in New Haven, USA, in a press release from the AHA. “The prevalence of PAD among Hispanic individuals has been difficult to determine because this population often experiences a lack of access to healthcare and is underrepresented in many population-based studies. Our study raises awareness and confirms some of these disparities.”
Harris and her team examined hospital admission data from the 2011–2017 National Inpatient Sample to study differences in the experiences of Hispanic and non-Hispanic white adults treated for PAD symptoms. They investigated whether people sought inpatient PAD care by presenting to the ER or if they came for a planned, elective visit, likely sent by an outpatient care professional.
During the study period, there were 1,018,220 PAD hospitalisations among adults age of 18 years and older in the USA (39% female; 14% Hispanic adults).
The percentage of people who accessed inpatient hospital care via the emergency department increased among both Hispanic adults and non-Hispanic white adults between 2011–2017. The increase was substantial among those who are Hispanic, the AHA press release reports, with the percentage of PAD hospital admissions occurring through the ER jumping from 50% to 70% over the course of the study period.
The researchers found that Hispanic adults with PAD were 80% more likely to access inpatient PAD care by going to the ER for symptoms compared with non-Hispanic white adults hospitalised with PAD. Additionally, Hispanic adults were 12% less likely to undergo elective hospital admissions for PAD.
Among the other findings in the study:
“Our findings reinforce other research that indicates Hispanic individuals often lack a usual source for routine healthcare and frequently defer or avoid care due to costs,” Harris said. “Instead of delaying care, a better way to manage PAD and reduce the risks of future complications is with regular evaluation and follow-up, usually with a primary care doctor or vascular specialist.”
Harris said prevention is key, and as with any other type of cardiovascular disease, people should be encouraged to quit smoking, be physically active and to manage diabetes, high blood pressure or high cholesterol, which all increase the risk for PAD. Individuals who develop pain in their feet or legs with walking not associated with muscle strain should seek medical care early for a comprehensive evaluation.
“This study highlights the importance of better tailoring PAD prevention and management, especially among Hispanic people, which could reduce the need for hospital ER care or hospitalisation,” she said. “Systematic efforts are needed to ensure Hispanic people with PAD have more accessible, affordable and culturally sensitive outpatient care. Efforts should include supports that educate the community regarding the signs and symptoms of PAD and encouragement to seek care early.”
The study reported no funding sources.
Medtronic has announced its ambition to achieve net zero carbon emissions by fiscal year 2045 across its operations and value chain to accelerate efforts to combat climate change. The announcement comes amidst the 2021 United Nations Climate Change Conference (COP 26), where world leaders are focusing on collectively cutting greenhouse gas (GHG) emissions and limiting global warming to 1.5 degrees Celsius compared to pre-industrial levels.
As published in Medtronic’s new Decarbonization Roadmap, the FY45 milestone builds on the company’s existing goal of reaching carbon neutrality in its operations by fiscal year 2030, to encompass GHG emissions reductions across its entire value chain. To achieve its ambition, Medtronic will pursue setting GHG emission reduction targets across scopes 1, 2, and 3 through the Science-Based Targets Initiative (SBTi) – a multi-year initiative that provides companies a clearly defined path to reduce emissions aligned with the Paris Agreement.
“As a global healthcare technology leader, our goal is to transform industry expectations and behaviour where health and climate change intersect,” said Geoff Martha, Medtronic chairman and chief executive officer. “Our teams across 150 countries are actively working to protect our planet by reducing our energy use, investing in renewables, and now moving toward net zero emissions throughout our operations, supply chain and logistic partners, by pursuing science-based targets.”
Randomised placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure, the findings of a systematic review and meta-analysis suggest.
Findings of the paper, authored by Yousif Ahmad (Yale School of Medicine, Yale University, New Haven) and colleagues, were published in JACC: Cardiovascular Interventions and presented during an oral abstract session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual).
In their paper, Ahmad and colleagues note that renal denervation has undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medication.
The authors performed an updated meta-analysis of randomised placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications. This included latest evidence from the RADIANCE-HTN TRIO trial, presented on the same day at TCT 2021 in a late-breaking trial session.
The study’s primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure, and analysis was stratified by whether there was background antihypertensive medication use.
Ahmad and colleagues report that there were seven eligible trials, totalling 1,368 patients.
Outlining the results, the study team notes that renal denervation significantly reduced ambulatory systolic (mean difference −3.61mmHg; 95% confidence interval [CI]: -4.89 to -2.33mmHg; p<0.0001), ambulatory diastolic (-1.85mmHg; 95% CI: -2.78 to -0.92mmHg; p<0.0001), office systolic (-5.86mmHg; 95% CI: -7.77 to -3.94mmHg; p<0.0001), and office diastolic (-3.63 mm Hg; 95% CI: -4.77 to -2.50; P < 0.0001) blood pressure.
There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (p-interaction=NS for each comparison).
Ahmad and colleagues conclude that the randomised placebo-controlled trials show “consistently” that renal denervation provides significant reduction in ambulatory and office blood pressure.
“Although the magnitude of benefit, about 4/2mmHg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents,” the study’s authors note. “Whether the effect changes with time is currently unknown.”
Six-month outcomes from the randomised RADIANCE-HTN TRIO trial, comparing endovascular ultrasound renal denervation to a sham procedure for treatment-resistant hypertension, demonstrate the additional effects of pharmacologic intervention with maintenance of a blood pressure-lowering effect of renal denervation at six months, according to investigators.
The six-month results were presented during a late-breaking trial session at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021; 4–6 November, Orlando USA and virtual) by Ajay Kirtane (Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, USA). These build upon the presentation of the trial’s two-month findings at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual) and also published in The Lancet.
Patients with hypertension require a multi-faceted approach for blood pressure control, Kirtane explained, detailing that in RADIANCE-HTN TRIO, patients with daytime ambulatory systolic blood pressure (dASBP) 135/85mgHg despite a fixed dose combination pill consisting of a calcium channel blocker, angiotensin receptor blocker, and thiazide diuretic, were randomised to renal denervation using the Paradise renal denervation ultrasound system (ReCor Medical, n=69) or a sham procedure (n=67).
The trial’s two-month results found that, in conjunction with the three-drug fixed-dose combination pill, renal denervation reduced dASBP by an additional 8mmHg, a 4.5mmHg greater reduction compared with a sham procedure (–8mmHg versus –3mmHg; median between-group difference–4.5mmHg; adjusted p=0.022).
During months two through five, the addition of a standardised stepped-care antihypertensive treatment (SSAHT) was recommended sequentially with the addition of spironolactone 25mg/d, bisoprolol 10mg/d, full dose of a centrally acting α2 receptor agonist, and an α1 receptor blocker if monthly measured home blood pressure was ≥135/85mmHg, with the goal of achieving blood pressure control in both groups. Adherence to prescribed medications was similar in both groups (71% for renal denervation versus 78% for sham, p=0.41).
The increase in the number of antihypertensive medications at six months following the addition of the SSAHT was 0.7±1 for renal denervation and 1.1±1.1 for sham (p=0.045). The use of aldosterone antagonists at two months was 3% for renal denervation and 11% for sham (p=0.16). At six months, the number increased in both groups but to a lesser extent in the renal denervation group (40% for renal denervation compared to 60.9% for sham, p=0.017).
The addition of the stepped care antihypertensive regimen to the initially randomised therapy further decreased blood pressures in both arms; the overall change from baseline in dASBP was -11.8±14.2mmHg in the renal denervation group versus -12.3±14.2mmHg for sham (p=0.65). Home blood pressure was lower in patients initially randomised to renal denervation when adjusted for baseline blood pressure and number of medications (-4.28mmHg, p=0.027). Safety outcomes were similar for both groups.
“Blood pressure reductions after renal denervation were achieved with a smaller increase in additional medications prescribed and less use of aldosterone antagonists compared with a sham procedure,” said Kirtane. “These results demonstrate the additional effects of pharmacologic intervention with maintenance of a blood pressure-lowering effect of endovascular ultrasound renal denervation at six months.”
During a press conference in which Kirtane presented the latest findings of the study, describing them as “exploratory”, he relayed that the addition of a pharmacologic intervention led to further blood pressure reductions after renal denervation with a smaller increase in additional medications prescribed and less use of diuretics.
In ensuing discussion during the press conference, David Kandzari (Piedmont Heart Institute, Atlanta, USA) described the findings as “welcome” as they add to the totality of evidence around renal denervation. Responding to a question as to whether, given the relative differences in the reduction in blood pressure in both arms, patients would be more willing to undergo an invasive intervention for hypertension, Kandzari noted that reducing medication burden is of “increasing importance” to patients.
He added: “The opportunity to reduce the medication burden in discrete choice experiment studies is one of the key drivers of patient motivation for an alternative therapy or approach like renal denervation.
“Indeed, patients do not typically want to undergo an interventional procedure, but if there is durability with it and if there is a meaningful reduction in blood pressure, which, interestingly by patients’ criteria does not have to be that large of a reduction in blood pressure to be meaningful, and the opportunity to reduce medicines, then it is clinically important to them.”
Kandzari also referred to new data to be presented at TCT 2021, that has sought to quantify US patient preferences for considerations of interventional procedures in the treatment of high blood pressure, including treatment mode, effectiveness and risks.
Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA) questioned if the results demonstrate the “durability” of renal denervation, but described the study as an “exciting next step”. “To me it is opening a window,” she remarked. “Previously the doors might have been closed for renal denervation, but I think the window is opening and it may be a large one!”
Medtronic today announced findings from a new study of patient preferences for the treatment of hypertension. The findings are set to be presented during the “What’s Novel in Interventional Hypertension” session at the 33rd Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando, USA and virtual)—the yearly scientific symposium of the Cardiovascular Research Foundation.
Medtronic has also announced the initiation of the SPYRAL AFFIRM study, evaluating the long-term safety, efficacy, and durability of the company’s Symplicity renal denervation (RDN) system—which uses a minimally invasive procedure that delivers radiofrequency energy to specific nerves near the kidneys that can become overactive and cause high blood pressure—in real-world patients with uncontrolled hypertension and comorbidities, such as diabetes, isolated systolic hypertension and chronic kidney disease (CKD).
Patient preference for the treatment of hypertension
For the first time, new data presented at TCT 2021 will quantify US patient preferences for considerations of interventional procedures in the treatment of high blood pressure, including treatment mode, effectiveness and risks, according to a Medtronic press release.
The study found that, in exchange for treatment risks, patients on average would require a minimal acceptable benefit of less than 2.5mmHg reduction in office-based systolic blood pressure. Additionally, on average, patients indicated a tolerance of at least 20% risk of adverse events (such as a vascular injury or drug side-effects) in exchange for being able to lower their office-based systolic blood pressure.
These findings suggest that, despite the risks of an intervention, patients may accept lower blood pressure reductions than those observed in published literature of the Medtronic Symplicity Spyral RDN procedure. Additionally, patients may be willing to tolerate risks higher than those observed in peer-reviewed published studies of Symplicity Spyral, the release adds.
The study also concluded that blood pressure reduction was the most important driver of patient preference over all other attributes like medication burden and treatment (including interventional treatment-related) risks.
When applying this model to a patient population that is interested in an interventional procedure without medication, up to 76.5% of patients would be willing to consider an interventional approach like RDN if they achieve a 10mmHg reduction in office-based systolic blood pressure. Including the maximum acceptable risk of 20%:
“This novel, patient preference study is particularly valuable for a new procedure like RDN, because it demonstrates that, for patients, lowering blood pressure—even by a small amount—is meaningful,” said Michael Weber, professor of cardiovascular medicine at State University of New York, Downstate Medical Center (Brooklyn, USA). “For the first time, these results give us quantitative insights into hypertension treatment preferences—importantly, patients are very open to considering a medical intervention procedure, such as RDN, with demonstrated improvements in the control of their high blood pressure.”
The study, which was designed based on the US Food and Drug Administration (FDA) Guidance for Patient Preference Information, surveyed 400 individuals in the USA who have high blood pressure (physician confirmed systolic office-based blood pressure greater than 140 mmHg), who were on up to three anti-hypertensive medications, and were not previously involved in a SPYRAL HTN [hypertension] study. The study uses a statistical method called a discrete choice experiment, often used to compare individuals’ preferences among two or more alternatives.
“The patient preference insights, combined with the breadth of real-world and randomised sham controlled trials we have for RDN, are aligned with the recent clinical consensus from the European Society of Hypertension, Society for Cardiovascular Angiography and Interventions, and National Kidney Foundation, that reinforce RDN as a potential treatment option for patients,” said Jason Weidman, senior vice president and president of the Coronary & Renal Denervation business, which is part of the Cardiovascular Portfolio at Medtronic. “Patient preference data will be important to help physicians understand patients’ acceptable benefits and risks related to minimally invasive procedures for the treatment of hypertension.”
SPYRAL AFFIRM study launch
Separately, Medtronic announced that the first patient was enrolled at Piedmont Heart Institute in Atlanta, USA for the SPYRAL AFFIRM clinical study. Using a performance goal, this clinical study will enrol 1,000 real-world patients with uncontrolled hypertension and associated comorbidities, such as isolated systolic hypertension, diabetes, and CKD. SPYRAL AFFIRM will follow these patients for three years. This investigational device exemption (IDE) trial was approved by the FDA in June 2021 and will be conducted at 100 sites globally.
“Through the strong investment in our clinical programme, the AFFIRM study will expand RDN research into a variety of patient groups,” said Weidman. “The AFFIRM clinical study adds to our body of evidence for RDN and will help us further answer questions about the use of this procedure in more complex, real-world patients such as those with isolated systolic hypertension, diabetes and CKD.”
The SPYRAL AFFIRM clinical study is part of the SPYRAL HTN Global Clinical Program, adding to the safety and efficacy data for RDN, the release continues. Along with the real-world data from the Global Symplicity Registry, when combined with commercial experience, there have been more than 20,000 procedures performed with Medtronic RDN technology. The clinical programme is backed by the most rigorous and extensive patient experience studied in the presence and absence of medication, and in patients with high baseline cardiovascular risk.
Inari Medical has announced positive acute and long-term interim results from the first 500 pulmonary embolism (PE) patients enrolled in the FlowTriever outcomes registry (FLASH).
A press release reports that, at 48 hours post procedure, the major adverse event rate and mortality rate were low, at 1.4% and 0.2%, respectively. None of the deaths or major adverse events were device related. Collectively, these PE patients experienced substantial on-table improvements in haemodynamics and symptoms, which translated to six-month improvements in cardiac function, functional status, and quality of life measures.
The outcomes were achieved while limiting utilisation of hospital resources, the release adds, with less than 4% of patients receiving adjunctive therapy and a median of zero days in the intensive care unit (ICU) post procedure.
FLASH is a prospective, multicentre, single-arm registry evaluating real-world patient outcomes after treatment of PE with FlowTriever. The 500-patient interim results were presented on 27 October via webcast at Transcatheter Cardiovascular Therapeutics (TCT) 2021 by principal investigator Catalin Toma, an interventional cardiologist at University of Pittsburgh Medical Center (UPMC) in Pittsburgh, USA. TCT 2021 will be held in person and broadcast live online 4–6 November in Orlando, USA.
“These interim results reinforce the strong safety profile of the FlowTriever system in real-world PE patients, with substantial on-table clinical improvements and immediate symptom relief,” said Toma.
“We believe these six-month follow-up data suggest that removal of clot burden without the risks of lytics has potential positive long-term implications for PE patients, including strikingly low rates of hospital readmissions, dyspnoea, CTED [chronic thromboembolic disease], and CTEPH [chronic thromboembolic pulmonary hypertension]. These data suggest that treatment with FlowTriever may fundamentally improve the natural course of the disease, and that is tremendously exciting.”
Shockwave Medical has announced that, as part of the calendar year 2022 Medicare Hospital Outpatient Prospective Payment System (OPPS) final rule, the Centers for Medicare and Medicaid Services (CMS) has reassigned the payment for peripheral intravascular lithotripsy (IVL) procedures performed on above-the-knee (ATK) arteries in the hospital outpatient setting. The resulting payment increases will become effective 1 January 2022.
As part of the 2022 OPPS final rule, CMS has announced new Ambulatory Payment Classification (APC) assignments for three Healthcare Common Procedure Coding System (HCPCS) codes that describe peripheral IVL procedures performed in lower extremity arteries in the outpatient hospital setting. The three HCPCS codes affected describe procedures in iliac, femoral and popliteal arteries when IVL is performed by itself or adjunctively with drug-coated balloons (DCB), stents or atherectomy. The new APC assignments will increase the payments hospitals receive for these procedures.
“We appreciate CMS’s collaborative relationship and their swift action in reassigning payment levels for IVL performed above the knee, as the data acknowledge the resources associated with performing IVL in these patients. Importantly, we believe the APC reassignment of these HCPCS codes and subsequent increased payment for IVL procedures performed ATK will further facilitate access to IVL technology for Medicare patients,” said Doug Godshall, president and chief executive officer of Shockwave Medical.
“We would like to acknowledge CMS for making an exception to this year’s standard rate-setting process by considering calendar year 2020 data when determining appropriate payment levels for the new peripheral IVL code set. We are also grateful for the support that came from CMS’ Hospital Outpatient Physician Advisory panel and medical societies during the public comment period.”
Fluidx Medical’s GPX embolic device has released initial results for Oncology Drug Delivery. Fluidx Medical Technology announced that a next-generation, doxorubicin-loaded GPX embolic device was featured at the recent symposium on clinical interventional oncology (CIO) conference highlighting the technology’s potential for oncology drug delivery.
“GPX is easy to prepare, deliver, and control,” said Ryan O’Hara (interventional oncologist, University of Utah, Salt Lake City, USA). “The initial results of GPX as a drug-loadable oncology solution are very promising. GPX would be the first loadable liquid embolic designed for tumour applications.”
Study results presented at CIO included an in vitro characterisation of the loading and drug release profile of the GPX Embolic Material loaded with doxorubicin (GPX-DOX). GPX-DOX provided a zero-order release profile for five weeks and sustained release out to 100 days. The long linear release profile is desirable in drug delivery, as a constant amount of drug is delivered regardless of the concentration within the carrier. These properties are unique in the field of liquid embolics.
The GPX Embolic Device is an innovative embolic designed for simple preparation and quick material delivery. GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolus upon delivery without polymerization or dimethyl-sulfoxide (DMSO) precipitation. GPX is designed to occlude blood vessels independent of a patient’s coagulation situation. The device is packaged ready-to-use in a syringe, requires less than 30 seconds of tableside preparation by the clinician, and may be delivered through standard catheters or small microcatheters (no complex mixing systems or special delivery catheters are necessary).
“We have not seen other liquid embolic devices that have demonstrated the ability to load and release oncology agents in a sustained manner,” said Libble Ginster, CEO of Fluidx Medical Technology. “The Fluidx team is excited about the future of GPX technology and inspired by bringing new innovations to cancer patient care.”
Fluidx Medical Technology is a Salt Lake City, Utah based company focused on developing the GPX Embolic Device and other innovative medical technologies.
The GPX Embolic Device is under development and does not have marketing clearance or approval in any market at this time. For investigational use (in New Zealand) only. GPX-DOX Embolic Device is under development and does not have marketing clearance or approval in any market at this time.
Varian is excited to announce David Hahn (clinical assistant professor of Radiology, University of Chicago Pritzker School, Chicago, USA) joined the company as vice president of Medical Affairs for Interventional Solutions. As a leading, practicing interventional radiologist, Hahn will bring his extensive experience to Varian to help expand access to personalized, multi-modal cancer care to patient populations worldwide.
“I am so excited to join the team at Varian, and work with such a fantastic group of colleagues as we focus on ways to expand access to new and innovative interventional radiology methods” said Hahn.
This hire reinforces Varian’s ongoing commitment to investing in the future of interventional radiology. Hahn’s extensive experience both in the clinical setting and private sector will bring a unique perspective as Varian works to deliver a portfolio of intelligent solutions and enhance the patient experience at every stage of care.
Based in Chicago, Hahn has held teaching faculty positions at Northwestern University Feinberg School of Medicine, Rush University of Chicago, and the University of Chicago Pritzker School of Medicine, where he is currently a Clinical Assistant Professor of Radiology. He has also authored numerous articles in peer-reviewed journals and has been an invited lecturer and moderator at congresses both nationally and internationally in addition to being a reviewer for the Journal of Vascular and Interventional Radiology since 2006.
There have been several positive expressions regarding Hahn joining Varian. Two quotes are shown below.
“David’s extensive experience in radiology makes him a fantastic addition to our team. I look forward to working together toward our goal of expanding access to personalized, multi-modal cancer care to patient populations worldwide.” Frank Facchini, FSIR, president, Varian Interventional Solutions
“I am thrilled to expand our medical affairs team with the addition of David Hahn. His deep expertise as a world-renowned Interventional Radiologist will be a fantastic resource for our team as we continue to grow and expand to serve new patient populations.” Dee Khuntia, chief medical officer and senior vice president of Medical Affairs, Varian.
Argon Medical Devices has announced the launch of two portal vein access sets intended for transjugular liver access in diagnostic and interventional procedures.
The Scorpion portal vein access series addresses the common challenges physicians encounter when placing a transjugular intrahepatic portosystemic shunt (TIPS) or conducting other portal vein access procedures. The Scorpion series includes two sets, Scorpion and ScorpionX, which offer improved visualisation, revolutionary navigation control, and enhanced durability to augment existing procedural techniques, according to Argon Medical.
The Scorpion portal vein access series utilises a patented curve-in-curve system to offer physicians 360-degree range of motion with the needle or stylet used to access the portal vein. Each curved component can work together or independently to accurately steer the device through the liver to the intended target. Existing systems utilise only a single curve limiting the steerability of the needle or stylet. The Scorpion series’ novel design was created by Lowell Kahn, a vascular and diagnostic interventional radiologist located in Springfield, USA, in conjunction with Hatch Medical.
“Establishing access to the portal venous system is often the longest and most challenging part of many procedures. This is particularly true when the liver is diseased, making the anatomy irregular. I designed the Scorpion’s independently controlled dual curves to improve the physician’s ability to navigate through liver parenchyma and reduce the number of attempts necessary to establish access to the portal vein,” said Khan.
“Argon Medical is proud to add the Scorpion Series into our product portfolio. 2021 is our ‘Year of Innovation,’ and we continue to develop and deliver innovative products to the interventional market. Launching Scorpion demonstrates our desire and ability to innovate to improve the lives of our customers and the patients they treat,” said George Leondis, CEO of Argon Medical.
The Scorpion portal vein access sets are currently available in the USA. Scorpion is licensed by Argon Medical and is a trademark of Hatch Medical.
Transit Scientific has announced US Food and Drug Administration (FDA) clearance of new hydrophilic-coated XO Cross microcatheters for guidewire support, exchange, and contrast media injection in the peripheral vasculature.
“The XO Cross devices deliver unique performance and control that make them an excellent tool for crossing above- and below-the-knee lesions,” said Jihad Mustapha, interventional cardiologist at Advanced Cardiac & Vascular Center in Grand Rapids, USA. “The non-tapered XO Cross shaft, lubricious coating, low crossing profile, and 1:1 torque response will be critical for workhorse performance and reducing the need for wire escalation techniques in CLTI [chronic limb-threatening ischaemia] cases.”
Microcatheters are commonly used to provide guidewire support, facilitate guidewire exchanges, access distal anatomy, cross lesions, deliver therapeutic embolics, and inject contrast media, during complex endovascular procedures. Hydrophilic coatings create a lubricious and slippery layer on the outside of catheters for improved navigation and tracking through tortuous vessels and lesions.
The XO Cross platform includes a metal-alloy exoskeleton, non-tapered shaft, proprietary hydrophilic lubricious coating, and large inner lumen for improved 1:1 torque, low-profile, pushability, tracking, crossing, fatigue-resistance, and angiography, a press release details.
According to Transit Scientific, XO Cross microcatheters have been safely and successfully used in challenging peripheral lesions above-the- including but not limited to above-the-knee and below-the-knee chronic total occlusions (CTOs) from contralateral femoral, antegrade femoral, and retrograde pedal access.
This 510k clearance includes new 2Fr XO Cross 14 microcatheters, 2.6Fr XO Cross 18 microcatheters, and 3.8Fr XO Cross 35 support catheters for use with standard 0.014”, 0.018”, and 0.035” guidewires in 90cm, 135cm, 150cm, and 175cm working lengths. The shorter 90cm devices support retrograde pedal and antegrade femoral access while the longer 175cm devices were designed specifically for radial access to peripheral use.
Marie Lannelongue Hospital of Paris Saint-Joseph Hospital Group (Paris, France) and Incepto, a European specialist in artificial intelligence (AI) applied to the medical field, recently announced the creation of ARVA (Augmented radiology for vascular aneurysm), a novel solution for automatic measurement of the maximum diameter of the aorta.
ARVA was developed by surgeons from the Paris Saint Joseph Hospital Group and engineers. According to a press release, this new application is the first solution in the world to fully automate the measurement of aortic aneurysms, providing radiologists and surgeons with a particularly effective aid in the diagnosis and follow-up of aneurysms.
The press release details that ARVA uses a dozen algorithms trained on a base of more than 1,000 scans annotated by experts to generate a pre-filled report in DICOM format that can be integrated into the radiologist or surgeon’s workflow.
“Before ARVA, in order to get accurate measurements of aortic diameter, we had to spend a lot of time analysing the scans. These measurements are complicated because in the presence of an aneurysm, the aorta is often tortuous. The AI we developed with Incepto is a tool that allows us to have precise and reproducible measurements of the diameter of the aorta and therefore to determine whether surgery is necessary,” says Dominique Fabre, surgeon at the Marie Lannelongue Hospital.
ARVA provides automatic measurements of the diameters per segment (S1 to S7) of the entire aorta, from its root near the heart to its division into two iliac arteries in the abdomen, the press release continues. In addition, it adds that ARVA provides a report including a three-dimensional (3D) reconstruction of the aorta, a schematic representation of the aorta by segment, stent detection, measurement of the largest diameter by segment and an oblique section of the largest diameter detected. The release specifies that one of the major benefits of ARVA is the comparison of measurements between different scans performed by the patient, with standardisation of the measurement and time saving for surgeons and radiologists.
ARVA is secure, implemented in the cloud and CE marked class I, according to the release. A first clinical study, published in the European Journal of Vascular and Endovascular Surgery, demonstrated the reliability of ARVA measurements on healthy and pathological aortas with and without stents, showing a median deviation of 1.2mm compared to the measurement performed by an expert. The median deviation between the six other doctors who participated in the study was 1.4mm.
“Since its inception in 2018, we have put forward a worldview of AI solutions rooted in collaboration between data scientists and physicians. Our main goal has always been to develop solutions that concretely help physicians and meet a real need. In line with this ambition, ARVA is the result of exciting work with the outstanding surgeons of the Marie Lannelongue Hospital whose driving force is excellence in patient care,” notes Gaspard d’Assignies, co-founder and chief medical officer of Incepto.
“This first version of ARVA will allow us to be more precise in our surgical indications, to save precious time on a daily basis, and to have at our disposal a document that will allow us to better inform patients. Future versions under development will revolutionise our profession, in particular with the automatic monitoring of aortic volumes. This is just the beginning of the AI adventure in medical imaging”, concludes Stéphan Haulon, head of the Aortic and Vascular Surgery Department at the Marie Lannelongue Hospital.
Twelve-month results from a first-in-human study of the Wrapsody cell-impermeable endoprosthesis (Merit Medical Systems) for the treatment of access circuit stenosis in haemodialysis patients are “very encouraging”. This is according to James Gilbert, a consultant transplant and vascular access surgeon at the Oxford University Hospitals NHS Foundation Trust in Oxford, UK, and president of the Vascular Access Society of Britain & Ireland (VASBI), who presented these data for the first time at the Cardiovascular and Interventional Radiological Society of Europe 2021 summit (CIRSE; 25–28 September, virtual).
Gilbert noted that this first-in-human study—dubbed WRAPSODY FIRST—produced positive results in terms of safety, detailing that no adverse events confirmed as being device-related were observed in 39 patients at one-year follow-up. Regarding effectiveness, he reported promising target lesion primary patency (TLPP) rates at 12 months across all lesion sites, in line with the study’s six-month data, and stated that access circuit patency rates also appear to remain high following treatment with the device. Gilbert went on to detail the pivotal WRAPSODY WAVE trial—a global randomised controlled trial (RCT) that is currently underway to assess the Wrapsody endoprosthesis.
Speaking to Renal Interventions, Gilbert said: “The 12-month effectiveness data, particularly of TLPP, are very exciting because we may have a stent that requires fewer reinterventions to maintain patency at the lesion site and, more importantly, ensures that the access circuit remains functional—which is key for any dialysis patient. The data were also reproducible at all lesion sites treated within the access circuit, from the cephalic arch in a brachiocephalic AVF [arteriovenous fistula] to the graft vein anastomosis site and the central veins. This is suggestive that there is something about the stent’s design, with its cell impermeable middle layer and softened end rows, that is key in minimising edge stenosis at both ends of the stent.
“We recognise that these very encouraging data are only from a small, first-in-human study and so the WRAPSODY WAVE trial will be key in confirming just how good this stent can be. The WAVE study will not only provide a bigger number of patients in which to assess the effectiveness of the stent, it will also provide experiences from a range of expert clinicians globally.”
Addressing the CIRSE audience, Gilbert described the Wrapsody endoprosthesis as a “unique, tri-layered stent graft” that is currently CE-marked for use in Europe and is available in sizes ranging from 6mm to 16mm, making it a viable treatment option for a “huge range” stenotic lesions, including those in the peripheral and central veins of an access circuit.
Gilbert went on to detail the design and purpose of WRAPSODY FIRST—a prospective, three-centre, single-arm, first-in-human feasibility study assessing the safety and effectiveness of the device, for which he is the primary investigator. The subject population consisted of dialysis patients with AVFs or arteriovenous grafts (AVGs) in their upper limbs, who experienced stenosis or occlusion within their access circuit. Gilbert reported the primary safety objective as being the proportion of patients without any localised or systemic safety events affecting the access or venous outflow circuit, and resulting in surgery, hospitalisation, or death, while the primary effectiveness objective was TLPP. Follow-up took place at 30 days, three months, six months and 12 months, he added.
Gilbert stated that a total of 46 patients (24 female, mean age=66.7 years) were enrolled in the study, with a cumulative access loss of five patients at the 12-month follow-up point, as well as a further two patients undergoing transplantation, leading to outcome data for 39 patients being available beyond one year. On safety outcomes at 12 months, he reported a total of five adverse events, four of which were adjudicated as being procedure-related, with the access circuit not being salvaged and a lack of imaging data making it impossible to determine if the one remaining event—a thrombosed fistula—was device- or procedure-related.
Touching on effectiveness next, Gilbert described the 12-month TLPP rate of 84.6% as “very encouraging”, and similarly positive to the 97.7% TLPP rate seen at six months, before reporting that reintervention was successful in all problematic cases—resulting in a 12-month assisted TLPP rate of 100%. Further, he noted an access circuit primary patency rate of 65.9% at 12 months. All but five of the remaining access circuits were salvaged via reintervention, he added, leading to a secondary patency rate of 88.6%. These data are also published in the journal CardioVascular and Interventional Radiology (CVIR).
Gilbert concluded his presentation by conveying details of the WRAPSODY WAVE trial, which is a multicentre RCT designed to further assess the Wrapsody endoprosthesis as a treatment option for dialysis access circuit stenoses and support US Food and Drug Administration (FDA) approval of the device. This trial is already underway, and will involve 1:1 randomisation of patients across two study arms—Wrapsody versus percutaneous balloon angioplasty (PTA) in AVF peripheral circuit stenosis (244 patients), and Wrapsody versus PTA in central vein stenosis of AVF and AVG circuits (120 patients)—in addition to a third, registry-based arm that will assess the device’s use at the graft-vein anastomotic site in 113 patients.
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This advertorial is sponsored by Argon Medical Devices
Placing a drain is an important, quotidian, “bread and butter” procedure that often has a tremendous impact on patients’ lives. “A drain is a drain until it is not,” says Sean Calhoun, who outlines the benefits of the Skater all-purpose, nephrostomy and biliary drainage catheters (Argon Medical Devices). He hones in on their anti-kinking and locking mechanisms, ease of insertion and transition and compatibility with both alcohol and doxycycline. Calhoun also shares his excitement about the recent commercial launch of the Skater mini-loop drainage catheters in the USA and the European Union, telling Interventional News: “I am hopeful that this will eliminate the problem of losing access to the abscess cavity by having the catheter track smoothly through the wall and into a small cavity. It is also going to be very helpful for external biliary drains.”
“The Skater drainage catheter is consistent, reliable, extremely easy to use and is visualised well under fluoroscopy due to its good radiopacity,” says Calhoun, vice chair of the Radiology Department and an interventional radiologist, Atlantic Health System, Morristown, USA. “Additionally, the locking mechanism is simple, intuitive and designed for patient comfort in that it is not bulky. The break-off tab is very easy to use and very easy to undo when it is time to remove the catheter—these catheters are also perceived to have excellent patency rates, which are the key features for any drainage catheter,” he adds.
Drainage is often seen as a quotidian, relatively routine procedure, with interventional radiologists placing five to 10 drainage catheters a week under different imaging modalities depending on the location. Drains are placed under imaging guidance for a wide variety of indications, including abscesses, biliary and ureteral obstructions, pleural effusions and pneumothoraces, Calhoun, who is also programme director for the Radiology Residency, indicates.
An important point he emphasises is that while a drain is seen as a standard piece of equipment, there are subtle differences that are not appreciated until you have a drain that fails, commenting that “a drain is a drain until it is not”. This is when you really appreciate the differences in the technology and design and the many advantages offered by drains such as Skater, he notes. Calhoun particularly draws attention to the hydrophilic coating, resistance to kinking and accordioning—three things that contribute to the ease of insertion and the reliability of the device.
“During insertion, drains can certainly accordion because the multiple side holes create a relative weakness in the catheter. I have had catheters in the past in which the side holes accordion, particularly in tight biliary strictures. This makes it very difficult to advance the drain. The Skater catheter seems to track very well through firm cirrhotic livers. When using other catheters in the past where there was challenging cirrhotic liver and a tight stricture, I recall going through several catheters that just continually weakened; that has almost never been the case with the Skater line. Those difficult situations now seem like distant memories, because we have been using this product for 10 years.
“The concept of durability and not having the catheter break down necessitates patients having to come in for avoidable changes, particularly when we start using the catheters for things like lymphocoele sclerosis and cyst sclerosis with alcohol, during which some catheters can break down and fragment. I have also seen patients come in with their catheters in all sorts of disarray; they can have kinks, be twisted and become occlusive. While many patients keep them in pristine condition, others do not, and we have observed that the catheter is twisted and wrapped around and coiled under a dressing that has not been well cared for, oftentimes with the catheter not draining in that situation. This might lead the physician to believe that the catheter is occluded, but in fact, there is a kink in the catheter under the dressing; we have seen that with other manufacturers in the past. The Skater catheter appears to be much more resistant to kinking.” 
Skater is compatible with both doxycycline and alcohol
One major advantage of the Skater catheter is that it is compatible with both alcohol and doxycycline. Calhoun explains why this dual compatibility is important: “Patients who have undergone drainage of a symptomatic cyst, a symptomatic renal cyst, or a hepatic cyst, or postoperative lymphocoele, will often be sclerosed to avoid cyst recurrence or promote healing. The primary compound that we use is alcohol, but doxycycline is another popular alternative these days with alcohol becoming less available due to manufacturing shortages. Many of the other non-compatible catheters will break down during this sclerosing procedure. You hear horror stories of interventional radiologists chasing catheter fragments in the cyst cavity, and trying to retrieve them can be very difficult. Fragmentation is not only cumbersome, it puts the patient at risk. So, being able to confidently use alcohol, or doxycycline, knowing that the catheter is going to stay intact is huge,” Calhoun elaborates.
He also calls out the flow rates as being important. “The fact that the Skater catheter has a consistent lumen even at the hub means that you avoid the problem of effectively putting in a smaller catheter than what you think you are putting in.”
Biliary drains and occlusions
Biliary drains can frequently be “management headaches” as patients, who are very sick with sepsis and life-threatening infections, can come in with occlusions. Early occlusions are very problematic for patients as they can lead to life-threatening infections. Other times it is just an inconvenience for the patient, notes Calhoun. “If there is poor drainage, it is often due to occlusion of the catheter side holes, so I think the skived side holes of the biliary drainage catheters certainly help to reduce the occlusion rates. All catheters are going to be subject to some rate of reocclusion, but it has been our perception that the Skater catheters have a much lower rate of early occlusion than some of the other catheters that we have used in the past.”
Skater mini-loop launch received with enthusiasm
Commenting on the recent commercial launch of the Skater mini loop catheter, an expansion of Argon’s Skater all-purpose and nephrostomy drainage portfolio, which uses a 40% smaller loop to help secure the catheter and drain fluid from smaller cavities, Calhoun says: “I have often been disappointed with the mini pigtail catheters available because the transition at the tip is unfortunately not ideal to get into a small abscess cavity. In these small cavities, you do not have a lot of guidewire purchase, so you want the catheter to track smoothly and easily through the wall, so that you can situate it without losing purchase. In my experience the transition is much smoother and uniform with the Skater range than the other catheters out there, so I am hopeful that this will eliminate that problem. It is also going to be very helpful for external biliary drains. If it performs the same as the other catheters in terms of drainage and reliability, then we have hit a home run.”
Product support and availability matter
While the pandemic seems to have impacted the availability of product ranges across the board, the Skater device has been relatively unaffected. “My technologists are regularly flagging back orders. Matters can come to a head when a patient is already here, and we have to pivot to find other alternatives. That has not been the case with Skater catheters, or any of the Argon products, which are all manufactured in the USA. They have always been available and the product support has been excellent. We have expanded our Skater inventory as there are multiple sizes and diameters available. We can always count on that catheter being on the shelf and having plenty of stock and it has now become our go-to product,” says Calhoun.
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Results of the randomised, prospective, multicentre STEP trial show that the FemoSeal vascular closure system (Terumo) is superior to the Perclose ProGlide suture-mediated closure system (Abbott) in peripheral arterial disease (PAD) patients in terms of technical success using a retrograde femoral puncture. Bahaa Nasr (Brest University Hospital, Best, France) presented the late-breaking data at Paris Vascular Insights (PVI) 2021 (21–23 October, Paris, France), concluding that FemoSeal should be used in PAD patients undergoing lower limb arterial endovascular treatment, especially if they are discharged on the same day as their surgery.
According to Nasr, many studies have compared vascular closure devices (VCDs) for the coronary arteries, while none have compared them for PAD. “We all know that the efficacy of a VCD is different for PAD patients because of the plaque nature in the common femoral artery,” he remarked.
In order to assess this gap in the literature, Nasr and colleagues initiated the STEP trial. “The aim of the study was to perform a direct, head-to-head comparison between ProGlide and FemoSeal,” he relayed, explaining that the FemoSeal is a double polymer resorbable disc, while the ProGlide involves a direct suture in the artery. He noted that the primary endpoint was VCD technical success, assessed five hours post-procedure, and defined as either haemostasis without the need for either an additional VCD or manual compression, or a drop in haemoglobin.
Patients were included in the study if they had received endovascular treatment for PAD with the use of 5–7Fr sheath, Nasr informed the PVI audience. He added that patients who had undergone previous ipsilateral open repair of the common femoral artery, previous stenting at the puncture site, or had either radial, brachial or antegrade femoral punctures were excluded.
Nasr relayed that all patients were treated with a duplex scan-guided, retrograde common femoral artery puncture. He detailed that the resumption of ambulation was assessed five hours after the procedure and that all the investigators were certified and trained for both VCDs.
A total of 230 patients were randomised, with 109 patients undergoing treatment with the assigned device in each group. According to Nasr, the baseline clinical and demographic characteristics were well balanced between the two groups. The presenter highlighted the fact that most of the patients included in the study had intermittent claudication—86% in the FemoSeal group and 85% in the ProGlide group.
The majority of the procedures were performed under local anaesthesia and the most commonly-used sheath was 6Fr diameter, Nasr told PVI delegates. He added that there were no differences in intraoperative antithrombotic regimens, and in fact the only difference between the two groups was the need for a compression dressing, which was higher in the ProGlide group.
Nasr reported that the intention-to-treat analysis showed an 80% technical success rate in the FemoSeal group, which was higher than the 50% rate achieved in the ProGlide group. The difference in technical success could be explained by the need for additional VCDs and a greater need for manual compression in the ProGlide group, the speaker explained. He elaborated: “In the ProGlide group, when taking into account the use of a second VCD, the technical success rate was 90%.”
Postoperative bed rest and hospital stays were similar in both groups, the presenter communicated. The rate of minor access-related complications were higher in the ProGlide group, he added, noting finally that the additional cost per patient valued between 23 and 30% in favour of FemoSeal.
Moderator Marianne Brodmann (Medical University of Graz, Graz, Austria) was “really impressed” that Nasr and colleagues had found the device to be more cost effective, adding a more general comment that it is a “very good idea” to compare two different VCDs for peripheral interventions. In this vein, Brodmann was keen to know if the speaker thought we should conduct more studies and compare more devices in order to end up with one device—“the most cost efficient, effective and safe one”.
“I think we have to talk about other devices,” Nasr replied, noting also that investigators must compare devices with magnet compression and low-profile sheaths.
Speaking from the audience, Eric Ducasse (Bordeaux University Hospital, Bordeaux, France) agreed with Brodmann that it is important to prove a device’s cost effectiveness, but stressed that “we need to go deeper into the comparison”. Data concerning other factors—such as the distance between the artery and the skin, previous fibrotic intervention, the amount of calcification, the position of the plaque, and the wideness of the artery that is punctured—is required, he stressed, in order to “really compare objectively” the different systems.
Percutaneous microwave and cryoablation allow for repeat minimally invasive treatment of sarcoma lung metastases with mild complications, according to the conclusions of a study published in the American Journal of Roentgenology (AJR).
“High primary technical success, local control, and overall survival” were the supporting findings, as reported by Florian Fintelmann (Massachusetts General Hospital and Harvard Medical School, Boston, USA) and colleagues. Fintelmann and colleagues’ retrospective cohort study included 27 patients, consisting of 16 women and 11 men, with a median age of 64 years and an Eastern Co-operative Oncology Group performance score of 0–2. The patients received 39 percutaneous computed tomography (CT) guided ablation sessions (21 microwave, 18 cryoablation) with one to four sessions per patient.
The sessions were to treat 65 sarcoma lung metastases (median 1 tumour per patient, range 1–12; median tumor diameter 11mm, range 5–33mm; 25% non-peripheral) from 2009 to 2021. Ablation modality complications were compared using generalised-estimating equations. Cox hazard methods were also used to evaluate ablation modality, tumour size, and location (peripheral versus non-peripheral) in relation to local tumour progression, with death as a competing risk. Overall survival was also estimated using the Kaplan-Meier method.
The median follow-up time was 23 months (range 1-102 months) and the estimated two-year microwave local control rate was 95% vs. 98% for cryoablation for tumours ≤1cm and 62% and 79% for tumours >1cm. Furthermore, decreased cumulative incidence of local progression was associated with tumour size ≤1cm. Fintelmann and colleagues also noted that ablation modality and tumour location did not affect local progression (p>0.05) and “treatment failure was low, especially for small tumours, with non life-threatening complications for tumours ≤1cm”.
Across 44% of patients, complications (≤grade 3) occurred, resulting in chest tube placement in 23% of these patients. No complications ≥grade 4 occurred and overall survival was 100%, 89%, and 82% at one, two, and three years respectively. Therefore, both percutaneous microwave and cryoablation are suited for the treatment of sarcoma lung metastases, especially in peripheral or non-peripheral tumours ≤1cm, the study’s authors conclude.
An investigational device invented at Sanford Health (Sioux Falls, USA) that helps high-risk vascular disease patients has been granted a Breakthrough Device designation by the US Food and Drug Administration (FDA).
Patrick Kelly, a Sanford Health vascular surgeon, invented the aortic stent graft system designed to treat a thoracoabdominal aortic aneurysm (TAAA). This complex condition can cause dangerous bulging of the aorta extending from the chest down into the abdomen. It typically involves the branch arteries that supply blood to multiple internal organs. Left untreated, the aneurysm can rupture and cause sudden death.
The standard of care is complex open surgery, which is associated with a high rate of complications and mortality, and 40% of patients are not considered candidates for open surgical repair.
Kelly’s concept has the potential to treat more of those people utilising his minimally invasive approach. Under a physician-sponsored investigational device exemption (PS-IDE), he has treated more than 150 patients at Sanford Health over the past nine years who otherwise had no other options.
“This helps move the device through the regulatory pathway,” said Kelly. “It opens the door for more patients to have an option for repair, even the potential for patients with aortic dissections, failed prior repairs and anatomies that were previously thought to be untreatable. The non-anatomical design allows broad applicability of our patient population.”
That unmet need, leaving some patients with no other option, was key to the Breakthrough Device designation, said Katie Pohlson, senior director of innovation and commercialisation at Sanford Health.
“With it, we will receive prioritised reviews, access to senior staff at the FDA and collaboration with the FDA to help with the development of the product,” she said.
A retrospective study supports the use of the Wound, ischaemia, and foot infection (WIfI) classification system to predict the revascularisation benefit for diabetic patients with chronic limb-threatening ischaemia (CLTI).
The WIfI classification system was developed to stratify the risk of major amputation at one year for patients presenting with chronic limb-threatening ischemia (CLTI). Recently, this system was used to identify patients most likely to benefit from revascularization. WIfI scores were used to define the estimated revascularization benefit quartiles ranging from high benefit (Q1) to questionable benefit (Q4).
“The aim of our study was to evaluate the revascularization benefit quartiles in a cohort of diabetic patients who had presented with critical limb ischemia,” said first author Caitlin Hicks, MD, of Johns Hopkins University.”
As reported in the October issue of the Journal of Vascular Surgery, researchers from the university’s Diabetic Foot and Wound Service, led by Hicks and senior author Christopher Abularrage, MD, evaluated 136 diabetic patients (187 limbs) who underwent lower extremity revascularization between 2012 and 2020 at their institution. The primary outcome of their study was one-year major amputation.
Demographic characteristics of these diabetic patients included:
Revascularization procedures were either endovascular (67%) or open (33%).
The estimated one-year amputation rates for each quartile were:
Analysis revealed the Q4 group had a significantly greater risk of amputation compared with the Q1 group (hazard ratio 4.3).
For the 137 limbs with greater than one-year follow-up after revascularization, a total of 16 (12%) required amputation. Nine of these were in the Q4 group.
“Overall, our data support the use of the WIfI benefit of revascularization quartiles for estimating the one-year major amputation risk for diabetic patients presenting with critical limb ischemia,” said Hicks. “We did, however, observe our actual amputation rate in the Q4 group was one half of what was expected. This may be explained by the fact that all of our diabetic patients are treated by our multidisciplinary team, which has been previously shown to have robust limb salvage outcomes.”
“Up to one half of the Q4 patients who underwent amputation did so despite patency of their revascularization procedure. This suggests wound size and infection burden are the driving factors behind the elevated risk in this group.”
The decision to perform revascularization in a patient with critical limb ischemia must be made carefully, particularly given their often extensive list of co-morbidities, researchers said. This study supports the use of the WIfI system to predict which diabetic patients with critical limb ischemia might best be served by revascularization and highlights the importance of multidisciplinary teams for complex medical and surgical patients.
A phase 1 clinical trial for the treatment of patients with inoperable mesothelioma, with both pembrolizumab immunotherapy and cryoablation, has begun in New Jersey and New York, USA. Starting 24 September 2021, the trial is expected to be completed by September 2023.
Pembrolizumab immunotherapy enhances the ability of the immune system to detect and kill cancer cells. In patients with inoperable mesothelioma in the chest of the abdomen, researchers are trialing the addition of cryoablation within a phase 1 trial. Cryoablation uses extreme cold applied through the needle into a tumour to break down and kill cancer cells. Researcher Micheal Offin and co-investigators Marjorie Zaudere and Etay Ziv (all Memorial Sloan Kettering Cancer Centre, New York, USA) have therefore begun to investigate the treatment impact of drugs that strengthen the immune system such as pembrolizumab, plus cryoablation for inoperable mesothelioma.
This single group assessment is designed as a single-arm and single-institution study, with an estimated 10 patients recruited. All patients must be over the age of 18 and have pleural or peritoneal mesothelioma that continues to grow despite previous treatment. Eligible patients must be fully capable of self-care, with the exception of carrying out strenuous activities. Patients who have received one previous line of systemic therapy which did not include pembrolizumab, are eligible for the study unless treated one year or more from the trial enrollment. Patients must also present a Karnofsky Performance Score (KPS) of ≤70% with adequate organ function. The criteria for adequate organ function is shown below:
Eligible patients will receive one cycle of pembrolizumab (200mg/dose) delivered intravenously, followed by image-guided cryoablation of an ablation index lesion which will occur one to seven days prior to the start of cycle two. Cryoablation will treat a lesion with preference given to a lesion that is symptomatic or at risk of causing symptoms. Following institutional standards, complete ablation will be attempted. In addition, pembrolizumab will be continued for up to 24 months, unless disease progression, or intolerable toxicity. The number of patients with an adverse event defined as grade three or higher non-haematologic toxicity within 12 weeks of cryoablation will be the primary outcome measure.
In this penultimate episode of a special five-part series on the history of drug-coated balloons (DCBs), Jos van den Berg (Lugano, Switzerland) is joined by Gunnar Tepe (Rosenheim, Germany) and Thomas Zeller (Bad Krozingen, Germany), with the trio discussing major highlights from the IN.PACT Global real-world study, which showed consistent outcomes with the IN.PACT SFA randomised controlled trial despite including patients with longer and more calcified lesions and those with in-stent restenosis.
Tepe elaborates on some of the key differences between the IN.PACT SFA trial, which had stringent exclusion criteria, to the IN.PACT Global study. The latter, notes Tepe, allows us to “really learn how this DCB works in the real world”.
Zeller compares some of the key findings between the two, noting that at five years freedom from clinically-driven target lesion revascularisation in the SFA trial was 74.5% compared to 69.4% in the IN.PACT Global study. The SFA trial was “very selective”, adds Zeller, with mean lesion lengths of about 8cm compared to the Global study which had a mean lesion length of more than 12cm, and going up to 35cm. The comparable results between the two sets of data show that the device “performs well not only in standard lesions but also in complex lesions”. Overall, this gives Zeller confidence that the IN.PACT Admiral DCB is “very efficient, regardless of what kind of lesion you are treating” and that lesion length only has a “mild impact on overall outcome”.
These favourable outcomes are “related to the unique formulation of a high dose of paclitaxel combined with urea and also the mechanism of action of this balloon,” says van den Berg. He also emphasises the importance of such data, concluding that it “really guides me in my choices in my personal practice”.
This video is sponsored by Medtronic.
Episode 2: Are all peripheral drug-coated balloons created equal?
Episode 3: The unique recipe for long-term clinical benefit with IN.PACT™ Admiral™ DCB
COMING SOON
Episode 5: The impact of long-term DCB outcomes on patients’ quality of life
Cryoablation is effective for local tumour control in patients with pulmonary metastatic disease. Within the ECLIPSE study, cryoablation had no significant impact on the patient’s quality of life (QoL), with the patient disease-specific survival rate remaining higher than the overall survival rate at both three and five years follow-up.
The multicentre single-arm ECLIPSE study1 prospectively evaluated the feasibility and effectiveness of CA in patients with pulmonary metastatic disease. Patients who had one to five metastatic lung tumours with a diameter of less than or equal to 3.5cm were eligible and treated with cryoablation. Local tumour control was the primary endpoint of this study, with cancer-specific survival, overall survival, and the QoL as secondary endpoints. QoL outcomes were assessed using the Karnofsky Performance Score, the eastern cooperative oncology group performance score, and the short form-12 health survey.
The ECLIPSE study enrolled 40 patients across three sites in the USA and one site in Europe, treating a total of 60 metastatic pulmonary tumours across 48 cryoablation treatments. Patients were followed over a period of five years and their disease status was monitored.
The study elucidated that cryoablation was effective in local tumor control within 87.9% of patients (29 of 33) and 79.2% (19 of 24) per tumour and 75.0% (15 of 20) per patient, at three and five years, respectively. Disease-specific survival was 74.8% at three years, and 55.3% at five years, whereas overall survival at three and five years was 63.2% and 46.7%, respectively. However, during the study, five patients experienced local disease progression. Patient QoL scores did not change significantly (p > 0.05). In the five follow-up years, only 55% of patients had to receive systemic anti-cancer treatment, with 27.5% of patients (11 out of 40) undergoing systemic chemotherapy and 7.5% (3 out of 40) of patients receiving radiation. Therefore, the ECLIPSE study illustrated that cryoablation is an effective method for long-term local tumour control in patients with metastatic pulmonary tumours, does not decrease patient QoL, and lowers the need for systemic treatment.
References
HistoSonics has revealed that the US Food and Drug Administration (FDA) has granted the company breakthrough device designation for its new histotripsy targeted liver therapy platform which is designed to help provide timely access to non-invasive liver treatment.
HistoSonics say that histotripsy of the liver provides clinicians with the first automated external beam therapy using acoustic energy to mechanically destroy and liquefy tissue in the liver without incisions, ionising radiation or heat.
Mike Blue, president and CEO of HistoSonics, sad: “the breakthrough device designation is a significant milestone for our company and validates our belief that our platform offers significant advantages over existing approved or cleared alternatives, per FDA requirements.
“Early and ongoing clinical results are promising and suggest that our ability to precisely destroy targeted liver tissue, completely non-invasively, and without the challenges associated with ionising radiation or other locoregional therapies, provides advantages to patients and physicians that don’t exist today, and we look forward to working with the FDA to make the technology accessible as quickly as possible.”
The company believes the novel mechanism of action of their proprietary technology may offer significant advantages to patients, including equivalent treatment effect throughout the entire treatment volume resulting in precise and predictable treatment zones. Early clinical and pre-clinical results also suggest that histotripsy largely preserves critical structures such as the liver capsule, and larger vessels and ducts within or adjacent to the treated volume of tissue.
In addition, histotripsy gives the treating physicians the ability to monitor the destruction of tissue under continuous real time visualisation and control, unlike any modality that exists today. The Breakthrough Designation will allow the company to engage with the FDA in a prioritised review during the regulatory market authorisation process, the company adds.
HistoSonics has worked with the FDA for over three years in developing pre-clinical and clinical data required for regulatory market authorisation and intends to continue collaborating with the agency throughout the ongoing Investigational Device Exemption (IDE) study, #HOPE4LIVER US, which is designed to evaluate the safety and technical efficacy of histotripsy in patients with primary and secondary liver tumours.
The company plans to share US and European #HOPE4LIVER study data and results with FDA to demonstrate the benefits of histotripsy in a broad patient population.
The HistoSonics system is investigational and is not available for sale in the United States or Europe. It is limited to investigational use in the approved IDE and European studies.
In support of the Legs Matter Campaign’s awareness week (11–15 October), Sam Everington, a GP at the Bromley by Bow Centre in London, UK, and former British Medical Association (BMA) chair, is calling on GPs, pharmacists and other primary care professionals to adopt a proactive approach towards “preventable,” life-threatening or serious leg and foot problems.
A press release reports that the growing epidemic, costing the UK National Health Service (NHS) up to £8.5 billion annually, affects an estimated 1.8 million people in the UK each year, often linked to obesity and caused by an underlying issue with circulation or neuropathy.
A report published earlier this year revealed that the number of patients with wounds annually has increased from an estimated 2.2 million between 2012/2013 to around 3.8 million in 2017/2018—an increase of 73%, the press release communicates.
Sam Everington said: “The Legs Matter Campaign is rightly focused on patient and public empowerment, identifying the small changes that people need to make to create change. Healthcare professionals providing services in primary care and community pharmacies also need to be at the forefront of this change.
“As GPs and pharmacists, we are there when people seek support for worrying changes or new injuries to legs and feet. We all need to act promptly and provide the right care swiftly so that these wounds do not deteriorate into long-lasting leg or foot ulcers or other serious, chronic conditions. It is simply not necessary and can be prevented.
“I would like to see all primary care professionals adopt a proactive approach to the spiralling number of serious leg and foot problems. If more patients and clinicians work together to address this national issue, we can start to turn the tide on this hidden epidemic.”
As part of the campaign targeting the public and patients; GPs, pharmacists, podiatrists, tissue viability, district and practice nurses are among the healthcare professionals being urged to take action, support the initiative and to sign up for online events during the third national week.
Nurse consultant Leanne Atkin from Pinderfields Hospital in Wakefield, UK, is chair of the campaign, working to increase understanding, awareness and action for serious lower leg conditions, including leg or foot ulcers, swollen legs and cellulitis.
Atkin said: “For this year’s campaign, we want to empower people to be proactive about their own health and we are also asking primary care professionals to take charge of leg and foot problems and ensure that patients have access to face-to-face care, so that any issues can be spotted quickly. Ensuring patients receive the right healthcare at the right time makes a huge difference to both healing times and outcomes.”
Campaigners hope that as part of the week, even more primary care professionals will get involved and help patients to make a positive change using tips and the latest information on the www.legsmatter.org website, including self-management, exercise and having a positive mindset. The site will feature free resources and virtual events, suitable for the public, patients and healthcare professionals, including live Q&A sessions with clinicians and patients.
Former Army medic and disability sportswoman Nerys Pearce is fronting the 2021 Legs Matter Awareness Week campaign—urging others to take positive action and to make a change for better leg and foot health.
After sustaining life-changing injuries, she has received ongoing support from podiatrist and Legs Matter Campaign member Joanne Casey, from The Royal College of Podiatry. Joanne said: “Often with spinal injuries, like those sustained by Nerys, there is a lack of feeling, so it is important for us as health professionals to check the skin on the feet and legs for signs of redness, swelling, bruising, cuts or splits, changes in temperature and deformity. As podiatrists we can quickly identify a problem, suggest treatment and stop it escalating into something which could be life-threatening.”
Supported by NHS England, the Legs Matter Campaign was formed by a group of the UK’s leading lower limb clinicians, who, together with patient partners, are campaigning to make serious leg and foot problems a thing of the past.
Operating under the governance of the charity, The Tissue Viability Society, Legs Matter is also made up of representatives from The British Lymphology Society, Accelerate, The Royal College of Podiatry, The Society of Vascular Nurses, The Lindsay Leg Club Foundation, Foot in Diabetes UK and The Leg Ulcer Forum. It wants to ensure that anyone with a lower leg or foot problem understands their condition and gets the urgent care and support that they need.
One-year results presented at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA) from the EMINENT trial demonstrated the superiority of the Eluvia drug-eluting stent (DES) system (Boston Scientific) compared to self-expanding bare metal stents for the treatment of patients with peripheral arterial disease (PAD) with superficial femoral artery (SFA) or popliteal artery lesions up to 210mm in length, the principal investigator (PI) said. The study enrolled 775 patients, making it the largest randomised trial of a drug-eluting stent for the treatment of PAD to date, Boston Scientific said in a press release.
In the trial, the Eluvia stent exhibited superiority with a primary patency rate of 85.4% vs. 76.3% with bare metal stents (p=0.0087), data presented by EMINENT study PI Yann Gouëffic, from the Department of Vascular and Endovascular Surgery at Paris Saint-Joseph Hospital, Paris, France, showed.
The analysis also showed a significantly greater rate of sustained clinical improvement without reintervention—83% for patients treated with the Eluvia stent compared to 76.6% for those treated with a bare metal stent (p=0.0450). Further, there was no significant difference in major adverse events or all-cause mortality rates between patients treated with the Eluvia stent and those treated with a bare metal stent through one year.
“I am honoured to have been part of this global study, which adds to the robust body of evidence from the IMPERIAL trial and confirms that the Eluvia stent should be considered the stent of choice for treating SFA and [popliteal] lesions of intermediate length,” said Gouëffic. “The superior primary patency rates and greater rates of clinical improvement without reintervention are reassuring for physicians looking to make clinically-based treatment decisions for their patients and reduce the need for repeat procedures.”
A worldwide committee of 40 cross-speciality medical experts achieved the first-ever consensus for the appropriate use of intravascular ultrasound (IVUS) in peripheral vascular disease (PVD) interventions.
Global experts conducted a systematic and comprehensive review of key clinical IVUS scenarios and decision-making processes before voting. The results were shared at a sponsored symposium during Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA). They established clinical consensus to identify optimal use of IVUS and potential gaps in a bid to to set a standard across clinical specialties and drive positive outcomes for patients.
The new consensus and recommendations are aimed at improving quality care in PVD and are based on evidence, expert practice standards, and clinical experience, according to a press release from Philips, the company behind IVUS.
“The results of the cross-speciality expert consensus demonstrate strong support for the use of IVUS during peripheral interventions,” said Eric A Secemsky, an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston, USA. “Future efforts need to focus on improving IVUS implementation into clinical practice and streamlining procedural workflow to help improve our patient outcomes.”
Today, healthcare providers’ use of IVUS in PVD interventions is not standardised and is therefore inconsistent, Philips stated in the press release. “The new appropriate-use expert consensus may help establish global standards of care to adopt into guidelines and improve quality care in PVD,” the company added.
Several subgroups of patients treated with the IN.PACT AV drug-coated balloon (DCB; Medtronic) for arteriovenous fistulas (AVFs) demonstrated a “statistically significant” higher rate of target lesion primary patency (TLPP) compared to those who underwent standard percutaneous transluminal angioplasty (PTA) through 24 months, investigators behind the IN.PACT AV Access study have reported.
Principal investigator Robert Lookstein, executive vice chair in the Department of Diagnostic, Molecular and Interventional Radiology at Mount Sinai Health System in New York, USA, delivered the two-year results from the trial during a late-breaking session at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
IN.PACT AV is a prospective, global, single-blinded, randomised controlled trial with 330 participants, with 170 receiving IN.PACT AV DCB and 160 undergoing PTA.
The investigators reported that the primary outcome of TLPP—defined as freedom from clinically-driven target lesion revascularisation—in patients with restenotic lesions, radiocephalic and brachiocephalic AVF types, cannulation zone lesions as well as anastomotic lesions treated with the DCB through 24 months was superior to those who received PTA treatment in all cases.
“Benefits were seen in all other subgroups, though sample sizes were small and the treatment effect was not statistically significant,” Lookstein told VIVA attendees.
The results showed higher TLPP with DCB versus PTA based on time-to-event analyses: restenotic lesions (46% vs. 30.2%), radiocephalic AVFs (53.6% vs. 43%), brachiocephalic AVFs (48.5% vs. 27.3%), anastomotic lesions (48.4% vs. 32.7%), and lesions in the cannulation zone (74.2% vs. 18.9%). The greatest TLPP benefit through 24 months was observed in “lesions treated with the smallest balloon diameter sizes”—those treated with balloon diameters of >6mm showed a TLPP of 52.2% in the case of the DCB group vs. 38.9% among PTA patients. Meanwhile, lesions tackled using balloons with diameters ≤6mm saw TLPP rates of 52.1% (DCB) vs. 32.6% (PTA), the data showed.
“I think this really starts to identify the specific patient population and lesions that are ideally suited for this technology,” Lookstein said. “These durable, long-term data suggest the use of this therapy may be considered stand-of-care for patients with end-stage renal disease [ESRD] at high risk for repeat interventions in their arteriovenous fistulas.”
An interim analysis from the DISRUPT PAD III observational study showed that intravascular lithotripsy (IVL; Shockwave Medical) performs “consistently well” across challenging peripheral vessels, lesions and subgroups of patients, Ehrin J Armstrong, medical director at Adventist Heart and Vascular Institute in St Helena, USA, told a clinical trials late-breaking session at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
Analysis of the full data set contained in the study—reputedly the largest angiographic core lab adjudicated real-world evidence for IVL in heavily calcified peripheral arteries according to Shockwave Medical—is due to be presented next year.
Findings from the first 752 patients included in the interim analysis demonstrated that IVL “consistently” showed its ability to safely and effectively modify superficial and deep calcium across multiple vascular beds, lesion types and in patients with chronic limb-threatening ischaemia (CLTI), Armstrong reported. IVL resulted in consistent reduction in the diameter of stenosis with no associated distal embolisation, abrupt closure or thrombotic events at any time, according to Shockwave. IVL outcomes were comparable to the previously reported DISRUPT PAD III randomised controlled trial (RCT) outcomes showing minimal procedural complications and consistent reduction in diameter stenosis. The technology was also successfully used in combination with adjunctive technologies, including specialty balloons and atherectomy, in the treatment of complex calcified lesions, the company further reported.
“Patients with heavy calcification have traditionally been excluded from endovascular treatment trials resulting in little available evidence to provide guidance for treating this challenging patient population,” said Armstrong. “The DISRUPT PAD III [observational study] shows that in common clinical situations that physicians encounter daily, peripheral IVL performs consistently well in a variety of peripheral vessels, lesions and subgroups.”
The observational portion of DISRUPT PAD III is a prospective, multicentre, single-blind study of real-world patients, which augments the DISRUPT PAD III RCT. The interim analysis involves patients enrolled between November 2017 and June 2019 at 18 global sites.
Of the 852 lesions treated in the iliac, common femoral, superficial femoral, popliteal and infrapopliteal arteries, 88% presented with moderate/severe calcification, with an average calcified length of 127mm. The use of IVL in these lesions resulted in a final residual stenosis of 24%, similar to the DISRUPT PAD III RCT finding of 22%, Armstrong told VIVA attendees. Patients also experienced minimal procedural complications, with only 0.9% and 0.1% of patients experiencing final dissections and perforations, respectively. “Notably, there were no instances of embolisation, thrombus, no reflow or abrupt closure.” The observational study completed enrolment in June 2021 with a total of 1,373 patients.
Late-breaking session panellist Benjamin W Starnes, the chief of Vascular Surgery at the University of Washington (UW) in Seattle, USA, commented: “Your one-year follow-up data happened right in the middle of a pandemic—what was it like to conduct a clinical trial in the setting of a pandemic?”
Armstrong said the dynamic of the COVID-19 virus was initially challenging, explaining: “At our own hospital, it was mandated that the research coordinators not interact with patients for the first few months, so I conducted a lot of the follow-up myself. That being said, our patients with peripheral arterial disease [PAD]—because they have such complex issues—in some cases we flexed to doing virtual visits, but we were able to get these patients in in most cases with outstanding follow-up. Which, to me, really demonstrated the versatility of conducting research, despite dealing with all these different complexities in the setting of a pandemic.”
Patients treated with the Ranger drug-coated balloon (DCB; Boston Scientific) sustained “improved primary patency” with fewer reinterventions than those treated with uncoated devices, two-year results from the RANGER II SFA randomised controlled trial have demonstrated, investigators revealed during a late-breaking session at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
Principal investigator Ravish Sachar, an interventional cardiologist at North Carolina Heart and Vascular at UNC REX Healthcare in Raleigh-Durham, USA, delivered the data, telling attendees that subgroup analyses—covering women, patients with baseline chronic total occlusions (CTOs) and calcified lesions—also suggest “consistent benefit” of DCB treatment versus standard percutaneous transluminal angioplasty (PTA).
Additionally, the two-year results showed no difference in mortality rate between the groups.
In a press release, Boston Scientific said the data confirmed the safety and efficacy of the Ranger DCB compared to standard PTA for the treatment of patients with peripheral arterial disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal artery. The new findings follow the May 2021 publication of the one-year results of RANGER II SFA in JACC: Cardiovascular Interventions.
Sachar and colleagues found that the Ranger DCB exhibited a higher primary patency rate of 84% compared to 71.4% in patients treated with standard PTA (p=0.0129). Additionally, the subgroup analyses found consistent benefit with greater long-term patency in patients with more complex lesions treated with the Ranger DCB, exhibiting an 89.1% vs. 72.4% primary patency rate in the moderate to severe calcium subgroup (p=0.0052) and a 76.6% compared to a 58.6% primary patency rate in patients with CTOs (p=0.1038).
“These two-year data demonstrate a sustained, high rate of efficacy—including in patients with more complex lesion subtypes, yet another proof point for physicians to consider when determining the best individualised treatment option for their patients with PAD,” said Sachar.
The Ranger DCB also demonstrated a significant reduction in reinterventions at two years, with a freedom from target lesion revascularization (TLR) rate of 87.4% vs. 79.5% observed with standard PTA (p=0.0316). Additionally, there was no significant difference in all-cause mortality: 5.7% for Ranger DCB patients and 3.2% in those treated with standard PTA (p=0.4218). Sachar added that there was no reintervention disadvantage based on gender.
Real-world data drawn from the IN.PACT Global study looking at five-year freedom from clinically-driven target lesion revascularisation (TLR) among prespecified chronic total occlusion (CTO), long lesion and de novo in-stent restenosis (ISR) cohorts “continues to confirm long-term clinical safety and effectiveness” of the IN.PACT Admiral (Medtronic) drug-coated balloon (DCB) in the treatment of complex femoropopliteal lesions.
Results from the study—involving 417 patients—were delivered by Gunnar Tepe, head of the Department of Diagnostic and Interventional Radiology at RoMed, Rosenheim, Germany, during a late-breaking session at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
Tepe reported that mean lesion lengths were 22.8±9.7cm, 26.4±8.6cm, and 17.1±10.5cm in the CTO, long lesion, and de novo ISR cohorts, respectively. The majority of lesions were calcified, he said. Kaplan-Meier estimates of freedom from clinically-driven TLR through five years were 69.8% for CTO, 67.3% for the long lesion group and 58% for ISR. The cumulative incidences of the composite safety endpoint were 69.8%, 65.7%, and 56% in the CTO, long lesion and ISR cohorts, respectively, Tepe continued.
The number of major target limb amputations were very low in all three cohorts, with no amputations in the CTO, two in the long lesion, and one in the de novo ISR cohorts, he told VIVA attendees. Kaplan-Meier estimates of five-year freedom from all-cause mortality rates with vital status were 78.2% (CTO), 75.2% (long lesion), and 81.4% (ISR).
“This is the first presentation of prospectively collected five-year data from prespecified in-stent restenosis, long lesion and chronic total occlusion cohorts from a large global DCB study,” said Tepe.
He concluded: “High five-year freedom from clinically driven TLR was demonstrated in all three prespecified cohorts, but it was slightly lower in the de novo ISR cohort, highlighting the challenging nature of ISR lesions. No safety issues were reported in any of the cohorts. All-cause mortality with vital status at five years was 81.4% for de novo ISR, 75.2% for long lesions and 78.2% for CTOs. These data support incorporating the use of the IN.PACT Admiral DCB into clinical treatment algorithms for complex femoropopliteal disease.”
The IN.PACT Global study was a prospective, multicentre, single-arm study conducted at 64 international sites that enrolled 1,535 participants, including some with complex lesions. Assessments through five years included freedom from clinically driven TLR, safety composite and major adverse events.
Preliminary clinical results from a first-in-human study assessing the Amplifi vein dilation system (Artio Medical) were presented at Vascular Interventional Advances (VIVA) 2021 (5–7 October 2021, Las Vegas, USA). Data were presented by Surendra Shenoy—an associate professor of surgery at the Washington University School of Medicine at Barnes-Jewish Hospital in St Louis, USA—during the event’s final late-breaking clinical trial session.
The Amplifi system is designed for percutaneous placement and up to 14 days of use to stimulate arm vein enlargement in haemodialysis patients using rapid, non-pulsatile, venous blood flow. The device includes a wearable, external blood pump, inflow and outflow catheters, and a controller, all of which are removed completely during arteriovenous fistula (AVF) creation. It aims to make more patients eligible for AVF surgery, reduce the time required for AVF maturation and increase successful maturation after AVF creation.
Data presented at VIVA came from the first five patients treated in a prospective, non-randomised, single-arm, first-in-human clinical study with the Amplifi system, and demonstrated that forearm and upper arm mean cephalic vein diameters had more than doubled over an average treatment period of 8.6 days.
AVFs were successfully created using treated veins in all patients. Maturation data are available for the first three patients and show that both the forearm and upper arm AVFs matured quickly with mean outflow vein diameters of 7mm and a mean blood flow rate of more than 1,000 ml/min after a six-week maturation period. No device-related or procedural adverse events were observed.
“Not long after AVFs were first pioneered for haemodialysis in 1966 by doctors Cimino, Brescia, and Appel, concerns were raised about patients who were not suitable for AVF surgery and the high rate of AVF maturation failure,” Shenoy said. “Despite these challenges, AVF remains the preferred option for most patients today. The Amplifi system is the first device I have seen that has real potential to address both of these challenges in a major way, to make good on the promise of providing reliable, long-lasting vascular access sites for this unique and vulnerable patient population.”
In a press release, Artio Medical stated it is planning to set up a US clinical trial of the Amplifi vein dilation system in 2022.
Boston Scientific announced positive results for the EkoSonic endovascular system (EKOS system) during a late-breaking clinical trial presentation at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA). Data from the KNOCOUT PE registry—established to measure institutional adoption of a lower dose and lower-duration thrombolysis protocol for the EKOS system—confirmed the safety and efficacy of the EKOS system for the treatment of patients with intermediate-high and high-risk pulmonary embolism (PE).
“PE remains a life-threatening and complex disease, but these results provide an opportunity to advance patient care by showcasing evidence that proves a lower drug dose and shorter infusion duration of a thrombolytic agent may result in enhanced safety and efficacy,” said Keith M Sterling (Inova Alexandria Hospital, Alexandria, USA), study principal investigator. “The findings in this registry analysis are very reassuring to physicians making critical evidence-based decisions for their patients in what are oftentimes emergent treatment situations.”
The international registry of 489 patients across 83 centres included data from patients treated with the EKOS system who were provided a lower drug dose and shorter infusion duration of a thrombolytic agent than administered in previous studies, reflecting contemporary clinical practice. In the data, there were no intracerebral haemorrhagic (ICH) events, or brain bleeding events, with a low major bleeding rate of 2.5%, compared to the rate previously observed with systemic thrombolysis treatment. Results also demonstrated a 23% post-procedure reduction in the main indicator of heart strain from PE, measured as right ventricular to left ventricular diameter ratio (RV/LV).
“As the largest prospective body of evidence in the interventional PE space to date, the KNOCOUT PE registry provides an accurate modern representation of patients with PE treated with the EKOS system every day,” said Michael R Jaff, chief medical officer and vice president clinical affairs, technology and innovation, Peripheral Interventions, Boston Scientific. “The strong safety and efficacy findings exhibited in this registry add to the existing clinical evidence supporting the EKOS system as a treatment option that physicians can trust, as it is already the most studied interventional device in the PE space.”
The ultrasound technology used by the EKOS system accelerates thrombolysis—the breakdown of the clot—minimising the time it takes to treat a patient and lowering the necessary thrombolytic dose, which can result in optimised outcomes and a lower risk of bleeding.
Eighteen-month results from the PRESTIGE below-the-knee (BTK) study were presented as a late-breaking clinical trial at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA). The objective of this clinical investigation is to evaluate safety and performance outcomes of Selution SLR (MedAlliance), a novel sirolimus-eluting balloon for the treatment of long tibial occlusive lesions (TASC C and D) in patients with chronic limb-threatening ischaemia (CLTI).
Freedom from target lesion revascularisation (TLR) was exhibited by 88% of patients and 79% demonstrated amputation-free survival (AFS). The rate of wound healing was 79% and 79% of the patients improved their Rutherford score by at least one category. The 18-month results have been sustained from the six-month and 12-month data.
PRESTIGE is a prospective, single-centre, physician-initiated clinical study, run at the Singapore General Hospital (SGH) by Chong Tze Tec and Tang Tjun Yip. Twenty-five patients were enrolled with an average age of 64. Eighty-eight had diabetes mellitus and 44% had end-stage renal failure. No patients required bailout stenting. Clinical follow-up was at one, three, six, 12 and 18 months.
“We have observed minimal slow-flow phenomena, seen with other paclitaxel drug-eluting balloons. We have observed several cases of fast wound healing with Selution SLR. It is easy to track and deliver. We are looking forward to gaining further clinical experience with this device,” commented Chong.
“Singapore has a high percentage of diabetics in its population and CLTI therefore constitutes a major challenge among patients seen with peripheral arterial disease (PAD) who may benefit from this technology,” commented Tang. SGH performs over 1,000 interventional procedures a year on patients suffering from CLTI, according to a MedAlliance press release.
Selution SLR was awarded CE mark approval for the treatment of PAD in February 2020 and for the treatment of coronary arterial disease in May 2020. The US Food and Drug Administration (FDA) has awarded Selution SLR with four Breakthrough designations: for the treatment of atherosclerotic lesions in native coronary arteries; coronary in-stent restenosis; peripheral BTK and arteriovenous fistula indications.
LimFlow SA has announced 24-month results from the PROMISE I study of the LimFlow percutaneous deep vein arterialisation system, confirming “excellent and sustained outcomes” for both amputation-free survival and wound healing, a press release reports. The late-breaking data were presented at Vascular Interventional Advances (VIVA) 2021 (5–7 October, Las Vegas, USA).
“The presentation of the PROMISE I 24-month results validate the benefits of the LimFlow system,” said Daniel Clair, chair of the Department of Vascular Surgery at Vanderbilt University Medical Center Section of Surgical Sciences in Nashville, USA, and PROMISE I principal investigator. “The high percentage of no-option CLTI [chronic limb-threatening ischaemia] patients that remained amputation free at 24-months is a major positive step forward for a condition characterised by high amputation and mortality rates.”
PROMISE I is a multicentre, prospective, single-arm study of the LimFlow system, conducted at seven study centres across the USA. All of the 32 patients enrolled in the study had non-healing wounds on the target foot. The primary endpoints were freedom from amputation, amputation-free survival, and survival overall. There were no amputations after day 75 in the study. At 24-months, freedom from amputation remained at 77% with an amputation-free survival of 59%. Three additional deaths within the second year of study resulted in 77% survival (two non-limb-related deaths; one from sepsis due to a non-healing wound in the non-treated foot). Ninety-two per cent had all wounds classified as healed or healing as adjudicated by an independent core lab. Technical success was reported at 97%.
“The two-year data from PROMISE I US feasibility study are highly encouraging and send a strong signal about the potential of the LimFlow system to strengthen our mission of no limb left behind,” said LimFlow CEO Dan Rose. “We are swiftly advancing our study of the LimFlow system in the ongoing PROMISE II US pivotal study in a patient population which is facing a very poor overall prognosis in terms of mortality and quality of life after major limb amputation. The LimFlow system is designed to help heal wounds and avoid major limb amputation, and we are proud of our mission of ‘No Limb Left Behind’.”
“I strongly believe that you cannot be what you cannot see. If you want more women or under-represented minorities (URMs) to enter the field and be at the table, then we need more women and URM leaders in the field,” Maureen Kohi (Chapel Hill, USA).
What attracted you to a career in interventional radiology?
My ‘a-ha’ moment that drew me into a career in vascular and interventional radiology was during my third year of medical school. I had observed countless prolonged open surgeries, and then scrubbed into one of my first cases of endovascular aneurysm repair of the abdominal aorta. I was moved by the precise and delicate deployment of the stent graft by a ‘vascular and interventional radiologist’ who forestalled a major abdominal surgery and resulted in the patient experiencing a quicker post-procedure recovery, faster hospital discharge, and lower complication rates. I loved the innovation of the field, the efficiency of the procedures, the delicate and yet deliberate procedural dance, and the monumental impact on clinical care provided through a pinhole. I knew I would be destined to become a vascular and interventional radiologist.
Who have been your mentors?
I owe my entire career to my mentors and sponsors along the way, as I truly believe we stand on the shoulders of giants, and I am forever grateful for their support. My most impactful mentor was Ernie Ring, who showed me the glorious world of academic interventional radiology. At the University of California, San Francisco (UCSF), I owe my research and academic success to my research mentors Karen Ordovas and Sharmila Majumdar who taught me how to become a physician-scientist and a research mentor. I also felt so incredibly supported and promoted by my chairman, Ron Arenson, who encouraged me to pursue a leadership career in radiology. During my junior faculty years, I was very fortunate to meet several luminaries who took me under their wing and helped to mentor and sponsor my career. I am forever indebted to Anne Roberts, Barry Katzen, Dan Sze, Jafar Golzarian, Jim Benenati, Jim Spies, Laura Findeiss, Mahmood Razavi, Mike Dake, Mike Darcy, Kathy Krol, Lindsay Machan and Ziv Haskal. During my transition from division chief to department chair, I relied a great deal on support and mentorship from Alan Matsumoto, Bob Ryu, Chuck Ray, Jim Spies, John Kaufman, Matt Mauro, and Reed Omary. Throughout my career, I have been very fortunate to have tremendous women peer mentors and I do not believe I could be where I am without the love and support of Kari Nelson, Theresa Caridi, Nadine Abi-Jaoudeh, Alda Tam, Alex Barnacle, Gloria Hwang, Janice Newsome, Nishita Kothary, Isabel Newton and Tze Wah.
Has COVID-19 provoked new ways of working for the interventional radiologist long-term?
In the clinical realm, we have learned a great deal about telehealth and the ability to offer our services to remote areas. In education, we have learned to leverage virtual platforms for conferences, grand rounds, and guest speakers. However, as good as we have become at assembling virtual meetings, I feel we all crave the in-person experience of socialising and networking. While the virtual component is ‘good enough’, it does not come close to the ideal of in-person meetings. In short, COVID-19 has taught us how to pivot, be nimble, and evolve, but some things are best left in the ‘old world’ such as meeting in-person, without social distancing, and masks. I really hope we can get back to that ‘old normal’ real soon!
Could you share a positive and negative experience you have had as a woman leader, and how you dealt with both?
As a female leader, I find any interaction where I promote or recruit a woman into the field of radiology or interventional radiology or within its leadership as a positive experience. Most recently, my most positive experience was my privilege to name Gloria Salazar as the very first woman Latin X division chief of Vascular Interventional Radiology at University of North Carolina and also nationwide. I have been fortunate in not having encountered many negative experiences as a female leader. However, the one that comes to mind is being repeatedly mistaken as a medical student, resident, fellow, nurse, or technologist. Once I was written up by a patient who felt I was a resident who placed her chest port when I was a first-year junior faculty. It reminds me of the eternal unconscious bias that as a young-appearing woman interventional radiologist, I look like every other member of the team, except for the attending physician or the leader of the team.
Could you describe your interventional radiology-suite personality?
I am a very efficient and fast-paced person who plans multiple steps ahead and enjoys a brisk procedural dance. I also like to set a relaxed and social procedural environment where I can teach my trainees about how I do a variety of procedures and also use the time to learn more about them. However, when the procedure gets more complicated or things are not going according to plan, I become quieter and more deliberate, knowing that as the attending, I set the cadence in the room. The calmer I am, the more relaxed the environment. The patient is always the focus of our work and the closer and more connected we are as a team, the more successful we will be at delivering excellent patient care.
What is the most exciting way of attracting women and URMs to the interventional radiology table?
I strongly believe that you cannot be what you cannot see. If you want more women or URMs to enter the field and be at the table, then we need more women and URM leaders in the field. We only have one woman interventional radiologist as department chair and currently there are no URM IRs as department chairs. There are no women or URM IRs as deans or CEOs of medical centres. However, we are seeing numerous women IRs become division chiefs and programme directors. This is the first step to bridging the gender and racial gap to ensure we have excellent role models at the table to attract the next generation of leaders, particularly women and URMs into the field.
In the last year, which new research paper has caught your attention?
One of the most interesting manuscripts was the publication of the FEMME (Fibroids with either embolisation or myomectomy to measure the effect) trial, which was a randomised controlled trial comparing quality of life associated with the two treatments among women wishing to avoid hysterectomy. The primary outcome of this trial was the change in the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire after two years. This trial was the very first of its kind to have a very diverse population with a large number of African American participants, women with large uteruses, and severe fibroid symptoms. The trial demonstrated that the myomectomy group had a longer hospital stay and almost double the complications than the uterine fibroid embolization (UFE) group. While both groups demonstrated improvement in their UFS-QOL scores after therapy, the myomectomy group demonstrated a slightly higher improvement compared to the UFE group. Overall, the trial demonstrated that UFE and myomectomy are more alike than different. In addition, it demonstrated that compared to myomectomy, UFE resulted in post-embolization syndrome, shorter hospital stay, quicker return to work, fewer severe adverse events, and potentially comparable fertility outcomes.
Could you describe a memorable case?
I was consulted about a 23-year-old female who had presented with massive vaginal bleeding due to a uterine arteriovenous fistula (AVF) following a dilation and curettage (D&C). She underwent UFE with particulate embolization, which was unsuccessful and continued to experience severe vaginal bleeding and was planned to undergo a hysterectomy. I was fortunate to have been consulted to see if there was any way to preserve her fertility. I was able to embolise the AVF by directly puncturing and embolising the nidus using ethylene vinyl alcohol copolymer. She went on to have a quick recovery and then become pregnant and give birth to a healthy baby. The case taught me that the innovative spirit of interventional radiology lives in all of us. In addition, it reminded me that we should not be so quick to recommend hysterectomy. Instead, we should take a step back and think of what else we can offer to preserve fertility and avert hysterectomy. We would never do a nephrectomy for a renal AVF or a pneumonectomy for a pulmonary arteriovenous malformation. So why remove a woman’s uterus because of a fistula? Go direct and obliterate the fistula, retain fertility, and avoid hysterectomy.
What interests you outside of medicine?
I most enjoy spending time with my 11-year-old son, husband, dog and our friends. I also love all things athletic: running, biking, hiking, kayaking, jet skiing, or going to a baseball or basketball game. I am a huge Tar Heel fan, so anything that applies to the University of North Carolina. I am inspired by music and played trombone in the Stanford band. My other interests include baking, travelling, and wine. Reading a book (anything by Jane Austen) at the beach with my feet in the water while my son and husband body surf is a favourite pastime. As I grew up in Northern California, I love wine tasting and learning about how wine is made. Moving to the South my interests have expanded into visiting breweries and distilleries and learning more about Southern cooking.
Is target lesion revascularisation (TLR) a meaningful clinical endpoint for research or should it be “tossed as a legitimate endpoint for peripheral vascular disease treatment success in US FDA [Food and Drug Administration] approval trials?” Recent keynote presentations and conference debate on appropriate care for peripheral vascular disease leave overuse of interventional therapy, particularly for claudication, staring down the end of a barrel. They also trigger a conversation around TLR becoming a target in and of itself.
Kim Hodgson, the 2019–2020 Society for Vascular Surgery (SVS) president, delivered a “delayed-due-to-COVID-19” presidential address at the 2021 Vascular Annual Meeting (SVS VAM 2021; 18–21 August, San Diego, USA and online) laying out a path to champion appropriateness in vascular care. He wasted little time in conveying the message he has long sought to convey to SVS members: that the threat posed to vascular surgery by a small number of “bad actors” carrying out inappropriate procedures is real—and that it is long past time to address the issue.
The day after Hodgson introduced the concept during the Crawford Issues Forum, data were presented by Caitlin W Hicks, associate professor of Surgery at Johns Hopkins Medicine in Baltimore, USA, and colleagues at VAM on the overuse of early peripheral vascular interventions for claudication. Since then, further research has built upon the charge that outliers are performing inordinate levels of certain procedures, including atherectomy carried out in the office-based lab (OBL) setting.
The impact of the explosive growth of atherectomy on patients and healthcare finances is problematic and growing exponentially, Hodgson lamented. He turned to further findings from Hicks showing that of the roughly US$267 million reimbursed by Medicare for first-time femoropopliteal peripheral vascular interventions in 2019, 90% was for atherectomy, “leaving only US$26 million to pay for all of the other therapies that actually have evidence showing that they work.”
Hodgson called out what he called “the enablers” of this type of practice—“people or constructs that encourage or enable negative behaviour in others.” The Centers for Medicare & Medicaid Services (CMS) was one, with “distorted reimbursement incentives” contributing to the problem, he argued.
Another enabler is the FDA, Hodgson said, calling for TLR to be “tossed as a legitimate endpoint for peripheral vascular disease treatment success in FDA approval trials.” Hodgson also called out vascular surgery’s industry partners. He said they should be “the canary in the coalmine for inappropriateness. You are uniquely positioned to spot abuse early—before patients are harmed. You know every one of the outliers in vascular care.”
Jim A Reekers, professor emeritus of Radiology at Amsterdam University, Amsterdam, The Netherlands, is currently the editor-in-chief of CVIR Endovascular and has served as president of several national and international organisations, such as the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the interventional radiology division of the European Union of Medical Specialists (UEMS). He tells Interventional News: “I read with great interest the address of Dr Hodgson during the 2021 iteration of VAM about inappropriateness in care. I fully agree with the content, and I am happy with this initiative for change. I truly hope that his address will mark the start of a new era where the patient will be again the focus of our work and not only the patient’s lesion. As mentioned by Dr Hodgson, there has never been any scientific evidence for atherectomy while there is overwhelming high[1]quality evidence for SET [supervised exercise therapy], and there has been for a long time. Dr Hodgson also touched on the holy grail of TLR, which is instrumental to what he says about inappropriateness in care. TLR is a flawed and constructed pseudo endpoint for peripheral vascular disease treatment success, without any relation to real clinical patient outcome, benefitting only commercial trials (as published by Reekers in The Lancet in 2019). His idea that industry partners are uniquely positioned to spot abuse is true and needs no further discussion.”
Speaking at a separate VAM sponsored session on paclitaxel safety, which drew a mix of sceptical and cautious responses to the latest meta-analysis from interventional radiologist Konstantinos Katsanos and colleagues (Patras University Hospital, Patras, Greece), that reported a heightened risk of major amputation after use of paclitaxel-coated balloons (PCBs) in femoropopliteal and infrapopliteal arteries, Joseph Mills, professor and chief, Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, Houston, USA, and SVS vice president, made the point that there was a real need for studies that are redesigned to look at […] clinically significant endpoints for patients.”
As specialists interested in patency, Mills continued, vascular providers tend to think that if a treated lesion stays patent for a bit longer, then the treatment “has got to be better for the patient. But the actual endpoint for a claudicant would be how far they can walk, what their quality of life is; and, for a chronic limb-threatening ischaemia (CLTI) patient, it is going to be: do they heal? do they have recurrent wounds? Those questions are a little bit different than the actual lesion-specific focus. I think if we can do anything from this, it would be to get industry to start looking at different endpoints.”
In the wake of the COVID-19 pandemic, the world of education went virtual. John Rundback (Advanced Interventional & Vascular Services LLP and American Endovascular & Amputation Prevention PC in Clifton, USA), who has been involved in interventional device education for more than 25 years, believes virtual procedural training is here to stay. In this interview, Rundback details how procedural training has adapted and is thriving in its new digital setting, with available systems offering increasingly immersive learning environments available to an international cohort of students. He predicts an 80:20 split between virtual and in-person training in the future.
What did training look like before the COVID-19 pandemic?
In-person training was the norm before COVID-19. Students would come in to our department to observe cases, to work on projects that we would assign to them and to be involved in live cases. For a live case, we would bring in audio and video crews so that we could broadcast the case for international meetings. There would also be various fellows and residents who would come in and rotate with us. Students had to physically be there, and that was great—you certainly had that personal interaction, but it was also time-consuming in that you had to devote your attention to an individual.
In-person training was dealt a blow due to COVID-19. How did it then transform?
When COVID-19 hit, obviously everything changed. I have been involved in medical education, and specifically interventional device education, for my entire career—more than 25 years now—and so it is part of who I am.
We have now moved towards using virtual platforms. Typically, a virtual platform will feature a video monitor that has several inputs and cameras. What this creates is a remote, immersive environment, and, in many respects, I think it is better than what we used to have. Rather than trying to see what is going on in a busy procedure room, where you are trying to find the optimal positioning to look at the monitors and look at what you are doing, you can now focus more on the patient. In addition, the user can control the inputs, and so there are no wasted efforts in teaching, and this has created a much better flow and a much more curated experience for the people who log in.
There are other advantages as well. Remote learning makes scheduling easier, both for us and for the attendees, who instead of having to set aside a day or longer, they can just log in for specific cases or specific portions of cases, and we can of course record portions of those as well.
Moving forward, I think this is going to be a new paradigm, and we have platforms that are expanding their capabilities with more inputs and more cameras, so we can really make this even more of a comprehensive environment and make the remote user feel like they are in the room.
How do virtual platforms change local training and have they maintained their value when tested for international training as well?
We have actually done some international training already with Avail, the technology that we have chosen for remote virtual training. We have had people who have logged in from Europe so far to watch us during our training and our courses. That is one of the beautiful things about remote learning—by training in a virtual or digital environment, distance is no longer a concern. The challenges of mobilising or disrupting your practice to go and learn, are completely resolved. Furthermore, not only can we potentially educate more people, but from the trainee’s point of view, you can train more often. You cannot necessarily understand everything the first time you go through it but, but remote training gives you the opportunity to participate in a number of different procedures until you reach a comfort level. That would be impossible if trainees had to repeatedly travel to a remote location to try to accomplish the same goal.
What is your lucky guess on the shape of training in the next couple of years?
I think that in the future device and procedural training is going to be 80:20, utilising a virtual platform more often than actual onsite or hands-on training. I think a big part of training is understanding the procedural steps, the cognitive processes behind that and the troubleshooting associated with getting through a case. That is actually 80% of it. Often interventionalists have the skills—the haptic skills, the hands-on skills—and so translating them into your own practice, actually being able to touch the devices and utilise them, is a much smaller part of the training.
In addition, we are increasingly getting a workforce for whom a virtual platform is a familiar and comfortable environment, and actually a preferred way of learning. We are getting people who have been raised during the digital revolution and this is how they interact with the world. So, I think in the future this is going to be the predominant mode of education.
I have heard quite a lot of people talking about this idea of there being a move to a more hybrid model of some being in-person and some being virtual in terms of conferences, and so it is interesting that training will also follow this path, but it does make sense in terms of getting the advantages of physical meetings and also the advantages you get from remote learning.
The reception on the personal interaction during online learning has been lukewarm. Is there a way this can be replicated online?
I think another part of millennial learning is that they very much engage with one another to further their knowledge and to further their comfort level. I think that still happens online. During the virtual live classes there is a conversation that is going on in the background. There is generally a Q&A portal as well so there is interaction there. I know just from my participation that Zoom meetings can be an effective way to share ideas.
Clearly, you lose something in terms of the personal interaction, but again there is the ability for students to see me, if not for me to see them. There was a professor at Harvard who was working in a virtual classroom model where not only could the students see the professor, but there was a video display where the professor could see the students as they spoke. Maybe that would be a nice addition—a separate monitor off to the side so that as people are talking, they can actually have a face-to-face conversation and of course where the students or trainees can also see each other. I think that will be the next evolution as digital advances allow.
Disclosures: John Rundback is a consultant for Avail Medsystems
Despite the well-known obstacles, it is time for a prospective, randomised clinical trial comparing percutaneous ablation (PA) and partial nephrectomy for the treatment of small renal cell carcinomas— and re-thinking the common practice of watching and waiting, rather than intervening, is long overdue, writes Christopher S Morris (Larner College of Medicine, University of Vermont, Burlington, USA).
Current studies with a moderate level of evidence have already confirmed decreased complications and similar effectiveness of PA compared to surgery in treating small renal tumours. Interventional radiologists (IRs) everywhere should be prepared for an increasing influx of patients seeking treatment of their small renal cell carcinomas with PA.
In developed countries, the incidence of renal cell carcinoma has increased over the past 20 years, mainly due to the increase in cross-sectional imaging and improving life expectancies. More than 50% of these tumours are diagnosed incidentally. In 2021, it is estimated that there will be more than 76,000 new kidney cancers diagnosed and almost 14,000 deaths attributed to kidney cancer in the USA alone. Like many solid malignancies, renal cell carcinoma is most effectively treated while small and prior to local and regional invasion, and certainly before the progression to distant metastatic disease.
Although the standard treatment of renal cell carcinoma is nephrectomy and partial nephrectomy, IRs have been treating small T1a (<4cm) renal cell carcinomas with PA, either cryoablation, radiofrequency ablation (RFA), or microwave ablation (MWA) for more than 20 years. Despite the proven safety and efficacy of PA for small renal tumors, less than 10% of these lesions are treated with PA. In addition, studies have shown that patients with small renal cell carcinomas are often surveilled with imaging, rather than treated with PA. Therefore, better awareness of the advantages and utility of PA in treating T1a renal cell carcinomas is needed.><4cm) renal cell carcinomas with PA, either cryoablation, radiofrequency ablation (RFA), or microwave ablation (MWA) for more than 20 years. Despite the proven safety and efficacy of PA for small renal tumors, less than 10% of these lesions are treated with PA. In addition, studies have shown that patients with small renal cell carcinomas are often surveilled with imaging, rather than treated with PA. Therefore, better awareness of the advantages and utility of PA in treating T1a renal cell carcinomas is needed.
Last year, the Society of Interventional Radiology published a Position Statement on the role of PA in renal cell carcinoma, which was endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology.1 The writing group consisted of a multidisciplinary collection of experts who reviewed the pertinent literature. Although currently there are no randomised controlled trials comparing PA with surgery in renal cell carcinoma, the writing group found many population-based registry studies and systematic reviews of small cohort studies. The writing group concluded that PA is an acceptable treatment option for stage T1a renal cell carcinomas in carefully selected patients and can be offered over active surveillance. Of the three different PA modalities, the writing group found no significant differences in safety and efficacy between cryoablation, RFA, and MWA.
Regarding efficacy, four large database studies have shown that patients with small renal tumours treated with PA had acceptable, but mostly lower overall survival rates than those patients treated with surgery.2,3,4,5 However, when looking at cancer specific survival, two of the four studies showed no significant difference between PA and surgery. One study reported no difference in five-year overall survival between PA and surgery. These results reiterate the necessity for a randomised controlled trial comparing PA and surgery for small renal cell carcinomas, as these database studies may be biased by patient selection and other confounders. Despite the fact that a randomised clinical trial is often hampered by funding restraints, difficulties in recruitment of eligible patients, and political obstacles, it will be essential in further establishing safety and efficacy of PA.
Wind-down “watch and wait”
Multiple database studies have demonstrated the utility of adopting PA in lieu of active imaging surveillance.4,6,7 All studies showed that cancer-specific survival was higher for patients treated with PA than those subjected to surveillance and one study also demonstrated significantly greater overall survival rates for PA over active surveillance. These results seem to argue against the common practice of active imaging surveillance of small renal tumours, which would present large numbers of patients who would be more appropriately treated with PA. One of the greatest advantages of PA compared with surgery is its safety. Simply put, PA is associated with significantly fewer complications than surgery. Multiple cohort, registry-based studies, and systematic reviews have confirmed that complication rates and post-procedure renal function outcomes are better with PA than surgery in treating small renal tumours.3,4,8,9,10
As PA is often performed as an outpatient procedure, the length of stay is shorter for PA than surgery. In the cohort and registry-based analyses, significantly lower complication rates were found for PA than surgery in the treatment of small renal cell carcinomas, with complications following PA ranging from 6 to 21% and the complications from surgery ranging from 29 to 40%. In one study, patients treated with PA had lower rates of acute renal failure when compared to surgery. Acute renal failure associated with PA was 3%, whereas it was 7% with partial nephrectomy and 11% with radical nephrectomy.
A systematic review of 107 studies demonstrated lower rates of urine leak, acute kidney injury, and other urologic complications, as well as shorter median hospital stay and decreased median blood loss in patients treated with PA vs. surgery.9 Another systematic review of 15 studies reported lower perioperative complications with PA than surgery.10 In addition, the surgery (partial nephrectomy) group was associated with decreased renal function at six-month and one-year follow up, compared to the PA patients.
A large registry database study of 773 patients compared outcomes of PA of T1a tumours performed with cryoablation vs. thermal PA (either RFA or MWA)6. No significant difference in cancer-specific survival was found between cryoablation or thermal PA.
The writing group also determined that a biopsy of a small renal tumour should be performed prior to PA at any time, either during the first part of the PA procedure or as a separate prior procedure. In addition, there may be a role for PA in treating some T1b (between 4 and 7cm in diameter) renal cell carcinomas and distant oligometastatic renal cell carcinoma in selected patients.
Overall, PA appears to offer similar cancer-specific survival with fewer complications compared to partial nephrectomy for the treatment of small renal cell carcinomas. In addition, patients with T1a renal cell cancers tend to fare better when treated with PA compared to management with active surveillance. Although a randomised controlled trial is needed to further confirm the promising results of these population-based registry studies and systematic reviews of small cohort studies, IRs should expect a greater demand for PA of small renal tumours in the future.
Christopher S Morris is a professor of Radiology and Surgery at Larner College of Medicine at the University of Vermont, Burlington, USA. He has reported no relevant disclosures.
References:
1: Morris CS, et al. Society of Interventional Radiology position statement on the role of percutaneous ablation in renal cell carcinoma: Endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology. J Vasc Interv Radiol 2020, 31:189–94
2: Zhou M, et al. SEER study of ablation versus partial nephrectomy in cT1A renal cell carcinoma. Future Oncol 2018, 14:1711–9
3: Talenfeld AD, et al. Percutaneous ablation versus partial and radical nephrectomy for T1a renal cancer: A population-based analysis. Ann Intern Med 2018, 169:69–77
4: Xing M, et al. Comparative effectiveness of thermal ablation, surgical resection, and active surveillance for T1a renal cell carcinoma: A surveillance, epidemiology, and end results (SEER)–medicare-linked population study. Radiology 2018, 288:81–90
5: Uhlig J, et al. Ablation versus resection for stage 1A renal cell carcinoma: National variation in clinical management and selected outcomes. Radiology 2018, 288:889–97
6: Uhlig A, et al. Treatment for localized T1a clear cell renal cell carcinoma: survival benefit for cryosurgery and thermal ablation compared to deferred therapy. Cardiovas Interv Radiol 2018, 41:277–83
7: Larcher A, et al. Population-based assessment of cancer-specific mortality after local tumour ablation or observation for kidney cancer: A competing risks analysis. BJU Int 2016, 118:541–6
8: Larcher A, et al. Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney cancer. Eur J Surg Oncol 2017, 43:815–22
9: Pierorazio PM, et al. Management of renal masses and localized renal cancer: systematic review and meta[1]analysis. J Urol 2016, 196:989–99
10: Hu X, et al. Partial nephrectomy versus ablative therapies for cT1a renal masses: A Systematic Review and meta-analysis. Eur J Surg Oncol 2019, 45:1527–35
Varian, a Siemens Healthineers company, today announced that the US Food and Drug Administration (FDA) has granted the company breakthrough device designation for its Embozene microspheres for genicular artery embolisation (GAE) for symptomatic knee osteoarthritis.
Embozene is a medical device that is FDA cleared for the embolisation of hypervascular tumours, arteriovenous malformations, uterine fibroids and benign prostatic hyperplasia.
According to Varian, Embozene microspheres received the designation due to their potential to offer a more effective treatment for appropriate patients with osteoarthritis of the knee. GAE is designed to reduce the blood flow to the periarticular tissue of the joints, limiting the inflammatory process.
Siddharth Padia, director of interventional radiology at UCLA Santa Monica and the David Geffen School of Medicine at UCLA, Santa Monica, USA, said: “GAE is the first minimally invasive procedure that has demonstrated a significant symptom improvement for a prolonged duration.
“In a 40-patient, prospective study, the procedure resulted in a marked improvement in pain and function, and adverse events were uncommon and mild. I remain excited about the possibilities of this technology and its benefit to patients.” Padia is currently working to initiate a randomised clinical trial and a 400-patient registry.
The FDA breakthrough device program is intended to provide patients with more timely access to medical devices that have the potential to provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. As part of the program, the FDA expedites the traditional review and assessment process to help accelerate the development, assessment and review of the device for possible approval.
Frank Facchini, president of Varian Interventional Solutions, added: “GAE holds great promise in providing clinicians with a new, non-invasive treatment option, which may not only ameliorate pain, but reduce the economic burden of this common disease. Varian’s investigational program for GAE exemplifies our commitment to investing in our core technologies to determine their potential to treat the world’s most debilitating diseases.”
IceCure submitted an amendment to the registration certificate granted for the IceSense3 system by China’s national medical products administration (NMPA), which will allow IceCure to sell the IceSense3 and cryoprobes for commercial procedures in China.
IceCure Medical recently announced the advancement of the regulatory strategy in China with the submission of an amendment to the registration certificate for the IceSense3 system, which was granted by China’s NMPA. The amendment, if approved, will allow the company to sell the disposable IceSense3 cryoprobes for commercial procedures. The company expects the NMPA to evaluate the amendment by the end of 2022 and providing the amendment is approved, the company expects to then launch the commercial sales program for the IceSense3 system in China in early 2023.
“We are excited to announce the advancement of our regulatory strategy for the IceSense3 system in China, as we look to bring our minimally invasive therapy to more cancer patients around the world. With more than 400,000 new breast cancer cases diagnosed in China in 2020, according to the World Health Organization, breast cancer continues to be a significant health concern in China,” commented Eyal Shamir, the chief executive officer of IceCure.
“As Chinese health providers continue to look for advanced technologies, we expect early adopters in China to provide a base for our commercial launch once the IceSense3 cryoprobes receive NMPA regulatory clearance. As part of our strategy to gain greater awareness of our systems and cryotherapy as a cancer treatment more broadly with healthcare providers in the region, we have been supportive of an ongoing independent clinical trial with a site in Hong Kong and a site in Shenzhen. Also, we expect another independent trial to start soon in a leading hospital in Shanghai” said Shamir, illustrating ongoing trail plans.
Sirtex Medical (Sirtex) has announced that the first procedure of selective internal radiation therapy (SIRT) using SIRSpheres Y-90 resin microspheres in China was successfully performed for a patient with hepatocellular carcinoma (HCC) on 28 September 2021. The milestone was reached with the support of Sirtex shareholder China Grand Pharmaceutical and Healthcare Holdings Limited.
“This achievement marks a major step forward in our global growth as a company and in our mission to bring effective treatments to patients with cancer,” said Kevin Smith, chief executive officer of Sirtex. “We are especially excited to advance our efforts in China, given the sizable numbers of colorectal and liver cancer cases in recent years. We thank everyone involved in this accomplishment and look forward to the promising future of SIR-Spheres in China and around the world.”
The procedure was performed by Jiahong Dong (Boao Super Hospital, Hainan, China) and his team. Jiahong is a world-renowned specialist in hepatobiliary pancreatic surgery and liver transplantation and was elected Academician of Chinese Academy of Engineering in 2017.
There are 400,000 new cases of liver cancer in China each year, accounting for more than half of all new cases of liver cancer worldwide. “The successful implementation of the first licensed access to the resin microsphere in the clinical treatment of liver cancer means that China’s liver cancer patients can receive international advanced selective in vivo radiation therapy,” said Jiahong Dong in a press conference. “This is a landmark and milestone in the history.”
Hainan’s first try, first pilot policy allows global new technologies, new ideas, and new products to be implemented through Hainan Hope City. The project of the introduction of SIR-Spheres Y-90 resin microspheres will benefit Chinese patients in China.
In November 2020, the National Medical Products Administration (NMPA) of the People’s Republic of China accepted the Sirtex new drug application (NDA) of SIR-Spheres Y-90 resin microspheres for the treatment of colorectal cancer liver metastases.
BD recently announced it has received 510(k) clearance for expanded indications from the US Food and Drug Administration (FDA) for the Rotarex atherectomy system.
The Rotarex atherectomy system is a rotational excisional device that is built to remove and aspirate varying lesion morphologies including plaque and thrombus in the peripheral arteries. The Rotarex system, already cleared for use in native arterial vessels, now has the expanded indications to treat within peripheral arteries fitted with stents, stent grafts, and native or artificial bypasses.
“The Rotarex atherectomy system is quick and efficient for treating arterial lesions,” said Prakash Krishnan, a cardiologist at the Icahn School of Medicine at Mount Sinai in New York, USA. “With ability to use it for both atherectomy and thrombectomy, it is now a great product to be able to treat in-stent restenosis. Rotarex has been a great device for me to have in my practice, and I am excited about these new indications.”
The FDA clearance of the Rotarex atherectomy system’s new expanded indications follows more than 10 years of real-world clinical experience involving the treatment of thousands of patients globally. Now, physicians can use a proven tool to address some of their most challenging peripheral arterial disease (PAD) lesions, including the treatment of in-stent restenosis.
“I have had the ability to use the Rotarex atherectomy system for over 10 years both within and outside the USA,” said Miguel Montero-Baker, a vascular surgeon at Baylor College of Medicine in Houston, USA. “This indication expansion is exciting and will allow me to utilise a device I trust to care for my complex PAD patients.”
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Cardiovascular Systems recently announced that the first patient has been successfully treated with its ViperCross peripheral support catheter.
Billy J Kim (The Surgical Clinic, Nashville, USA), treated the first patient with ViperCross.
Kim remarked: “ViperCross offers the right balance of support and flexibility to successfully navigate tortuous anatomy and cross challenging lesions. In addition, ViperCross provides excellent guidewire support and facilitates easy guidewire exchange.”
Peripheral support catheters are used during peripheral vascular intervention (PVI) procedures for guidewire support to enable lesion crossing, as well as for guidewire exchanges. Physicians use support catheters in approximately 50% of PVIs, primarily in below-the-knee and complex interventions. When calcium is present, lesions can be challenging to cross with an interventional guidewire and often require advanced tools prior to vessel preparation and treatment.
Scott R Ward, chairman, president and chief executive officer of CSI, commented: “With the commercial launch of ViperCross, CSI now offers a complete portfolio of products for the treatment of peripheral arterial disease, including atherectomy, balloon catheters, guidewires, support catheters and embolic protection. Combined, these products advance our ability to help physicians improve outcomes for patients undergoing complex peripheral interventions.”
Siemens Healthineers has launched the Luminos Impulse fluoroscopy system, including features such as a seamless imaging chain, comprehensive dose optimisation, cybersecurity features, and detector-sharing capabilities for radiography.
In a press release, Siemens Healthineers said that the fully digital Luminos Impulse offers high-end features and superior imaging that have not been available at this economical price in the past. “Being able to offer such a compelling product in this price segment makes me really proud of what our team has achieved. We work diligently to bring high-end features to our ‘smaller’ systems while also maintaining their excellent image quality and clinical versatility. Customers can use Luminos Impulse for fluoroscopy and radiography with virtually no limitations,“ says Ronald Fröhlich, head of marketing X-ray Products at Siemens Healthineers.
Luminos Impulse is built for the needs of modern-day fluoroscopy and radiography, the company’s press release said.
Fluoroscopy enables the continuous dynamic observation of moving processes in the human body using pulsed X-rays.
Surmodics today announced the successful first clinical uses of the Sublime radial access 0.018 RX percutaneous transluminal angioplasty (PTA) dilatation catheter.
Ankur Lodha, perfomed the first procedures with the device at Cardiovascular Institute of the South’s office-based catheterisation lab in Lafayette, USA. Subsequently, Imraan Ansaarie, utilised the Sublime radial access 0.018 RX PTA dilatation catheter in cases at Advanced Endovascular Institute of St Augustine in St Augustine, USA. The device is the latest addition to the Sublime radial access platform, joining the Sublime radial access guide sheath and the Sublime radial access 0.014 RX PTA dilatation catheter.
“Sublime radial access RX PTA dilatation catheters will allow physicians to treat the most distal blockages in the foot with just radial access. This will help us perform more complex interventions via this approach which was not possible prior,” said Lodha.
“This Sublime radial access 0.018 RX PTA dilatation catheter is a great addition to the current devices available for minimal arterial access lower extremity intervention procedures,” added Ansaarie.
The Sublime radial access 0.018 RX PTA dilatation catheter, which received US Food and Drug Administration (FDA) 510(k) clearance in June 2021, allows above- or below-the-knee access through a transradial approach by providing the longest working length (220cm) on the market. Outer balloon diameters range from 2–6mm, allowing for treatment in larger vessels, with balloon lengths between 20mm and 220mm. With a proprietary shaft construction incorporating a flexible distal segment, a supportive proximal segment, and a mid-shaft that transitions from supportive to flexible, the Sublime 0.018 RX PTA dilatation catheter is designed to provide improved pushability, trackability and crossability in an RX platform.
The Sublime radial access 0.018 RX PTA dilatation catheter is indicated for PTA dilation of peripheral vasculature stenosis in the iliac, femoral, iliofemoral, popliteal, infrapopliteal, and renal arteries, and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulas. The device is contraindicated for use in the coronary arteries and the neurovasculature.
Medtronic today announced it has received CE mark approval for its radial artery access portfolio, which includes the Rist radial access selective catheter and the Rist 079 radial access guide catheter—the first catheter specifically designed for the unique demands of accessing the neurovasculature to treat stroke, brain aneurysms and other conditions through the radial artery versus access through the transfemoral artery, according to a company press release.
The Rist 079 radial access guide catheter is 510(K) cleared by US Food and Drug Administration (FDA) and has been in use at limited sites in the USA, receiving strong customer feedback in more than 100 cases on its outperformance in navigability and support for the radial pathway, the release adds.
“With excellent navigability, this first-of-its-kind device will allow clinicians to reach distal locations while still achieving excellent stability to the system,” said Alejandro Tomasello, head of the Interventional Neuroradiology Unit at Vall d’Hebron Hospital in Barcelona, Spain. “The radial artery access portfolio works well in tandem with Phenom PLUS, Phenom 021 microcatheter for stent deployment or Phenom 027 microcatheter for flow diverter deployment, which is a fantastic set up for the Pipeline Vantage embolisation device with Shield technology treatments [all Medtronic].”
Transradial techniques have been the standard of care in the cardiac interventional community since the American Heart Association (AHA) recommended a radial-first approach for acute coronary syndrome in 2018, citing lower bleeding and vascular complications than transfemoral artery access.
Other advantages demonstrated in cardiovascular procedures to radial access include strong patient preference, immediate ambulation and reduced costs, which have led the neurointerventionist community to examine adoption of the transradial approach to their practice, the release also states.
“We are committed to exploring ways to improve outcomes through complication reduction, reducing the cost of care and improving overall patient experience,” said Dan Volz, president of the Neurovascular Therapies business, which is part of the Neuroscience Portfolio at Medtronic. “We believe radial access is a meaningful addition to the clinical armamentarium. The CE mark approval of the Rist radial access portfolio emphasises our focus on driving innovation that gives clinicians who perform neurovascular procedures the broadest product portfolio so they can customise their care based on a patient’s condition and anatomy.”
Biotronik has announced the first patient enrolment in the BIONETIC-I study of the safety and efficacy of the Dynetic-35 cobalt chromium balloon-expandable stent system for the treatment of atherosclerotic peripheral arterial disease (PAD) lesions in the iliac arteries. The study will also evaluate the use of the stent system in association with Biotroniks’s Passeo-35 Xeo peripheral dilatation catheter. The first patient was enrolled by investigator Koen Keirse, vascular surgeon at the Tienen Medical Center in Tienen, Belgium.
The prospective, international, multicentre, single-arm, observational study will evaluate treatment of iliac lesions in approximately 159 patients with up to 60-month follow-up. The primary endpoint is major adverse events (MAEs) at 12 months. MAEs include device- or procedure-related death within 30 days post-index procedure, clinically-driven target lesion revascularisation and major index limb amputation up to 12 months post-index procedure.
“I was impressed by the performance of the latest balloon-expandable iliac stent on the market. The cobalt chromium structure is, to me, very important,” said Keirse. “I am sure that the Dynetic-35 stent’s unique characteristics and fantastic size range—including stents up to 78 mm—will be of added value in many cath labs.”
“I am enthusiastic to collect new clinical data to add to the body of literature regarding iliac artery bare-metal stenting, as we have not had new data in this field for some time,” added principal investigator Marianne Brodmann, head of the Clinical Division of Angiology, Department of Internal Medicine at the Medical University Graz in Graz, Austria.
The next-generation Dynetic-35 iliac stent system, which was launched in the EU and other CE mark-accepting countries last year, is 6Fr compatible across the entire size matrix, and is indicated for the treatment of de novo or restenotic lesions in the iliac arteries.
This advertorial is sponsored by Argon Medical Devices.
Placing a drain is an important, quotidian, “bread and butter” procedure that often has a tremendous impact on patients’ lives. “A drain is a drain until it is not,” says Sean Calhoun, who outlines the benefits of the Skater all-purpose, nephrostomy and biliary drainage catheters (Argon Medical Devices). He hones in on their anti-kinking and locking mechanisms, ease of insertion and transition and compatibility with both alcohol
and doxycycline. Calhoun also shares his excitement about the recent commercial launch of the Skater mini-loop drainage catheters in the USA and the European Union,telling Interventional News: “I am hopeful that this will eliminate the problem of losing access to the abscess cavity by having the catheter track smoothly through the wall and into a small cavity. It is also going to be very helpful for external biliary drains.”
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Gore has announced the EMEA launch of the lower profile, large diameter Viabahn endoprosthesis with Propaten bioactive surface.
The device enhancements build on a market-leading stent graft device, which has become an important tool for treating complex vascular disease, Gore said in a press release. According to the company, the device design reduces the delivery profile for larger 9–13 mm diameter stent grafts by up to 3Fr, enabling delivery through smaller sheaths. Smaller introducer sheaths have resulted in a lower risk of vascular access complications in select patient populations.
New radiopaque markers, now also on the larger diameter device configurations, enhance visualisation under fluoroscopy, facilitating positioning and device delivery, as well as precise and predictable placement, the company added.
“In addition to the radiopaque markers that facilitate positioning and deployment, the new lower profile enables use of a smaller sheath, potentially reducing the risk of damage at the access site,” said Manuel Alonso, Vascular Surgeon, Oviedo, Spain. “Combined with the trackability and flexibility this new lower profile offering will become very instrumental for treating complex patients across disease states in my practice.”
“The story of the Gore Viabahn endoprosthesis is a story of physician collaboration across four patient-centric indications and of proving performance over and over,” said Benjamin Beckstead, Gore Vascular category leader.
Issue 83 Highlights
After a successful introduction of Azurion with SmartCT in 2020, many users have experienced working with the new solution from Philips. Watch the video to learn from our early users how 3D imaging capabilities on their image-guided therapy system has impacted interventional radiology procedures in their facilities.
This video was filmed by Philips and is being sponsored for distribution in association with Interventional News.
Interventional News 83 Highlights:
Late-breaking trial data has demonstrated improved progression-free survival in patients with metastatic colorectal cancer after treatment with TheraSphere Y-90 Glass Microspheres (Boston Scientific).
Findings from the EPOCH clinical trial, which were presented at the European Society for Medical Oncology (ESMO) Congress 2021 and are to be published in the Journal of Clinical Oncology, showed that the TheraSphere treatment met both its primary endpoints, including progression-free survival (PFS) and hepatic progression-free survival (hPFS) of patients with metastatic colorectal cancer (mCRC) of the liver.
In the trial, TheraSphere treatment—a selective internal radiation therapy (SIRT) comprised of microscopic glass beads containing radioactive yttrium (Y-90) that are specifically delivered to target tumors—was used as a second-line treatment in combination with standard of care systemic chemotherapy (SOC) for patients who had disease progression during or after first-line chemotherapy.
Riad Salem, interventional radiologist at Northwestern Memorial Hospital (Chicago, USA) and co-principal investigator of the trial, said: “The EPOCH trial not only demonstrated positive safety and efficacy data for the patients treated in this study, but underscores the success of integrating a device-based therapy like TheraSphere treatment in the continuum of care with systemic chemotherapy and biologic regimens, thereby providing the rationale and setting the stage for future investigation in other cancer types.”
Peter Pattison, president, Interventional Oncology, Peripheral Interventions at Boston Scientific, added: “EPOCH is the first positive phase 3 SIRT trial in any disease setting and the data is expected to support our regulatory submission to the US Food and Drug Administration (FDA), with the hope that more patients with liver dominant mCRC will gain access to TheraSphere as a treatment option in the future.”
The global, prospective EPOCH pivotal clinical trial is a phase 3 study, designed to assess therapeutic benefit compared to SOC, which randomized 428 patients with mCRC to second line chemotherapy, with or without the addition of TheraSphere treatment. Both primary endpoints were met and included progression-free survival and hepatic progression-free survival, which reflect how long patients live without the disease progressing further, both systemically and within the liver.
The addition of TheraSphere treatment significantly increased both PFS (p=0.0013) and hPFS (p<0.0001). Patients receiving TheraSphere treatment with second-line chemotherapy were 31% less likely to show disease progression or death (HR= 0.69) and 41% less likely to show hepatic disease progression or death versus with chemotherapy alone (HR= 0.59).
Mary Mulcahy, medical oncologist at Northwestern Memorial Hospital and co-principal investigator of the trial, commented: “In the second line of therapy for metastatic colorectal cancer, with disease isolated to the liver, the addition of TheraSphere with chemotherapy resulted in a significant delay in overall tumor progression. Additionally, chemotherapy-related adverse events were comparable between the trial arms.”
Earlier this year, the FDA approved TheraSphere for the treatment of unresectable hepatocellular carcinoma (HCC) and granted breakthrough device designation for expedited review as a treatment of patients with glioblastoma. In the USA, the use of TheraSphere for mCRC is for investigational use only as the safety and effectiveness have not been established, say Boston Scientific.
The development of new research guidelines for interventional oncology that standardise treatment outcomes and the reporting of data represents a major step forward for an increasingly important medical subspecialty, according to a report in Radiology.
Interventional oncology is a fast-growing offshoot of interventional radiology in which treatment is applied directly to the tumour through a catheter. Compared with conventional treatments like surgery and chemotherapy, these minimally invasive image-guided procedures have lower complication rates, superior toxicity profiles and often comparable or superior outcomes—so much so that international guidelines have already adopted thermal ablation, or the destruction of tumours through heat, as a first-line treatment option for certain smaller-sized malignant tumours.
Treatment effectiveness is measured through a variety of means such as disease-free and progression-free survival. A lack of consensus regarding these parameters in oncology-related studies and how to uniformly share these outcomes amongst investigators worldwide has created a host of problems. Issues like different complication-related outcomes reported for the same treatment modality and inconsistencies in the reporting of overall survival data means that study results cannot always be reliably compared.
“Study results are being collected, analysed and reported in many different ways, and we tend not to speak the same language within the field of clinical oncology,” said study lead author Robbert S Puijk, a radiology resident and researcher at the Onze Lieve Vrouwe Gasthuis Hospital and Amsterdam University Medical Centers in Amsterdam, The Netherlands.
To address these shortcomings, an international panel of 62 experts recently convened and developed important recommendations on how to uniformly collect, analyse and report outcomes for patients treated with image-guided tumour ablation.
Among key recommendations, the panel determined that, to compare different treatment techniques, outcomes should be analysed and reported per patient and per tumour. This is because multiple index tumours within one unique patient, such as multiple liver metastases from colorectal cancer, are often treated simultaneously and cannot be regarded as independent.
The panel agreed that parameters like overall survival and disease-free survival should be analysed per patient and not on a per tumour or per procedure basis. Parameters that address both procedure-related side-effects and direct costs such as short-term complications and anaesthesia techniques should be addressed per procedure, the panellists concluded.
The panellists reached several other important agreements, including ones regarding the definitions for recurrence-free, disease-free and progression-free survival.
The new guidelines will boost interventional oncology in a variety of ways, according to Puijk.
“The given definitions in these current guidelines will provide the necessary foundation for scientific reproducibility between interventional oncology studies as they will ensure an objective and reliable interpretation of study outcomes, allow for accurate comparisons of results and avoid misinterpretations,” he said.
Puijk called the participation of a large number of international experts on the panel a key motivating factor to putting the guidelines on paper.
“Together with the help of independent biostatisticians and epidemiologists, it strengthens our methodology and indicates the importance of this project,” he said. “Widespread adoption of these guidelines is another step forward in the professionalisation of our field, interventional oncology.”
The researchers hope to extend these guidelines to regional and systemic cancer treatments and ultimately attract the participation of other medical societies.
The project represented a collaboration between the Society of Interventional Oncology (SIO) and the Definition for the Assessment of Time-to-event Endpoints in Cancer (DATECAN) trials initiative. Martijn R Meijerink, was senior author on the paper.
Biotronik is proud to announce the completion of enrolment of the investigator-initiated BIOPACT randomised controlled trial (RCT). This non-inferiority study evaluates the safety and efficacy of paclitaxel drug-coated balloons (DCBs), comparing the Biotronik Passeo-18 Lux paclitaxel-releasing percutaneous transluminal angioplasty (PTA) balloon catheter to the IN.PACT Admiral paclitaxel-coated PTA balloon catheter (Medtronic).
The study enrolled 302 patients in Austria, Belgium, France and Switzerland and will collect follow-up at one, six, 12, 24, 36, 48 and 60 months. Patients with Rutherford class 2–4 disease were randomized 1:1 to either the Passeo-18 Lux DCB or IN.PACT Admiral DCB for the treatment of stenotic, non-stented restenotic or occlusive lesions in the femoropopliteal artery. A non-inferiority hypothesis will be tested to compare the clinical performance of Passeo-18 Lux to IN.PACT Admiral.
The primary efficacy endpoint is freedom from clinically-driven target lesion revascularisation at 12 months post-procedure. The primary safety endpoint is a composite of freedom from device- and procedure-related death through 30 days post-index procedure, freedom from major target limb amputation and clinically-driven target vessel revascularisation through 12 months post-index procedure. Key secondary endpoints include primary patency, major target limb amputation and all cause of death.
“I am thrilled about this milestone for the BIOPACT RCT and thank all of our investigators for their participation and contribution to the fast enrolment despite the pandemic-induced challenges in patient care over the last year and a half,” said principal investigator Koen Deloose (AZ Sint Blasius Hospital, Dendermonde, Belgium). “Having more head-to-head data is critical to better understand differences in device design and drug dosage and the more data we can add to the safety debate of paclitaxel-coated balloons, the better. We eagerly await the follow-up results of this trial.”
“This head-to-head clinical trial will add to the already extensive evidence supporting our Passeo-18 Lux DCB,” said Alexander Uhl, president Vascular Intervention at Biotronik. “We look forward to these data confirming Passeo-18 Lux’s position amongst the leading DCBs.”
The primary endpoint is intended to be presented upon completion of 12-month follow-up in late 2022.
A large, multicentre cohort study provides a simple, practical method to effectively stratify patients preoperatively into low- and high-risk major amputation categories.
According to lead author Leigh Ann O’Banion (University of California, San Francisco, San Francisco, USA), “traumatic popliteal artery injuries present a serious clinical challenge because they are associated with the greatest risk of limb loss of all peripheral vascular injuries, with major amputation rates of 14–25%.”
Previous scoring systems, such as the Mangled Extremity Severity Score (MESS), attempt to determine a threshold beyond which repair is futile. O’Banion states: “The aim of the present study, unlike the older systems, was to provide an easy to use scoring system that could be used to preoperatively and effectively risk stratify patients with traumatic popliteal vascular injuries for major amputation.”
As reported in the September 2021 issue of the Journal of Vascular Surgery, O’Banion and colleagues from 11 medical centres from the Western Vascular Society retrospectively examined the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries from 2007–2018 and identified the factors independently associated with limb loss.
They compared the clinical data between those who ultimately required major (above ankle) amputation with those who did not, and subsequently validated the new scoring system in a random 20% of this population.
Characteristics of the study population (n=355) included:
At a mean follow-up of 69 days, the overall amputation rate was 16%, but those who lost primary patency had a major amputation rate of 46%. These findings underscore the critical need for close follow-up.
Significant preoperative risk factors for amputation included:
Using this information, a Popliteal Scoring Assessment for Vascular Extremity Injuries in Trauma (POPSAVEIT) score was created, assigning one point for blood pressure and two points for both the orthopaedic injury and no Doppler signals.
The study validated the scoring system revealing amputation rates were:
O’Banion explains: “When evaluating the patient comprehensively, the POPSAVEIT score divides the findings into three critical components: measures of global physiologic insult (blood pressure), musculoskeletal deformity (orthopaedic injury), and ischaemia (Doppler examination).
“This preoperative assessment tool could be used to effectively communicate and risk stratify patients across centres similar to the American Association for the Surgery of Trauma’s injury scoring scales, which are widely accepted and used across trauma centres. Additionally, the ability to risk stratify could be useful in discussing the prognosis and setting expectations with patients, their families, and other providers.”
This study confirms that patients with popliteal vascular injuries are at significant risk for amputation. The POPSAVEIT tool is a valuable tool to assess this risk as soon as the patient enters the emergency room.
Today, Boston Scientific announced an agreement to acquire Devoro Medical, developer of the Wolf thrombectomy platform. The non-console and lytic-free Wolf technology targets and captures blood clots using finger-like prongs that retrieve and remove thrombi in the arterial and venous systems.
“The addition of the Wolf platform advances our efforts to ensure physicians have the right tools to improve procedural efficiencies,” said Jeff Mirviss, executive vice president and president, Peripheral Interventions, Boston Scientific. “Clot management remains a core focus of our business, and upon commercialisation, this highly differentiated technology will complement and expand our offerings to a full suite of interventional strategies for thromboemboli, which also includes the EkoSonic endovascular system (EKOS) and the AngioJet thrombectomy system.”
Boston Scientific has been a strategic investor in Devoro Medical since 2019 and currently holds an equity stake of approximately 16%. As a result, the transaction consists of an upfront payment of approximately US$269 million for the 84% stake not yet owned and up to US$67 million upon achievement of certain clinical and regulatory milestones.
“The Wolf platform is a compelling new option for physicians performing thrombectomy procedures and, importantly, it is designed to target and remove clots without damaging blood vessels, while also minimising blood-loss, which may improve outcomes,” said Michael R Jaff, chief medical officer and vice president of clinical affairs, technology and innovation, Peripheral Interventions, Boston Scientific. “We look forward to accelerating the progress of this platform technology so that we help patients who are dealing with these common, yet challenging health conditions.”
Ten centres have achieved the International Accreditation System for Interventional Oncology Services (IASIOS) accreditation, a benchmark of quality standard and assurance, since 2018. Wesley Medical Imaging has just achieved this recognition to become the first hospital in the Southern Hemisphere to do so. Interventional News speaks to Nicholas Brown (clinical director at I-MED, The Wesley Hospital, Queensland, Australia) on this significant achievement and how it certifies that this hospital is providing the highest standards of interventional oncology (IO) care. “Personally, I am convinced it will bring game-changing renewal and evolution to interventional radiology practice around the world,” he says.
Commenting on the main benefits he foresees as a result of being granted this recognition, Brown says: “The IASIOS accreditation will allow our centre to promote our high standards to patients, referrers and hospital administrators. The process of seeking IASIOS accreditation allowed us to review and critically appraise our existing practices, and to ensure that how we work is aligned with the international standard. The promise of accreditation provided us with the motivation to examine every facet of our practice, including areas where we needed to improve our practices to comply with the IASIOS requirements.”
Brown is categorical about what prompted Wesley Medical Imaging to undergo the rigorous IASIOS accreditation process. “The IO service offered at the Wesley Hospital has always been comprehensive and progressive, and the IASIOS accreditation now provides us with an opportunity to ensure that our practices are benchmarked against an international quality standard. IASIOS accreditation provides us with the confidence that we are providing the highest standard of care, and will allow us to adopt new and evolving technologies within a quality framework. Furthermore, it will provide confidence to patients and referrers that our centre can be trusted to deliver the best possible care.”
The IASIOS award, in addition to being the bright line that separates centres that deliver top quality IO care, has wider implications for the growth and development of IO in Australia and New Zealand. Brown elaborates: “Quality assurance and quality control in interventional radiology and IO is critical. ‘Quality’ is the yardstick by which specialty practice is measured and judged by our clinical colleagues, and demonstrates a mature, professional approach to clinical care. The IASIOS system in Australia will help to ensure that quality standards remain a guiding focus as interventional radiology and IO evolve. It particularly demonstrates that specialist IRs can fulfil their potential as equals within the multidisciplinary team environment. Quality assurance is the mark of a true clinical speciality, and an accreditation programme that seeks to uphold standards of practice is a tremendous boost towards promoting these in interventional radiology. IASIOS is an effective tool that legitimises the high standards that we all strive for day-to-day, and provides an easy riposte to any out-dated attitudes from colleagues who doubt the notion of IRs being true clinicians. If ever we needed proof that IRs are clinicians and not just technicians, IASIOS provides it in abundance.”
A challenging process, huge achievement and the team’s unforgettable reaction
The IASIOS process is challenging, as is appropriate for a system designed to set and maintain high quality standards (see box). “It provided a thorough analysis of work practice and required an in-depth review of every part of what we do and how we interact with patients, referrers and the broader hospital setting. The process also takes longer than anticipated. Not all the information required for a successful application will necessarily be readily available, and may have to be reviewed, reproduced or re-written. A critical component—the case audit—is an opportunity to demonstrate the depth of specialty practice but it requires time to compile all the necessary aspects.
The IASIOS process definitely requires a team effort, but also needs one or two local champions who can take responsibility for the process and spearhead progress towards a completed application. A leadership team that involves clinical, nursing and administrative insights is very important.
An 18-month process, involving hard work and contributions from clinical, nursing, technical, administrative and managerial staff culminated in a successful accreditation. The whole team was absolutely thrilled and rightly proud of this achievement and the recognition that it brings. The affirmation of our high standards of practice is both reassuring and motivates us to continue to improve and evolve. We are also very pleased to be able to share this exciting news with our patients and referrers, as we look to grow not only our practice, but represent the capabilities of the broader interventional radiology profession,” says Brown.
Specifically addressing other global centres who might wish to undertake the accreditation process, Brown says: “It is good to remember that persistence will pay off, eventually. The Accreditation Certificate is just reward for a great effort and lots of difficult work. Attaining and promoting high quality standards in clinical care are important ways of supporting your practice and your profession.
“We are extremely grateful to CIRSE for embarking on the IASIOS journey, and personally I am convinced it will bring game-changing renewal and evolution to IR practice around the world. We are also thankful for the confidence (and patience!) shown to us by CIRSE in having the Wesley Hospital as a pilot site and encouraging us to complete the accreditation programme.”
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What is the process of IASIOS accreditation? The accreditation process begins once a facility has registered. By initiating the process, they receive the first seal—that of an IASIOS Enrolled Centre. With the first step, they have shown that they are dedicated to increasing the quality of the patient pathway in their IO service line. The goal of IASIOS is not to make a judgement on the quality of the department at the time of registration, rather it is to help the centre make the necessary adjustments and changes to bring their service to the level outlined in the core requirements of the Standards of Quality Assurance document. The centre can remain an Enrolled Centre for as long as necessary to make the changes and they can utilise the full support of the IASIOS team along the way. Each application is independently reviewed by two assessors who must both come to the same agreement that compliance has been demonstrated before the seal of IASIOS Accredited Centre has been granted. If there is any doubt on the answers given in the application form, the facility will be able to provide additional documentation or the assessors may request a remote audit for a detailed discussion. After a centre has been an IASIOS Accredited Centre for four years, they have the option of becoming re-certified, or they can ambitiously aim to demonstrate compliance to every single standard outlined in the Standards of Quality Assurance document, which would grant them the IASIOS Centre of Excellence seal. How does CIRSE guide centres across the globe through the process? The IASIOS team is readily available for any questions that may arise or obstacles that may be encountered during the application process, whether by email or video call. We have manuals and guidelines that have been developed, and are constantly gathering feedback and information that we can collect and make available to the centres going through the accreditation process so they can learn from the centres that have gone through the process before them. We have been developing a system that is completely online and digitised so it can be easily accessed by multiple people and multiple assessors regardless of time zone or location in the world. Our goal is to create a truly global community of people dedicated to advancing interventional oncology, learning from each other and increasing its quality of care and recognition. As the community grows further, we will be able to offer enrolled centres guidance from council members and consultants in all areas of the world. We received an overwhelmingly positive response from dedicated IO experts worldwide supporting this initiative and joining the IASIOS community as Council Members. How many centres have achieved accreditation since the 2018 pilot phase? From the 12 centres that participated in the pilot phase, 10 centres have achieved accreditation and two are undergoing accreditation. These include hospitals from Europe, Asia and the Southern Hemisphere, more specifically: The UK, France, Germany, Switzerland, Italy, the Netherlands, Turkey, Singapore and most recently – Australia. Since the launch of the scheme in April 2021, eight centres have initiated their enrolment and are awaiting administrative approval from their hospitals. These include hospitals from Canada, Switzerland, Italy, Germany, Austria, Sweden, the UK and the Netherlands. |
MedAlliance, with its Japanese partner MDK Medical, has completed enrolment in the clinical study of its novel sirolimus drug-eluting balloon (DEB), Selution SLR, for the treatment of peripheral arterial disease (PAD). This follows the acceptance of a Clinical Trial Notification (CTN) by Japan’s Pharmaceutical and Medical Device Agency (PMDA) in June 2020.
The study involves 133 patients across 13 centres in Japan. Its objective is to assess the safety and efficacy of Selution SLR for the treatment of lesions of superficial femoral arteries and/or popliteal arteries. The study is a prospective, controlled, multicentre, open, single-arm clinical investigation. Its primary endpoint is the primary patency rate at 12 months. Secondary endpoints include major adverse events/target lesion revascularisation (TLR), primary patency, and the change of Rutherford classification/ankle-brachial index (ABI)/walking impairment questionnaire (WIQ).
“We are extremely pleased with the regulatory and quality expertise demonstrated by our partner MDK, and particularly proud that Japanese patients can now benefit from our unique technology. This is the first sirolimus DEB implanted in Japan, where the current paclitaxel coated balloon market generates more than US$100 million in revenue per year”, commented MedAlliance chairman and CEO Jeffrey B Jump.
Selution SLR was awarded CE mark approval for the treatment of PAD in February 2020 and for the treatment of coronary arterial disease in May 2020. The US Food and Drug Administration (FDA) has awarded Selution SLR with four breakthrough designations: for the treatment of atherosclerotic lesions in native coronary arteries; coronary in-stent restenosis; peripheral below-the-knee and arteriovenous fistula indications.
In August 2021, the first of over 3,000 patients was enrolled in a coronary randomised controlled study comparing Selution SLR with a limus drug-eluting stent (DES). According to a press release, this is the largest DEB study ever initiated and has the potential to change medical practice.
Merit Medical Systems has announced positive results from a prospective, observational, first-in-human study to evaluate the safety and effectiveness of Wrapsody—a self-expanding, cell-impermeable endoprosthesis designed for the treatment of arteriovenous (AV) fistula access circuit stenosis and AV graft access circuit stenosis.
The prospective, observational study published in CardioVascular and Interventional Radiology by James Gilbert (Oxford University Hospitals, Oxford, UK) et al, reported 100% target lesion primary patency (TLPP) rate without reintervention through 30 days, with a 12-month TLPP rate of 84.6% and a 12-month access circuit primary patency (ACPP) rate of 65.9%.
The authors state that these results suggest that the Wrapsody endoprosthesis is a safe and effective treatment for AV access circuit stenosis.
The study enrolled 46 subjects with clinically relevant stenosis, who were treated at three centres. The eligible population consisted of patients undergoing haemodialysis through an AV circuit with clinical and radiological evidence of stenosis at the graft-vein anastomosis, in the peripheral outflow veins or in the central veins up to the superior vena cava. The subjects did not have clinically relevant secondary stenosis or thrombus in the access circuit.
The primary safety outcome measure was the proportion of subjects without localised or systemic safety events affecting the access circuit that resulted in surgery, hospitalisation or death during the first 30 days following device placement. All but one subject was free from such a safety event in the first 30 days following device placement (97.8%). The safety event was adjudicated as not related to the device or study procedure. Over the remainder of the study, there was one adverse event adjudicated as possibly device-related.
The primary effectiveness outcome measure for the study was the TLPP rate at 30 days following device placement, which was 100%. At six months following device placement, the TLPP rate was 97.7% and at 12 months following device placement, it was 84.6%.
The six- and 12-month ACPP rates were 84.4% and 65.9%, respectively. TLPP rates were similar regardless of access type and lesion location or whether subjects were treated with a single device or overlapping devices. In all cases, reintervention at the target lesion was successful in maintaining patency (12-month assisted TLPP rate of 100%.)
Primary investigator, Gilbert, said: “Early first-in-human study results show that the Merit Wrapsody endoprosthesis can be safely used to treat stenoses at key sites within a dialysis access circuit
“Even more encouraging are the very promising primary one-year target lesion patency rates of 84.6% and access circuit patency rate of 65.9%. To my knowledge, these are higher than any other published data and suggest that the novel features of the Wrapsody endoprosthesis may have a key role in preserving the longevity of precious dialysis access for our patients.”
Merit is also conducting a large multinational, multicentre study, the WAVE Study, which it plans to use to support a premarket approval application to the US Food and Drug Administration. Enrollment in the randomised WAVE Study comparing the Wrapsody endoprosthesis to percutaneous transluminal angioplasty for treatment of venous outflow circuit stenosis or occlusion in hemodialysis patients began in March 2021. Merit anticipates that the WAVE Study will include 477 subjects.
Fred Lampropoulos, Merit’s chairman and CEO, added: “Merit has built its commercial legacy on innovative products that benefit patients and advance standards of care.
“We are encouraged by the Wrapsody First study’s positive results and excited to help shape the future of arteriovenous access circuit stenosis treatment. We look forward to assessing future study results regarding the Merit Wrapsody endoprosthesis, and to making a positive impact in the lives of patients suffering from kidney disease.”
Bluegrass Vascular Technologies (Bluegrass Vascular) announced today that the Centers for Medicare & Medicaid Services (CMS) has finalised a new Healthcare Common Procedure Coding System (HCPCS) code and New Technology Ambulatory Payment Classification (APC) assignment for use of the Surfacer Inside-Out access catheter system (Surfacer system) procedure.
The new code is C9780, Insertion of central venous catheter through central venous occlusion via inferior and superior approaches (e.g. inside-out technique), including imaging guidance. It is assigned to New Technology APC 1534, with a national average payment rate of US$8,250.50. As a result of this decision, hospitals and ambulatory surgery centres (ASCs) will be able to utilise HCPCS code C9780 to report the Inside-Out procedure when performed with the Surfacer system beginning on 1 October 2021.
The Surfacer system employs a novel Inside-Out approach and is the first US Food and Drug Administration (FDA)-cleared medical device to facilitate upper body central venous access in patients with venous obstructions or other conditions that preclude access by conventional methods.
“The CMS decision to assign a New Technology APC for the Surfacer system is a major milestone and will ensure that our innovative technology will be reimbursed for Medicare beneficiaries. This is a significant development, given the prevalence of thoracic central venous obstruction in patients dialysing via a central venous catheter,” stated Gabriele Niederauer, CEO and president of Bluegrass Vascular. “This decision is a testament to the positive clinical evidence and cost data that support the use of the Surfacer system as a critical, lifesaving technology.”
Thoracic central venous obstruction occurs in roughly 40% of patients where haemodialysis is performed via a central venous catheter, a Bluegrass Vascular press release states. While permanent arteriovenous fistulas are the preferred form of vascular access for haemodialysis patients, central venous catheters continue to serve as an important bridge to securing long-term access for life-saving haemodialysis treatment. The current approach for most patients with central venous obstructions is to use an alternative vein, which reduces the ability to place and mature a functioning fistula, resulting in increased catheter days and costs.
According to CMS, more than 62.4 million Americans are enrolled in the Medicare programme. Approximately 80% of patients on haemodialysis are covered by Medicare fee-for-service as primary payer or by a Medicare Advantage managed care plan. Patients who live with kidney failure represent 1% of the total US Medicare population yet account for 7% of the Medicare costs.
The use of the Surfacer device also avoids left-side catheter placement, better enabling the maturation of permanent arteriovenous access options in the left arm and minimising unnecessary access-related procedures and complications. The National Kidney Foundation’s current Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for vascular access recommend that the ideal access site for haemodialysis catheters is the right internal jugular vein. This preferred right-sided access path is supported by the Surfacer system’s novel “Don’t Go Left” approach.
The Surfacer system received FDA de novo clearance in the USA in February and is CE marked in Europe. The device is available in North America, Europe and other territories.
Following the release of the European Society of Hypertension’s (ESH’s) updated position paper on renal denervation Konstantinos Tsioufis, professor of Cardiology at the University of Athens, Athens, Greece and immediate past president of ESH, discusses the use of renal denervation in the treatment of hypertension, considers the latest evidence in favour of the approach, and outlines the questions still to be answered.
What are the advantages of using renal denervation to treat hypertension?
In all recent sham-controlled trials there were clinically favourable effects of renal denervation for treatment of uncontrolled hypertension. The great advantage is that the intervention has shown meaningful office and ambulatory blood pressure decrease across multiple phenotypes of patients with mild to moderate as well as more severe hypertension in the presence and absence of medication. This constant reduction in blood pressure over 24 hours—the “always on” impact—of renal denervation differentiates the intervention-induced changes in blood pressure from those by drugs due to the diverse pharmokinetic profiles and dosing regiments along with patient non-adherence.
How does renal denervation compare to other treatment approaches that are available?
According to latest second generation randomised controlled trials and the Global SYMPLICITY Registry (GSR), average blood pressure reduction induced by renal denervation compared to sham ablation is 8-10mmHg in office systolic blood pressure reading and 5-7mmHg in ambulatory systolic blood pressure readings. Other interventional approaches to modulate sympathetic tone by baroreceptor activation is still under investigation.
What do trial data tell us about this approach and its outcomes in the long-term?
The antihypertensive effect of renal denervation is durable and taking into consideration the average drop of 10mmHg in office blood pressure, the renal denervation effect can be translated to significant improved cardiovascular prognosis (approximately 20% reduction in cardiovascular events and 26% in stroke). Renal denervation is also an early and late-term safe procedure with minimal complications based on data from registries and recent sham randomised controlled trials. The observed blood pressure reduction caused by renal denervation is maintained long term with data available up to three years after the procedure.
Are there any unanswered questions to be investigated?
Currently there is an urgent need to define predictors of blood pressure response post renal denervation and there are efforts focusing on diverse parameters both clinical and laboratory. There are data showing that in untreated patients with higher baseline heart rate and plasma renin aldosterone levels renal denervation are associated with better blood pressure reduction. Moreover, the average and standard deviation of night-time ambulatory blood pressure has been identified as a potential robust predictor, which requires further research. Another question is the long-term durability of blood pressure lowering and safety beyond three years as well as safety and efficacy in patients with comorbidities such as renal failure. Further studies are also needed on the renal denervation-induced clinical impact in patients with heart failure, atrial fibrillation and increased overall cardiovascular risk. The cost-effectiveness of the procedure for the health systems is an additional point to be addressed.
Are there any drawbacks to this approach?
Given the established efficacy and safety the only drawback for renal denervation is physicians’ inertia to consider and refer hypertensives for this approach. Additionally, there is a lack of information on the clinical impact of neuromodulation from the stand point of hypertensive patients that limits the implication of the technology to everyday practice.
How should physicians evaluate which patients are suitable for renal denervation treatment for hypertension?
According to the latest evidence, the criteria for considering hypertensive patients for renal denervation is persistent uncontrolled hypertension despite guideline-based therapy including ameliorated lifestyle measures and efforts to increase adherence. Heightened cardiovascular risk (i.e. evident organ damage) or established disease (i.e. coronary artery disease, heart failure) might be pointing towards treatment priority with renal denervation in hypertension. Additionally, patients who are unable or unwilling to take medication might be another renal denervation group, especially in the first stages of the hypertensive disease. The shared decision making process is mostly important for renal denervation and according to patients’ preferences this interventional approach could be selected for diverse phenotypes of hypertension.
Do you see renal denervation as having a significant role to play in the future treatment of hypertension?
Renal denervation constitutes today the most advanced and efficacious device-based interventional approach to treat hypertension, expanding therapeutic options as an alternative and not as a competitive strategy. This would be of important clinical value since approximately half of individuals with hypertension do not meet guideline-directed blood pressure goals. Based on the available evidence, renal denervation is definitely included in the individualised treatment strategy of the future for better hypertension control and reduction of overall cardiovascular disease burden.
Proposed cuts to physician reimbursements could shutter practices and leave thousands of medically vulnerable patients without access to care, the Society of Interventional Radiology (SIR) said in a comment letter submitted to Centers for Medicare and Medicaid Services (CMS) in September.
The letter was submitted in response to the July 13 proposed rule for the 2022 Medicare Physician Fee Schedule (MPFS). Under the proposal, IRs could see an aggregate cut of 13% for all interventional radiology treatments, with certain procedures performed in office-based lab settings experiencing cuts greater than 20%. Treatments with the highest cuts include limb-saving peripheral arterial disease treatments, clot-busting venous treatments, venous stenting and other vascular work.
“The rule represents a perfect storm resulting from CMS’s decision to allow their labour rates and product cost tables to lag behind inflation,” said SIR President Matthew S
Johnson, an interventional radiologist and Gary J. Becker Professor of Radiology Research at Indiana University School of Medicine in Indianapolis, USA. “In many cases, practice costs have not been updated in 20 years. Due to purported budget neutrality, CMS made apparently arbitrary cuts rather than reimburse all practices and specialties at their true cost of care.” While CMS c onsiders such cuts “budget neutral” they disproportionately affect procedures performed by IRs in office-based settings, such as treatment of venous ulcers and dialysis access. More importantly, the services most affected treat diseases that disproportionately affect patients of colour, such as peripheral artery disease, venous disease, renal disease and cancer.
“As a result, the profound cuts will negatively affect health equity in communities who have already been particularly hard hit by the COVID-19 pandemic,” said Johnson. “By making it difficult for outpatient, officebased labs to continue to operate, patients seeking care will have to do so in hospital settings, which are still reeling from COVID-19. For some patients, this could mean traveling hours outside of their community to receive treatment.”
Throughout the pandemic, office-based facilities have allowed hospitals to focus on the sickest COVID-19 patients while allowing lifesaving cancer treatments and limb-saving vascular procedures to continue. The cuts may make some practices unsustainable, directly impacting readiness for future COVID-19 surges or new pandemics. In addition, office-based lab facilities deliver quality care to patients far from major hospital centres.
Community-based, outpatient care allows patients to return to their normal lives sooner.
“We must protect patients’ access to that crucial care and prevent private practices from closing down, especially in underserved areas,” said Johnson.
SIR is joining with other healthcare organisations, such as the American Medical Association (AMA), the American College of Radiology, the CardioVascular Coalition and other medical specialty societies, to combat these cuts and plead with CMS and Congress to:
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Scitech Medical has announced it has begun enrolling patients for the company’s PMCF (SOLARIS Peripheral PMCF Trial) study.
Led by Michel Bosiers (St. Franziskus-Hospital, Münster, Germany) the study is coordinated by the Foundation for Cardiovascular Research and Education and will enrol 70 patients with occlusive disease from sites in Germany, The Netherlands and Italy.
The study aims to evaluate the long-term safety and efficacy of the Solaris vascular stent graft, a flexible and self-expanding endograft which, according to the company, is designed to cover and seal off diseased tissue, providing an endoluminal bypass option for physicians facing complex lesions.
Enrolment started in May 2021 and the final results are expected in May 2023.
The European Society of Hypertension (ESH) has presented an updated position paper on renal denervation (RDN) in a pre-ESH congress satellite symposium (10–11 September, Athens, Greece). The paper was recently published in the September issue of the Journal of Hypertension.
This position paper written by an ESH expert Working Group confirms that RDN is considered a safe endovascular procedure without significant short-term or long-term adverse effects based on data available up to three years.
“In light of the recent publication of several second-generation sham-controlled clinical trials, we thought it was important to provide an updated position paper on RDN and its role in treating uncontrolled hypertension,” said Roland Schmieder, professor of Internal Medicine, Nephrology and Hypertension at the University Hospital Erlangen, Erlangen, Germany and chairman of the ESH Working Group on interventional treatment of hypertension.
RDN is a minimally invasive procedure intended to regulate overactivity of nerves that lead to and from the kidney, which play an important role in controlling blood pressure.
In recent sham-controlled randomised trials and registries, clinically favourable effects of RDN have been consistently demonstrated across a wide spectrum of patients with uncontrolled HTN, in the absence and presence of prescribed antihypertensive medications.
”RDN represents an evidence-based option to treat HTN, in addition to lifestyle changes and blood pressure lowering drugs. RDN expands therapeutic options to address the first objective of HTN treatment, to effectively reduce elevated blood pressure and achieve blood pressure targets,” said Konstantinos Tsioufis (University of Athens, Athens, Greece), professor of Cardiology and immediate past president of ESH. “Heightened cardiovascular risk such as evident organ damage or established disease like coronary artery disease or heart failure might be pointing towards treatment priority with RDN in hypertension. Additionally, patients who are unable or unwilling to take medication might be another RDN group, especially in the first stages of the hypertensive disease.”
Arterial hypertension constitutes the most prevalent and important risk factor for cardiovascular morbidity and mortality globally despite the availability of pharmacological treatments. In addition, approximately half of individuals with hypertension do not meet guideline-directed blood pressure (BP) goals.
”Many patients with uncontrolled hypertension struggle to adhere to lifelong drug therapy for a variety of reasons and may look to other options that complement traditional treatments,” said Reinhold Kreutz, professor of Clinical Pharmacology and Hypertension at the Charité Universitaetsmedizin in Berlin, Germany and president of ESH. “We believe this advance could help clinicians work with patients to better manage their high blood pressure.”
At the Athens pre-ESH meeting, experts discussed various hypertensive profiles that could benefit from RDN including those unable to achieve BP control despite application of guideline-recommended therapies, and those with high baseline cardiovascular risk or comorbidities or poor tolerance to medications.
Biotronik has announced the expansion of the Fortress reinforced introducer sheath line, which is now available in 7- and 8Fr-compatible sizes in the USA and countries that recognise European CE mark approval.
The Fortress introducer sheaths are intended to provide access and facilitate percutaneous introduction of guidewires, catheters and other devices into the femoral, popliteal and infrapopliteal arteries while maintaining haemostasis during diagnostic and interventional procedures. The sheath is reinforced with a polymer-embedded stainless steel coil to ensure excellent kink and deformation resistance.
“In complex vascular procedures, we as interventionalists need the right tools that simplify our workflows and lower risks for patients,” said Torsten Fuß, head of Internal and Intensive Care Medicine at the Elblandklinikum Radebeul in Radebeul, Germany. “The Fortress 7Fr and 8Fr introducer sheath sizes have a very smooth dilator-to-sheath transition, reducing friction when going over the bifurcation. It is easier to insert compared to other introducers on the market and has excellent pushability in typically challenging access presentations like preoperated and calcified groins.”
The new line extension sizes not only preserve the existing benefits of Fortress introducer sheaths but are designed to offer compatibility with 7Fr and 8Fr devices for endovascular procedures, including the use of covered stents and atherectomy devices. With the addition of these new sizes, the Fortress introducer sheath is now available in a full size range from 4Fr to 8Fr.
“The Fortress introducer sheaths have proven a favourite with interventionalists due to their ease of use and excellent kink resistance,” commented Alexander Uhl, president Vascular Intervention at Biotronik. “The expansion of Fortress introducer sheaths to 7Fr and 8Fr-compatibility allows physicians to use Fortress with a broader range of procedures such as most atherectomy devices and covered stents.”
“Like anything in the medical community, there can be positive and negative,” Agnieszka Solberg (Bismarck, USA) tells Interventional News discussing the impact of social media in the fields of interventional and neuroradiology.
As a founder of the RadChicks movement—an online community for women working in the field of radiology—Solberg believes that social media networks such as Twitter, LinkedIn and Facebook provide vital networking opportunities for women and underrepresented minorities, but warns that physicians must use these platforms with caution, paying particular attention to patient confidentiality, among other potential pitfalls.
Physicians also have an important role in building trust with the public, and should be at the forefront of effort to combat medical misinformation, Solberg argues.
A Singapore team of scientists and clinicians from Nanyang Technological University, Singapore (NTU Singapore) and Tan Tock Seng Hospital (TTSH), have developed a three-dimensional (3D) model of the human artery blood vessel wall. Called an “arterial wall-on-a-chip”, it will help researchers study atherosclerosis.
Cardiovascular diseases account for some 32% of deaths worldwide, claiming some 17.9 million lives annually. In Singapore, about 6,990 deaths or about one third of all deaths in 2020 were due to heart disease or stroke.
Using the 3D model, the researchers discovered new knowledge about the early stages of atherosclerosis: as oxidative stress increases, an increase of inflammation happens together with a build-up of plaque.
The team also observed that Vitamin D and a common diabetes medication, metformin, helped to prevent certain key processes leading to the plaque formation. This suggests that their 3D model can be potentially used to screen and test new drug molecules that can treat or prevent atherosclerosis.
Carotid artery surgery and stenting have comparable long-term effects on fatal or disabling stroke in asymptomatic patients with severe carotid artery stenosis. That is the finding of late-breaking ACST-2 data presented in a Hot Line session at the European Society of Cardiology’s 2021 congress (ESC 2021; 27–30 August, virtual) and published simultaneously in The Lancet.
Patients with severe carotid artery stenosis are at elevated risk of stroke and both carotid artery stenting (CAS) and carotid endarterectomy (CEA) can restore patency and reduce the long-term risk of stroke. Nationwide registry data from Germany have shown among asymptomatic patients, CAS and CEA are both associated with an approximately 1% risk of disabling stroke or death. Comparative data are lacking on the long-term protective effects of the two procedures.
ACST-2 was the largest trial to compare the long-term effect of CAS versus CEA on stroke in asymptomatic patients with a severely narrowed carotid artery that had not yet caused a stroke. The trial enrolled patients with severe carotid artery narrowing (60% or more reduction in diameter on ultrasound) found by chance, but with no recent stroke or other neurological symptoms. Participants were thought by their doctor to need CAS or CEA but both doctor and patient were substantially uncertain about which procedure was preferable.
A total of 3,625 patients were enrolled from 130 centres in 33 countries. Participants were randomly allocated 1:1 to CAS or CEA and followed up for an average of five years. The main outcomes were: 1) procedural risks (morbidity and mortality within one month after the procedure); and, most importantly, 2) non-procedural stroke, subdivided by severity.
Regarding procedural risks, 1% of patients in both groups had a disabling stroke or died within 30 days (15 allocated to CAS and 18 to CEA) and 2% had a non-disabling procedural stroke (48 allocated to CAS and 29 to CEA).
The main outcome was five-year non-procedural stroke; fatal or disabling stroke occurred in 2.5% of patients in each group, for a rate ratio (RR) of CAS versus CEA of 0.98 (95% confidence interval [CI] 0.64–1.48; p=0.91), and any non-procedural stroke occurred in 5.3% of the CAS group versus 4.5% of the CEA group (RR 1.16; 95% CI 0.86–1.57; p=0.33). A meta-analysis of this and all other major trials of CAS versus CEA yielded a similarly non-significant result for any stroke (RR 1.11; 95% CI 0.91–1.32; p=0.21).
Principal investigator Alison Halliday (University of Oxford, Oxford, UK) said: “We have shown that, for patients with a severely narrowed carotid artery, stenting and surgery have similar effects on the chances of having a disabling or fatal stroke. The risk from each procedure is about 1%. After that, however, the annual risk over the next five or more years is halved, from 1% down to 0.5% per year.”
Recently released clinical data from the NAVABLATE study has shown that microwave ablation used bronchoscopically—with the Emprint Ablation Catheter Kit with Thermosphere Technology (Medtronic) in conjunction with the firm’s electromagnetic navigation bronchoscopy system—is an option for primary and oligometastatic malignant lung nodules in patients who decline or are not candidates for both surgery and stereotactic body radiation therapy (SBRT).
highlighted the safety and performance of microwave ablation used bronchoscopically with the Emprint Ablation Catheter Kit with Thermosphere Technology (Medtronic) in conjunction with the firm’s electromagnetic navigation bronchoscopy system.
The findings were released at a late-breaking presentation at the European Respiratory Society International Congress (September 5, 2021; virtual).
Kelvin Lau, a consultant thoracic surgeon at St. Bartholomew’s Hospital (London, UK) and a principal investigator for the NAVABLATE study, said: “Patients with malignant lesions in the lung often have limited therapy options due to lesion locations, comorbidities, and treatment side effects.
“The results from the NAVABLATE study explore the potential benefit of a more individualised treatment for patients and offer a new option for surgeons and physicians to provide a minimally invasive, localised treatment of malignant lesions in the lung.”
NAVABLATE is a prospective, multi-centre study that enrolled 30 subjects in the UK and Hong Kong to characterise the safety and performance of the CE Marked Emprint Ablation Catheter Kit. All patients underwent a bronchoscopic ablation procedure using the Emprint Ablation Catheter Kit and were followed for one-month post procedure.
Ablation using the Emprint Ablation Catheter Kit achieved 100% technical success in all 30 subjects immediately post-procedure. One-month imaging showed ‘satisfactory’ ablation of the nodule in 100% of subjects.
The composite rate of adverse events related to the Emprint Ablation Catheter Kit was 3.3% (one subject with mild haemoptysis). There were no deaths or pneumothoraces.
Emily Elswick, vice president and general manager of lung health and visualisation at Medtronic, added: “Despite advances in treatment that can extend survival, the challenges of long-term management of tumours in the lung have been a significant barrier to improving outcomes, quality of life, and extended time with loved ones.
“Medtronic continues to take a broad transformative approach to the care continuum for the treatment of lung disease to improve diagnostics, optimise therapy and accelerate recovery.”
The Emprint Ablation Catheter Kit received Breakthrough Device Designation status from the US Food and Drug Administration (FDA) in April 2021. This device is not approved or cleared by FDA and is not available for sale in the US.
Medtronic say they will continue to study the safety and efficacy of the Emprint ablation catheter kit under an upcoming FDA investigational device exemption (IDE) study, with the intent to submit for device approval or clearance at a future date.
Medtronic has announced the European launch of the 200mm and 250mm IN.PACT Admiral drug-coated balloons (DCBs) following CE mark approval. The product is intended to treat long complex femoropopliteal lesions efficiently in patients with peripheral arterial disease (PAD). The 200mm and 250mm IN.PACT Admiral DCB enables physicians to treat longer lesions using a single DCB instead of multiple DCBs.
Thomas Zeller, director of the Department of Angiology at Universitaets-Herzzentrum, Freiburg-Bad Krozingen, Germany, performed the first case using the new sizes of the IN.PACT Admiral DCB in Europe. He stated, “Patients with SFA [superficial femoral artery] disease often present with longer and more complex lesions as time goes on, which makes it challenging to effectively treat the entire segment. We know the IN.PACT Admiral DCB is effective in providing durable results, and now with the longer sizes, it is a more efficient treatment option for these difficult to treat lesions. Using the new sizes of the IN.PACT Admiral DCB could potentially lead to saving both time and money by using one balloon instead of multiple balloons.”
About the IN.PACT Admiral DCB
The IN.PACT Admiral DCB is a clinically established, primary endovascular therapy, which has been shown to provided durable, consistent and safe outcomes across multiple clinical trials, as well as across complex patient and lesion types. With more than 3,500 patients enrolled in 21 clinical studies and 600,000+ patients treated worldwide, the IN.PACT Admiral DCB is the preferred DCB for treatment of femoropopliteal disease allowing reduced interventions and preserving future treatment options. A DCB’s primary mode of action is physical dilatation of the vessel lumen by percutaneous transluminal angioplasty (PTA), followed by the delivery of paclitaxel. The unique formulation of IN.PACT Admiral DCB with its drug dose, excipient and crystallinity, provides sustained drug residence in the tissue, leading to an effective and durable outcome.
The 200mm and 250mm IN.PACT Admiral DCBs received FDA approval in May of 2018.
R3 Vascular has reported the successful initiation of its first-in-human clinical study evaluating the technical and clinical performance of the R3 Vascular Magnitude bioresorbable sirolimus-eluting scaffold (BRS) in patients suffering of chronic limb-threatening ischaemia (CLTI) due to occlusive below-the-knee (BTK) arterial disease.
A press release details that the R3 Vascular platform incorporates an innovative scaffold design and bioresorbable polymer technology resulting in biomechanical performance comparable to metallic stents. At a 98-micron strut thickness across all its usable range of diameters, the Magnitude BRS device is the thinnest BRS ever tested in this clinical setting, the release adds.
“Given the dire and unmet clinical need of patients presenting with CLTI undergoing BTK revascularisation, we are extremely pleased by the rapid progression of our programme,” said R3 Vascular CEO Kamal Ramzipoor. “Our Magnitude BRS is well-positioned to improve the clinical outcomes of these patients by providing temporary mechanical support and sustained drug delivery while reducing the well-established complications associated with permanent implants.”
“In this early clinical experience, we successfully tested the deliverability and mechanical performance of the Magnitude BRS. Post-procedural angiographic and duplex ultrasound data confirm the mechanical properties and ‘stent-like’ results of the Magnitude BRS device in presence of a high-disease burden. We are looking forward to expanding the patient population cohort and following the clinical results over time,” said Marianne Brodman (Medical University of Graz, Graz, Austria).
Juan F Granada, a strategic advisor to R3 Vascular, added: “In BTK intervention, the prevention of vessel recoil following balloon dilatation is key to prevent negative remodelling and maintain vessel patency over time. BRS offer the best of both worlds by providing vessel support while it is needed and allowing the opportunity for future reinterventions, which is important in this type of patient. The successful validation of this technology may finally offer an effective and durable way to treat patients with this complex medical condition.”
The CardioVascular Coalition (CVC), a coalition of physicians, care providers, advocates, and manufacturers working to improve awareness and prevention of peripheral arterial disease (PAD), has called on Congress and the Centers for Medicare & Medicaid Services (CMS) to address severe proposed cuts to specialty provider services in order to help increase access to care.
CMS recently proposed cutting payments for revascularisation services by approximately 23% in the proposed Physician Fee Schedule (PFS) Rule for CY2022. The proposed cuts, which are being driven by a provision that purports to update clinical labour data, would have a severe impact on cardiology, vascular surgery, venous, radiation oncology, and radiology practices. Though outpatient health services—including revascularisation—are cost-effective and convenient for patients, the proposed cuts would have profoundly negative effects on patient access and health equity. If the proposed cuts are finalised as currently proposed, Medicare beneficiaries will face more serious risks of limb loss.
“As we recognise PAD Awareness Month and the major impact that PAD has on Americans—particularly people of colour—I am deeply troubled by CMS’ flawed proposal to cut vital services like revascularisation by as much as 23%,” said CVC Board member Jeff Carr (Tyler Cardiac and Endovascular Center, Tyler, USA) . “At a time when America is suffering a PAD and amputation crisis on top of the COVID-19 pandemic, it is absolutely critical to ensure patients’ continued access to the services that are proven to help prevent amputations and slow disease progression. Unless Congress and CMS act to address these proposed cuts, I fear that it will be harder for patients to access necessary care, resulting in even more amputations, worse outcomes, and even greater healthcare disparities.”
According to estimates, PAD affects nearly 20 million Americans and is responsible for 80% of the 200,000 non-traumatic limb amputations that take place in the USA each year. These non-traumatic amputations often occur without any diagnostic testing, meaning PAD patients are losing limbs before they receive testing to determine if limb-saving interventions are an option.
PAD is exacerbated by conditions like diabetes, chronic hypertension, and renal disease, which are most prevalent in minority populations. Access to revascularisation therapies is especially vital to the African American, Hispanic, and Native American populations who are two to four times more likely to undergo a limb amputation due to PAD because of the increased prevalence of diabetes, obesity, and other risk factors.
“To address the issues of patient access and systemic health inequity in our country, CMS must reverse course and not finalise the clinical labour policy in the 2022 PFS Proposed Rule,” continued Carr. “Further, CMS should work closely with Congress to fundamentally reform the Physician Fee Schedule so that any future unjustified cuts to specialty provider services can be avoided.”
To learn more about PAD and PAD Awareness Month, click here.
Xact Robotics, the developer of the Xact Ace robotic system, recently announced it has successfully completed patient enrolment in the first US study evaluating Xact Ace for use in percutaneous lung procedures including biopsies to confirm the presence of cancer. The Xact Ace robotic system is the world’s first and only “hands-free” robotic system that can help improve targeting accuracy, efficiency, and consistency in computed tomography (CT)-guided percutaneous procedures including ablations, biopsies and targeted drug delivery.
Lung cancer is the second most common form of cancer around the world and millions of percutaneous procedures are performed in the lung each year. When using traditional manual methods to reach areas of interest in the lung, clinicians will sometimes suggest that patients wait until the lesion becomes larger and easier to access. Use of a robotic system may help access areas in the lung earlier, potentially supporting earlier diagnosis and treatment.
“Even among the most skilled radiologists, efforts to reach small areas of interest in the body, especially in the lungs, can be challenging,” said Sebastian Flacke (Lahey Hospital & Medical Center [LHMC], Burlington, USA). “With the completion of this study, we can more precisely assess the ability of the Xact Ace robotic system to help us reach target areas in the lung in a single insertion with a very high level of accuracy.”
During procedures with the Xact Ace robotic system a physician plans the route of an instrument and the robot then inserts and steers the instrument directly to the area of interest, typically reaching the target on the first insertion. In many cases during percutaneous procedures, the area of interest moves during instrument insertion, making it necessary to reinsert an instrument to reach the target. With the Xact Ace robotic system, the advanced algorithm and steering mechanisms can reformulate the insertion pathway to continually remain on route to reach a specific target, even if it moves during the procedure, maximising the rate of success on the first insertion.
The pilot trial primarily looked to evaluate safety of the Xact Ace robotic system when used in percutaneous procedures in the lung. Secondary performance evaluations included the proportion of procedures in which the instrument reached the predefined target based on the physician’s determination and CT imaging confirmation. The study also looked at system accuracy, which was defined as the measured distance from the tip of the instrument to the target location at the end of the insertion.
“The use of the Xact Ace robotic system to help radiologists reach small areas of interest in the lung is another major milestone showing the potential benefits of this technology for patients and clinicians,” said Chen Levin, CEO, Xact Robotics. “The outstanding work of the radiologists at LHMC and Sarasota Interventional Radiology [Sarasota, USA] significantly expands our understanding of the potential of our technology to set the new standard in percutaneous procedures in the lung with the potential to reduce risks for patients while supporting earlier diagnosis and treatment.”
As we start to emerge from the strictures imposed by the COVID-19 pandemic, it is timely to reflect on the delivery of education and training to interventional radiologists (IRs) around the world, especially those living in countries with limited access to the educational opportunities that are generally available to interventionists in the more developed world, writes Robert Morgan (St George’s University Hospitals NHS Foundation Trust, London, UK).
Before the COVID-19 pandemic affected populations worldwide, several major international interventional radiology societies (Cardiovascular and Interventional Radiological Society of Europe [CIRSE], Society of Interventional Radiology [SIR] and Asia Pacific Society of Cardiovascular and Interventional Radiology [APSCVIR]) had spearheaded programmes to deliver education and training in several countries around the world. Some medical device companies had also begun their own initiatives sponsoring senior IRs to visit countries to participate in the training of the local IRs. The concept of training IRs travelling to less well-developed countries and systems—i.e. outreach training—had been going on for some years from the start of this millennium. In the last decade, we saw a significant increase in this practice with ever-larger delegations of training IRs visiting a wider number of countries.
These outreach training programmes usually offered exposure to hands-on device training, and in some cases procedural training in addition to more formal teaching through lectures and small group tutorials. Where possible, the local outreach training experience was designed to complement standard training delivered by local senior IRs and online education and attendance at live educational events, where feasible, depending on the financial and political constraints of each country.
Although quality education can be delivered remotely, in-person training such as can be provided by outreach training enables valuable interactions and discussions between training faculty and trainees that are difficult to replicate online. My recent experiences as an outreach training faculty in Myanmar serve to illustrate the benefits of in- person outreach training.
In both January 2019 and 2020, I travelled to Myanmar as a member of an intersociety collaborative endeavour to provide training and education in two IR outreach workshops. The workshops were organised by senior members of the Asia Pacific Society of Interventional Radiology (APSCVIR) with participating members from CIRSE and the SIR in collaboration with senior Myanmar IRs.
In each programme, workshops were held in Yangon and in Mandalay General Hospitals. Both hospitals are of moderately large size with over 500 beds each. Each of the radiology departments are well equipped with two or more computed tomography (CT) scanners, at least one magnetic resonance imaging (MRI) scanner, one angiographic machine and general radiographic equipment.
The vast majority of the interventional radiology staff at these hospitals had never had the opportunity to attend a major congress, such as APSCVIR, CIRSE or SIR. All visiting international faculty members were impressed by the enthusiasm of the local staff and trainees to learn about interventional radiology. It was very evident that they were highly appreciative of receiving training from the visiting faculty.
A comprehensive scientific programme was delivered at both workshops covering a wide range of interventional radiology procedures including transarterial chemoembolization (TACE), radiofrequency ablation (RFA) of liver tumours, uterine fibroid embolization (UFE), haemodialysis interventions, central venous access, lower limb arterial interventions, urological interventions, hepatobiliary interventions and abscess drainage. The workshop programme involved lectures, small group teaching and hands-on device training. In addition, there were several live cases performed by the faculty, including myself. Live case topics included TACE, RFA, lower limb arterial angioplasty and stenting, and haemodialysis access angioplasty and stenting.
One less obvious benefit of in-person training was that local IRs strongly encouraged clinicians from other specialties to attend the workshop, particularly specific lectures and live cases that were relevant to their practice. This meant that during each lecture or tutorial, aspects of procedures were highlighted to increase the attractiveness of interventional radiology to these referring clinicians with specific emphasis put on the favourable comparison of interventional radiology procedures with the competing alternative treatments. The desired result of such an interaction would be to increase the number of referrals to interventional radiology by these local clinicians, which in my opinion, was an effective method—and one that is less translatable to an online educational format.
In summary, the main benefits of outreach training included: enabling local IRs without the financial resources to attend in-person congresses to receive a programme of tailored education to their specific requirements and surroundings; and raising the awareness of the potential of interventional radiology among other clinical specialties, which may result in increased referrals of patients for these minimally invasive, typically outpatient procedures.
Inevitably, as a result of the effect of the COVID-19 pandemic worldwide and the severe restrictions on international travel, these outreach training programmes have come to a halt. In a similar manner to international congresses, which have currently moved almost exclusively to an online/virtual format, some societies have endeavoured to provide outreach training online through webinars and live discussion forums. This method of education has similar drawbacks for the delivery of outreach educational workshops as it does for international meetings. These are relatively obvious but are worth stating nevertheless: reduced impact of online lectures compared with live lectures; a lack of interpersonal interactions for educational and networking purposes; reduced opportunity for small group discussions; and the complete absence of hands-on device or procedural training. Finally, a specific disadvantage of online teaching for less well-developed countries is the dependence on the local information technology (IT) structures and ability of the local IRs and trainees to access the internet adequately for online teaching, which may be demanding in terms of the bandwidth required.
The experiences of the past 18 months have reminded us that the internet is an effective method to deliver education and training. However, the majority of doctors, both trainees and trainers, are firmly of the opinion that virtual methods do not, and must not, completely replace in-person educational methods.
However, the pandemic is a worldwide phenomenon. Although vaccination programmes in many countries, particularly in Europe and North America are well advanced, this is not the case in Asia, South America or Africa where a significant proportion of outreach programmes take place. It is likely that international congresses will return as live educational events in 2022, but they will be restricted by COVID-19 testing and impacted by the country of origin of delegates. Unfortunately, it may be longer before IRs are able to travel to countries with lower vaccination rates to deliver outreach training. However, this is not to say that this form of training must be abandoned or forgotten. International societies such as CIRSE, SIR, and APSCVIR must continue to commit to the concept of outreach training and to make plans for the day when this valuable training format once again becomes feasible to deliver.
In summary, international societies have the ability and an obligation to deliver local education and training to IRs in lower- and middle-income countries. Local in-person outreach training has significant benefits that cannot be provided by the virtual format. Although a return to outreach training workshops may not be feasible for a year or more, this important method of training must not be forgotten and interventional radiology societies must continue to devise schedules for outreach training as soon as this becomes possible again.
Robert Morgan is a consultant and reader in interventional and diagnostic radiology. He is deputy editor-in-chief CVIR Endovascular and a past president of CIRSE. He has reported no disclosures relevant to this article.
From a cost-effectiveness standpoint, primary stenting of the superficial femoral artery (SFA) for the treatment of intermittent claudication can, in many countries, be used as an adjunct to exercise training advice. This is the main conclusion of Henrik Djerf (Sahlgrenska University Hospital, Gothenburg, Sweden) and colleagues, reporting two-year results of a randomised, multicentre trial online in the European Journal of Vascular and Endovascular Surgery (EJVES).
Djerf et al consider what their paper add to the literature: “This examination of the cost effectiveness within a randomised controlled trial for endovascular treatment of the SFA in patients with intermittent claudication adds longer follow-up data than previous studies.”
The authors write that invasive treatment of intermittent claudication is commonly performed, despite limited evidence of its cost effectiveness. In addition, they note that endovascular treatment is performed frequently due to the fact that symptoms of intermittent claudication are mainly caused by atherosclerotic lesions in the SFA. The aim of the present study, Djerf and colleagues relay, was to investigate the cost effectiveness of endovascular treatment versus its non-invasive counterpart.
The researchers randomised 100 patients with intermittent claudication due to lesions in the SFA to treatment with primary stenting, best medical treatment and exercise advice, or to best medical therapy and exercise advice alone (the control group), noting that patients were recruited from seven hospitals in Sweden. For their present analysis of cost effectiveness after two years, the investigators analysed 84 patients with data on quality-adjusted life years (QALYs).
Writing in EJVES, Djerf et al report that the mean cost per patient was €11,060 in the stent group and €4,787 in the control group, resulting in a difference of €6,273 per patient between the groups. In addition, they found that the difference in mean QALYs between the groups was 0.26, in favour of the stent group, which resulted in an incremental cost-effectiveness ratio (ICER) of €23,785 per QALY.
The authors conclude that the costs associated with primary stenting in the SFA for the treatment of intermittent claudication were higher than for exercise advice and best medical therapy alone. They add that, with concurrent improvement in health-related quality of life, primary stenting was a cost-effective treatment option according to the Swedish national guidelines (ICER <€50,000–70,000) and approaching the UK’s National Institute for Health and Care Excellent threshold for willingness to pay (ICER <£20,000–30,000).
In many countries, primary stenting of the SFA is cost-effective and therefore can be used as an adjunct to exercise training advice, Djerf and colleagues summarise. However, they stress that successful implementation of structured exercise programmes and longer follow-up may alter these findings in the future.
Hancock Jaffe Laboratories has announced that promising two-year post-VenoValve implantation data are being presented today at the Society for Vascular Surgery’s Vascular Annual Meeting (SVS VAM 2021; 18–21 August, San Diego, USA and online) by Jorge Ulloa (Fundacion Santa Fe-Universidad de los Andes, Bogota, Colombia), who was the principal investigator for the company’s first-in-human VenoValve trial.
Key highlights from Ulloa’s presentation indicate that:
The data reported are for a group of eight patients who participated in the VenoValve first-in-human study and who agreed to participate in a one-year post-study follow-up. Three additional first-in-human patients elected to not participate in the one-year post-study follow-up, but reported no negative VenoValve-related events during the one-year follow-up period. The average post-VenoValve implantation time for this cohort of patients is two years, and the comparative results are based on pre-VenoValve levels compared to the patients’ most recent office visit.
Marc Glickman, Hancock Jaffe’s senior vice president and chief medical officer stated, “These data are exactly the results that we were looking for as we begin our VenoValve SAVVE [Surgical anti-reflux venous valve endoprosthesis] pivotal trial. Our patients are continuing to benefit from the VenoValve, with no safety issues and no ulcer recurrences. Chronic venous insufficiency [CVI] in the deep venous system has frustrated patients and physicians for decades and our primary investigators for the SAVVE study are as excited and enthusiastic as we are about the upcoming study.”
The SAVVE US pivotal trial for the VenoValve will include 75 patients at up to 20 sites. The primary endpoints for the SAVVE trial will be the same as for the first-in-human trial: the primary safety endpoint is the occurrence of a major adverse event (MAE) in less than 10% of patients at 30 days post-VenoValve implantation, and the primary effectiveness endpoint is improvement of reflux equal to or greater than 30% at six months following VenoValve surgery. MAEs are defined as the composite of all-cause mortality, deep wound infection, major bleeding, ipsilateral deep vein thrombosis (DVT), or pulmonary embolism. Improvement of VCSS and visual analogue scale (VAS) scores are also included in the SAVVE study as secondary endpoints.
As recently announced, the US Food and Drug Administration (FDA) has granted Breakthrough Device designation status to the VenoValve.
Joseph V Lombardi (Cooper University Hospital, Camden, USA) reported long-term outcomes favouring the continued safety and effectiveness of a composite device (proximal covered stent graft plus distal bare stent) deployed for the endovascular repair of acute, type B aortic dissection (TBAD) complicated by aortic rupture and/or malperfusion.
“STABLE II results place freedom from all-cause mortality at 80.3% at one year, and 68.9% at five years [with the use of the Zenith dissection endovascular system from Cook Medical]. Further, there were two procedure-related deaths, and the freedom from dissection-related mortality remained 97.1% at one year through five years,” he told delegates of the Society for Vascular Surgery’s Vascular Annual Meeting (SVS VAM 2021; 18–21 August, San Diego, USA and online).
The Zenith endovascular system includes a proximal covered stent graft to cover the primary entry tear plus a distal bare metal stent, built on a nitinol Z-stent platform, for true lumen support. The bare metal component provides expansible support along the length of the dissected aorta without blocking critical branch vessels to provide a scaffolding to aid adjunctive interventions and facilitate favourable aortic remodelling of the entire dissected aorta.
Outlining the adverse events seen in the study, Lombardi commented that notable adverse events at one year were one instance of aortic rupture, one instance of conversion to open repair and two instances of stroke—there were no instances of paraplegia or paraparesis. “Freedom from secondary intervention was 88.2% in one year, and 70.7% at five years and secondary interventions were used to treat a number of presentations, including distal aortic growth. Aortic growth distal to the stent graft suggests the need for continuous monitoring,” he added.
Study details
STABLE II is a prospective, single-arm, multicentre study that enrolled 73 patients between August 2012 and January 2015 at institutions in the USA and Japan. The mean age of patients was 60.7 years with nearly 66% being male with acute TBAD complicated by malperfusion (78.1%), rupture (27.4%). Patients were treated with either a composite device (proximal covered stent-graft plus distal bare stent, 79.5%) or the proximal stent graft alone (no distal bare stent, 20.5%). Dissections were more extensive in patients receiving the composite device (408.9±121.3mm long, with 47.4% of dissections extending into the iliac arteries) compared with those who did not receive the distal bare stent (315.9±100.1mm long, with 6.7% of dissections extending into the iliac arteries). Five-year follow-up was available for 86.1% of eligible patients.
False lumen thrombosis and the composite device
The researchers also communicated that proximal dissection events were reported in seven patients, including four patients with retrograde progression of dissection and three patients with a new tear/type A dissection. Importantly, Lombardi called out the progressive false lumen thrombosis seen within the stent graft region and the dissected stent region. “Complete false lumen thrombosis rate increased (75% of patients at five-year vs. 51.4% post-procedure), with a higher complete thrombosis rate at five years in patients who received the composite device (81%) compared with the rate in patients who did not receive the distal bare stent (57.1%).
“There were no incidences of device fracture or infolding reported and these five-year data suggest a positive influence of composite device use on false lumen thrombosis,” he summarised.
Bare metal stent necessities
To a question posed on how the decision was made to deploy or not deploy the bare metal stent, Lombardi clarified: “We left that up to our investigators to determine the need for additional stenting using the bare metal stent. A lot of the dissections were very focal on the thoracic aorta and some thought that an additional dissection stent was not needed to support normal aorta distally. So, this was a primary reason why dissection stents were not deployed, but the fact that we did not have dissection stents in a small cohort of patients gave us a nice control group to look at afterwards.
When pressed on recommendations regarding when to use the dissection stent and tips on how far to place it, especially when the dissection was particularly distal, Lombardi explained: “The data is very supportive of the distal aortic remodelling using the dissection stent. And oftentimes, as you saw in the data, secondary interventions are not infrequent, and we will have to go back and reintervene for distal aortic growth to remedy ongoing expansion. The use of the dissection stent in that situation for me and for a lot of our colleagues has been very, very helpful in mitigating a continued false lumen flow. So, I am a believer in using it in all settings, as long as I’m putting it across dissected aorta.”
Poverty and Black race were associated with higher rates of lower leg amputation among people with peripheral arterial disease (PAD) who live in metropolitan areas, according to new research published today in a special issue of the Journal of the American Heart Association (JAHA), an open access journal of the American Heart Association (AHA).
The analysis on PAD-related amputations is one of 16 new research studies highlighting health disparities among people from diverse population groups and published in the special spotlight issue of JAHA.
JAHA senior associate editor Pamela Peterson (University of Colorado Denver, Denver, USA) and associate editor Sula Mazimba (University of Virginia Health System, Charlottesville, USA) note that while management of cardiovascular disease has reduced death rates over time, there are still “striking disparities” in the USA that have widened along racial, ethnic, socioeconomic and geographical lines.
“We hope that this issue of JAHA will reinforce the recent America Heart Association’s presidential advisory statement urging all stakeholders to a committed path towards transforming the conditions of historically marginalised communities, improving the quality of housing and neighbourhood environments of these populations, advocating for policies that eliminate inequities in access to economic opportunities, quality education and health care, and enhancing allyship among racial and ethnic groups,” they wrote.
The study, “Geographic and socioeconomic disparities in major lower extremity amputation rates in metropolitan areas”, by Alexander Fanaroff (University of Pennsylvania, Philadelphia, USA) et al, is an analysis of national Medicare claims data to determine ZIP code-level variation in rates of amputation among Medicare beneficiaries.
“Limb amputation can be delayed and or prevented by timely and aggressive treatment. However, lack of access to specialised care may delay PAD diagnosis and limit efforts to save the limbs if it has progressed to the advanced disease stage,” explained Fanaroff.
Fanaroff and colleagues found that ZIP codes with a higher proportion of Black residents had higher amputation rates than ZIP codes with lower proportions of Black residents. In addition, ZIP codes with lower median household income, more residents eligible for Medicaid and worse scores on the Distressed Communities Index scale (a composite marker of socioeconomic status), had higher amputation rates compared to ZIP codes with higher socioeconomic status, even after adjusting for clinical and demographic characteristics.
“Though amputation rates are generally higher in rural areas, this finding shows that the association between lower socioeconomic status, race and amputation rate extends to major metropolitan areas as well as rural regions,” Fanaroff said. “We found that closer proximity to specialised PAD care within metropolitan areas does not ensure access to high quality care. Strategies targeted to communities with high amputation rates are also needed in urban areas to reduce these disparities.”
A recent AHA scientific statement noted sex and ethnic disparities exist in the diagnosis and treatment of the most severe form of PAD, chronic limb-threatening ischaemia (CLTI).
Another article in the spotlight issue is a retrospective study of more than 425,000 women (ages 12–49; 59% non-Hispanic white women, 31% non-Hispanic Black women and 10% Hispanic women) in South Carolina who gave birth from 2004–2016 and were followed through 2017. The study, “Incident heart failure within the first and fifth year of delivery among women with hypertensive disorders of pregnancy and pre-pregnancy hypertension in a diverse population”, by Angela M Malek (Medical University of South Carolina, Charleston, USA) et al, found racial and ethnic differences in heart failure rates among women who experience hypertensive disorders during pregnancy as well as among women who experience hypertensive disorders both before and during pregnancy.
Non-Hispanic Black women who had hypertensive disorders of pregnancy with and without pre-pregnancy hypertension had a higher incident heart failure risk within five years of giving birth compared to non-Hispanic white women without hypertension (before or during pregnancy). Among women who had pre-eclampsia or other hypertensive disorders during pregnancy, heart failure event rates were substantially higher in non-Hispanic Black women than non-Hispanic white women: 2.28 compared to 0.96 per 1,000 person-years, respectively. In women who had hypertensive disorders of pregnancy with pre-pregnancy hypertension, heart failure event rates were also substantially higher among non-Hispanic Black women than non-Hispanic white women: 4.3 compared to 1.22 per 1,000 person-years, respectively.
“These racial and ethnic differences are important since we already know non-Hispanic Black women experience higher pregnancy-related deaths than non-Hispanic white women,” said Malek. “Clinical and public health prevention efforts are needed to reduce complications and death rates in women who have hypertensive disorders before or during pregnancy as they are at increased risk of heart failure or dying from heart failure within five years.”
Additional research is needed to further examine racial/ethnic differences in maternal incident heart failure after delivery. The clinical and public health implications of this research could inform changes to clinical practice to reduce modifiable cardiovascular risk factors and screening for adverse maternal outcomes in women identified as high risk, according to the study.
Other research featured in the JAHA spotlight issue on health disparities can be accessed in full here.
Shape Memory Medical has announced the initiation of AAA-SHAPE Netherlands, the company’s prospective, multicentre early feasibility study of the Impede-FX RapidFill device when used for abdominal aortic aneurysm (AAA) sac management during elective endovascular aneurysm repair (EVAR). The Dutch study’s first procedure was performed by Michel Reijnen, vascular surgeon at Rijnstate Hospital in Arnhem, The Netherlands.
Ted Ruppel, president and chief executive officer of Shape Memory Medical said, “We would like to congratulate Michel Reijnen and the clinical study team at Rijnstate Hospital for a successful first AAA-SHAPE case in The Netherlands. The addition of Dutch sites to the AAA-SHAPE programme accelerates our ability to evaluate Impede-FX RapidFill and its potential to improve sac regression in AAA patients following EVAR.” The study will enrol up to 15 patients across three centres in The Netherlands, contributing to the AAA-SHAPE safety study, which is also currently enrolling up to 15 patients in Auckland, New Zealand.
The Impede-FX RapidFill device contains five Impede-FX, 12mm embolisation plugs preloaded into a single delivery introducer for fast and efficient delivery of the embolic material. This high-volume platform incorporates the novel Shape Memory Polymer, a porous, embolic scaffold that is crimped for catheter delivery and self-expands upon contact with blood for rapid conversion to organised thrombus. Preclinical and clinical studies have shown that Shape Memory Polymer offers effective and predictable space filling, stable clot formation for sac embolisation, and progressive healing as the material biodegrades.
“We are excited to contribute to AAA-SHAPE,” said Reijnen, principal investigator for AAA-SHAPE Netherlands. “Patients who develop aneurysm sac shrinkage following EVAR have better outcomes than patients with a stable or growing aneurysm sac. We look forward to learning how the use of Impede-FX RapidFill in combination with EVAR influences sac behaviour,” continued Reijnen.
“We are very pleased to be working together with colleagues from the Netherlands to add to our growing experience with AAA-SHAPE,” said Andrew Holden, interventional radiologist at Auckland City Hospital in Auckland, New Zealand. “Our preliminary experience with AAA-SHAPE has been very encouraging, and the first few patients have shown a reduction in AAA sac diameter at early follow-up,” continued Holden.
The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the US Food and Drug Administration (FDA) has approved an expanded peripheral arterial disease (PAD) indication for the Xarelto (rivaroxaban) vascular dose (2.5mg twice daily plus aspirin 100mg once daily) to include patients following recent lower-extremity revascularisation (LER) due to symptomatic PAD.
The approval is based on data from the Phase III VOYAGER PAD study. According to a press release, Xarelto is now the first and only therapy indicated to help reduce the risks of major cardiovascular events in patients with coronary artery disease (CAD) and major thrombotic vascular events, such as myocardial infarction, ischaemic stroke, acute limb ischaemia, and major amputation of a vascular aetiology, in patients with PAD, including patients who have recently undergone LER due to symptomatic PAD.
“For more than 20 years, many physicians have used dual antiplatelet therapy after lower extremity revascularisation due to symptomatic PAD with limited data to support efficacy and safety in this setting. Now, the VOYAGER PAD and COMPASS clinical studies have demonstrated the utility of dual pathway inhibition in targeting both platelets and thrombin in patients with PAD. These data provide a new mechanism of treatment using an evidence-based strategy for this vulnerable population,” said Marc P Bonaca (University of Colorado Anschutz Medical Campus, Aurora, USA). “This FDA approval of rivaroxaban plus aspirin is a major advancement for PAD management and sets the stage to evolve the current standard of care for patients with PAD.”
Xarelto now has nine indications in the USA. Today’s approval is based on the Phase III VOYAGER PAD trial, which demonstrated the Xarelto vascular dose (2.5mg twice daily plus aspirin 100mg once daily) reduced the risk of major adverse limb and cardiovascular events by 15% in patients with symptomatic PAD post-LER compared to aspirin alone. The VOYAGER PAD trial saw no significant difference in Thrombolysis in Myocardial Infarction (TIMI) major bleeding between Xarelto with aspirin compared to aspirin alone.
The results from the VOYAGER PAD study complement findings from the landmark Phase III COMPASS trial, which also examined the dual pathway approach of Xarelto with aspirin in CAD and/or PAD patients and further supports this FDA label extension in PAD patients. Data from the Phase III COMPASS trial resulted in FDA approval in 2018 to reduce the risk of major cardiovascular events, such as heart attack, stroke and cardiovascular death in people with chronic PAD and CAD. While there were more major bleeds with the Xarelto vascular dose in COMPASS, there was no significant difference in rates of fatal bleeding, intracranial bleeding or symptomatic bleeding into a critical organ.
Argon Medical Devices has announced the commercial launch of Skater mini-loop drainage catheters in the USA and the European Union.
The Skater mini-loop is a drainage catheter placed through the skin using imaging guidance as a minimally invasive way to remove or drain an unwanted fluid collection. The device, an expansion of Argon’s Skater all-purpose and nephrostomy drainage portfolio, uses a 40% smaller loop to help secure the catheter and drain fluid from smaller cavities.
“The Skater mini-loop drainage catheter is easily inserted and forms a tight loop formation to prevent drainage occlusion. Unlike other drainage catheters in the class, Skater mini-loop is compatible with alcohol and has durability to resist kinking,” says Sujoy Menon (Newark Beth Israel Medical Centre, Newark, USA), one of the first physicians in the USA to use the device.
Argon Medical Devices has introduced several new devices in the biopsy, drainage, and vascular therapy segments in 2020 and is planning on expanding their product list aimed at facilitating interventional vascular and oncology procedures in 2021.
“We are excited to complete our Skater portfolio of drainage solutions and celebrate this next launch in our Year of Innovation [2021],” commented George A Leondis, president and CEO of Argon Medical Devices.
“A strategy of adding rivaroxaban 2.5mg twice daily to aspirin should be considered after lower extremity bypass regardless of conduit type,” concluded Nicholas Govsyeyev (University of Colorado, Aurora, USA) during the William J von Liebig Forum at the Society for Vascular Surgery’s Vascular Annual Meeting (SVS VAM 2021; 18–21 August, San Diego, USA and online). Govsyeyev was giving an update on the VOYAGER PAD trial, addressing the efficacy of rivaroxaban and aspirin in peripheral arterial disease (PAD) patients with venous and prosthetic surgical bypass conduits.
“The optimal antithrombotic therapy following infrainguinal bypass is not known,” Govsyeyev began. He noted that two major trials have examined the role of dual antiplatelet therapy (DAPT) and oral anticoagulation following infrainguinal bypass—CASPAR and DUTCH BOA. While both these trials had neutral results, the presenter detailed, there was significant heterogeneity by conduit type, with the CASPAR trial showing the potential benefit of DAPT in prosthetic conduits and the DUTCH BOA trial demonstrating the potential benefit of anticoagulation in venous conduits. Both trials, however, had a significant increase in major bleeding.
“The VOYAGER PAD trial provides a large, prospective database to further examine the optimal antithrombotic regimen following infrainguinal bypass,” Govsyeyev remarked. This trial randomised 6,554 patients with symptomatic PAD undergoing lower extremity revascularisation and receiving standard of care to rivaroxaban 2.5mg taken twice daily or placebo, with standard of care consisting of aspirin, clopidogrel use per the investigator’s discretion, and the encouragement of statin use.
Govsyeyev summarised the key findings: “The trial demonstrated a 15% reduction in the primary composite endpoint of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, and cardiovascular death; bleeding was increased, but overall incidence was low with rivaroxaban; there was no significant interaction for efficacy or safety on the basis or surgical or endovascular revascularisation; and surgical patients’ risk for primary endpoint events was reduced by 19% with rivaroxaban.”
The objectives of the current study, Govsyeyev explained, were to compare limb outcomes with venous versus prosthetic conduits in VOYAGER PAD patients who underwent bypass, and to evaluate whether the efficacy of rivaroxaban is consistent across conduit types.
In order to assess this goal, the researchers used a multivariate adjusted model to determine the risk of limb outcomes in patients with venous and prosthetic conduits, and Cox proportional hazards to assess for efficacy.
Govsyeyev detailed that a total of 1,448 (66%) patients underwent bypass in the VOYAGER trial. Breaking this down by conduit type, he noted that prosthetic use was slightly more frequent (773 patients; 54%) than venous use (646 patients; 46%).
In terms of baseline characteristics, the speaker communicated that the median age of the venous cohort was 65 (59–70) compared to 66 (61–72) in the prosthetic group, and that the number of female patients in the venous group was slightly lower than in the prosthetic group, at 17 and 22, respectively. Medical comorbidities were not different between the two groups, he added.
With regard to distribution by target artery, Govsyeyev stated that venous conduits were more likely to be used below the knee, whereas three-quarters of prosthetic conduits had an above-the-knee target artery.
Govsyeyev reported that, in the placebo group, the cumulative incidence of unplanned limb revascularisation at three years from randomisation was 29.6% in the prosthetic cohort (n=388) compared to 13.1% in the venous cohort (n=314), with a risk difference of 16.5%. Regarding acute limb ischaemia, the figures were 13.6% and 5.4%, respectively, with an 8.2% risk difference.
The presenter then outlined results related to the efficacy of rivaroxaban on the primary composite endpoint by conduit type. “Prosthetic patients were at higher risk for primary endpoint events, and this was reduced with rivaroxaban, with an absolute risk difference of 6.4%,” Govsyeyev revealed. Among the venous conduits, the data showed an absolute risk difference of 7.9% with rivaroxaban. Govsyeyev added that there was no significant interaction by conduit type and overall bleeding was quite low in the rivaroxaban and placebo groups.
Furthermore, the speaker informed the audience that there was consistent benefit of rivaroxaban on limb outcomes regardless of conduit type. He summarised the results: “Prosthetic conduits had a higher risk for limb outcomes; acute limb ischaemia was reduced in both venous and prosthetic conduits with rivaroxaban, with a particularly strong benefit among venous conduits with a greater than 50% reduction; major amputation was reduced in venous conduits but not in prosthetic; unplanned limb revascularisation was reduced in prosthetic but not in venous; and there was no significant interaction for any limb outcome by conduit type.”
Addressing the VAM audience, Govsyeyev concluded that a strategy of rivaroxaban 2.5mg twice daily reduces irreversible harm events and increases bleeding with a 6:1 benefit risk ratio, and that the magnitude of benefit appears robust in surgical patients. He added that prosthetic conduit patients are at a roughly three-fold risk of acute limb ischaemia and unplanned revascularisation relative to those receiving venous conduits, and that the benefit of rivaroxaban is consistent across conduit types with around a 2% absolute reduction in acute limb ischaemia and around a 6% reduction in primary outcome. Taking all these factors into account, Govsyeyev commented: “A strategy of adding rivaroxaban 2.5mg twice daily to aspirin should be considered after lower extremity bypass regardless of conduit type.”
Fist Assist Devices has announced that data associated with the p-FACT cohort, a subset of the recently completed, non-significant risk Fist Assist clinical trial (FACT trial) that focused on vein dilation in stage four patients with chronic renal failure, show clear evidence that the Fist Assist device dilates the perforator vein.
The p-FACT data derived from the FACT trial evaluated the use the FA-1 device developed by Fist Assist Devices, a novel, intermittent pneumatic compression device, to promote superficial vein dilation in patients with chronic kidney disease to enable creation of all types of arteriovenous fistulas (AVFs) and to ensure the safety of the device in this patient population.
“We are thrilled to announce the results of the p-FACT data. The statistically significant data, with a p value of <0.05, shows that the FA-1 device clearly dilates the perforator vein in stage four chronic renal failure patients” said Tej Singh, chief executive officer and founder of Fist Assist Devices.
“These are very important data as they not only show that the FA-1 device is safe, but also demonstrate that intermittent pneumatic pressure dilates superficial veins including, most importantly, the perforator vein needed for endoAVF success. Condition of the perforator vein is critical for endoAVF planning, and we can now show without a doubt that the Fist Assist FA-1 device can dilate that clinically important vein and have a key role in endoAVF consideration and planning!”
“These are revolutionary data for the ESRD [end-stage renal disease] community, namely the patients, physicians, and companies associated with endoAVF procedures” said FACT investigator John Lucas (Greenwood Leflore Hospital, Greenwood, USA).
“Larger veins not only make vascular access surgery easier and more likely to succeed, but a larger, dilated perforator vein is essential for the endoAVF to mature properly. Both endoAVF technologies presently approved and available for treatment of ESRD utilise the perforator vein as a key component of the procedure. The statistically significant p-FACT data demonstrate that intermittent compression results in a larger perforator vein for stage four patients. Based on the FACT trial p-FACT data, almost every stage four renal disease patient planning to have having an endoAVF procedure should consider using the FA-1 device in preparation for their procedure. Larger veins, especially the perforator vein, will surely improve outcomes! This is very exciting data for all patients and the global ESRD community.”
A research letter published in Circulation: Cardiovascular Quality and Outcomes highlights a “very low” utilisation of supervised exercise therapy (SET) in symptomatic peripheral arterial disease (PAD) patients during the first 19 months after approval by the Centers for Medicare & Medicaid Services (CMS) despite a Class IA guideline endorsement. Authors Sanjay Divakaran (Brigham and Women’s Hospital, Boston, USA) and colleagues write that greater effort is needed to increase SET enrolment across the USA, as well as to improve adherence once enrolled.
In addition to low utilisation of SET and limited participation in therapy following enrolment, the researchers also found that patients referred to SET differed in race, sex, socioeconomic status, and geographic region compared with those unenrolled, suggesting disparities emerging early during implementation.
Divakaran et al detail that SET is recommended in consensus guidelines, based on its proven ability to reduce symptoms of PAD and improve walking performance. A lack of reimbursement for SET was a barrier to access and utilisation up until May 2017, when the CMS determined that that the evidence was sufficient to cover SET for beneficiaries with intermittent claudication. The present study aimed to address a lack of data on utilisation and outcomes associated with SET since the introduction of reimbursement.
The research team included in their study patients with a Current Procedural Terminology code for SET or International Classification of Diseases, Tenth Revision Clinical Modification code for intermittent claudication required by CMS for SET reimbursement between 1 June 2017 (corresponding with CMS’ reimbursement agreement) and 31 December 2018.
Among 129,699 patients with a diagnosis of intermittent claudication, 1,735 (1.3%) were enrolled in SET during the study period, the authors relay in their research letter. The investigators further detail that the median number of SET sessions attended was 16 (interquartile range [IQR], 6–28), and that only 89 patients (5.1%) completed the programme, attending all 36 sessions.
Writing in Circulation: Cardiovascular Quality and Outcomes, the authors report that one-year cumulative incidence of endovascular and surgical revascularisation among patients participating in SET were 11.9% and 2.4%, respectively, adding that no patients undergoing SET underwent amputation during the follow-up period.
Divakaran et al further relay that, in a matched cohort analysis (n=6,940), the use of endovascular or surgical revascularisation was significantly lower among those who underwent SET—endovascular: hazard ratio (HR), 0.49 (95% confidence interval [CI], 0.4–0.6), p<0.001; surgical: HR, 0.27 (95% CI, 0.18–0.42), p<0.001. The researchers add that there were no other differences in outcomes between groups.
Addressing some limitations of their study, Divakaran and colleagues recognise that only a small number of patients were referred to SET and that follow-up time was short. In addition, they acknowledge the possibility of treatment selection bias and residual confounding, the inability to assess severity of symptoms due to the use of claims codes, and the lack of detail regarding SET protocols.
July’s top 10 features a video interview with Jonathan G Moss (Institute of Cardiovascular and Medical Sciences, Glasgow, UK), chief investigator of the CAVA (Central venous access devices for the delivery of systemic anticancer therapy) trial, results of which were published online in The Lancet. A meta-analysis looking at the risk of major amputation after use of paclitaxel-coated balloons (PCBs) in the peripheral arteries has attracted debate, with leading physicians propose that the methodology used needs to be carefully considered and scrutinised before these conclusions are accepted.
VIDEO: For most patients receiving systemic anticancer treatment (SACT), totally implanted ports (PORTs) are more effective and safer than both Hickman-type tunnelled catheters (Hickman) and peripherally inserted central catheters (PICCs). The CAVA trial’s results, just published online in The Lancet, recommend reshaping current guidelines and practice, so that most patients requiring chemotherapy for solid tumours receive a PORT within the UK National Health Service, foreshadowing a pivot in practice that might be “slow to start with”.
“There appears to be heightened risk of major amputation after use of paclitaxel-coated balloons [PCBs] in the peripheral arteries,” findings from a systematic review and meta-analysis of randomised controlled trials (RCTs) published in the European Journal of Vascular and Endovascular Surgery (EJVES) suggest. However, the authors clarify that the level of evidence is graded moderate, not high, due to scarce events in some studies.
A large, single-centre retrospective study has revealed the risk of acute kidney injury (AKI) following pharmacomechanical thrombolysis (PMT) for lower extremity deep vein thrombosis (DVT) is as high as 22%.
Scitech Medical has announced that it has received CE mark approval for the Embosoft microspheres for use in vascular embolization of hypervascular tumours, symptomatic uterine fibroids and prostatic arteries to relieve symptoms related to benign prostatic hyperplasia, as well as for haemostatic embolization.
Endologix announced the company’s ChEVAS (chimney endovascular aneurysm sealing) system has been granted a Breakthrough Device designation from the US Food and Drug Administration (FDA). The ChEVAS system is an investigational endovascular abdominal aortic aneurysm (AAA) sealing therapy designed to combine the Nellix 3.5 endograft with parallel visceral stents to enable treatment of patients with juxtarenal, pararenal, and suprarenal AAA.
Artio Medical announced it has completed enrolment in its first-in-human study evaluating the Amplifi vein dilation system. In the study, five patients were treated by Adrian Ebner, head of the Cardiovascular Department at Sanatorio Italiano Hospital in Asunción, Paraguay.
A population-based study from 2013 to 2015 in Germany has found that nearly one fifth of patients with peripheral arterial disease (PAD) did not receive guideline-based vascular diagnostics three months before incidence amputation. Writing online in the European Journal of Vascular and Endovascular Surgery (EJVES), authors Kristina Hagenström (University Medical Center Hamburg-Eppendorf, Hamburg, Germany) and colleagues say this “reflects an underuse of health services”.
Terumo Medical Corporation has announced the introduction of its Azur vascular plug. The addition to Terumo’s embolisation portfolio is indicated for use to reduce or block the rate of blood flow in arteries of the peripheral vasculature.
Percutaneous Deep Vein Arterialisation (pDVA) with the LimFlow System offers a cost-effective and high-value alternative to traditional therapies or amputation, according to a recent study published in the Journal of Critical Limb Ischemia.
A German claims-based cohort study has revealed that—in 13,204 patients treated with a paclitaxel-coated device for peripheral arterial disease (PAD)—mortality differences were mostly attributable to a female subgroup treated above the knee, while no statistically-significant differences were observed in male patients. These findings were recently published in the Journal of Clinical Medicine (JCM).
MedAlliance has announced completion of patient enrolment in the PRISTINE clinical trial with the Selution SLR 018 drug-eluting balloon (DEB) for the treatment of patients with below-the-knee (BTK) disease. According to a MedAlliance press release, Selution SLR is the first DEB to be awarded Breakthrough Device designation by the US Food and Drug Administration (FDA).
The objective of the prospective PRISTINE trial is to evaluate the safety and efficacy of the Selution SLR sirolimus DEB in the treatment of infra-inguinal occlusive lesions (TASC C and D) in patients with chronic limb-threatening ischaemia in 75 patients over 12 months at Singapore General Hospital in Singapore.
PRISTINE is a follow-up registry to the PRESTIGE trial. The 12-month data from PRESTIGE were presented at LINC 2021 (The Leipzig Interventional Course, 25–29 January, online), showing sustained benefits up to one year. Eighteen-month data is to be presented at VIVA 2021 (Vascular InterVentional Advances; 4–7 October, Las Vegas, USA), where it is anticipated that these benefits will be further sustained. A similar outcome benefit is expected from PRISTINE in a larger real-world population.
“One of the important things to note is that we had few exclusion criteria, unlike many of the randomised controlled trials using drug-coated balloons in the peripheral vasculature, and the data represent real-life lesions that we face every day as vascular specialists in Singapore”, said lead investigator Tjun Yip Tang (Singapore General Hospital, Singapore).
“PRISTINE will offer further insight, leveraging on our initial experience with the PRESTIGE trial, into whether this sirolimus-eluting balloon will become an established device in our angioplasty armamentarium to fight the neointimal hyperplasia effect and restenosis phenomenon that lead to a significant number of clinically driven target lesion revascularisations in the BTK arteries, in this frail and challenging cohort of patients, whose ischaemic foot wounds are difficult to heal.”
In February 2020, MedAlliance received CE mark approval for Selution SLR in the treatment of peripheral arterial disease (PAD) and in May 2020 received CE mark approval for treatment in coronary arterial disease (CAD). MedAlliance has been awarded FDA Breakthrough designation for the Selution SLR for use in BTK and expects to begin the investigation device exemption (IDE) study later this year.
Following its acceptance into Frontiers in Neurology, Phenox has announced the results of a paper exploring the benefit of choosing a longer stentriever for mechanical thrombectomy procedures.
In a paper authored by Carmen Serna-Candel (Neuroradiologische Klinik, Klinikum Stuttgart, Stuttgart, Germany) et al, the outcomes of the pRESET 4×20 and pRESET 5×40 stentrievers (both Phenox) were examined against one another. The results “speak for themselves”, a Phenox press release states, and add to existing evidence that longer stentrievers lead to better patient outcomes.
With the use of the longer stentriever, a significant improvement in recanalisation rates was observed, along with improved mortality rates and fewer passes required to full recanalisation. First pass success was seen in 68.4% of cases with the pRESET 5×40 while the pRESET 4×20 resulted in first pass success in 48.7% of cases.
This led Serna-Candel et al to conclude that “the size of the stent retriever matters in acute M1 occlusions treated with aspiration-assisted thrombectomy”.
“We, in the Phenox engineering team, are delighted to offer to the market another device that will improve the outcomes of patients,” said Ralf Hannes, managing partner of Phenox. “And now, with these data, the 5×40 pRESET has proven its value.”
“We are proud to continue to innovate the neurovascular market and the most important aspect of developing new devices is clinical outcomes,” said Hermann Monstadt, managing partner of Phenox. “This publication is a testament to how we work with feedback from physicians to provide devices to improve patients’ lives.”
At the Society of NeuroInterventional Surgery’s 18th annual meeting (SNIS; July 26–29 2021, Colorado Springs, USA and virtual), Jeffrey Saver, professor of Neurology at the University of California, Los Angeles (UCLA) Medical Center and director of the UCLA Stroke Center (Los Angeles, USA), discussed the various ethical considerations that need to be taken into account regarding robotic applications in neuroendovascular interventions, and remote stroke care, stating that “we all need to work together to make sure patients have the best outcome”.
During a session that also saw multiple presentations demonstrating the potential benefits and new possibilities enabled by these novel technologies, Saver claimed this is an area that brings up “several unique domains of challenging bioethics”—including the ethics of remote care, the ethics of introducing new surgical techniques and training protocols, the ethics of robot-assisted procedures, and even autonomous, artificial intelligence (AI)-powered robotic systems, which are currently physician-supervised but may be unsupervised in the future.
The first specific ethical consideration Saver outlined was “compromised informed consent” on the patient’s part. He emphasised the criticality of full disclosure of the fact many of these procedures are fairly new, and, as such, there is limited evidence on both their benefits and their risks. “There is a general tendency for patients to equate newness with increased benefit—and we have to counter this tendency when we talk with them,” he added. Saver also noted that, while trust in the authority of the interventionist performing the given procedure should be encouraged, “humility”—to reflect their often-limited experience in performing these procedures compared to more traditional surgeries—is important here too.
Saver went on to state that various conflicts of interest on the physician’s side are significant too, and should be fully disclosed to the patient, with these ranging from direct financial benefits and other incentives, and brand loyalty, to the “elevated social status” of being a surgical innovator and bias towards performing a technique in which training has been invested—referring to the phenomenon of “sunk cost” here as well.
He noted that harm to the patient, including increased morbidity and mortality, is the “most important” ethical consideration that may be associated with robotic or remote procedures. “We need stringent QI [quality improvement] and reviews of every case,” Saver added. He went on to state that research burdens should not be placed disproportionately on disadvantaged or poorer communities, despite the fact that patients from these backgrounds may only gain access to advanced care by participating in innovative therapy systems—something he described as a “challenging ethical issue”—and added that these expensive technologies should not take too many resources away from proven care approaches either.
Another factor that Saver claimed is especially pertinent to remote intervention is the notion of a “diminished physician-patient relationship”, whereby the patient has reduced access to the interventionist. “We need to be sure that the interventionist maximises their availability to the patient—not just during the case, but by telemedicine pre and post if they are doing a case remotely,” he stated. Saver noted that there could be a risk for decreased empathy on the part of the physician for patients and families with whom they have never had direct contact too.
On a similar note, he alluded to the “diffusion of responsibility” that may be seen to be associated with these novel surgeries, referring to a “broader network of interdependent care” than is common in medicine. This network involves the remote interventionist, local physicians and nurses, hardware manufacturers, software coders, the AI system being deployed, and more. “We need to make sure we have an active, continuous partnership,” Saver also said.
As well as giving a nod to the more distant future in this ever-evolving space within neurosurgery—that being the ethics of fully autonomous, robotic interventionists—Saver chose to end his presentation on a more positive note. Firstly, he encouraged the attending audience to consider the future of their own patients, but also future generations of patients who, further down the line, stand to benefit from many of the innovations currently being advanced, adding that “a procedural speciality does require a little bit of risk taking”. Saver concluded his talk by addressing the need to consider the wellbeing of the physicians themselves in this debate—noting that the minimised radiation exposure and reduced lead-wearing risks that neurointerventionists may gain via robotic or remote surgical techniques are “a very important ethical goal” as well.
The American Heart Association (AHA) has released a new scientific statement on lower extremity peripheral arterial disease (PAD), focusing on contemporary epidemiology, management gaps, and future directions.
The statement, authored by Michael H Criqui (University of California, San Diego, San Diego, USA) and colleagues, has been published in Circulation.
Lower extremity PAD affects more than 230 million adults worldwide, the authors detail, adding that the condition is associated with an increased risk of various adverse clinical outcomes, including cardiovascular diseases such as coronary heart disease and stroke, and leg outcomes such as amputation.
Despite its prevalence and clinical importance, however, Criqui et al highlight a multifactorial underappreciation of PAD by healthcare professionals and patients, combining limited availability of the first-line diagnostic test—the ankle-brachial index—in clinics, and incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice. In addition, the authors relay that many patients with PAD are not receiving evidence-based therapies.
The new statement is designed to address these issues by providing an update for healthcare professionals regarding contemporary epidemiology (i.e., prevalence, temporal trends, risk factors, and complications) of PAD, the current status of diagnosis (physiological tests and imaging modalities), and describing major gaps in the management of PAD (i.e., medications, exercise therapy, and revascularisation), Criqui and colleagues write.
In concluding their statement, the authors look to the future: “Orchestrated efforts among different parties (e.g., healthcare providers, researchers, expert organisations, and healthcare organisations) will be needed to increase the awareness and understanding of PAD and improve diagnostic approaches, management, and prognosis of PAD.”
Fist Assist Devices has just announced completion of the FACT trial, which evaluated the use of an intermittent pneumatic compression device, model FA-1, to promote vein dilation in patients with kidney disease. The trial’s results suggest the device could enable an increase in the creation of functional arteriovenous fistulas by enlarging superficial veins. The trial also demonstrates the device’s safety in this patient population.
“This is groundbreaking research that will drive efficiencies in the end-stage renal disease community as it really proves that intermittent compression enlarges superficial veins, and larger veins provide better surgical or endoAVF options and outcomes” said John Ross, director of Regional Medical Center in South Carolina and Inductee in the American College of Surgeons and Academy of Master Surgeon Educators.
The Fist Assist technology is patent protected and focused on developing an intermittent, external wearable pneumatic compression for arm massage and increased vein circulation in the United States, and increased forearm vein enhancement and AV fistula dilation/maturation in India, Canada, Europe, Australia, and New Zealand.
“We are ecstatic to complete FACT and are very thankful to all patients, physicians, and hospitals that worked to complete this trial during the COVID-19 pandemic, which was possible as the device is a patient-centric wearable in the home” said Mary Hammes, primary investigator of the trial and associate professor of Medicine and director, Chronic Hemodialysis, at the University of Chicago, USA. “This is a landmark, global trial evaluating the effectiveness of the FA-1 intermittent compression device on pre-surgery, stage 4 chronic renal failure patients.”
Patients were enrolled in three locations: The University of Chicago Medical Center, Chicago, USA; a medical clinic in Greenwood, USA, under the direction of John Lucas; and MS Ramaiah Medical Center, Bengaluru, India, under the direction of Sanjay Desai.
On preliminary analysis, most enrolled patients showed statistically significant superficial vein dilation (p<0.05) without any safety concerns. A press release from the company states: This will be a gamechanger for the over 40 million stage 4 chronic kidney disease patients in the United States alone because larger veins will help ensure improved arteriovenous fistula creation, whether they are created surgically or by new EndoAVF procedures. “This data is likely to be the foundation for additional indications of use for the Fist Assist device and continues to add more information on novel ways to increase pre-surgery vein size and distensibility for eventual dialysis,” the release adds.
Ross outlines the benefits of larger preprocedural veins: “[…] with the recent focus of fistulas being created percutaneously through EndoAVF technology, this data is critically important as larger, presurgical veins will enable more patients to be candidates for the less invasive EndoAVF procedures. This data could and should even drive CMS reimbursement as larger superficial veins will help improve outcomes, which drastically reduces the cost burden on patients, providers, and the entire healthcare system.”
Boston Scientific has commenced enrolment in the HI-PEITHO clinical trial, a collaborative research study with the Pulmonary Embolism Response Team (PERT) Consortium and the University Medical Center of the Johannes Gutenberg University of Mainz (Mainz, Germany) comparing use of the EkoSonic endovascular system (EKOS) in combination with anticoagulation to anticoagulation alone for the treatment of acute, intermediate-high-risk pulmonary embolism (PE).
The EKOS system uses ultrasound energy in combination with a thrombolytic drug to dissolve blood clots and restore blood flow in patients with PE and peripheral arterial occlusions. According to a company press release, the ultrasound technology used by the EKOS system accelerates thrombolysis, minimising the time it takes to treat a patient and lowering the necessary thrombolytic dose, which can result in optimised outcomes and a lower risk of bleeding.
“I am honoured to be part of this study’s global leadership whose mission is to bring forth guidelines-informing data that will ensure physicians can feel confident in the most appropriate strategy for treating patients with intermediate-high-risk PE,” said Stavros Konstantinides (University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany), study co-lead principal investigator.
The randomised HI-PEITHO trial will enrol up to 544 patients with confirmed acute, intermediate-high-risk PE at as many as 65 sites in the USA and Europe. The trial, which will follow patients for one year, will assess whether treatment with the EKOS system in combination with anticoagulation is associated with a significant reduction in adverse events compared to anticoagulation alone, within seven days of randomisation. The composite primary endpoint is defined as PE-related mortality, cardiorespiratory decompensation or collapse and non-fatal symptomatic and objectively confirmed recurrence of PE.
“Optimal treatment of PE is still poorly understood and there is a need for a coordinated institutional approach to this complex, life-threatening problem,” said Kenneth Rosenfield (Massachusetts General Hospital, Boston, USA), study co-lead principal investigator. “The lead investigators of the trial are pleased to collaborate with the PERT Consortium, which is committed to evidence-driven therapy and is proud to take part in the HI-PEITHO study, aiming to advance the care of patients with PE.”
The Society of Interventional Radiology (SIR) has issued a new position statement on percutaneous lung ablation in the August edition of the Journal of Vascular and Interventional Radiology (JVIR), along with an accompanying quality improvement document, which establishes performance thresholds for patient safety.
Mark Baerlocher, SIR’s standards division councillor and an author of the position statement and quality improvement document, said: “Minimally invasive, image-guided thermal ablation offers patients with early stage, non-small-cell lung cancer, recurring lung cancer, and metastatic disease a safe and effective treatment option.
“The two publications provide physicians with guidance on everything from patient selection to treatment delivery and post-treatment care and follow-up, ensuring high-quality care that improves patients’ lives,” added Baerlocher, an interventional radiologist at the Royal Victoria Hospital in Ontario, Canada.
Lung cancer is the second most common newly diagnosed cancer in the United States, with an estimated 228,000 new cases diagnosed in 2020. It is also the leading cause of cancer-related death.
Interventional radiologists use image-guided thermal ablation to treat primary and secondary lung tumours. Based on the current evidence, the position statement recommends that radiofrequency ablation, cryoablation and microwave ablation are all appropriate forms of image-guided thermal ablation to treat these tumors. The method of ablation should be determined by lesion characteristics and risk mitigation, according to the new document.
SIR president, Matthew Johnson, said: “Evidence-based position statements are important means of improving patient outcomes. Future comparative studies on the use of thermal ablation to treat these forms of lung cancer will help improve the evidence base and allow us to make stronger recommendations to the benefit of patients.”
The position statement was developed by a multidisciplinary group of authors including interventional radiology, medical oncology, thoracic surgery and radiation oncology specialists. It is endorsed by the Canadian Association for Interventional Radiology, the Cardiovascular and Interventional Radiological Society of Europe and the Society of Interventional Oncology.
Read the full position statement and quality improvement document on jvir.org.
Abstract submissions are now open for next year’s Society of Interventional Oncology annual meeting (SIO2022), which takes place from 3—7 February in San Francisco, USA.
Abstracts must be submitted by 30 September 2021 at 11.59pm CDT and those submitting for the first time must follow the instructions to create a new account on the submission site.
Successful abstracts will have the opportunity to share their research with more than 600 professionals in the global interventional oncology community. There is no restriction to the number of abstracts that can be submitted.
SIO say that while it does not have a policy that limits prior presentation of data, the reviewing committee gives higher priority for abstracts that have not yet been presented.
Abstracts can be submitted in the following categories:
The abstract character limit is 4000 with a minimum of 50 characters, including spaces and any tables and/or graphs. Abstracts may be submitted for an oral or poster presentation and must include objectives, results, and conclusions.
Selected presenters will be notified by November 2021.
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Surmodics has announced that J. Michael Bacharach, a vascular interventionalist/cardiologist at North Central Heart, a division of Avera Heart Hospital in Sioux Falls, USA, successfully treated the first patient with the company’s Pounce thrombectomy system.
The procedure involved a patient presenting with increasing pain in the left leg and was diagnosed with an occluded superficial femoral artery (SFA). Three passes of the Pounce device removed 30cm of subacute thrombus and blood flow was successfully restored. Eight additional cases have since been performed in the US with positive outcomes reported following each procedure.
“Despite the challenge presented by this particular case, I could not have asked for anything more. The device’s performance was really amazing,” said Bacharach. “I was able to safely and effectively achieve a positive outcome for this patient with minimal blood loss and without the use of thrombolytics. I’m very excited about the results of this case. I’m a believer in the Pounce system.”
The Pounce Thrombectomy System, which received US Food & Drug Administration 510(k) clearance in September 2020, is a mechanical thrombectomy device intended for the non-surgical removal of thrombi and emboli from the peripheral arterial vasculature.
Depending on the age and magnitude of the occlusion and the viability of the threatened limb, existing treatments for this condition may include catheter directed thrombolysis, surgical embolectomy, and/or percutaneous mechanical thrombectomy. In cases in which the occlusion has caused irreversible damage to the limb, acute limb ischemia can result in the amputation of a lower extremity.
Gary Ansel, founder and former chief medical officer of Embolitech—from which Surmodics acquired the technology and intellectual property behind the Pounce thrombectomy system—said: “I am delighted that the Surmodics team is providing peripheral interventionalists with this innovative tool for treating arterial thrombotic occlusions.
“I also congratulate the company on its continued efforts to advance therapies for patients dealing with arterial thrombosis and peripheral arterial disease while focusing on ease of use and efficiency for the physicians treating these patients.”
Artio Medical announced today it has completed enrolment in its first-in-human study evaluating the Amplifi vein dilation system. In the study, five patients were treated by Adrian Ebner, head of the Cardiovascular Department at Sanatorio Italiano Hospital in Asunción, Paraguay.
“I am very pleased with my initial experience using the Amplifi system,” Ebner said. “The device was simple to implant and well-tolerated by all patients. We observed significant vein enlargement in each enrolled patient and were able to successfully create arteriovenous (AV) fistulas in all patients after treatment, including patients who were poor candidates for AV fistula before treatment.”
The Amplifi system is designed to stimulate arm vein enlargement in haemodialysis patients using rapid, non-pulsatile venous blood flow. After seven days of treatment, the device is removed during surgery to create an AV fistula. The Amplifi vein dilation system aims to make more haemodialysis patients eligible to receive an AV fistula, increase fistula maturation success, reduce maturation time, and prolong the usable life of these fistulas. Amplifi is the first and only medical device intended to dilate and prepare veins prior to AV fistula surgery, according to an Artio Medical press release.
“I am grateful for Dr Ebner and the entire team at Sanatorio Italiano who contributed to the success of this first-in-human study,” said F Nicholas Franano, president and CEO of Artio Medical. “The company looks forward to sharing data on these first five patients in the coming months and building upon this promising early clinical experience. We remain focused on delivering a much-needed solution to the millions of patients worldwide who need haemodialysis.”
Percutaneous Deep Vein Arterialisation (pDVA) with the LimFlow System offers a cost-effective and high-value alternative to traditional therapies or amputation, according to a recent study published in the Journal of Critical Limb Ischemia.
Peter Schneider, professor of surgery at the University of California (San Francisco, USA) and co-author of the published article, said: “The cost-effectiveness analysis builds on recently published 12-month data from the PROMISE I study by showing that pDVA with the LimFlow System can be a high-value therapy alternative to the status quo for no-option CLTI patients.
“This research highlights the health economic benefits of reducing amputations and the need to offer patients a better alternative worldwide.”
The findings highlighted significant and promising data from cost-effectiveness analysis comparing pDVA with the LimFlow System to the status quo treatment for no-option CLTI patients, according to the study authors.
The status quo was defined by a meta-analysis conducted by the Yale Cardiovascular Research Group on no-option patient outcomes from other reputable studies ranging from 2006 to 2018, which is pending publication in the Journal of Critical Limb Ischemia.
The comparative analysis demonstrates that expected outcome improvements with pDVA justify its incremental costs and qualifies it as a “high-value” therapy per established willingness-to-pay thresholds.
Dan Rose, CEO of LimFlow, added: “Avoiding major amputation is a key treatment goal in CLTI due to its associated high costs, loss of functional status and quality of life, and high mortality.
“The analysis using data from PROMISE I demonstrates our technology can provide significant clinical and health-economic value to patients and healthcare providers who are drastically underserved by the status quo.”
“There appears to be heightened risk of major amputation after use of paclitaxel-coated balloons [PCBs] in the peripheral arteries,” findings from a systematic review and meta-analysis of randomised controlled trials (RCTs) published in the European Journal of Vascular and Endovascular Surgery (EJVES) this week suggest. However, the authors clarify that the level of evidence is graded moderate, not high, due to scarce events in some studies.
And, leading physicians propose that the methodology used needs to be carefully considered and scrutinised before these conclusions are accepted.
Clarifying at the outset that he is not an expert on statistical methodology, globally recognised leader in the development of new less-invasive procedures, Barry T Katzen, founder and medical director of Miami Cardiac & Vascular Institute and the president of the CLI Global Society, tells Vascular and Interventional News: “As a physician engaged in multidisciplinary limb salvage with a view to improving quality of life by preventing amputations and death due to critical limb ischaemia, the conclusions from this meta-analysis are of concern, of course, and need to be taken seriously. However, I have in parallel questions about the complex methodologies used in this paper to arrive at a finding that prospective randomised controlled trials have not demonstrated. From a practical point of view, before accepting the conclusion regarding the risk of paclitaxel drug-coated balloon use, there needs to be a significant discussion and analysis of the methodologies employed in this paper. This needs to be undertaken by appropriate statistical experts before these findings change practice, if they do so at all.”
This latest meta-analysis, authored by Konstantinos Katsanos (Patras University Hospital, Rion, Greece) and colleagues with co-authors from France, Germany, Finland and The Netherlands, drills down on the long-term risk of major amputation alone associated with use of PCBs in the lower limbs. The findings point to a significantly higher long-term risk of major limb loss using these devices in the femoropopliteal and/or infrapopliteal arteries.
Anna Maria Belli, a former consultant radiologist and Professor of Interventional Radiology at St. George’s Hospital and Medical School in London, UK, a past president of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and proponent of evidence-based trials, comments: “It is essential that we have publications such as this interrogating data on new technologies in an unbiased way. There is a natural tendency to believe new technologies will provide better results than old ones. It is only by pooling results from published trials that enough numbers are amassed to detect trends which might be missed by individual trials. Katsanos and colleagues are to be commended for highlighting the increased risk of amputation with PCBs and, as they say, this now needs to be confirmed or refuted by further investigations.”
Commenting on the publication in EJVES, Younes Jahangiri, statistical editor of the Journal of Vascular and Interventional Radiology, says: “The manuscript has used a robust search strategy and meta-analysis techniques. Nevertheless, there are a considerable number of back-calculations and imputations that have been performed for data generation, which might not necessarily fit with real-world data. Additionally, exclusion of studies with no events in both arms, especially if the studies were of high quality and adequate follow-up, might have led to overestimation of the crude risk in both groups and potentially to the statistical significance of between-group differences. Although the meta-analysis itself suggests an alarming signal in a heavily computational way, confirmation of accuracy and adequacy of the signal would still require real-world targeted data.”
The harm signals suggested for paclitaxel devices from previous meta-analyses have not been substantiated by a wealth of real-world datasets that have shown no long-term safety concerns, and instead suggested increased benefits with the use of paclitaxel-coated devices. Importantly, an interim mortality analysis of the SWEDEPAD registry randomised trial did not confirm a heightened mortality risk in cases of paclitaxel treatment, as noted in the EJVES paper.
As reported in EJVES, the investigators performed a literature search last updated on 20 February 2021 to analyse 21 RCTs with 3,760 lower limbs treated nearly equally for intermittent claudication (52%) and chronic limb threatening ischaemia (CLTI; 48%). The median follow-up period was two years. Authors report 87 major amputations in 2,216 limbs in the paclitaxel arm (4% crude risk) compared with 41 major amputations in the 1,544 limbs in the control arm (2.7% crude risk). The risk of major amputation was significantly higher for paclitaxel-coated balloons with a hazard ratio (HR) of 1.66 (95% CI 1.14–2.42; p=0.008, one stage stratified Cox model). The observed amputation risk played out equally across femoropopliteal (p=0.055) and infrapopliteal (p=0.055) arteries. The number needed to harm was 35 for CLTI. In this systematic review and meta-analysis, authors suggest the summary effect demonstrated a 66% higher relative risk of major amputation in the limbs treated with PCBs, and call for further investigations.
Further, Katsanos and colleagues write that there was good evidence of a significant non-linear dose relationship with accelerated risk per cumulative paclitaxel dose (chi square model p=0.007). The results were also stable across sensitivity analyses (clarified as pertaining to different models and subgroups, based on anatomy and clinical indication and excluding unpublished trials).
Ziv Haskal (University of Virginia, Charlottesville, USA), the former editor (2011–2020) of the Journal of Vascular and Interventional Radiology (JVIR) tells Vascular News and Interventional News: “Dr Katsanos and the research team stand, again, to shake-up the PCB planet with a suggested finding of worse amputation—the same goal paclitaxel was intended to make better, and with a dose-dependent effect. Unsurprisingly, it is a rigorous and clear-headed analysis. But there are interpolations, intercalations and imputations, likely to bring out critics, with force. This may be a curtain raiser, but the main play is yet to unfold.”
A large, single-centre retrospective study has revealed the risk of acute kidney injury (AKI) following pharmacomechanical thrombolysis (PMT) for lower extremity deep vein thrombosis (DVT) is as high as 22%.
PMT is an established treatment for selected patients with acute DVT. Despite significant clinical success, haemolysis can lead to AKI with unknown longer-term implications. Researchers in the USA therefore aimed to characterise the rate of AKI after PMT, and identify those patients at the greatest risk.
“Recent evidence has suggested that catheter-direct therapy (CDT) in the setting of acute iliofemoral DVT improves vein patency and post-thrombotic severity with an equivocal risk of bleeding,” said principal author Karim M Salem (University of Pittsburgh, Pittsburgh, USA).
“Catheter thrombolysis can be accomplished by dripping thrombolytic agents through a multiside-hole catheter over several hours, or using PMT devices,” Salem added. “Plenty of evidence has supported the use of PMT over catheter thrombolysis because PMT can achieve fast lytic therapy at a lower tissue plasminogen activator (tPA) dose. Aggressive PMT, however, can cause haemolysis, which can result in AKI.”
As reported in the July 2021 issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, Salem’s team studied the records of 137 patients who underwent PMT for acute iliofemoral DVT at the University of Pittsburgh between 2007 and 2018.
The mean age of the 137 patients was 47±17 years, 50% were male, and their preoperative creatinine levels were found to be 0.99mg/dL, on average.
Ultimately, 30 of these patients (22%) developed postoperative AKI, defined as a creatinine 1.5x baseline. According to the report, multivariable analysis demonstrated three significant risks factors for the development of AKI:
Of the 30 patients who did develop AKI, two progressed to severe renal failure (glomerular filtration rate <30ml/min) and one required long-term haemodialysis.
“Contemporary studies have reported the results of more rapid and aggressive thrombolysis protocols that can be completed in a single session,” Salem noted. “This approach has been associated with a development of acute renal failure owing to the haemolysis caused by the PMT devices.
“Our focus was to identify the preoperative factors that might influence our decision to pursue aggressive single-stage intervention versus multistage CDT. With the results of the present study, we avoid single-stage intervention in women with bilateral extensive DVT to minimise the risk of postoperative AKI.”
This study adds “significant knowledge” to understanding the risks of lytic therapy in patients with iliofemoral DVT, a statement from the Society for Vascular Surgery (SVS) concludes.
Viz.ai has partnered with Avicenna.AI in an effort to enable intelligent care coordination and improve patient triage of patients suffering from pulmonary embolism (PE) and aortic disease.
It is hoped that the collaboration will pave the way for faster clinical decision making and care for patients suffering from these two life threatening conditions.
Avicenna.AI’s FDA-approved algorithms for PE and Type A and Type B aortic dissection (AD), leveraged on the Viz intelligent care coordination platform, aim to empower multidisciplinary care teams to easily coordinate patient care by sending notifications paired with dynamic imaging and detailed patient information to each provider’s desktop or mobile device as soon as a PE or an aortic dissection is detected.
As part of Viz.ai’s commercial aortic module offering, access to imaging and workflows supporting the coordination of care for patients with abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), rupture, stenosis and transection will be available in addition to the AD algorithm. Similarly, the PE algorithm will be available on Viz.ai’s commercial PE module.
Richard Saxon, interventional radiologist at Tri-City Medical Center (Oceanside, USA), said: “The addition of AI powered workflows should decrease the time from diagnosis to treatment and help to coordinate care for patients suffering from life-threatening PE and aortic disease, as it has in the treatment of ischaemic stroke. It will help to facilitate faster and easier treatment decisions across health systems, and this should improve outcomes for patients.”
Cyril Di Grandi, chief executive officer of Avicenna.AI, said: “We are proud to become a trusted partner of Viz.ai, who is committed to giving access to high-standard healthcare systems worldwide. Thanks to our AI-based solutions, we hope to facilitate an optimal medical response within a short time frame and improve patient care. We look forward to bringing the benefits of our pulmonary embolism and aortic dissection triage tools to the emergency room and beyond.”
PE is a potentially deadly form of venous thromboembolic disease, a common cause of cardiovascular death, and is associated with multiple inherited and acquired risk factors affecting hundreds of thousands of people every year globally. PE occurs when a blood clot gets lodged in an artery in the lung, blocking blood flow to part of the lung. Similar to PE, aortic disease is potentially deadly and can require urgent surgical intervention to prevent death.
Chris Mansi, Viz.ai CEO and co-founder, added: “We’re delighted to partner with Avicenna to bring intelligent care coordination to the peripheral vascular and vascular fields. This will form part of a broader Viz platform, where any patient with life threatening diseases can benefit from AI powered triage, fast mobile communication and synchronized care coordination.
“This partnership will bring the advantages of artificial intelligence to more patients and help hospitals achieve better clinical outcomes.”
The Journal of Vascular and Interventional Radiology’s (JVIR’s) Impact Factor—one measure of a journal’s influence based on the number of article citations compared to the total number of citable articles published—jumped 14% in 2020.
According to the Journal Citation Reports, published by Clarivate Analytics, JVIR’s Impact Factor rose to 3.464 in 2020, up from 3.037 in 2019.
Daniel Sze, editor-in-chief of JVIR and professor of interventional radiology at Stanford University School of Medicine (Stanford, USA) said: “The continued growth of JVIR’s Impact Factor is a testament to the quality of the scientific research we publish and the journal’s authority in the medical community.
“Across the years—thanks to the leadership of editors emeriti Gary Becker; Daniel Picus; Karim Valji; Albert Nemcek; and Ziv J Haskal—JVIR has become a destination journal for IRs around the world to publish their most impactful endovascular research.
“As I take the reins this year, I will aim to build on success of these IR luminaries by expanding our international programs, furthering JVIR’s commitment to evidence-based patient care worldwide.”
The Impact Factor, which reflects citations in the previous two years, is often used as a measure of the quality and influence of medical journals within scientific, professional and academic communities. JVIR citations appeared in radiology, nuclear medicine, medical imaging and peripheral vascular disease journals.
Society of Interventional Radiology president Matthew Johnson, who is also the Gary J. Becker professor of radiology research at Indiana University School of Medicine (Indianapolis, USA), added: “SIR and SIR Foundation are dedicated to building a culture of research within the IR community and JVIR is a key component to demonstrating the clear benefits image-guided treatments have on the lives of our patients.”
Tara Graham (Trillium Health Partners, Toronto, Canada) has become the new president of the Canadian Association for Interventional Radiology (CAIR), assuming the new role at the board’s meeting on June 14th, 2021.
Amol Mujoomdar (London Health Sciences Centre, London, Canada), the outgoing president, will continue to serve on the CAIR executive board in the role of past president replacing Jason Wong (University of Calgary, Calgary, Canada), who will transition into a director position.
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Alessandra Cassano-Bailey (Health Sciences Centre in Winnipeg, Winnipeg, Canada) will be assuming the role of vice president; and David Valenti (McGill University Health Center, Montreal, Canada) will replace Darren Klass (Vancouver Coastal Health, Vancouver, Canada) as the new CAIR board secretary-treasurer.
A population-based study from 2013 to 2015 in Germany has found that nearly one fifth of patients with peripheral arterial disease (PAD) did not receive guideline-based vascular diagnostics three months before incidence amputation. Writing online in the European Journal of Vascular and Endovascular Surgery (EJVES), authors Kristina Hagenström (University Medical Center Hamburg-Eppendorf, Hamburg, Germany) and colleagues say this “reflects an underuse of health services”. In addition, the researchers report that, in one third of patients who did not receive vascular surgery, major amputation “probably could have been avoided”.
Due to a wider international variance in major amputation, high mortality rates and follow-up, and the “significantly reduced quality of life for patients with amputations,” the authors stress that vascular diagnostics and vascular surgery treatments “are of great importance” for lower limb preservation in patients with PAD. They note that patients with PAD have an increased risk of lower limb amputation, and that the prevalence of PAD and chronic limb-threatening ischaemia (CLTI) is expected to increase due to demographic trends.
The guidelines state that vascular diagnostic and vascular surgical treatments can contribute significantly to the preservation of the lower extremities, and also that early revascularisation can minimise the risk of amputation. In a retrospective longitudinal study, Hagenström et al examined these guideline-based procedures in patients before a first lower limb amputation and PAD.
The researchers analysed data from a large German statutory health insurance (SHI) scheme on patients with first amputation of lower extremities and PAD between 2013 and 2015. They considered pre-defined vascular diagnostic and vascular surgical procedures, as specified by guidelines with inpatients and outpatient care in a defined time before lower limb amputation, Hagenström and colleagues detail.
Reporting their findings in EJVES, the authors relay that the overall estimated incidence of lower extremity amputations in the total population was 0.12% from 2013–2015. Of these patients, they specify, 51.7% had PAD, 81.8% had received at least one diagnostic measure, and 61% a vascular surgery procedure before the lower extremity amputation.
Hagenström et al add that there were only minor variations in the use of diagnostic or surgical treatments between patients with major and minor amputations. “In total, 63.9% of patients had vascular surgery before the incidence major amputation compared with 60% of patients with a minor amputation,” they reveal.
The investigators highlight “noticeable” regional differences in the data, ranging from 91% (Berlin) to 67% (Bremen) regarding diagnostic procedures provided before amputation, and from 83% (Hamburg) to 55% (Saxony-Anhalt) regarding vascular surgery before amputations.
“Timely interventions by specialists and guideline-based treatments could reduce the number of amputations and subsequent costs,” the authors conclude. Commenting on the strengths of their study, they write that its design “permits analyses of a vast and unselected nationwide cohort” and is thus comparable with publications from other countries where population-based data were used. However, they stress that different healthcare systems must be considered.
Hagenström and colleagues also acknowledge some limitations of their study, including the fact that the analysed administrative data are based on only one of several SHI companies in Germany, which limits the transferability of the statements made to the population of Germany as a whole.
Royal Philips today announced the US Food and Drug Administration (FDA) has granted Breakthrough Device designation for a laser-assisted inferior vena cava (IVC) filter removal device. The proposed device is intended for ablating tissue to remove an IVC filter when previous methods of removal have failed.
The failure rate for IVC filter removal is high and limited options for removal exist if the filter has become difficult to remove. Advanced retrieval tools and techniques are required if the IVC filter becomes embedded in the vasculature. Physicians have very few tools to remove the filter when this happens and there are no FDA-approved devices for this type of advanced removal.
Two independent and prospective clinical studies have demonstrated that laser-assisted retrieval was 96–99% effective with a major adverse event rate of 0.7–2%, a Philips press release reports.
“Laser-assisted filter retrieval may be a critical tool for the safe retrieval of filters with extended implantation times,” said Kush R Desai, associate professor of Radiology, Surgery, and Medicine, and director of Deep Venous Interventions at Northwestern University Feinberg School of Medicine (Chicago, USA). “Breakthrough Device designation reflects the potential impact that this technology could have on countless patients where this technology can be applied to safely retrieve filters by an expert physician, thereby reducing their risk of significant filter-related complications.”
“There is a clear need for an innovative device to help physicians more safely perform advanced IVC filter removal and I believe that the Philips excimer laser sheath may greatly enhance the options available to succeed in filter retrieval,” said Atul Gupta, chief medical officer for Image Guided Therapy at Philips and also a practicing interventional radiologist in Philadelphia, USA. “Breakthrough Device designation is an important step for a medical innovation such as this one to help fill an unmet need in patient care.”
For most patients receiving systemic anticancer treatment (SACT), totally implanted ports (PORTs) are more effective and safer than both Hickman-type tunnelled catheters (Hickman) and peripherally inserted central catheters (PICCs). The CAVA trial’s results, just published online in The Lancet, recommend reshaping current guidelines and practice, so that most patients requiring chemotherapy for solid tumours receive a PORT within the UK National Health Service, foreshadowing a pivot in practice that might be “slow to start with”.
The CAVA (Central venous access devices for the delivery of systemic anticancer therapy) trial is a National Institute for Health Research- (NIHR-) funded open–label, multicentre, randomised controlled trial that compared complication rates and costs of the three devices used to deliver anticancer drugs via a central vein.
It is reported to be the largest randomised trial to date to compare all three devices, and set out to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT for three months, or more.
“The bottom line is, for a solid cancer, if you are going to need intravenous chemotherapy for three months or more, you should be offered the option of a PORT. We should try and empower patients so that that this will be something they think will be best for them,” Jonathan G Moss (Institute of Cardiovascular and Medical Sciences, Glasgow, UK), chief investigator, tells Interventional News on the subject of increased PORT take-up.
The paucity of good evidence comparing central venous access devices (CVADs) entails that neither the European Society of Medical Oncology nor the American Society of Clinical Oncology make specific recommendations regarding the type of device to be used.
CAVA showed that PORTs were associated with a reduction in complication rate of about 50% when compared to a PICC line, and when compared with the Hickman line. “There was a fairly strong preference for PORTs, amongst both the patients receiving them and also the healthcare staff who look after them. These were basically felt to be better devices and the only downside is the cost and whether these services are set up and geared to deliver these devices compared to the other two in a timely manner,” he added.
Moss outlines that decision-making processes behind the choice of device are “poorly understood” globally. Eye-catchingly, PICC use has been captured to be buoyant. “PICC usage has increased over the past decade and is now the dominant strategy in many western European countries and the USA.” This spike in PICC popularity may be underpinned by the ease of insertion of these devices enabling prompt placement and removal by nurse-led teams, local availability of devices, technical issues such as the avoidance of the vital structures in the neck, and perceived lower up-front costs—but there is a sketchy evidence base behind this uptick, the authors say. “PORTs, by contrast, are the most expensive and least frequently used of the three devices,” Moss emphasises.
On stemming the tide of PICC use, the lead author continues: “Changing policy in institutions like the NHS [UK National Health Service] is never easy. There will be all sorts of reasons why people do not want to change—with costs being one and who is going to be putting in the PORTs [being another], and how quickly they can be put in. […] There are lots of nurse teams at the moment who have been trained to place PICC lines. We need to be able to sell the message to them that we are not saying they should not provide a service for patients but trying to persuade them to put in a different device. I think we need to try and move away from doctors putting in the PORTs and nurses putting in the PICC lines. These are all fairly straightforward procedures to place, and I have great confidence that we can empower nursing teams to place all three devices, but particularly PORTs.”
Moss acknowledges that the complication rates and costs of nurse-led teams placing PORTs was not tested by CAVA, but emphasises that most skill mix is not evidence-tested. “We did not compare different operator groups regarding complication rates as that was not the purpose of the trial. We do know the technical (or periprocedural) complication rates in CAVA were exceptionally low, reflecting well-trained staff using ultrasound guidance. Most of the complications related to these devices arise from their subsequent usage and maintenance. We simply do not have enough events to compare periprocedural complications across operator groups, and have no reason to believe that based on this very low complication rate, that any one group (nurses, anaesthetists or radiologists) was technically better than another. We continue to support the concept of nurse-led vascular access teams in order to make widespread practice change practical to deliver.”
The authors back the challenge “to change the service delivery model so that PORTs can be provided in a more timely and cost-effective manner. There will still be a small group in whom the other devices are preferred. Guidelines should be updated to reflect this new evidence,” they write.
They also probed the issue of cost, which is another factor that will play into service transformation. “We have got to persuade the people that pay for these, the managers, that although the PORT is more expensive at the shop front, at the end of the day, when you look at the total package of care [when dwell time is taken into account], that they actually are no more expensive, or a little bit cheaper. And again, that is sometimes difficult to sell in the NHS because we tend to focus on frontline costs,” explains Moss.
CAVA randomised patients with an algorithm taking into account centre, body-mass index, type of cancer, device history, and treatment mode. The trial included adults receiving SACT over a three-month or longer period for solid or haematological malignancy from 18 oncology units in the UK. There were four available randomisation options: Hickman vs. PICCs vs. PORTs (2:2:1), PICCs vs. Hickman (1:1), PORTs vs. Hickman (1:1), and PORTs vs. PICCs (1:1) and these then allowed three 2×2 comparisons, PICC vs. PORT, PICC vs. Hickman and PORT vs. Hickman to be made.
“The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or one-year follow-up,” the authors report in The Lancet.
The triallists screened 2,714 individuals for eligibility, 1,061 were enrolled and randomly assigned (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC).
Between 2013 and 2018, 1,061 patients were enrolled and randomly assigned (PICC vs. Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs. Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs. PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC).
Painting a picture of the trial’s main findings, Moss and colleagues report: “There was little difference between PICCs and Hickman in terms of complications. CAVA showed that PORTs reduced the adverse event rate by approximately 50% compared with Hickman and PICCs. A device specific quality of life instrument showed no difference between PICCs and Hickman, but a preference for PORTs. PORTs were associated with the highest total costs; however, after allowing for the dwell time of the devices, there was no difference between PICCs and Hickman, but the cost associated with PORTs was lower when compared with PICCs and Hickman.”
See Moss’ views on the value of randomised controlled trial data:
Scitech Medical, has announced that it has received CE mark approval for the Embosoft microspheres for use in vascular embolization of hypervascular tumours, symptomatic uterine fibroids and prostatic arteries to relieve symptoms related to benign prostatic hyperplasia, as well as for haemostatic embolization.
According to the company, Embosoft’s high rate of viscoelasticity and its hydrophilic surface allow a selective distal embolization that is safe and effective.
Embosoft microspheres are composed of the company’s Polifit 70 material, which guarantees a well-defined spherical shape and a superior compressibility rate. Because of these characteristics, it is possible to reduce approximately 40% of its size during its delivery and will return to the initial spherical shape without fragmentation or deformation in the target vessel, the company stated.
The CAVA (Central venous access devices for the delivery of systemic anticancer therapy) randomised controlled trial (RCT), just published in The Lancet, has revealed that totally implanted ports (PORTs) are more effective and safer than both Hickman-type tunnelled catheters and peripherally inserted central catheters (PICCs). These findings provide important high-quality evidence from more than 1,000 patients to steer choice. Currently, PICCs are by far a dominant strategy in the West, and PORTs the least frequently used of the three devices. “Decision-making processes behind the choice of device are poorly understood globally,” the authors report, but the ease with which PICCs are inserted by nurse-led teams may favour their regular use.
Jonathan G Moss (Institute of Cardiovascular and Medical Sciences, Glasgow, UK), chief investigator of the National Institute of Health Research- (NIHR-) funded trial, tells Interventional News that despite the higher upfront costs associated with PORTs and the fact that they are relatively more difficult to place, most patients receiving systemic anticancer treatment for solid tumours for more than three months should receive a PORT within the UK National Health Service.
See the full article, here: https://interventionalnews.com/cava-rct-ports/
A systematic review and meta-analysis has demonstrated that patients undergoing carotid interventions after thrombolysis have a higher risk of periprocedural hazards, compared with those patients who did not have prior thrombolysis. Authors Stavros K Kakkos (University Hospital of Patras, Patras, Greece) and colleagues report their findings in an article published online in the European Journal of Vascular and Endovascular Surgery (EJVES).
“Patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS) after thrombolytic therapy have a higher risk of periprocedural stroke and death, compared with patients undergoing CEA or CAS without prior thrombolytic therapy,” the authors write. However, they note that the difference was statistically significant only for CAS. In regards to other hazards, Kakkos et al note that there was also a higher risk of periprocedural intracranial haemorrhage (ICH) and local haematoma in patients undergoing carotid interventions after thrombolysis.
One of the findings that Kakkos and colleagues state is “of most practical importance” is that periprocedural risks of stroke and death appeared to be higher if CEA was performed in the first few days after thrombolysis. This inverse relationship between timing to CEA and periprocedural stroke/death “mandates careful patient selection and suggests that it may be safer to defer CEA for six to seven days after thrombolytic therapy,” they posit in EJVES.
Using the Medline, Scopus, and Cochrane databases, Kakkos et al identified 25 studies involving patients who underwent either CEA or CAS after thrombolytic therapy to include in their systematic review and meta-analysis. There were a total of 147,810 patients in these 25 studies, 2,557 of whom underwent either CEA (n=2,076) or CAS (n=481) following thrombolytic therapy.
After CEA, the authors report that the pooled periprocedural stroke/death rate was 5.2% (95% confidence interval [CI], 3.3–7.5) and intracranial haemorrhage was 2.4% (95% CI, 1.7–5.6). After CAS, they relay, the pooled perioperative procedural stroke/death rate was 14.9% (95% CI, 11.9–18.2) and ICH was 5.5% (95% CI, 3.7–7.7).
In case control studies comparing CAS outcomes in patients receiving thrombolytic therapy versus no thrombolytic therapy, the authors communicate that periprocedural stroke/death was significantly higher after thrombolytic therapy (5.2% vs. 1.5%; odds ratio [OR] 8.49; 95% CI, 2.12–33.95), as was ICH (5.4% vs. 0.7%; OR, 7.48; 95% CI, 4.69–11.92).
Kakkos and colleagues also detail that meta-regression analysis demonstrated an inverse association between the time interval from intravenous thrombolytic therapy to undergoing CEA and the risk of periprocedural stroke/death (p=0.032). “Perioperative stroke/death was 13% when CEA was performed three days after thrombolytic therapy and 10.6% when performed four days after thrombolytic therapy, with the risk reducing to within the currently accepted 6% threshold after six–seven days had elapsed,” they write in EJVES, communicating the results of their analysis.
The authors acknowledge that a “major limitation” of their systematic review and meta-analysis is that there were no randomised controlled trials to inform clinical practice. “This is especially relevant regarding stratifying procedural risks in stroke patients who do not have any computed tomography (CT)/magnetic resonance imaging (MRI) evidence of infarction post-thrombolytic therapy and for evaluating the benefits of deferring CEA for six-seven days,” they comment.
In addition, Kakkos et al recognise that case control studies have inherent biases because of study design, so that patients receiving thrombolysis “may have had more severe strokes”. This, they note, could explain the worse outcomes observed in their systematic review.
Finally, the researchers state that varying exclusion criteria, timing, and mode of thrombolytic therapy administration, may have caused heterogeneity, and “should be explored in future studies”.
Endologix today announced the company’s ChEVAS (chimney endovascular aneurysm sealing) system has been granted a Breakthrough Device designation from the US Food and Drug Administration (FDA). The ChEVAS system is an investigational endovascular abdominal aortic aneurysm (AAA) sealing therapy designed to combine the Nellix 3.5 endograft with parallel visceral stents to enable treatment of patients with juxtarenal, pararenal, and suprarenal AAA.
ChEVAS is currently being evaluated through the ChEVAS ONE investigational device exemption (IDE) clinical study that is approved to enrol approximately 120 patients at up to 50 clinical sites worldwide. The national principal investigators of the ChEVAS ONE study are Francis Caputo (Cleveland Clinic Foundation, Cleveland, USA); William Jordan (Emory University School of Medicine, Atlanta, USA); Joseph Lombardi (Cooper University Health Care, Camden, USA); and William Quinones-Baldrich (UCLA, Los Angeles, USA).
“The aneurysm sac sealing technology featured in the ChEVAS system is designed to reduce endoleaks, including gutter endoleaks, that are reported after endovascular treatment of complex aneurysms,” said James McKinsey (The Icahn School of Medicine at Mount Sinai, New York, USA), the leading enroller in the ChEVAS ONE IDE study. “Our initial clinical results of this therapy have been promising in a challenging group of patients.”
McKinsey will present his initial experience with ChEVAS at the Eastern Vascular Society Annual Meeting (23–26 September, Charleston, USA).
Terumo Medical Corporation has announced today the introduction of its Azur vascular plug. The addition to Terumo’s embolisation portfolio is indicated for use to reduce or block the rate of blood flow in arteries of the peripheral vasculature.
“The Azur vascular plug represents a balance of properties—stability, accuracy, and reliable occlusion. This technology has unique advantages that truly make it a market first in embolotherapy, in line with Terumo’s ongoing efforts to deliver improved clinical outcomes and economic benefits,” said Chris Pearson, executive vice president, commercial operations, Terumo Interventional Systems.
A Terumo press release details that the Azur vascular plug comes in sizes to treat arterial anatomy ranging from 2.5–8mm, with a short deployment length for increased precision.
Features include a conformable nitinol braid and an expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (PET) inner composite membrane to facilitate mechanical occlusion. Another key element in the plug’s design is its “advanced, predictable” detachment mechanism, the statement reads, which allows for “immediate and reliable deployment with the push of a button”.
The launch of the Azur vascular plug is complemented by the introduction of the PG Pro peripheral microcatheter, which is indicated for the peripheral vasculature for the infusion of diagnostic and therapeutic agents.
The PG Pro microcatheter is designed specifically to deliver all three sizes of the Azur vascular plug. It comes in radial lengths up to 165cm and a 1,200 PSI rating for clearer fluoroscopic imaging. Both are currently only available in the USA.
“Together, these next-generation technologies allow physicians to treat larger, more difficult vessels through smaller delivery options. It is yet another way Terumo is providing the opportunity for operators to take advantage of the benefits of radial access for increasingly complex procedures, while enhancing therapeutic options in the peripheral vasculature with a microvascular plug. It is a welcome addition to our innovative, best-in-class portfolio,” added Michael Martinelli, chief medical officer, Terumo Medical Corporation.
A German claims-based cohort study has revealed that—in 13,204 patients treated with a paclitaxel-coated device for peripheral arterial disease (PAD)—mortality differences were mostly attributable to a female subgroup treated above the knee, while no statistically-significant differences were observed in male patients. These findings were recently published in the Journal of Clinical Medicine (JCM).
Authors Christian-Alexander Behrendt (University Medical Center Hamburg-Eppendorf, Hamburg, Germany) and colleagues note that, while randomised controlled trials have reported excess mortality in patients treated with paclitaxel-coated devices versus uncoated devices, observational studies have reported the opposite. The researches aimed, therefore, to elucidate the underlying factors driving an observed improvement in mortality associated with paclitaxel exposure in patients with PAD.
Behrendt et al studied multicentre health insurance claims data from a large German insurance fund, BARMER. They detail that a homogenous sample of patients with an index of endovascular revascularisation for symptomatic peripheral arterial occlusive disease between 2013 and 2017 was included.
In total, 13,204 patients (54% females, mean age 74±11 years) were followed for a median of 3.5 years. The authors report that female patients were older (77 vs. 71 years), and had less frequent coronary artery disease (23% vs. 33%), dyslipidaemia (44% vs. 50%), and diabetes (29% vs. 41%), as well as being less likely to have a history of smoking (10% vs. 15%) compared with male patients.
In regard to mortality differences, Behrendt and colleagues relay that these were mostly attributable to the female subgroup who were revascularised above the knee (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.64–0.95), while no statistically significant differences were observed in male patients.
“This study found that female treated above the knee benefitted from paclitaxel-coated devices, while no differences were observed in males,” the authors conclude in JCM. In addition to this fact, which Behrendt et al state has not previously been reported, they found evidence once again for a female patient disadvantage in real-world data. They write: “It appears likely that previously underprivileged female patients benefit from treatment with paclitaxel-coated devices, an association that is moderated through improved optimal pharmacological treatment during follow-up.” However, they note that this subgroup seems to be excluded from previous trials (in Germany)—a fact that would explain a selection bias, they state.
Considering how their findings might impact further research in the area, the authors posit: “Ongoing and future trials should take sex disparities into account”.
In this third episode of a special five-part series on the history of DCBs, Jos van den Berg (Lugano, Switzerland) moderates a Interventional News roundtable discussion where he is joined by John Laird (St Helena, USA) and Peter Schneider (San Francisco, USA).
Study design
Laird examines the context and background to the IN.PACT SFA trial and outlines the study design. He notes that there was a need to change the way superficial femoral artery (SFA) disease was treated, as there were many complications “particularly with the full metal jacket stents…We wanted to create a paradigm and where we could avoid stenting and permanent implants in the SFA,” he adds.
Early expectations through to latest data
Schneider himself notes that in the beginning he was “not at all sure that we were going to be successful” in showing DCB to be superior to percutaneous balloon angioplasty (PTA). Despite having relatively modest expectations, Schneider notes the results were much better than expected, with 75% of patients in the DCB arm reintervention-free at five years. These results were “unheard of” at this time for SFA intervention in lesions up to 18cm. The trial “definitely exceeded my expectations” and “ushered in a new era and a huge advance for our patients,” believes Schneider.
A three-minute balloon inflation
Laird goes on to highlight how a three-minute balloon inflation with the IN.PACT Admiral™ DCB was chosen in order to “achieve the best angiographic and haemodynamic results”, as well as to “maximise drug uptake into the vessel wall” with a “unique formulation of paclitaxel” . The device showed “spectacular results”, at three and five years, he adds.
Safety concerns addressed
Schneider concludes by touching on the paclitaxel safety concerns raised by a meta-analysis and the lessons that have been learnt following its release. There was “ascertainment bias and treatment bias” in the meta-analysis, Schneider says, concluding that the two biases are “why we cannot find a danger signal in the massive amount of data that has been collected since 2018”.
This video is sponsored by Medtronic.
Episode 2: Are all peripheral drug-coated balloons created equal?
Episode 4: Real world data show IN.PACT Admiral DCB is “very efficient” even in complex lesions
COMING SOON
Episode 5: The impact of long-term DCB outcomes on patients’ quality of life
Using selective internal radiation therapy (SIRT) to down-stage hepatocellular carcinoma (HCC) tumours or act as a bridge to surgery is feasible for both small and large growths, regardless of whether or not the patient has undergone portal vein thrombosis. This is the conclusion presented by Lambros Tselikas (Gustave Roussy Cancer Campus, Paris, France) at the European Conference on Embolotherapy (ET; 17–19 June, online).
In his virtual presentation, Tselikas emphasised the importance of dosimetry optimisation, which he said is crucial “to increase the response, to get a high complete response rate, and to increase the FLR [future liver remnant]. Time of surgery [following SIRT] is probably between three months and one year,” he concluded.
When thinking about the reasons why the decision might be made to use radioembolization as a bridge to surgery, Tselikas said simply: “Because we can”.
He cited a review series published in Frontiers in Oncology in 2014 from Arthur J A T Braat (University Medical Center Utrecht, Utrecht, The Netherlands) and colleagues that showed that, depending on the population, it is possible to bridge patients to transplantation. Tselikas also noted that, depending on the selection criteria applied, the percentage of patients that can be staged down varied hugely, from 25–100% of patients, depending on the liver function and the tumour size.
“What is interesting,” the ET speaker continued, “is the relationship between the pathological response you find in the imaging and in the histopathology. These are not very well correlated in some studies. The important message is, depending on the size, when you have complete necrosis on imaging, you will find complete necrosis on pathology.”
Writing in 2014, Braat et al explain the rationale for using radioembolization to downstage tumours: “Inducing significant tumour reduction can downstage patients for resection or, through attaining stable disease, patients can stay on the liver transplantation waiting list. Hereby, radioembolization could make a difference between curative of palliative intent in oncologic patient management. Prior to surgery, the future remnant liver volume might be inadequate in some patients. In these patients, forming an adequate liver reserve through radioembolization leads to prolonged survival without risking post-operative liver failure and minimising tumour progression while inducing hypertrophy. In order to optimise results, developments in procedures surrounding radioembolization are equally important. Predicting the remaining liver function after radical treatment and finding the right balance between maximum tumour irradiation and minimising the chance of inducing radiation-related complications are still challenges.”
Tselikas also presented the positive results of the DOSISPHERE-1 trial, which reported improvement in tumour response rate and overall survival in patients who had HCC treated with Yttrium-90 (Y-90) radioembolization utilising personalised dosimetry. Patients in the DOSISPHERE-1 trial were either given personalised or standard radioembolization; in the personalised group, 35% (10 of 28 patients) went on to have surgery with curative intent, whilst only 4% (one of 28 patients) went on to have surgery with curative intent following standard dose radioembolization.
He also shared the results of the LEGACY (Local radioembolization using glass microspheres for the assessment of tumour control with Y-90) study—a multicentre, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. The study aimed to evaluate objective response rate and duration of response. Clinical meaningful response rates and prolonged duration of response were observed in the treatment of unresectable, solitary HCC ≤8cm.
June 2021 saw the publication of issue 82 of Interventional News, and both our cover stories were amongst those most widely-read on our site this month: see our coverage of the Global Embolization and Cancer Symposium Technologies (GEST) 2021 Focus Day on prostate artery embolization (PAE), summarising the passionate discussions that took place concerning PAE’s place in the American Urological Association’s guidelines, and also learn about the latest developments in the COLDFIRE 2 trial, which recently determined that irreversible electroporation (IRE) is an effective and relatively safe treatment for colorectal liver metastases 5cm or smaller that are deemed unsuitable for partial hepatectomy, thermal ablation, or further systemic therapy.
In this Philips-sponsored educational supplement, Interventional News speaks with Hicham Kobeiter, Marc Sapoval, and Wouter Van Den Eynde about their experience on using the Azurion platform with SmartCT to simplify 3D imaging.
The cover story of our latest issue, this story delineating the road to prostate artery embolization (PAE) gaining a recommendation by the American Urological Association (AUA) via inclusion in their guidelines made a splash. The Global Embolization and Cancer Symposium Technologies (GEST) 2021 Focus Day on PAE (6 March, online) sought to open discussion between urologists and interventional radiologists regarding the place of PAE in the treatment algorithm, a topic of heated debate in recent years.
In this video interview, Constantinos Sofocleous (New York, USA) sits down with Interventional News to discuss how image-guided thermal ablation, when it is deployed with an intent to cure small colorectal liver metastases, can be fine-tuned so that its outcomes match those achieved by open surgery.
Holmium-166 (166Ho) radioembolization is a safe treatment option for patients with hepatocellular carcinoma (HCC), show results from the prospective, clinical phase I/II HEPAR Primary study, presented at the European Conference on Interventional Oncology (ECIO; 10–13 April, online). Interventional News speaks with Marnix Lam (University Medical Centre Utrecht, Utrecht, The Netherlands) about these latest data, which are anticipated to be published in the coming months, as well as what to expect from the iHEPAR study, which looks at a fully individualised treatment approach, and which Lam claims is the future of HCC treatment. This article is sponsored by Terumo Interventional Systems.
Andreas H Mahnken (Clinic of Diagnostic and Interventional Radiology, Marburg University, Marburg, Germany) enthuses to Interventional News about the potential of degradable starch microspheres (DSM) in transarterial chemoembolization, specifically drawing on his 20 years’ experience with DSM particles (PharmaCept). Indicated for chemoembolization of primary and secondary liver and lung tumours, EmboCept S DSM 50μm are the best-calibrated DSM available, ensuring good vasculature penetration and with a flexible application. This article is sponsored by PharmaCept.
A new study, published online in The Journal of Vascular Access (JVA), suggests that arteriovenous fistulas (AVFs) contribute to higher survival of haemodialysis patients with COVID-19. Authors Ahmet Murt (Istanbul University-Cerrahpasa, Istanbul, Turkey) and colleagues urge that end-stage renal disease (ESRD) patients “should be given the opportunity to have their vascular access properly created,” even in the pandemic era.
Cagent Vascular recently announced the investment of US$9 million by Sectoral Asset Management. Along with the investment, Marc-Andre Marcotte has joined the board of directors. The proceeds will be used to accelerate the commercialisation and scaling of manufacturing for the Serranator below-the-knee (BTK) product. Further uses of proceeds include expanding the product offering to include larger sizes to treat the above-the-knee arteries.
Irreversible electroporation (IRE) is an effective and relatively safe treatment for colorectal liver metastases 5cm or smaller that are deemed unsuitable for partial hepatectomy, thermal ablation, or further systemic therapy, results of the COLDFIRE-2 study, published in Radiology, report. The two-centre, prospective, single-arm, Phase II clinical trial was conducted by Martijn Meijerink, Alette Ruarus (both Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands) and colleagues.
The June 2021 issue of Interventional News was published and distributed this month! Read it online and subscribe here to be sent a free physical copy quarterly.
Chair of the 2022 and 2023 European Conference on Interventional Oncology (ECIO), Philippe L Pereira muses on the status of interventional oncology (IO) in 2021, following more than a year of disruption from the ongoing COVID-19 pandemic. Through his work on various European guidelines delineating cancer care pathways, he has been instrumental in shaping the discipline and flying the flag for IO within multidisciplinary working groups. “Most oncologists recognise the value of our minimally invasive therapies and know very well how to integrate our treatments into the therapeutic armamentarium that currently exists for cancer patients,” he says.
The Roadsaver carotid stent system (Terumo France/Europe and MicroVention Europe) has been reimbursed in France. This follows the positive assessment from the French National Authority for Health (HAS), which highlighted a therapeutic benefit of the device.
“This decision bears out the wisdom of our strategy in the adoption of this technology since its availability in France,” says interventional cardiologist Max Amore (Clinic Louis Pasteur, Essey-Lès-Nancy, France). “We are glad that, now, more carotid patients will have access to Roadsaver, with its advanced design that provides a sustained embolic protection, [and] also after the procedure”.
This is the first dual-layer micromesh carotid stent to be approved by HAS and to be added to the list of reimbursed medical products (LPPR). The approved indication for Roadsaver is the same as for the previously approved “single-layer” platforms. It includes the treatment of symptomatic atherosclerosis when endarterectomy is not an option, or exceptionally in asymptomatic patients.
“The Roadsaver Dual-Layer Micromesh stent is considered a valuable alternative for open surgery in selected patients, based on its safety and efficacy profile, proven in an extended clinical programme,” comments Koen Deloose, director of ID3 Medical and head of the Department of Vascular Surgery at AZ Sint Blasius Hospital, Dendermonde, Belgium.
Terumo’s Roadsaver carotid artery stent system is designed to prevent a plaque protrusion through the struts and provide a sustained embolic protection, a press release explains. Its design incorporates a flexible nickel-titanium (Nitinol) dual-layer micromesh platform. Low crossing 5F profile allows for easy stent delivery in complex anatomies and is compatible with trans-radial approach.
Ghada Farah, SVP of Terumo Interventional Systems EMEA, adds: “We are delighted with this approval, which makes double layer micromesh stents available to all hospitals in France and confirms the robustness of our Roadsaver European registry data, the largest Carotid Artery stenting study in Europe”.
This reimbursement has been granted based on clinical evidence supporting the good safety and performance of Roadsaver carotid artery stent system in both symptomatic and asymptomatic patients, including the interim analysis of a large ROADSAVER observational study, currently being conducted in 13 European countries (52 sites) on about 2,000 patients enrolled.
Chair of the 2022 and 2023 European Conference on Interventional Oncology (ECIO), Philippe L Pereira muses on the status of interventional oncology (IO) in 2021, following more than a year of disruption from the ongoing COVID-19 pandemic. Through his work on various European guidelines delineating cancer care pathways, he has been instrumental in shaping the discipline and flying the flag for IO within multidisciplinary working groups. “Most oncologists recognise the value of our minimally invasive therapies and know very well how to integrate our treatments into the therapeutic armamentarium that currently exists for cancer patients,” he says.
My mother wanted me to go to law school, my father preferred business, so I decided to become a doctor! No, in actual fact, as far back as I can remember, I have always wanted to be a doctor. That said, I wanted to be a psychiatrist, and I am now on the other side of medicine, the more technical side. Why interventional radiology (IR)? IR, well, because I like the operational side and being able to have an immediate influence on the disease, so as to help patients as soon as possible—the diagnosis alone without the interventional side would never have satisfied me. What we do as interventional radiologists is just incredible.
Alain Roche would be the first one I would like to mention: I did not work with him for very long, but it was his enthusiasm that convinced me that IR was what I wanted to do in my life. The mentor I have learned the most from in the angiographic room was my colleague in Tübingen, Germany, Peter Huppert. One day, he brought back a radiofrequency generator that he had in his office; I quickly recognised the huge potential of this technology, and I have been using this therapeutic modality since 1996. I would also like to thank two other mentors who helped me a lot with their ideas: Fritz Schick, a physicist, and Claus Claussen.
First of all, I hope it will be a physical meeting, in person, and a great event to attend. It is a great honour for me that my European colleagues offer me this important position. My main purpose for this meeting is to emphasise the importance of clinical and pre-clinical studies, and to provide all possible support, starting from having the right idea—i.e. the study that will advance IO—then defining the design of the clinical study, right up to its funding. We will also highlight the multidisciplinary nature in the care of cancer patients: we are fortunate to include an oncologist, a surgeon, and a radiotherapist in the scientific programme committee (SPC). We also aim to cover the role that IO can play in combination with new immunological therapies, and to help define the contribution of artificial intelligence (AI) in our daily practice. All this will make ECIO 2022 an exceptional event.
At the beginning of the pandemic, I thought that many conferences would become “digital”; I no longer think so. I feel that colleagues need to meet and discuss their latest experiences in person, candidly exploring the latest innovations or their most recent cases, discussing why they did not work as expected or how they achieved such success. Nevertheless, this pandemic has stimulated us, forcing us to find new options to continue education and research. We will probably keep some of these options and make our meetings a kind of hybrid, with sessions that may be live (in person) or half-live (also available digitally).
Yes, under the leadership of Andy Adam, this Alliance is addressing, among other things, the recognition of IO, defining international criteria for quality of cancer care, helping to design working groups to explore new and complex aspects of cancer care, and supporting the role of interventional oncology. The list of activities we undertake goes on and on.
This is a question for which I would need a full journal to answer! When you are working on new guidelines, you need to know all the results of the clinical studies in order to get the best recommendations for the patients. This is a particularly complex job, as you also need to know the results obtained by other medical disciplines as well as those from your own specialty. In cancer care, you have to recognise and support the interdisciplinary aspect: no one has a monopoly on the ideal treatment alone. These collaborations are very important, firstly to define the best treatments for our patients, and secondly to secure (and defend) the position of IR. As we do not have the resources of the pharmaceutical industry for large randomised studies, we need the results of our treatments in large, prospective and controlled registries, which also have the advantage of presenting “real-world” results with a good level of evidence.
My experience is in fact very positive: IO has found its place in most guidelines, and this is in the interest of the patients. Most oncologists recognise the value of our minimally-invasive therapies and know very well how to integrate our treatments into the therapeutic armamentarium that currently exists for cancer patients.
IO is one of the most fascinating and promising specialties in medicine. To mention just a few aspects, I would like to emphasise the extraordinary opportunity that we must seize as interventional oncologists working in what we refer to as “the era of personalised medicine”. There are few medical disciplines that are as patient-oriented as ours. Each therapy is individualised: the application, the doses of drugs that are applied under imaging control, the change of therapies, and the possibility to combine our treatments with systemic treatments, surgery, or even radiotherapy.
Another key development is the enormous interest in new targeted therapies in the immunooncology space. Who can deliver these new therapies more locally than interventional radiologists? Another is to boost the immune response by combining our local treatments with systemic therapies. This is a great opportunity for our specialty. The interventional radiologist can be at the centre of this evolution, at least for some cancers in selected patients, if we are able to participate in preclinical and clinical studies. I say participate and unfortunately not lead because I must admit that we are not the first doctors to be contacted by the pharmaceutical industry.
To achieve this recognition we need first to make IR known to medical students (what could be more attractive than combining minimally-invasive treatments with minimised instruments, intelligent programmes, 3D images, and artificial intelligence). Second, we need to increase our influence in the education of young colleagues, to further the development of experts, and to be able to offer IO services in the same way that surgeons offer surgery: in all hospitals, not just in some specialised centres. Several scientific societies, such as the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), are working hard on this.
Our position is much better recognised than it was 20 years ago, but there is still a lot to do. The main challenge is to establish IO truly as one of the four pillars of cancer care. It seems to me that it is less necessary to convince oncologists—good oncologists know the benefit we can bring to patients—than it is to inform them of what we can do in the first place. Still too many oncologists are not aware of the wide spectrum of treatments we have to help cancer patients.
Another challenge I would like to mention here is the need to conduct good prospective clinical studies and to stop with retrospective studies on small cohorts that are generally not recognised for guidelines. Again, personalised medicine is a huge opportunity for interventional oncology.
I have a fantastic daughter, Anne-Sophie, of whom I am very proud, and with whom I try to make up for (past) lost time, and my wife, Bettina, with whom I have so many things in common. When I have some spare time, I take one of my electric guitars and play Hendrix, Led Zeppelin, Clapton… or at least I try to! My secondary hobby is definitely sports: tennis, jogging, and rowing, at least twice a week. When it rains, my reading is mostly focused on astronomy, from GNz11 to the acceleration of the universe and the quintessence!
Issue 82 highlights:
This educational supplement is sponsored by Philips.
In this supplement:
This advertorial is sponsored by PharmaCept.
Andreas H Mahnken (Clinic of Diagnostic and Interventional Radiology, Marburg University, Marburg, Germany) enthuses to Interventional News about the potential of degradable starch microspheres (DSM) in transarterial chemoembolization, specifically drawing on his 20 years’ experience with DSM particles (PharmaCept). Indicated for chemoembolization of primary and secondary liver and lung tumours, EmboCept S DSM 50μm are the best-calibrated DSM available, ensuring good vasculature penetration and with a flexible application.
Besides drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE), there is a subset of TACE called DSM-TACE, where you use degradable starch microspheres roughly 50μm in size. These microspheres have a half-life of approximately 35 minutes, which means they are only around for a couple of hours at most. This allows you to re-access the same vessel for repeated TACE. The half-life is also short enough to prevent the proliferation of growth factors such as VEGF [vascular endothelial growth factor], which usually enter the bloodstream after a few hours of ischaemia. One of the major advantages of [microsphere] degradability is that you do not have this additional vascular growth. There are actually no limits to the indication within the liver, and you can also use the degradable starch microspheres in the lung for transpulmonary chemoembolization (DSM-TPCE) or in the bronchial arteries, so DSM-TACE has a really broad scope of indications. Our main focus in my department is for liver metastases and primary liver cancer, but we also use it for lung cancer.
You have fewer limits. You can combine the procedure with any drug—not only, for example, doxorubicin or epirubicin, but you can really use it with any cytostatic that can be given intra-arterially, also in combinations, so it allows you to be much more flexible. That gives you a broader range of indications.
DSM-TACE also has excellent tolerability, so the patient experiences less pain. You can even perform a whole organ embolization with limited pain, which is pretty advantageous for the patient. It is much better-tolerated by the patient in terms of liver function and degradation, as well as in terms of pain. You can do it even in organs that would be critical for a cTACE or a DEB-TACE, so it gives you more flexibility—that is really the key for me.
If you have a patient with an organ that is already limited, for example a patient with cirrhosis, who then develops multinodular hepatocellular carcinoma (HCC), you may be concerned about having to treat multiple places in the liver. For example, with cTACE, there may be a limit because the function of the organ is not enough to allow treatment of all the tumours, but with DSM-TACE you can embolize all these tumours in a single session, and you will come out with enough remaining liver function to make sure that the patient can tolerate the procedure. In terms of efficacy, it is excellent.
To the best of my knowledge there are no limitations. You can even combine it with cTACE; there is a very small prospective randomised trial that combines DSM-TACE with cTACE. That is another opportunity.
Future applications could include combining DSM-TACE with systemic or even regional immunotherapy—it can be combined with many new drugs. We are living in the time of immunotherapy, and DSM-TACE can be combined with several immune modulators. I feel that this is a really exciting possibility. We have preclinical data that shows us that there is T-cell homing in the tumour after DSM application, so that would be an ideal target for immune modulators, not only interleukins but modern drugs as well. I feel that is one of the greatest potentials DSM-TACE has for the next decade.
Cholangiocarcinoma is a highly lethal hepatic neoplasm with a median overall survival rate of about 16 months (Waseem 2017). Even after resection, the prognosis is poor, with reported three- and five-year survival rates after resection for perihilar cholangiocarcinoma (pCCA) of around 45% and 30% (Cillo 2019). In unresectable pCCA, common treatment options included chemotherapy with gemcitabine and cisplatinum, and transarterial chemoembolization (TACE).
A 78-year-old female patient suffering from unresectable pCCA (Bismuth IV) was referred to our interventional radiology clinic for treatment after failure of first line chemotherapy. Magnetic resonance (MR) imaging revealed progression of the histologically-proven mass-forming pCCA, with multiple new histologies proving the presence of intrahepatic tumours and no extrahepatic tumour (Fig. 1).
On clinical examination, the patient was considered fit for interventional therapy. Laboratory testing showed mild anaemia and a moderately-elevated alkaline phosphatase. Her renal function was normal. She had previously undergone endoscopic biliary stenting, so her bilirubin was normal. We opted for a treatment with TACE and adjuvant capecitabine (Kelley 2020).
Our TACE protocol for cholangiocarcinomas includes a so called DSM-TACE with 300mg degradable starch microspheres (EmboCept S DSM 50μm, PharmaCept, Berlin, Germany) combined with intra-arterial application of 75mg/m2 Cisplatinum (PlatiCept, PharmaCept, Berlin, Germany) and Gemcitabine (1,000mg/m2). In addition, a premedication for nausea, pain, and a single shot of intravenous (IV) antibiosis in case of biliodigestive- anastomosis or stenting.
Diagnostic catheter angiography at the beginning of the first treatment session showed a fixed high-grade stenosis of the celiac trunk with subsequent collateral flow from the superior mesenteric artery (Fig. 2). For whole liver treatment, a 2.7F microcatheter was placed in the proper hepatic artery and DSM-TACE with flow-controlled slow infusion of the chemotherapeutics was performed (Fig. 3). Unlike in conventional TACE (cTACE), drugs were infused over a 30-minute period in order to minimise gastrointestinal toxicity in terms of nausea and vomiting. During administration of chemotherapy, EmboCept S DSM 50μm was repeatedly applied under angiographic control via a three-way stopcock. In Germany, PlatiCept is the only available cisplatinum powder. Its major advantage is its good solubility. Therefore, relatively high doses of cisplatinum can be administered with a small injection volume. The latter is considered helpful for maintaining the embolic effect of TACE. With DSM such as EmboCept S DSM 50μm, repeat treatments are feasible, as the target lesion remains accessible. Moreover, the half-life time of about 35 minutes for EmboCept S DSM 50μm minimises systemic expression of proangiogenic growth factors such as vascular endothelial growth factor (VEGF) (Schicho 2016). It moreover reduces side effects such as ischaemic pain, thereby facilitating whole liver treatment.
At six week intervals, the patient underwent three successful DSM-TACE procedures. The procedures were well tolerated, with only a mild one-week fatigue as the only symptom of post-embolization syndrome. The eight-month follow-up MR imaging showed partial response according to RECIST 1.1, with only very little tumour left (Fig. 4). So far, no change on laboratory testing has been seen. Almost two years after the initial diagnosis, the patient feels well without limitations in her daily activity. She is now scheduled for a three-month treatment holiday followed restaging.
References:
1. Waseem D, Tushar P. Intrahepatic, perihilar and distal cholangiocarcinoma: Management and outcomes. Ann Hepatol. 2017 Jan–Feb 2017;16(1):133-139.
2. Kelley RK, Bridgewater J, Gores GJ et al. Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol. 2020 Feb;72(2):353–363
3. Cillo U, Fondevila C, Donadon M et al. Surgery for cholangiocarcinoma. Liver Int. 2019 May;39 Suppl 1(Suppl Suppl 1):143–155
4. Schicho A, Hellerbrand C, Krüger K et al. Impact of Different Embolic Agents for Transarterial Chemoembolization (TACE) Procedures on Systemic Vascular Endothelial Growth Factor (VEGF) Levels. J Clin Transl Hepatol. 2016 Dec 28;4(4):288–292
This article is sponsored by Terumo Interventional Systems.
Holmium-166 (166Ho) radioembolization is a safe treatment option for patients with hepatocellular carcinoma (HCC), show results from the prospective, clinical phase I/II HEPAR Primary study, presented at the European Conference on Interventional Oncology (ECIO; 10–13 April, online). Interventional News speaks with Marnix Lam (University Medical Centre Utrecht, Utrecht, The Netherlands) about these latest data, which are anticipated to be published in the coming months, as well as what to expect from the iHEPAR study, which looks at a fully individualised treatment approach, and which Lam claims is the future of HCC treatment.
In the HEPAR Primary study, the investigators set out to establish the toxicity profile of 166Ho radioembolization (average liver absorbed dose of 60Gy) in patients with HCC. The primary endpoint was the rate of unacceptable toxicity, defined as total bilirubin increase grade 3 or higher (common terminology criteria for adverse events; CTCAE v.4.03) in combination with ascites and low albumin (radioembolization-induced liver disease; REILD), or any serious adverse event that was related to study treatment. Secondary endpoints included efficacy (according to modified response evaluation criteria in solid tumours; mRECIST), alpha fetoprotein response, dosimetry, quality of life, and liver function. Clinical and laboratory follow-up took place at three and six weeks, and three and six months. Patients included had measurable and liver-dominant disease and no curative treatment options.
Of the 31 patients included in the study, 71% were Barcelona Clinic Liver Cancer (BCLC) stage B, and 29% were BCLC stage C. Most (87%) had multifocal disease, and the median diameter of the largest tumour was 56mm (range 15–195mm). Lam describes this patient cohort as a “real-world” population.
Unacceptable toxicity related to the study treatment occurred in three patients; no REILD was encountered. New or worsened toxicity observed were: fatigue (71%), back pain (55%), ascites (32%), dyspnoea (23%), nausea (23%), and abdominal pain (23%), mostly grade 1. At three- and six- months follow-up, 54% and 84% of the target liver lesions showed complete or partial response. Median overall survival was 14.9 months, and no significant decline in quality of life was observed.
Most importantly, the primary endpoint of the HEPAR Primary study was safety. It was a Phase I/II study, in which safety was the primary endpoint and efficacy a secondary endpoint. From the study, we concluded that the toxicity is acceptable. We had pre-defined safety limits: in short, we considered grade III or higher toxicity, which was related to treatment, as unacceptable—but we only found this rate in three out of 31 patients, which confirms the safety in this patient population This result gives us the confidence to move on to further clinical studies of 166Ho-radioembolization in HCC patients.
The efficacy results of the HEPAR Primary study are also very encouraging, both in terms of response rate and in terms of survival for this patient population. This inspires us to continue to investigate this treatment for HCC patients.
I think what is very important for the HEPAR Primary study is the treatment planning involved. We chose an average absorbed dose for the whole perfused volume, so we did not make the differentiation between how many of these microspheres go to the tumour, and how many go to the surrounding liver tissue. For example: in one patient, the microspheres may all end up in the tumour, and none in the surrounding liver tissue (which is ideal, of course, because you hit the tumour hard and you do not damage the surrounding liver), but in another patient, it may be the other way around—you damage the surrounding liver tissue and you do not hit the tumour. So if you choose an average dose, and you treat all patients with a similar number of microspheres and just see where they end up, you are utilising a one-way-fits-all approach. Considering that we used this very rough treatment planning technique, I think the results are even more encouraging, with a lot of room for further improvement.
For every patient, after treatment, we can see the dose that went to the tumour and to the liver, and therefore we can ascertain how that correlates to effect and toxicity. We expect that the harder we hit the tumour, the better the effect, and the same for toxicity. So if we know that correlation, we can say, ‘OK, in terms of safety, the surrounding liver tissue can tolerate this amount of dose as a maximum’, and then in the next study, we will use that for individualised treatment planning.
These data are important to establish the safety profile of 166Ho-radioembolization. The HEPAR Primary study is the start of where we want to go with this therapy.
I think it is important to understand that previous studies on radioembolization in HCC—large, Phase III studies—all failed. These particular studies did not use individualised treatment. Because of that, the majority of patients were under-dosed. If you are treating blindly, then of course you need to be careful. I think for us now, it is incredibly important to show that the technique works.
The HEPAR Primary study is really the first step. The second step is showing that individualised radioembolization is feasible and has a benefit. The third step will be to compare it to the standard of care. That is also important—to show that this treatment option has a role to play in the HCC treatment algorithm.
To this end, we are currently working on the iHEPAR (individualised HEPAR) study. In this study, we are using a scout dose as part of the entire Holmium Platform to further individualise the selective internal radiation therapy (SIRT) planning. We have two procedures: the first procedure involves using a limited number of microspheres—enough to visualise where we are going, but not enough to cause damage. That is the scout procedure. We use a scout dose for three reasons:
In the HEPAR Primary study, we did use 166Ho scout dose, but it wasn’t applied to perform dedicated treatment planning. As a result, we treated patients with a one-size-fits-all approach. We used this information to establish the dose-effect relationship, which allowed us to determine the safety threshold dose for the liver. In the iHEPAR study, we will start using the information we obtain from the 166Ho scout dose to personalise the treatment using the entire end-to-end Holmium Platform. For example, if there is a patient where all the microspheres end up in the tumour, we can give him a higher dose.
Another area of future work is investigating the potential of combining 166Ho radioembolization with immunotherapy.
Especially in the era of immunotherapy, combining a locoregional treatment with an immunotherapy treatment is, I think, very interesting. To me, that seems to be the most logical next step: there are already studies underway that combine transarterial chemoembolization (TACE) with immunotherapy, so it seems logical to start combining radioembolization with immunotherapy.
I think that the best candidates for radioembolization are patients with large tumours. Usually, the larger the tumours, the greater the vasculature, so the better they absorb the microspheres, so to speak. This means you are able to target the tumour without damaging the surrounding tissue. So if, for example, you were treating a patient with a very large tumour on the right side of the liver, and multiple small ones on the left, this would be a super interesting candidate for combination therapy. You could hit the big tumour on the right side with 166Ho radioembolization, and then treat the smaller ones with systemic therapy (e.g. immunotherapy).
Cagent Vascular recently announced the investment of US$9 million by Sectoral Asset Management. Along with the investment, Marc-Andre Marcotte has joined the board of directors. The proceeds will be used to accelerate the commercialisation and scaling of manufacturing for the Serranator below-the-knee (BTK) product. Further uses of proceeds include expanding the product offering to include larger sizes to treat the above-the-knee arteries.
The Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter is an angioplasty device with serrated metal strips embedded on a semi-compliant balloon. The Serranator’s unique technology is designed to create multiple longitudinal lines of interrupted micro-serrations within the luminal surface to aid in arterial expansion. The result is predictable and controlled lumen gain using low atmospheres of pressure.
“Our BTK product launch is going extremely well. Early commercial adoption and clinical outcomes are confirming the positive results seen in the PRELUDE-BTK study. We are delighted to have a high-quality investor like Sectoral join our team. Their deep experience investing and advising device companies focused on peripheral vascular interventions will enable a more rapid expansion of our commercial efforts,” stated CEO Carol A Burns.
Marc-Andre Marcotte, of Sectoral, added, “We have been very impressed by Cagent’s achievements thus far and are excited to partner with them. We are confident that the unique features and high-quality clinical data of Serranator will drive strong market adoption.”
The Serranator’s differentiated mechanism of action is driving adoption. “The BTK space is in desperate need of innovation. These vessels are more challenging in terms of size, lesion length, and calcification and non drug-based balloon angioplasty is still the primary treatment. My experience with Serranator has been excellent and with its novel mechanism of action it has become an important tool in treating BTK disease. In the near future I look forward to using this technology in vessels above the knee to further optimise my angioplasty results,” explained Sarang Mangalmurti interventional cardiology specialist at Bryn Mawr Hospital (Philadelphia, USA).
Issue 82 highlights:
There are substantial differences amongst guideline recommendations regarding the use of prostate artery embolization (PAE) in the treatment of lower urinary tract symptoms/benign prostatic obstruction (LUTS/BPO), which can be partially explained by different interpretation of the evidence. This is the conclusion presented by Dominik Abt (Klinik für Urologie, Institut für Medizin, Universität St Gallen, St Gallen, Switzerland) at the Global Embolization and Cancer Symposium Technologies (GEST) 2021 Focus Day on prostate artery embolization (PAE; 6 March, online). This virtual meeting sought to open discussion between urologists and interventional radiologists regarding the place of PAE in the treatment algorithm, a topic of heated debate in recent years.
Speaking during the final session of the day, panel chair and co-course organiser Jafar Golzarian (University of Minnesota, Minneapolis, USA) praised the “unique” collaborative attitude of the virtual meeting, where attendees heard from four urology panellists and four interventional radiology (IR) panellists: “This session exploring the level of evidence and directions for future research in PAE is unique in both the IR and urology communities,” he said, “taking a truly interactive and multidisciplinary approach, which is not common practice.” He noted that he hoped this cross-disciplinary collaboration would continue in future meetings.
The American Urological Association (AUA) does not recommend PAE for the treatment of LUTS/benign prostatic hyperplasia (BPH) outside the context of a clinical trial, a recommendation attributed to the expert opinion of a panel of urologists. This news was unwelcome to the IR community when first announced in 2019, as interventional radiologists have been advocating for the procedure’s acceptance by the wider medical world. Multiple IR societies conclude that PAE is a safe, effective, minimally invasive treatment option in select BPH patients.
Evidence for PAE
Speaking first, Mark Little (Royal Berkshire NHS Foundation Trust, Reading, UK) discussed the most important PAE articles published in the last two years. In the last two years, 113 papers on PAE have been published. Of these, five were randomised controlled trials (RCTs), and eight were meta-analyses of systematic reviews.
Regarding the clinical effectiveness of PAE, Little said: “We cannot go beyond the superb sham RCT study that came out of Lisbon.” This was a 2019 study published in European Urology, the official journal of the European Association of Urology (EAU), from João Pisco, Tiago Bilhim (Hôpital Saint-Louis, Lisbon, Portugal) et al that found that the improvements in quality of life measurements and International Prostate Symptom Score (IPSS) in patients following PAE are “far superior” to those due to the placebo effect. Speaking to Interventional News at the time, Bilhim noted that publishing a paper positively describing PAE in a urology journal has historically been difficult for interventional radiologists. He hoped that this publication “might help our way into the urology guidelines with PAE”.
“Anyone who has tried to design a sham trial—which I am trying to do now for genicular artery embolization [GAE]—knows that it is hard work,” Little commented, in praise of the Lisbon group. “On the one hand it is the gold standard study design to refute the placebo effect, but there are a number of ethical dilemmas. So it is an ambitious study design, and one that the Lisbon group did extremely well to set up and running and recruit to.”
In the sham study in question, 80 patients were enrolled, randomised 1:1 to PAE versus a sham procedure with a cross-over design at six months. Summarising their findings, Little relayed: “They found a statistically significant refutation of the placebo effect—PAE does better than sham”. Asking the question, “Is PAE clinically effective”, Little argued that the answer was a definitive “Yes”, based off this Level 1 evidence.
Giving a more practical perspective, Little then turned to covering the evidence for altering clinical practice, focusing on papers dedicated to patients with median lobes and to the question of repeat PAE.
“I remember having conversations at CIRSE [the annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe] five or so years ago saying ‘Well, perhaps we should exclude patients with a median lobe, they seem to be difficult to treat’,” he said. Presenting a 2019 publication from Riad Salem (Northwestern University, Chicago, USA) and colleagues in Abdominal Radiology, looking predominately at imaging correlates: “A simple study,” Little opined, “but nevertheless [it] gives the idea and the introduction of where we sit with regard to the technique of embolizing the median lobe.” This cohort study showed that 37% of patients had a median lobe—intravesical prostatic protrusion (IPP)—and that 100% of those IPP-positive patients treated with PAE had a decrease in median lobe size following the procedure.
While this demonstrated that it was feasible to embolize the median lobe, Little asked “What does that mean clinically, do these patients get better?” He turned to a 2021 study from GEST co-founder Marc Sapoval, first author Tom Boeken (both Hôpital Européen Georges-Pompidou, Paris, France) et al that concluded that IPP is “not a prognostic marker of ineffective PAE in men with benign prostatic hyperplasia (BPH)”. Sapoval, Boeken and colleagues also wrote that severe protrusion could lead to a better response to PAE, “though expected prostate height reductions are mild”. They found that the degree of IPP did not limit the efficacy of PAE in patients with lower urinary tract symptoms (LUTS) due to BPH.
Furthermore, a 2020 paper in the Journal of Vascular and Interventional Radiology (JVIR) from Aaron Fischman (Mount Sinai, New York, USA) and colleagues answered the direct question “Should we be treating median lobes?”, Little reported. Stratifying the median lobes by size (patients were categorised as having non-severe IPP if their median lobe was <10mm, as was the case in 17 patients enrolled in the study, and as having severe IPP if their median lobe was >10mm, as was the case in 37 patients), Fischman et al found that both groups had a statistically significant improvement in IPSS and quality of life scores. “So we should not be scared of median lobes in terms of PAE,” Little concluded.
Concentrating on repeat PAE, Little relayed how approximately 20% of PAE patients could be deemed “clinical failures”, in need of further intervention. “Does that mean one in five need surgery?” he asked. Again turning to work from the Lisbon group, which focused on how these patients failed, Little recounted how patients in the study were categorised into two groups: group A (n=39), those who never showed a response to PAE; and group B (n=69), those who had clinical improvement in the first six months following PAE, but then relapsed. The investigators found that in 75% of patients, the blood flow was coming from the previously embolized prostate artery, perhaps indicating under-treatment, while in the remaining 25% of patients, the blood supply was from collateral vessels. At 24–26 months follow-up, 17% of group A had a clinical benefit from repeat PAE. This led Little to comment: “Effectively, if you have got a patient that does not respond initially, they are unlikely to respond. They [those in group A] probably need to be treated with surgery.” In group B, meanwhile, 52% had a significant clinical benefit from repeat PAE.
AUA guidelines
Little also considered the Society of Interventional Radiology (SIR) consensus panel conclusions, which were the focus of much of the day’s discussion. Published in JVIR and authored by Clifford Davis (College of Medicine and Radiology, University of South Florida, Tampa, Florida) et al, the summary of the SIR consensus panel on PAE regarding the development of a research agenda for the procedure concluded without direction: “Level 1 data are required to be included in the AUA guidelines for treatment of BPH. Because of concerns with all three study designs, the panel did not reach a consensus. Further meetings are planned with the panel to select among these research designs.”
The three research designs mentioned were: i) RCT of PAE versus sham with crossover of the sham group. (ii) RCT of PAE versus simple prostatectomy. (iii) RCT of PAE versus holmium laser enucleation of the prostate/thulium laser enucleation of the prostate.
The SIR consensus panel ultimately recommended a non-industry-funded registry to obtain real-world data.
Currently, the AUA guidelines state that “PAE for the treatment of LUTS secondary to BPH is not supported by current data and trial designs, and benefit over risk remains unclear; therefore, PAE is not recommended outside the context of clinical trials.” The guidelines claim this advice is based on expert opinion.
“I am a UK interventional radiologist,” Little acknowledged, “so I will be as objective as I can be in this argument.” He talked the GEST audience through the guidelines from the perspective of the SIR consensus paper. He noted that the AUA guidelines included RCTs with more than 12 months of outcome data, but that the AUA wanted PAE studies to include a 24-month follow-up “to be equivalent to current data on other surgical therapies for LUTS resulting from BPH”.
Citing a 2020 JVIR study from Iñigo Isausti (Complejo Hospitalario de Navarra, Pamplona, Spain) et al, Little related how the group set out to compare clinical and functional outcomes of PAE with those of transurethral resection of the prostate (TURP) for the treatment of LUTS secondary to BPH. Isausti and colleagues reported: “Reduction of LUTS in the PAE group was similar to that in the TURP group at 12 months, with fewer complications secondary to PAE.”
However, AUA require two-year data. “We are very fortunate to have Dominik [Abt] here,” Little said, “as the lead author of this paper”. Abt (Klinik für Urologie, Institut für Medizin, Universität St Gallen, St Gallen, Switzerland) et al conducted a study comparing the efficacy and safety of PAE and TURP in the treatment of LUTS at two-year follow-up.
They concluded in February 2021: “Inferior improvements in LUTS/BPO [benign prostatic obstruction] and a relevant re-treatment rate are found 2 years after PAE compared with TURP. PAE is associated with fewer complications than TURP. The disadvantages of PAE regarding functional outcomes should be considered for patient selection and counselling.” Their patient summary was: “PAE is safe and effective. However, compared with TURP, its disadvantages regarding subjective and objective outcomes should be considered for individual treatment choices.”
As the reintervention rate was 20% in the PAE group, Little said what treatment these patients should get next is “where the debate now lies”.
“I do not think this paper is a death knell for PAE at all,” he opined. “Actually, I think it shows that it is safe and effective, but, we need a reasonable discussion with our patients about what we can achieve with the technology based on patient selection, anatomy selection, pre-procedural imaging and planning.”
He concluded that PAE is safe and effective, and, in his eyes, gives patient’s a choice, which he believes is “really important”. Citing the sham trial and RCT data to two-years follow-up, Little summarised that there is “lots of level 1 and 2 evidence on PAE, which cannot be argued against in terms of the position statement of ‘Benefit over risk remains unclear’ [from the AUA guidelines].”
He continued: “I am not sure that we can say that with the current evidence case we have,” something fellow panellist and interventional radiologist Riad Salem (Northwestern Memorial Hospital, Chicago, USA) said he agreed with.
Going through the AUA guidelines comparing how PAE was assessed compared to alternative therapies, James Spies (MedStar Georgetown University Hospital, Washington, DC, USA) said he thought the recommendation not to perform the procedure outside of clinical trials was “actually a value judgement of one specialty of another” that “seems a little unusual”.
“This is not pointing fingers at the AUA,” he added. “I was former chair of the standards committee of the SIR, and I am a former [SIR] president—clinical practice guidelines really are intended to be evidence-based, and by-and-large they are. The process the AUA use is actually very good. But when it gets down to it, it is difficult to separate our preconceived notions from our review of evidence.”
“Again, this is not a knock on the AUA, but my opinion is that guidelines reflect the opinions of the organisations that create them. That is because it is almost impossible for a group in a room to go beyond what is not comfortable for them. In some ways, the SIR is never going to write a guideline that says PAE is bad, probably, unless we have some definitive data, and the AUA may never write one that says it is good or at least should be on the list. So I would agree we need to increase our data, but I am just not sure we are ever going to be able to get there. This is a benchmark procedure for urologists, and, just like some other specialties that we work with, it can be difficult to get adoption.”
When thanking Spies for his talk, Golzarian noted that Spies is a “pioneer” for uterine fibroid embolization (UFE), a procedure now widely recognised and performed by interventional radiologists: “It is like revisiting history; we are 15 years behind with PAE [compared to UFE], but hopefully we will see the same acceptance,” he commented.
Quality of evidence for PAE: The urologist perspective
Speaking next, urologist Philipp Dahm (Minneapolis VA Medical Center and University of Minnesota, Minneapolis, USA) gave a talk entitled, “Objective rating of evidence: Why it matters and how it applies to PAE”. He recommended the following: “Current best evidence on PAE should be assessed on the basis of a high-quality, protocol-driven systematic review. The focus should be on patient-important outcomes with explicit consideration of clinically important differences [in the case of PAE, this includes IPSS and quality of life scores, adverse events, and retreatment rates; flow rate and prostate volume are deemed “not important for decision-making” by Dahm]. The certainty of evidence rating should be provided on a per outcome basis to qualify how much confidence we have. Lastly, judgements about net benefit need to consider both relative and absolute effect size estimates.”
Dahm is a founding member of the US grading of academic assessment, development, and education (GRADE) network, an informal working group formed in 2000 to develop a new system for rating the certainty of evidence in healthcare and also for making guidelines. Currently, GRADE has over 500 members, and is used by more than 120 organisations.
Unlike the traditional “hierarchy of evidence”—which treats systematic reviews, meta-analyses, and randomised controlled trials at the gold standard—GRADE is based on an alternate hierarchy that Dahm said reflects the flaws in these assessment methods. In particular, he noted that RCTs “can be fatally flawed” in their design, and noted that systematic reviews are only as good as the individual studies they evaluate, so could suffer from a “garbage in, garbage out” scenario. In the GRADE system, systematic reviews are “undocked” from the very top of the triangle in the traditional hierarchy of evidence graphic, and are used as a tool for assessing a body of evidence.
The GRADE system works thus: formulate a question; select outcomes; rate the importance of these outcomes (on a scale from critical, to important, to less important) look at outcomes across studies; create an evidence profile with GRADEpro, which includes a summary of findings and an estimate of the effect for each outcome; rate the quality of evidence for each outcome (from high, through moderate and low, to very low).
“It is really important to provide a certainty of evidence rating that reflects the confidence that we have that an estimate of effect is adequate to support a clinical decision or recommendation,” Dahm said. So a GRADE rating of “high” corresponds to “We are very confidence that the true effect lies close to that of the estimate of the effect”. A “very low” rating translates to “We have very limited confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect”.
He talked the audience through the GRADE summary of findings table for Cochrane review conducted by urologist Jae Hung Jung (Yonsei University Wonju College of Medicine, Wonju, South Korea) and colleagues and published in 2020, which set out to assess the effects of PAE compared to other procedures for treatment of LUTS in men with BPH. Using an updated version from March 2021, Dahm recounted how the GRADE interpretation of the change in IPSS and quality of life scores following PAE is that there is “little or no difference for these outcomes short-term compared to TURP”. In addition, he said that “we are very uncertain” about PAE having a lower major adverse event rate than TURP. Lastly, he noted that the “greatest certainty” the GRADE reviewers had was regarding retreatment rates in the short-term, which they believed were “probably increased” after PAE.
Quality of evidence for PAE: The IR perspective
Salem offered an interventional radiologist’s perspective, which served as a riposte to Dahm’s previous talk, and detailed the strength of evidence for PAE’s safe and efficacy. While he said he understood the initial scepticism about the success of embolizing the prostate gland, he noted that there have been technical improvements in the procedure since its inception. Furthermore, while attempts at “gold standard” PAE versus TURP trials had failed in the USA, more recent propensity-matched, prospective comparisons of the two procedures and randomised trials of TURP versus sham a procedure are positive indicators that PAE has a positive future.
“More importantly, to Philipp [Dahm]’s point,” Salem commented, “there is a growing patient interest in alternate therapies.”
Following a review of the evidence for PAE, Salem concluded: “In my opinion, no one can say PAE does not work. It does in my opinion satisfy all criteria for a reasonable treatment, and it should be an option presented to patients. At minimum, it should have a limited recommendation for large glands [prostate volumes >80cc], where effectively all of the MISTs [minimally invasive surgical therapies] are ineffective, by the AUA guidelines.
“The AUA guidelines are important, but they are not the final word. Respectfully, no one has a monopoly on the management and the clinical development of managing patients with BPH-LUTS. It should be a team effort. As Philipp said, Level 1 evidence is not the only method of generating high-level, relevant data. Good Phase II data can do that as well—there are ethical and technical challenges with RCTs, as Mark [Little] spoke about.
“Unfortunately, we have been slowed down by—in my opinion—the emotional and polarising reaction by KOLs [key opinion leaders] to evolving PAE data. It is my observation that there is a perceived inconsistency in the manner PAE data are interpreted compared with that [for] MISTs. I think we need to work together, and PAE needs to be offered to the right patient. We need a collaboration between IR and urology, and this collaboration must evolve, not devolve, in a multidisciplinary manner that will benefit patients.”
He ended with a specific request of the attending urologists: “At the end of the day, patients are not satisfied with TURP and MISTs as the only options; they are demanding something else. What I would ask is, given this, what is the pathway for recognition of PAE, at least in a limited scope, [in the AUA guidelines]? If the response is a clinical trial, I would like to know which clinical trial explicitly.”
Offering one urologist’s perspective (with particular emphasis afforded to the “one”), John Kellogg Parsons (Moores UC San Diego Cancer Center, San Diego, USA) took to the virtual podium next. Despite being chair of the AUA BPH guidelines panel, he noted that he was not speaking on behalf of the AUA in any capacity.
He suggested some potential ways forward for interventional radiologists and urologists: “[Look for] other study populations and indications. I think LUTS is unlikely to gain significant traction within the urological community as an indication for performing PAE, so I would encourage you to look for other indications. Haematuria is what I hear constantly as a very compelling indication to investigate, but there are no clinical trials to investigate this. Neoadjuvant therapy, I have heard that hypothesised, I think that is a reasonable avenue to explore; urinary retention and very large prostate, I think that is very reasonable to explore. Always longer term data, and absolutely more multidisciplinary collaboration and coordination.
Addressing his fellow panellists, he said: “I think it is important for this group to know that this field is always rapidly evolving. There is an enormous amount of capital in the private sector in biotech that is investing in newer technologies for BPH. To my knowledge there are at least eight novel urethral stents that are in late phase clinical trials, all with urologists—they come to us when they want to run BPH clinical trials. I would ask you to ask yourselves—the PAE technology, is it static, or dynamic? What kind of future relevance does it have, knowing that this field is constantly evolving with new devices?”
Closing the session, Abt, a principal investigator and sub-investigator in various clinical trials on the treatment of LUTS/BPO (including on PAE, TURP, HoLEP, Aquabeam, and PVP) and a guideline panel member for the Germany Society of Urology document on benign prostatic syndrome, summarised the structural and methodological, problems of guidelines in a bid to understand the reasons for the discrepancies between the SIR and AUA recommendations.
“There are widespread financial and professional conflicts of interest among the sponsors of guidelines, so the societies,” he said, “and also among the authors. Industry funds a network of lobbyists, researchers, and opinion leaders, which then write our guidelines. ‘Panel stacking’ is another problem: if a novel panellist is nominated, they are probably nominated because they believe in the same school of thought, so that leads us to imbalanced guideline panels.”
He commented that the most important part, in his view, is that guidelines often have “highly biased panel compositions”—drawing a “very provocative” comparison, he asked rhetorically: “Which institution would you ask to get the most reliable data on gun violence in the USA? The National Rifle Association (NRA), Americans Against Gun Violence, or a more independent source?
“The same is true for the guidelines for PAE. On the one hand, we have a group of persons that are highly interested in a broad application of PAE, as they work for a society that of course has to represent the interests of their members [indicating the SIR multisociety consensus position statement on PAE for the treatment of LUTS]. The same is absolutely true for the AUA guideline panel.
BPH treatment is a billion-dollar business, and here we have panels where at least some of the people involved have substantial conflicts of interest. In my opinion, it is just plausible that both societies reach different conclusions.”
Abt also touched on the lack of “proper, independent peer-review” prior to the publication of most guidelines, and the idea that recommendations are often provided “despite the data [that form the basis of this advice] being judged as unreliable”.
He agreed with the Institute of Medicine suggestion of removing individuals with a financial conflict of interest from guideline panels, and to implement a limitation on the involvement of clinicians with a professional conflict of interest. “Content experts should be consulted, but not write the guidelines,” he concluded. “Instead, we should use independent statisticians and methodologists, patient representatives, and general practitioners that are interested in the field, but do not earn their money from it.” Abt advocated for the inclusion of a guideline panel review and a checklist to score guidelines ahead of publication, to minimise bias.
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“Improving vessel compliance with focused force longitudinal plaque fracture seems to be a promising strategy instead of standard percutaneous transluminal angioplasty [PTA],” states interventional angiologist Michael Lichtenberg (Arnsberg Vascular Center, Arnsberg, Germany), detailing that the technique avoids “significant vessel damage”. In this case report for Vascular News, Lichtenberg evidences this claim, outlining a case involving the recanalisation of a long superficial femoral artery (SFA) occlusion involving lesion preparation with an Ultrascore™ Focused Force PTA Balloon (BD) followed by angioplasty using a Lutonix™ 018 Drug Coated Balloon PTA Catheter (BD).
An 80-year-old man with severe claudication of the right leg was admitted to our vascular centre. Cardiac risk factors included poorly-controlled diabetes, hyperlipoproteinaemia, and smoking. On duplex ultrasound, a long occlusion of the right SFA from the origin to the popliteal artery was diagnosed (Figures 1 and 2). Ankle brachial index (ABI) on the right side was 0.6. No wounds were present on the right extremity.
Subsequent diagnostic angiography confirmed the long SFA occlusion with diminished contrast flow below the knee and into the foot. For recanalisation of the long SFA occlusion, a crossover approach from the left groin was performed using the new Halo One™ Thin-Walled Guiding Sheath (BD) 70cm, 5 French. This sheath provides a 1 French wall thickness, which reduces the size of the arteriotomy compared to standard sheaths of the same French size without sacrificing inner diameter. The flush occlusion of the SFA (Figure 3) was penetrated with a 0.018” Glidewire Advantage (Terumo Interventional Systems). It was easy to achieve distal re-entry into the true lumen. Next, a two-minute lesion preparation was performed with an Ultrascore™ Focused Force PTA Balloon 5x150mm 5 French with repetitive inflation to 8atm over the whole length of the target lesion. This scoring balloon is designed to longitudinally fracture plaque at a lower inflation pressure. Compared to a standard balloon angioplasty, the Ultrascore™ Focused Force PTA Balloon provides approximately 24 times more force where the wire contracts the lesion. This lesion preparation was then followed by two-minute drug-coated balloon (DCB) angioplasty (Lutonix™ 018 Drug Coated Balloon PTA Catheter 5x220mm and 5x120mm; Figure 4). Subsequent angiographic analysis ruled out a persistent dissection or significant recoil.
After revascularisation, a brisk flow was seen within the whole length of the target lesion, as was a straight flow into the foot (Figures 5 and 6). Follow-up examination of the patient the next day showed an ABI of 0.95 on the right side and a significant improvement in pain-free walking distance with no pain in the target limb during a treadmill test after 500m.
Many options for endovascular revascularisation therapy exist today. Most therapeutic approaches involve PTA as the primary therapy, which consists of adventitial stretching, medial necrosis, and controlled dissection or plaque fracture. Acute vessel damage is frequently seen in non-compliant calcified atherosclerotic vessels and may range from simple plaque rupture to severe flow-limiting dissection, or even local perforations. Dissections can induce pathologic haemodynamic defects, and have been implicated as a contributing factor in acute procedural complications as well as restenosis at the target lesion site. Therefore, improving vessel compliance with focused force longitudinal plaque fracture seems to be a promising strategy instead of standard PTA to avoid significant vessel damage, which may lead to long stent implantation. Reassuringly, the results of the SWEDEPAD interim analysis adds further important safety data on drug-coated devices when used to treat femoropopliteal disease.
Case images
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A new study, published online in The Journal of Vascular Access (JVA), suggests that arteriovenous fistulas (AVFs) contribute to higher survival of haemodialysis patients with COVID-19. Authors Ahmet Murt (Istanbul University-Cerrahpasa, Istanbul, Turkey) and colleagues urge that end-stage renal disease (ESRD) patients “should be given the opportunity to have their vascular access properly created,” even in the pandemic era.
The Kidney Disease Outcomes Quality Initiative (KDOQI) clinical guidelines recommend arteriovenous access instead of central venous catheters for haemodialysis, the authors state. However, the American College of Surgeon’s case triage guideline for COVID-19 deemed AVF or arteriovenous graft (AVG) operations to be elective and suggested that “postponing should be considered”. Against this background, the investigators sought to analyse the effect of vascular access on the outcomes of haemodialysis patients with COVID-19—a group they note are highly clinically vulnerable.
Murt and colleagues retrospectively analysed 104 haemodialysis patients with COVID-19 from two tertiary care hospitals located in Istanbul. Seventy-two of these patients had AVF as the vascular access, with the remaining 32 patients having had tunnelled catheters. They report that COVID-19 had a high mortality rate in haemodialysis patients (36.5%), with AVFs (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.05–10.72; p=0.041) and using medium cut-off dialysers (OR, 7.99; 95% CI, 1.53–41. 65; p=0.014) being related to higher survival.
In the discussion of their findings, the authors note that those patients with an AVF and those with a catheter were similar for age and comorbidities. “In spite of similarity for COVID-19 severity, peak CRP [C-reactive protein] and ferritin levels were higher for patients in whom catheters were used as vascular access,” they relay, noting that such higher levels in the catheter group point to a higher inflammatory response in catheterised patients.
Murt et al believe that delaying AVF operations “might have socioeconomic, medical, and ethical consequences,” stressing that more frequent use of catheters for haemodialysis will results in more catheter-related complications, requiring longer hospitalisations and, in turn, a higher economic burden.
While the authors recognise that the small sample size may be a limitation of the study, they stress that ESRD patients “should not miss proper vascular access opportunities” based on their findings, especially given that “it does not seem that the pandemic will end in the near future”. They conclude: “Balancing the use of resources with patient-centred decisions should be the approach going forward”.
Constantinos Sofocleous (New York, USA) sits down with Interventional News to discuss how image-guided thermal ablation, when it is deployed with an intent to cure small colorectal liver metastases, can be fine-tuned so that its outcomes match those achieved by open surgery.
There are several minimum requirements for ablation to be curative, and Sofocleous outlines these as: adequate imaging to see the target tumour well; tools that allow for optimal placement of the electrode; intraprocedural ability to see the ablation zone and the ability to confirm tumour eradication with adequate margins at the end of the procedure.
Sofocleous also discusses the ACCLAIM trial, of which he is the principal investigator with particular reference to the ablation margins (5mm, and ideally 10mm), stating that when margins are adequately ablated, local tumour control is similar, if not better, than wedge resection for small colorectal liver metastases.
The Society of Interventional Oncology aims to use the trial’s findings to raise the bar and demonstrate that with minimum requirements and standards, ablation can be moved to being a standard of care across different global health care systems.
Irreversible electroporation (IRE) is an effective and relatively safe treatment for colorectal liver metastases 5cm or smaller that are deemed unsuitable for partial hepatectomy, thermal ablation, or further systemic therapy, results of the COLDFIRE-2 study, published in Radiology, report. The two-centre, prospective, single-arm, Phase II clinical trial was conducted by Martijn Meijerink, Alette Ruarus (both Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands) and colleagues.
IRE is a non-thermal ablative technique that uses high-voltage electrical pulses, and, according to the study authors, has shown promise for eradicating tumours near critical structures, including blood vessels and bile ducts. This is exactly why it presents an attractive treatment option to many interventionalists: those patients treated in COLDFIRE-2 were all inappropriate candidates for partial hepatectomy or thermal ablation due to the proximity of their tumours to critical structures. Indeed, up to 70% of patients with colorectal liver metastases are not eligible for surgery because of comorbidities or owing to the number, location, or distribution of the metastases.
Meijerink, Ruarus et al explain that, although most current guidelines consider thermal ablation (radiofrequency and microwave; RFA and MWA) to be the standard of care for small, unresectable colorectal liver metastases, its contraindication for tumours close to large hepatic vessels presents an unmet clinical need that can be catered for by IRE.
The COLDFIRE-1 study (Colorectal liver metastases disease: efficacy of irreversible electroporation, a single-arm, Phase 1 clinical trial) first demonstrated IRE’s ability to eradicate colorectal liver metastases in humans. The COLDFIRE-2 triallists write: “The reported efficacy of hepatic IRE varies widely (45.5–100%) because of the heterogeneity of patient and tumour characteristics, and most studies represent small retrospective cohort studies or case reports with short-term follow-up. The early adaptation of electroporation into the toolbox of ablative methods by the European Society for Medical Oncology in 2016 seems premature given the nonexistence of larger-scale prospective controlled efficacy studies.”
Between June 2014 and November 2018, 50 participants, with 76 fluorine 18 (18F) fluorodeoxyglucose (FDG) PET-avid colorectal liver metastases 5cm or smaller between them, underwent percutaneous or open IRE. Follow-up included tumour marker assessment and 18F-FDG PET/CT imaging every three months for the first year after IRE, and every six months thereafter. The median follow-up after the first, second, and third IRE procedures was 23.9 months, 9.5 months, and 6.3 months, respectively.
The study mets its primary endpoint, which mandated that at least 50% of treated participants had to be alive without local tumour progression at 12 months, defined as local tumour progression-free survival. Per-participant one-year local tumour progression-free survival was 68% (95% confidence interval [CI]: 59, 84) according to competing risk analysis.
Outlining why this primary endpoint measure was used, Meijerink, Ruarus and colleagues explain: “Because the participants in this trial were often heavily pre-treated, overall survival would not properly reflect the efficacy of IRE, and therefore one-year local tumour progression-free survival was chosen as the primary end point.”
The authors go on to say that these results “are in line with those of recent retrospective series”, and conclude: “Thus, we believe that IRE should be accepted as a niche indication for difficult-to-reach colorectal liver metastases, but only in the salvage setting of permanent unresectability and unsuitability for thermal ablation.”
Writing in an accompanying editorial in Radiology, S Nahum Goldberg (Hadassah Hebrew University Medical Center, Jerusalem, Israel) claims the COLDFIRE-2 trial “has the potential to provide a substantial impact on the treatment of this malady and on interventional oncology as a whole”.
Speaking of the trial, he says: “This well-designed and superbly executed effort represents a pivotal clinical trial of IRE for the treatment of intrahepatic colorectal metastases unsuitable for partial hepatectomy, thermal ablation, and further systemic treatments. The authors offer hope for achieving successful treatment for a larger population of difficult-to-treat patients—namely those with centrally located tumours and those with tumours between 3 and 5cm in diameter.”
He continues: “Although the populations were relatively small and will require further confirmation, these data suggest that IRE techniques may enable adequate coverage to expand the range of successfully treated tumours. Some of these benefits may be due to synergistic effects between IRE and the chemotherapy administered in a majority of patients. Combination therapy between thermal ablation and induction chemotherapy—administered systemically or by means of chemoembolization—has demonstrated results that can even outperform surgery.
“Further research and collective experience are warranted if we are to achieve the best clinical results possible. […] The final results of COLDFIRE-2 have been long anticipated and are of great interest to interventional, medical, and surgical oncologists and the patients we serve.”
Secondary endpoints: IRE effective, but depends on operator experience
Secondary aims included safety, technical success, local control allowing for repeat procedures, disease-free status, and overall survival.
The per-tumour one-year local tumour progression-free survival rate was 79% (95% CI: 68%, 88%). Median distant progression-free survival was 5.3 months (95% CI: 2.5, 8.1). The most frequent site of first recurrence was the liver; median extrahepatic progression-free survival was 12.5 months (95% CI: 5.9, 19.1). Median overall survival from was 2.7 years (95% CI: 1.6, 3.8) from the first IRE and 4.8 years (95% CI: 3.1, 6.6) from the date of resection of the primary tumour.
The study authors detail that after repeat procedures, local tumour control was achieved in 74% of participants (37 of 50 patients). They expand: “Six participants were considered unsuitable for local repeat treatment at first local tumour progression because of coexisting distant disease progression, making local treatment futile”.
Local control was not achieved in two participants despite multiple attempts to eradicate the tumours. Recurrences were treated with repeat IRE (n=12), thermal ablation (n=three), stereotactic body radiation therapy (n=three), or selective internal radiation therapy (n=one). In a comparison of the first five versus the next 45 participants, the eventual local tumour progression rate was 80% (four of five) versus 33% (15 of 45) (p=0.06).
Meijerink, Ruarus, and colleagues state that, although this did not reach statistical significance in their study, “the local tumour progression rate of 80% versus 33% in the first five versus the next 45 participants strongly suggests that IRE is dependent on operator experience.”
They determine that, in their opinion, this “underlines the necessity to set up dedicated training programmes and preferably claim minimum volume thresholds” for performing IRE.
Cox regression analysis showed no statistically significant difference in local tumour progression-free survival between small and medium-size tumours (hazard ratio, 1.7; p=0.22). Therefore, Meijerink, Ruarus, et al speculate that technique efficacy may be less susceptible to size with IRE, in which tumours are bracketed by the electrodes, compared with single-probe thermal ablation.
The overall complication rate was 40%: 23 participants experienced a total of 34 adverse events in 25 of the 62 procedures. The most common grade 3 adverse events were de novo biliary obstructions (n=3), periprocedural cardiac arrhythmias (n=4), and portal vein thrombosis (n=3). Two participants experienced a grade 4 adverse event. One participant (2%), who an an infected bilioma after IRE, died fewer than 90 days after the procedure—classified as a grade 5 event. “Our higher complication rate can be partially explained by our prospective study design and allowance for simultaneous procedures during IRE. […] Therefore, not all reported adverse events are likely to be related to the IRE procedure itself,” Meijerink, Ruarus, and co-authors write.
Embolx has announced the launch of its balloon occlusion microcatheter, Sniper, to the European market. Sniper is a delivery system for pressure-directed arterial embolisation therapy and is designed to increase embolic loading and improve tumour response.
The device alters blood flow-dynamics by controlling pressure to increase therapeutic agent delivery into target areas for the treatment of tumors, benign prostatic hyperplasia (BPH), and uterine fibroids. Embolx say that the therapy allows interventional radiologist physicians to deliver drugs and embolic agents to targeted treatment areas while protecting surrounding healthy tissues.
Embolx’s second generation Sniper microcatheter is available in Europe in two tip options–straight tip and K-tip and two lengths 130cm and 150cm–enabling interventional radiologist physicians to access both femoral and radial sites and to navigate torturous arterial anatomy.
Michael Allen, president and CEO of Embolx, said: “I am pleased to offer our technology to the European market, which brings with it the experience of over 5,000 cases completed here in the US
“Now, interventional radiologists can do everything they would do with standard microcatheters, but with the added benefits of balloon occlusion. This is a big step forward and provides physicians with the most advanced transarterial delivery system for tumor and prostate treatment.”
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Researchers have found that the AMPREDICT decision support tool (DST) demonstrates “strong usability characteristics and clinical relevance” in amputation level decision making for patients with chronic limb-threatening ischaemia (CLTI). Daniel C Norvell (VA Puget Sound Health Care System, Seattle, USA) and colleagues suggest in an online European Journal of Vascular and Endovascular Surgery (EJVES) article that, following “extensive iterative development and testing,” the tool should now be applied in clinical practice.
The authors describe the AMPREDICT DST as “a novel, web-based, clinical DST that calculates individual one-year postoperative risk of death, reamputation, and probability of achieving independent mobility by amputation level”.
They detail that there are currently a lack of individual patient risk factors informing available evidence on amputation level decision making in patients with CLTI, which instead relies on average population risks. As a result, there is “significant variation of amputation levels across health systems, geographical regions, and time,” the authors state.
While prediction models have been published to hone in on individual patient risk factors, translation to clinical application “has not been undertaken,” Norvell et al write—a gap in the literature this study sought to address. Specifically, the investigators aimed to translate the previously validated AMPREDICT prediction models by “developing and testing the usability of the AMPREDICT DST”.
The investigators explain that a mixed-methods approach was applied to assess the AMPREDICT DST. “Previously validated prediction models were translated into a web-based DST with additional content and format developed by an expert panel,” they explain.
Elaborating on their methods, Norvell and colleagues note that ten clinician end users “from diverse specialities, sex, geography, and clinical experience” assessed tool usability while interacting with the tool using a hypothetical case scenario and an example from their practice. The clinicians engaged in a “think aloud” approach so that investigators could go back and review the interactions. After the interaction, each clinician participated in a semi-structured qualitative interview to evaluate the AMPREDICT DST’s look and feel, user friendliness, readability, functionality, and potential implementation changes. In addition, they completed the Post-Study System Usability Questionnaire (PSSUQ)—a 16-item scale with scores ranging from 1–7, with lower scores indicating greater usability.
Writing in EJVES, the authors report that “most providers said they were eager to use the AMPREDICT DST and some requested to use it as soon as possible”. Furthermore, the qualitative interviews suggested the potential utility of the DST included the following: assistance in counselling patients on amputation level decisions, setting outcome expectations, and use as a tool in the academic environment to facilitate understanding of factors that contribute to various outcome risks. The authors also communicate “favourable” overall and subscale PSSUQ scores, with a mean overall total score of 1.57 (standard deviation [SD], 0.69) and a range from 1–3.21.
Norvell et al acknowledge that the AMPREDICT DST has limitations. For example, they recognise that “the risks produced by the tool are generated from models developed in patients undergoing their first major amputation who did not have severe comorbidities (e.g. coma, paraplegia, quadriplegia, disseminated cancer, tumour of the central nervous system, ventilator dependent) that would put them at high risk of death and more likely a candidate for transfemoral amputation only.
Another issue raised is that the models were developed and validated in a US Veteran population with CLTI, comprising mainly males. Therefore, the use of the DST in other populations “should be considered with caution, since the management and risks of patients in VHA [Veteran Health Administration] hospitals may differ from other populations”.
Despite these drawbacks, the authors stress that the tool is set to move into the next phase of development and evaluation with integration into the VHA electronic health record (EHR). This, they state, will allow for assessment of its impact on physician and patient shared amputation level decision making.
Boston Scientific has initiated the European launch of its SpaceOAR Vue Hydrogel, which is designed to create a temporary space between the prostate and the rectum, minimising the potential side effects of radiation therapy.
The new radiopaque SpaceOAR Vue Hydrogel can be seen on computerised tomography (CT) scans, negating the need for physicians to include magnetic resonance imaging (MRI) in the treatment planning, and accommodating patients who are contra-indicated for MRI
According to the World Health Organisation prostate cancer is the most common cancer affecting men in Europe. More than 400,000 new cases are diagnosed each year, and the the European Association of Urology consider radiotherapy a highly effective treatment.
However, due to the close proximity of the rectum to the prostate, prostate radiation therapy can cause unintended damage to the rectum, which can lead to fecal incontinence issues or other long-lasting side effects.
Clive Peedell, consultant clinical oncologist from the South Tees Hospitals NHS Trust (Middlesbrough, UK), said: “SpaceOAR Vue Hydrogel helps to reduce rectal dose in radiation planning, as well as increase clinician confidence in accurate contouring of the prostate and rectum.
“The increased visibility of the gel also helps in the image-guided targeting of the radiotherapy delivery to the prostate, ensuring treatment accuracy and high-quality care for patients.”
The SpaceOAR Vue Hydrogel perirectal spacer offers the same clinical benefits as traditional SpaceOAR Hydrogel, which was the first FDA-cleared and CE Marked hydrogel perirectal spacer, and has been used in over 100,000 patients worldwide, say Boston Scientific.
In a randomised clinical study of SpaceOAR Hydrogel, at median three years, more patients in the control group experienced declines in bowel (41% vs 14%) and urinary (30% vs 17%) quality of life than in the spacer group.
Additionally, more patients who were potent at baseline and treated with SpaceOAR were able to achieve erections sufficient for intercourse (66.7%, vs. 37.5%) than in the control group.
Miguel Aragon, vice president EMEA, urology and pelvic health at Boston Scientific, added: “SpaceOAR Vue Hydrogel demonstrates our commitment to addressing unmet patient and physician needs with innovations that provide the best possible care.
“SpaceOAR Vue Hydrogel’s design may enable physicians to streamline the department’s procedural workflow by reducing the need for post-procedural MRI scan, while reducing radiation exposure for patients undergoing radiation therapy.”
AngioDynamics recently announced that it has received 510(k) clearance from the US Food and Drug Administration (FDA) for the AlphaVac mechanical thrombectomy system.
According to a company press release, AlphaVac is an off-circuit, multipurpose mechanical aspiration thrombectomy device for the non-surgical removal of thrombi or emboli from the vasculature.
AngioDynamics continues to anticipate the commercial release of the AlphaVac system in the second half of calendar year 2021.
Royal Philips recently announced positive two-year results from the TOBA (Tack optimised balloon angioplasty) II below-the-knee (BTK) clinical trial.
The data show the Philips Tack endovascular system (4F), a first-of-its kind dissection repair device, provides a sustained treatment effect and positive impact on quality of life for peripheral arterial disease (PAD) and chronic limb-threatening ischaemia (CLTI) patients at two years. George Adams (Rex Hospital, Chapel Hill, USA), co-principal investigator, presented the findings at the 2021 New Cardiovascular Horizons (NCVH) conference (1–4 June, New Orleans, USA).
Across all patients in the TOBA II BTK clinical trial at two years, 73.6% had freedom from clinically-driven target lesion revascularisation (CD-TLR) and did not require a repeat procedure for the treated artery segment. CD-TLR is a commonly used indicator of treatment efficacy durability. In the more complex CLTI patient population, which is typically associated with high rates of amputation and mortality, the data showed 94.7% target limb salvage (freedom from major amputation).
“The global endovascular community is diligently working to better understand how to restore blood flow in small limb vessels, promote healing and ultimately preserve limbs for people with CLTI, one of the most vulnerable and critical patient populations,” said Adams. “These positive two-year data reiterate the clinical importance of below-the-knee dissection repair and validates the sustained durability of Tack-optimised interventions.”
The two-year TOBA II BTK data also show sustained improvement in patients’ quality of life. In a patient questionnaire that assesses activity, pain, and overall health, patients report having more control of their health and increased improvement in mobility.
The Tack endovascular system is currently available for sale in the USA and some European Union countries. Further information, including safety information, is available here.
SoundBite Medical Solutions recently announced the use of its novel Active Wire 0.014” platform at a first site in the USA in the successful treatment of patients suffering from chronic limb-threatening ischaemia (CLTI) with heavily calcified lower limb chronic total occlusions (CTO).
The Active Wire was used in procedures at the UNC REX Hospital (Raleigh, USA) by George Adams, who commented: “Peripheral arterial disease (PAD) and CLTI in particular are a threat to life and limb. Our early experience with the 0.014” platform of the SoundBite crossing system in eight patients with severely calcified disease shows impressive CTO crossing efficacy coupled with safety and simplicity”.
He continued: “In several cases, crossing and treatment would not have been possible with standard techniques. With an increased demand for devices to aid in treatment algorithms for calcific plaque morphologies, we look forward to building on our experience with the system. The broader introduction of the SoundBite system holds promise to be game-changing in treating calcified CTOs and enabling better treatment outcomes in a difficult-to-treat patient population suffering from PAD and CLTI,” commented Adams.
The SoundBite crossing System—Peripheral (SCS-P) consists of the reusable SoundBite console, a single-use sterile SoundBite Active Wire, and their respective accessories. SCS-P leverages SoundBite’s proprietary method to produce and safely deliver shock waves via guidewire platforms to selectively “micro-jackhammer” through calcified lesions. SCS-P is now approved in major markets with CE mark, US Food and Drug Administration (FDA) 510(k) clearance, and Health Canada approval in both 0.018” and 0.014’’ platforms.
Two of our top stories this month come from the International Symposium on Endovascular Therapy (ISET; 9–11 May, Miami, USA), which returned as an in-person meeting in 2021: the live and online audiences heard a run-down of new tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI), and the Auryon atherectomy system showcased at the conference offered “a new look at laser”. A commentary from Gerard S Goh (Melbourne, Australia) and Markus P Schlaich (Perth, Australia) explored the potential of multi-organ denervation, and, in terms of vascular access coverage, readers were offered insight into a new wearable device for AV fistula remote monitoring that shows promise, but is facing commercial challenges. top 10
“I am going to give you reasons to be excited about your critical limb practice,” Peter Schneider (University of California San Francisco, San Francisco, USA) told delegates attending the International Symposium on Endovascular Therapy (ISET; 9–11 May, Miami, USA), in a talk focusing on innovative tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI). “I think critical limb ischaemia has come to the forefront of our practices and of community awareness, and finally now the tools are starting to show that,” he opined.
Following a successful proof-of-concept study, Gerard S Goh and Markus P Schlaich have embarked upon a first-in-human study to explore the safety and efficacy of combined renal and common hepatic artery denervation in patients with type 2 diabetes and hypertension. Here, the co-principal investigators describe the rationale behind their single blinded, multi-centre, prospective feasibility study—named the MODUS trial—and explore the “pandemic” of cardiometabolic disease.
A new wearable device designed to remotely monitor arteriovenous (AV) fistulae function in dialysis access patients uncovered promising data leading one set of researchers to conclude the technology offers hope for improved care and lower costs among a challenging patient population.
Additional randomised controlled data regarding the effectiveness of drug-coated balloons (DCBs) in maintaining arteriovenous (AV) access offers new evidence, but it is freighted with uncertainty. However, specific modelling suggests fewer reinterventions could reinforce economic benefits when the IN.PACT AV device (Medtronic) is used, and sirolimus presents new directions, experts say.
The Auryon atherectomy system (AngioDynamics) “represents an exciting new technology”, John Rundback (Advanced Interventional and Vascular Services, LLP, Teaneck, USA) opined at the International Symposium on Endovascular Therapies (ISET; 9–11 May, Miami, USA, and online), speaking on behalf of the Pathfinder I registry investigators. “I think it has really got a lot of traction; we found it a very useful tool across a wide range of plaque morphologies and vessel beds. Further iterations of this platform will hopefully improve its performance further.”
Volumetric assessment of the periablational safety margin can be used as an intraprocedural tool to evaluate local treatment success in patients with colorectal liver metastases referred to stereotactic radiofrequency ablation (SRFA), a recent study in European Radiology concludes. This could replace the visual, side-by-side evaluation of periablational safety margins, the investigators suggest, which is “challenging, even for experienced radiologists”. Authored by Gregor Laimer, Reto Bale (both Medical University Innsbruck, Innsbruck, Austria) and colleagues from Dresden (Germany), Milan (Italy), Jerusalem (Israel), and Boston (USA), the report offers an objective tool that enables the immediate, real-time determination of the extent and percentage of the safety margin requiring ablation, enabling the reliable prediction of procedural outcome success.
iVascular has received CE mark approval for its balloon-expandable covered stent, iCover, a press release from the company states.
Micro Medical Solutions (MMS) announced this month that the US Food and Drug Administration (FDA) has granted breakthrough device designation for its MicroStent vascular stent. This novel technology is designed to achieve and maintain vessel patency, enhance wound treatment, and improve quality of life and blood flow in order to reduce amputation and mortality for patients with chronic limb-threatening ischaemia (CLTI) resulting from peripheral arterial disease (PAD).
A study has found that bifurcated T-stent reconstruction offers a safe and effective treatment option for hepatic venous outflow obstruction (HVOO) with anastomotic stenoses in orthotopic liver transplantation (OLT) recipients.
Transit Scientific recently announced it has received CE mark clearance in the European Union for the XO Score scoring sheath platform to facilitate dilation of stenotic material in the peripheral vasculature including popliteal, infrapopliteal, and native or synthetic arteriovenous dialysis fistulae. top 10 top 10
In setting up an interventional radiology (IR) COVID-19 response plan, “the most important initial step is to recognise the problem,” stated John A Kaufman (Oregon Health & Science University, Portland, USA) at this year’s European Conference on Interventional Oncology (ECIO; 10–13 April, online). Based on the experience of one US institution, the presenter conveyed various crucial factors, stressing in particular the importance of supporting providers, the impact on whom will be “long lasting”.
“Our response to COVID-19 has evolved over time,” Kaufman began, noting an initial “very inward-facing approach”, focusing on personal protective equipment (PPE), workflow, personnel, and case selection. Subsequently, he explained, the plan became more “outward facing”, involving the wider institution and focusing in more detail on issues such as testing, staffing, hospital case-loads, and policies. Provider support ran parallel to these two main stages, he added, an element of the plan designed to address factors such as stress, income loss, and family concerns.
The first step was to recognise the issue, said Kaufman, noting that this was complicated by the US political environment. He exemplified the atmosphere at the time: “Mask-wearing was a political statement rather than a healthcare concern”. What followed was the founding of a cross-establishment professional leadership group, including physicians, nurses, technologists, and managers, he detailed.
During the “inward-facing” phase of the IR response, PPE was a top priority due to limited supply as well as uncertainty regarding what to wear and when. Testing was another important issue at this stage. Initially, testing was very limited and took a long time. Decisions surrounding workflow, including which sites to keep operational, how many dedicated COVID-19 rooms were necessary, and room turnover for COVID-19-positive patients, were all addressed during this stage. Finally, the team recognised the need to organise personnel. All office and support workers began to work remotely, and prover schedules were adapted to minimise exposure, the presenter recounted.
“Case selection became very important,” Kaufman continued, detailing that it was important for the institution to observe state and national rulings, such as the ban of all elective cases in Oregon that was initiated in March 2020. During the early months of the pandemic, operating room (OR) volume dropped by 90%, compared to a 30% drop in IR volume, the presenter reported, attributing this to there being “few truly elective cases” in IR. Meanwhile, emergent cases, as well as all cancer treatment, continued.
The presenter detailed a “silver lining” of this early phase of the pandemic as being the increased availability of anaesthesia resulting from OR closures. In the discussion following Kaufman’s presentation, session moderator Otto van Delden (Amsterdam University Medical Center, Amsterdam, The Netherlands) remarked that, in Europe, the number of IR procedures performed fell “considerably”, and to a level far lower than in the USA, due to a lack of anaesthesia support. Van Delden was keen to know what impact a good supply of anaesthesia had on case load, with Kaufman responding that the team certainly noted that, as well as IR cases, they were also treating patients who would have, in normal circumstances, been treated surgically.
In terms of written guidance, Kaufman relayed that the team created a COVID-19 standard operating procedure manual. This was updated as needed, including all aspects of hospital and clinical operations relating to IR, and was shared on a public website. Other elements of this initial stage included holding weekly IR leadership meetings and the conversion of all clinics to either telephone or virtual appointments, with in-person consults reserved for acutely-ill patients.
In the “outward-facing” phase of the team’s COVID-19 response, involving higher levels within the institution, the first “big issues” were PPE, testing guidelines, and isolation rules, Kaufman communicated. In addition, staffing shortages became a major issue, with reassignments and travel restrictions having an ongoing impact. The availability of staff, as well as of intensive care unit (ICU) beds, determined elective admissions and saw a shift of cases to partner hospitals.
Finally, Kaufman stressed the importance of provider support in a successful IR COVID-19 response plan. There are numerous factors that needed to be addressed, he detailed, noting a fear of infecting family members, problems finding childcare and the demands of home-schooling, reduced incomes, isolation, the loss of friends and family members, working longer hours, and treating sicker patients.
“Faculty and families may need to adjust priorities,” Kaufman commented, noting for example the need to change jobs to be closer to family. Other important ways in which the pandemic has affected providers included reduced caseload for learners, decreased academic productivity—which he noted has disproportionately affected women—and the proliferation of virtual meetings and conferences. “Keep in mind the impact on providers will be long lasting,” he concluded.
A randomised trial—AB-LATE02—will assess the efficacy of a combination of neoadjuvant atezolizumab, and adjuvant atezolizumab and bevacizumab with radiofrequency ablation (RFA) as a treatment option for patients with hepatocellular carcinoma (HCC). According to the principal investigator Boris Guiu (St-Eloi University Hospital, Montpellier, France), the treatment could improve recurrence-free survival (RFS) at two years, and may reduce the risk of distant recurrence, due to the synergistic effects of the treatment strategies. LATE02
Guiu outlined the rationale for the multicentre randomised trial, taking place in 16 centres across France, during a live “Meet the PI” session at the 2021 European Conference on Interventional Oncology (ECIO 2021, 10–13 April, online). During the session, Guiu was questioned by Philippe Pereira (Academic Hospital of Heilbronn, Ruprecht Karl University of Heidelberg, Germany) and Alban Denys (Lausanne University Hospital, Lausanne, Switzerland).
Ablation has become the first curative treatment for HCC, Guiu told attendees to the session, commenting that its use has increased steadily from 2013 to the present day. Discussing published data looking at RFA, however, he identified two problems. Firstly, the incidence of local recurrence, which occurs in between 5–20% of cases, and predominantly relates to the ability to obtain adequate margins around the tumour. “This is probably more of a technical than an oncological problem,” Guiu said.
Furthermore, he noted that intra-hepatic distant recurrence occurs very frequently—in around 60–80% of cases—and the debate is often whether its origin is a metastases or a de novo HCC. Guiu detailed the publication of a recent paper from his centre, which aimed to look at factors that may explain the presence of distant recurrence, including patient, disease, tumour and disease-related factors.
“We only found two factors associated with distant recurrence,” Guiu said, adding that these were alpha-fetoprotein (AFP) and tumour size. “In a way, these factors reflect the aggressiveness of the tumour and are more in line with the concept of metastases, at least during the first two years.” Further data show that de novo HCC are probably more frequent, Guiu noted.
In the case of a distant recurrence, there is a high risk that the patient cannot be treated using a curative approach, Guiu went on to add, meaning that the need to fight against metastatic escape and tumour growth becomes increasingly important. “There is a drift to palliative care, there is a drift to a palliative prognosis, and this is probably the key time where the patient is losing a good prognosis,” he commented. “We have to fight against this incidence of intra-hepatic distant recurrence and this a very important rationale to support the trial.”
A “new challenger” has recently entered the field of advanced HCC, Guiu said, the combination of atezolizumab and bevacizumab, which he commented show “synergistic effects”. The emergence of this treatment creates a strong rationale to combine immunotherapy and ablation, Guiu added.
AB-LATE02 will assess the treatment of small HCC (<3cm). In the standard arm, patients will be ablated using RFA, with follow-up carried out as normal. In the experimental arm, patients will undergo an induction with neoadjuvant atezolizumab, then ablation, and then treatment with the combination of atezolizumab and bevacizumab for one year.
The trial’s primary endpoint is RFS at two years, which Guiu said the study will aim to extend to 65%, compared to 45% seen in current literature. The study will enrol a total of 202 patients, who will be randomised 1:1 to either the experimental or standard treatment arm.
“What is important is that in addition to the primary endpoint we have to look to overall survival at five years, because we have the chance to change the game in these patients based on the results of this trial,” said Guiu.
The trial will also assess quality of life (QoL), which Guiu said will be important to consider, given the frequency of the treatment in the experimental arm. He explained: “We include QoL in this trial because it is very important to see if there is any impairment. In the experimental arm, we not only have ablation, but every three weeks the patient must go to the hospital to get immunotherapy, and this is something we need to look at and see if the balance, even if the trial might be positive, is positive for the patient.”
Finally, a comprehensive translational study is full part of the trial and notably includes immuno-monitoring, circulating tumour DNA (ctDNA) exome analysis, and peripheral blood mononuclear cell (PBMC) based on serial biological and tissue assessments.
At the time of the presentation, Guiu said that enrolment had already begun in three participating centres, and he anticipated that this would be the case in all 16 centres by the end of April 2021. Results are expected from 2025.
Many individuals with kidney failure have been unable to self-isolate during the COVID-19 pandemic because they require dialysis treatments in clinics several times a week. New research that will appear in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN) highlights the risks faced by these patients and the factors involved.
For the study, Ben Caplin (University College London, London, UK) and colleagues, on behalf of the Pan-London COVID-19 Renal Audit Group, examined information on 5,755 patients who received dialysis in 51 clinics in London. Between 2 March and 31 May 2020, a total of 990 (17%) patients tested positive and 465 (8%) were admitted to hospitals with suspected COVID-19.
COVID-19 risks were higher in patients who were older, had diabetes, lived in local communities with higher COVID-19 rates, and received dialysis at dialysis clinics that served a larger number of patients. Risks were lower in patients who received dialysis in clinics with a higher number of available side rooms and that had mask policies for asymptomatic patients. No independent association was seen with sex, ethnicity, or measures of deprivation.
“Taken together, the findings confirm the high rates of symptomatic COVID-19 among patients receiving in-centre dialysis and suggest sources of transmission both within dialysis units and patients’ home communities,” said Caplin. “The work also suggests that, in addition to isolation of confirmed cases, addressing factors that might reduce transmission from patients without suspected or confirmed disease might provide an additional opportunity to further modify the impact of COVID-19 in this population.”
Medical imaging AI specialist Avicenna.AI has received CE mark certification for its CINA ASPECTS AI tool for stroke severity assessment. CINA ASPECTS automatically processes non-contrast computed tomography (CT) scans and calculates an “ASPECT” score in order to assist radiologists within their existing systems and workflow—according to an Avicenna.AI press release.
“CINA ASPECTS supports stroke physicians and radiologists in the assessment and characterisation of early ischaemic brain tissue injury using CT image data,” said Cyril Di Grandi, co-founder and CEO of Avicenna.AI. “This new tool demonstrates our commitment to providing radiologists with AI solutions that can enhance their capabilities. Securing a CE Mark is a key milestone and we are delighted to be able to start offering the benefits of CINA ASPECTS to our European customers. We look forward to FDA clearance in due course.”
ASPECTS (Alberta Stroke Program Early CT Score) is a topographic scoring system used to quantify the severity of a stroke from a CT scan of the brain. It divides the brain territory affected by a stroke into 10 areas of interest, and provides a score between zero and 10, where 10 is normal and zero indicates widespread ischaemic damage throughout the affected area.
CINA ASPECTS computes a heat map indicating the probability of hypodensity and/or sulcal effacement in the brain, and displays a list of infarcted regions. It also provides tilted and resliced CT images to allow easy comparison of the right and left hemisphere. In addition to assisting clinicians to evaluate the ASPECT score from CT scans, CINA ASPECTS also helps improve the reproducibility of the score, which often varies depending on the radiologist reading the scan.
CINA ASPECTS is part of Avicenna.AI’s CINA Head family of AI tools that support the treatment of stroke and neurovascular emergencies. CINA Head also includes FDA-cleared and CE-marked tools for detecting intracranial haemorrhages (ICHs) and large vessel occlusions (LVOs) from CT scans.
Andrew Holden (Auckland, New Zealand) presents the latest results from the IN.PACT™ AV Access trial (Medtronic), which indicate “outstanding” target-lesion primary patency rates of 52.2% through 24 months in dialysis patients with dysfunctional arteriovenous fistulas (AVFs), offering a “highly-significant advantage” over standard balloon angioplasty procedures. These findings were announced in a podium 1st presentation at the Charing Cross (CX) 2021 Digital Edition (19–22 April, online).
Holden, who is director of interventional radiology at Auckland Regional Public Health Service and the trial’s presenting author, stated that the IN.PACT™ AV drug-coated balloon (DCB) met its primary safety and effectiveness endpoints after 24 months—including demonstrating “absolutely no difference” in all-cause mortality rates between the trial’s DCB and standard percutaneous transluminal angioplasty (PTA) arms.
Presenting the longer-term patency results through 24 months, Holden said it was “very pleasing to see” a flattening of the Kaplan-Meier curves in both the DCB and standard PTA arms of the trial—as well as a target-lesion patency rate of 52.2% in the DCB group. He added that a “highly-significant advantage” was observed compared to the PTA group, which demonstrated a patency rate of 36.2% through 24 months.
This video is sponsored by Medtronic.
Following a successful proof-of-concept study, Gerard S Goh and Markus P Schlaich have embarked upon a first-in-human study to explore the safety and efficacy of combined renal and common hepatic artery denervation in patients with type 2 diabetes and hypertension. Here, the co-principal investigators describe the rationale behind their single blinded, multi-centre, prospective feasibility study—named the MODUS trial—and explore the “pandemic” of cardiometabolic disease.
Cardiometabolic disease has evolved into a pandemic, resulting in substantial loss in quality of life and enormous economic burden on healthcare systems world-wide. Cardiovascular and metabolic regulation is governed by neural signaling from the sympathetic nervous system in critical organs including the heart, kidneys, liver, pancreas, skeletal muscle, and adipose tissue. Increased sympathetic activation is a hallmark of cardiometabolic disease and has been demonstrated in obesity, metabolic syndrome, type 2 diabetes, hypertension, heart failure, chronic kidney disease, and many other relevant conditions. Insulin resistance, non-alcoholic fatty liver disease (NAFLD), and a systemic pro-inflammatory state are key mediators of the adverse consequences associated with cardiometabolic disease. A self-perpetuating cycle develops where sympathetic overdrive contributes to insulin resistance and subclinical inflammation, which in turn maintain increased sympathetic signaling.
Direct therapeutic targeting of the sympathetic nervous system therefore appears as a rational approach to improve both cardiovascular and metabolic control. Indeed, catheter-based renal denervation using either radiofrequency energy or therapeutic ultrasound has now been shown in four sham-controlled trials to be safe and to effectively lower ambulatory blood pressure in patients both treated and untreated with antihypertensive medications (SPYRAL OFF-MED, SPYRAL ON-MED, RADIANCE-HTN SOLO, RADIANCE-HTN TRIO). Additional salutary effects on glucose metabolism have been reported in some renal denervation studies, suggesting that the beneficial effects of selectively targeting the sympathetic nerves may not be limited to the management of cardiovascular disorders, but may also help to restore metabolic homeostasis. This approach would perhaps be most effective if the sympathetic drive to metabolically-active organs such as the liver (gluconeogenesis), pancreas (insulin release), and duodenum could be inhibited directly.
A recent preclinical proof-of-concept study in a porcine model where percutaneous denervation in both renal arteries and the common hepatic artery (CHA) was performed with the iRF Denervation System demonstrated that denervation of both the kidneys and the liver could safely be achieved with reductions in tissue norepinephrine concentration when compared to control animals of 78% and 88% (p<0.001 for both), respectively. Pancreatic and duodenal norepinephrine concentration was also reduced significantly.
Consequently, a first-in-human study has recently been initiated to explore the safety and efficacy of combined renal and common hepatic artery denervation in patients with type 2 diabetes and hypertension.
The MODUS trial (Multi-organ denervation to reduce sympathetic drive, a single blinded, multi-centre, prospective feasibility study) is a multicentre randomised trial that is examining the effects of hepatic and/or renal denervation in patients with hypertension, diabetes, and metabolic syndrome. Patients on one or two antihypertensive and oral anti-diabetic drugs within certain BP and HbA1c ranges undergo a ‘wash-out’ phase of four weeks with regular BP and glucose monitoring before receiving a single session denervation therapy. The trial utilises the iRF denervation system (Metavention), which is a radiofrequency balloon-based catheter with internal cooling where the catheter is inserted into the renal and/or common hepatic arteries and denervation performed. Centres in Perth, Melbourne, and Sydney (Australia) are participating in the trial, and the first two patients were recently enrolled at the Alfred Hospital, Melbourne, treated by Gerard Goh and Warren Clements.
Gerard S Goh is head of Interventional Radiology at The Alfred Hospital, Melbourne Australia, and is adjunct associate professor in the department of Surgery at the Monash University, Melbourne, Australia. He is also president of the Interventional Radiology Society of Australasia (IRSA).
Markus P Schlaich is the Dobney chair in Clinical Research and a nephrologist and hypertension specialist at the School of Medicine—Royal Perth Hospital Unit and the University of Western Australia, Perth, Australia.
Disclosures: Gerard S Goh and Markus P Schlaich are co-principal investigators of the MODUS trial, and as such receive research funding from Metavention.
Koya Medical announced today that it has received US Food and Drug Administration (FDA) 510(k) clearance for its active compression therapy system Dayspring for the treatment of lymphoedema and venous diseases that impact lymphatic flow in the lower extremities. The company also announced the appointments of three veteran executives to its leadership team to support commercialisation.
Patients treated with Dayspring receive standard of care active compression therapy with a mobility-enabling wearable device. The system includes a low-profile active garment made of soft, breathable mesh using Koya’s proprietary Flexframe technology; a rechargeable, hand-held controller that can be worn on a lanyard; and a mobile app that allows users or their clinicians to programme custom treatment options. Koya previously received FDA clearance for Dayspring for the upper extremities in June 2020.
Koya Medical also announced the appointments of additional executive leaders to propel commercialisation plans. As head of sales, Rick Biro will be responsible for building and executing Koya’s go-to-market sales strategy. He joins Koya after serving as area sales director, Central USA at PolarityTE where he was part of the commercial leadership team during the company’s most expansive growth period. Prior to joining PolarityTE, Biro spent more than 15 years in the lymphoedema and wound care space where he held a number of leadership positions with Wright Therapy Products, BSN Medical, and Galaxy Medical Products.
As head of market access and clinical affairs, Liesl Oldstone will work to articulate the clinical value of the company’s highly differentiated product and minimise barriers for patients to access. Her leadership in market access, health economics, and reimbursement has spanned more than two decades in both pharma and the medical device industry for industry-leading companies including ResMed, Bristol-Myers Squibb, Covidien (now Medtronic), Cordis (formerly J&J), and Eli Lilly & Company.
Damian Rippole will join as CFO, and brings more than 20 years of financial leadership experience in both private and public medical technology companies. Rippole was most recently CFO at Ebb Therapeutics (acquired in a private transaction funded by leading global investment firm KKR), maker of an innovative FDA-cleared device for treating insomnia. Prior to that, Rippole was corporate controller for Respironics, a global leader in the sleep and respiratory markets that was acquired by Philips for US$5 billion in 2008. Following the acquisition, Rippole led the global finance integration of Respironics into Philips and served as the group controller for Philips Home Healthcare Solutions business.
Exactly 20 years on from his first stereotactic radiofrequency ablation (SRFA) procedure to treat a cancerous liver tumour, Reto Bale (Medical University Innsbruck, Innsbruck, Austria) speaks to Interventional News about the future of this procedure, and warns interventionalists that this may be the next arena for a potential turf struggle: interventional radiologists should start learning now, he urges, as, in his view, “90% of current liver resections could be replaced by SRFA”. At Bale’s institution, proceduralists are able to use up to 36 coaxial needles to ablate tumours, achieving results that rival those of their surgical counterparts, leaving no residual mass behind.
When did you first start using this approach?
The story begins in 1994, when I was using navigation systems in ENT and neurosurgery. Back then, as a student, I developed a few things together with my student fellow Michael Vogele: We had a patent for a navigation device and a head fixation device, amongst other technologies. In 1995 I developed the first aiming device initially for neurosurgical work. I wanted to expand beyond neurosurgery, because I wanted to use navigation not just in the brain, but everywhere. That was why I moved to interventional radiology (IR), and in 1996, as an assistant doctor, I set up the SIP—the Stereotactic Interventional Planning lab in Innsbruck, Austria.
I think stereotaxy is the ideal tool for radiofrequency ablation (RFA). The problem is that there is often a discrepancy between the tumour volume and the ablation volume. This is the reason for recurrence. The simple solution to this is to use multiple coaxial needles. However, although the idea is simple, it is difficult to place multiple coaxial needles in order to ablate the entire tumour volume with conventional ultrasound (US) and computed tomography (CT) guidance. This is why, in my opinion, using stereotaxy is the way to go.
We did the first procedure in the liver in May 2001. I am sure that the way we do radiofrequency ablations has to change—I have always been sure, but when we started this everyone said ‘Oh that crazy Austrian, advancing 10 needles into the body!’ But now, 20 years later, people have changed their minds.
What value does stereotaxy add to radiofrequency ablation?
SRFA helps you not only to guide the needles and visualise placement, but to plan the procedure as well. In most cases, you need multiple overlapping zones in order to ablate the complete volume. Even with microwave ablation (MWA), the maximum short ablation diameter is approximately 3.6cm. So, if a lesion is larger than 2–3cm, it is very difficult to achieve an adequate ablation margin; you need overlapping ablation zones.
How do results from SRFA compare with surgical outcomes?
It [SRFA] is actually better than surgery!
From our results, it is at least as good as surgery in terms of local control rates, and it is dramatically less invasive, of course, and parenchyma-sparing. There is no doubt in my mind: if you can ablate the lesion completely, why would you do a resection? No patient would like you to open them up if there was a less invasive option with comparable outcomes.
In 2019, myself and several colleagues published a retrospective study in Hepatology that evaluated the efficacy of three-dimensional (3D)-navigated, multiprobe radiofrequency ablation (SRFA) with intraprocedural image fusion for the treatment of hepatocellular carcinoma (HCC) by histopathological examination.
From 2009 to 2018, 97 patients were transplanted after bridging therapy of 195 HCCs by SRFA. The rate of residual vital tissue could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using haematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last CT imaging before liver transplantation. Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%), and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3cm, complete tumour cell death was achieved in 50 of 52 nodules (96.2%). Residual tumour did not correlate with tumour size (p=0.5).
We therefore concluded that multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumour sizes larger than 3cm, and without the need of a combination with additional treatments. For us, the results justify the additional efforts related to the stereotactic approach.
A very interesting thing about SRFA is that image fusion is part of the procedure. Image fusion is now—now [Bale’s stress]—a key issue. We have been doing this for 20 years.
What developments would you like to see in image fusion?
Firstly, we use image fusion to check the accuracy of needle placement. We do two CT scans: a planning CT, before we place any needles, and a control CT, which is taken with the needles in place. This native dataset is then superimposed onto the planning CT, and onto the virtual pathways we planned. Thereby, we can measure the accuracy of every needle.
The second step is the verification of the ablation zone—we want to know if there is a sufficient ablation margin covering the tumour. This is extremely important, and very helpful. It is better than the pathological report the surgeons receive, for example. One week following surgery, they get a pathology report telling them if they have achieved R0 or R1, whereas we see this immediately, while the patient is still under anaesthesia, and we see it in three dimensions, not only in a two- dimensional rendering. In most cases it is not possible for the pathologists to look at the whole margin under the microscope, it would take far too long! So, they just take a representative specimen. But when we use image fusion, it is a 3D tool, so we can assess the margin in all dimensions.
This allows us to be adaptive intraprocedurally. If we do not achieve the ablation zone, and we have some residual tumour, we can put another needle into the patient.
In our tumour board meetings, the first question used to be “Is it resectable?” Now the first question is – in most cases – “Is it ablate-able?” But this is only at Innsbruck! I hope it will change around the world—this is just the start for SRFA.
What are the barriers to this being adopted at other institutions?
Getting the word out! Our problem is that we do not get refunds for the additional effort. Our department gets money for the ablation probes, like you would need for an US- or CT-guided intervention, which is completely different from SRFA. We need support from insurance companies, and they will only finance this if there are enough data. Currently, we only have data [on SRFA’s safety, efficacy and long-term outcome] from our institution.
We have a prospective database. It includes more than 1000 SRFA patients with more than 4000 tumors treated by SRFA over the last 20 years. It is linked to the hospital’s record of patient files, so it is hard data that is very transparent and auditable. All of our replications are based on this registry.
However, in order to support reimbursement for SRFA, insurance companies need to see prospective, randomised data—my next aim is therefore to conduct a multicentre, prospective, randomised controlled study to obtain these data and hopefully to get reimbursement for the procedure.
What would your advice be for interventional radiologists wishing to do SRFA at their own centres?
Get in touch! I would be happy to assist them to set up a programme. I have done it in Innsbruck, and it works very well, so I would be delighted to assist. It is hard work at the beginning, organising the system and teaching everyone the technical details, but I think it is necessary that more interventional radiologists have this training.
The good thing is that, though it was initially challenging, now we have so much experience. We have many standards of practice; it is much easier to train someone to do SRFA than it is to perform liver surgery, for example. I have a colleague who has completed just three months training, and then he did a procedure completely alone, with great results. My other colleague has been training with me for a year, and he performs extremely complicated procedures that no one else does in the world, outside of Innsbruck.
A very important point: you can do a lot of training without even touching a patient, because we have such extensive datasets, with information (such as CT images) available. So you can train if you want on more than thousand patients before you start with real patients! That is really cool, because the path planning is the most difficult part. It is quite easy to use the navigation system to place a needle; I will turn you into an expert in two weeks, with that, as long as you have some experience with ablation already. But it is difficult to make the path plan; this can be learned in the virtual dataset. My aim is therefore to teach interventionalists with these datasets; I think we could make something big happen here.
It is extremely important that interventional radiologists start now, before it is too late, because I know that otherwise the surgeons will start performing SRFA themselves. In my view, 90% of current liver resections could be replaced by SRFA. If it is possible to completely ablate the tumour and leave no residual mass behind, then there is no argument for a more invasive procedure.
What does the future look like for SRFA?
My hope is that it will become a lot more common practice at several institutions around the world. In addition, at Innsbruck, we aim to make the preprocedural path-planning process at least semi-automatic, through the use of machine learning. We have just recently secured funding for a PhD candidate to get started on this work, so it will be exciting to see what they can achieve.
Histotripsy, which was invented at the University of Michigan, uses pulsed sound waves to destroy tissue. It is a non-invasive and non-thermal mechanism that is currently being studied for its “completely different mechanism for ablating tissue, which […] we will be able to leverage to our advantage in treating cancer”, says Fred T Lee (Madison, USA). Lee, a professor (tenure) of Radiology, Biomedical Engineering, and Urology, The Robert A Turrell Professor of Imaging Science, and the chief of Abdominal Intervention at the University of Wisconsin, asserts that histotripsy could overcome some of the limitations of thermal ablation.
More evidence is needed and there is a “still a lot of work to be done”, Lee cautions, while suggesting that in the future, histotripsy could be used as an immune primer in conjunction with checkpoint inhibitors. It might, therefore, be useful in treating patients with very advanced tumours or multiple tumours that “we ordinarily would not be able to treat with ablation”, he says.
The European Union (EU) Medical Devices Regulation (MDR) takes effect from today (26 May 2021).
The Regulation revises quality and safety standards and the range of regulated devices and was first initiated in May 2017, with an initial three-year transition period applied. Implementation was delayed by 12 months due to the COVID-19 pandemic.
According to the European Commission there are over 500,000 types of medical devices and in vitro diagnostic medical devices (IVDs) on the EU market. These have a “fundamental role in saving lives by providing innovative healthcare solutions for the diagnosis, prevention, monitoring, prediction, prognosis, treatment, or alleviation of disease” according to information on the Commission’s website. Separate regulations governing IVDs come into effect in May 2022.
According to the Commission, the new regulations create a “robust, transparent, and sustainable” regulatory framework, that will improve clinical safety and create fair market access conditions for manufacturers.
The new regulations maintain the current grouping of devices into four classes—Class I, IIa, IIb, and III—although certain devices are reclassified and have a wider scope.
The Regulation also clarifies the respective obligations of manufacturers, authorised representatives, importers and distributors, with manufacturers required to put systems in place for risk and quality management, to conduct clinical or performance evaluations, and to draw up technical documentation and keep this up to date. Further to this, the Regulation also requires manufacturers to implement post-market surveillance follow-up plans.
Volumetric assessment of the periablational safety margin can be used as an intraprocedural tool to evaluate local treatment success in patients with colorectal liver metastases referred to stereotactic radiofrequency ablation (SRFA), a recent study in European Radiology concludes. This could replace the visual, side-by-side evaluation of periablational safety margins, the investigators suggest, which is “challenging, even for experienced radiologists”. Authored by Gregor Laimer, Reto Bale (both Medical University Innsbruck, Innsbruck, Austria) and colleagues from Dresden (Germany), Milan (Italy), Jerusalem (Israel), and Boston (USA), the report offers an objective tool that enables the immediate, real-time determination of the extent and percentage of the safety margin requiring ablation, enabling the reliable prediction of procedural outcome success.
“Ablations with [a] 100% three-dimensional (3D) periablational safety margin of 3mm and ablations with at least [a] 90% 3D safety margin of 6mm can be considered indications of treatment success,” the study authors report. They further conclude that their results indicate image fusion of pre- and post-interventional computed tomography (CT) scans with the Ablation-fit software is feasible, and “could represent a useful tool in daily clinical practice”.
SRFA takes a multiple-needle approach, utilising 3D treatment planning, stereotactic needle placement, and image fusion for the intraoperative assessment of the periablational safety margin. According to Laimer, Bale et al, in some centres, this technique can overcome the limitations associated with standard radiofrequency ablation (RFA).
They write: “Several studies have reported that the periablational safety margin, defined as the shortest distance between tumour border and margin of the necrosis zone, independently predicts the local tumour progression in colorectal liver metastases, whereby ablations with safety margins >5–10mm exhibit lower local tumour progression rates [a better outcome]. In conventional CT or ultrasound-guided RFA, the creation of large necrosis zones extending 5–10 mm beyond tumour borders is often hampered by technical limitations, especially for larger tumors (i.e. >3cm), which may result in local tumour progression ranging from 4–70%. In contrast, these limitations have been overcome in some centres with stereotactic thermal ablation.”
In total, 45 patients with 76 colorectal liver metastases between them were treated with SRFA and analysed in this study. During image fusion of pre- and post-interventional contrast-enhanced CT scans, Laimer, Bale et al used a software with non-rigid registration (called Ablation-fit) to assess the percentage of predetermined periablational 3D safety margin and colorectal liver metastases successfully ablated (i.e. with no evidence of residual tumour tissue).
Periablational safety zones (1–10mm) and percentage of the periablational zone ablated were calculated, analysed, and compared with subsequent tumour growth to determine an optimal safety margin predictive of local treatment success.
Presenting their results, Laimer, Bale, and colleagues relayed that the mean overall follow-up was 36.1±18.5 months. Nine of 76 colorectal liver metastases (11.8%) developed local tumour progression; the mean time to local tumour progression was 18.3±11.9 months. Overall one-, two-, and three-year cumulative local tumour progression-free survival rates were 98.7%, 90.6%, and 88.6%, respectively. The periablational safety margin assessment proved to be the only independent predictor (p<0.001) of local tumour progression for all calculated safety margins. The smallest safety margin that was 100% ablated and that displayed no local tumour progression was 3mm, and at least 90% of a 6mm, circumscribed 3D safety margin was required to achieve complete ablation.
“With this work, we confirm prior reports demonstrating the importance of achieving a periablational margin for ablation, as we too established the periablational safety margin as the only significant predictor of local tumour progression in patients with colorectal liver metastases treated with SRFA,” the study investigators write in their discussion. “Apart from the periablational safety margin, no other conventional risk factor such as age, gender, tumour size, tumour location, or previous therapies significantly influenced local tumour progression. Importantly, this observation held true for all calculated 3D safety margins, namely, 1–10mm. Yet, in our study, the smallest safety margin displaying no local tumour progression for ablations with 100% circumscribed 3D safety margin was 3mm (0/55 [0%] target tumours).
“This indicates that an ablation with a 100% circumscribed 3D safety margin of 3mm can be considered successful at the time of the intervention. Given that larger volumes of ablation are more difficult to achieve, this may represent an improvement when considering that previous studies recommend a periablational safety margin of at least 5mm, with better results only seen with a 10mm periablational safety margin for colorectal liver metastases. One possible explanation for this discrepancy might be the exact image fusion and volumetric safety margin assessment achieved with the non-rigid registration software used for this study. Regardless, the small but precise margins in our study may actually represent larger volumes given known tissue shrinkage during ablation.”
Speaking to this newspaper, Bale adds: “Another explanation for this discrepancy may be related to the fact that deformation of the datasets for image fusion during stereotactic thermal ablation (intraprocedural arterial and portal venous phase planning and control CTs) is mimimised by respiratory triggering. This is achieved by temporary disconnection of the endotracheal tube and full muscle relaxation.”
Noting that this study is retrospective in design and is reliant on the experience of a single centre, and also that there is “scarce use of stereotactic approaches in the ablation of liver malignancies” outside of the Medical University in Innsbruck, Laimer, Bale, et al hope that their work aids in generating further interest in this technique.
Transit Scientific today announced that its XO Score scoring sheath platform has been named a winner in the 2021 Medical Design Excellence Awards (MDEA). The MDEA is a premier design competition in the medtech industry, recognising significant achievements in medical product design and engineering that improve the quality of healthcare delivery and accessibility.
“We are honoured that our XO Score platform has been recognised by the MDEA organisation,” said Greg Method, president of Transit Scientific. “We designed XO Score as a novel way to expand angioplasty-based tools available to physicians for treatment of peripheral arterial disease (PAD), chronic limb-threatening ischaemia (CLTI), and end-stage renal disease (ESRD). The award is a testament to the dedication and hard work of the team at Transit Scientific and reflects our commitment to bringing new technologies to market for the advancement of patient care.”
XO Score is a novel scoring sheath that works by fitting over physician selected off-the-shelf percutaneous transluminal angioplasty (PTA) balloons to enable scoring and cutting vessel preparation. The unique balloon-expandable scoring element enables a single XO Score device to work with a large range of balloon diameters and lengths for in-procedure adaptability. XO Score has been used successfully to dilate calcified and fibrous lesions during a multisite, multiuser limited market release.
“XO Score’s proprietary rotating strut design ensures the device remains low profile for tracking to and from the treatment site”, continued Method. “The ability to engage the wall and dilate at a low inflation pressure has yielded great outcomes in a broad range of PTA-resistant lesions.”
The device is currently indicated for treatment of peripheral vascular stenosis including haemodialysis fistulas and grafts.
Concept Medical has released a series of status updates on their head-to-head SIRONA (Sirolimus versus paclitaxel drug-eluting balloon angioplasty in femoropopliteal diseases) randomised controlled trial (RCT).
SIRONA is an investigator-initiated and -driven, prospective, multicentre, corelab-adjudicated trial involving peripheral arterial disease (PAD) patients with Rutherford classification 2–4. The study will enrol a total of 478 patients randomised 1:1 (MagicTouch PTA, Concept Medical: paclitaxel-coated balloon) across 30 sites in Germany and Austria. Led by Ulf Teichgräber (Jena University Hospital, Germany), a press release states that the study is moving “rapidly,” with 20 patients already enrolled.
According to a press release, SIRONA is the world’s first RCT investigating the use of a sirolimus drug-coated balloon (DCB) versus a paclitaxel DCB for the treatment of femoropopliteal artery disease.
The primary objective of the SIRONA trial is to determine the safety and efficacy of sirolimus-coated balloon application in the superficial femoral artery (SFA). The primary endpoint of patency at 12 months has been defined as absence of target lesion revascularisation [TLR] or restenosis and the primary safety endpoint determined as composite of freedom from device- or procedure-related death at 12 months as well as major target limb amputation.
The trial will include all patients with a disease in the SFA segment (either de novo or restenotic) falling under Rutherford class 2–4 and suffering from intermittent claudication to chronic limb-threatening ischaemia (CLTI).
Teichgräber communicates his optimism regarding the trial: “I believe that SIRONA will be a game changer trial by giving new evidence on how to perform PTA [percutaneous transluminal angioplasty] following the principle of nothing leaving behind.”
The US Food and Drug Administration (FDA) have granted breakthrough device designation for the Emprint ablation catheter kit (Medtronic). This is an investigational device not yet approved or cleared in the USA.
The catheter is intended to be used in conjunction with the Emprint microwave generator and lung navigation platform (also Medtronic) to provide a minimally invasive, localised treatment of malignant lesions in the lung, and it can be used together with standard-of-care therapy when indicated.
The FDA breakthrough device programme is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide Medtronic with priority review and interactive communication regarding clinical trial designs through to commercialisation decisions, a press release details.
Current clinical guidelines for the management of malignant lung lesions support a multimodal approach, which may include surgery, radiotherapy, and/or systemic drug therapy, depending on the tumour stage. Because patients with lung malignancies have been shown to have survival benefit from a combination of systemic and local therapy, less invasive local treatment modalities such as the Emprint ablation catheter kit have been developed. Using an endoluminal approach, the Emprint ablation catheter kit will be studied with Medtronic’s lung navigation system to allow for the delivery of microwave energy to the targeted lung lesion(s). Clinical guidelines recommend incorporating local therapies such as thermal ablation, in combination with systemic therapies when suitable.
Though not yet available in the USA, the Emprint ablation catheter kit is CE Marked and the NAVABLATE study completed enrollment of 30 patients in Europe and Hong Kong in 2020.
“This new technology has allowed me to personalise treatment of lung lesions for each patient, particularly lesions that may be challenging to manage,” says Kelvin Lau, a consultant thoracic surgeon at St Bartholomew’s Hospital, London, UK, and principal investigator for the NAVABLATE study.
The Medtronic lung navigation platform enables precise and accurate placement of the ablation catheter within the target lesion, which is critical for the success of this minimally invasive procedure. With 15 years of experience, the navigation platform has been used in more than 200,000 lung procedures.
“At Medtronic, we strive to transform outcomes by taking bold actions to ensure that patients with tumours in the lung receive care sooner, less invasively, and more effectively,” comments Emily Elswick, vice president and general manager, Lung Health and Visualisation, within the Surgical Innovations business, which is part of the Medical Surgical Portfolio at Medtronic. “Breakthrough designation from the FDA is just the first-step in realising our broader commitment to providing less invasive treatment options to patients with lung disease.”
Additional randomised controlled data regarding the effectiveness of drug-coated balloons (DCBs) in maintaining arteriovenous (AV) access offers new evidence, but it is freighted with uncertainty. However, specific modelling suggests fewer reinterventions could reinforce economic benefits when the IN.PACT AV device (Medtronic) is used, and sirolimus presents new directions, experts say.
“DCBs for the prevention of restenosis in haemodialysis fistulas have now undergone rigorous evaluation, arguably more than any other AV access intervention apart from stent grafts for venous stenosis,” write Scott Trerotola (University of Pennsylvania, Philadelphia, USA), Prabir Roy-Chaudhury (University of North Carolina Kidney Center, Salisbury, USA) and Theodore Saad (Christiana Care Health System, Newark, USA) in a May 8 editorial published online in the American Journal of Kidney Diseases (AJKD). They elaborate that it is “perplexing and disappointing” to see conflicting results from a host of DCB studies with similar designs—leading to their claim that more data in this space has not equalled more clarity.
Trerotola, Roy-Chaudury and Saad’s editorial follows in the wake of Yanqi Yin (Peking University First Hospital, Beijing, China) and colleagues’ publication in the same journal in January this year of a multicentre randomised controlled trial evaluating the efficacy and safety of DCBs in preventing fistula restenosis in Chinese haemodialysis patients. The triallists report that, compared to conventional high-pressure balloon angioplasty, DCB treatment achieved superior primary patency defined using ultrasound-measured peak systolic velocity ratio (PSVR) at six months, and superior intervention-free survival of both the target lesion and the target shunt at 12 months, without evidence of greater adverse events.
Importantly, Trerotola and colleagues clarify that the compound, unvalidated endpoint incorporating a “peculiar” patency measure used in this trial confounds the interpretation of the results, as do the procedural differences across the two groups, with both of these factors detracting from the positive results of the study.
These results (obtained with Cardionovum’s Aperto OTW DCB; 3μg/mm2 paclitaxel dose) sit amidst two other previously reported large pivotal trials, the Lutonix AV trial that came within striking distance of achieving its primary endpoint (with BD’s Lutonix AV DCB; 2μg/mm2 paclitaxel dose), and the IN.PACT AV Access trial (with Medtronic’s IN.PACT AV DCB; 3.5 μg/mm2 paclitaxel dose), which was the only trial to successfully do so. A third, as-yet unpublished trial, PAVE, which also used the Lutonix AV DCB, did not demonstrate a benefit to using the antiproliferative. With this conflicting evidence of efficacy, the usual suspects of drug dose, excipient, patient, procedure, fistula and lesion specifics come into the foreground to understand discrepancies in outcome, although Trerotola and colleagues use the Chinese trial results to suggest discounting dose, but not excipient, differences.
But, if the efficacy outcomes of DCBs are mined from the IN.PACT AV Access trial data alone and modelled to demonstrate economic benefit, there are savings gains for systems to be had, investigators maintain.
Robert Lookstein (Mount Sinai, New York, USA), first author of the six-month IN.PACT AV Access trial results, published in the New England Journal of Medicine and showing that DCB angioplasty was superior to standard angioplasty for the treatment of stenotic lesions in dysfunctional haemodialysis AV fistulas, has previously outlined that using the IN.PACT AV DCB can confer economic advantages to healthcare systems.
Lookstein and colleagues used 12-month reintervention rate data from the IN.PACT AV Access pivotal trial within a Budget Impact Model of the US and German healthcare systems to demonstrate cost savings almost immediately. “As those savings were projected out [from 12 months] to 36 months, each individual patient projected out a saving of over €3,000 in the German economic model and over US$3,300 in the US healthcare system”, he stated, elaborating that these numbers—when applied in conservative modelling to the entire end-stage renal disease population in both systems—would demand a lot of attention from payers.
Economic benefits to patients and health systems with DCB use accrue over time
This theme was further explored at the recent Charing Cross (CX) 2021 Digital Edition (19–22 April, online).
Presenting on the economic outcomes of DCBs in AV access at two years in the US healthcare system, professor of radiology Sanjay Misra (Mayo Clinic, Rochester, USA) reported gains over time for DCB compared to standard balloon angioplasty. The IN.PACT AV access trial one-year results underpinned the calculations used in the analysis with two approaches being used: a primary analysis involving index and reintervention-based costs, and a secondary analysis for comprehensive vascular access costs. The results from the primary analysis showed meaningful reductions in projected reintervention costs. If the DCB cost is US$1,800 or less, the strategy would break even at the two-year mark, and achieve savings of US$1,400 at the three-year horizon, said Misra, noting that “as time goes by, savings become larger.” Even earlier cost neutrality and slightly higher savings at the two-and-a-half-year mark were achieved using the secondary analysis. At a healthcare system level, Misra proposed that Medicare savings to the tune of US$160–250 million could be made at one year, growing to more than US$420 million at three years if half of the 233,000 annual procedures of standard angioplasty were converted to DCB use instead.
Misra said: “Using two independent calculation approaches, treatment with the IN.PACT AV DCB can be expected to lead to substantive per patient and health system savings.” Further, these savings vary by site of service, with the greatest savings being obtained in the in-hospital setting, he noted.
Misra’s recent research has focused on the use of stem cells to aid AV fistula maturation and prevention of venous stenosis. He attributed the patient gains with the use of DCBs to the reductions in reinterventions, which can help reduce patient morbidity and help improve quality of life, but cautioned that these findings were based specifically on data from the IN.PACT AV Access trial and may not apply to other DCB devices.
These data led session moderator Nicholas Inston (Queen Elizabeth Hospital Birmingham, Birmingham, UK) to ask whether DCBs should be rationed and reserved to maintain access in patients who were likely to survive beyond the two-year mark on a cost basis. “I think it is very difficult to determine who is going to live for two years […] so I would be a little hesitant to ration the use of this technology,” responded Misra, noting that things to look out for included determining which patients might thrombose. Co-moderator Domenico Valenti (King’s College Hospital, London, UK) intervened to clarify whether the costs of using high-pressure balloons had been accounted for in the analysis, prompting Misra to explain that these had been bundled within the costs attributed to standard angioplasty.
Exciting new direction for drug treatment accelerates with sirolimus use
The dialysis vascular access circuit is often fated for failure due to neointimal hyperplasia formation, which is widely accepted to be the main pathophysiological reason for vessel narrowing. What man tries to create, nature tries to “take back”, quipped Suai Chieh Tan (Singapore General Hospital, Singapore). The use of sirolimus as an alternative drug coating to paclitaxel to arrest neointimal hyperplasia is advancing, but is still at early stages, he said during the same CX 2021 session on access maintenance.
The two drugs, sirolimus and paclitaxel, are vastly different, Tan made abundantly clear, with the former described as being a cytostatic, immunosuppressant antiproliferative and the latter a cytotoxic, chemotherapeutic agent.
Describing the emerging evidence from Singapore using sirolimus-coated balloons to treat thrombosed AV grafts, which are plagued by abysmal results, Tan drew attention to published results in the Journal of Vascular and Interventional Radiology (JVIR) from last year showing a three-month primary patency of 65% that dropped to 55% at six months—figures he described as encouraging when compared to similar data stemming from the employment of cutting balloons or stent grafts.
Turning tack to the outcomes of sirolimus balloons with AV fistulas, he presented data from PLOS One, also from last year, showing six-month circuit access patency rates of 68% and target lesion primary patency rates in the same timeframe of 82.9% with Concept Medical’s MagicTouch device.
Spurred on by these initial data with small numbers of patients, the team at Singapore has embarked on a prospective, multicentre, double-blinded randomised controlled trial and begun enrolling patients with failing AV fistulas from January 2021. The triallists plan to enrol 170 patients who will be allocated to receive either standard angioplasty or treatment with a sirolimus-coated device.
Inston then looked back to the use of sirolimus as an immunosuppressant in renal transplants to seek reassurance that using this potent drug would not eventually lead down a path of “having our fingers burnt” due to impaired wound healing, provoking Tan to reply that these studies were an effort to harness the potential of this drug in slowing down the process of neointimal hyperplasia within the blood vessel being treated.
Tan closed his presentation by noting that the application of sirolimus-coated balloons in dialysis access appears to be safe and effective, but said that larger randomised trials were ongoing to verify these early findings.
This is essentially the same thought Trerotola and colleagues conclude their AJKD editorial on the wider topic of DCB use in failing fistulas with: “[…] nephrologists may be heartened in the knowledge that there are multiple additional large multicentre randomised controlled trials forthcoming, hopefully with commonly used and well-accepted endpoints, which will perhaps provide both more data and more clarity. Only time will tell.”
BoneView, an artificial intelligence (AI) software from French company GLEAMER, provides a gain of 8.7% increase in sensitivity and a 4.1% gain in specificity without loss of reading speed, and thus is an effective aid for radiologists and emergency physicians in the detection and localisation of appendicular skeletal fractures.
The interpretation of radiographs suffers from an ever-increasing workload in emergency and radiology departments, the study investigators write in Radiology, while missed fractures represent up to 80% of diagnostic errors in the emergency department. Lead author Loïc Duron (Adolphe de Rothschild Foundation Hospital, Paris, France) and colleagues therefore set out to assess the performance of BoneView in an effort to improve radiograph interpretation.
“To our knowledge, this is the first study that evaluates the performance of AI‐assisted reading for radiographic fracture detection over the entire appendicular skeleton and on multicentre data, from a variety of imaging systems, some of which were not present in the training database,” comments Duron, who is currently doing a science thesis on AI in medical imaging.
“This study is the result of significant collaborative work between specialists in radiology, data science, biostatistics, and GLEAMER teams to evaluate the clinical performance of BoneView. This is an important step that quantifies and scientifically validates the benefits of this AI solution available to healthcare institutions, in a context where several solutions are marketed without published objective results,” adds Antoine Feydy, osteoarticular radiologist at Cochin Hospital (Paris, France). “Publication in Radiology, a journal with the highest impact factor in the field, reflects on the one hand the rigor of the methodology used but also the magnitude of the obtained results. ”
“We are delighted and proud of the publication in Radiology of our ambitious clinical study with BoneView, whose results are unequivocal on the benefits of the cross‐interpretation of AI and the physician: 30% decrease in the rate of undetected fractures, while reducing the radiographs reading time by 15%, on exams specifically selected for their difficulty, i.e. with so‐called non‐obvious fractures. In 10 years, the number of exams to be analysed by radiologists has doubled, while the number of radiologists has increased by only 20%. We are continuing our developments to improve and enrich our range of AI software to progressively automate the diagnosis of standard radiography to ensure very high reliability of the examination and optimal patient care,” says Christian Allouche, CEO and co‐founder of GLEAMER.
Prior to the study, the BoneView AI system was trained on 60,170 radiographs obtained from trauma patients. For the study, between 2016 and 2018, 600 adult patients in whom radiographs were obtained after a recent trauma, with or without one or more fractures of the shoulder, arm, hand, pelvis, leg, or foot, at 17 French imaging centres, were retrospectively included. Six radiologists and six emergency physicians were asked to detect and localise fractures with and without the help of BoneView software. Sensitivity, specificity, and reading times with and without assistance were compared after averaging the performance of each reader. AI assistance improved physician sensitivity per patient by 12% (and 22% for patients with multiple fractures), and specificity by 5%; it also reduced the average number of false positives per patient by 42% in patients without fractures and the average reading time by 15%. Finally, the stand‐alone performance of a newer version of the AI system was superior to that of all unassisted readers, including osteoarticular expert radiologists.
GLEMER state: “The help of AI improves the diagnostic performance of radiologists and emergency physicians, which will allow better patient management from their first imaging examination. Among the expected consequences, the help of AI should allow to improve the specificity of the complementary exams prescribed after the radiography, to avoid delays in care, and to direct patients into the right therapeutic pathway.”
LimFlow SA recently announced the publication of 12-month data from the full patient cohort in its PROMISE I study of the LimFlow percutaneous deep vein arterialisation (pDVA) system in the Journal of Vascular Surgery.
Results showed sustained positive outcomes for both amputation-free survival and wound healing. The minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated blood back into the foot via the veins in chronic limb-threatening ischaemia (CLTI) patients who are facing major amputation and have exhausted all other therapeutic options.
PROMISE I is a multicentre, prospective, single-arm study of the LimFlow system. It was conducted at seven US centres and enrolled 32 end-stage—or “no option”—CLTI patients, 100% of whom had non-healing wounds on the target foot, 69% of whom had diabetes, and 34% of whom had renal insufficiency. No-option CLTI is defined as being ineligible for surgical or endovascular arterial revascularisation as adjudicated by an independent committee of vascular surgeons.
“The publication of the PROMISE I results in the Journal of Vascular Surgery further validates the benefits of the LimFlow system,” said Daniel Clair, PROMISE I principal investigator and chair of the department of surgery at the University of South Carolina (USC) and Prisma Health-USC Medical Group (Columbia, USA). “The LimFlow pDVA system was effective in treating no-option CLTI resulting in a high percentage of treated patients healing their wounds and surviving free of major amputation at 12 months.”
In the PROMISE I study, 70% of patients achieved amputation-free survival at 12 months following treatment with the LimFlow system, and 75% had all wounds classified as healed or healing at 12 months as adjudicated by an independent core lab. Technical success was reported at 97%.
“Given the unacceptable rates of major amputations globally we are encouraged by the publication of the 12 month PROMISE I data in the prestigious Journal of Vascular Surgery,” said LimFlow CEO Dan Rose. “We are making great strides in our currently enrolling PROMISE II pivotal trial in the USA and Japan, and we look forward to advancing our mission of leaving no limb left behind.”
Researchers have found no statistically significant difference in mortality between patients treated with drug-coated devices and non-drug-coated devices in the SAFE-PAD study. Eric Secemsky (Beth Israel Deaconess Medical Center [BIDMC], Boston, USA) reported this conclusion at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual), with results published simultaneously in JAMA Internal Medicine.
At the behest of the US Food and Drug Administration (FDA), Secemsky and Robert Yeh (BIDMC, Boston, USA), designed the SAFE-PAD (Safety assessment of femoropopliteal endovascular treatment with paclitaxel-coated sevices) study to provide information on the safety of paclitaxel-coated devices.
Using claims data from the Centers for Medicare & Medicaid Services (CMS), the researchers evaluated survival following treatment with paclitaxel-coated devices in more than 160,000 leg artery revascularisation procedures conducted between 2015 and 2018.
“Our study of Medicare beneficiaries includes more than 160,000 patients, including more than 30,000 patients with survival data extending past four years, making it one of the largest and most comprehensive evaluations of the safety of drug-coated devices to be published since the initial analysis,” said Secemsky. “Although the 2018 findings [reported by Konstantinos Katsanos et al] raised concerns about the safety of these drug-coated devices, there were many issues with that analysis—including the study’s small size and a lack of complete patient follow-up.”
Secemsky and colleagues’ study included Medicare patients treated with either a drug-coated or non-drug coated peripheral device between 2015 and 2018 at nearly 3,000 hospitals across the USA. Deaths were evaluated through May 2020, and after accounting for any differences in demographics and co-morbidities between the two groups, the investigators found no evidence that drug-coated devices were associated with higher mortality rates through an average 2.7 years of follow-up, with some patients having follow-up through five years.
“We used a number of novel statistical methods to assure these results were accurate, and found consistent results across a number of different patient groups—including among those of lower overall risk, those with more severe disease, and those treated in outpatient centere,” Secemsky said. “We have provided these results to the FDA [US Food and Drug Administration] to make decisions on whether to continue to restrict these drug-coated devices to only those at high risk of needing another leg procedure, or to return to the previous indications where these were used without restriction.”
The current publication is the first report of seven planned biannual reports as part of the SAFE-PAD study, which was designed to continue until all patients in the study had follow-up exceeding five years. As such, Secemsky and colleagues will continue to analyse these Medicare beneficiaries and update their findings until this study completes in late 2023.
“The SAFE-PAD study is a model example for collaboration between industry, academia, and the FDA to carry out rigorously designed, real-world studies to evaluate important medical device safety signals,” said Yeh. “We believe that applying stringent scientific standards to observational studies can create greater confidence in validity of these ‘big data’ approaches to the evaluation of medical therapies.”
Rivaroxaban (Xarelto, Bayer/Janssen), in addition to low-dose aspirin, should be considered as an adjunctive therapy after lower extremity revascularisation to reduce first and subsequent adverse outcomes, analysis from VOYAGER PAD, presented during a late-breaking trial session at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual), indicates. The findings were simultaneously published online in the Journal of the American College of Cardiology (JACC).
Rupert Bauersachs, director of vascular medicine at the Darmstadt Clinic (Darmstadt, Germany) and lead author of the study told ACC.21 attendees that the use of rivaroxaban significantly reduced the occurrence of total severe events of the heart, limb or brain and issues related to other vascular complications in patients with symptomatic peripheral arterial disease (PAD) who underwent lower extremity revascularisation. The findings underscore the broad benefits of this strategy in this high-risk patient population, he said.
“To our knowledge, this is the first time that the addition of low-dose rivaroxaban to aspirin has been clearly shown to reduce the occurrence of both first and total adverse events in patients with PAD who have undergone lower extremity revascularisation but remain at high risk for a heart attack, stroke or recurrent arterial blockage in a limb,” Bauersachs said. “The benefits we saw in the trial for total events were statistically significant and entirely consistent with those for first events. Rivaroxaban 2.5mg twice daily with aspirin should be considered as adjunctive therapy after revascularisation to reduce first and subsequent adverse outcomes.”
Recent data have shown that, after lower extremity revascularisation, there is a four-fold risk of acute limb ischaemia, Bauersachs told ACC.21 attendees, adding that this is associated with a high incidence of limb-related complications.
“There is a need for greater awareness that PAD is a distinct disease state and that patients with PAD have a high risk for cardiovascular adverse events and are generally a very vulnerable population, especially in the post-revascularisation setting,” Bauersachs said. “Care for these patients is often fragmented because the surgeon or interventionalist who performs the revascularisation may not follow them for complications or recurrences. They deserve to receive optimal treatment to reduce the risk of recurrences.”
The randomised, double blind VOYAGER PAD trial enrolled 6,564 patients in 34 countries who had PAD and had undergone lower extremity revascularisation. The patients’ median age was 67 years and 74% were men.
Patients were randomly assigned to receive either rivaroxaban or a placebo in addition to daily aspirin. The trial’s primary endpoint was timed to the first event of a composite of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction (MI), ischaemic stroke or cardiovascular death. Another prespecified endpoint was the total number of vascular events, including recurrent primary endpoint events as well as other vascular events. The median follow-up time was 28 months after revascularisation.
The research team reported in a late-breaking clinical trial presented at ACC.20/WCC that VOYAGER PAD met its primary endpoint, with a 15% statistically significant reduction in the risk of a first major adverse limb or cardiovascular event seen in patients who received rivaroxaban compared with those who received the placebo. The current study reports on the total number of vascular events, with over 4,700 occurring in the 6,564 patients randomised over three years.
“There were 342 fewer adverse events in the rivaroxaban group than in the placebo group, which translates to an absolute reduction in risk of 12.5%,” Bauersachs said. “In a high-risk population, that is a big gain in avoiding the need for patients to come back with vascular complications.”
The 6,564 study participants experienced a total of 4,714 vascular events during the study period with 2,301—or about one-third—experiencing at least one vascular event, Bauersachs said.
“So, during approximately three years of follow-up, about two to three out of six patients with PAD had a vascular event in spite of high utilisation of background medical therapy. This overall rate of vascular events is eye-opening and speaks to the high vulnerability of this patient population,” Bauersachs said. “First events are just the tip of the iceberg.”
A limitation of the study is that the trial was designed to assess the occurrence of first adverse events following lower extremity revascularisation, Bauersachs said. Therefore, in a double blinded trial, patients may come off study treatment or go on to other therapies after an event, which can attenuate the observed benefit. Assessment of the total number of adverse events, however, was a prespecified secondary endpoint and despite this limitation, the findings were statistically significant and robust in absolute terms.
VOYAGER PAD was funded by pharmaceutical companies Bayer and Janssen, who in a press release highlighting the presentation of the results, said that the analysis showed a very high burden of subsequent events and a consistent 14% reduction in both primary endpoint events and total vascular events over a median of 2.5 years.
“The VOYAGER PAD trial is the first and only study of antithrombotic therapy in the past 20 years to demonstrate a significant benefit in patients with PAD after lower extremity revascularisation,” James List, global therapeutic area head, Cardiovascular & Metabolism, Janssen Research & Development, was quoted as saying in the release. “With these new data, we now have a full picture of evidence demonstrating the potential of Xarelto in treating patients through various stages of PAD—chronic, symptomatic, those requiring revascularisation and beyond.”
“Even years after revascularisation, patients with PAD continue to have a markedly high risk for future thrombotic events due to excessive thrombin generation and platelet aggregation,” added Marc P Bonaca, Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, (Aurora, USA). “This analysis from VOYAGER PAD looked beyond the first event and found subsequent thrombotic event reduction with rivaroxaban plus aspirin, underscoring the importance of long-term prevention in these high-risk patients.”
Medtronic today announced new clinical data from the Global SYMPLICITY registry (GSR) indicating that renal denervation with the Medtronic Symplicity renal denervation system was associated with clinically significant and sustained blood pressure reductions in a real-world hypertensive patient population through three years. Results from the prospective, single-arm, global, observational study are being presented as a late-breaking clinical trial session at EuroPCR 2021 (18–20 May, virtual).
The study analysed nearly 3,000 patients with uncontrolled hypertension (HTN) and other comorbidities typical in HTN patients (chronic kidney disease, diabetes). Patients were treated with the Symplicity renal denervation system utilising the single electrode Symplicity catheter or the Symplicity Spyral multi-electrode catheter, and their outcomes were analysed up to three years post procedure. RDN with the radiofrequency based Symplicity renal denervation system is a minimally-invasive procedure intended to regulate overactivity of nerves that lead to and from the kidney, which play an important role in blood pressure control.
The GSR study results demonstrated the Symplicity renal denervation System led to significant and clinically meaningful reductions in blood pressure that were sustained out to three years postprocedure. Patients experienced a mean reduction of 16.7mmHg office systolic blood pressure (OSBP) at three years compared to baseline.
Investigators also evaluated the benefit of renal denervation within various patient subgroups using a clinical composite endpoint; a retrospective analysis comprised of both OSBP, 24-hour ambulatory blood pressure (ABPM), and medication burden. They found a consistent benefit of renal denervation in patients with versus without diabetes, chronic kidney disease, or patients who were 65 years and above. The similar clinical composite endpoint was used in a recent EuroIntervention publication that showed patients were nearly three times more likely to benefit from renal denervation compared to remaining on a regime of anti-hypertensive medications alone (Win Ratio=2.78, p<0.001).
“As we continue to expand our clinical data around renal denervation for uncontrolled hypertension management, we wanted to broaden our understanding of the long-term benefits for our patients who suffer from multiple chronic conditions and are typically prescribed multiple medications,” said Felix Mahfoud, cardiologist at Saarland University Hospital in Homburg, Germany and principal investigator in the study. “With this new analysis, we can now help patients continue to see the real-world benefits of renal denervation.”
EuroPCR: New analysis on estimated risk reduction from Symplicity renal denervation system
In addition to the late-breaking clinical trial results at EuroPCR, investigators also reported a new analysis estimating the reduction in clinical events in patients treated with the Symplicity renal denervation system. The analysis used the clinical events observed at three years in the Global SYMPLICITY registry and put these in perspective with a modelled control. The results showed a 26% relative risk reduction in major cardiovascular events (MACE) over three years for the full study cohort treated with renal denervation, and a 34% reduction for patients suffering from resistant hypertension over the same timeframe.
Medtronic expands renal denervation real-world data collection with the new GSR-DEFINE study
Building on the success of GSR and continuing its commitment to providing real-world evidence for the Symplicity Spyral renal denervation system, Medtronic also announced today launch of the GSR-DEFINE study. This new phase of patient data collection aims to enrol an additional 2,000 patients suffering from uncontrolled hypertension, who will be treated with the Medtronic Symplicity Spyral multi-electrode renal denervation catheter. The study will collect data for a subgroup of patients out to five years.
About the Medtronic Symplicity Spyral clinical programme
Along with the GSR and GSR-DEFINE studies, the Medtronic Symplicity global clinical programme also includes the SPYRAL HTN-OFF MED PIVOTAL and SPYRAL HTN-ON MED trials, both prospectively powered, randomised, sham-controlled studies evaluating patients with uncontrolled blood pressure in the absence and presence of prescribed anti-hypertensive medications respectively.
Approved for commercial use in more than 60 countries around the world, the Symplicity Spyral renal denervation system is limited to investigational use in the USA, Japan, and Canada.
In a recent study, Victor Demaerel (University Hospitals Leuven, Leuven, Belgium) and colleagues found that tunnelled haemodialysis catheter (THC) survival in 352 patients was more than 70% after five years. This finding, they conclude, “supports [THC] use for permanent dialysis access”.
The literature is divided about the potential role of THC as a permanent access for haemodialysis and about which patients are at high risk of THC-related complications, the authors write in the Journal of Vascular Access (JVA). They elaborate: “The native arteriovenous (AV) fistula is widely recognised as the optimal vascular access,” noting its association with “excellent” long-term patency and a low complication rate. THCs, on the other hand, “are considered a less reliable permanent access for haemodialysis due to higher rates of infection and thrombosis”.
However, Demaerel et al state, while the THC “definitely has its place”—specifically as a temporary access during AV fistula maturation in patients who need urgent dialysis—it is also “increasingly being considered in the elderly population because of difficulties with maturation of an AV fistula and a potential risk of right heart failure”.
Against this backdrop, the investigators decided to review the incidence and type of THC complications in a large cohort of patients with end-stage renal disease, and also assess the longevity of the THC and factors predicting high risk for complications.
Damaerel and colleagues relay that, between August 2009 and December 2016, a cohort of 538 patients underwent primary THC insertion, detailing that they excluded 67 patients from their analysis who did not have clinical follow-up data available.
The authors report the following results from the 352 patients in whom a THC was inserted in a virgin neck:
The authors acknowledge some limitations of their research. “This is a retrospective, single-centre study,” they recognise, noting that this might prevent generalisation of the conclusions. They do stress, however, that the number of patients included is still “substantial”. They also state that the team did not perform any randomisation or categorisation of types and brands of THC. However, they reference a systematic review and meta-analysis by Xiao-Chun Ling (Taipei Medical University, Tapei, Taiwan) et al, published in the Journal of Vascular Surgery in 2019, in which no catheter type was found to exhibit features that could potentially enhance their suitability for use.
Damaerel and colleagues conclude in JVA that this study “demonstrates the safe and efficient placement of THC under ultrasound and fluoroscopic placement,” and that late complications “mainly include infection and mechanical/thrombotic THC dysfunction”. Patients with more comorbidities, they note, “might be at higher risk of lower catheter survival rates,” and older patients “might experience THC-related adverse events beyond 18 months of follow-up”.
The Auryon atherectomy system (AngioDynamics) “represents an exciting new technology”, John Rundback (Advanced Interventional and Vascular Services, LLP, Teaneck, USA) opined at the International Symposium on Endovascular Therapies (ISET; 9–11 May, Miami, USA, and online), speaking on behalf of the Pathfinder I registry investigators. “I think it has really got a lot of traction; we found it a very useful tool across a wide range of plaque morphologies and vessel beds. Further iterations of this platform will hopefully improve its performance further.”
The Pathfinder registry is a post-market, prospective, multicentre, single arm, all-comers registry of 104 patients with femoropopliteal and tibial stenoses or occlusions or in-stent restenosis (ISR), with peripheral arterial disease (PAD) classified as Rutherford class 2–5. “Lesions of all levels, lesions of all types are included in this real-world registry,” Rundback said.
Patients were treated with either the Auryon atherectomy system or adjuvant therapy. The primary endpoints were acute success (measured as ≤30% final residual stenosis by corelab evaluation) and freedom from peri-procedural major adverse events or complications through 30 days. Long-term results were collected through 24 months, including patency, major adverse events, target lesion revascularisation, and patient-reported outcomes.
Presenting the findings, Rundback said: “These are really important results I think. Across the board, the stenosis reduction or the luminal gain was between 24 and 31%, and this is the laser-cut phenomenon that I think is unique to this laser. In CTOs [chronic total occlusions], there [is an average] 26% luminal gain; [in vessels with] moderate to severe calcium, there was a 27% luminal gain, [in vessels with] ISR, [there was a] 21% luminal gain, and above and below the knee, we see similar levels of luminal gain. So it does not matter what vessel, what vessel calibre, or what the plaque morphology is, this is a very precise, deliverable, controllable, and reproducible result.”
In terms of safety, there was an absence of major adverse events in 99% of lesions. There was one dissection, which was after angioplasty alone, not after laser passage. There were two cases of distal embolization, one of which Rundback said was “probably attributed to the laser”, and one of which was following the treatment of an in-flow lesion that had angioplasty, shockwave, and atherectomy. There were a total of four bailout stents, three of which were for recoil and one of which was for dissection. There was one amputation, which occurred 180 days after follow-up; the patient had Rutherford category 5 disease and gangrene at baseline, and they failed to improve following treatment of their 37cm-long lesion.
The Auryon atherectomy system is a proprietary, solid-state laser with a wavelength of 355nm (different to the currently-available 308nm laser). “What is really unique about this is it is not just the wavelength, but it has a very short pulse duration of 10ns, which results in a very precise, controllable, and reproducible laser energy delivery to the vessel wall,” Rundback explained.
He went on to describe how this particular wavelength (355nm) has a “very high” affinity for atheroma compared to the vessel endothelium, resulting in a reduced risk of perforation. Indeed, in the Pathfinder I trial, no perforations were reported. There is also less overall thermal damage to the vessel wall, he explained, and the laser system is agnostic to the presence of contrast. It also requires minimal warm-up time: “From a practical point of view, it only needs a 15 second warm-up; if you do not like where it is placed in the room, you can pick it up and move it to another spot.” In addition, Rundback claimed the Auryon atherectomy system is optimal for treating all lesion types.
There are four catheters that are used with this system, ranging from a 0.9mm catheter for below the ankle and in the tibial arteries, to a 2.35mm catheter for the popliteal and superficial femoral arteries. There is also a 2mm catheter for the femoropopliteal and tibioperoneal trunk, and a 1.5mm catheter, for tibial and femoropopliteal arteries.
The Pathfinder registry builds on prior investigational device exemption (IDE) and CE studies, which combined investigated 147 patients with 163 lesions. In these previous research, there were no distal emboli events, and no perforations. Of 107 lesions included in the IDE study, there were just 16 graded as minor dissections (grades A or B). In terms of debulking, there was a 34% reduction post-procedure (the FDA threshold for efficacy is 20%). “Clinical results and patient-reported outcomes were very favourable at 12 months,” Rundback stated.
Session moderator Daniel Clair (Vascular Surgery, University of South Carolina (USC) and the Palmetto Health-USC Medical Group, Columbia, USA) praised Rundback for his talk, saying it offered, “A new look at laser”.
Siemens Healthineers launches its Somatom X.ceed, a new high-resolution, high-speed computed tomography (CT) scanner. To support medical staff in their workflows during critical situations, two “companions” for automated user guidance are integrated: myExam Companion guides users through diagnostic procedures; myNeedle Companion supports targeted needle path planning as well as laser-guided insertion across multiple modalities. As a result, the fastest single-source CT scanner from Siemens Healthineers can assist healthcare providers with their clinical decisions in areas like emergency imaging, cardiac CT, and CT-guided interventions.
Somatom X.ceed has an 82cm bore and a “user-friendly” tablet operation, Siemens state in a press release. The integration of myExam Companion allow the system to achieve high-speed and high spatial resolution, key for cardiac, emergency, and spectral imaging.
myNeedle Companion for minimally invasive treatment
CT is one of the most used imaging modalities when cross-sectional image guidance is needed for percutaneous interventional procedures, like biopsies, ablations, or pain therapy. Almost 50% of sites perform at least three CT-guided interventions per day. In these procedures, time and precision are critical. But the time needed, and the success rate, depend greatly on the users and their experience level. Patient cooperation influences the success rate as well. Complex hardware and user interfaces or limited guidance may even increase these challenges and lead to variations in outcome.
Siemens claim that myNeedle Companion simplifies the workflow in minimally invasive treatments. myNeedle Companion is a unique combination of hardware and software designed to greatly reduce the complexity in CT-guided interventions. In addition, it is the first universal solution with a harmonised user interface for the planning and guidance of percutaneous needle procedures across imaging modalities, be it for a CT or an angiography system. Once the workflow is trained on one modality, the training efforts on another modality are expected to be much shorter. This can help to reduce unwarranted variations and minimise training efforts. Familiar user interfaces let the radiologist concentrate on what matters: accurate needle positioning with the help of the unique myNeedle Laser, a powerful, fully-integrated option that projects the needle entry point and insertion angle directly on the body of the patient—even in advanced double-angulated procedures with multiple needle paths.
Emergency and cardiovascular procedures are challenging and growing clinical areas for CT
Emergency radiology is rapidly evolving. In the last 20 years the demand for CT-imaging in emergency departments has increased by 250%. In a busy emergency environment, inefficient workflow can slow down radiologists who need to triage patients and perform multiple, demanding tasks quickly. With the support of myExam Companion, staff members can speed up procedures from patient preparation to image evaluation. Applications powered by artificial intelligence provide ready-to-read results aimed to facilitate diagnostic tasks.
The ability of cardiac CT to rapidly evaluate multiple cardiovascular conditions has allowed CT to become an important diagnostic instrument for steadily rising numbers in cardiovascular diseases (CVD). From 2011 to 2019, CT cardiac procedures more than doubled from 1.4 to 3 million. These procedures, some of the most complex in CT, are now performed routinely by staff of all skills levels. Here, as in emergency imaging, myExam Companion plays a major role in guiding the user towards more standardised results and low dose levels.
“As the number and complexity of radiological procedures increase, demands on staff are reaching heightened levels. This continues to cause unwarranted variation, in both diagnostic and interventional procedures. Somatom X.ceed, together with myNeedle Companion, is a true game changer for CT-guided interventions. After the introduction of myExam Companion last year, reducing the overall complexity of scanner operation in as many aspects as possible was our next logical step,” says Philipp Fischer, head of CT at Siemens Healthineers.
The first patient has been enrolled in DOORwaY-90, a study evaluating the safety and efficacy of selective internal radiation therapy (SIRT) using SIR-Spheres Y-90 resin microspheres (Sirtex) in patients with unresectable hepatocellular carcinoma (HCC).
DOORwaY-90, which stands for “Duration of Objective Response with Arterial Y-90,” is the first prospective, US-based, multicentre, open-label, single arm study of its kind. The study will assess the duration of response and objective response rate of SIR-Spheres. It is being led by co-principal investigators Cheenu Kappadath and Armeen Mahvash (both The University of Texas MD Anderson Cancer Center, Houston, USA). Study enrollment is underway, with the first patient enrolled at Inland Imaging Associates and Providence Sacred Heart Medical Center in Spokane, USA.
“We are thrilled to enroll the first patient in DOORwaY-90,” comments Mark A Turco, global chief medical officer and EVP of research and development for Sirtex. “This clinical trial studying a heterogeneous population of patients with HCC using personalised dosimetry planning has the potential to advance the treatment of HCC patients worldwide. We are deeply thankful to every clinical investigator and patient who will be part of this ground-breaking journey.”
With a planned enrollment of 100 patients across 15 sites both academic and non-academic, DOORwaY-90 is enrolling patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B1, and B2 who are not eligible for resection or ablation at the time of study entry. The study is unique because it is the first FDA-approved US-based prospective trial to utilise and delineate personalised dosimetry treatment planning and to define actionable post-treatment dosimetric verification for endpoint assessment.
“It is important for physicians to have confidence that their planned Y-90 dose is being delivered in the right amount and to the right place,” says Douglas Murrey, vascular and interventional radiologist at Inland Imaging Associates and Providence Sacred Heart Medical Center in Spokane, USA. “The personalised dosimetry component of the DOORwaY-90 study will provide meaningful insights to advance our practice and patient outcomes.”
HCC is often diagnosed when potentially curative resection or transplantation is not feasible. SIRT has the potential to deliver a lethal dose of radiation to hepatic tumours, while sparing surrounding healthy liver tissue. In countries outside the USA, SIRT has been successfully used to bridge patients to transplantation or downstage HCC to within transplantation criteria or resection.
Transit Scientific recently announced it has received CE mark clearance in the European Union for the XO Score scoring sheath platform to facilitate dilation of stenotic material in the peripheral vasculature including popliteal, infrapopliteal, and native or synthetic arteriovenous dialysis fistulae.
XO Score is a new type of scoring and cutting technology that enables low-pressure lesion dilatation and vessel prep with a broad range of standard off-the-shelf percutaneous transluminal angioplasty (PTA) balloons. Scoring sheaths have the ability to deliver enhanced angioplasty with basic balloons while addressing the cost and performance limitations of traditional scoring or cutting technologies.
“We need novel, safe, and appropriately aggressive vessel prep devices to continue fighting the increasingly difficult stenotic lesions encountered in CLTI [chronic limb-threatening ischaemia] patients,” said Jihad Mustapha (Advanced Cardiac & Vascular Center, Grand Rapids, USA). “XO Score helps fill that unmet need by enabling variable scoring depths and improved pushability which are essential when dealing with tough calcifications.”
The XO Score incorporates a unique one-piece metal-alloy exoskeleton design which adapts to the shape, size, and length of the PTA balloon used inside it. This approach lets physicians select the PTA platform of their choice for use in conjunction with XO Score, potentially reducing inventory and procedural costs. Future ultra-low-profile over-the-wire and rapid-exchange versions are under development for smaller vessel and coronary use.
“The ability to scale this technology down to below 3Fr is especially important for treatment of pedal loop stenosis and deployment in the tibiopedal junction,” continued Mustapha. “This is at the forefront of our fight against CLTI as the disease state continues to worsen.”
This CE mark clearance covers the XO Score platform in 65cm and 125cm working lengths with 0.25mm (0.010″), 0.35mm (0.014″), or 0.50mm (0.020″) scoring or cutting depths to enable precise dilation of calcified and fibrous lesions.
“I am going to give you reasons to be excited about your critical limb practice,” Peter Schneider (University of California San Francisco, San Francisco, USA) told delegates attending the International Symposium on Endovascular Therapy (ISET; 9–11 May, Miami, USA), in a talk focusing on innovative tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI). “I think critical limb ischaemia has come to the forefront of our practices and of community awareness, and finally now the tools are starting to show that,” he opined.
Covering developments in assessment (including monitoring, perfusion, and wound evaluation), reconstruction, and medication delivery, Schneider left his audience with an optimistic outlook for the future of CLTI treatment.
Assessment: Wearables, implantables, and artificial intelligence
Turning first to wearables and implantables, which he said “are just around the corner”, Schneider expanded: “[In terms of] implantables, there is a patent application for a stent with a sensor on it, which of course makes sense that someday that is how we will be doing our surveillance.
“Wearables are available now, and are essentially a transfer from other types of technology.” Citing a JAMA Network Open article from late 2020, which looked at the association between wearable device–based measures of physical frailty and major adverse events following lower extremity revascularisation, Schneider said he expected to see “more articles like this one”, adding: “I am sure we are going to have [investigations into the use of wearable devices to assess frailty] for claudication patients on a regular basis as well.”
In addition to wearables and implantables, he also directed the ISET audience’s attention towards the use of artificial intelligence (AI): “A couple of companies have taken it upon themselves to do a digitised wound evaluation, and then use AI to help the programme get smarter over time about identifying the cause of the wound and the progress of the wound. So much of what we are doing is an inexact science: when we think of screening, population management, treatment guidelines, we are thinking about the population as a whole, and just trying to do the right thing, but each of these patients comes having their own code and their own set-up, so the transfer of existing technology I think will help us to individualise the way we would like to.
Reconstruction: Modified balloons, new implants, alternative bypass, below-the-ankle angioplasty
“Below-the-knee [BTK] angioplasty is just sitting there waiting for us to really develop it,” Schneider stated, telling delegates listening in Miami and online that the medical community is now starting to see data showing improved wound healing. However, he noted that the patency data are “still unclear”, and in his opinion needs to be further assessed. “But I think we are really developing [in this arena],” he concluded.
The speaker first highlighted the lithotripsy with Shockwave. Lithotripsy waves travel outside the balloon, and disrupt both superficial and deep calcium. It is a way to improve vessel wall compliance prior to controlled, low pressure dilatation. “The question is how valuable is this going to be in BTK interventions?” Schneider asked. “I think it remains to be seen, but it certainly is a technology for interrupting calcium.”
Another technology Schneider considered was serration angioplasty. Noting his conflict of interest due to his involvement with Cagent Vascular, a developer of serration technology for vessel dilatation in endovascular interventions, Schneider explained how the novel Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter works: “The idea is that you poke little holes in the artery, and allow a stress relief line along the vessel so that it can be opened. I really believe that BTK angioplasty is due for a makeover by one method or another, and here is just an example of the flexibility of this tool.” The Serranator PTA serration balloon catheter is the first and only angioplasty balloon to receive Food and Drug Administration (FDA) approval and the CE Mark that embeds serration technology into a semi-compliant balloon for treating peripheral arterial disease (PAD). Earlier this year, results of Cagent Vascular’s PRELUDE-BTK study—a prospective, single-arm, multicentre feasibility study investigating the safety and efficacy of serration angioplasty—were presented at the Leipzig Interventional Course (LINC; 25–29 January, online).
Forty-six patients were treated with the Serranator device and 53 lesions were analysed by the core lab. The average final residual stenosis was 21.8%, with an average BTK arterial lumen gain of 1.55mm. These results were achieved with a low average maximum atmospheric pressure of six atmospheres. The bailout stent rate was 1.9%. A subset of lesions (n=10) were imaged with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) and analysed by a core lab. All showed a serration effect. At 30 days, the freedom from primary safety events was 95.7%. Freedom from clinically driven-target lesion revascularisation (TLR) was 97.7%, and there were no serious adverse events related to the device.
Following this discussion on modified balloons, Schneider turned to a new method of post-angioplasty dissection repair: focal dissection repair. He showcased a new implant, the Tack endovascular system (Intact Vascular), the first FDA-approved vascular implant for BTK post-angioplasty dissection repair. Regulatory approval for the device was based on data from Intact Vascular’s Tack optimised balloon angioplasty II BTK (TOBA II BTK) clinical trial, which met all primary endpoints with 100% acute dissection resolution. The TOBA II BTK results demonstrated 95.7% amputation-free survival, 87.3% target lesion patency, with significant improvement in toe-brachial index (TBI), and 92.0% freedom from clinically-driven reintervention at six months.
Schneider mused: “The issue is; do we need IVUS? We know IVUS is more sensitive—all of the trials we did with focal dissection repair were angiographically-driven, however, could the results have been better if we used IVUS routines? Just something to think about as BTK disease gets more sophisticated, what will the role of IVUS be?”
Another implant Schneider explored in his presentation was a bioabsorbable vascular scaffold, the Abbott Esprit. This is an everolimus-eluting device, designed for the superficial femoral artery and iliac arteries. Recently-published data from Ramon Varcoe (Sydney, Australia) and colleagues show “excellent” patency out to five years. The LIFE-BTK randomised controlled trial, where participants will be randomised 2:1 Esprit versus PTA, is now enrolling in the USA.
Lastly in the “reconstruction” portion of his talk, Schneider mentioned percutaneous bypass. “The mean lesion length in the PQ bypass trial is in excess of 30cm, so we have not typically had an option for lesions of that length using percutaneous devices,” he announced. DETOUR II is a prospective, multicentre trial evaluating the Detour system for percutaneous femoral-popliteal bypass in patients with extremely long, complex lesions in the SFA. The study enrolled 202 patients in 36 sites in the USA and Europe, and is assessing freedom from major adverse events (MAE) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness is primary patency at 12 months.
Speaking to Interventional News about the potential of percutaneous bypass, principal investigator Jihad Mustapha (Advanced Cardiac and Vascular Centers, Grand Rapids, USA) said at the end of 2020: “If percutaneous femoral-popliteal bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR1 study, it could be a game changer for the way we treat complex, long-segment SFA disease today.”
Medication delivery
“We do not have any paclitaxel BTK drug-coated balloons (DCBs) in the USA,” Schneider said. While he noted that there are several paclitaxel DCB trials currently underway in the USA—he showed three of them: IN.PACT DEEP, Lutonix BTK, and BIOLUX P-II—he commented that “nothing is close to being approved”, though some show promise. “In particular, Medtronic has some preliminary data,” he said, before continuing: “My personal opinion is that the paclitaxel issue will fade over time. I think we have had such a hard time finding a danger signal in any subsequent data. Nevertheless, the whole issue has bought forward the concept of limus-based compounds.”
The “paclitaxel issue” he is referring to here is the increased association with mortality reported by Konstantinos Katsanos (University of Patras, Patras, Greece) et al in December 2018 when paclitaxel devices are used in the lower leg, which caused an international furore about the safety of these devices. Since, multiple analyses have failed to replicate this signal, but, as Schneider pointed out at ISET, the publication opened the door wider for research and development into alternative drugs.
“Here is just one,” Schneider said, showcasing the MED Alliance Selution, a sirolimus-coated balloon from Swiss start-up MedAlliance. “This is their SFA device. It uses micro-reservoirs made out of biodegradeable polymer intermixed with sirolimus for sustained and controlled drug release—typically, the slow and difficult uptake has been the problem with sirolimus.” MedAlliance’s planned clinical programme includes specific trials focusing on BTK disease (SELUTION BTK IDE) and CLTI patients (PRESTIGE, PRESITINE, and STEP).
Concept Medical, another start-up, from India, has recently published a first-in-human series from its XTOSI study, demonstrating good six-month primary patency of its MagicTouch PTA sirolimus-coated balloon in the treatment of BTK arterial lesions, in addition to femoropopliteal lesions. In addition, the US-based Surmodics has a BTK DCB (the Sundance DCB) currently in a first-in-human trial.
“There is also a method of administering limus-based compounds using the Mercator Bullfrog catheter,” Schneider said, which has 510(k) clearance. The Bullfrog device delivers generic dexamethasone to the adventitia, reducing inflammation that can be caused by interventional revascularisation. Delivery is confirmed with the co-administration of contrast.
The final technology Schneider mentioned is the “Eluvia-type technology”, seen in the SAVAL BTK drug-eluting stent system from Boston Scientific, which utilises a polymer as well as paclitaxel, and has been successful in SFA trials. It is now being enrolled in BTK trials. The SAVAL BTK stent system was the first CLTI device to be recognised by the FDA breakthrough device programme.
Three of our top 10 stories of April 2021 highlight new data and ideas presented at this year’s Charing Cross (CX) Symposium, Digital Edition (19–22 April, online), covering the potential of Philips’ Fiber Optic RealShape (FORS) technology to reduce radiation exposure, a call on medical agencies to change their paclitaxel recommendations in peripheral arteries, and two-year IN.PACT AV Access results. Last month, the world’s first accreditation programme for interventional oncology also opened for enrolment, and Interventional News readers heard about the latest offerings from Philips Healthcare.
The International Accreditation System for Interventional Oncology Services (IASIOS) is now open for public enrolment, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) has announced. Twelve pioneering hospitals from nine countries participated in the IASIOS pilot phase, and the accrediting system, tested and optimised over the past two years, now stands ready to accept applications from facilities offering interventional oncology (IO) services worldwide, regardless of the institution’s size or location.
Opening the CX 2021 Digital Edition, experts deliberated crucial controversies in the abdominal aortic space. Discussion emphasised the potential of Philips’ Fiber Optic RealShape (FORS) technology to reduce radiation and ease technical success, with moderator Gustavo Oderich (Houston, USA) suggesting that “radiation will be a thing of the past” thanks to this new technology. Other key takeaways were a ringing endorsement that endoanchors have a part to play in the treatment of challenging necks, and consensus among the panel that parallel grafts should be used as little as possible in this hostile anatomy.
More than half (58%) of radiology leaders say they do not have enough diagnostic and interventional radiologists to keep patients safe, new data from National Health Service (NHS) trusts and health boards across the UK show. The data, recently published in a Royal College of Radiologists (RCR) report, also show that, despite many imaging doctors staying in the NHS last year to help the coronavirus effort, the NHS radiologist workforce is now short-staffed by 33% and needs at least another 1,939 consultants to meet safe staffing levels and pre-coronavirus levels of demand for scans.
In a Philips-sponsored video, Constantino Peña (Miami, USA) moderates an Interventional News webinar focusing on how the SmartCT system (Philips) can “transform” interventional radiology (IR) suites and the importance of 3D imaging within this setting. Peña is joined by two early-users of the technology, Marc Sapoval and Hicham Kobeiter, both from Paris, France.
Addressing representatives from the US Food and Drug Administration (FDA) and UK Medicines and Healthcare products Regulatory Agency (MHRA) directly, Thomas Zeller (Bad Krozingen, Germany) argued at the CX Digital Edition 2021 that “it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions”. Moderators Andrew Holden (Auckland, New Zealand) and Gunnar Tepe (Rosenhein, Germany), Podium 1st presenters Gary Ansel (Columbus, USA) and William Gray (Wynnewood, USA), as well as a 71% majority of the CX audience, supported this view.
Soundbite Medical Solutions has announced US Food and Drug Administration (FDA) 510(k) approval for the SoundBite crossing system—Peripheral (SCS-P) with the 0.014” active wire (14P).
Shivank Bhatia and Vedant Acharya highlight the importance of multidisciplinary collaboration between urologists and interventional radiologists when it comes to forming a successful prostate artery embolization (PAE) clinic, citing a decade of experience at the Miami Miller School of Medicine (Miami, USA).
The results of a two-year study support the continued safety and effectiveness of the Zilver Vena Venous Stent (Cook Medical) in treating symptomatic iliofemoral venous outflow obstruction, according to findings presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online).
Last month, Medtronic announced the safety and effectiveness results through 24 months for the IN.PACT AV Access clinical study. The data, which were presented virtually as a Podium 1st at the CX 2021 Digital Edition, demonstrated that the IN.PACT AV drug-coated balloon (DCB) is the first and only DCB to show sustained and superior effectiveness through two years compared to standard percutaneous transluminal angioplasty (PTA) in end-stage renal disease (ESRD) patients with de novo or non-stented restenotic native arteriovenous fistulae (AVF) in the upper extremity.
The results of a recent investigation have revealed no association between infrainguinal bypass tunnelling technique and primary outcomes in patients with limb ischaemia. “Compared to subfascial tunnelling,” write Nallely Saldana-Ruiz (University of Southern California, Los Angeles, USA) and colleagues in the Journal of Vascular Surgery (JVS), “the superficial tunnelling technique is not associated with primary patency or major amputation in limb ischaemia patients undergoing infrainguinal bypass with a single-segment great saphenous vein”.
A new wearable device designed to remotely monitor arteriovenous (AV) fistulae function in dialysis access patients uncovered promising data leading one set of researchers to conclude the technology offers hope for improved care and lower costs among a challenging patient population.
The SmartPatch monitoring system (Alio Medical)—which involves the extraction of real-time data through a series of sensors from a patch placed over an AV fistula, subsequent cloud-based machine learning, and then actionable clinical alerts—is currently undergoing testing in a series of pilot studies aimed at tackling the healthcare burden of kidney failure and vascular access failure.
The first analysed dataset demonstrated the device “has the ability to measure haemoglobin, volumetric flow, and haemodynamically significant stenosis in AV fistulas,” Richard F Neville (Inova Heart and Vascular Institute, Falls Church, USA) recently revealed during the Society for Clinical Vascular Surgery (SCVS) annual meeting (13–17 March, Miami, USA).
Neville and colleagues looked at 128 patients at three dialysis centres, with all study participants wearing a SmartPatch device over an AV fistula either in the upper or lower arm.
“In this particular study, we utilised state-of-the-art optical technology with a particular patented array that allows for better data acquisition,” explained Neville, who disclosed that he serves on the scientific board of Alio Medical. “This took into account position, motion, light, temperature, and pulse of the patient. There was no need for patient interaction. This was all done remotely, and the clinical alerts are in real time.”
The intention of the study was to evaluate the ability of such a device to monitor AV fistula function, degree of stenosis, flow rate and the physiologic parameter of haemoglobin levels as a marker that impacts fluid management.
All participants wore a SmartPatch for a week. Each of the three clinical centres involved focused on one of the three metrics. The location focused on haemoglobin analysis studied 57 patients, the facility looking at volumetric flow looked at 21, and the centre monitoring percentage stenosis evaluated 71 study participants.
For each metric, Neville said, machine training algorithms were developed using the first 116 data streams from the device sensors. The algorithms were subsequently tested and correlated on the next 157 data streams, correlating with haemoglobin standard measurement, transonic flowmeters, and the standard fistulagram, he added.
The resulting data, Neville et al found, showed that haemoglobin was measured with comparative accuracy “and only a standard deviation of 0.41 as compared to haemoglobin measurement using standard techniques.”
The SmartPatch detected low volumetric flow—a potential indicator for access failure—with 100% sensitivity and 75% specificity, Neville continued. “Additionally, the degree of stenosis was also detected, looking at haemodynamically significant stenosis of great than 50%, with 100% sensitivity and 100% sensitivity as compared to subsequent fistulagrams, and arteriographic and angiographic imaging.”
He commented: “Therefore, we concluded in this study that this initial dataset shows us that this remote wearable monitoring system has the ability to measure haemoglobin, volumetric flow, and haemodynamically significant stenosis in AV fistulas. We are also hopeful that this remote monitoring system will allow us—and shows promise to allow us—to improve the care and lower the costs associated with other healthcare factors associated with this patient population.”
Neville said potential future biologic metrics that the device might monitor include oxygen saturation, blood pressure, heart rate, and haemoglobin and sodium levels.
Co-moderating the SCVS session in which Neville delivered his team’s findings, Jean Bismuth (Houston Methodist, Houston, USA) queried how placement of the patch might impact on the reliability of the data collected.
Neville explained that Alio had “spent a lot of time” on the material involved in the patch to ensure it is not injurious to skin, and that it can be used and worn for extended periods of time, among other considerations.
Meanwhile, W Charles Sternbergh (Ochsner Health, New Orleans, USA) who was co-moderating alongside Bismuth, raised the spectre of potential pitfalls toward commercialisation of the technology. Among Medicare patients, Sternbergh said, “evaluation of how their fistula is doing is baked in” to evaluation and management (E/M) services conducted at dialysis centres. “Typically, it is not allowed to have prophylactic testing, and it would even be suggested that that’s fraudulent, as some freestanding centres that do fistulagrams every three months no matter what have found out.”
Sternbergh asked: “How might this device intersect those issues?” Neville admitted this question got to the heart of the studied approach Alio has taken toward commercialisation.
“The technology has evolved rapidly,” he said. “When we first started this project in the animal lab, there was one sensor, a photo acoustic sensor. Now there is an array of sensors, and that is why we are able to generate the variety of information that I showed you.”
But, Neville continued, commercialisation remains an important step yet to be thrashed out. There are number of possibilities, he explained. One option might involve the device being given away for free, with an in-app-based subscription fee then applied for the data. Another would necessitate approaching dialysis companies with the benefits of keeping dialysis access fistulas functioning, and also keeping patients out of the emergency room, Neville said. “There were some initial cost savings shown in a dialysis population in the UK in the national health system [NHS] there, where just monitoring the haemoglobin accurately allowed [doctors] to adjust erythropoietin—which is a very expensive medication—and possibly decrease it, saving money just on the medications that are used on these folks.”
In the end, Neville added, he sees the device incorporated as a value-added part of care for the AV fistula patient population, as large dialysis companies realise close monitoring of access health and physiologic parameters “may actually save the overall cost of the patient in the long term.”
iVascular has received CE mark approval for its balloon-expandable covered stent, iCover, a press release from the company states.
Balloon-expandable covered stents are commonly used for treating arteriosclerotic lesions in renal and iliac arteries, and for the treatment of aneurysms and ruptures.
According to iVascular, iCover can adapt to the most tortuous vessels due to its high flexibility and post-expansion capacity. “It also offers excellent visibility, as it is the only balloon-expandable covered stent with radiopaque markers on the ends of the stent, to facilitate the implantation and the post-expansion,” a company press release details.
iCover is encapsulated with iVascular’s new proprietary technology, CoverTech. This technology attaches the inner and outer expanded polytetrafluoroethylene (ePTFE) layers to ensure a complete encapsulation.
“The first clinical experiences with iCover are remarkable,” states Vicente Riambau (Hospital Clinic of Barcelona, Barcelona, Spain). He adds that “iCover stands out for its excellent navigability and flexibility, while the radiopaque tantalum markers on its ends provide better visibility under X-rays, which enhances precision during implantation. With the launch of iCover, iVascular offers a complete portfolio to treat all type of peripheral lesions.”
Micro Medical Solutions (MMS) recently announced that the US Food and Drug Administration (FDA) has granted breakthrough device designation for its MicroStent vascular stent. This novel technology is designed to achieve and maintain vessel patency, enhance wound treatment, and improve quality of life and blood flow in order to reduce amputation and mortality for patients with chronic limb-threatening ischaemia (CLTI) resulting from peripheral arterial disease (PAD).
“FDA breakthrough device designation is an exciting step forward for MMS and for patients with CLTI, who will have expedited access to MicroStent. We are pleased that the FDA is recognising the importance and severity of CLTI and look forward to collaborating with them as we go through the PMA [premarket approval] process,” said Micro Medical Solutions CEO Gregory Sullivan. “As we remain focused on the completion of our FDA clinical study, STAND, it is gratifying to know we are now one step closer to our goal to help as many CLTI patients as possible live without the trauma of amputation.”
MMS is currently engaged in an FDA randomised, multicentre pivotal clinical study for MicroStent, called STAND (A clinical evaluation of the MicroStent peripheral vascular stent in subjects with arterial disease below the knee), which began in May 2020 and will continue at up to 25 sites across the USA. In addition, the MMS study HEAL (An all-comers observational study of the MicroStent peripheral vascular stent system in subjects with peripheral arterial disease) is currently enrolling patients at centres in the EU.
“Not all Drug-Coated Balloons (DCBs) are created equal”, Juan Granada (New York, USA), tells Vascular News in this second episode of a four-part series on the history of DCBs.
Granada discusses why there are differences in these devices, noting that some have a longer term retention of drug, while some have opted for a more soluble drug so it can disappear more quickly from the tissue. Although many companies are using paclitaxel, the resulting biological effects between the devices may be “quite different”. The IN.PACT™ Admiral™ DCB (Medtronic) originally followed a “different technological principle” compared to other devices, and has a crystalline coating allowing for long-term retention of the drug, says Granada. He adds that this is why coatings and formulations that maintain therapeutic tissue levels over time have a higher chance to have a better clinical result long term.
Local drug delivery in the peripheral field has “changed our lives forever” and “we all need to be grateful that these technologies were aggressively pushed forward and now we have therapies that can really help critically ill patients,” concludes Granada.
This video is sponsored by Medtronic.
Episode 1: Go behind the scenes to delve into the birth and evolution of drug-coated balloons for Peripheral Interventions: Insight from two pioneers
EPISODE 3: The unique recipe for long-term clinical benefit with IN.PACT™ Admiral™ DCB
Episode 4: Real world data show IN.PACT Admiral DCB is “very efficient” even in complex lesions
COMING SOON
Episode 5: The impact of long-term DCB outcomes on patients’ quality of life
A study has found that bifurcated T-stent reconstruction offers a safe and effective treatment option for hepatic venous outflow obstruction (HVOO) with anastomotic stenoses in orthotopic liver transplantation (OLT) recipients.
The findings of this study were presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online), and indicated that this interlocking stent construct may also offer advantages in treating complex stenosis involving the hepatocaval junction—while minimising the risk of stent migration or the jailing of hepatic venous (HV) outflow by an inferior vena cava (IVC) stent.
Clinical success, as demonstrated by an improvement in the presenting symptoms of HVOO, was seen in six (75%) of the eight OLT patients included in the study, while the remaining two (25%) patients required repeat intervention, which was performed within two months due to a lack of clinical response in both cases.
The study was presented by Dillon Brown, a medical student at the University of Washington School of Medicine (Seattle, USA), who said: “The bifurcated hepatocaval stent model employed in our study could mean lower rates of complications such as stent migration and hepatic vein jailing for OLT patients experiencing hepatic venous outflow insufficiency. It could also allow the operator to treat more severe anastomotic stenosis, and treat both IVC and HV stenosis simultaneously.”
The study involved a total of eight OLT patients with symptomatic HVOO (six males; mean age: 57.6±7.6 years; range: 48–69 years), all of whom underwent combined IVC and HV bifurcated T-stent placement between 2004 and 2019. Indications observed in these patients included seven refractory ascites (87.5%), four liver function abnormalities (50%), and one hepatic hydrothorax (12.5%) in the setting of hepatocaval anastomotic stenoses, diagnosed using either Doppler ultrasound or computed tomography.
According to Brown, success, adverse events, and stent patency were all assessed, with technical success being defined as intended bifurcated hepatocaval stent placement and clinical success being defined by improvements in presenting symptoms.
All of the patients included in the study underwent technically successful bifurcated hepatocaval stent reconstruction with supra/intrahepatic IVC stent (Wallstent, Wallflex [Boston Scientific] or Gianturco Z-stent [Cook Medical]) placement followed by HV stent (Venovo [BD], Smart [Cordis], or Wallstent [Boston Scientific]) placement through the interstices of the IVC stent. The mean number of stents placed in each patient was 2.3 ± 0.5 (range: 2–3), with a mean IVC stent diameter of 22.6±4.7mm (range: 14–30mm) and a mean HV stent diameter of 12.4±2.2mm (range: 10–16mm).
While no IVC stent migrations occurred over the course of the study, one HV stent migration occurred 18 days after placement, requiring retrieval from within the IVC stent and replacement. One patient also died 66 days after intervention due to graft rejection, according to Brown.
In six of the eight patients included in the study, Brown stated clinical success was achieved at a mean time of 41±28.4 days (range: 7–91 days). For the remaining two patients, repeat intervention was performed within two months due to a lack of clinical response—including angioplasty (n=2) and additional IVC stent placement (n=1) for in-stent stenoses.
All of the stents demonstrated patency at the last follow-up appointment (mean: 2,126 days; range: 32–4,846 days), leading the researchers to conclude that bifurcated T-stent reconstruction offers a safe and effective therapy for HVOO with anastomotic stenoses in OLT.
“The next steps in researching the bifurcated hepatocaval stent construct will be to increase the size of our study by increasing the number of patients who receive this treatment, and also comparing the patient outcomes of patients receiving the bifurcated stents with conventional single-stent therapies,” Brown said.
Vascular Therapies recently announced results from its phase 3 clinical trial in which Sirogen showed encouraging arteriovenous fistula (AVF) outcomes in elderly end-stage renal disease (ESRD) patients. Sirogen is the company’s proprietary sirolimus formulation for intraoperative local drug delivery to reduce surgical stenosis in blood vessels.
Following positive clinical results from a phase 2 clinical study (n=30; two international sites, two surgeons), the company embarked on the ACCESS study, a phase 3, randomised, controlled, multicentre clinical trial. The ACCESS study enrolled 243 patients with ESRD and chronic kidney disease (CKD) from 20 US sites, including 20 nephrologists and 26 surgeons.
The study was designed to evaluate the safety and effectiveness of Sirogen to improve outcomes in patients undergoing the surgical creation of an AVF to provide vascular access for haemodialysis. The primary endpoint of fistula suitability for dialysis at six months was not achieved; however, in exploratory subgroup analyses that reflected the demographics of the enrolled population, the ACCESS study revealed important potential benefits for ESRD patients age 65 and older who required an AVF for dialysis, namely:
Maria DeVita, senior nephrologist at Lenox Hill Hospital in New York, USA, and medical monitor for the study, commented, “The clinical results from the ACCESS study are very encouraging, especially for ESRD patients age 65 and older, who represent 50% of the haemodialysis population in the USA. Additionally, there were no unexpected adverse events, confirming the overall favourable safety profile of the product.”
Sriram Iyer, chief scientific officer of Vascular Therapies, added, “The findings from the ACCESS study address an important unmet need for elderly dialysis patients. We would like to thank the nephrologists, surgeons, clinical coordinators, and patients for their participation in the study.”
More than half (58%) of radiology leaders say they do not have enough diagnostic and interventional radiologists to keep patients safe, new data from National Health Service (NHS) trusts and health boards across the UK show. The data, recently published in a Royal College of Radiologists (RCR) report, also show that, despite many imaging doctors staying in the NHS last year to help the coronavirus effort, the NHS radiologist workforce is now short-staffed by 33% and needs at least another 1,939 consultants to meet safe staffing levels and pre-coronavirus levels of demand for scans.
Furthermore, half of trusts and health boards (47%) do not have the staff or transfer arrangements needed to run safe 24/7 interventional radiology services, meaning patients are potentially missing out on life-saving procedures. Without more consultants in training, investment in new models of care and better staff retention and recruitment, by 2025 the UK’s radiologist shortfall will hit 44% (3,613 consultants short of real terms demand).
Mark Callaway, radiology workforce lead at The Royal College of Radiologists (RCR), comments: “Our new report has found the NHS needs thousands more radiologists to ensure patients get the safe and effective treatment they deserve, amplified by the first-hand experience of frontline doctors who witness the impact of consultant shortages on patient care on a daily basis.
“The staffing forecast for 2025 makes grim reading, but, even more worryingly, swathes of demoralised radiologists are imminently looking to work less or leave the NHS.”
The RCR’s latest workforce census reveals the NHS needs nearly 2,000 extra radiologists to clear scan backlogs, meet safe staffing quotas, and keep up with demand.
Meanwhile, a recent poll to gauge radiologists’ morale found half intend to cut their hours, and three times as many consultants than normal plan to leave the NHS in the next year.
Waiting lists for hospital treatment have now hit record highs in England and tens of thousands of patients currently face long waits for scans3.
Understaffed radiology departments across the UK are working hard to bring down backlogs caused by last year’s pause in non-urgent hospital work, while having to scan at a slower rate because of infection control and social distancing measures.
The census shows radiologist staffing has reached a tipping point, with imaging leaders warning that shortages pose a serious threat to NHS recovery and that patients facing “long, anxious and inevitable” waits for diagnoses and surgery as a result.
Hospital leaders completing the RCR’s census said radiologist shortages now continually jeopardise patient safety, reporting: “We cannot deliver adequate services for our patients” and “we can no longer provide cancer and acute care safely”.
The report shows the UK now has 4,277 radiology consultants, equating to 3,902 doctors working full-time, an increase of 170 full-time consultants compared to 2019.
Consultant numbers are increasing, but not fast enough to keep up with patient demand. RCR shortfall calculations, which use rota and service demand figures to give a realistic estimate of NHS requirements, show radiologist shortfalls range from 24–38% across the UK.
England now has 146 more full-time imaging experts than it did in 2019. However, it still needs another 1,675 consultants to keep up with NHS demand.
Radiologist numbers in other home nations have barely risen
Northern Ireland gained 19 extra full-time radiology consultants in 2020. Scotland gained five. Wales’ radiologist workforce has stalled and the country has incurred huge patient backlogs for scans during the pandemic. Wales also has the most severe radiologist shortage of any UK nation.
If nothing improves, the RCR predicts the UK’s 33% actual radiologist shortfall will hit 44% by 2025.
Closing the forecast gap between consultant supply and demand would require the number of new radiologists in training across the UK to treble, from 300 to 900 training places per year.
However, shortages could deepen even more quickly than forecast if findings from a recent RCR member survey are realised.
A poll of 1,089 UK radiology consultants at the start of April 20217 found:
Last year, NHS England’s top diagnostics adviser Mike Richards called for a major increase in hospital scanners and radiology staff in England.
On the back of these “stark” staffing data, the RCR is calling for these measures to be urgently realised across the whole of the UK.
The RCR’s radiology workforce lead Mark Callaway says: “The coronavirus pandemic has bluntly contrasted the every-day heroism of NHS teams with the chronic under-funding of services, and the cracks in radiology, as elsewhere, are becoming undeniable.
“Our new report has found the NHS needs thousands more radiologists to ensure patients get the safe and effective treatment they deserve, amplified by the first-hand experience of frontline doctors who witness the impact of consultant shortages on patient care on a daily basis.
“The staffing forecast for 2025 makes grim reading, but, even more worryingly, swathes of demoralised radiologists are imminently looking to work less or leave the NHS.
“Unless hospital imaging capacity is massively improved, the UK will continue to lag behind other countries on cancer survival rates and patients will face worse outcomes for trauma care and all kinds of conditions. The need for investment is urgent.
“The UK’s political leaders have made encouraging pledges around catching up with scan backlogs and implementing new diagnostic pathways and community-based scanning away from hospitals.
“The NHS also came through last year with emergency funding for scanners and private provider support, and we strongly support emerging plans to introduce diagnostic hubs to speed up access to scans, but the vital issue remains—we need more staff.
“Without thousands more radiologists—as well as radiographers, nurses and support staff—patients will inevitably continue to face long, anxious waits for radiology services, missing out on crucial early diagnoses and life-saving image-guided surgery.”
BD announced today that enrolment has begun and the first patients have been treated in the postmarket surveillance study, CONNECT-AV.
CONNECT-AV is a prospective, single-arm, open-label study that will follow patients treated with the WavelinQ endovascular arteriovenous fistula (endoAVF) system for 24 months.
The study’s dual primary effectiveness endpoints are the percentage of subjects dialysing using successful two-needle cannulation for at least 75% of the dialysis sessions over a continuous 28-day period at six months, and the subjects maintaining primary patency at six months.
The primary safety endpoint is freedom from device- and procedure-related serious adverse events through 30 days. The trial is expected to enrol 280 participants in the USA.
“For more than 50 years, medicine has looked for a next-generation haemodialysis access procedure for patients with end-stage kidney disease (ESKD) that can truly change the treatment paradigm,” said Brandon Repko, medical director of nuclear imaging and therapeutic services at Butler Memorial Hospital in Butler, USA, who treated the first patient in the CONNECT-AV trial in March 2021. “The CONNECT-AV trial is the next step in proving WavelinQ endoAVF system’s role in 21st century AVF creation. My colleagues and I are thrilled to be a part of that patient care evolution.”
CONNECT-AV is one of two postmarket studies of the WavelinQ endoAVF aystem. The second study, WAVE-Global is a prospective, single-arm, open-label study that will follow patients treated with the WavelinQ endoAVF system for 24 months.
The WAVE-Global primary endpoints are the number of interventions needed post creation to facilitate and/or maintain AVF use at six months, and the proportion of participants with freedom from Clinical Events Committee adjudicated device- or procedure-related serious adverse events at 30 days. The trial is expected to enrol 150 participants globally (outside of the USA).
“Physicians already have real-world experience using the WavelinQ endoAVF system to create AVFs that make life-preserving haemodialysis possible,” said Panagiotis M Kitrou, assistant professor in interventional radiology at Patras University Hospital in Patras, Greece, and a principal investigator in the WAVE-Global study. “Both of these studies will provide important long-term data on the safety and effectiveness of WavelinQ endoAVF aystem to help make informed decisions about patient care.”
The first patient in the WAVE-Global trial was treated by Kitrou in December 2020 at Patras University Hospital.
Opening the Charing Cross (CX) 2021 Digital Edition (19–22 April, online), experts deliberated crucial controversies in the abdominal aortic space. Discussion emphasised the potential of Philips’ Fiber Optic RealShape (FORS) technology to reduce radiation and ease technical success, with moderator Gustavo Oderich (Houston, USA) suggesting that “radiation will be a thing of the past” thanks to this new technology. Other key takeaways were a ringing endorsement that endoanchors have a part to play in the treatment of challenging necks, and consensus among the panel that parallel grafts should be used as little as possible in this hostile anatomy.
All Abdominal Aortic sessions are available to view on demand. Click here to register and access the recordings.
FORS addresses “major area of need” in abdominal aortic surgery
Marc Schermerhorn (Boston, USA) gave a presentation on the “disruptive” technology of FORS, which opened a panel discussion on the topic of radiation. Oderich stated that FORS “addresses a major area of need, which is the ability to look at the anatomy on any view we want without being radiated”, highlighting that the technology offers both an ease of technical success and parallel reduction of radiation. Looking ahead, he posited: “Radiation is going to be a thing of the past”.
Following Schermerhorn’s presentation, a Philips’ Meet the Experts session offered a deep dive into FORS technology, with a panel of users and experts discussing latest clinical experience and three-dimensional (3D) catheter agnostic guidance.
Registrants can view Schermerhorn’s presentation on demand here and Philips’ Meet the Experts session here.
Endoanchors in challenging necks come of age
In a Podium 1st presentation, William Jordan (Atlanta, USA) revealed preliminary five-year data from the primary arm of the ANCHOR registry (Aneurysm treatment using the Heli-FX EndoAnchor system global registry). This is a multicentre, prospective study designed to capture real-world usage of the Heli-FX EndoAnchor system (Medtronic) in patients with challenging AAA anatomy, particularly those with hostile aortic neck anatomies. Jordan concluded that, out to five years, patients with hostile necks “may have acceptable durability when the EndoAnchor fixation method is used, particularly at the index operation”.
Registrants can view this presentation on demand here.
Showcasing the practical use of endoanchors in the challenging neck anatomy, Giovanni Pratesi (Genoa, Italy) presented an edited case, with postoperative computed tomography angiography (CTA) showing complete aneurysm exclusion in a challenging proximal aortic neck.
Registrants can view this edited case on demand here.
Audience vote against use of standard EVAR in majority of challenging necks
A CX Debate addressed another pressing issue regarding hostile neck anatomy—that being whether standard endovascular aneurysm repair (EVAR) can be used in most challenging necks. Colin Bicknell (London, UK) stood for the motion, while Vascular Society of Great Britain and Ireland (VSGBI) president Michael Jenkins (London, UK) put forward the counterargument.
“There is significant, successful innovation to ensure short-term sealing and prevent long-term complications,” argued Bicknell, who resolved that EVAR is therefore appropriate for “most” patients with AAA who prefer this approach. Jenkins, on the other hand, contended that standard EVAR cannot be used in most challenging necks “because it does not work”. He elaborated: “It is outside IFU [instructions for use], aortic neck dilatation leads to loss of seal, and sac expansion causes positional change and effacement of seal zone.” He added that while adjuncts may help transiently, they are not durable. “What may have been heroic 10 years ago, perhaps maverick five years ago, now is criminal”, Jenkins concluded.
Following the debate, polling revealed that 71% of the CX 2021 audience disagreed with the motion that standard EVAR can be used in most challenging necks.
Registrants can view this debate on demand here.
Consensus among panel that parallel grafts should be used as little as possible in hostile necks
Also addressing a challenging neck controversy, Alexander Zimmermann (Zürich, Switzerland) gave a presentation on parallel graft use in the anatomy of a hostile neck, focusing in particular on “disappointing” clinical results thus far. He concluded that, in the majority of cases, he aims to “stay away” from using such grafts in challenging necks; the moderators were in agreement, with Ian Loftus (London, UK) voicing that he would only use parallel grafts in “very selective emergency cases” and Roberto Chiesa (Milan, Italy) stating that he uses parallel grafts as infrequently as possible.
Registrants can view this presentation on demand here.
All CX 2021 content is available to view on demand. Click here to access the recordings.
Addressing representatives from the US Food and Drug Administration (FDA) and UK Medicines and Healthcare products Regulatory Agency (MHRA) directly, Thomas Zeller (Bad Krozingen, Germany) argued at the Charing Cross (CX) Digital Edition 2021 (19–22 April, online) that “it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions”. Moderators Andrew Holden (Auckland, New Zealand) and Gunnar Tepe (Rosenhein, Germany), Podium 1st presenters Gary Ansel (Columbus, USA) and William Gray (Wynnewood, USA), as well as a 71% majority of the CX audience, supported this view. While there was agreement that it was right to be concerned about the paclitaxel mortality signal raised by Konstantinos Katsanos (Patras, Greece) et al in their December 2018 meta-analysis, there was strong consensus that the evidence is now clear there is no mortality effect when paclitaxel is used in the peripheral arteries. In addition, it was noted that several individual patient-level meta-analyses failed to confirm the high mortality signal flagged by Katsanos and colleagues. There was some discussion surrounding the place of limus as an alternative to paclitaxel, but experts agreed that there is no need to move to another drug—which would have its own set of challenges—given the proven safety and efficacy of paclitaxel. The takeaway message was clear: that, with proper caution and the correct dose, paclitaxel can and should be used in peripheral interventions.
All Peripheral Arterial Proximal sessions are available to view on demand. Click here to register and access the recordings.
More data find no mortality associated with paclitaxel
Patient safety has been at the centre of CX discussion on the paclitaxel issue since the Katsanos meta-analysis was published. This year, further data were presented that support the conclusion of vascular pathologist Elena Ladich (Hollywood, USA) who two years ago at CX 2019 stated that there are “no causal links or mechanisms to explain the reported association of paclitaxel in the lower limbs and patient mortality”.
Sabine Steiner (Leipzig, Germany) gave the first presentation on long-term paclitaxel data at CX 2021, outlining five-year results of the REAL-PTX study—an investigator-initiated, prospective, European, multicentre randomised controlled trial (RCT) comprising 150 patients with femoropopliteal disease. Patients were randomised to treatment with either a drug-eluting stent (100% Zilver PTX, Cook) or a drug-coated balloon (DCB; 77.3% IN.PACT Admiral/IN.PACT Pacific, Medtronic; 21.3% Lutonix, BD). Steiner reported that mortality rates after five years were “comparable to prior reports investigating long-term outcomes for drug-eluting and non-drug-eluting devices”.
Registrants can view this presentation on demand here.
Also presenting data in support of the safety of paclitaxel, Mårten Falkenberg (Gothenburg, Sweden) gave the latest analysis and interpretation of the SWEDEPAD trial concerning mortality. “It is very unlikely that devices coated with paclitaxel used for the treatment of peripheral arterial disease [PAD] do increase late mortality”, he concluded.
Registrants can view this presentation on demand here.
In a Podium 1st presentation on the topic, Andrew Holden (Auckland, New Zealand), on behalf of co-authors Ramon Varcoe (Sydney, Australia) and Peter Schneider (San Francisco, USA), revealed a five-year meta-analysis update regarding drug-coated technologies in femoropopliteal interventions and all-cause mortality concerns that included the SWEDEPAD update. Holden stressed that there is a “clear benefit of paclitaxel-coated devices in femoropopliteal disease” and relayed that the investigators recommend the continued use of these devices in this patient population. “The time has arrived for regulators to provide updated and clear guidance on these devices for the benefit of patients globally”, he stated.
Registrants can view this presentation on demand here.
Consensus that paclitaxel recommendations need to be changed
With a growing pool of data showing no association between paclitaxel and mortality, representatives from the FDA and MHRA reiterated current agency positions on the topic. Sara Royce, team lead of the plaque modification devices team at the FDA, talked the CX audience through regulatory approaches to the next-generation of drug-coated devices for PAD. Roopa Prabhakar, senior medical devices specialist at the MHRA, offered a UK perspective on paclitaxel device regulation, saying the agency will “continue to assess the significance of any new data in relation to patient safety”.
Registrants can view Royce’s presentation on demand here and Prabhakar’s presentation here.
Following these presentations, Thomas Zeller argued that it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions. “Withholding such devices to patients with severe peripheral arterial occlusive disease may even harm them and result in increased global healthcare costs”, he stated, concluding that “the benefit outweighs the hypothetical risk”.
Registrants can view this presentation on demand here.
Audience polling following Zeller’s talk revealed that 74% of the audience agree it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions.
“What you do not leave behind is a suboptimal result”
In a Podium 1st presentation, Gary Ansel (Columbus, USA) announced results of the IN.PACT Global stented versus non-stented analysis, comprising 353 patients stented and 1,044 non-stented patients. The purpose of this study was to compare outcomes of standalone IN.PACT Admiral DCB usage versus IN.PACT Admiral DCB followed by provisional stenting. Ansel concluded that, in this complex lesion subset from the study, the IN.PACT Admiral DCB “demonstrates durable safety and effectiveness through five years”. He added: “In the event of suboptimal angioplasty results (i.e. persistent residual stenosis >50%, flow limiting dissection), the addition of a stent did not appear to decrease the optimal results through five years”.
In the discussion following Ansel’s presentation, the presenter stressed that, regardless of whether or not you leave a stent behind, “what you do not leave behind is a suboptimal result, just to not leave a prosthetic device in. That is the worst thing to leave behind.”
Registrants can view this presentation on demand here.
Time to look at “the whole patient”
William Gray (Wynnewood, USA) delivered another Podium 1st presentation, giving the five-year results from a patient-level meta-analysis of the ILLUMENATE RCTs. He told attendees how “The Stellarex DCB continues to consistently demonstrate no difference in mortality compared to percutaneous transluminal angioplasty (PTA) year-over-year through five years, both within individual RCTs and pooled analysis.”
When asked by moderator Robert Hinchcliffe (Bristol, UK) if this was “the definitive trial to put the paclitaxel issue to bed”, Gray commented: “When you ask a US physician what puts an issue to bed, that is when the FDA rescinds their statement about danger. In order for them to do that, I think we have to see a high quality, patient-level meta-analysis that includes all the original studies included in Katsanos’ meta-analysis, followed up to five years, plus all the other datasets that have come forward since that time. The key piece here, that we do not talk enough about but we need to recognise, is that the missing data, which were on the order of 20% of the original analysis, even at the patient level, are now only about 5%, as we have gone back and done all the vital statistics. I think that will make a big difference in the ultimate analysis.”
Gary Ansel (Columbus, USA) chimed in to comment on the fact that mortality is largely due to cardiovascular issues or cancer. “I do not think we are really focussed on that,” he said. “Forget the paclitaxel, which has been really put to bed, and let us get back to good patient care and see if we can decrease those cardiovascular and cancer rates.”
Gray agreed, saying that the “major message” was that cardiovascular risk factor modifications (smoking cessation, diabetes and hypertension management) were important to consider, and that it was time to look at “the whole patient”.
Registrants can view this presentation on demand here.
All CX 2021 content is available to view on demand. Click here to access the recordings.
Soundbite Medical Solutions has announced US Food and Drug Administration (FDA) 510(k) approval for the SoundBite crossing system—Peripheral (SCS-P) with the 0.014” active wire (14P).
The SoundBite crossing System—Peripheral (14P) is a recanalisation tool, designed to help physician’s placement of conventional guidewires or treatment devices in the intraluminal space beyond chronic total occlusions (CTOs) in patients suffering from heavily calcified above-the-knee (ATK) and below-the-knee (BTK) peripheral arterial disease (PAD).
The SoundBite crossing system—Peripheral (14P) consists of the reusable SoundBite console, a single-use sterile SoundBite active wire 14P, and their respective accessories. SCS-P leverages Soundbite’s proprietary method to produce and safely deliver shock waves via guidewire platforms to selectively “micro- jackhammer” through calcified lesions. SCS-P is now approved in major markets with CE mark, FDA 510(k), and Health Canada approvals in both 0.018” and 0.014’’ platforms.
The results of a recent investigation have revealed no association between infrainguinal bypass tunnelling technique and primary outcomes in patients with limb ischaemia. “Compared to subfascial tunnelling,” write Nallely Saldana-Ruiz (University of Southern California, Los Angeles, USA) and colleagues in the Journal of Vascular Surgery (JVS), “the superficial tunnelling technique is not associated with primary patency or major amputation in limb ischaemia patients undergoing infrainguinal bypass with a single-segment great saphenous vein”.
Saldana-Ruiz et al detail in JVS that they queried the National Vascular Quality Initiative database infrainguinal bypass module from 2008–2017 in order to address a potential association between tunnelling technique and outcomes. They also communicate that tunnelling type was not associated with primary patency, primary-assisted patency, secondary patency, or major amputation, according to multivariate analyses (p>0.05).
The main exposure variable, Saldana-Ruiz and colleagues relay, was the type of tunnelling—either subcutaneously or subfascially. Primary outcomes were primary patency and amputation, while secondary outcomes included primary-assisted patency and secondary patency. They detail: “We excluded non-greater saphenous vein grafts, grafts using multiple segments, indications of aneurysmal disease, bypass locations outside of femoral to below-knee popliteal artery or tibial arteries, and those missing data on the tunnelling type and limb ischaemia”.
The investigators state that they included a total of 5,497 bypasses—2,835 subcutaneous and 2,662 subfascial—in their study. Writing in JVS, they report the following headline results: “Age, race, graft orientation (reversed/non-reversed), bypass donor and recipient vessels, harvest type, end-stage renal disease, smoking, coronary artery bypass graft, congestive heart failure, P2y12 inhibitor at discharge, surgical site infection at discharge, and indication (rest pain/tissue loss/acute ischaemia) were associated with tunnelling technique,” stating a p-value of <0.05.
Medtronic recently announced the safety and effectiveness results through 24 months for the IN.PACT AV Access clinical study. The data, which were presented virtually as a Podium 1st at the Charing Cross (CX) 2021 Digital Edition (19–22 April, online) demonstrated that the IN.PACT AV drug-coated balloon (DCB) is the first and only DCB to show sustained and superior effectiveness through two years compared to standard percutaneous transluminal angioplasty (PTA) in end-stage renal disease (ESRD) patients with de novo or non-stented restenotic native arteriovenous fistulae (AVF) in the upper extremity.
“A patient who receives haemodialysis will often need to have several reinterventions each year to maintain patency and keep critical access sites open and functioning properly,” said Andrew Holden (Auckland Hospital and Auckland University, Auckland, New Zealand), who presented the results at CX 2021. “Being able to show these results at two years will ultimately impact standard of care for patients undergoing dialysis. For my patients, these durable results translate into fewer reinterventions and a better quality of life.”
Over two years, the IN.PACT AV DCB group demonstrated a continued clinical benefit compared to the PTA control group. Key data highlights per Kaplan-Meier estimates for this dataset include:
About the IN.PACT AV Access study
The IN.PACT AV Access study is a prospective, global, single-blinded, randomised controlled trial, which enrolled 330 patients at 29 sites in the USA, Japan, and New Zealand. Results of the six-month pivotal IN.PACT AV Access study were presented at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting in 2019 (7–11 September, Barcelona, Spain) and also published in The New England Journal of Medicine in August 2020.
NOTE: This video is ONLY available to watch in selected countries and geographies
NOTE: This video is ONLY available to watch in selected countries and geographies
NOTE: This video is ONLY available to watch in selected countries and geographies
The International Accreditation System for Interventional Oncology Services (IASIOS) has passed its pilot phase with flying colours, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) has announced in a press release, and is now open for public enrolment. Twelve pioneering hospitals from nine countries successfully participated in the IASIOS pilot phase. This robust accrediting system, tested and optimised over the past two years, now stands ready to accept applications from facilities offering interventional oncology (IO) services worldwide, regardless of the institution’s size or location.
IASIOS is the world’s only accreditation scheme focussed exclusively on minimally-invasive treatments for cancer. Its main goal is to establish the highest quality standards in IO care throughout the entire service line and patient pathway.
Cancer patients can benefit greatly from IO treatments whose minimally invasive nature is proven to provide numerous advantages, such as less pain, fewer complications, and shorter recovery times than conventional surgery, radiation, or chemotherapy. Furthermore, many IO procedures can be performed on an outpatient basis, increasing efficiency, reducing costs and waiting times, and allowing earlier resumption of normal life. This is especially important in these challenging times, as the pandemic has resulted in backlogs in cancer care which IO could help to substantially reduce.
With the continued growth and recognition of IO as an important clinical discipline and the fourth pillar of cancer care, facilities providing IO therapies must follow appropriate guidelines if the relevant treatments are to be used safely and appropriately. It is likewise essential for patient safety and satisfaction that interventional oncologists have the ability and means to officially prove their value and expertise to patients and hospital administrators, not merely as technicians, but rather as primary clinical healthcare providers. In order to achieve exactly that, the Standards of Quality Assurance in Interventional Oncology, published by CIRSE, were used as a blueprint and set the foundation for developing an accreditation system that will be instrumental in the standardisation of IO services on a global scale.
Chair of the IASIOS supervisory board, Andreas ‘Andy’ Adam (Guy’s and St Thomas’ NHS Foundation Trust, London, UK), provides insight into this global launch, commenting: “IASIOS is the culmination of years of dedicated work by CIRSE. It is exciting to reach this stage, as this pioneering accreditation scheme will help improve cancer care around the world.”
Adam told Interventional News last year that as IASIOS focuses on the entire patient pathway, it is a way of recognising that interventional oncologists are “clinicians, not just technicians”. Speaking in April 2020, he said that the project “will help establish IO as a mainstream clinical discipline, so is very important to IO as a whole”.
Centres that enrol in the IASIOS system become part of a greater worldwide community of top IO centres working together to further develop and promote the practice of IO and raise awareness of the benefits of this discipline amongst both patients and medical providers.
The first patient has been enrolled in the LAVA study to evaluate the safety and effectiveness of the BlackSwan Lava liquid embolic system (LES) for the embolic treatment of arterial haemorrhage in the peripheral vasculature, Sirtex Medical and BlackSwan Vascular have announced in a press release.
The LAVA study, which stands for Liquid embolization of arterial haemorrhages in peripheral vasculature, is a prospective, multicentre, single-arm study of 113 subjects at 20 investigational sites in the USA. The first patient has been enrolled at the University of North Carolina School of Medicine in Chapel Hill, USA, where a clinical team successfully treated a patient with a bleeding hypervascular tumour in the liver using the Lava LES.
“I was able to experience first-hand the impact of embolization with the Lava LES for patient treatment, and I am very pleased with the result,” says Clayton Commander, assistant professor of Radiology at University of North Carolina School of Medicine, who treated the first patient in the LAVA study. “The system has been well studied in pre-clinical testing, and we are thankful to BlackSwan for leading this clinical programme with support from Sirtex that has the potential to bring meaningful advancement to the peripheral vascular field.”
LAVA is led by co-principal investigators Bulent Arslan at the Rush University Medical Center in Chicago, USA, and Mahmood Razavi at St Joseph Heart and Vascular Center in Orange, USA. The study population will include patients with active arterial bleeding from the peripheral vasculature.
“We are thrilled for the launch of the LAVA study, which has the potential to lead to the first US Food and Drug Administration [FDA]-approved liquid embolic for a peripheral vascular application in the USA,” comments Kevin Smith, Chief Executive Officer of Sirtex. “We are proud to partner with BlackSwan on its clinical journey and look forward to the potential expansion of treatment options in the endovascular field for interventionalists and patients in need.”
The LAVA study will assess the primary safety endpoint of a composite of freedom from 30-day major adverse events and the primary effectiveness endpoint of clinical success, defined as absence of bleeding from the target lesion after embolization with the Lava LES, without the need for emergency surgery, re-embolization, or other target lesion reinterventions within 30 days of the index procedure.
“Currently, there is no liquid embolic agent that is indicated for peripheral vascular applications in the USA. Lava has key differentiators of optimised radiopacity, availability in two viscosities, reduced preparation time, and controlled delivery, which can enable treatment of a wide array of peripheral vascular diseases,” says Suresh Pai, Chief Executive Officer of BlackSwan. “Moving the LAVA study forward advances our mission to provide the interventional community with the tools they need that drive safe, effective, and value-based treatments. We are eager to discover the findings.”
The LAVA study enrollment follows the strategic collaboration Sirtex and BlackSwan entered in December 2020. Under the collaboration, Sirtex made a significant equity investment in exchange for preferred shares in BlackSwan, as well as an option to purchase the remaining shares of the company at an agreed price.
Siemens Healthineers AG has completed the acquisition of Varian Medical Systems, Inc. The acquisition was previously announced on 2 August 2020.
“With Varian, Siemens Healthineers has the most comprehensive portfolio in the MedTech sector, which offers the company considerable potential for value creation. With a highly integrated approach, Siemens Healthineers will take the global fight against cancer to a new level,” says Ralf P Thomas, chair of the Supervisory Board of Siemens Healthineers AG.
“With the completion of this transaction, we are now best-positioned to take two leaps together: a leap in cancer care and a leap in our impact on healthcare overall. Together, we are establishing a strong and trusted partner capable of supporting customers and patients along the entire cancer care continuum as well as through all major clinical pathways,” comments Bernd Montag, CEO of Siemens Healthineers AG.
Chris Toth, CEO of Varian, adds: “Through the transformative combination of Varian and Siemens Healthineers, our united company will address the growing need for personalised, data-driven diagnosis and precision cancer care that enables us to fight back against globally increasing cancer rates. By bringing together our unique and highly complementary portfolios and capabilities, we will support oncology clinicians and patients in achieving better outcomes and move even closer to achieving our vision of a world without fear of cancer.”
According to a company press release, the acquisition of Varian will allow Siemens Healthineers to leverage AI-assisted analytics to advance the development and delivery of data-driven precision care and redefine cancer diagnosis, care delivery, and post-treatment survivorship. Through early and accurate detection as well as more efficient diagnosis, increased treatment quality and access, Siemens Healthineers will support and accelerate Varian’s mission to reduce uncertainty for cancer patients and increase the level of cancer survivorship.
Varian’s common stock ceased trading on the New York Stock Exchange prior to the opening of trading today.
One-year findings from B Braun’s CONSEQUENT ALL COMERS observational study were recently published by principal investigator Ralf Langhoff (Sankt Gertrauden Hospital, Berlin, Germany) et al online in Angiology. The data were first presented earlier this year at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online).
In this prospective, single-arm, multicentre observational study, the SeQuent Please over-the-wire (OTW) drug-coated balloon (DCB; B Braun) was used in above-the-knee (ATK) and below-the-knee (BTK) peripheral arterial occlusive disease. The investigators report that, despite the high prevalence of comorbidities, target lesion revascularisation (TLR) and mortality rates were comparable for clinical outcomes of other contemporary DCBs.
Langhoff and colleagues detail that the overall technical success rate of the 1,269 DCBs used was 99.6% (1.6±0.79 DCBs/patient), adding that 12-month TLR rates were 6.3% in patients with chronic limb-threatening ischaemia (CLTI) and 9.6% in claudicants, with a primary patency rate of 89.9% and 87.1%, respectively. They also write that all-cause mortality was 4.3%.
Constantino Peña (Miami, USA) moderates an Interventional News webinar focusing on how the SmartCT system (Philips) can “transform” IR suites and the importance of 3D imaging within this setting. Peña is joined by two early-users of the technology, Marc Sapoval and Hicham Kobeiter, both from Paris, France.
Discussing the transition to SmartCT, Sapoval says his team was “very impressed” by the ease of adoption, adding that the “learning curve is quite short”. Kobeiter further states that he is “more comfortable” in the Azurion room with the SmartCT than he was with previous systems.
Asked about improvements to the tableside and workflow, Sapoval says that SmartCT is “very convenient” in that it allows the physicians to conduct all appropriate 3D imaging without leaving the lab and compromising sterility. Kobeiter adds that another advantage is that it helps in teaching others who are outside of the room and gives the user greater control and manipulation of the room. These experiences, says Peña, highlight how the system has made the workflow “more efficient”.
They also highlight advantages of using the system in the current environment with Kobeiter noting that when there is a COVID patient he goes immediately to the room with the SmartCT because “we know that once we step in we do not need to go out”.
This video is sponsored by Philips.
The results of a two-year study support the continued safety and effectiveness of the Zilver Vena Venous Stent (Cook Medical) in treating symptomatic iliofemoral venous outflow obstruction, according to findings presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online).
The stent met primary safety and effectiveness endpoints at one month, and continued to do so through one- and two-year intervals during the VIVO Clinical Study.
In addition, the Zilver Vena Venous Stent demonstrated high rates of patency by ultrasound, freedom from clinically-driven reinterventions and freedom from reinterventions more generally throughout—all of which were clinical outcomes being assessed in the study.
According to Lawrence “Rusty” Hofmann, professor of interventional radiology at Stanford Medicine (Stanford, USA) and the study’s presenting author, the stent’s integrity was also indicated by the fact there were no core laboratory reports of stent fractures across the two-year study period.
“There has been concern over the years at some centres about stenting below the inguinal ligament,” he said. “In this study, more than 20% of stents extended into this region, and there were not any stent fractures.”
The VIVO Clinical Study took place between December 2013 and October 2016, and enrolled 243 patients (70% female; mean age: 53±15 years) with symptomatic obstruction of one iliofemoral venous segment.
Data assessed during the study included baseline patient characteristics, primary and secondary endpoints—such as 30-day freedom from major adverse events, 12-month primary quantitative patency, and changes in venous clinical severity score (VCSS) from baseline to one month and 12 months—as well as patency, reintervention, clinical outcomes and stent integrity through two years.
The Zilver Vena Venous Stent met primary endpoints for both safety and effectiveness, with a 96.7% rate of 30-day freedom from major adverse events and an 89.9% rate of 12-month primary quantitative patency.
In addition, Hofmann said the mean change (-3.0; p<0.0001) in VCSS from baseline was “significant” at one month and was sustained through 12 months (-4.2), and maintained at two years. Specifically, two-year outcomes included high rates of patency by ultrasound (90.3%±2.2%), freedom from clinically-driven reinterventions (93.2%±1.8%), and freedom from reinterventions (83.4%±2.5%).
“This landmark study moves the ball forward in the treatment of deep venous disease,” Hofmann concluded.
While there is large variability based on the site of insertion, patient characteristics and previous accesses, fluoroscopically-guided insertion of tunnelled central venous catheters (td-CVC) for dialysis can be considered a “low exposure” procedure, according to a report.
The report, which is published in The Journal of Vascular Access (JVA), also concludes, however, that patient exposure to ionising radiation during these dialysis access procedures is “significantly higher” than the levels associated with oncological port-a-cath CVC procedures—and nephrologists should be aware of the administered dose to ensure they comply with the 2013 European Directive on protection against ionising radiation exposure (IRE).
In concluding the report, Andreana De Mauri, the lead author and a researcher in the Nephrology and Dialysis Department at the Maggiore della Carità University Hospital (Novara, Italy), states: “In the next years, nephrologists have to take into account the legal implications, following the directives either of the scientific societies or governments, with regard to the high levels of competences, the clear definition of responsibilities and tasks of all professionals involved in the medical exposure, to ensure adequate protection of patients undergoing medical radio-diagnostic procedures.”
In spite of the indications laid out in the aforementioned 2013 European legislation, existing literature lacks information about the doses associated with fluoroscopically-inserted dialysis td-CVC, according to the report.
And, while td-CVC procedures are used worldwide—either for rescue vascular accesses or a first access in elderly and ill populations—the IRE related to them remains a knowledge gap among nephrologists, and clinical practitioners in general.
The researchers therefore conducted a retrospective study to quantify both the effective dose and the organ dose to relevant organs—including bone marrow, heart, lung, breast, thyroid and skin—in td-CVC, revising these procedures while taking into account radiation risk via dose-per-area product, fluoroscopy timings, and the different anatomical sites of catheter introduction.
The study involved 88 consecutive td-CVCs (Arrow Cannon II Plus, Teleflex), which were placed in 42 male patients (48%) and 46 female patients (52%). The anatomical districts they were used to access included a mix of the right internal jugular vein (RIJV), left internal jugular vein (LIJV), subclavian veins (SVs) and femoral veins (FVs).
Alongside this, the study also retrospectively revised 46 oncological port-a-cath CVC procedures acquired on Philips Healthcare’s Integris 5000 angiographic system, in order to compare the IRE levels in these procedures to those associated with td-CVC.
While the subsequent report concludes that fluoroscopically-guided td-CVC insertion procedures can be considered generally “low exposure”, with a minimal-to-very low risk of fatal cancer induction, it states that large variability and some exceptions exist in this area—mainly driven by the site at which the insertion took place, the characteristics of the patient, and the number of previous accesses carried out.
In addition, it states that the radiological exposure was similar for the LIJV, SV and FV access sites, but all of these were higher than the exposure in the RIJV and, as a result, the latter area should be preferred when the clinical conditions allow it.
The report also claims that, in the select few exceptional cases observed, organ doses are “not negligible” for procedures concerning the heart, lung, breast and bone marrow, and, as such, they should be added to the cumulative dose from all diagnostic and interventional procedures a dialysed patient is undergoing.
Due to the “minimal radiological risk” connected to td-CVC procedures, however, the report states that nephrologists should consider the “definitely superior benefit” deriving from this form of catheter insertion for patient dialysis—especially in patients without arteriovenous fistulae or a prosthetic loop on native vessels who require haemodialysis, as CVCs are mandatory here.
In spite of these minimal IRE-related risks, the report also concludes that these procedures should still be optimised where possible, as the nephrologist or other medical practitioner involved is still required to take part in this process by the 2013 European Directive. For example, it suggests that, depending on single-centre protocols, physicians could choose to insert a CVC using only ultrasound guidance and then perform the necessary radiological checks later via traditional chest radiography, for which the associated IRE is very low, and the related risks are negligible.
The report’s conclusion recommends that the nephrologist or practitioner in question should be aware of the ionising dose administered during a td-CVC procedure, so they can correctly inform the patient and ensure these details are included as part of the final report, as required by the law.
Endologix recently announced it has completed the acquisition of PQ Bypass, a medical technology company pioneering a first-of-its-kind technology that addresses an unmet need for new treatments for severe peripheral arterial disease (PAD).
PQ Bypass’ proprietary Detour platform for percutaneous femoral-popliteal bypass has been designated by the US Food and Drug Administration (FDA) as a Breakthrough Device. The Detour system consists of the TORUS stent graft and the PQ crossing device. The Detour system is currently being studied in a US and European clinical trial, DETOUR2.
“The acquisition of PQ Bypass is a seminal moment in Endologix’s history, building upon our leadership in the treatment of abdominal aortic aneurysm to champion disruptive technologies for the treatment of vascular disease,” said Richard Mott, CEO and chairman, Endologix. “We intend to actively pursue new and innovative vascular technologies that are clinically relevant to surgeons, hospitals, and patients, with a commitment to world-class medical education, clinical research, and excellent procedural outcomes.”
NOTE: This video is ONLY available to watch in selected countries and geographies
NOTE: This video is ONLY available to watch in selected countries and geographies
Jason Levy (Atlanta, USA) and Elizabeth David (Toronto, Canada) talk to Interventional News about the final cohort data from the OPuS One clinical study, the results of which were awarded as Abstract of the Year at the 2021 annual scientific meeting of the Society of Interventional Radiology (20–26 March, online).
The “compelling” data showed “improvement in pain and quality of life” both at three days and sustained out to 12 months following use of the OsteoCool Radiofrequency Ablation System. It also indicated a “lack of delayed skeletal events” such as fractures or neurologic injuries following the procedure. The fact that there were no skeletal-related events is something “you will never see in a radiation oncology trial” adds Levy.
The “significant decrease” in pain scores that were seen within hours and days of the procedure were “pretty startling”, adds David, who also discusses the use of stereotactic body radiation therapy (SBRT), its limitations and where RFA should sit within the standard of care for patients with cancer-related fractures.
Levy goes on to state that the data “really should move the needle more” towards further utilisation of radiofrequency ablation for this patient population.
This video is sponsored by Medtronic.
Inari Medical has announced the enrolment of the first high-risk pulmonary embolism (PE) patient in the FLAME (FlowTriever for acute massive pulmonary embolism) study. One in 20 PE diagnoses is categorised as high risk and these are associated with a mortality rate of up to 40% at 90 days.
The first FLAME patient was enrolled at the Penn Presbyterian Hospital & Hospital of the University of Pennsylvania (HUP) in Philadelphia, USA, by co-principal investigators Sameer J Khandhar and Jay S Giri. “We are pleased to be the first site to enrol a patient in FLAME,” said Khandhar (Penn Medicine, Philadelphia, USA). “We frequently see on-table normalisation of haemodynamics using FlowTriever to extract large clots in PE patients. We are eager to formally study this effect in high-risk PE patients in whom the immediacy of this impact might reverse the death spiral and save lives,” he added.
FLAME is a prospective, multicentre, parallel-group observational study evaluating treatment outcomes for up to 250 high-risk PE patients. It is the largest ever high-risk PE study of any intervention and its design, informed by evidence development guidance from the American Heart Association (AHA), aims to change the high-risk PE treatment guidelines. “Conservatively managed high-risk PE is associated with high mortality, but there are limited data supporting interventional treatment. We have designed FLAME to prospectively examine all patients at participating centres with high-risk PE, including those not treated with FlowTriever, to maximise generalizability of the study,” said Giri (HUP, Philadelphia, USA).
Beyond FLAME, Inari continues to invest in its clinical study pipeline. Positive long-term late-breaking results were recently presented at VENOUS2021, (17–20 March, virtual), the annual meeting of the American Venous Forum, from both the CLOUT and FLASH studies. FLASH—already the largest prospective haemodynamic study of any PE treatment ever—is being doubled in size to 1,000 patients to collect data from a conservatively managed subgroup and include sites outside the USA. In addition, for the first time ever, 200 patients will be monitored and studied using the Apple Watch.
Royal Philips today announced US Food and Drug Administration (FDA) 510(k) clearance for its Philips SmartCT application software. SmartCT is a key component of Philips’ image guided therapy system—Azurion—providing interventionalists with computed tomography (CT)-like three-dimensional (3D) images (cone beam CT) to support diagnosis, therapy planning, treatment, and follow-up for interventional radiology procedures.
Bringing intuitive touchscreen control of advanced 3D image acquisition, visualisation, vessel/organ segmentation, and quantitative measurements to the table-side, within the interventional lab’s sterile zone, SmartCT helps enhance clinical confidence, smooths workflows, and increases productivity. It includes software applications for angiography, neurology, soft-tissue imaging, and guidewire/catheter navigation, supporting a wide range of procedures such as the treatment of aneurysms, vascular diseases, and liver tumours.
Philips’ latest Azurion image-guided therapy platform integrates essential lab systems and tools needed for complex interventional procedures into an uncluttered laboratory environment in which interventionalists can focus on treating the patient rather than being distracted by the technology. SmartCT brings total control of the Azurion platform to a touchscreen tablet situated alongside the interventional radiology table. This eliminates the need for clinicians to leave the sterile field and step into an adjacent control room, as well as supporting faster and better-informed decision making.
“A key part of our image-guided therapy strategy is to combine high-quality, low X-ray dose imaging with a superior user experience that allows interventional radiologists to diagnose and treat patients as part of smoother, safer and less interrupted workflows,” said Ronald Tabaksblat, general manager Image Guided Therapy Systems at Philips. “Philips SmartCT is a major step forward in 3D imaging, enhancing confidence in the interventional suite and supporting key elements of the quadruple aim of better patient outcomes, enhanced patient and staff experiences, and lower cost of care.”
“Changing to a new technology can be challenging, but if the system itself can show you the way, it makes it much easier to adopt new advances,” Hicham Kobeiter, chief of radiology and interventional radiology, Hôpitaux Universitaires Henri-Mondor in Crétiel, France. “SmartCT leads you through each step of the procedure, bringing us more confidence and more precision across cardiovascular, oncology, and emergency cases.”
“With the new SmartCT interface we can go into more detail more quickly and safely, with fewer staff in the room,” said Marc Sopval, interventional radiologist at Hôpital Européen Georges Pompidou AP-HP in Paris, France. “SmartCT has brought Cone Beam CT to life in everyday practice: all the tools and guidance capabilities are used by the entire team each day.”
With SmartCT, users are guided through the image acquisition process and can review and interact with the acquired CT-like 3D images on the system’s table-side touch screen module using 3D visualisation and measurement tools. These tools have been designed to support procedures in a range of clinical domains, including neurology, oncology, and cardiovascular procedures, and feature intuitive two-point distance measurements on 3D images, the ability to remove structures from the images that obstruct the region of interest, and the ability to select and store optimum projection angles for recall during procedures.
Philips SmartCT image acquisition, visualisation, and measurement software is an integral part of the next-generation Philips image guided therapy system—Azurion—which was launched in September 2020, marking an important step forward in optimising clinical and operational lab performance and expanding the role of image-guided interventions in the treatment of patients. Azurion has achieved rapid global adoption, reflecting the accelerating trend toward minimally-invasive surgery thanks to its benefits in terms of reduced patient trauma, shorter recovery times and hospital stays, and lower healthcare costs.
Atul Gupta (Philadelphia, USA), chief medical officer of Image Guided Therapy at Philips, comments on the SmartCT clinical application software–part of the Azurion image guided therapy platform–which, he notes, makes 3D and CT imaging “really simple”.
Gupta outlines which clinical areas would benefit most from the platform and states that he is “excited” by its use in interventional oncology. Setting up 3D acquisition can be challenging, particularly with new staff or out of hours, notes Gupta, who adds that the built-in SmartCT application simplifies the process “tremendously”.
As well as benefit to interventional oncology, the platform offers physicians full table side control of the 3D images and high-level measuring tools which can offer benefits for procedures like prostate artery embolization, fibroid embolization and stroke.
This video was filmed by Philips and is being sponsored for distribution in association with Interventional News.
Surmodics recently announced the successful first uses in patients for two devices within its Sublime radial access platform: the Sublime radial access guide sheath and Sublime radial access .014 RX percutaneous transluminal angioplasty (PTA) dilatation catheter.
Constantino Pena, Andrew Niekamp, and Brian Schiro, interventional radiologists at Baptist Health’s Miami Cardiac & Vascular Institute (Miami, USA), performed the first set of procedures utilising the Sublime radial access guide sheath earlier this year. In early March, Osama A Ibrahim (Ashchi Heart and Vascular Center, Jacksonville, USA) utilised the Sublime radial access .014 RX PTA dilatation catheter in multiple cases, including a below-the-knee procedure which showcased the benefits of both Sublime products.
“We are thrilled and humbled to be the first facility to use the Sublime .014 RX PTA dilatation catheter, and our initial experience with this PTA catheter and the Sublime radial access guide sheath was outstanding. Delivery of the catheter was easy, even below the knee. The pushability, trackability, and crossability all were exceptional. We performed multiple inflations in the below-the-knee case and the crossing profile of the balloon was impeccable,” said Ibrahim. “Our goal at Ashchi Heart and Vascular Center is to go radial-first for all cases. The Sublime platform products we evaluated could certainly aid us in this effort.”
The Sublime radial access .014 RX PTA catheter, which received US Food and Drug Administration (FDA) 510(k) clearance in August 2020, allows above- or below-the-knee access through a transradial approach by providing the longest working length (250cm) on the market. Outer balloon diameters range from 2–4mm with balloon lengths between 20mm and 220mm. The device is compatible with a 5Fr guide sheath and is designed to provide the performance of an over-the-wire PTA catheter in an RX platform. Its proprietary reinforced shaft technology with flexible, kink-resistant construction and 250cm hydrophilic coating are designed for optimal trackability and push through distal tortuosity.
The FDA-cleared Sublime radial access guide sheath is the industry’s first 5Fr sheath available in lengths up to 150cm and sets a new standard for lower extremity treatment through a transradial approach. Designed to meet the specific demands of transradial access to the periphery, the Sublime radial access guide sheath incorporates a proprietary braiding technology and high metal composition within the shaft to provide a unique balance of kink resistance, flexibility, radial strength, and torque power. The device is also available with a 6Fr outer diameter and 120cm lengths.
The Sublime radial access .014 RX PTA dilatation catheter is indicated for PTA dilation of peripheral vasculature stenosis in the iliac, femoral, iliofemoral, popliteal, infrapopliteal, and renal arteries, and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulae. The device is contraindicated for use in the coronary arteries and the neurovasculature.
The Sublime radial access guide sheath is intended to introduce therapeutic or diagnostic devices into the vasculature, excluding the coronary and neuro vasculature.
There are some amazing things planned for GEST 2021. Hear from the course directors on why you should attend on April 30–May 2 and the focus days throughout the year. Although the event is virtual, attendees should expect the same level of high-quality, engaging and forward-thinking content that they typically experience during GEST!
This video was filmed by GEST and is being sponsored for distribution in association with Interventional News.
Adept Medical first launched its overhead arm support in March 2019, and, following discussions with imaging professionals, is today launching a new, updated version to market. The company say it has made product improvements to the original design, removing metallic components to ensure compatibility with magnetic resonance imaging (MRI) machines.
According to Adept Medical, the overhead arm support is designed to comfortably support the patient’s arms, eliminating extreme shoulder flexion, allows for abdominal access, and removes unwanted artefacts when imaging with MR, C-arm or computed tomography (CT) machines. The overhead arm support has been designed for use with existing lab and imaging equipment and fits within the bore of a 70cm CT and MRI centre, and can be used with any C-arm imaging centre. The wing design can support one or both arms and will accommodate a wide range of patient sizes.
“We had compelling interest from clinical teams and distributors to adapt this product for the MRI application. With the same procedural requirements as C-arm and CT imaging, it seemed like a logical progression for the product. Our challenge has been removing all metal from the product and maintaining the same level of functionality,” comments Matt Lazenby, Adept Medical’s product development manager.
Soft, pliable, latex-free polyurethane straps may be used for additional patient safety and comfort. These can be installed and adjusted to loosely contain the patient’s arm. Two strap mount locations for each arm ensures that the patient’s arms are fully supported, reducing the risk of arm displacement and aiding patient assurance and comfort, a company press release states.
Many of our top 10 stories of March 2021 highlight new data and ideas presented at the annual scientific meeting of the Society of Interventional Radiology (SIR; 20–26 March, online), with our coverage of the Charles T Dotter and InspIRed Lectures, reporting on the two-year outcomes of Embosphere microspheres (Merit Medical) in genicular artery embolization (GAE), and write-up of the Medtronic-sponsored OPuS One clinical trial results garnering attention. Issue 81 of the newspaper was also published this month, featuring a cover story exploring the trend towards increased precision and quantification with ablative procedures in cancer treatments.
Ziv J Haskal (University of Charlottesville, Charlottesville, USA) delivered the 2021 Charles T Dotter Lecture at SIR 2021. He told his virtual audience that the “adrenaline-rush” of seeing or doing an elegant procedure that can alter the course of a patient’s life is often the career-inspiring doorway into interventional radiology. But cautions that, over time, there needs to be a pivot to a different approach—one in which drama and thrill-seeking play second fiddle to perfecting procedural medicine by standardisation and a focus on outcomes, so that satisfaction rests on providing planned, precise, evidence-based, immediate and longitudinal clinical care.
In the cover story for our latest issue, Interventional News spoke to various leading interventional radiologists working to make advance ablation. They argue that ablation is entering a new era of increased precision and quantification, with outcomes that match or surpass those of surgery. Whilst reaching equipoise with their surgical counterparts has been a goal for interventional radiologists since the advent of ablative treatments for cancer, some expert interventionalists claim that the increased precision of modern thermal ablation techniques, coupled with improvements in radiology, mean physicians are often treating smaller volume tumours. This now positions the procedure as the “definitive” treatment for select patients in some cancers.
Trisacryl gelatin microspheres 100–300μm in size can be considered for genicular artery embolization (GAE), a new study presented at SIR 2021 reports. Presenting the two-year outcomes of a study comparing Embosphere microspheres (Merit Medical), which are made of trisacryl gelatin, with Imipenum Cilastatin microspheres for GAE in patients with moderate to severe knee osteoarthritis, Shivank Bhatia (University of Miami Miller School of Medicine, Miami, USA) informed delegates that the particles are comparable in terms of pain reduction, and that there is a sustained effect up to two-years of follow-up.
In this Medtronic-sponsored educational supplement to issue 81 of Interventional news, the OsteoCool RF ablation system is under the spotlight. Elizabeth David (University of Toronot, Toronto, Canada) describes watching a “small Canadian invention” transform cancer care, and offers her insights from working at one of the first centres to use the device. Jason Levy (Northside Hospital, Atlanta, USA) gives the “compelling” OPuS One trial results, detailing how they confirm the role of percutaneous ablation in musculoskeletal metastases. He also authors a case report: Treating expansile L1 breast cancer metastases with the OsteoCool RF ablation system.
Fluidx Medical released details this month on the clinical use of their GPX embolic device, demonstrating its ability to block flow to small microvasculature and large tumour feeding vessels.
Our write-up of Haskal’s 2021 SIR Charles T Dotter Lecture (see 1 on this list for our video interview with Haskal). Speaking to the online audience, he claimed it is time for interventional radiologists to leave behind the “cowboy culture” that was the foundation of the discipline’s early, exploratory days, and to become “legionaries marching in service of data”.
“If interventional radiologists wish to become competitive with surgeons, the availability of software enabling the accurate comparison of pre- and post-interventional CT [computed tomography] or MRI [magnetic resonance imaging] scans must become mandatory and routinely employed,” Luigi Solbiati argues in this opinion piece. He discusses the ablation-confirmation software he has developed with his team in Milan, Italy, and enthuses about the potential of artificial intelligence to refine and improve ablative outcomes in interventional radiology.
Genicular artery embolization (GAE) is “highly effective and durable” in reducing symptoms due to moderate-to-severe knee osteoarthritis that is refractory to other conservative therapy (such as joint injections and medication), and has an acceptably low toxicity profile. So concludes Siddharth Padia (University of California, Los Angeles, USA), in his SIR 2021 abstract presentation.
Treating patients with metastatic bone disease by radiofrequency ablation (RFA) using the OsteoCool system (Medtronic) results in rapid and statistically significant improvement in pain scores, and provides sustained, long-term relief. SIR 2021 attendees were the first to hear the full cohort data from the Medtronic-sponsored OPuS One post-market clinical study in the “Abstract of the year” presentation, delivered by Levy to the virtual audience.
President of the American College of Radiology (ACR) Geraldine McGinty, also a radiologist and the chief strategy officer, as well as the chief contracting officer, at Weill Cornell Medicine (New York City, USA), presented the InspIRed Lecture at SIR 2021. She offered her reflections on “being a first”—in May 2018, McGinty was elected chair of the Board of Chancellors of ACR, the first woman to hold this office in the society’s nearly 100-year history.
Shivank Bhatia and Vedant Acharya highlight the importance of multidisciplinary collaboration between urologists and interventional radiologists when it comes to forming a successful prostate artery embolization (PAE) clinic, citing a decade of experience at the Miami Miller School of Medicine (Miami, USA).
Prostate artery embolization (PAE), an endovascular treatment for benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), was initially performed to control pelvic bleeding of prostatic origin. It was found that the prostate decreased in size. With this insight, the first use of PAE to intentionally treat BPH-associated LUTS was performed in 2000. Larger case series published in 2010–2011 reproduced these initial findings. The presentation of these results at the Society of Interventional Radiology (SIR) 2011 conference [26–31 March, Chicago, USA] led to increasing international interest in studying the effects of PAE.
Over the past 10 years, the PAE landscape has seen a tremendous explosion of research interest.
At the University of Miami Miller School of Medicine, we have developed one of the largest PAE practices in North America. From the outset, we applied a multi-disciplinary approach, working with the department of Urology to better evaluate and identify optimal candidates for PAE. This effort allowed our urology colleagues to evaluate the data regarding PAE’s safety and efficacy and observe, first-hand, the benefit provided to patients who otherwise were not surgical candidates. We have continued to take this multidisciplinary approach by creating data-driven PAE educational materials to build relationships with local urologists and primary care physicians in academia and the community.
At our institution, we have performed more than 850 PAE procedures since 2014, and we currently see over 250 PAEs per year. We have consistently optimised our technique and standardised our preprocedural evaluation and post-procedure follow-up to create a robust clinical practice. Additionally, we have moved to a primarily radial (left wrist) approach. This access is optimal for most patients as it allows immediate ambulation, faster recovery, and features lower risks overall compared to the femoral approach. In addition, we have performed over 250 procedures in a surgery centre with no incidence of need for transfer to the hospital.
Our team is excited to be at the forefront of research in PAE and contribute to the broader interventional radiology and urology communities. The University of Miami Miller School of Medicine hosted Evolution: Miami 2019 [15–17 November, Miami, USA], a multi-disciplinary conference with over 270 attendees, at which PAE best practices and current debates were discussed by international leaders. Over the past decade, we have presented more than 50 manuscripts on PAE at national and international conferences and in peer-reviewed journals. Recognising the necessity of high-quality data to advance the field, we are delighted to be sharing our results in the presentation titled “Prostate Artery Embolization—Single centre experience of 576 patients with five years follow up” at SIR 2021 [20–26 March, online]. To our knowledge, this is the largest series of the patients treated with PAE in North America presented to date.
Brian Malling (Rigshospitalet, Copenhagen, Denmark) et al conducted a meta-analysis and evaluated the clinical outcomes of 1,254 patients who underwent PAE and found that PAE improved International Prostate Symptom Score (IPSS) by 67% at 12 months and reduced prostate volume by 32% at three months. Several high-quality randomised control trials evaluating PAE versus transurethral resection of the prostate (TURP) have shown consistent and reproducible results. Most recently, Gabriel Knight (Northwestern University, Chicago, USA) et al performed a meta-analysis comparing PAE and TURP and found no significant differences between changes in IPSS, IPSS quality of life, and erectile function.
Future developments in PAE include: gaining a greater understanding of the effects of PAE on ejaculatory dysfunction, performing a randomised control trial comparing PAE with Holmium laser enucleation of the prostate (HoLEP; the current gold-standard size-independent prostate procedure), and evaluating the long-term durability of the procedure. We hope that the development of research will provide the American Urology Association (AUA) the required evidence to recommend PAE as a treatment option.
Research on PAE has developed from a small case series to a multicentre international effort over the past decade. We are excited to have built a robust multidisciplinary clinical practice, to have contributed to the literature, and to be a part of further developments to bring this minimally invasive treatment option to more patients with BPH.
Shivank Bhatia is professor of Interventional Radiology and Urology at the University of Miami Miller School of Medicine, Miami, USA.
Vedant Acharya is a fourth year medical student and past Interventional Radiology Research Fellow at the University of Miami Miller School of Medicine, Miami, USA.
Daniel Sze (Palo Alto, USA) recently took the reins of the Journal of Vascular and Interventional Radiology (JVIR) as editor-in-chief.
He plans to extend specific efforts to encourage increased contributions from underrepresented groups such as women, under-represented minorities (URMs), and the LGBTQ+ community to the JVIR ecosystem, and to build on previous international outreach efforts aimed at the Chinese interventional radiology (IR) community, with a similar outreach into the Spanish-speaking world.
Sze also tells Interventional News how expanded and improved graphics may amplify the impact of JVIR content and help to disseminate important IR research on digital platforms.
From an early understanding in medical school that interventional radiology (IR) was “the future”, Parag Patel has dedicated his career to the discipline, notably as a primary investigator of the BEST-CLI and ATTRACT trials, and now as the incoming president-elect of the Society of Interventional Radiology (SIR). He has also been integral to the design and implementation of a universal IR education curriculum in the USA. In so doing, he has played a large part in shaping that future he once envisioned.
I entered medical school with no knowledge of the field. I loved patient care but wanted to be able to treat the pathology as well. All of my medical school research was done within vascular surgery. During my surgery clerkship, we routinely followed our patients for tests or studies. One such patient had a postoperative bleed and I assumed we would go back to the operating room, but instead we ventured down to “Special Procedures” (a thankfully historic term for interventional radiology [IR]). Marc Borge successfully embolized the bleeding source. That was my first exposure to angiography and the opportunities that it provided—I was hooked. That was such a light bulb moment for me. IR was the future. Innovative, elegant, minimally invasive, and, in my mind, the future of medicine. I was all in.
My parents instilled in me a genuine work ethic as well as respect and appreciation of your fellow persons. They gave up so much certainty to provide for me and my brother as immigrants to the USA. Much of who I am today is because of them.
With regards to IR, Marc Borge introduced me to the specialty and fostered a young, naïve, but genuinely interested trainee. Nicos Labropoulos served as a research mentor and emphasised the importance of good science and knowing the data. As a resident, Marc invited me to attend the local Chicago angioclub, which at the time had many leaders in the field that impressed on me the ingenuity and novelty of the specialty. I was fortunate to train at Miami Vascular. Jim Benenati and Barry Katzen led a phenomenal group of faculty that instilled the importance of true clinical practice, exhibiting leadership and grace under pressure. I was privileged to join the group in Milwaukee and continue my growth under the leadership of Bill Rilling, Sean Tutton, Rob Hieb, Eric Hohenwalter, and soon after Sarah White, formed a small but formidable group of interventional radiologists that grew our clinical practice. We supported each other’s research, education, and clinical efforts through a model of shared leadership.
I was very fortunate to receive support from gracious mentors, and can only hope to serve a similar guiding role for other young trainees. This is much of the driving force behind my desire to continue as programme director of our vascular and interventional radiology (VIR) fellowship [that of the Society of Interventional Radiology (SIR)], and now IR residency training programmes.
The BEST-CLI trial (Randomised, multicentre, controlled trial to compare best endovascular versus best surgical therapy in patients with critical limb ischaemia) completed enrolment over a year ago and strives to complete follow-up during the coming year. The study is important as we have very limited high-quality data on the management of critical limb ischaemia (CLI) patients, specifically comparing best surgical versus best endovascular treatments. Our multidisciplinary collaborative practice at the Medical College of Wisconsin (MCW) has routinely followed a shared model of decision making with surgical and endovascular strategies employed in our local practice. Our involvement in BEST-CLI was seen as a natural extension of our practice and may shed light on how to best treat these patients or support how we already practice. Further studies in this space are needed to allow for a more structured and uniform algorithmic approach to be taken in the care of these patients.
I learned much from my involvement in ATTRACT (Acute venous thrombosis: thrombus removal with adjunctive catheter-directed thrombolysis), namely, the exhaustive work it takes to consistently beat the drum for screening, enrolment, and follow-up and see a trial through to completion. Much credit goes to Suresh Vedantham for his leadership and effort. We struggled with maintaining clinical equipoise in the trial. We were studying the role of an approved treatment in the hopes of identifying a benefit for our patients long term. Many felt they already knew the best course for their patients and enrolment would prevent proper treatment if they randomised to the non-intervention arm. Nonetheless, the trial did not support routine use of pharmacomechanical catheter-directed thrombolysis (PCDT) for all acute lower extremity deep venous thrombosis (DVT) for prevention of post-thrombotic syndrome (PTS). This has helped inform our practice algorithm, as we no longer offer PCDT for isolated femoropopliteal DVT or in older patients with acute iliofemoral DVT (aside from those with phlegmasia). We will treat younger patients with symptomatic acute iliofemoral or iliocaval DVT in the hopes of improving acute symptoms and minimising the severity of PTS.
The Residency Essentials project came about through a strategic planning exercise for the SIR. As Graduate Medical Education Councillor during the time of our IR Residency implementation, I was tasked to champion support for the new training model. The idea of a universal IR education curriculum available for all IR trainees aimed to minimise the significant differences in training experiences across the country. While the technical experiences may vary from institution to institution, the fundamental knowledge base of disease management, role of interventional therapies, and management of these patients could be taught to all trainees nationally. The project was a massive undertaking with cross-divisional collaboration within the SIR and significant staff support. It took over three years and a number of physician volunteers to develop the extensive curriculum outline, identify and curate content (video lectures, timely reviews, and assessment questions), and then neatly package them into modules available on a new learning management system. The project launched in July 2020 to great success. The content will continually be reviewed and periodically updated. The timing of this launch was in the midst of the pandemic and coincided with distance learning mandates across the country. The new Residency Essentials fits this quite nicely as it is an online curriculum. Now that the curriculum is complete, we have the opportunity to support IR education efforts abroad.
SIR, like any big organisation, is a big ship and abrupt changes are not easily handled. I hope to make incremental improvements to the organisation to better serve our members. Namely, we will continue to grow our education and research efforts, and increase awareness of IR treatments to patients and the value of IR to health systems.
We continue to have much work to do in placing the treatments we provide within the algorithm of management for the diseases we treat. Early on, we struggled with maintaining a hold on our procedures, when maintaining a hold on our patients should have been the focus. If we all agree that minimally invasive, image-guided interventions are the future, then we cannot complain if others adopt this strategy as long as they do it well. I think a bigger concern is why some of our proven therapies still remain outside the standard management guidelines of basic disease entities. This requires a long view with a strategic approach and collaboration amongst our stakeholders to accomplish. I believe we can do it.
Art, architecture, and industrial design. I am also an avid traveller, immersing myself in new cultures and enjoy any time spent in nature. Prepandemic, I have hiked the narrows at Zion National Park, down to the Colorado River at the Grand Canyon, trekked the Inca Trail to Machu Picchu, and am now (hopefully) planning a summit of Mount Kilimanjaro for next year. Family time is a priority, and I enjoy cooking up new recipes with my wife, Mona, or rallying tennis balls on the court with my two daughters, Simrin (age 12) and Siana (age nine). interventional interventional
Nicholas Inston (Queen Elizabeth Hospital Birmingham, Birmingham, UK) speaks to Vascular News ahead of this year’s Charing Cross Symposium (CX), which is being held online 19–22 April. In 2021, the conference will focus on controversies within the vascular and endovascular space.
Could you outline the Vascular Access highlights from the programme you have put together for CX 2021?
The CX 2021 Vascular Access programme as usual covers a lot of ground, but there are some real highlights this year. We are going to start the day by talking about device-created fistulas, and of course we now have the options of surgically-created or device-created fistulas. Where we use these, how we use these, and what are the expected outcomes will be discussed. We are also going to delve into the field of high-flow fistulas. This is an area that has not really been discussed very much in the past and I think this will be the first Masterclass where high-flow fistulas will be in the spotlight. New devices and new evidence is emerging, such as which balloons are best in vascular access, which stents, and where and when they should be used. We aim to explore all of this.
Why should physicians attend the CX 2021 Vascular Access sessions and what do you think they might learn?
I think it is imperative that people keep up their education during this pandemic. The way that we work and the way that patient care is delivered has been hugely disrupted, and there are definitely things that we can learn from the last year. With these changes in practice, it is important to find out what has actually happened to those patients that have not been able to have treatment, or their treatment has been altered. We need to make sure that we learn lessons from each other about new and different approaches to vascular access care.
If you had to pick one controversy in the programme to turn the spotlight on, what would that be?
A topic of controversy that is poorly understood is that of high-flow fistulas. This is a really interesting area and one I think will create a lot of debate. As well as defining a high-flow fistula, the session will address a number of key questions: Does a high-flow fistula have cardiovascular risks? Does it have risks in terms of increasing interventions, increasing problems? Why do we need a fistula that runs at high flow when actually you only need a fistula that runs about a litre a minute?
Why is this controversy important to the global vascular community?
We do not really know how to deal with high-flow fistulas. International practice differences exist in cannulation and dialysis provision with some approaches aiming for fistulas to suit the logistics of dialysis rather than best long-term outcomes for the fistula and the patient. I think this session will raise many questions about vascular access in general and stimulate some interesting discussion.
The initial patients have been enrolled in the Embrace hydrogel embolic system (HES) global randomised clinical trial for the treatment of hypervascular tumours, Instylla has announced. As demonstrated previously in the completed first-in-human (FIH) study, Embrace HES was effective at embolizing malignant and benign hypervascular tumours by blocking tumour blood supply with complete technical success and persistent embolization as noted in imaging follow up at 30-days.
“I am pleased to be evaluating this new technology for hypervascular tumour embolization,” comments Gerard Goh, head of Interventional Radiology at The Alfred Hospital, Melbourne Australia, and president of the Interventional Radiology Society of Australasia (IRSA). “While participating in the first-in-human study prior to this trial, Embrace showed great promise with good control, favourable patient outcomes, and no tumour revascularisation. We are excited to be the first centre to enrol in this global, randomised trial.”
A hypervascular tumour, which can be found in the liver, kidney, or elsewhere, has an increased number of blood vessels relative to other tissues. These tumours are often associated with low survival rates. Due to the increased risk of bleeding, hypervascular tumours can be challenging to remove. Transcatheter arterial embolization (TAE) and conventional transarterial chemoembolization (cTACE) are established treatments for hypervascular tumours, particularly for patients with limited progressive disease. Embrace HES, an investigational product, is a liquid embolic designed to deeply penetrate the tumour vascular bed, solidify, and stop blood flow. The Embrace HES embolization uses no solvents, does not need sizing to the vessel diameter, and eliminates the possibility of catheter entrapment. Its main components are water and polyethylene glycol (PEG). PEG has a long history of safe use in implantable medical devices, Instylla claim.
“We are thrilled to be the first centre in the USA to treat a patient on this study. Embrace’s predictability helps me embolize the tumour while avoiding non-target embolization,” adds Edgar D St Amour, interventional radiologist from CARTI Cancer Center in Little Rock, USA. “I look forward to continued evaluation of this new advancement in treating hypervascular tumours.”
Fluidx Medical have released details on the clinical use of their GPX embolic device, demonstrating its ability to block flow to small microvasculature and large tumour feeding vessels.
“The versatility of the GPX product has been demonstrated in a variety of interventional oncology uses,” says Andrew Holden, director of Interventional Radiology, Auckland City Hospital, Auckland, New Zealand. “We have seen excellent distal penetration and backfilling of larger vessels in our tumour cases.”
According to Fluidx Medical, the GPX embolic device is an embolic designed “to combine the benefits of other embolics like coils, particles, and liquids with simplified preparation, delivery, precision, and control leading to durable, long-term occlusions”. GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolic material upon delivery without polymerisation or dimethyl-sulfoxide (DMSO) precipitation.
“We saw excellent filling of the distal branches and complete tumour devascularisation,” says Martin Krauss, head of Interventional Radiology, Christchurch Hospital, Christchurch, New Zealand. “The patient exhibited marked decrease in haematuria following the procedure. Since we were not worried about catheter entrapment, we could take our time and ensure that we occluded all the feeding vessels of the tumour.”
GPX is packaged ready-to-use in a syringe, requires less than one minute of tableside preparation by the clinician, and may be delivered through standard catheters or microcatheters, according to Fluidx Medical Technology data on file. Clinicians can decide at time of care to use GPX alone or as a complement to coils or other embolic technologies.
In a recent case at Christchurch Hospital, the GPX embolic device was delivered through long, thin microcatheters, including the 2Fr Terumo Progreat Alpha 130cm length microcatheter with an inner diameter of 0.019 inches (0.48mm).
The GPX embolic device is under development and does not have marketing clearance or approval in any market at this time. It is for investigational use (in New Zealand) only.
During the annual scientific meeting of the Society of Interventional Radiology (SIR; 20–26 March, online), Matthew Hawkins and Raymond Liu jointly hosted a session conveying the value of interventional radiology (IR) services. During the session, the touched on how interventional radiologists can communicate the value their field brings to hospitals and health systems and what other interventionalists can be doing to help move the field forward. Interventional News caught up with Hawkins and Liu for a discussion on the topic.
How can interventional radiologists communicate the value their field brings to hospitals and health systems?
MH: IR has become a specialty that treats a multitude of conditions in nearly every area of the body. Our specialty is an essential component to many revenue-generating service-lines offered by hospitals, such as organ transplant, oncology, stroke care, and trauma. In addition to some of the more complex interventions performed by interventional radiologists, our specialty has become healthcare system experts of central venous access, minimally-invasive biopsies, enteric access management, and percutaneous drainage procedures. But while interventional radiologists are valued for their universal skillsets, it has been difficult for the specialty to communicate how these skillsets translate to the bottom line for hospitals and health systems.
The most important thing interventional radiologists can do is to demonstrate the positive impact they have on generating revenue, containing costs, optimising resource utilisation, and providing high-quality patient care. As it pertains to quality, hospitals/healthcare systems value improved outcomes for patients, shorter lengths of stay (LOS), avoidance of unnecessary admissions, and post-discharge outpatient management to avoid re-admissions and financial penalties. They want to invest in specialties that can deliver on these targets. We know that IR does this, but having robust data and research to support it will be crucial in the future. We hope that interventional radiologists will conduct more research into these areas to further support IR as a value-driven, patient-centered specialty.
How have you personally worked with colleagues across disciplines to provide best patient care? How do you initiate forming an interdisciplinary team—what are the opportunities here?
RL: Interventional radiologists are always open to working in partnership across specialties, and there are more opportunities for partnership with other physicians than many realise. In developing an interdisciplinary team, it starts with identifying the holes within your health system that need filling. Where could your services be most useful in a team environment? Where do you think a team could provide the most value? The next step is to simply reach out to the other physicians within that service-line and have a conversation. Find out if they are interested in forming an interdisciplinary team. Most likely they will be enthusiastic about working together because we all have the same goal—getting patients the best care they deserve. The final step is to get support from hospital leadership. Their backing will help to nurture your team model and even scale it up for the future so it can continue to grow. A great example beyond the well-known oncology model are Hereditary Haemorrhagic Telangiectasia (HHT) teams that draw in specialists such as ENT, haematologists, geneticists, and pulmonologists. And, of course, multidisciplinary teams should not just be considered for clinical issues—at Massachusetts General Hospital, we have created interdisciplinary teams for operational redesign, such as on-time efforts for first case in the operating room, or best practice workflows for anaesthesia support for IR.
A strong team that works across specialties is better for both physicians and patients, so I encourage other interventional radiologists to reach out to their colleagues if they are interested in working in this capacity.
What are the biggest challenges to the spread of IR generally, and how can interventional radiologists work on combating these?
RL: Some of the biggest challenges facing the profession include misperceptions among referring physicians and hospital administrators about what interventional radiologists can do. For a long time, interventional radiologists have been viewed as technicians, but as the field has exploded into other realms of treatment across all areas of the body, other physicians continued to hold the same notions about interventional radiologists’ capabilities. Yes, we can help treat a patient’s complex condition, but we can also provide patients the full clinical spectrum that allow discussions around all treatment options. We need to ensure that other physicians understand that we can be a partner in their patients’ care. Interventional radiologists can change this by strengthening relationships with other physicians in other specialties; by demonstrating to hospital administrators the ways interventional radiologists can help generate revenue, contain costs, and provide patients high-quality care.
I would also say access to IR services is a hurdle our specialty needs to overcome. In some metropolitan areas, there is an abundance of IR specialists that allow many choices for patients. But in many areas, even just a few miles outside major cities, there is a dearth of IR physicians that can address complex conditions and provide best practice treatments. Our specialty needs to identify those geographical areas, as well as improve communication of our services in those locations where there are interventional radiologists, and ensure that every patient has access to an interventional radiologist anytime.
What are biggest misconceptions pertaining to pediatric IR, and how can these be addressed?
MH: As endovascular equipment has continued to get smaller and smaller, it has made many minimally-invasive IR procedures safe for children. Now, rather than open surgical procedures, many paediatric diseases can be treated with minimally invasive, image-guided treatments. Pediatric IR is evolving rapidly and has become an essential specialty in the management of vascular malformations, paediatric organ transplant, and many paediatric benign bone tumors. Paediatric interventional radiologists have also become institutional experts in less-complex, but critical procedures, such as biopsies, enteric access, and central venous access, which are necessary for the care of a wide-array of paediatric diseases. In general, parents are grateful to have minimally-invasive, image-guided alternatives to open surgery.
Thriving paediatric IR practices are generally based out of tertiary referral paediatric hospitals, with an increasing percentage of pediatric interventional radiologists obtaining subspecialised paediatric IR training to supplement their foundational adult IR residency curriculum.
Matthew Hawkins is a paediatric vascular interventional radiologist and associate professor at Emory University and the Children’s Pediatric Institute, Atlanta, USA.
Raymond Liu is an interventional radiologist at Massachusetts General Hospital, Boston, USA. He is a Society of Interventional Radiology (SIR) board member and executive director of Partners HealthCare International (PHI).
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Trisacryl gelatin microspheres 100–300μm in size can be considered for genicular artery embolization (GAE), a new study presented at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online) reports. Presenting the two-year outcomes of a study comparing Embosphere microspheres (Merit Medical), which are made of trisacryl gelatin, with imipenem cilastatin for GAE in patients with moderate to severe knee osteoarthritis, Shivank Bhatia (University of Miami Miller School of Medicine, Miami, USA) informed delegates that the particles are comparable in terms of pain reduction, and that there is a sustained effect up to two-years of follow-up.
“Genicular artery embolization has potential to provide midterm relief of pain for patients with mild-to-moderate knee osteoarthritis resistant to conservative management,” he said.
Detailing their methodology, Bhatia described how the investigators conducted a comparative study, assessing a total of ten patients (15 knees) who had a GAE with 100–300μm Embosphere microsphere particles, and comparing them to a subsequent cohort of eleven patients (18 knees) who underwent GAE with Imipenum Cilastatin microspheres. Clinical outcomes were evaluated at six-month and 24-month follow-up and compared to baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire.
Bhatia noted that, at baseline, there were no significant differences in sex, age, body mass index (BMI), duration of pain before the procedure, prior treatment, or Kellgren-Lawrence grade between the two cohorts. Baseline median pain WOMAC and total WOMAC scores were 13 (interquartile range [IQR], four) and 46 (IQR, four) in the Embosphere group and 13 (IQR, three) and 47 (IQR, 28) in the Imipenum Cilastatin group [p=0.875 and p=0.738], respectively.
The median follow-up was 796 days (range, 736–808). Clinical success (measured as 50% reduction in WOMAC pain score vs. baseline) was achieved in 69.23% of the embolized knee joints in both groups (p=1) at six months.
At two-years follow-up, the investigators report clinical success in 61.5% of knees treated with the Embosphere microspheres, versus a 53.8% clinical success rate in the Imipenum Cilastatin group (p=1).
Both embolic materials resulted in a significant decrease in pain WOMAC and total WOMAC scores at six months compared to baseline (p<0.05), and the effect of GAE on pain WOMAC and total WOMAC scores was sustained until the 24-month follow-up visit in both groups (p<0.05).
Relating the adverse events, Bhatia commented: “Minor events included transient cutaneous colour change [in five patients] or transient leg numbness observed in one patient], and was only identified after GAE with Embosphere microsphere particles (p=0.00387), which resolved spontaneously at one-month follow-up (Clavien-Dindo classification grade I).” There were no major adverse events.
This educational supplement is sponsored by Medtronic.
In this supplement:
Interventional radiologists were often at the frontlines, doing remarkably large numbers of procedures treating COVID-19 patients and among the only specialties that carried on staffing hospitals, providing daily services such as putting in dialysis catheters or treating COVID-19 related pulmonary emboli. “That was a very valuable experience for others to see. We were there, we stepped up – and patients benefitted,” Matthew S Johnson, who took on the Society of Interventional Radiology (SIR) presidency on 23 March 2021, tells Interventional News.
Johnson, who is the Gary J. Becker Professor of Radiology Research at Indiana University (Indianapolis, USA), outlines that distilling the lessons learned from the COVID-19 experience and emphasising and building a diverse society membership and leadership form the bedrock upon which SIR aims to employ research as a mature specialty to guide what interventional radiologists do to serve patients better and demonstrate the value of image-guided procedures – to patients, referring physicians and payers.
“We are pushing as a society, as a specialty, for people to become involved in research, to do high quality research and also to join us in [the] Virtex [registry],” he says.
Researchers suggest that, in patients with chronic limb-threatening ischaemia (CLTI), two-dimensional (2D) perfusion angiography is a “reliable tool” when used according to standardised methods. Jetty Ipema (St Antonius Hospital, Nieuwegein, The Netherlands) and colleagues write in the European Journal of Vascular and Endovascular Surgery (EJVES) that theirs is the first study to test the reliability of this method in CLTI patients.
Ipema et al explain that 2D perfusion angiography provides quantitative foot perfusion information from standard digital subtraction acquisitions. In the present study, the investigators aimed to test the reliability of this method in patients with CLTI by investigating repeatability, as well as intra-observer and interobserver agreement.
The team included 20 patients with CLTI and below-the-knee endovascular revascularisation in a prospective, clinical study. Two patients were excluded from repeatability analyses because of major motion artefacts, they note. Prior to treatment, the authors state that two perfusion angiography runs were acquired with a five-minute interval without performing an intervention. In these recordings, regions of interest were selected and time–density curves and perfusion parameters were recorded.
Ipema and colleagues specify that, to investigate intra-observer agreement, one observer performed five measurements on the same acquisition for each patient; to investigate interobserver agreement, three observers performed measurements on the same acquisition for each patient. They presented the results in Bland–Altman plots and as the intraclass correlation coefficient (ICC) per parameter.
Writing in EJVES, the authors report that repeatability analyses of the 18 eligible patients showed excellent correlation for every parameter, with an ICC >0.9 for each. In addition, they relay similarly positive results regarding intra-observer and interobserver agreement for all 20 patients, with an ICC of 1 for every parameter.
Ipema et al note that the study has some limitations. “Although the number of patients was sufficient to show excellent repeatability results,” the authors write, “the Bland-Altman plot shows outliers that could not be fully explained.” They hope that as more data become available in the future, there will be a better understanding of these observations.
Furthermore, they acknowledge that the study only validated the reliability of 2D perfusion angiography. They detail that other aspects of test validation, such as the ability to demonstrate increased blood flow after intervention (responsiveness) and the relationship with clinical outcomes (validity) were not investigated but are “important further research topics”.
Ipema et al conclude that repeatability, as well as intra-observer and interobserver agreement of 2D perfusion angiography in patients with CLTI were excellent. Based on the results of their findings, they suggest that future research can be performed to investigate the relation between perfusion angiography and clinical outcomes.
The adrenaline-rush of seeing or doing an elegant procedure that can alter the course of a patient’s life is often the career-inspiring doorway into interventional radiology. But, over time, there needs to be a pivot to a different approach – one in which drama and thrill-seeking play second fiddle to perfecting procedural medicine by standardisation and a focus on outcomes, so that satisfaction rests on providing planned, precise, evidence-based, immediate and longitudinal clinical care.
So says Ziv J Haskal (Charlottesville, USA), who presented the 2021 Charles T. Dotter Lecture at the Society of Interventional Radiology’s annual scientific meeting titled “The Reluctant Cowboy: Moving Past Myth and Dogma”.
In the lecture, Haskal notes that the problem-solving, lone-ranger cowboy interventional radiology mindset needs to give way to the drumbeat of an army marching in search of, and in support of, evidence. Importantly, sceptical analysis, which must underpin this quest, must turn its sights “at home” with a reappraisal of the common myths and accepted truths that masquerade as evidence – and this can reveal the often shaky ground for decision making in interventional radiology, he says.
“We are not cowboys doing things because we ‘think it makes sense’, rather we must seek to understand the limits of known data, and adhere to science, where it exists,” he tells Interventional News. And, he also talks about skydiving.
Registrants can watch the lecture on-demand at SIR’s Digital Video Library.
President of the American College of Radiology (ACR) Geraldine McGinty, also a radiologist and the chief strategy officer, as well as the chief contracting officer, at Weill Cornell Medicine (New York City, USA), presented the InspIRed Lecture at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online). She offered her reflections on “being a first”—in May 2018, McGinty was elected chair of the Board of Chancellors of ACR, the first woman to hold this office in the society’s nearly 100-year history.
McGinty also highlighted the importance of taking an intersectional approach to mentoring and networking, with several of her key takeaways referencing using your privilege and access to enable opportunities “not just for people who look like you”.
Delivering her InspIRed Lecture on 21 March, McGinty gave ten central lessons for women and other under-represented groups in interventional radiology (IR):
President of the American College of Radiology (ACR), Geraldine McGinty is also a radiologist and the chief strategy officer, as well as the chief contracting officer, at Weill Cornell Medicine (New York City, USA). She presented the InspIRed Lecture at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online) and offered her reflections on “being a first”. In May 2018, McGinty was elected chair of the Board of Chancellors of ACR, the first woman to hold this office in the society’s nearly 100-year history.
McGinty discusses the state of female representation within interventional radiology, how far things have come and what more needs to be done. “We are certainly not where we need to be” in this regard says McGinty, who explains that roughly only 8% of IRs in the US are women.
McGinty outlines some of the main barriers to adoption and notes that a “really powerful deterrent is when you are not seeing women leader and women role models”. She goes on to explain that this is where the Society of Interventional Radiology and the Women in IR group have “done such a terrific job in highlighting pioneering women”.
Attracting more women to IR early in their careers is vital. “We have to connect with students early in their training” says McGinty who adds that having “robust medical outreach is critically important to increasing the diversity of the specialty overall”.
She also draws on her own experience as the first chair of the American College of Radiology, noting that she “wasn’t the first woman who could have done it or should have done it”. “I’d like to think that I’ve opened the doors for other women”, McGinty adds, concluding that it is “not success if it’s just you; you have to help the next woman up”.
The US Food and Drug Administration (FDA) have approved the DOORwaY90 study, a trial evaluating the safety and efficacy of selective internal radiation therapy (SIRT) using SIR-Spheres yttrium-90 (Y-90) resin microspheres (Sirtex Medical) in patients with unresectable hepatocellular carcinoma (HCC).
Unique to other recently published Y-90 studies, DOORwaY90, which stands for “Duration of objective response with arterial Y-90,” is the first prospective, multicentre study to utilise and delineate personalised dosimetry treatment planning and to define actionable post-treatment dosimetric verification for endpoint assessment. The study will assess the duration of response and objective response rate of SIR-Spheres.
Outside the USA, SIR-Spheres are indicated for the treatment of patients with advanced non-operable liver cancer, including HCC.
The DOORwaY90 study is being led by co-principal investigators Cheenu Kappadath and Armeen Mahvash (both University of Texas MD Anderson Cancer Center, Houston, USA). “We are honoured to participate in this important study that could greatly impact the treatment of HCC patients in the USA,” notes Mahvash. “We look forward to working closely with Sirtex in executing and reporting the findings of DOORwaY90.”
DOORwaY90 is a 15-centre, 100-patient, US-based, open label, single arm study run in accordance with Good Clinical Practice. The study population consists of patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B1, and B2 who are not eligible for resection or ablation at the time of study entry. For each patient, an eligibility review committee will review diagnostic imaging and confirm final eligibility and treatment planning prior to treatment. Enrollment is expected to begin at the start of the second financial quarter of 2021.
HCC is often diagnosed when potentially curative resection or transplantation is not feasible. SIRT has the potential to deliver a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy liver tissue. In countries outside the USA, SIRT has been successfully used to bridge patients to transplantation or downstage HCC to within transplantation criteria or resection.
It is time for interventional radiologists to leave behind the “cowboy culture” that was the foundation of the discipline’s early, exploratory days, and to become “legionaries marching in service of data”, Ziv Haskal (University of Virginia, Charlottesville, USA) argued in his 2021 Dotter Lecture, delivered during the Annual Scientific Meeting of the Society of Interventional Radiology (SIR; 20–26 March, online).
“IR knowledge is not atomic: it is complex,” the former Journal of Vascular and Interventional Radiology (JVIR) editor told virtual attendees. “You cannot live with ‘I read the abstract’ or ‘I cruised the conclusion’”, he joked, cautioning SIR delegates against accepting certain ideas as gospel without first scrutinising the data. Indeed, Haskal’s lecture, “The reluctant cowboy: Moving past myth and dogma” deconstructed commonly held interventional radiology (IR) “myths” and dogmatic approaches to practice, and called for a more rigorous culture of data and research.
“We need to be accountable and adopt a sceptical approach that can only be satisfied through repetition and replication,” he said.
In order to do this, he advised his audience to act at various levels: “On a personal level: embrace this constant self-query, self-reflection, scepticism, and patience. Read in detail. Embrace the dialectic.
“On a local level: cheer on developing prospective research; it is five to ten times more effort to write protocols, but they are durable, and impactful, and can be built upon, or will lead to other work.
“On a national level: support initiatives for data that can be congregated, through registries, through standardised reporting, through NIH [National Institute of Healthcare] efforts. Open your pocketbooks with patronage; lend your financial support to societal initiatives.
“And on the big blue planet, think about the large-scale questions, so we can get together with other groups. We have to mine the facts for truth and work daily to be clinical scientists.”
Alan Matsumoto (University of Virginia, Charlottesville, USA), who delivered the 2019 Dotter Lecture, presented the Dotter Lecture award to Haskal on 22 March.
The apodictic versus the apoplectic: Moving beyond a narrow, dogmatic vision in IR
He began his talk by noting that “many or most of us [interventional radiologists] remember that signal case” that led them to pursue a career in IR, which he likens to skydiving due to the “adrenaline thrill”. However, he warned that now is the time for the speciality to turn towards “creating data and our own science”.
Haskal made the distinction between “the apodictic—knowledge we are certain of” and the apoplectic, the “you will do it this way because I was trained this way, and therefore you will be trained this way” school of thought.
He highlighted some specific examples of “apoplectic” thinking “to highlight the types of narrow vision that we have on a daily, or on a field-wise basis”. One such belief he questioned was the idea that pulmonary arteriovenous malformations (PAVMs) less than 3mm do not need to be embolized to prevent stroke. “Are bacteria just too big to fit through a 3mm PAVM?” Haskal asked rhetorically. He traced the origins of this belief to an abstract presented orally at the 1992 meeting of the Radiological Society of North America (RSNA), which did not state that there was no need to embolize smaller than 3mm, but rather found clinically-evident stroke in four patients with feeding artery measuring 2.9–4.5mm. “That is pretty shaky ground for decision-making,” Haskal opined.
“How about gall bladder catheters—they have to be transhepatic, right?” he continued. He cited a 1988 article in the American Journal of Roentgenology (AJR) and a 1994 paper in JVIR that refute this, demonstrating the safety of a transperitoneal route. “If that was not enough, I was recently asked by a plaintiff’s lawyer to be a medical expert on a case in which there was a hepatic bleed, and she insisted the interventional radiologist was negligent because they had gone through the liver, and there was a bleed.”
He also addressed common practice assumptions. “Why do we always get called at night for nephrostomies or arterial lysis?” he asked. But according to a review of cases conducted at the 800-bed University of Virginia Hospital over the course of one year, 84% of nephrostomies and 80% of lysis procedures took place between 8am and 8pm.
According to Haskal, this is due to frequency bias, also known as the Baader-Meinhof effect—after you notice that you have done several night-time lysis procedures, you will notice it more often and believe that it has a high recurrence.
The risks of skimming
In addition to these commonly-held IR “myths”, Haskal also warned his audience of the dangers of “reading light”. Presenting an example, he discussed an “excellently-written, multicentre trial, [conducted] under the auspices of the FDA [the US Food and Drug Administration]”. He published the study, which was an approval trial for a vena cava filter, when JVIR editor. “Here are the conclusions from the abstract,” he read: “The rate of freedom from new symptomatic PE [pulmonary embolism] through 60 days was 100% (n=129, confidence interval [CI] 97.1–100%). [….] There were no cases of PE through 12 months for either therapeutic or prophylactic indications.”
Commenting on this, he said, “So that is pretty good, we want that device,” before adding, “But here is what happens when you read inside [the paper].” A third of the patients were purely prophylactic, “that means they had no DVT [deep vein thrombosis] or PE to begin with”, Haskal said. “That is like taking people with cancer and people who might get cancer, and following them for a year, and then saying ‘Look, we did not have cancer [amongst the total cohort]’. But you put those people in! [Referring to the cohort without any cancer at the start of the study].”
“Papers are this long for a reasons—we have got to read the detail,” he emphasised.
“Three out of four meta-analyses are garbage in, garbage out, cannot be trusted”
“Surely meta-analyses are the path to truth?” Haskal posited. “It is the analysis of the analyses, it is integration and power, it is rigour over narrative, it is signal over noise, it is the superman!” he enthused.
However, he showed a meta-analysis that had to pool 95 trials to show that neutropenic cancer patients have lower mortality with antibiotics, saying “even large, individual trials were not enough to pull it together [and reach this conclusion]. That is a life-altering signal.
“But guess what? In one analysis of 7,200 systemic reviews, once you take out the Cochrane analyses, one quarter, 27%, had low risk of bias, compared to 87% of Cochrane analyses. That means that three out of four meta-analyses are garbage in, garbage out, cannot be trusted.
“You have to stay vigilant as a reader,” he advised, counselling his listeners to have a mental checklist when reading papers:
“We must train scientific methods into the next generation of interventional radiologists”
To stray from the IR echo chamber, Haskal noted, interventional radiologists have to have scientific flexibility.
“The perfect gold standard is not possible in clinical research,” he said. Iteration, reiteration, renewal, and replication is the best that can be done. “We have to have ongoing scepticism and constrain exuberance,” he said.
He closed his lecture with a call to arms: “We must train scientific methods into the next generation of interventional radiologists, and we have to standardise it.”
Writing in JVIR in 2016, Haskal put: “We have new trainees now entering the specialty; we have five years of opportunity to inculcate them with methodical training and research exposure—to methods, critical reading, analysis and study design”.
He continued: “This will require a fundamental and intentional mutation in IT training DNA—potentially a centralised CRISPR insert available to all residencies. We cannot expect that each programme will have the ability to teach this, we need to develop this nationally, and make this available to our trainees [in the USA], and across the planet, because this is our long-game.”
IR and COVID-19: “When diagnostic volumes cratered, […] our volumes went up”
Speaking more broadly of the hardships SIR members and attendees have experienced in the past year due to the ongoing COVID-19 pandemic, and in particular noting how this has affected the SIR meeting, Haskal commented: “On a professional level, 25 years of the Dotter Lecture means sitting in that giant hall, surrounded by thousands of our colleagues, the lights go down, an extraordinary speaker comes out, and something revealing, and visionary, pulls us all together. Instead, we are all separated, watching this on screens, alone.
“But I want to remind everybody what we have done as interventional radiologists this year. Pulling protocols across the planet, trying to figure out how to manage in this plague year; doing all those procedures—PD catheters at bedside, we had not done that before, dialysis catheters, gastrostomy catheters in acute or chronically-ill patients, arterial lysis for hypercoagulability or pulmonary embolism. When diagnostic volumes cratered and people were furloughed and elective surgeries were cut, whether you were in a big metropolitan area or in smaller hospitals hit by COVID patients, our volumes were maintained or went up.”
“We are always going to have the professor Dotter spirit,” Haskal said in his closing remarks. “But we have to embrace the next evolution and work daily to be clinical scientists.”
Matthew S Johnson, an interventional radiologist and Gary J Becker professor of Radiology Research at Indiana University School of Medicine in Indianapolis, USA, assumed the office of president of the Society of Interventional Radiology (SIR) on 23 March, during the society’s annual Members’ Business Meeting.
“COVID has truly placed interventional radiologists on the frontline, which is both a challenge and an opportunity—people are now recognising us as the frontline workers we have always been and seeing what tremendous value we bring to patients and the care team,” Johnson comments. “SIR is committed to provide all interventional radiologists with the tools they need to thrive in their chosen practice setting, to combat burnout and promote wellness, and to foster a more diverse and inclusive specialty, all to the benefit of the patients we serve. Our members can best serve our patients if those interventional radiologists are healthy, happy, and well supported.”
Other incoming officers of SIR’s 2021–2022 Executive Council include president-elect Parag J Patel (Medical College of Wisconsin, Milwaukee, USA), newly appointed secretary Alda L Tam (Anderson Cancer Center, Houston, USA), and immediate past-president Michael D Dake (University of Arizona Health Sciences, Tucson, USA).
Interventional radiologists were often at the frontlines, doing remarkably large numbers of procedures treating COVID-19 patients and among the only specialties that carried on staffing hospitals, providing daily services such as putting in dialysis catheters or treating COVID-19 related pulmonary emboli. “That was a very valuable experience for others to see. We were there, we stepped up – and patients benefitted,” Matthew S Johnson, who took on the Society of Interventional Radiology (SIR) presidency on 23 March 2021, tells Interventional News.
New and re-elected members of the SIR Executive Council are:
The SIR Foundation also appointed the following members to its Board of directors:
Shape Memory Medical recently announced that it has received approval from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) to market its Impede-FX embolisation plug in Japan. Cosmotec championed the approval process in Japan and is Shape Memory Medical’s distribution partner for its peripheral embolisation products.
The Impede-FX embolisation plug is indicated for use in Japan as an adjunct to devices such as stents, coils, and plugs, and the Impede embolisation plug which previously received PMDA approval in 2019. Impede-FX is percutaneously deployed in an artery or vein for obstructing blood flow in abnormal blood vessels like arteriovenous malformation and fistula, aneurysms, bleeding by traumatic vascular injury, tumours, etc. except for intracranial and cardiac vessels. Impede-FX is available in three sizes, with the maximum device having an expanded diameter of 12mm.
Impede embolisation plugs feature the proprietary Shape Memory polymer technology, a porous, embolic scaffold that is crimped for catheter delivery and self-expands upon contact with blood for rapid conversion to organised thrombus. Preclinical and clinical studies have shown that Shape Memory polymer offers effective and predictable space filling compared to traditional coils and plugs, stable clot formation for reduced intradevice recanalisation, and progressive healing as the material biodegrades. To date, nearly 600 patients have been treated worldwide with the Impede embolisation plug family of devices.
LimFlow announced today that the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) has approved its Clinical Trial Notification (CTN) for the Japanese cohort of the ongoing PROMISE II pivotal trial of the LimFlow percutaneous deep vein arterialisation (pDVA) system.
PROMISE II is a multicentre, prospective, single-arm study being conducted in the USA and Japan as part of the Medical Device Harmonization by Doing (HBD) regulatory collaboration between the two countries.
Using an adaptive statistical design, the study plans to enrol 60–120 “no option” chronic limb-threatening ischaemia (CLTI) patients at 25 sites, four of which will be in Japan. The primary endpoint is amputation-free survival at six months; additional endpoints include limb salvage and wound healing. Subjects will be followed out to three years.
The “no option” patients who are candidates for the PROMISE II study are no longer eligible for conventional endovascular or surgical therapy for CLTI, as determined by an independent physician committee.
“Late-stage CLTI patients have a terrible quality of life, where they live with pain and limited mobility. Treatment success with these patients is defined by wound healing and amputation-free survival. The investigational LimFlow therapy has the potential to achieve both—by restoring oxygen-rich blood flow to the ischaemic foot, it may create the conditions for chronic wounds to heal, which may enable patients to avoid amputation and keep their limb,” said Hiroyoshi Yokoi (Cardiovascular Center, Fukuoka Sanno Hospital, Fukuoka, Japan), PROMISE II Japanese principal investigator. “We recently received Investigational Review Board approval to begin the PROMISE II trial at Fukuoka Sanno Hospital and I am enthusiastic about being able to offer a promising new option to my no-option patients.”
Nobuyoshi Azuma (Asahikawa Medical University, Asahikawa, Japan), a PROMISE II investigator said, “In Japan’s ageing society, arteriosclerosis of the lower limbs is increasing, and severe lower limb ischaemia encompassing foot pain, ulceration and necrosis due to impaired blood flow associated with diabetes and dialysis is becoming a major problem. We hope that pDVA with the LimFlow system will be a viable option and we look forward to starting the trial in Japan soon.”
The pivotal PROMISE II clinical trial of the LimFlow system is currently enrolling patients at centers in the USA and Japan.
Cardiovascular Systems recently announced that it has acquired a line of peripheral support catheters from WavePoint Medical.
Peripheral support catheters are used during peripheral vascular intervention (PVI) procedures for guidewire support to enable lesion crossing, as well as for guidewire exchanges. Physicians use support catheters in approximately 50% of PVIs, primarily in below-the-knee and complex interventions. When calcium is present, lesions can be challenging to cross with an interventional guidewire and often require advanced tools prior to vessel preparation and treatment. CSI anticipates it will introduce the acquired catheters as its new ViperCross line in the first half of its fiscal year ending 30 June 2022.
In addition, as part of this transaction, WavePoint will also develop a portfolio of specialty catheters used in the treatment of chronic total occlusions (CTO) and complex percutaneous coronary intervention (PCI) procedures for CSI. CTOs represent a significant and growing segment of PCIs and often contribute to poor patient outcomes. Commercial availability of these specialty catheters is anticipated in CSI’s fiscal year ending 30 June 2023.
Michael Darcy (Washington University School of Medicine, St Louis, USA), David Sacks (The Reading Hospital and Medical Center, West Reading, USA), and Richard Towbin (Phoenix Children’s Hospital, Phoenix, USA) each received an SIR Gold Medal during the third day of the 2021 meeting of the Society of Interventional Radiology (20–26 March, online), in recognition of their “distinguished and extraordinary service to the society or to the discipline of interventional radiology [IR]”. The Gold Medal is the highest honour presented by SIR.
In his outgoing presidential address to the virtual attendees, Michael Dake (University of Arizona Health Sciences, Tucson, USA) congratulates the 2021 Gold Medallists: “The 2021 Gold Medallists, through their practice, mentorship, and leadership, have driven interventional radiology to unprecedented heights, and revolutionised patient care through the power of minimally invasive, image-guided medicine.”
Michael Darcy
Known for his expertise in portal vein interventions and interventional management of gastrointestinal bleeding, Darcy has devoted himself to the best interests of the society and the IR community, SIR state in their award ceremony. Darcy served as president of SIR from 2002–2003, and was chair of the SIR Foundation from 2007–2009. He has authored or co-authored over 140 research papers and 39 book chapters, and has been an investigator on all of the major transjugular intrahepatic portosystemic shunt (TIPS) trials in the USA. Darcy was also a founding member of the Association of Chiefs of Interventional Radiology (ACIR), and served as its president from 2016 to 2018. He gave the 2016 Dotter Lecture at that year’s SIR meeting.
David Sacks
Sacks has authored more than 130 peer-reviewed articles, the society says. Sacks served as president of SIR from 2007 to 2008, and has been standards division councillor, chair of the technologies assessment committee, and a member of many SIR and American College of Radiology (ACR) committees. He has been an editorial board member of the Journal of Vascular and Interventional Radiology (JVIR), and was named a JVIR distinguished reviewer in 2019. Sacks is currently chair of the board of the Intersocietal Accreditation Commission, and president of the Intersocietal Commission for the Accreditation of Carotid Artery Stenting Facilities. SIR says that in this latter position, he is “strengthening an important collaborative relationship for the specialty”. Sacks is also one of the founders of SIR’s clots course, designed to train interventional radiologists to treat acute stroke. Sacks was a principal investigator of the KAVIAR trial, comparing vertebroplasty and kyphoplasty, and the National Institute of Health (NIH)-funded ATTRACT trial.
Richard Towbin
Towbin is one of the founders of the Society of Paediatric Interventional Radiology (SPIR), and one of the first full-time paediatric interventional radiologists. He also established the first paediatric interventional radiology (IR) fellowship, and has trained numerous paediatric IR fellows. Towbin has served on both the SIR Executive Council and SIR Foundation board of directors, and has been a member of the Standards committee for over 25 years. According to the society, he was “instrumental” in initiating the paediatric interventional subcommittee. One of his most significant contributions was serving as treasurer for SIR, the society continue. In 2019,Towbin was the recipient of one of the first Gold Medals given by SPIR. He has authored over 375 papers, many of which SIR claim are considered “seminal” to the field of paediatric IR.
Delineating the path towards personalised dosimetry in order to “maximise response to therapy”, David McNiel (University of Arizona Health Sciences, Tucson, USA) presented clinical predictors of yttrium-90 (Y-90) uptake in patients with hepatocellular carcinoma (HCC) at the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online). In the presented research, a multiple regression model demonstrated that prior ablation was a significant predictor of an increased tumour-to-normal ratio (T:N) for Y-90 uptake.
“Radioembolization with Y-90 microspheres is a commonly performed procedure for the treatment of HCC,” he began. “Methods for calculating prescribed activity can be divided into two categories: semi-empirical methods and partition model.”
Due to the prior success of the DOSISPHERE-1 trial, which reported improvement in tumour response rate and overall survival in patients who had HCC treated with Y-90 radioembolization utilising personalised dosimetry, McNiel and colleagues conducted a retrospective institutional review board-approved study on all patients who underwent planning angiography with SPECT-CT for radioembolization of HCC between 9 January 2016 and 31 August 2020 (n=106, over a total of 128 angiography procedures). All patients had pre-procedural contrast-enhanced MRI evaluations of the abdomen. According to the speaker, a multitude of patient characteristics were also collected from the electronic medical record for inclusion in analysis.
MR, cone beam CT (CBCT), and SPECT-CT images were exported to SimpliciY90 image-fusion and dosimetry planning software (version 2.2; Mirada Medical) for evaluation.
“Our initial hypothesis with this work was that T to N ratio would be significantly correlated with the aetiology of the patient’s cirrhosis,” McNiel explained. “Surprisingly, however, this was not the case, and despite the apparently diverse group of patients that go on to develop HCC, including patients with NASH-based [non-alcoholic fatty liver disease] cirrhosis, viral aetiologies of cirrhosis, and alcoholic cirrhosis, none of these groups demonstrated significant differences in T:N ratio in our dataset.
“Similarly, clinical factors that we anticipated would likely have correlation with T:N ratio, including Child-Pugh classification, prior surgical resection, and prior systemic therapy also demonstrated no significant differences in T:N ratio in our dataset.”
Turning to the positive results of their study, McNiel detailed how prior intra-arterial liver-directed therapy (including previous Y-90, transarterial chemoembolization [TACE], and/or ablation therapy) demonstrated significant positive correlation with T:N ratio with their dataset.
In addition, tumour volume, while not significantly correlated, showed “a strong negative trend”; larger volumes of tumour took up less macroaggregated albumin (MAA) activity than their smaller counterparts. “This finding is likely artefactual, based on our methodology, as larger tumours are more likely to contain necrotic, poorly-perfused components, and thus, they are likely to take up less relative MAA than their smaller counterparts.”
Patient age was negatively correlated with T:N ratio by univariate analysis. However, with multivariate analysis, the investigators found non-significance between the two variables.
A subgroup analysis of patients who had undergone prior liver-directed therapy “also demonstrated interesting results,” McNiel continued. Patients who had prior liver-directed therapy could be divided into two groups, he explained: those who had undergone intra-arterial directed therapy, in the form of Y-90 or TACE, and patients who had prior ablation therapy.
“Interestingly, patients who had prior intra-arterial therapy demonstrated no significant difference in T:N ratio, whereas patients who had prior ablation therapy demonstrated a strong significant difference in T:N ratio,” SIR attendees heard (mean 3.39 vs. 2.25; p=0.003).
“These findings raise interesting questions,” McNiel concluded. “Is there some different mechanism of ablation therapy versus intra-arterial therapy that affects this activity? Also, is recurrent disease following either of these therapies somehow inherently different in their angiogenesis or their aggressiveness that could explain these findings?”
The US Food and Drug Administration (FDA) have granted approval of the TheraSphere Y-90 glass microspheres (Boston Scientific), developed for the treatment of patients with hepatocellular carcinoma (HCC). The approval expands access to this life-prolonging therapy for a greater number of patients, which, to date, has been utilised under a humanitarian device exemption (HDE)—an FDA classification that required institutional review board approval and limited the number of patients treated with the therapy per year. TheraSphere is now the only radioembolization technology indicated for the treatment of unresectable HCC in the USA.
HCC is one of the most prevalent cancers in the world and the most common type of primary liver cancer, with more than half a million new global cases diagnosed annually. The American Cancer Society estimates that approximately 32,000 new cases of HCC will be diagnosed in the USA in 2021. It is most often treated through surgery, liver transplantation, chemotherapy, or embolization, including both chemoembolization and radioembolization (selective internal radiation therapy [SIRT]). TheraSphere treatment, a type of SIRT with low toxicity, is comprised of millions of microscopic glass beads containing radioactive yttrium (Y-90), which are delivered directly to liver tumours via a catheter and result in minimal exposure to surrounding healthy tissue.
Approval of TheraSphere was based on results from the LEGACY study, designed to evaluate the safety and efficacy of the therapy for the treatment of early and advanced HCC. The study analysed data from 162 patients and met both primary endpoints of objective response rate and duration of response rate (72.2% at four weeks and 76.1% at six months, respectively). Data demonstrated 100% complete or partial patient response up to two TheraSphere treatments—disappearance of all lesions or ≥30% decrease in target lesion diameter —and a 93% overall survival rate in patients with transplant or resection following treatment at three years.
“I am honoured to have spearheaded the LEGACY trial in which we found that patients with early and advanced HCC exhibited very high response rates as well as clinically meaningful durations of response and survival, establishing TheraSphere as a standard treatment for this patient population,” comments Riad Salem, an interventional radiologist at Northwestern Memorial Hospital (Chicago, USA) and principal investigator of the LEGACY trial. “The trial results, which have been accepted for publication in Hepatology, produced one of the most comprehensive databases for TheraSphere, empowering physicians to make informed, data-driven decisions for their patients.”
Treatment with TheraSphere does not require hospitalisation and is typically performed as an outpatient procedure in as little as an hour, potentially alleviating pressure on healthcare systems in an increasingly complex care environment. Recognition of the benefits of SIRT (both to patients and hospitals) were reflected in recently issued guidance from the National Institute for Health and Care Excellence (NICE) when they recommended the use of TheraSphere for the treatment of patients with HCC through the National Health Service (NHS) in England, Wales, and Northern Ireland.
Penumbra today announced US commercial availability of the Indigo system Lightning 7. Lightning 7 expands Penumbra’s offering of the Indigo aspiration system with Intelligent Aspiration for mechanical thrombectomy and is designed for single session arterial thrombus removal.
Offering a new option for physicians to address arterial thrombus removal, the Indigo system Lightning 7 combines the new Indigo system CAT7 aspiration catheter with Lightning Intelligent Aspiration powered by Penumbra Engine. CAT7 is a high power, low profile catheter that features laser-cut hypotube technology and circumferential sweep designed for dependable delivery and maximised clot extraction.
The Indigo system’s proprietary Separator technology is also available with Lightning 7 (Separator 7) and is designed to enable unobstructed aspiration for the duration of the procedure. Lightning Intelligent Aspiration features Penumbra’s proprietary clot detection technology that enables the operator to identify thrombus location and is also designed for blood loss reduction.
“My experience with Lightning 7 suggests that it streamlines clot removal in the peripheral arterial vasculature with low profile access, excellent trackability, and similar power to the CAT8 Penumbra catheter that was previously used for this application. The torquability makes vessel navigation much easier,” said Christopher Metzger (Holston Valley Medical Center, Kingsport, USA). “Penumbra continues to forge ahead with yet another game-changing technology that has the potential to increase single-session thrombus removal and thereby may help improve outcomes.”
“If interventional radiologists wish to become competitive with surgeons, the availability of software enabling the accurate comparison of pre- and post-interventional CT [computed tomography] or MRI [magnetic resonance imaging] scans must become mandatory and routinely employed,” Luigi Solbiati argues. He discusses the ablation-confirmation software he has developed with his team in Milan, Italy, and enthuses about the potential of artificial intelligence to refine and improve ablative outcomes in interventional radiology.
Many studies in the literature have demonstrated that the outcome of any local tumoural treatments (be it surgery, ablation, or radiotherapy) is largely dependent on the technical success achieved, i.e. if the tumour has been completely or partially treated and, when the treatment is complete, if the peritumoural margins of normal parenchyma are sufficiently and homogeneously thick.
Surgeons have always told interventional radiologists that one of the most significant—if not the most significant—differences between surgical resection and thermal ablation is the modality of assessment of technical success. While surgical specimens are sent to a different department (Pathology) to obtain an accurate assessment, for thermal ablation, technical success is monitored by the same interventional radiologist who performed the treatment (or by other colleagues in the same department). This is done through the comparison of pre- and post-interventional CT or MRI scans in side-by side juxtaposition. This method contains many possible sources of error and can be very challenging, even for experienced radiologists. In a recently published study,1 38 radiologists from many different countries (18 with considerable experience in percutaneous tumour ablation and 20 with limited experience) were asked to assess whether technical success and technical efficacy after thermal ablation of nine hepatocellular carcinomas (HCCs) in nine patients with known outcomes had been achieved using the traditional side-by-side juxtaposition of pre- and post-interventional CT scans. As many as 44.1% of cases per radiologist were misjudged and, more importantly, there was no significant difference between the experienced and unexperienced radiologists.
Consequently, if interventional radiologists wish to become competitive with surgeons, the availability of software enabling the accurate comparison of pre- and post-interventional CT or MRI scans must become mandatory and routinely employed. For this reason, over the last few years I have collaborated with colleagues on the development of a software with these characteristics (Ablation-fit; R.A.W. Srl, Milan, Italy). Our software is based on the automatic segmentation of liver parenchyma and major blood vessels, the semi-automatic segmentation and reconstruction of tumoural targets and post-ablation necrotic areas, and the non-rigid, fully automatic registration of pre- and post-ablation CT scans. This allows for the deformation of liver parenchyma section by section, based on the location of intrahepatic blood vessels, enabling us to achieve an extremely precise image fusion regardless of differences in body position, respiratory motion, or liver deformation. In addition, in very short time (just five to 10 minutes), the software calculates the percentages of residual unablated volumes of both the target tumour and the predetermined 3D safety margin.
In a retrospective study on 90 HCCs that have undergone microwave ablation (MWA) with apparent technical success and followed for at least one year, we demonstrated that, if we could have used this software, we would have discovered incomplete treatments at 24-hour CT scan (enabling immediate re-treatment) in 76.6% of the HCCs that actually had local tumour progression at one year.2
In a recently published clinical study on colorectal liver metastases that had undergone radiofrequency ablation (RFA),3 with volumetric assessment of the periablational safety margin performed with this software, it was proven that the safety margin assessment was the only independent predictor of local tumour progression, and that at least 90% of a 6mm circumscribed 3D safety margin was required to achieve complete ablation.
Ablation-confirmation software like this can be used in different modalities. When ablations are performed in sonographic rooms under the control of contrast-enhanced ultrasound (US), potentially integrated with real-time US-CT/MRI image fusion, ablation-confirmation software like this can be used only after the end of the treatment. In this situation, a level of assessment closer to that achieved by pathologists after surgical resection can be obtained, but if incomplete treatment or insufficient ablative margins are seen, the procedure will have to be repeated, just as in surgery. On the other hand, if ablations are performed under ultrasound or CT guidance in the CT room (as is recommended nowadays),4 the software could be used immediately, intraprocedurally, and the treatment could be adapted in order to complete the intervention without the fear of only obtaining partial or insufficient ablative margins. This intraprocedural use represents an advantage even over surgical resection.
In addition, this kind of software can trace out the ideal path to the portion of tumour to be retreated, thus significantly facilitating the completeness of the procedure.
In the near future, it is hoped that such easily usable and extremely fast software will be increasingly employed in interventional departments. We are currently working to extend their applicability also to extrahepatic organs, such as the kidneys, lungs, lymph nodes, and prostate, as well as to MRI scans.
In the end, it is important to point out that there is a perfect integration between the type of software described above, and one of the most attractive (if not the most attractive) incoming modalities for the guidance of any interventional procedure: augmented reality (AR).5 In addition to the already known and much discussed advantages of AR (its low cost, ergonomic feel, diminishment of the learning curve, particularly in younger users, the opportunities this technology provides for educational purposes), it can be particularly helpful for the guidance of interventional devices into incompletely treated tumoural areas, thanks to its ability to define precise trajectory lines that the operator can simply and automatically follow to reach the targets. The association of increasingly accurate and simple ablation-confirmation software and AR is likely one of the milestones of near future interventional radiology.
Luigi Solbiati is an interventional radiologist at the Humanitas University in Milan, Italy. Disclosure: He is a developer of the Ablation fit software.
References
Ablation is entering a new era of increased precision and quantification, the interventional radiology (IR) community argues, with outcomes that match or surpass those of surgery. Whilst reaching equipoise with their surgical counterparts has been a goal for interventional radiologists since the advent of ablative treatments for cancer, some expert interventionalists claim that the increased precision of modern thermal ablation techniques, coupled with improvements in radiology mean physicians are often treating smaller volume tumours. This now positions the procedure as the “definitive” treatment for select patients in some cancers. Several clinical trials including the ACCLAIM, COLLISION, and COVER-ALL trials—are currently underway, and aim to bolster the evidence-base demonstrating favourable patient outcomes from thermal ablation.
“We are now talking about ablation 2.0,” past Society of Interventional Oncology (SIO) president Stephen Solomon (Memorial Sloan Kettering Cancer Center, New York, USA) says. “Ablation 1.0”, in his eyes, is the basic concept underpinning the minimally invasive procedure: put a needle in, use image guidance, burn or freeze the cancerous tissue to destroy it. “But ablation 2.0,” he explains, “means that we are focusing more on precision, on margins, and specifically the road to A0 [where all tumour cells are eradicated].”
When discussing soft and hardware advances in ablation, David Breen (University Hospital of Southampton, Southampton, UK) adopts the framework of “planning, execution, confirmation”. Planning uses preprocedural scans to map out probe positions and angles, along with estimation of the ablation zone—all the steps taken ahead of performing the ablation. Execution is the act of probe positioning, sometimes using guidance tools. The final stage, confirmation, involves determining the adequacy of treatment margins in order to verify complete ablation. “Of these three stages, confirmation and perhaps planning are the two that are beginning to enter a higher level of engineering maturity and reliability. Guidance tools, as they currently stand, must still be used with careful operator insight,” Breen explains.
The upcoming European Conference on Interventional Oncology (ECIO; 10–13 April, online) is hosting a session entitled “Different ways of killing cancer and why we need all of them”, which explores advances in ablation.
In a further sign of the times, several large companies are positioning themselves to buy smaller businesses operating in this space. In 2020, for example, imaging behemoth Siemens Healthineers acquired all shares of Varian, a radiotherapy company, which in 2019 itself acquired Endocare, a company specialising in cryoablation and microwave ablation, and Alicon, a provider of embolic therapy for liver cancer treatment.
Cascination is another company offering an over-arching solution for ablation, with products designed for imaging, planning, navigation, validation, treatment, and treatment verification. Breen believes this is the direction industry is taking, and represents a shift away from a more modular approach where one organisation may only offer products for part of this pathway.
Developing improved planning software
Several different groups around the world are working on developing planning software for ablation treatments with the goal of obtaining a predictable technical outcome. “In order to do this effectively,” current SIO president Matthew Callstrom (Mayo Clinic, Rochester, USA) explains, “it is necessary to have accurate registration software for all phases of the ablation, including planning, intraprocedural evaluation of device placement, and postprocedural measurement of the margins of the ablation. This approach will transition thermal ablation from a subjective technical endpoint to an objective technical endpoint. I think the exciting aspect of this is that many efforts are underway and will become more widely available to proceduralists.”
From the department of Interventional Radiology at the University of Texas MD Anderson Cancer Center (Houston, USA), Bruno Odisio tells Interventional News that he and imaging physicist Kristy Brock have received a National Institute of Health (NIH) grant (Academic-industry partnership–Raysearch Laboratories) for the development of a dedicated liver ablation planning and assessment software. “We are using this software to simulate and evaluate intraprocedurally the treatment endpoint, because we know that when we perform a liver ablation, the most important thing that we can do to improve local tumour control is to effectively cover the tumour with adequate margins in all planes,” he explains.
Odisio and colleagues are enrolling for a phase II trial (COVERALL) to study how well software-aided imaging works in confirming tumour coverage with ablation on patients with liver tumours. The primary objective of the COVERALL trial is “To evaluate if the intraprocedure feedback of a biomechanical deformable registration volumetric image method during percutaneous ablation will increase the minimal ablation margins on a three-dimensional (3D) computed tomography (CT)-generated analysis.”
Clinicaltrials.gov registers: “The current standard for targeting tumour cells and evaluating the outcome of a liver ablation procedure is a visual inspection of the pre- and postprocedure computed tomography (CT) scans. Software-aided imaging systems (such as Morfeus, the one utilised in the COVER-ALL study) may help to improve the accuracy and effectiveness of liver ablation.”
Prior to receiving the NIH grant for the COVER-ALL study, Odisio and Brock conducted a preliminary, retrospective analysis using their software to make a fusion image of the preprocedural and postprocedural CT images. The software utilises a biomechanical model to align the images, which Odisio says allows them to account for patient breathing, positioning, and tissue desiccation associated with the ablation itself. “We noticed that many times, our simple visual inspection of the CT scans before and after the ablation gave us a false sense of confidence regarding covering the entire tumour. In fact, among the patients who had recurrence after the ablation, we noticed based on our software assessment that ablation did not cover the tumour properly in all three-dimensional planes. Also, usually the lack of sufficient ablation margins occurs in an oblique plan between the axials, coronal, and sagittal plans”. He adds: “Based on what we have learned so far, many of the cases we define as tumour recurrence are in fact residual unablated tumour. That was our motivation to use the software.” Using the software with biomechanical modelling negates the issues with trying to decipher simple axial imaging in a complex 3D environment.
He adds that it is very hard to analyse the imaging data intraprocedurally: “You have a constrained timeline; you have too much data for you to run. Our software uses artificial intelligence [AI] and a biomechanical model to analyse the data on probe placement and ablation margins during the liver ablation. We hope that this will solidify the idea that using software really helps to improve treatment endpoints.” This work is part of the Image Guided Cancer Therapy (IGCT) Research Program run through The University of Texas MD Anderson Cancer Center.
Luigi Solbiati and his team at Humanitas University in Milan, Italy, have also developed software to aid ablation (Ablation-fit, R.A.W. Srl). “If interventional radiologists wish to compete with surgeons, the availability of software enabling an accurate comparison of pre- and postinterventional CT or magnetic resonance imaging (MRI) scans must become mandatory and routinely employed,” Solbiati opines.
Describing the software to this newspaper, he comments: “It is based on automatic segmentation of liver parenchyma and major blood vessels, semi-automatic segmentation, and reconstruction of tumoural targets and post-ablation necrotic areas and [employs a] non-rigid, fully automatic registration of pre- and postablation CT scans that allows us to deform the liver parenchyma section by section, based on the location of intrahepatic blood vessels. This allows for an extremely precise image fusion regardless of differences in body position, respiratory motion, or liver deformation. In addition, in very short time (five to 10 minutes) the software calculates the percentages of residual, unablated volumes of both the target tumour and predetermined 3D safety margin.”
In a retrospective study of 90 hepatocellular carcinomas (HCCs) that had undergone microwave ablation with apparent technical success and followed for at least one year, published in the International Journal of Hyperthermia, Solbiati et al demonstrated that, if they could have used this software, they would have discovered incomplete treatments at 24-hour CT scan (enabling immediate re-treatment) in 76.6% of the HCCs that actually had local tumour progression at one year.
In a clinical study recently published in European Radiology of colorectal liver metastases that have undergone radiofrequency ablation (RFA) with volumetric assessment of the periablational safety margin performed using this software, it was proved that the safety margin assessment was the only independent predictor of local tumour progression, and that at least 90% of a 6mm circumscribed 3D safety margin was required to achieve complete ablation.
“Ablation-confirmation software like this can be used in different modalities,” Solbiati says. “When ablations are performed in sonographic rooms under the control of contrast-enhanced ultrasound (US), potentially integrated with real-time US-CT/MRI image fusion, ablation-confirmation software like this can be used only after the end of the treatment. In this situation, a level of assessment closer to that achieved by pathologists after surgical resection can be obtained, but if incomplete treatment or insufficient ablative margins are seen, the procedure will have to be repeated, as it would occur for surgery. If ablations are performed under US guidance (or CT guidance) in the CT room (as would be recommended nowadays), the software would be used immediately, during the procedure, and the treatment could be immediately completed if partial or with insufficient ablative margins. This would represent even an advantage over surgical resection.
“In addition, this kind of software can trace out the ideal path to the portion of tumour to be treated, thus significantly facilitating the completeness of the procedure.
“In the near future, it is hoped that such easily usable and extremely fast software will be increasingly employed in interventional departments, while we are currently working to extend their applicability also to extrahepatic organs (kidney, lung, lymph nodes, prostate) and to MRI scans.”
ACCLAIM and COLLISION: Trial to watch
The SIO is also currently planning a multicentre clinical trial—the ACCLAIM trial—that incorporates software that looks at margins into the ablation, and which will aim to determine if achieving complete margins during an ablation equates to procedural success, assessed through disease progression or recurrence postprocedurally. Constantinos Sofocleous (Memorial Sloan Kettering Cancer Center, New York, USA) will be the principal investigator.
“The ACCLAIM trial will be the first liver ablation trial to use a well-defined objective technical outcome measure as a critical aspect of the trial design,” Callstrom tells Interventional News. “We anticipate that this will help drive adoption of this approach as the standard for liver mass ablation”.
Sofocleous comments: “The ACCLAIM trial is a single-arm, prospective, multicentre, international phase II study where thermal ablation will be offered in patients with limited number and relatively small CRC [colorectal cancer] liver metastases. A mandatory requirement for enrolment in the trial is the use of real-time 3D software to assess the ablation zone and show that the target tumour has been completely covered with ideally 10mm and not less than 5mm of minimal ablation margins. The study hypothesis is that if ablation margins are larger than 5mm, local progression-free survival at 12 months after ablation will be over 85%.”
Another hotly anticipated trial is the COLLISION trial. Sofocleous tells this newspaper: “I am very interested to see the results of the COLLISION trial that compares thermal ablation to resection for well-selected small colorectal liver tumours. This trial is now enrolling in The Netherlands, and will address a lot of the questions that exist for the value of ablation. I am particularly interested to find out whether the trial will provide high-level evidence about thermal ablation and whether this treatment can be equally effective and potentially safer than limited resection as a local curative therapy for CRC liver metastases.”
In an additional attempt to further improve margin confirmation, Solomon informs this newspaper that he and Sofocleous are conducting research into performing biopsies around the edges of the tumour intraoperatively, in order to gain a quick pathological assessment of whether or not any cancer cells are left alive. This allows them to be more adaptive during the procedure: “If, during the procedure, we find there is still live tissue, we would do something about it. If the software shows us that the margins are close, maybe we would expand it [the ablation zone] a bit. All of these things allow us to finesse and improve our results.”
Cardiovascular Systems has announced that the first patients in the USA have been treated with the Wirion embolic protection system. Wirion is a distal embolic protection filter used to capture thrombus and debris that can be associated with all types of peripheral vascular intervention procedures, including atherectomy.
Lawrence Garcia, St Elizabeth’s Medical Center, Boston, USA and Nicolas Shammas, Unity Point Health-Trinity Bettendorf, Davenport, USA participated in the WISE LE study where Wirion demonstrated a major adverse event (MAE) rate of 1.9%, which is lower than previously reported rates for other lower extremity embolic protection filters. Importantly, no clinically significant distal embolization was observed when Wirion was used.
Garcia commented: “Wirion represents a critical advancement for distal embolic protection devices. With Wirion, I can use my preferred 0.014” guidewire to cross the lesion and then place the filter anywhere on the wire. As a result, I am able to provide extensive support, individualized to each patient and intervention.”
Shammas added: “Delivery and retrieval of Wirion are easy with a minimal learning curve. Debris capture is very efficient making Wirion exceptionally suited for use with any atherectomy device.”
Scott R Ward, CSI Chairman, president and chief executive officer, said: “We are excited to announce the commercialisation of Wirion. This product will be an important part of our comprehensive portfolio of differentiated products designed to save limbs and improve outcomes for patients undergoing complex peripheral interventions.”
MedAlliance recently announced that it has raised over US$50 million in equity funding. The new investor is Trustar Capital (formerly known as CITIC Capital Partners).
Proceeds from the financing will be used to fund commercialisation of Selution SLR—a novel sirolimus-eluting balloon that provides a controlled sustained release of a limus drug. They will also support global clinical programmes including enrolment of four additional US Food and Drug Administration (FDA) investigational device exemption (IDE) studies this year. The US coronary ISR study is underway and began enrolment in July 2020.
MedAlliance, the first drug-eluting balloon (DEB) company in the world to receive FDA breakthrough device designation status for a sirolimus DEB, was recently awarded breakthrough status for Selution SLR in the treatment of atherosclerotic lesions in native coronary arteries. This was the fourth breakthrough designation awarded to MedAlliance for its sirolimus DEB, following coronary in-stent restenosis, peripheral below-the-knee and AV fistula indications.
In February 2021, MedAlliance enrolled the first patient in SUCCESS PTA, a 700-patient post-market study with Selution SLR for the treatment of peripheral arterial disease (PAD). This is the largest study undertaken to date with the device. Data from the SUCCESS PTA study will be part of the clinical evidence supporting CE mark renewal in 2023/2024 under the new European Medical Device Regulation (MDR).
Selution SLR was awarded CE mark approval for the treatment of PAD in February 2020 and for the treatment of coronary arterial disease in May 2020. It is now available in Europe and all other countries where the CE mark is recognised. The global market for DEB is estimated to be worth over US$1.5 billion.
Treating patients with metastatic bone disease by radiofrequency ablation (RFA) using the OsteoCool system (Medtronic) results in rapid and statistically significant improvement in pain scores, and provides sustained, long-term relief. Attendees of the 2021 meeting of the Society of Interventional Radiology (SIR; 20–26 March, online) will be the first to hear the full cohort data from the Medtronic-sponsored OPuS One post-market clinical study in the “Abstract of the year” presentation, to be delivered by Jason Levy (Northside Hospital, Atlanta, USA) to the virtual audience. This latest dataset follows previous announcements from the OPuS One team also detailing positive results following RFA with the OsteoCool system.
OPuS One is the largest clinical study—with the most meaningful clinical results—considering the OsteoCool technology to date. Principal investigator Sandeep Bagla (Vascular Institute of Virginia, Woodbridge, USA), along with Levy and other colleagues, set out to assess the effectiveness of the OsteoCool RF ablation system. They conducted a global, prospective, nonrandomised, multicentre study of RFA for the palliative treatment of patients with painful osseous metastases.
In addition to pain, osseous metastases can cause fractures and some “pretty debilitating symptoms”, such as spinal cord or neurovascular compression, Levy said.
He continued: “Radiation treatments have been commonly used for this, but they do not always provide pain relief, they can take weeks to occur, and they can set a patient up for fractures down the road. When the effects of their treatment are delayed for weeks, in this population of palliative care patients, that may consist of a significant proportion of that patient’s life.”
The investigators therefore wanted to ascertain the ability of RFA to provide quick and long-lasting pain relief for these patients.
Opining on their results, Levy enthuses: “We are really excited by what we saw. The first thing we noticed is that we had pain relief as fast as three days, which is obviously very significant in this patient population, especially when the standard-of-care treatment right now, radiation, takes four to six weeks.
“In addition, this was sustained. At one year, the majority of patients continued to report pain improvements, which is also a significant improvement over radiation treatment.”
Patients also experienced significant improvement in average pain, pain interference, and quality of life.
“I think the most important outcome from this study is that RFA can give patients a very rapid, improved quality of life within three days, and this is sustained out to 12-months,” Levy reiterated. As the OPuS One trial largely focused on lytic metastases, which are very common, Levy says these results demonstrate that RFA with OsteoCool is a “good option” for a wide range of cancer patients.
“I believe this treatment should be available in the patient paradigm than what we saw in this study, where it was mostly a palliative treatment,” he concluded. “[We should offer it to] more patients where we can prevent future fractures, and prevent pain from lasting a long time.”
Levy and Bagla spoke to Interventional News following the results of the first 100 patients treated in the OPuS One clinical study. The full interview can be viewed here, or below.
Genicular artery embolization (GAE) is “highly effective and durable” in reducing symptoms due to moderate-to-severe knee osteoarthritis that is refractory to other conservative therapy (such as joint injections and medication), and has an acceptably low toxicity profile. So concludes Siddharth Padia (University of California, Los Angeles, USA), speaking at a press briefing in advance of the Society of Interventional Radiology (SIR) annual meeting (20–26 March, online). He will present these results to attendees of the virtual congress.
Padia cites GAE as a “promising therapy” to treat patients with symptomatic knee osteoarthritis by reducing synovial arterial hypervascularity. “As we all know, having arthritis is a very common problem, resulting in pain and physical dysfunction,” he said. Current treatment options for this disease are to “do nothing” and rest up, to take medications (including nonsteroidal anti-inflammatory drugs; NSAIDs), or, if these have failed, to receive a joint injection: “typically a steroid, such as cortisone, or a gel,” Padia said.
“While those can work,” he continued, “they have relatively short-term results. A typical joint injection lasts for anywhere from one to three months, so it is not really built as a long-term solution. Currently, the only long-term solution is a knee replacement, which does work, and is recommended for people with severe, symptomatic osteoarthritis, but the problem, the challenge with total knee replacement is it involves anaesthesia, it involves a hospital stay, and it has a long recovery and rehabilitation time. Many patients are either not candidates, or want to defer their operation to a later date.”
The investigators therefore conducted a prospective, single-centre, open-label, US Food and Drug Administration (FDA)-approved investigational device exemption (IDE) study that aimed to evaluate the safety and efficacy of the minimally invasive GAE procedure for the treatment of symptomatic knee osteoarthritis, with an eye to looking at potential long-term outcomes.
“In theory, if we can reduce the inflammation, we can make people’s pain go away, and make their overall function improve,” Padia explained, justifying the rationale underpinning GAE. “The goal is to normalise or even decrease the blood flow in the knee joint, because right now, in a patient with arthritis, the blood flow is abnormally increased.”
Knee osteoarthritis is age-related, Padia explained, and as such the study enrolled patients aged 49–80 years (median age of 69). All patients had moderate or severe focal knee pain and osteoarthritis on knee radiograph (Kellgren-Lawrence grades 2–4; 18% were grade 2, 43% were grade 3, and 40% were grade 4), no prior knee surgery, and were not candidates or not willing to undergo total knee replacement surgery. Patients had to have failed conservative therapy, including NSAIDs and/or joint injections. Baseline pain (visual analogue scale) and symptom scores (Western Ontario and McMaster Universities Osteoarthritis Index; WOMAC) were assessed. Median body mass index (BMI) was 28 (range 18–44).
After obtaining femoral arterial access, GAE was performed using 100μm particles (Embozene, Varian) of one to three genicular arteries supplying the location of the patient’s pain, as determined by digital subtraction angiography and cone-beam computed tomography (CT). GAE is performed as an outpatient procedure, and not under general anaesthesia, because “the procedure itself is completely painless”.
Over a nine-month period, 40 patients were treated with GAE. The left knee was treated in 25 of the 40 patients (62%), and the right knee was treated in the remaining 15 (38%). Medial knee pain was treated in 27 of 40 patients (68%), and lateral knee pain was treated in 13 (32%). Technical success was achieved in 100% of patients.
WOMAC and pain scores decreased from a median of 52 (out of 96) and eight out of 10 at baseline to 21 out of 96 (60% decrease) and three out of 10 (63% decrease) at 12 months, respectively. “We saw an immediate drop in WOMAC score, from quite a high score at baseline [52 out of 96] to a median of 22 at one month. It further improved with time: at three months, WOMAC score was 15, and it stayed low for the entire duration of the study.”
Padia and colleagues used a cut-off of 50% to consider their procedure a success. In total, 27 out of the 40 patients (68.5%) had a greater than 50% reduction in WOMAC score, and a further 28 patients from the full cohort (70%) experienced a more than 50% reduction in pain score. “A 50% reduction is quite an aggressive threshold to use,” Padia stated. “The orthopaedic surgery literature uses a much smaller cut-off when they define success. When we use a higher threshold, such as a 75% reduction—a 75% reduction in WOMAC score essentially means you are pain free—that was achieved in 43% [of patients]. There are significant improvements in pain in the majority of patients.”
The investigators also noted any adverse events and symptoms scores, assessing these at one week, one month, three months, six months, and one year after GAE. Transient skin discoloration and transient mild post-procedure knee pain were common and expected. Treatment-related adverse events included: one patient with a groin haematoma requiring overnight observation, seven patients with self-resolving focal skin ulceration, and two patients with asymptomatic small bone infarct on MRI at three months.
Despite lower mortality and shorter hospital stays, uterine artery embolization (UAE) is used far less commonly than hysterectomy in the management of clinically significant postpartum haemorrhage. This conclusion, presented at the Society of Interventional Radiology (SIR) annual meeting (20–26 March, online) by Janice Newsome (Emory University Hospital, Atlanta, USA), has led investigators to call for a postpartum haemorrhage response team, akin to a trauma response team. MD candidate Linzi Ardnt, also at Emory University Hospital, is the lead researcher for this work.
Speaking to press ahead of the annual meeting, Newsome expanded on her vision: “When our Ob-Gyn [Obstetrician and gynaecologist] colleagues make the decision to perform a hysterectomy, most of the time the estimated blood loss or the actual blood loss is under-calculated or unknown—so we are in a real dire situation at that point. Interventional radiologists are at many of these hospitals as well. So I believe, in order for UAE to become more utilised in these situations, we need to develop more techniques so we can find out earlier what the actual blood loss is, mobilise a team of people early so that these women can actually have this procedure [UAE] done, before a hysterectomy is chosen at the last minute. We are advocating for forming a postpartum haemorrhage team, so we can train together with our colleagues in Ob-Gyn—I believe that then, we can save more lives.”
Ardnt, Newsome et al picture the postpartum response team consisting of “anyone who cares for mothers and babies”, including anaesthesiologists, interventional radiologists, Ob-Gyns, and in some cases possibly neonatologists.
Contextualising this research, she stated: “Unfortunately, roughly 100,000 mothers will experience significant postpartum haemorrhage, a leading cause of the loss of life associated with childbirth”. The research identified 31 incidences of postpartum haemorrhage per 1,000 live births in the USA, of 9.8 million identified live births in total.
“Additionally,” Newsome continued, “20% of new mothers will have no risk factors. Because postpartum haemorrhage can occur quickly and threaten the life of the mother, the treatment options are sometimes limited. Currently, the most common treatment is just a transfusion [with an average incidence of 116.4 per 1,000 cases of postpartum haemorrhage]. But because physicians must act quickly, in many cases, the mother’s uterus is removed via hysterectomy.”
UAE represents an “underutilised”, less invasive second option, she explained, going on to note that the procedure has the benefit of being uterus-sparing, with quicker recovery times, and fewer adverse events.
The study investigators therefore set out to evaluate the utilisation and comparative effectiveness of hysterectomy versus UAE in patients with clinically significant postpartum haemorrhage requiring blood transfusion.
Using the Healthcare Cost and Utilisation Project Nationwide Inpatient Sample database from 2005 through 2017, they identified all women with live-birth deliveries who experienced clinically significant postpartum haemorrhage (defined as those receiving a blood transfusion only or transfusion plus hysterectomy or UAE). They utilised univariate analysis chi-square testing to determine demographic and clinical predictors of receipt of various therapies. Logistic regression was used to compare mortality and prolonged length of hospital stay (>14 days) for different treatment groups correcting for statistically significant predictors of receipt of various therapies.
The investigators noted that the incidence of hysterectomy to treat postpartum haemorrhage was significantly greater than incidence of UAE (20.4 vs. 12.9; p< 0.001). The following factors predicted the type of therapies received: race, maternal age, year of admission, elderly primigravida, previous or current caesarean section, breech position of foetus, placenta previa, pre-existing hypertension, pre-eclampsia, eclampsia, gestational diabetes, post-date pregnancy, premature rupture of membranes, cervical laceration, uterine rupture, dystocia, forceps delivery and haemorrhagic shock (all p<0.001).
Newsome noted: “We saw this disparity [between the number of hysterectomies and the number of UAEs] across racial lines and geography as well. Hysterectomy was twice as common as embolization in Latinx patients, and also more common in rural and non-teaching urban hospitals, as well as in the South [of the USA], and among Medicare and self-paying patients.
“Additionally, prolonged hospital stays of more than 14 days were twice as likely [2.1 times more likely with hysterectomy than UAE; p<0.001] in patients who had hysterectomies, and the hysterectomy procedure resulted in higher hospital charges—around US$18,000 more than if it were for UAE,” Newsome commented.
On logistic regression, the likelihood of mortality from hysterectomy was 3.1 times that of UAE (p< 0.001).
“Because of the evidence supporting UAE and benefits it provides to patients, we encourage hospitals to provide this treatment option to these women who may be at risk from postpartum haemorrhage. To do this, hospitals can create postpartum haemorrhage teams with an interventionalist, similar to other trauma teams, where we would train together and develop response protocols so they are better able to identify the risk factors o postpartum haemorrhage and ensure that the proper staff is on hand, for any delivery, and to be able to respond quickly, so that we can save mother’s lives before it goes too far, to the point where radical surgery is needed.”
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Cardinal Health recently announced that it has signed a definitive agreement to sell its Cordis business to Hellman & Friedman (H&F) for approximately US$1 billion, which includes buyer’s assumption of certain liabilities and seller’s retention of certain working capital accounts. The transaction is expected to close in the first half of Cardinal Health’s fiscal year 2022, subject to customary closing conditions and regulatory clearances.
“Cordis has a long history of innovation in minimally-invasive cardiovascular technology, and we are confident that with H&F as its owner, Cordis will be well-positioned for growth, innovation and success,” said Mike Kaufmann, CEO of Cardinal Health. “Cardinal Health and H&F have a shared passion for delivering high-quality medical products to customers and we are excited about the future for the Cordis business under H&F’s ownership.”
“Our decision to divest Cordis demonstrates our disciplined approach to evaluating our portfolio and focusing our resources in our strategic growth areas where we are an advantaged owner,” Kaufmann continued. “Looking forward, we remain committed to our medical distribution and global medical products businesses.”
“Cordis is an excellent fit with our philosophy of investing in great businesses as a market-leading cardiovascular device manufacturer known for high-quality products, strong physician satisfaction and superb patient outcomes,” said Hunter Philbrick, partner at H&F. “We are excited to invest in the talented Cordis, Ajax and Zeus teams to drive industry leadership, therapeutic innovation and improved patient experiences.”
“We at Ajax Health and Zeus Health are ecstatic about injecting growth into Cordis’ powerful platform, and will do so through investments in the core business and through an independent R&D engine—the ‘Cordis Accelerator’—to develop and commercialise a new pipeline of products exclusively for Cordis,” said Duke Rohlen, CEO of Ajax Health and Zeus Health, partners to H&F in the transaction, and executive chairman-designate of Cordis and CEO of Cordis Accelerator. “We see an unparalleled opportunity to partner with both existing Cordis leadership and H&F to combine a best-in-class innovation engine with a strong and robust commercial chassis. Together, we will establish Cordis as the standard bearer for medical device innovation.”
After closing, most assets and liabilities associated with the Cordis business will transfer to H&F. Cardinal Health will retain full authority for lawsuits related to inferior vena cava filters in the USA and Canada, as well as liability associated with these matters. Cardinal Health estimates that, after completion of the transition services agreement, the divestiture of the Cordis business will decrease Medical segment profit by approximately US$60 million to US$70 million on an annual run-rate basis.
In connection with the entry into this definitive agreement, Cardinal Health will classify the Cordis business as held for sale, which Cardinal Health expects to result in a pretax loss of up to US$120 million in the third quarter of its fiscal year 2021. Additionally, Cardinal Health was authorised to incur costs associated with the planned divestiture of up to US$125 million, primarily in its fiscal years 2021 and 2022.
Shape Memory Medical has announced CE mark approval for the Impede-FX RapidFill device, an expansion of the Impede family of biodegradable peripheral vascular embolisation plugs.
Ted Ruppel, president and CEO of Shape Memory Medical said, “We are excited to introduce Impede-FX RapidFill to the endovascular community in Europe. This is the first device on the market that enables the delivery of multiple embolisation plugs in a single application, which may provide an advantage in cases where the goal is to quickly fill and occlude large spaces such as aneurysms, venous insufficiency, or trauma with reduced procedure and fluoroscopy time, contrast media, and blood loss.”
The Impede family includes the Impede embolisation plug, the Impede-FX embolisation plug, and now Impede-FX RapidFill which consists of five Impede-FX-12 embolisation plugs preloaded into a single delivery introducer. This peripheral vascular platform incorporates the Company’s novel Shape Memory polymer technology, a porous, embolic scaffold that is crimped for catheter delivery and self-expands upon contact with blood for rapid conversion to organised thrombus.
Preclinical and clinical studies have shown that Shape Memory Polymer offers effective and predictable space filling compared to traditional coils and plugs, stable clot formation for reduced intradevice recanalisation, and progressive, intradevice healing as the material biodegrades.
To date, nearly 600 patients have been treated worldwide with the Impede family of devices.
Point-of-care duplex ultrasound (PAD-scan) is a cost-effective test for the detection of peripheral arterial disease (PAD) in patients with diabetes. This is the conclusion of a study recently published online in Annals of Surgery.
Authors Pasha Normahani (Imperial College NHS Healthcare Trust, London, UK) and colleagues write that PAD is a risk factor for cardiovascular disease, diabetic foot ulceration, and amputation in diabetic patients. They state that diagnosis enables optimisation of therapies to manage these risks, and highlight that PAD-scan can be performed by frontline staff and has been shown to be the most accurate bedside test. However, they stress that its cost-effectiveness has not been investigated.
Normahani et al detail that in the present study, a Markov model was constructed to estimate the health outcomes and costs over five years of different testing strategies applied to a cohort of diabetic patients. Bedside tests investigated were PAD-scan, ankle-brachial pressure index (ABPI), toe-brachial pressure index (TBPI), audible and visual Doppler, transcutaneous pressure of oxygen (TcPO2), and pulse palpitation, they specify. The authors note that health outcomes were incidence of new diabetic foot ulcer, major cardiovascular events, amputation, death, and diabetic foot ulcer healing rates.
“PAD-scan was the most cost-effective bedside test with an incremental cost-effectiveness ratio of £11,391/quality adjusted life years (QALY),” the authors communicate, adding that PAD-scan superiority in incremental cost-effectiveness ratio occurred at a PAD prevalence threshold of 0.24. Furthermore, they report that PAD-scan had the highest probability (78.7%) of having the greatest net benefit at a willingness to pay threshold of £20,000 per QALY. Finally, they reveal that the test reduced the number of amputations by 24% and the number of cardiovascular deaths by 10% over five years, compared to TBPI—the next best alternative.
Speaking to Vascular News about the significance of the team’s findings, Normahani commented: “Our results encouragingly suggest that point-of-care duplex ultrasound is accurate, cost-effective, and that its adoption may improve clinical outcomes. These results require external validation but provide a promising target for future research aiming to address the high burden of amputation and mortality in this group of patients.”
Renal artery involvement (RAI) in endovascular aneurysm repair (EVAR) is “highly predictive of the need for postoperative and permanent dialysis,” Anastasia Plotkin (University of Southern California, Los Angeles, USA) and colleagues write in the Journal of Vascular Surgery (JVS). They also report that RAI without revascularisation is associated with lower overall survival.
Plotkin et al detail that revascularisation after intentional or unintentional renal artery coverage “is not always technically successful,” adding that loss of a single renal artery in this patient population may result in the need for postoperative dialysis. In the present study, the investigators aimed to compare outcomes after EVAR stratified by RAI.
The researchers analysed data from the EVAR and thoracic endovascular aortic repair (TEVAR)/complex EVAR modules in the Vascular Quality Initiative (VQI) registry from 2009–2018. The primary outcome was postoperative dialysis, and secondary outcomes were 30-day mortality, dialysis at follow-up, postoperative renal function, and two-year survival.
Plotkin and colleagues detail that repair type cohorts were defined as: 1) no RAI (NRAI); 2) renal artery involvement with revascularisation (RAI-R); and 3) RAI and no revascularisation (RAI-NR). They relay that 25,724 out of 54,020 patients in the EVAR and TEVAR/complex EVAR modules in the VQI met the criteria for inclusion—24,879 NRAI, 733 RAI-R, and 112 RAI-NR.
The investigators report that postoperative dialysis was higher in RAI-NR (0.7% NRAI vs. 2.2% RAI-R vs. 17% RAI-NR, p<0.0001), as were 30-day mortality and dialysis at follow-up. On multivariate analysis, they add, RAI-R (odds ratio [OR], 2.2; p=0.03) and RAI-NR (OR, 5.9; p<0.0001) were independent predictors of postoperative dialysis and remained so after excluding ruptures: RAI-R (OR, 3; p=0.003) and RAI-NR (OR, 22.3; p<0.0001).
Finally, Plotkin et al communicate that other independent predictors of postoperative dialysis were worse preoperative renal function, symptomatic presentation, any preoperative/intraoperative blood transfusion, and larger blood loss (≥200ml).
“These risks should be taken into consideration with planning and performing EVAR and should be weighed against the risks of open repair when considering treatment options,” the authors conclude.
After hepatic artery embolization, preserved flow (≥4 segmental hepatic artery) lowered the risk of hepatic complications regardless of the portal venous flow. This is the conclusion presented by Won Seok Choi, Chang Jin Yoon (both Seoul National University Bundang Hospital, Seongnam, Korea), and colleagues in the Journal of Vascular and Interventional Radiology (JVIR).
The investigators set out to determine the association between hepatic ischaemic complications and hepatic artery collaterals and portal venous impairment after hepatic artery embolization for postoperative haemorrhage.
Between October 2003 and November 2019, 42 patients underwent hepatic artery embolization for postoperative haemorrhage. Hepatic artery collaterals were classified according to hepatic artery visualisation after embolization (grade 1, none; grade 2, 1–4 segmental hepatic artery; grade 3, ≥4 segmental hepatic artery). Transhepatic portal vein stent placement was performed in the same session in five patients (11.9%) with poor hepatic artery collaterals (grade 1 or2) and compromised portal venous flow (>70% stenosis). Hepatic ischaemic complications were analysed for relevance to hepatic artery collaterals and portal venous compromise.
Following hepatic artery embolization, hepatic artery flow was preserved (grade 3) through intra- and/or extrahepatic collaterals in 23 patients (54.8%), and hepatic complications did not occur regardless of portal venous flow status (0%). Of the 19 patients with poor (grade 1 or 2) hepatic artery collaterals (45.2%), segmental hepatic infarction occurred in two out of 15 patients with preserved portal venous flow (10 naïve and five stented; 13.3%). The remaining four patients with poor hepatic artery collaterals and untreated compromised portal venous flow experienced multi-segmental hepatic infarction (n=three) or hepatic failure (n=one) (100%; p<0.005).
“Transhepatic portal venous stent placement seems to be an effective intervention for the prevention of hepatic complications in cases of poor hepatic artery collaterals and compromised portal venous flow,” Choi et al conclude.
Merit Medical Systems recently announced the enrolment of the first patients in its Wrapsody arteriovenous (AV) access efficacy pivotal (WAVE) study of the Wrapsody endovascular stent graft, an investigational device being studied for the treatment of stenosis or occlusion within dialysis outflow circuits. Jeffrey Hoggard (RAC Surgery Center, Raleigh, USA) successfully enrolled the first two subjects with venous outflow peripheral lesions.
“We are pleased to announce the first subjects enrolled into the Merit Medical WAVE study. Stent grafts have a proven track record in dialysis AV access, and we are excited to evaluate the Wrapsody stent fraft in our patients for this clinical trial,” said Hoggard.
Over two million patients with kidney disease worldwide receive haemodialysis. Preferred long-term vascular access in these patients is generally achieved by the surgical creation of an arteriovenous fistula (AVF) or implantation of an arteriovenous graft (AVG). Vascular access circuit dysfunction is a common complication over time in AVFs and AVGs, accounting for 20% of hospitalizations in end-stage renal disease patients. Stenosis or occlusion of these vascular access circuits is most common in the venous outflow segment.
The Wrapsody endovascular stent graft is an investigational device with an expandable nitinol stent frame fully enveloped by an external layer of expanded polytetrafluoroethylene (ePTFE) and an internal layer of spun PTFE with an interposed non-porous fluoropolymer bonding layer.
The multicentre WAVE study comparing the Merit Wrapsody endovascular stent graft to percutaneous transluminal angioplasty (PTA) for treatment of venous outflow circuit stenosis or occlusion in haemodialysis patients plans to enrol 357 patients across multiple sites in the United States, Europe, Canada, and New Zealand. The study has been designed to include a population of 244 patients with AVFs and 113 with AVGs. Merit intends to randomize treatment in patients with AVFs to the Wrapsody stent graft or PTA and follow study subjects for two years postprocedure.
The WAVE study follows successful completion of the Wrapsody FIRST feasibility study which included 46 patients in Europe. The Wrapsody system previously received the CE mark and complements other vascular access products distributed by Merit, including the Hero graft and the Surfacer inside-out access catheter system.
Former Editor of the Journal of Vascular and Interventional Radiology (JVIR) Ziv Haskal (University of Virginia, Charlottesville, USA) has started a petition calling for his interventional radiology (IR) colleagues to pledge to help get their patients vaccinated against COVID-19.
In full, the petition reads: “As interventional radiologists, we see many patients in our clinic who are, by pre-existing conditions, eligible for COVID-19 vaccinations, yet many or most seem unaware or do not know how to seek vaccinations in this turbulent time of vaccine distribution. We have the ability to make every single one of our clinic patients aware of this with counselling at every clinic visit.
“Once you start asking your outpatients about their and their eligible family members vaccine status—prepare to be amazed by how many patients lack the information—or urging to actively seek it—that they need.”
Speaking directly to Interventional News, Haskal explains his motivations for starting this petition. He says, “In the last few weeks of holding my outpatient interventional radiology clinic, I asked every one of my patients if they, or their significant others, had been vaccinated—they are all current candidates due to their underlying conditions or age. With rare exception, the answer was disappointingly low. Patients expressed a desire to be vaccinated but had little idea where to begin and stated that they were waiting to be contacted.
“As endovascular specialists and interventional radiologists, we have first-hand contact with our patients and can help reinforce the message and counsel them about their vaccine candidacy and how to move forward and get vaccinated now.
“I am hoping this campaign will raise awareness so that we can all help our patients step forward, and provide them with the local expertise in how and where to get booked for vaccines appointment today.”
Sharing the petition on Twitter, Haskal put: “Interventional radiologists worldwide: Pledge to counsel & help [get] all our clinic patients COVID vaccinated—fill the gap! Retweet #IRVAX Sign the petition! Act Today.” He is using the hashtag #IRVAX to spread the message on social media.
The petition can be found here.
Humacyte has announced that the clinical results of five-year outcomes in patients receiving the human acellular vessels (HAV) for arteriovenous (AV) access in haemodialysis have been accepted for oral presentation at the Charing Cross (CX) Symposium (19–22 April, online).
On 17 February 2021, Alpha Healthcare Acquisition Corp, a special purpose acquisition company, and Humacyte announced the execution of a definitive business combination agreement along with a fully committed US$175 million PIPE financing agreement.
The presentation will include five-year outcomes on patients who completed the prospective Phase 2 trial and continued routine dialysis utilising the HAV for access to the bloodstream. The results are supportive of Humacyte’s ongoing development program in AV access which includes a Phase 3 trial in AV access to enable haemodialysis in which patients are randomized to receive either an HAV or an autogenous fistula, the current standard of care.
The details of the presentation are as follows:
Title: Update on bioengineered grafts for vascular access
Date / time: Tuesday 20 April, 14:00–19:30 GMT (9:00–14:30 ET)
Presenting author: Jeffrey Lawson, chief surgical officer, Humacyte
The CX Symposium is the leading global vascular symposium that brings together more than 4,000 vascular specialists from nearly 80 countries to discuss vascular and endovascular controversies. For more information, visit www.cxsymposium.com.
To mark the 20-year anniversary of drug-coated balloons, Bruno Scheller (Homburg/Saar, Germany) and Gunnar Tepe (Rosenheim, Germany), talk to Vascular News about their contributions to the birth and evolution of these devices.
Scheller discusses his work in the 1990s with Ulrich Speck (Berlin, Germany) in the field of contrast media and the early use of paclitaxel, noting that, coupled with the contrast medium, it led to a “long-term biological effect”. However, the problem with the contrast media approach was that “it was not really lesion-specific” in relation to local drug delivery.
Data from early animal testing and first clinical trials, using balloons coated with contrast media and paclitaxel, elicited “strong opposition” from the scientific community, says Scheller. Nevertheless, the researchers were convinced about what they were doing and continued to establish high-quality clinical research. Scheller recalls the unblinding of the first-in-man trial, the PACCOCATH-ISR as “an extremely good moment” because it provided proof that the research direction that had been viewed with scepticism and described “crazy” was “exactly the right way”.
Tepe, who also collaborated with Scheller and Speck in the early days of DCBs, talks about some of the difficulties the researchers encountered in gathering support for the idea. He highlights the THUNDER trial–which examined DCB versus plain balloon angioplasty for the treatment of femoropopliteal artery disease–noting that “expectations for success were really low”.
When he saw the first images of the patients who received drug-coated balloons Tepe was “astonished” because “we could see something different here”. Tepe further outlines his experience presenting the data to a packed auditorium, adding that soon “people started to believe” the results and that ultimately “we could prove that these drug-coated balloons were safe and effective in all patients”.
Tepe alludes to the fact that the involvement of Invatec, that was later acquired by Medtronic, was key to transforming the first home-made balloons into devices that could be widely used in patients and backed by long-term level one evidence. “Only with this support”, says Tepe, “we could prove that these drug-coated balloons are safe and effective in all patients”, adding “we could bring something new and something different to the patients”.
This video is sponsored by Medtronic.
Episode 2: Are all peripheral drug-coated balloons created equal?
EPISODE 3: The unique recipe for long-term clinical benefit with IN.PACT™ Admiral™ DCB
Episode 4: Real world data show IN.PACT Admiral DCB is “very efficient” even in complex lesions
COMING SOON
Episode 5: The impact of long-term DCB outcomes on patients’ quality of life
The Royal College of Radiologists (RCR) has called for a fully-costed, long-term funding package to safeguard the future of National Health Service (NHS) radiology and oncology. The calls follow the release of the UK government’s annual Budget, which was predominantly concerned with measures aimed at boosting the UK’s post-coronavirus economic recovery.
The Treasury’s previous Spending Review announced a one-year settlement for the NHS, which included a fund for tackling coronavirus backlogs and £325 million to upgrade aging imaging equipment, and was welcomed by the RCR.
Responding to this most recent budget statement, RCR president Jeanette Dickson said: “Following the autumn spending review—which did grant some welcome funding for parts of the health service—this budget understandably centred on ongoing economic safeguards and stimuli.
“However, the long-term needs of the NHS cannot be ignored forever. The backlogs and delivery challenges caused by coronavirus continue to impact hospital patients and the services that treat them. This statement could have been an opportunity to give much-needed, additional relief to a very tired NHS.
“Imaging and cancer teams are working through recent backlogs but demand only goes in one direction. Even before the immense pressures of COVID-19, the UK radiologist workforce was understaffed by 33%, and the clinical oncology workforce by 19%. There is only so much our stretched medical specialties can do without more resources.
“Treatment waiting lists are now at a record high, and millions of those patients waiting will need some form of radiological diagnosis or treatment.
“At the end of last year, more than 72,000 patients in England were waiting six weeks or more for a CT or MRI scan7, and the most recent COVID-19 winter surge will be hitting waits further.
“Tens of thousands of cancer cases potentially went undiagnosed last year, and front line cancer teams across the UK are telling us that they are seeing more patients presenting with later stage, often less curable cancers.
“To tackle these ongoing care demands, protect against endemic surges of COVID-19, and ensure we can give future patients the high-quality imaging and cancer treatment they deserve, we must have a fully-costed, sustainable funding package from the UK Government that deliberately addresses the equipment, IT and, crucially, workforce needs across NHS radiology and oncology.
“We will work hard over coming months to engage with NHS leaders and training colleagues, and vigorously champion these fundamental long-term priorities ahead of the Treasury’s comprehensive spending round anticipated later this year.”
Our top 10 stories of February 2021: a success story for interventional oncology as intra-arterial delivery of chemotherapeutic agents is shown to improve survival, and a new trial investigating combined radioembolization and immunotherapy for hepatocellular carcinoma (HCC) treatment launches; the vascular community gears up for paclitaxel discussions at the 20–21 Charing Cross Symposium (CX; 1922 April, virtual); and various devices cleared by the US Food and Drug Administration (FDA).
The use of intra-arterial delivery for the treatment of malignant brain tumours is safe and provides clinical benefits in terms of survival when used with the appropriate therapeutic agents, according to a small phase II study presented at the virtual European Conference on Interventional Oncology (ECIO; 24 February, online). Delivering these results, Gérald Gahide (Sherbrooke University Hospital, Sherbrooke, Quebec, Canada) told delegates that while the present study demonstrated the technical feasibility and safety of this application, “there is a dire need for designing multicentre, prospective, phase III studies to properly compare intra-arterial and intravenous treatments”.
The National Institute for Health and Care Excellence (NICE) has issued guidance recommending the use of selective internal radiation therapy (SIRT) for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, with more than 6,400 cases diagnosed annually through the National Health Service (NHS) in England, Wales, and Northern Ireland.
One-year outcomes of patients with chronic-limb threatening ischaemia (CLTI) treated in an outpatient-based vascular limb salvage clinic show an improved rate of major amputation. Authors Andrew Nickinson (University of Leicester, Leicester, UK) and colleagues write in an online European Journal of Vascular and Endovascular Surgery (EJVES) article that their study supports the recommendations of the Global Vascular Guidelines and “provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting”.
An FDA advisory panel has recommended against premarket approval of BD’s Lutonix 014 drug-coated balloon (DCB) for use in below-the-knee (BTK) arteries. In a meeting on 17 February, the majority of the FDA Cardiovascular Devices Panel concluded that the device was likely safe in BTK arteries, but not effective. The benefit-risk ratio also did not appear favourable for the Lutonix 014 DCB, it claimed.
Andrew Holden (Auckland City Hospital; University of Auckland, Auckland, New Zealand) speaks to Interventional News ahead of this year’s Charing Cross Symposium (CX), which is being held online 19–22 April. In 2021, the conference will focus on controversies within the vascular and endovascular space.
Terumo Corporation has signed a definitive agreement to acquire all assets of Health Outcomes Sciences, a specialist in predictive analytics and clinical decision support for healthcare organisations.
Access Vascular has announced US Food and Drug Administration (FDA) clearance of its HydroMID midline catheter.
The Society of Interventional Oncology (SIO) and Boston Scientific have announced a new multicentre, prospective, randomised trial to study combination therapy of radioembolization and immunotherapy in early and intermediate hepatocellular carcinoma (HCC) patients not eligible for curative treatments: ROWAN.
Rist Neurovascular recently announced that it has received FDA 510(k) clearance to market the Rist Cath Radial Access Long Sheath (Rist Cath) for the introduction of interventional devices into the peripheral, coronary, and neurovascular system.
Tobias Steinke (Düsseldorf, Germany), Matteo Tozzi (Varese, Italy) and Robert Shahverdyan (Hamburg, Germany) give their reactions to the publication in the New England Journal of Medicine of the IN.PACT AV Access clinical trial data, focusing on some of the key data as well as delving into how it has changed their practice and what impact the findings might have in terms of the quality of life for their patients. This video is sponsored by Medtronic.
ControlRad has announced US Food and Drug Administration (FDA) 510(k) clearance to market ControlRad Select, a technology that utilises proprietary semi-transparent filters, a user-interface tablet, and image processing algorithms to reduce radiation exposure during fluoroscopically guided procedures.
The technology is retrofitted onto customers’ existing Siemens Artis zee interventional imaging systems. In preparation for the commercialisation efforts, ControlRad has entered into an exclusive agreement with Boston Scientific to sell the ControlRad Select technology.
“With the FDA clearance and the reach of the global medical device sales team, every cath [catheterisation], EP [electrophysiology], and IR [interventional radiology] lab in the country that has a Siemens Artis zee will now have the opportunity to reduce their radiation dose by 85%1 without compromising image quality,” stated Guillaume Bailliard, CEO of ControlRad.
“The health risks to the medical staff due to lifetime radiation exposure in cath labs have been well documented, including increased incidence of cataracts, atherosclerosis and even left-brain tumours,” stated Simon Dixon, chief of cardiology at Beaumont Hospital, Royal Oak, USA. “We recently completed a clinical trial designed to evaluate how this novel technology might reduce radiation exposure in the cath lab. I have long been passionate about finding innovative ways to improve safety for my colleagues in the lab while they are performing lifesaving procedures for our patients.”
Medtronic has announced the launch of IN.PACT AV drug-coated balloon (DCB) in Japan. IN.PACT AV DCB is indicated for the treatment of obstructive lesions up to 100mm in length in the native arteriovenous (AV) dialysis fistulae in patients with end-stage renal disease (ESRD) undergoing haemodialysis. It is the first DCB to be approved in Japan for this vessel bed.
In Japan, IN.PACT AV DCB received regulatory approval on 23 September 2020 and it became eligible for health insurance reimbursement on 1 February 2021.
According to a press release, IN.PACT AV DCB has the potential to maintain AV access site patency, which can extend the time between reinterventions, therefore maximising a patient’s uninterrupted access to dialysis care has been needed.
In a global clinical trial, patients treated with IN.PACT AV DCB maintained target lesion primary patency longer and required 56% fewer reinterventions to maintain target lesion patency as compared to those treated with standard percutaneous transluminal angioplasty (PTA) through six months.
Mixed reality dose visualisation is expected to improve exposure dose management for interventional radiology (IR) patients and health professionals by depicting invisible radiation exposure in real space, a study published in Journal of Medical Systems reports. First author Takeshi Takata (Graduate School of Medical Care and Technology, Teikyo University, Tokyo, Japan), senior author Jun’ichi Kotoku (Graduate School of Medical Care and Technology, Central Radiology Division, Teikyo University, Tokyo, Japan) et al examined for the first time in the relevant literature the concept and feasibility of an immersive, real-time dose visualisation system using mixed reality for dose management.
Contextualising this research, the study authors write: “For interventional radiology, dose management has persisted as a crucially important issue to reduce radiation exposure to patients and medical staff.” Currently, IR patient dose management generally uses only a displayed dose area product, they continue, saying that this parameter does not identify the exposed position. “For that reason, a dose distribution on the patient’s skin cannot be managed,” they note. Similarly, despite measuring the radiation exposure of the health professionals involved in IR procedures with personal dosimeters, Takata and colleagues explain that the dose is unknown until the dosimeter is read out.
“To optimise exposure for all involved, health professionals must note their exposure dose in real-time according to each situation,” they claim. “An intuitive, real-time dose management system is expected to facilitate management of the dose and to improve patients’ and health professionals’ medical safety.”
Their mixed reality dose visualisation system uses a wearable mixed reality holographic device (Microsoft HoloLens; Microsoft). According to the investigators’ description, the HoloLens uses a simultaneous localisation and mapping algorithm for spatial mapping and detection of the wearer’s position, and provides an accurate three-dimensional holographic representation of digital objects with a full sense of depth. The objects can be viewed by a group of viewers simultaneously from all angles, enabling shared interaction. The display can be flipped up if it gets in the way.
“Projection of the patient’s skin dose onto the patient’s body and estimation of the health professional’s dose requires accurate tracking of their positions and movements in a room,” they explain. “Nonetheless, position tracking using an external tracking system is adversely affected by disturbances such as the movement of staff members and fluoroscopy systems during a procedure. Therefore, an object recognition tracking method is preferred for [our] mixed reality dose visualisation system.” Using a three-dimensional graphics platform and the object detection and tracking functionalities built into a software development kit, they were able to register images in real-time by tracking the relative position and orientation of the real objects using an RGB camera on HoloLens; this positional information was then used to update the transformations within the virtual world for dose projection and estimation. “The optical detection and tracking of a target are useful for real-time high-accuracy registration with no need for an external tracking system,” Takata et al write.
Although HoloLens is a stand-alone device, it lacks sufficient computational power to run the real-time dose simulation, they add. “Therefore, we separated computation of the visualisation and dose calculation, respectively, to HoloLens and an external server.” The patient skin dose distribution and operator eye lens dose were estimated using the Monte Carlo system on an external computer in real time. The estimated doses were transported sequentially to HoloLens and were projected in a real space.
A fast, accurate measure of dose and distribution
The number recognition system accurately recognised all displayed fluoroscopic conditions every 0.2 seconds. In addition, validation of the measured values of the sensor unit (judged based on a comparison with the laser sensor value) revealed that averages of the error were less than 0.18% in three directions between the mixed reality dose visualisation system sensors and the laser displacement sensor.
Average patient skin dose distribution was estimated within three seconds. The dose distribution was visualised with four seconds latency. Takata and colleagues describe how the dose distribution appears in practice: “It is depicted as coloured cubes on the skin. A colour bar shown in the air represents the absorbed dose level. The health professional’s eye lens dose rate was updated continuously. It was indicated as numerical values in the air. [The] mixed reality dose visualisation system has the following functions.”
This led them to conclude: “More than other real-time dose estimation systems for IR, this mixed reality dose visualisation system provides an immersive experience and a detailed depiction of the dose distribution. Although several visualisation systems can be used for dose distributions, our mixed reality dose visualisation system can visualise the dose distribution in three dimensions in front of the user’s eyes. This visualisation mode will help procedures proceed smoothly, because the surgeon need not look at a distant monitor to know the dose.”
The Zenith fenestrated+ endovascular graft (ZFEN+) product (Cook Medical) has received breakthrough device designation from the US Food and Drug Administration (FDA). This designation is granted for devices that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions.
While the product is not commercially available yet, it will now receive priority review, and Cook will engage in “interactive and timely communication” with the FDA during the clinical trial and premarket review phases. The ZFEN+ is the first product from Cook Medical to receive a breakthrough device designation.
The product is intended for use in the endovascular treatment of patients with aortic aneurysms for whom the graft seal zone requires fenestrations and involves one or more of the major visceral vessels: celiac artery, superior mesenteric artery, and/or renal arteries.
The Zenith fenestrated+ endovascular graft includes up to five fenestrations to accommodate the visceral vessels. Cook say in a press release that this extra customisation allows the graft “to be tailored to the patient’s unique anatomy and maximise the seal zone to exclude the aneurysm”. Cook is seeking investigational device exemption (IDE) approval in the coming months with the intention of beginning a pivotal clinical study later this year.
Contrast developer Guerbet has launched OptiProtect 3S, a new range of technical services for its contrast injectors.
OptiProtect 3S offers technical service and support for all Guerbet contrast injectors, ranging from preventive maintenance to equipment protection that includes service continuity. Servicing comes from a team of certified local experts, trained at Guerbet’s centres of excellence in either Lyons, France, or Cincinnati, USA, who renew their certifications every 24 months, Guerbet has said in a statement.
The use of intra-arterial delivery for the treatment of malignant brain tumours is safe and provides clinical benefits in terms of survival when used with the appropriate therapeutic agents, according to a small phase II study presented at the virtual European Conference on Interventional Oncology (ECIO; 24 February, online). Delivering these results, Gérald Gahide (Sherbrooke University Hospital, Sherbrooke, Quebec, Canada) told delegates that while the present study demonstrated the technical feasibility and safety of this application, “there is a dire need for designing multicentre, prospective, phase III studies to properly compare intra-arterial and intravenous treatments”.
Beginning his talk with reference to the “important” primary malignant cerebral nervous system tumours, Gahide explained that both glioblastomas and lymphomas are quite rare (with an incidence of 8.85 out of 100,000 and seven out of 1,000,000, respectively, of the adult population in the USA). Standard treatment for the former tumour is cytoreductive surgery, “meaning you remove as much of the tumour as possible without harming the patient—it is a debulking strategy, used in conjunction with complementary external beam radiation and chemotherapy (mostly with temozolomide)”. The median survival time is 14.6 months. Gahide told delegates: “Unfortunately, it is impossible to remove all of the tumour because it is a very infiltrated disease and relapse is the norm, and five-year survival is less than 10%”.
Commenting on the treatment of cerebral nervous system lymphoma, he said: “The only point that people agree on is that there should be high IV [intravenous] dose of methotrexate (3g/m2) during the induction, but as of today, there is no consensus regarding what other drugs to use for induction or consolidation.”
One of the main reasons explaining the poor prognosis and responses to treatment is the presence of the blood-brain barrier that presents “significant obstacles” to drug delivery, Gahide explained. The blood-brain barrier selectively transports substances into the brain, maintaining the right concentration of essential compounds and protecting the central nervous system from harmful substances. Typically, small (less than 180Da) and lipophilic molecules (oxygen, carbon dioxide, ethanol) diffuse freely and enter a normal blood-brain barrier. Larger hydrophilic molecules need an active transcellular transport to gain access to the central nervous system. According to reports in the literature, 98% of small drugs do not cross the blood-brain barrier.
“Because of these restrictive entities, the role of potentially active chemotherapeutic agents remains marginal in the treatment of malignant astrocytomas,” Gahide said.
Giving an example, he discussed the use of temozolomide in the treatment of primary brain tumours. The intratumoural concentration of the chemotherapeutic agent reaches “only” 20–30% of the serum concentration, he reported, and less than 10% of cerebral metastases reach 10% of the drug concentration measured in the other organs. “So how can we improve that?” he asked.
Intra-arterial drug delivery technique is “quite straightforward”
According to Gahide, the technique used for intra-arterial drug delivery is “quite straightforward”. His team take a femoral approach: “It is a conscious sedation,” he explained, “and we place a catheter in to the carotid or the vertebral artery, depending on the location of the tumour.” Angiography is used to confirm the position of the catheter and the integrity of the cerebral arteries. Patients must have a measurable disease on initial contrast-enhanced MRI scans, and a Kamofsky performance score >50. Chemotherapies are infused with an automated injector: carboplatin, 400mg/m2, 20cc/min; melphalan, 10mg/m2, 20cc/min. Treatment takes place every four weeks (representing one cycle) for up to 12 cycles after a systematic monthly MRI scan.
A history of intra-arterial delivery
In 1950, Calvin Klopp (George Washington University, Washington, DC, USA) reported the first intra-arterial delivery of chemotherapy for nine head and neck tumours, including one glioblastoma.
The rationality behind this approach is that you can increase the local plasma drug concentration via a first pass effect—Gahide noted that it has been demonstrated that you can increase the intratumoural concentration by up to 90% with this approach compared with systemic (IV) delivery.
In addition, despite Gahide recounting how early studies showed severe brain toxicity (including reports of encephalitis and brain necrosis) triggered by chemotherapeutic agents, he reassured the ECIO audience that “we now have a panel of drugs that have demonstrated their efficacy and their innocuity when used intra-arterially for brain tumours treatment.”
Osmotic blood-brain barrier disruption technique can increase intratumoural drug concentration to more than 300 times that of IV
Another way of circumventing the blood-brain barrier is to open it, Gahide said, introducing the concept of osmotic blood-brain barrier disruption (OBBBD). “In order to improve on the delivery obtained with IA [intra-arterial] infusion, the idea of osmotic manipulations for transiently opening the blood-brain barrier has been explored,” he said. “IA infusion of a hyperosmolar agent causes a rapid diffusion of fluid out of the cells, shrinkage of the endothelial cells, and widening of the tight-junctions. Of the many hypertonic solutions with potential to disrupt the blood-brain barrier, mannitol is the typical choice in both preclinical and clinical studies. This increase in blood-brain barrier permeabilisation is transient in the ipsilateral hemisphere and lasts from 30 minutes to two hours.”
Preclinical studies consistently showed higher intratumoural concentrations with OBBBD delivery compared to intra-arterial infusions or systemic administration. It has been reported in the literature that IA infusions with blood-brain barrier disruption increased the intratumoural concentration of carboplatin 18-fold compared with IA administration alone, and 320-fold compared with IV.
“We use it mostly for lymphomas and in young patients with recurrent glioblastomas,” Gahide commented. Patients must have a Kamofsky performance score >50, and the absence of a significant effect on MRI scan. The procedure is performed under general anaesthesia, unlike intra-arterial delivery alone, and Gahide describes how he and his team take a transfemoral approach to the main artery perfusing the tumour. The catheter is placed at the level of C2–C3 for the carotid circulation, and at the level of C3–C4 for the vertebral circulation. The interventionalists obtain angiographic confirmation of the position of the catheter and integrity of the cerebral arteries, and infuse mannitol at high flow for 30 seconds. A second angiogram is taken to ascertain vessel integrity, before chemotherapy is infused at a constant rate with an automated injector to prevent streaming. Like more traditional IA delivery, patients are treated every four weeks for 12 cycles.
Andrew Holden (Auckland City Hospital; University of Auckland, Auckland, New Zealand) speaks to Interventional News ahead of this year’s Charing Cross Symposium (CX), which is being held online 19–22 April. In 2021, the conference will focus on controversies within the vascular and endovascular space. paclitaxel
What can delegates expect from this year’s meeting in terms of understanding the paclitaxel controversy?
This year, we are focusing on controversies. While 2020 was clearly the year of the pandemic, those of us who are endovascular specialists remember 2019 as being the year of the paclitaxel controversy, provoked by a meta-analysis that was published just a month or so before the start of 2019 [in the Journal of the American Heart Association (JAHA) by Konstantinos Katsanos (University of Patras, Patras, Greece) et al]. While it is very import to take reports on safety very seriously, many of us were concerned for patients who, subsequent to this meta-analysis, were not receiving some of the profound benefits of paclitaxel-based anti-restenotic therapies in the lower limb arteries, drug-coated balloons and drug-eluting stents. Clearly, these paclitaxel eluting devices have shown superior patency with lower reintervention rates compared to standard treatment, sustained for many years. Because of that controversy, the use of these devices significantly decreased and there has been real interest in trying to assess if the paclitaxel safety issue was real or due to some other factors, such as trial design, trial patient numbers, and length of follow-up. With that in mind, there has been a huge effort to re-evaluate the data in terms of randomised controlled trials and real-world data, and I am delighted to say that a new meta-analysis with updated five-year data, sheds new light on the paclitaxel mortality issue.
If the paclitaxel mortality issue proves to be incorrect, we need to think about how we integrate paclitaxel into our current practice, and how the regulators in particular deal with this issue. This is important for the global vascular community, because paclitaxel-based products are such a vital component of offering state-of-the-art care for our lower-limb arterial occlusive patients.
I really look forward to joining you in the controversies sections at Charing Cross 2021.
One-year outcomes of patients with chronic-limb threatening ischaemia (CLTI) treated in an outpatient-based vascular limb salvage clinic show an improved rate of major amputation. Authors Andrew Nickinson (University of Leicester, Leicester, UK) and colleagues write in an online European Journal of Vascular and Endovascular Surgery (EJVES) article that their study supports the recommendations of the Global Vascular Guidelines and “provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting”.
While vascular limb salvage services are recommended by the Global Vascular Guidelines to help improve outcomes for patients with CLTI, the authors write that literature on the topic is limited. It was the aim of this study, therefore, to provide data on the effect of treating CLTI patients in an outpatient-based vascular limb salvage clinic on amputation outcomes.
The George Davies Research Group, based at the University of Leicester, undertook an analysis of a prospectively-maintained database, involving all consecutive patients diagnosed with CLTI within the Leicester Vascular Limb Salvage (VaLS) clinic from February 2018 to February 2019.
They compared data with two comparator cohorts, identified from coding data: 1) patients managed prior to the clinic, between May 2017 and February 2018 (Pre-Clinic [PC]); and 2) patients managed outside of clinic, between February 2018 and February 2019 (Alternative Pathways [AP]). Freedom from major amputation at 12 months was the primary outcome.
Writing in EJVES, Nickinson et al detail that 566 patients were included (median age 74 years) in the study. They report that patients managed within the VaLS cohort were statistically significantly more likely to be free from major amputation (90.5%) compared with both the AP (82.1%; adjusted hazard ratio [aHR] 0.52; 95% confidence interval [CI] 0.28–0.98; p=0.041) and the PC (80%; aHR 0.5; 95% CI 0.28–0.91; p=0.022) cohorts at 12 months, after adjustment for age, disease severity, anti-platelets/lipid lowering therapies and presence of diabetes.
Following the publication of these results, Nickinson spoke to Interventional News about their significance: “We are really excited about the publication of these results in the EJVES, the culmination of a great deal of effect by the whole team in Leicester. Our sincere thanks go to George Davies Charitable Trust, who’s generous donation has made the VaLS clinic a reality. Looking forward, a number of centres have now setup similar services across the UK and with the ongoing work of the Vascular Society’s PAD Quality Improvement Programme, it is great to see how interest is building across the UK in improving the outcomes for patients with CLTI.”
The National Institute for Health and Care Excellence (NICE) has issued guidance recommending the use of selective internal radiation therapy (SIRT) for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, with more than 6,400 cases diagnosed annually through the National Health Service (NHS) in England, Wales, and Northern Ireland.
The NICE website states: “After considering the feedback from consultation, the Appraisal Committee has prepared a Final Appraisal Determination (FAD) on Selective internal radiation therapies (SIRT) for treating hepatocellular carcinoma [ID1276] and submitted it to the Institute.”
This document includes recommendations for SIR-Spheres (Sirtex) and TheraSphere Y-90 glass microspheres (Boston Scientific).
Specifically, it reads:
“The SIRT SIR-Spheres is recommended as an option for treating unresectable advanced hepatocellular carcinoma (HCC) in adults, only if:
“The SIRT TheraSphere is recommended as an option for treating unresectable advanced hepatocellular carcinoma (HCC) in adults, only if:
The SIRT QuiremSpheres (Terumo) is not recommended, within its CE marking, for treating unresectable advanced HCC in adults.
SIRT can be used performed an outpatient procedure and typically does not require lengthy hospitalisation, with the potential to alleviate pressure on the NHS. Recent statistics from University College London suggest there could be an additional 18,000 cancer deaths in England due to the COVID-19 pandemic, which Boston Scientific and Sirtex say further highlights the importance for physicians and patients having access to new options.
At the virtual 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (12–15 September, online), positive results from the largest European-wide observational study on the treatment of primary and metastatic liver tumours with SIR-Spheres microspheres were presented, demonstrating the product’s safety and showing good overall survival from its 1,027-patient cohort for the first time.
“It is excellent news that NICE has recommended SIRT for the treatment of HCC,” comments Paul Ross, consultant medical oncologist at Guy’s & St. Thomas’ NHS Foundation Trust and clinical lead for HCC at King’s College Hospital (both London, UK). “The expanded options will advance the quality of life for patients and provide meaningful alternatives to existing treatments.”
“The British Liver Trust is delighted that NICE has now approved the use of SIRT as an option for treating unresectable advanced HCC in adults,” says Pamela Healy OBE, chief executive of the British Liver Trust. “HCC is the most common form of liver cancer. It is particularly aggressive and a diagnosis is devastating for patients, carers and their families. Treatment options for patients with advanced liver cancer have been very limited and this decision will make this innovative treatment more easily available and improve options for patients. Evidence shows that outcomes for people with advanced liver cancer are particularly poor so this is a very important step.”
As stated in a Boston Scientific press release, the outcomes of more than 100 clinical studies demonstrate the effectiveness of TheraSphere in improving tumour response across all stages of liver cancer, and in extending and improving the quality of life for patients globally. TheraSphere is a medical device consisting of radioactive yttrium-90 (Y-90) glass microspheres, which are delivered directly to liver tumours via a catheter, resulting in an increased tumour response while preserving surrounding healthy tissue.
Globally, more than 70,000 patients have been treated with TheraSphere, which has been approved for use as an HCC treatment option in 16 other countries. TheraSphere is also indicated for the treatment of metastatic colorectal cancer (mCRC) in patients who have failed second line treatment in the UK . The company plans to further investigate TheraSphere as a treatment for different cancer segments, including prostate and brain cancers.
In a recent meta-analysis, Yang Liu, Huan Lu (Henan Cancer Hospital, Zhengzhou, China), and colleagues found insufficient evidence to prove that inferior vena cava (IVC) filters can reduce pulmonary embolism (PE)-related mortality and overall mortality. However, they did find that IVC filters decrease the occurrence of PE without increasing deep venous thromboembolism (DVT) and major bleeding. Therefore, they conclude: “IVC filters should be considered after balancing the benefits and risks for the patients with contraindications to anticoagulant therapy of high risk for PE.”
Writing in the Journal of Vascular Surgery: Venous and Lymphatic Disorders, Liu, Lu, et al outline the scale of the issue at the core of their analysis: “Venous thromboembolism (VTE), which mainly presents as DVT and PE, is an important and potentially fatal disease with a high incidence and causes a huge burden.”
Considering treatment options, they write that, besides anticoagulation, the application of IVC filters is “commonly used” in patients with contraindications to anticoagulation therapy—for example, those who have been injured or who are at high risk of bleeding—or patients with a high risk of embolism occurrence. “However,” they write, “there is no clear consensus on the benefits and risks of IVCs from randomised controlled trials (RCTs)”.
Liu, Lu, and colleagues elaborate: “Systematic reviews have shown that IVC filters appear to reduce the incidence of subsequent PE, while appearing to increase the chance of DVT, and they have a limited effect on overall mortality. However, data in half of the included trials were not pooled into the effect size (odds ratio), which weakens the evidence of the conclusion.” Due to this lack of clarity on the subject, the researchers performed a systematic review and meta-analysis of RCTs with “more appropriate effect measures and more trials” in order to investigate the effect of IVC filters on PE-related mortality and complications.
The team searched PubMed and Cochrane libraries from inception to 31 October 2019 to identify RCTs for their meta-analysis. They detail that the primary outcome was mortality related to PE; secondary outcomes were overall mortality, occurrence of PE, DVT, and major bleeding.
Overall, the investigators included seven articles, comprising 1,274 patients, in their meta-analysis. They report that there was no significant difference in mortality related to PE between the IVC filter groups and the control group within three months (risk difference, -0.01; 95% confidence interval [CI], -0.03–0; p=0.11) and during the whole follow-up time with low heterogeneity (I2=0%).
However, they relay that the rates of new occurrence of PE within three months and during the whole follow-up period were lower in the IVC filter group than those in the control group (0.81% vs. 5.98%; risk ratio, 0.17; 95% CI, 0.04–0.65; p=0.01; 3.2% vs. 7.79%; risk ratio, 0.42; 95% CI, 0.25–0.71; p=0.0001, respectively).
Finally, Liu, Lu, et al communicate that there were no significant differences in the rates of new occurrence of DVT, major bleeding, and mortality rates during the whole follow-up period between the groups (p>0.05).
The authors acknowledge some limitations of the present study. They recognise, for example, that patients who were recruited in the included trials were “not completely consistent” regarding disease conditions and that performing subgroup analyses was limited because of the paucity of trials. Finally, they state that performance bias was a high risk, which was attributed to the “dramatic difference” in therapy between the two groups. “This made participants and personnel blinding from the intervention strategy impossible, and might have affected the outcomes to a certain extent,” they remark.
Looking forward, Liu, Lu, and colleagues suggest that large RCTs are required “to provide more robust evidence”.
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Tobias Steinke (Düsseldorf, Germany), Matteo Tozzi (Varese, Italy) and Robert Shahverdyan (Hamburg, Germany) give their reactions to the publication in the New England Journal of Medicine of the IN.PACT AV Access clinical trial data, focusing on some of the key data as well as delving into how it has changed their practice and what impact the findings might have in terms of the quality of life for their patients.
Steinke says he was “really impressed” by the results since “this is the only and first trial that met both safety and effectiveness end points”. He also states that the finding that the use of a drug-coated balloon (DCB) is “superior” to plain balloon angioplasty “really helps us for therapy decisions in our daily practice”, concluding that “we now have scientific proof to justify the use of the DCB.”
Tozzi highlights some of the key data points including the primary patency of the target lesion which was 24.5% higher in the DCB group (72.5%) than the PTA group (48.0%). He further adds that a big advantage with the use of DCBs is the lower number of reinterventions needed, concluding that there is “strong and incontrovertible evidence” that the “DCB must be the gold standard in the treatment of vascular access stenosis”.
Shahverdyan explains that the publication of the IN.PACT AV Access results in the NEJM “changed the way I decide to use balloon angioplasty”. He notes that this data now confirms “that you can and should use a DCB” in the first instance. Shahverdyan also suggests that patients will have “better quality of life” due to the reduction in hospitalisation.
This video is sponsored by Medtronic.
A US Food and Drug Administration (FDA) advisory panel has recommended against premarket approval of BD’s Lutonix 014 drug-coated balloon (DCB) for use in below-the-knee (BTK) arteries. In a meeting on 17 February, the majority of the FDA Cardiovascular Devices Panel concluded that the device was likely safe in BTK arteries, but not effective. The benefit-risk ratio also did not appear favourable for the Lutonix 014 DCB, it claimed.
Prior to the meeting, the FDA released an Executive Summary of the premarket approval application for the Lutonix 014 for the treatment of patients with critical limb ischaemia (CLI) who have obstructive de novo or non-stented restenotic lesions in native popliteal, tibial, and peroneal arteries up to 320mm in length and 2–4mm in diameter.
In the document, they detail results of the Lutonix BTK investigational device exemption (IDE) pivotal study on which they based their conclusions. This was a prospective, multicentre, 2:1 randomised controlled trial comparing the Lutonix 014 DCB (test group) to PTA (control group) for the treatment of BTK arteries. The study was terminated after enrolling 507 of the prespecified 840 vessels.
The FDA summarised the outcomes of the study: “The Lutonix 014 DCB met the non-inferiority primary safety endpoint at 30 days. The primary effectiveness endpoint results did not reach statistical significance, although a 10.5% improvement was noted at six months. However, a durable benefit was not seen at later timepoints, with the KM [Kaplan-Meier] curves converging at 12 months and primary effectiveness event rates favouring the PTA group thereafter.”
Looking in more detail at the benefits and risks, the FDA has not found any safety concerns with this device for this indication from the data provided: “To date, the FDA has not noted any safety concerns associated with the use of the Lutonix 014 DCB that would be expected to exceed those of current standard of care with non-drug containing devices. While a safety signal for increased mortality was noted for the use of paclitaxel-coated devices in the superficial femoral artery, this trend was not evidenced in the current study in the BTK anatomy.”
However, they express concern regarding effectiveness: “A modest benefit in regard to the primary effectiveness endpoint compared to PTA can be seen at six months, but a reversed outcome was noted at 12 months and beyond. Both prespecified and post hoc secondary endpoint effectiveness evaluations did not demonstrate a clear benefit of the Lutonix 014 DCB versus PTA.”
“Overall, the study was terminated early and did not meet the prespecified hypothesis test success criteria. It remains unclear whether the effectiveness differences at six months are clinically meaningful, and that the benefits of the paclitaxel-coated Lutonix DCB outweigh the risks compared to treatment with an uncoated balloon for treatment of atherosclerotic lesions below the knee,” they conclude.
Terumo Corporation has signed a definitive agreement to acquire all assets of Health Outcomes Sciences, a specialist in predictive analytics and clinical decision support for healthcare organisations.
“The acquisition of Health Outcomes Sciences and the ePRISM platform expands Terumo’s presence in the digital healthcare arena and represents a compelling growth opportunity for our company. It further allows Terumo to deliver innovative digital solutions, providing healthcare systems with critical data needed to lower the cost of healthcare delivery while substantially improving patient outcomes,” said Toshi Osada, president of Terumo Corporation’s Cardiac and Vascular Company.
ePRISM delivers a patient’s unique risks to physicians prior to treatment, based upon a calculation that includes their unique disease severity, co-morbidities and demographics. The use of validated predictive models in routine care has the capacity to improve the consistency, outcomes and cost-effectiveness of care across various cardiac procedures and care pathways, Terumo said in a press release.
“When combined with Terumo’s 100-year history and commitment to transforming global healthcare, our ePRISM technology will enable healthcare providers to deliver uniquely focused patient care; improving patient satisfaction, decreasing variability, optimising outcomes and minimising costs. This acquisition provides Terumo with a digital solutions platform that can be scaled globally across multiple healthcare segments,” said John Spertus, founder of Health Outcomes Sciences.
The acquisition is expected to close in February 2021. Following the close, the ePRISM platform will be integrated into Terumo Business Edge, a business unit of Terumo Medical Corporation.
Access Vascular has announced US Food and Drug Administration (FDA) clearance of its HydroMID midline catheter.
A press release from the company states that HydroMID, which is made of Access Vascular’s proprietary biomaterial that has been shown to reduce thrombus accumulation by up to 97% when compared to standard polyurethane catheters, is the second device in its planned portfolio to obtain clearance.
Midline catheters have grown in popularity due to inclusion in the MAGIC (Michigan appropriateness guide to intravenous catheters) guidelines, and the elimination of the need for confirmatory chest X-rays for midline placement. Standard midlines are composed of polyurethanes or silicones, which may lead to protein adsorption. This can result in thrombus accumulation or catheter-related infections.
HydroMID is a 4 French, single-lumen, midline catheter with a maximum usable length of 20cm. HydroMID will be made available over the next few weeks to gain clinical feedback on the usage of this midline catheter.
The company’s expansion into midlines enables healthcare professionals to choose either a midline or peripherally inserted central catheter made of this novel, thrombus-resistant biomaterial, depending on their needs. Midlines, intended for use of up to 30 days, have the advantage of a generally higher level of patient comfort when compared to peripheral intravenous catheters (IVs) due to a fewer number of restarts.5
The release of the midline also furthers the company’s plans to develop a portfolio of thrombus-resistant venous catheters and devices composed of its proprietary biomaterial to address the US$4.4 billion venous access market. The company’s first product—HydroPICC—was FDA-cleared last year and is currently rolling out commercially in the USA with the focus of obtaining real-world clinical data.
“FDA clearance for our second device demonstrates our commitment to a full product portfolio of venous access solutions and our commitment to help clinicians address the thrombus accumulation and catheter occlusion complications plaguing patients,” said Access Vascular CEO James Biggins. “I am proud of our entire team for securing clearance. We look forward to working with clinicians to integrate our devices into their workflow and better understand the benefits that we can bring to patient treatment and care.”
In response to the COVID-19 pandemic reducing medical student presence on clinical services and in classrooms, academic institutions are utilising a virtual format to continue medical student education, Daniel M DePietro (Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA) and colleagues write in Academic Radiology. Appraising this new form of medical education, the authors describe a successful virtual interventional radiology (IR) elective, and claim that this model “provides a framework for others to continue IR medical student education during the pandemic and grow the specialty’s presence within an increasingly virtual medical school curriculum”. They add that it may be modified to improve IR education beyond the COVID-19 era.
The team created a two-week virtual IR elective curriculum, utilising a combination of synchronous and asynchronous learning and a “flipped” classroom educational model. According to DePietro et al, students virtually participated in daily IR resident education conferences, resident-led case review sessions, and dedicated lectures. Asynchronous pre-learning material consisted of text and video correlating to lecture topics. All ten students who participated in the course completed an anonymous pre-course survey, and seven (70%) completed an anonymous post-course survey.
Enrolled students were considering residencies in surgery (50%), internal medicine (40%), interventional radiology (30%), and/or diagnostic radiology (30%). Students’ understanding of what interventional radiologists do and the procedures they perform (p<0.001), when to consult IR for assistance in patient management (p=0.005), and the number of IR procedures students could recall (p=0.015) improved after the course. Case-review sessions and virtual lectures ranked as having the highest education value. Students recommended additional small-group case workshops.
“While the core IR clinical experience comprised of hands-on procedures and patient-care cannot be replaced, the challenges of finding new ways to engage learners and showcase the scope of IR offers opportunities to positively reshape the future of IR medical student education,” the authors write. “The described experience demonstrates that a highly effective virtual IR elective can be created and implemented.”
While the virtual elective was created in response to restrictions imposed on in-person gatherings due to the COVID-19 pandemic, the authors believe it is the start of a trend towards remote or virtual learning. They state: “Interventional radiologists must leverage their ability to embrace technology in order to adapt to the increased emphasis on virtual learning in the wake of COVID-19. This successful initial experience with a virtual IR elective provides a framework for continuing IR medical student education during the pandemic and growing the specialty’s presence within an increasingly virtual medical school curriculum.”
They acknowledge some limitations to their study, notably the small cohort size. DePietro et al add that the generalisability of their institutional experience may be limited by the availability of adequate video conferencing software, ability of IR attendings and residents to participate in synchronous teaching sessions, and access to previously created educational content at other institutions. Furthermore, how participation in a virtual elective impacts student’s abilities to obtain letters of recommendation or impacts their application to IR residency was not evaluated. “Requests to participate in the elective were received from students from outside institutions, however, no institution-approved mechanism for participation of such students were in place during this initial experience,” they say.
Acute kidney injury is a common complication after intervention for peripheral arterial disease (PAD), and is associated with “medium-term mortality” following percutaneous transluminal angioplasty (PTA), a new study in the British Journal of Surgery (BJS) finds. Authored by Emmanuel Katsogridakis (National Institute for Health Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, UK) and colleagues, the paper concludes that while the present work makes evident the fact that the development of acute kidney injury is independently associated with medium-term mortality at two years, the observational nature of the study means the authors “cannot fully elucidate the pathophysiological mechanisms underlying this association”. They call for future research using relevant subclinical markers and mechanistic assessments to shed light on this.
Symptomatic PAD is frequently managed with PTA, particularly in patients with significant co-morbidities, including chronic kidney disease (CKD) and cardiovascular disease. These patients are at risk of developing acute kidney injury after PTA. Postprocedural AKI is not innocuous, the authors write, even for patients with a transient decline in renal function, as it is strongly associated with more complications and a higher financial burden for healthcare providers. As the incidence of, and risk factors for, acute kidney injury after endovascular intervention for PAD are unknown, the study investigators sought to assess the proportion of patients who develop acute kidney injury, and to explore the risk factors.
Their primary aim was to assess the incidence of acute kidney injury after PTA. The primary outcome was therefore the proportion of patients who developed acute kidney injury after PTA, using the Kidney Disease Improving Global Outcomes (KDIGO) reporting criteria. Secondary outcomes were the proportion of patients who died, underwent a major amputation, required dialysis within 90 days of intervention, remained dialysis-dependent after 90 days of intervention, or developed the major adverse kidney events (MAKE) endpoints—death, dialysis, and/or drop in estimated glomerular filtration rate of at least 25%—at 30 or 90 days (MAKE30 and MAKE90, respectively).
Katsogridakis et al prospectively collected and analysed data on 2,041 patients undergoing femoropopliteal endovascular intervention for symptomatic PAD (Rutherford stages III–VI) between 2014 and 2019 across three vascular centres.
Acute kidney injury developed in 239 patients (11.7%), with 47 (2.3%) requiring dialysis within 30 days, and 18 (0.9%) requiring ongoing dialysis. The MAKE30 and MAKE90 composite endpoints were reached in 358 (17.5%) and 449 (22%) patients respectively. Risk factors for acute kidney injury were age, sex, congestive heart failure, chronic limb-threatening ischaemia, emergency procedure, and pre-existing chronic kidney disease. Acute kidney injury, dementia, congestive heart failure, and major amputation were risk factors for medium-term mortality, the authors report.
Commenting on these findings, Katsogridakis and colleagues note: “The acute kidney injury-specific risk factors identified in this series are mostly non-modifiable. Older age, male sex, history of congestive heart failure, CLTI [chronic limb-threatening ischaemia], and preoperative renal function have all been associated with acute kidney injury development previously in a variety of clinical settings, and were strongly associated with acute kidney injury in this study. It is not surprising that these parameters are associated with acute kidney injury in patients with severe PAD. Alongside these findings, the absence of correlation between contrast volume and subsequent acute kidney injury in this series further confirms that acute kidney injury encompasses a plethora of other pathophysiological mechanisms, including perioperative volume depletion, nephrotoxicity, and renal microembolization. Efforts in the prevention of this complex and important complication of endovascular therapy, addressing high-risk groups (elderly, men, CLTI, CKD, and heart failure), are a priority.”
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The CLI Global Society is launching the first peer-reviewed academic journal focusing on interventional techniques pertaining to critical limb ischemia (CLI). The new journal, Journal of Critical Limb Ischemia, is launching in the spring of 2021.
According to the CLI Global Society, the goal of the journal is to provide an international forum for the presentation of original ideas and recent results related to all aspects of diagnostic, therapeutic, and pathophysiologic aspects of critical limb ischemia. These articles will likely substantially influence the clinical practice of treating the co-morbidities present in patients presenting with advanced disease, the society states.
Regarding the journal’s content, the society say that priority will be given to original research and on randomised trials and registry studies. In addition, it adds, pharmacological, diagnostic, and pathophysiological aspects of CLI will be given special attention in this online-only journal.
Secretary, treasurer, and co-founding member of the CLI Global Society Jihad Mustapha (Advanced Cardiac and Vascular Centers for Amputation Prevention and Michigan State University College of Human Medicine, Grand Rapids, USA) comments: “The first issue of CLI Global launched in November 2014 to help meet an unmet educational need in CLI. Over the years, the issue has provided data, tips and tricks, and case studies to CLI enthusiasts internationally. The CLI Global Society came into existence in January of 2016 adopting CLI Global as its official publication.
“Over the years, the society worked to bring together a multidisciplinary group of healthcare providers around the globe to discuss contributing factors that create challenges for CLI. Over the past six years we have seen increased awareness for CLI, development of more research in the field, and an increase in the number of dedicated CLI specialists.
“We have seen interest and growth in CLI educational opportunities such as the Amputation Prevention Symposium, which has more than doubled in attendance since the first issue of CLI Global was published.
“We have seen expansion of CLI care into the outpatient arena. I ponder why highly performing physicians who specialise in CLI leave large institutions to focus exclusively on CLI. I believe my story is like many. When we truly look at the CLI patient and the challenges they encounter, we realise the limitations in their care. It takes a very dedicated and passionate provider to work with the patient to coordinate care with their podiatrist, cardiologist, revascularisation specialist, infectious disease physician, nephrologist, and wound clinic. There is a cascade of care for the CLI patient that can start with entry into any one of the specialists listed. CLI is a chronically managed illness that is managed for the lifetime of the patient. And we know that the CLI patient’s prognosis is grimmer than most aggressive cancers. I find great reward in the complex care of CLI patients that require an intricate diagnostic workup, revascularisation, and post-revascularisation surveillance. Starting an outpatient CLI centre of excellence that focuses on leadership, best practices, research, and training all dedicated to CLI has been one of the most rewarding steps in my career.
“However, despite advances in care for CLI patients, we know there is still a long row to hoe. More attention to awareness, research, guidelines, and education must occur. The CLI Global Society board members and members of the society recognise this. With this last issue of CLI Global, the society is taking the next step forward to continue its mission. The society strives to improve quality of life by preventing amputations and death due to CLI by collaborating with like-minded organisations that share an interest in CLI to address treatment, outcomes, coding, and reimbursement to globally improve care.
“I am honoured to report the launch of a new peer-reviewed journal in 2021 that will focus exclusively on CLI. The Journal of Critical Limb Ischemia will bring to light original research from global experts on CLI in a format that will be available internationally. We encourage you to consider submission of your work where it will be reviewed by CLI experts who understand the complex nature of critical limb ischemia.”
There was no increased risk of long‐term, all‐cause mortality associated with paclitaxel-coated device (PCD) use among patients undergoing femoropopliteal peripheral endovascular intervention within the Veterans Health Administration (VHA). This is the conclusion of Jorge Antonio Gutierrez (Duke University Medical Center, Durham, USA) and colleagues, published ahead of print in the Journal of the American Heart Association (JAHA). Theirs was the first study examining the impact of PCD use on mortality with the VHA; they found that in more than 10,000 veterans with peripheral arterial disease (PAD) undergoing femoropopliteal intervention, the rates of two‐year and three‐year all‐cause mortality were similar among patients undergoing revascularisation with PCD (drug-coated balloons [DCB] and/or drug-eluting stents [DES]) and non‐PCD (percutaneous angioplasty balloon and/or bare metal stent) devices.
“The long‐term safety of PCDs for peripheral endovascular intervention is uncertain,” Gutierrez et al write. They therefore used data from the VHA to evaluate the association between PCDs, long‐term mortality, and cause of death, aiming to shed further light on the controversy first sparked in December 2018 by Konstantinos Katsanos (University of Patras, Patras, Greece) and colleagues, who reported in JAHA a potential association between increased mortality and PCD use in the leg.
In the present study, the investigators used the Veterans Administration Corporate Data Warehouse in conjunction with International Classification of Diseases, Tenth Revision (ICD‐10) Procedure Coding System, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes to identify patients with PAD treated within the Veterans Administration for femoropopliteal artery revascularisation between 1 October 2015 and 30 June 2019. An adjusted Cox regression, using stabilised inverse probability-weighted estimates, was used to evaluate the association between PCDs and long‐term survival. They also obtained cause of death data using the National Death Index.
In total, 10,505 patients underwent femoropopliteal peripheral endovascular intervention; 2,265 (21.6%) with a PCD and 8,240 (78.4%) with a non‐PCD (percutaneous angioplasty balloon and/or bare metal stent). Survival rates at two years (77.4% vs. 79.7%) and three years (70.7% vs. 71.8%) were similar between PCD and non‐PCD groups, respectively.
The adjusted hazard for all‐cause mortality for patients treated with a PCD versus non‐PCD was 1.06 (95% confidence interval [CI], 0.95–1.18; p=0.3013). Among patients who died between 1 October 2015 and 31 December 2017, the cause of death according to treatment group, PCD versus non‐PCD, was similar.
Gutierrez et al state: “All‐cause mortality risk related to exposure to PCD was no different when stratified according to claudication or chronic limb-threatening ischaemia (CLTI) presentations. […] After adjustment for treatment assignment, no statistically significant risk in all‐cause mortality was observed between the use of PCD and non‐PCD devices.”
“The endovascular community is now left with difficult decisions regarding when to use PCDs in clinical practice”
Before the reporting of a late mortality signal in the 2018 Katsanos et al meta‐analysis, PCDs were frequently used in femoropopliteal endovascular procedures, as they improved short‐term and intermediate‐term primary patency rates, Gutierrez and colleagues write. The late mortality signal was confirmed by a subsequent analysis from the US Food and Drug Administration of long‐term follow‐up data from pivotal premarket randomised trials for PCD, and most recently by an individual patient data meta‐analysis of US commercially available PCDs.
“However,” the authors of the present study explain, “limitations with these early studies have been recognised, including small sample sizes, substantial amounts of missing data, and poor patient follow‐up”.
They continue: “Nevertheless, PCDs now carry revised package labelling with information detailing the potential for late mortality. Globally, international clinical trials were initially halted (SWEDEPAD [Swedish drug‐elution trial in peripheral arterial disease] and BASIL‐3 [Bypass versus angioplasty in severe ischaemia of the leg]), and the UK Medical and Healthcare Products Regulatory Agency has advised against PCD use in intermittent claudication. The endovascular community is now left with difficult decisions regarding when to use PCDs in clinical practice, leading to wide variability in practice patterns. The Circulatory System Devices Panel and the US Food and Drug Administration acknowledge that additional clinical study data, particularly those evaluating long‐term safety of PCDs, are needed.”
FDA guidance “remains clear” amid developing situation, editorial concludes
An editorial on the new findings were simultaneously published ahead of print in JAHA. Douglas E Drachman and Joseph M Garasic (both Massachusetts General Hospital, Boston, USA) conclude in ‘Paclitaxel-coated devices: Safety and efficacy are in the PVI of the beholder’ that, “For now, the guidance from the [FDA] remains clear: reserve use of PCDs for anatomic and clinical situations where their efficacy may be most advantageous and where their risk is lowest, while participating in shared, individualised consideration of risk and benefit with our patients.”
Considering future directions, they add: “With a growing body of data, including randomised controlled assessments on the horizon, our understanding of the safety and efficacy of PCDs continues to evolve, as will our optimal interventional strategies for the care of patients with symptomatic lower-extremity [PAD].”
PatenSee has initiated a first-in-human clinical trial to assess its machine vision-based surveillance system, a press release from the company reveals. The trial, led by Benaya Rozen-zvi, director of the Institute for Nephrology and Hypertension at Rabin Medical Center (Petah Tikva, Israel), will evaluate the system’s ability to perform contact-free surveillance of fistula stenosis similar to a nurse’s physical exam of haemodialysis patients.
“The clinical data we collect will be the first of its kind and will provide a critical step towards a reliable contact-free early detection tool for fistula stenosis,” explained Rozen-zvi. “Keeping the fistula open is a major clinical need, and early detection of stenosis allows for both simpler treatment and better prognosis for the patient. The non-invasive, contactless nature of PatenSee’s system adds another important benefit for both inpatient settings as well as in homecare in the future. The ability to assess patients effectively at a distance has become particularly important for both patients and clinicians during the worldwide COVID-19 pandemic.”
“The trial initiation is a significant milestone for PatenSee,” said Gal Goshen, CEO of PatenSee. “We are excited to complete all bench testing required to bring the system to the clinical stage and look forward to providing a reliable early detection system for fistula stenosis that can save lives, reduce suffering, and address a challenge currently costing for payers and providers millions of dollars every year.”
The press release states that collaboration with the medical doctors and nurses involved in the trial enabled easy integration of PatenSee’s system into the patient workflow of the dialysis centre. The system is used in the pre-dialysis waiting room with minimal to no intervention of the medical staff and no interruption to the workflow.
One-year findings of the CONSEQUENT all-comers observational study of the paclitaxel drug-coated balloon (DCB) SeQuent Please OTW (B Braun) were reported at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online). Principal investigator Ralf Langhoff (Sankt Gertrauden Krankenhaus, Berlin, Germany) relayed low target lesion revascularisation (TLR) and mortality rates.
The prospective, multicentre study evaluates the safety and efficacy of the SeQuent Please OTW in the treatment of de novo and restenotic lesions in peripheral arteries above and below the knee. It includes a total of 784 patients and 879 lesions (almost one third TASC II C/ D lesions, 78.8% calcified and 44.6% occluded).
“We have represented real-world data in this all-comers registry,” said Langhoff. “Many registries are including mostly claudicants. But here, we had a really large group of CTLI [chronic limb-threatening ischaemia] patients—almost 50% had CLTI. Lesion length is also more challenging—13.3±9.3cm in the CLTI group and 10.8±9.1cm in the claudicant group. That is fairly realistic in terms of what we treat every day.”
Twelve-month findings include a TLR rate of 8.1% (CLTI patients, 6.3%; non-CLTI, 9.6%), a patency rate of 88.3% (CLTI, 89.9%; non-CLTI, 87.1%), and an all-cause mortality rate of 4.3% (CLTI, 7%; non-CLTI, 2%). Predictors for TLR included in-stent restenosis at baseline, lesion length, and female gender.
TLR rates were similar above and below the knee, commented Langhoff: “Restenosis rates are generally much higher in BTK [below-the-knee] arteries, but this was just not the case in the CONSEQUENT registry. This is another hint that the SeQuent Please OTW DCB seems to work in BTK arteries”.
The group also carried out additional analysis with respect to mortality in response to the findings of the 2018 meta-analysis by Katsanos et al: “We did not see any difference—as predicted—in all-cause mortality in terms of paclitaxel dose. This is only one-year data, but we didn’t see any correlation so far. Three- and five-year data will be collected and presented later.”
“Using an objective system that discriminates between aetiology and outcome allows a more complete, objective understanding of relative infection risks and outcomes for arteriovenous grafts (AVGs).” This is the conclusion of a review published online in The Journal of Vascular Access (JVA). Authors David Kingsmore (Queen Elizabeth University Hospital, Glasgow, UK) and colleagues suggest that such a system can inform discussions with patients requiring vascular access for haemodialysis.
The authors summarise that AVG infection was not found to be common, that it was caused by a systemic infection in only one-third of patients, did not lead to metastatic infection, and, “importantly,” was treatable without loss of access in one-half of all cases.
“The perception that AVG infection is frequent and severe is not based on contemporary data from large units using modern AVG,” the authors begin. Furthermore, they write that older reports “compounded misperceptions” by using non-standardised reporting that prevents easy comparison against the alternative modalities.
In their review, Kingsmore et al used a recently-published reporting scheme to analyse the frequency, management, and outcome of AVG infection in a large series of sequential early-cannulation AVGs with long-term follow-up. The aim was to assess the application and implications of a standardised reporting system for AVG infection.
The investigators performed a single-centre series analysis of 277 early-cannulation AVGs with a minimum of one-year follow-up. They note that infections relating to the AVG were classified, root-cause analysed, and the outcomes presented.
Writing in JVA, Kingsmore and colleagues report that 16% of all AVGs implanted, representing 51 episodes, developed infection related to the AVG. However, they also relay that more detailed analysis shows that this can be broken down into the following results: primary AVG infection (related to the insertion procedure or within 28 days) occurred in only 3% of AVGs assessed, or nine times; secondary AVG infection (related to AVG in use) occurred 33 times (rate 0.27/1,000) haemodialysis days), at a mean of 382 days; and tertiary AVG infection (in AVG no longer in use) occurred nine times. Finally, they add that only one-third of all AVG infections led to bacteraemia, and that one-half did not lead to loss of functional access.
“Our solution to the limitations of ethanol ablation is the polymer ethyl cellulose,” Erika Chelales (Center for Global Women’s Health Technologies, Duke University, Durham, USA) told delegates attending the abstract presentations at the 2021 meeting of the Society of Interventional Oncology (SIO; 3–6 February, online). In a radiologic-pathologic analysis of a novel ethanol gel formulation involving the ethyl cellulose polymer, Chelales and colleagues found that their newer technique was superior to traditional ethanol for percutaneous ablation in an ex vivo rat liver model.
Comparing a world map of hepatocellular carcinoma (HCC) mortality rates by region and one of human development index (HDI) rates, Chelales showed that countries with lower HDI have higher HCC mortality rates. “This means that the countries with the highest HCC burden have lower income and fewer resources available for treatment,” she commented.
“Many regions lack routine access to safe and affordable standard of care, and can therefore not access [Barcelona Clinic Liver Cancer] BCLC-defined curative treatment options like microwave ablation, radiofrequency ablation, and cryoablation,” she continued. “Unfortunately, ablative therapies are also not easily accessible or affordable in these settings. This is due to inadequate access to supplies, like thermal ablation systems or gas tanks for cryotherapy, as well as cost. Often, the only accessible and affordable ablative therapy in these settings is ethanol ablation.”
Ethanol induces cytosis through cell membrane and cytoplasm dehydration and the disruption and irreversible denaturation of intracellular proteins, resulting in coagulative necrosis. For HCC <3cm, ethanol has comparable five-year survival to RFA, and for HCC <1.5cm, ethanol has comparable overall survival to RFA. But, most importantly, according to Chelales, it is cheaper and more readily-available than RFA. “Although it is low cost, ethanol ablation is still not widely used, and this is due to its limited efficacy,” she said, before saying that its effectiveness is limited by non-target ablation from unpredictable ethanol leak. “Off-target effects result in poor tumour coverage, and then require the patient to return for multiple subsequent treatment sessions. A treatment paradigm involving multiple treatment sessions is not suited for low and middle income settings, where patients are often lost to follow-up.
“Our solution to the limitations of ethanol ablation is the polymer ethyl cellulose”. Ethyl cellulose is an ethanol-soluble but water-insoluble polymer, and induces a phase change from liquid to fibrous gel upon injection into tissue. In the presented study, the investigators sought to compare the spatial distribution of gel, ethanol, and liquid ethanol ablation, and the correspondence of each to the results of necrosis.
“Although we envision ultrasound-guided delivery for use in settings without access to imaging techniques with a large technical footprint, for these validations we used CT [computed tomography] imaging to examine the spatial distribution of ethanol in tissue. This is because ethanol has endogenous CT contrast (pure ethanol is significantly hypodense relative to water),” Chelales explained.
Exploiting the fact that there is a linear relationship between radiodensity and ethanol concentration, the investigators used a two-point calibration equation to provides them with a method of accurately converting radiodensity units from CT images to ethanol concentration in tissue.
They first used this method to determine the optimal gel ethanol formulation in ex vivo rat liver. They injected the target tissue with 100µl of either liquid ethanol or gel ethanol, at various concentrations (6%, 8%, 10%, 12%, or 15%) of the ethyl cellulose polymer at 10mL/hr (n=six). They acquired pre- and post-ablation CT images.
“The CT images show a larger region of low radiodensity corresponding to the injected ethanol in the gel ethanol group compared to the pure ethanol groups,” Chelales noted.
The research team next created maximum intensity projections “to show a clearer picture of cytotoxic ethanol concentrations within the tissue”. For the 12% ethyl cellulose ethanol group, the regions of high ethanol concentration were located centrally within the distribution block, while for the liquid ethanol group, regions of high ethanol concentration were dispersed throughout the tissue, indicating poor localisation.
The research team then quantified the total cytotoxic ethanol volume, and found that liquid ethanol and 12% ethyl cellulose ethanol yielded the smallest and greatest distributed volumes, respectively. They also examined the shape of the distribution by measuring the aspect ratio: a lower aspect ratio was indicative of a more localised distribution, which Chelales said is more desirable for ablation planning, and more comparable to standard-of-care treatment. She reported that all the gel ethanol groups had a better distribution than the liquid ethanol, “indicating improved localisation with the use of ethyl cellulose polymer”. 12% ethyl cellulose ethanol (ECE) yielded a significantly lower aspect ratio than liquid ethanol, and also a significantly greater distribution volume. “Therefore, we determined that 12% ECE was the optimal concentration for use in rat liver tissue,” she said.
Next, the investigators performed a radiologic-pathologic comparison of liquid ethanol (0% ECE) and gel ethanol (12% ECE) ablation in ex vivo rat liver. Post-ablation CT images again showed a larger area of low radiodensity, corresponding to the injected ethanol, for the gel ethanol group compared to the liquid ethanol group. Chelales et al then excised the liver 24 hours after the ablation procedure, and used a dye that would discriminately stain viable tissue over necrotic tissue. In the gel ethanol group, they observed a greater area of necrosis compared to the liquid ethanol.
“We quantified both the distribution and the necrotic volume, and found that both were significantly greater for gel ethanol compared to liquid ethanol ablation,” Chelales summarised. “Therefore, gel ethanol ablation achieves superior CT distribution volume, and increased target treatment. We calculated the average volume of the necrotic volume to ethanol distribution volume, to quantify the correspondence of the distribution as visualised on CT, and the ablative extent. This ratio is closer to one for gel ethanol than for liquid ethanol, although this was not statistically significant. This may indicate that CT imaging provides a more accurate depiction of necrosis for ethyl cellulose ethanol compared to pure ethanol, and a possible explanation for the necessity for the need for multiple treatment sessions with traditional ethanol ablation.
“We determined that 12% ECE achieves minimal leakage and optimal control, and have demonstrated the superiority of 12% ECE ablation to traditional ethanol ablation in an in vivo rat liver model. [As such], ECE is an injectable gel formulation of ethanol that holds promise as a reliable and lower-cost ablative option, and that, compared to thermal ablation, is envisioned to be faster, delivered through a smaller needle with a smaller technological footprint, and can avoid non-target thermal injury for precarious tumour locations.”
Chelales ended by saying that these positive results mean further studies should be conducted in larger animals, and said that the development of ultrasound-based treatment criteria for necrosis is needed.
Soundbite Medical Solutions has announced Health Canada approval for the SoundBite Crossing System – Peripheral (SCS-P) with the 0.014” Active Wire (14P).
The SCS-P (14P) is intended for the treatment of patients suffering from peripheral arterial disease (PAD) with heavily calcified above-the-knee (ATK) and below-the-knee (BTK) chronic total occlusions (CTOs).
“Expanding our technology and product portfolio in Canada is an important milestone for our company in the journey to commercialise the SoundBite system. This is welcome news on the back of our recent positive experience with the system in the EU. We are looking forward to making a positive impact on patients by providing a novel and safe solution around the world,” said Lori Chmura, president and CEO of SoundBite Medical.
The SCS-P 14P system comprises the SoundBite Console and the 0.014” SoundBite Active Wire. SCS-P leverages Soundbite’s proprietary method to produce and safely deliver shock waves via guidewire platforms to selectively ‘micro- jackhammer’ through calcified lesions. SBCS-P has CE mark and Health Canada approval in both 0.018” and 0.014’ platforms; the 0.018” platform has also US Food and Drug Administration (FDA) (510k) approval.
New clinical evidence for the use of the Luminor drug-coated balloon (DCB; Luminor) in complex lesions with long-term follow-up has been presented on the main session of the Leipzig Interventional Course 2021 (LINC; 25–29 January, online). These outcomes show Luminor DCB has “outstanding performance” in the most common peripheral lesions.
Evidence in femoropopliteal arteries: “Amazing” results from EffPac trial at three-and-a-half years follow-up
Ulf Teichgräber (Jena University, Jena, Germany), principal investigator of the EffPac Trial, explained during his presentation at LINC that at three-and-a-half years, a significant clinical and haemodynamic improvement was achieved, with an “amazing” target lesion restenosis (TLR) rate (freedom from TLR: 90.1%). He also remarked that no increased risk of death was detected, and that all-cause mortality was similar to plain balloon angioplasty. Luminor demonstrates “good” efficacy and safety outcomes, even at long-term follow-up, he said.
Evidence in complex and long femoropopliteal lesions: TINTIN trial two years follow-up
Investigating the performance of the Luminor DCB in complex and long femoropopliteal lesions, the newly-released two-year follow-up outcomes of the TINTIN trial corroborate the efficacy of the Luminor DCB. In lesions with a main length of 24.3cm, the combined therapy of Luminor and the iVolution self-expanding stent obtained a primary patency of 90.5% at one-year, and freedom from TLR of 89.4% at two years. Koen Deloose (AZ Sint Blasius, Dendermonde, Belgium), principal investigator of the trial, stated that: “The combination of vessel preparation, DCB, and self-expanding stent is the key to success in real life lesion treatment”.
Endovascular stimulator company CATHI has launched a campaign promoting CATHIS Smart, its portable system, to medical technology and pharmaceutical companies. The system displays all types of endovascular intervention in any medical field, and is designed for neuroradiology, cardiology, radiology, angiology, and pneumology training.
CATHIS Smart is the size of a laptop, and can be customised to individual user needs, such as being set up with specific devices or instruments.
According to CATHI, the system enables sales teams to give “simplified yet high-definition demonstrations of complex products to their customers”. Their company press release states that sales teams can “quickly learn simple-to-follow step-by-step procedures to gain a basic understanding of vessel anatomy, plus the handling of instruments or devices”. CATHIS Smart can also be used by engineers as a tool for aiding product design by facilitating visualisation and the extrapolation of ideas, as well as factoring in ease of operation and a positive user experience.
Users of CATHIS Smart can jump directly to specific steps within the workflow, which the company say is useful for educational purposes.
“Simulators are essential items of equipment for the cath lab, both for initial training and maintaining vital skills,” says Andreas Götte, head of Cardiology at the St Vincenz Hospital, Paderborn, Germany. “But to be effective they must resemble ‘real life’ clinical practice: we must see the coronary artery as it really is, being able to manipulate guide wires as well as catheters and balloons.”
The CATHIS Smart simulator is supported by a range of hardware including a control unit, notebook, and foot pedal.
The sustained release of anthracyclines and durable embolization from LifePearl microspheres (Terumo Europe) makes transarterial chemoembolization (TACE) with these embolic agents a safe and effective treatment option for patients with early and intermediate stage hepatocellular carcinoma (HCC). This was the conclusion presented by Filipe Veloso Gomes (Hepato-biliary-pancreatic and Transplant Center, Hospital Curry Cabral, Centro Hospitalar Universitario de Lisboa Central, Lisbon, Portugal) at the 2021 meeting of the Society of Interventional Oncology (SIO; 3–5 February, online).
Today, TACE is indicated for the treatment of unresectable HCC, according to the latest European Society for Medical Oncology (ESMO) clinical practice guidelines, with level IA evidence for Barcelona Clinic Liver Cancer (BCLC) stage B tumours (intermediate stage tumours), and level IB evidence for tumours categorised as BCLC 0–A (early) stage. TACE is recommended for patients awaiting liver transplants.
Veloso Gomes and his colleagues set out to assess contemporary interventional oncology practice in HCC, and conducted a pooled analysis of patient-level data from more than 550 patients with this liver cancer, enrolled across five different single arm studies and treated with anthracyclines-loaded LifePearl.
Safety was assessed by close monitoring of adverse events, according to the Common Terminology Criteria for Adverse Events (CTCAE). Tumour response was evaluated following hospital practice, according to mRECIST (modified Response Evaluation Criteria In Solid Tumours; used in four studies) and RECIST1.1 (in one study) and analysed as best overall response. Kaplan-Meier analysis was used to estimate event rates for time to event outcomes: progression-free survival, time to un-TACE-able progression, and overall survival.
Of the 586 patients included in the study, 57% were in BCLC 0/A stage, which the presenter said “clearly demonstrates the indication for TACE in a wide spectrum of patients”.
Adverse events were reported in 197 (33.6%) patients; the majority of these (23.3% of all patients) were grade 3. A further 2.3% were grade 4, and 1.5% were grade 5. The most frequent adverse events were related to post-embolization syndrome. Hepatobiliary toxicities were detected in 6.9% of all patients. Veloso Gomes therefore told SIO delegates that there was “a good tolerability and acceptable toxicity” of TACE with LifePearl.
In addition, he commented: “Hepatobiliary toxicities as [assessed by] imaging findings were lower than with other drug-eluting microsphere TACE [procedures] and similar to conventional TACE studies.” He specifically mentioned the recently published, prospective PARIS registry in his talk, which reported a higher hepatobiliary toxicity of 12.9% (in 30 of 233 procedures). Veloso Gomes noted that this 12.9% toxicity rate was still lower than that published in the literature from previous studies of drug-eluting microsphere TACE, and was more comparable to the rate seen in conventional TACE (cTACE) procedures.
He continued: “There was a high tumour response rate [in the pooled analysis that was the key focus of his presentation] that translated into promising progression-free survival, time to un-TACE-able progression, and overall survival. The overall survival observed in this analysis is among the best overall survival observed in recent TACE trials and meta-analyses.”
The presenter also cited some limitations to their methodology, which boil down to the fact that this pooled analysis was not planned prior to conducting the individual studies. Therefore, he said that there was heterogeneity in the populations enrolled, as well as differences in the recording of variables, including frequency, timing, type of imaging, and follow-up duration.
The Society of Interventional Oncology (SIO) and Boston Scientific have announced a new multicentre, prospective, randomised trial to study combination therapy of radioembolization and immunotherapy in early and intermediate hepatocellular carcinoma (HCC) patients not eligible for curative treatments: ROWAN.
Led by investigators Beau Toskich (Mayo Clinic Florida, USA) and Aiwu Ruth He (Georgetown University Lombardi Comprehensive Cancer Center, USA), ROWAN will evaluate the safety and efficacy of TheraSphere Y-90 glass microspheres (Boston Scientific) administered before initiation of durvalumab with tremelimumab compared to treatment of TheraSPhere alone. The study will assess local tumour control, progression-free survival, and the effect of TheraSphere radiation dosimetry on immune response.
Patient enrollment will begin later this year.
Our top 10 stories of January 2021: musings on ethical decision-making during the COVID-19 pandemic, a reflection on the status and future of paediatric interventional radiology, further developments in the ongoing discussion concerning paclitaxel-device use in the peripheral arteries, the future of radioembolization, and new device indications.
In an effort to raise the profile of paediatric interventional radiology (PIR), CVIR Endovascular Editor-in-Chief Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands) invited Alex Barnacle (Great Ormond Street Hospital, London, UK) and Anne Marie Cahill (The Children’s Hospital of Philadelphia, Philadelphia, USA) to guest edit the journal’s first thematic series on the topic.
Following the publication of the SWEDEPAD interim analysis, Andrew Farb, Misti Malone, and William H Maisel, representatives of the Center for Devices and Radiological Health, US Food and Drug Administration (FDA), authored a perspective piece in the New England Journal of Medicine (NEJM), titled, “Drug-coated devices for peripheral arterial disease [PAD]”.
The European Trainee Forum of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Residents, Fellows, and Students section of the Society of Interventional Radiology (SIR), the Society of African Interventional Radiology & Endovascular Therapy (SAFIRE), and Road2IR—a collaborative effort between several partner institutions aiming to build self-sustaining interventional radiology (IR) training programmes in East Africa—published an open letter to the World Health Organisation (WHO) this month in CVIR Endovascular, calling for an increase in the efforts to understand the needs of low income countries regarding image-guided therapies.
Data from the EXRACT-PE trial, published online first in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions, found that the Indigo Aspiration system (Penumbra) met its predefined safety and efficacy endpoints for the treatment of pulmonary embolism (PE). In this multicentre, prospective study, the Indigo aspiration system was associated with a significant reduction in the right ventricular-to-left ventricular (RV/LV) ratio and a low major adverse event rate in submassive PE patients. Intraprocedural thrombolytic drugs were avoided in 98.3% of patients.
VasQ, a high haemocompatibility biosynthetic vascular device from Laminate Medical Technologies, could be protective against the haemodynamic modifications that occur during arteriovenous fistulae (AVF) creation, a recent article in The Journal of Vascular Access reports. Roberto Palumbo (Saint Eugenio Hospital, Rome, Italy) and co-authors caution that their results, which derive from their clinical experience and are thus representative of a “real-life setting”, should be considered preliminary. They call for further research of the VasQ device in AVF creation, and say that “further effective treatments are needed to prevent or treat AVF failure”.
Personalised treatment selection and planning based on controlled dosimetry will lead to improvements in treatment accuracy. This is the conclusion presented by Marnix Lam (University Medical Center Utrecht, Utrecht, The Netherlands) at ECIO Virtual (27 January, online), a series of afternoon webinars that the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) is hosting in lieu of the 2020 European Conference on Interventional Oncology (ECIO). Lam spoke on the differences between Yttrium-90 (Y-90) and Holmium-166 (Ho-166) radioembolization, and told delegates that it was “very important” to ensure interventionalists conduct a “good” scout procedure with control over selection and planning.
The US Food and Drug Administration (FDA) has granted premarket approval (PMA) for the Woven EndoBridge (WEB) 17 system from MicroVention, a US-based subsidiary of Terumo. This is a new addition to the WEB aneurysm embolization system for the treatment of intracranial wide-neck bifurcation aneurysms.
The US Food and Drug Administration (FDA) has granted Pedra Technology a breakthrough device designation for the periprocedural use of the company’s Pedra Xauron perfusion system in the treatment of critical limb-threatening ischaemia (CLTI).
“Practicing ethical inquiry and reflection may mitigate the moral distress that can arise from ethical dilemmas,” write Michelle Shnayder-Adams, Eric J Keller, and Mina S Makary—and there have certainly been a number of emotionally-challenging ethical dilemmas for healthcare providers treating patients against the backdrop of the COVID-19 pandemic. The authors of this opinion piece discuss the intersection of medical ethics and interventional radiology (IR) amidst this crisis, and propose a framework interventionalists can use to enable decision-making when faced with multiple, conflicting moral obligations, which they say can cause stress and uncertainty.
New data presented for the first time at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online) are positive for the IN.PACT AV drug-coated balloon (DCB) and the Ellipsys vascular access system (both Medtronic). The IN.PACT AV Access study investigated the use of DCB angioplasty versus percutaneous transluminal angioplasty (PTA) for the treatment of dysfunctional arteriovenous fistulas (AVFs). In a second presentation at the virtual congress, delegates were treated to a comparison of surgically-created versus percutaneously-created AVFs.
In a late-breaking trial session at LINC 2021 (The Leipzig Interventional Course, 25–29 January, online), key updates on below-the-knee (BTK) interventions were in the spotlight.
Francesco Liistro (Azienda Usl Toscana Sud Est, Arezzo, Italy) presented nine-month outcomes from the IN.PACT BTK randomised study. He revealed that the IN.PACT 014 BTK drug-coated balloon (DCB; Medtronic) demonstrates efficacy through nine months compared to percutaneous transluminal angioplasty (PTA) in a complex population.
The study was a prospective, multicentre, randomised (1:1) feasibility study. Fifty chronic limb-threatening ischaemia (CLTI) patients with infrapopliteal chronic total occlusions (CTOs) were enrolled at nine sites across five European countries and followed through 60 months.
Focusing on key eligibility criteria, Liistro told viewers that the “most challenging” lesions were purposefully included in the study, comprising single or multiple total occlusions with lesion lengths ≥40mm.
Focusing on nine-month angiographic outcomes, Liistro communicated that sub-segmental late lumen loss was 0.59±0.94 in the IN.PACT 014 DCB group, compared to 1.26±0.81 in the PTA group (p=0.017). In terms of classic late lumen loss, he informed viewers that this was 0.89±0.77 in the DCB group and 1.31±0.72 in the PTA group (p=0.07).
In addition, the presenter detailed that functional flow by duplex ultrasound (DUS) at nine months was 84.6% in the DCB group and 60.6% in the PTA group (0.341). Finally, he reported that 91.3% of patients reached the composite safety endpoint.
“This novel, randomised, feasibility study with a 014 BTK balloon utilising the 3.5μg/mm2 drug formulation and enhanced study design provides an opportunity to affect future BTK studies and treatment algorithms,” Liistro concluded.
ACOART II and ACOART BTK Italy studies support safety and efficacy of Litos DCB
Wei Guo (Chinese PLA General Hospital, Beijing, China) presented 24-month results of the multicentre, randomised ACOART II study. Addressing LINC viewers, Guo described ACOART II as the first randomised BTK trial in China, and—following on from ACOART I—further demonstrates the safety and efficacy of the Litos DCB (Acotec) for the treatment of BTK artery disease.
Regarding 24-month patency, Guo detailed that the rate of clinically-driven target lesion revascularisation (CD-TLR) was 10.3% in the DCB group (6/58) compared to 24.6% in the PTA group (14/57; p=0.042), the rate of wound healing was 90% in the DCB group (27/30) vs. 81.3% in the PTA group (26/32; p=0.342), and the rate of major amputation was 3.4% (2/58) vs. 1.8% (1/57) in the two groups, respectively (p=0.565).
Presenting 12-month results of the ACOART BTK Italy study, Liistro noted their similarity to those of the ACOART II study, and concluded that the Litos DCB “shows efficacy and safety in the treatment of complex BTK lesions in CLTI patients”.
“The strongest message for clinicians is the drastic reduction of reocclusion showed by the DCB in baseline occluded vessels,” he informed LINC viewers, adding that future studies should include only occluded vessels at baseline and that the primary endpoint of these studies should be reocclusion by DUS.
Luminor DCB yields “excellent” results out to 12 months
Also to present in the late-breaking session was Tjun Tang (Singapore General Hospital, Singapore), who outlined 12-month outcomes from the MERLION trial of the Luminor DCB (iVascular) in BTK lesions.
The MERLION trial assessed the treatment of long tibial occlusive lesions (TASC C and D) in CLTI patients, the presenter relayed. A total of 50 patients—94% with diabetes, 50% with end-stage renal failure, and 88% with a Rutherford score of either five or six—were included in the study. The cohort had a total of 66 atherosclerotic lesions with a mean lesion length of 13.7±9.5cm.
Tang reported a 100% technical success rate in conjunction with a low rate of bailout stenting (4.5%). Treatment with the Luminor DCB yielded “excellent” results, he stated, including no deaths within 30 days, and a 12-month amputation-free survival rate of 74%.
In addition, the Luminor DCB proved to be efficacious out to 12 months, with a 69% rate of target lesion primary patency and a 12-month freedom from TLR rate of 82%.
Finally, Tang communicated that wound closure was achieved in 66% of patients and that 60% of patients had improved by at least one Rutherford category at 12 months.
Use of limus-based devices highlighted in four late-breaking trials
Presenting results of the multicentre, dual-blinded, phase II, randomised controlled TANGO study, Ehrin Armstrong (University of Colorado, Aurora, USA) relayed that temsirolimus adventitial drug delivery has provided “robust outcomes” so far, and that a “sizeable effect” has been seen in more complex lesions with temsirolimus delivery.
Twelve-month results from the prospective, single-centre, physician-initiated PRESTIGE BTK study were also revealed. The objective of this clinical investigation has been to evaluate safety and performance outcomes of the SELUTION SLR novel sirolimus-eluting balloon (MedAlliance), for the treatment of long tibial occlusive lesions (TASC C and D) in patients with CLTI.
Presenter Tze Tec Chong (Singapore General Hospital, Singapore) announced that the primary patency rate was 78% and the rate of wound healing was 81%. In addition, freedom from target lesion revascularisation (TLR) was exhibited by 93% of patients and 84% demonstrated amputation free survival (AFS). All these figures have been sustained from the six-month data.
“We have observed minimal slow-flow phenomena and some cases of fast wound healing with SELUTION SLR. It is also easy to track and deliver. We are looking forward to gaining further clinical experience with this device,” commented Chong.
Marianne Brodmann (University of Graz, Graz, Austria) revealed results of the DEEPER LIMUS study—a pilot study examining the performance and safety of the limus-coated Temporary Spur stent system (Reflow Medical), which is for clinical investigational use only, in infrapopliteal arteries.
Broadmann stressed that the Temporary Spur stent system provides localised drug delivery, and may prevent acute vessel recoil and increase luminal gain. In addition, she relayed that the system reduced dissection risk through controlled penetration of the vessel wall, and leaves nothing behind, preserving the natural function of the vessel and allowing future treatment options.
The presenter summarised that there were now “promising” clinical data on the Temporary Spur stent system, not only from DEEPER LIMUS, but also from the DEEPER OUS and DEEPER studies.
Reporting outcomes from the multicentre, single-arm DEEPER OUS trial of the Temporary Spur stent system in conjunction with a commercially available paclitaxel-coated balloon, Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany) echoed the findings presented by Brodmann.
New data show potential of Limflow system to improve outcomes for no-option CLTI
“Deep vein arterialisation is safe and technically feasible,” stated Peter Schneider (University of California San Francisco, San Francisco, USA) in a presentation on 12-month data from the PROMISE I early feasibility study of the LimFlow system (LimFlow).
Schneider announced that limb salvage for patients with ‘no-option’ revascularisation was achievable in 77% of patients at 12 months, and concluded that lesion from this initial trial will be “incredibly valuable” moving forward. “We continue to gain insights into technical issues and methods to improve outcomes for these patients,” he stated.
Transit Scientific has announced the close of its Series A financing round. The round was led by a large multinational investor and joined by previous seed investors.
Transit Scientific achieved US Food and Drug Administration (FDA) clearances and multicentre, multi-user, safe-patient-use of its XO Score angioplasty scoring-cutting platform and separate XO Cross 0.014” and 0.035” microcatheter platform in late 2020.
“XO Score successfully dilated multiple lesions that were resistant to standard or high-pressure balloon angioplasty during our 1st patient uses in haemodialysis fistulas,” said Jeffrey Hoggard (Raleigh Access Center, Raleigh, USA). “It was particularly beneficial to be able to deploy the XO Score device with a standard percutaneous transluminal angioplasty (PTA) balloon in the juxta-anastomotic position and dilate the lesion at low and controlled inflation pressure.”
The XO Score is a novel sheath that converts regular angioplasty balloons into vessel prep scoring and cutting systems. The device is indicated for treatment of peripheral vascular stenosis including haemodialysis fistulas and grafts.
XO Score’s 22 individual scoring and cutting struts rotate 90 degrees to score and cut upon balloon inflation and then rotate 90 degrees back upon balloon deflation to facilitate balloon re-wrap. The technology also allows for infusion at the site of treatment.
“The XO Cross 014, 018, and 035 microcatheter platform adds new torque, pushability and catheter control,” said Richard Saxon (Tri-City Medical Center, Oceanside, USA. “We have used a 014 XO Cross to redirect the guidewire intraluminally while crossing a tibial artery chronic total occlusion (CTO). This would have been very difficult to achieve with other available technology.”
The XO Cross is a non-tapered exoskeleton based microcatheter technology designed to improve torque response, trackability, and control.
Biomodex has announced its partnership with two of the top medical centres in France and a health system in the USA to develop Evias Plus, a training solution for treatment of ischaemic stroke.
“Thrombectomies are very complex in nature and carry a high risk of complications. What is more, these procedures continue to evolve, given the development of new devices and approaches, requiring neuroradiologists to continually advance their skills,” said Francois Eugene, interventional neuroradiologist at the Centre Hospitalier Universitaire, Rennes, France, a partnering medical centre.
Anthony Le Bras, interventional neuroradiologist at the Centre Hospitalier Universitaire, Rennes, France, added, “Biomodex’s solution will not only enable physicians to stay up to date but will also accelerate training of fellows to help ensure we have enough physicians to support this rapidly expanding field.”
According to the company, Evias Plus offers an innovative approach for physician training, particularly fellowship programs. Biomodex adds that the solution for ischaemic stroke enables neurointerventionalists to simulate fluoroscopy-guided procedures in a real-life catheterisation laboratory environment. The company reports that the models come with several realistic, 3D printed blood vessel models or cartridges that plug into a station that simulates systemic flow using Biomodex Bloodsim to replicate blood density and viscosity and other key features include:
“Mechanical thrombectomy (MT) has revolutionised the neurological outcome of acute ischaemic stroke patients. Nonetheless, still a large proportion of eligible patients are not treated with MT because of a lack of physicians trained to perform this procedure in an emergency. We therefore have an urgent need to train more physicians to offer this treatment to more patients. This new simulation solution offers highly realistic navigation sensations with the possibility to switch within minutes from one anatomy to another,” said Raphael Blanc, co-chief interventional neuroradiologist at the Fondation Adolphe de Rothschild, Paris, France.
“Biomodex’s advanced training system is a significant improvement over traditional training approaches because the models are incredibly realistic and allow us to gain hands-on training for the manipulation of catheters under fluoroscopy. We can also practice navigating realistic aortic arch anatomies ranging from common to complex,” said Ajay Wakhloo, chief of interventional radiology at Beth Israel Lahey Health, Boston, USA.
Cardiovascular Systems (CSI) has partnered with Chansu Vascular Technologies (CVT) to develop novel peripheral and coronary everolimus drug-coated balloons (DCBs).
Under the terms of the agreements, CSI will provide milestone-based financing to CVT for the development of the DCBs. Under an acquisition option agreement, upon CVT’s completion of key technical and clinical milestones in the development programme, CSI will have exclusive rights and obligations to acquire CVT, subject to the satisfaction of closing conditions set forth in the agreement.
CVT, which is based in Sunnyvale, USA, develops peripheral and coronary DCBs using everolimus.
“The CVT DCBs will be designed to capitalise on the proven long-standing anti-restenotic benefits of everolimus for the treatment of patients with cardiovascular lesions,” comments CVT founder Philippe Marco in the company’s announcement. “This collaboration enables us to develop a new class of DCBs that we believe will improve patient outcomes.”
Ryan Egeland, chief medical officer of CSI, states: “This partnership is consistent with our strategic vision to develop an innovative portfolio of new products. We believe these next-generation DCBs will complement our current and growing portfolio of products for the treatment of complex coronary and peripheral disease. We are thrilled to be working with CVT in this partnership and are extremely confident that Dr Marco and his team’s extensive past DCB experience will prove invaluable in developing these next-generation DCBs.”
The Approach Authority Workhorse microwire guide (Cook Medical) is now commercially available in the USA and Canada.
Designed as an 0.018-inch diameter workhorse wire guide, Approach Authority can be used for multiple purposes in the same procedure.
A company press release states that Approach Authority combines “resilient” nitinol tip technology with a hydrophilic coating. This expands the options to physicians placing balloon dilatation catheters during percutaneous transluminal angioplasty (PTA) in peripheral arteries. Physicians can deliver a variety of devices across this wire to offer a broader range of treatment options for patients.
“Cook Medical is proud to introduce this wire to our customers in the USA and Canada. Wire guides have been used in interventions for decades, and we are still innovating,” comments Mark Breedlove, vice president of Cook Medical’s Vascular division.
Fluidx Medical Technology has announced that GPX Embolic Device first patient use cases were presented at LINC 2021 (25–29 January, online).
“This is very promising technology,” said Andrew Holden (Auckland City Hospital, Auckland, New Zealand), who presented the cases at LINC. “The very radiopaque GPX penetrates distally extremely well with excellent control and devascularised the renal tumour entirely.”
According to a Fluidx Medical Technology press release, GPX Embolic Device is an innovative embolic designed to combine the benefits of other embolics like coils, particles, and liquids with simplified preparation, delivery, precision, and control leading to durable, long-term occlusions. The GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolic material upon delivery, without polymerisation or dimethyl-sulfoxide (DMSO) precipitation associated with other embolics.
In the presentation, Holden showed cases in which GPX had successfully embolized the arterial vasculature of a renal angiomyolipoma and in another case, portal vein embolization in a patient with metastatic colon cancer. Of the latter case, Holden said the successful procedure “resulted in complete occlusion of the portal vein branches and excellent visualisation of the target site. At the six-week computed tomography (CT) scan, we can see the branch impact of the occlusion and the patient experienced good left lobe hypertrophy.”
GPX is packaged ready-to-use in a syringe, requires less than one minute of tableside preparation by the clinician, and may be delivered through standard catheters or microcatheters.
The German Institute for Hospital Remuneration (InEK) has renewed the new examination and treatment methods (NUB) Status 1 designation of VasQ external support (Laminate Medical Technologies) for 2021.
NUB Status 1 provides supplemental reimbursement for innovative medical devices that have the potential to improve the standard of care for patients. VasQ external support first received NUB Status 1 in 2017 with 35 participating hospitals and has since grown to 321 participating hospitals to date, which represents the second most among devices that serve the dialysis patient population.
The VasQ external support is implanted around the anastomosis during the creation of an arteriovenous fistula (AVF) to promote more usability without the need for the frequent additional procedures typically required for standard AVFs. AVFs created with the VasQ external support have reported in publications and presentations usability rates as high as 86% or better by six months in seven clinical studies. Growing clinical evidence in support of VasQ as well as the building momentum of usage in InEK calculating hospitals are critical components to support a permanent diagnosis-related group (DRG) code for reimbursement.
“My practice relies on VasQ as our standard of care for creating almost all of our forearm and upper arm surgical fistulas,” stated Robert Shahverdyan, head of Vascular Access Center Hamburg at Asklepios Klinik Barmbek (Hamburg, Germany). “The device has improved my fistula outcomes for my patients, and I am grateful for the NUB designation so my work with VasQ can continue with sufficient reimbursement to cover the additional costs of the device.”
The device is currently being implanted across Europe under a CE mark and has also completed enrolment in an investigational device exemption (IDE) pivotal clinical study to be evaluated by the US Food and Drug Administration (FDA) through the de novo pathway for use in the USA. The FDA has already awarded the device a breakthrough designation based on the breadth of clinical evidence collected so far for VasQ that consistently demonstrates improvement over the standard of care for AVF creation. The designation provides VasQ with the substantiation of clinical improvement required by the Centers for Medicare and Medicaid Services for providing additional reimbursement for new technologies once cleared for the US market.
Cagent Vascular announced the results of its PRELUDE-BTK study at LINC 2021 (25–29 January, online). The PRELUDE-BTK study was a prospective, single-arm, multicentre feasibility study to show the safety and efficacy of serration angioplasty.
The study was led by co-principal investigators, Andrew Holden (Auckland City Hospital, Auckland, New Zealand), who presented the data, and Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany). Four other centres from Europe participated in the trial which included 30-day and six-month follow-up.
According to a Cagent Vascular press release, the Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter is the first and only angioplasty balloon cleared by the US Food and Drug Administration (FDA) and CE marked that embeds serration technology into a semi-compliant balloon for treating peripheral arterial sisease (PAD). The device is designed to create multiple longitudinal lines of interrupted micro-serrations to aid arterial expansion.
Forty-six subjects were treated with the Serranator device and 53 lesions were analysed by the core lab. The average final residual stenosis was 21.8%, with an average below-the-knee (BTK) arterial lumen gain of 1.55mm. These results were achieved with a low average maximum atmospheric pressure of six atmospheres. The bailout stent rate was 1.9%. A subset of lesions (n=10) were imaged with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) and analysed by a core lab. All showed a serration effect. At 30 days, the freedom from primary safety events was 95.7%. The freedom from clinically-driven target lesion revascularisation (CD-TLR) was 97.7% with 70% of subjects achieving one or more Rutherford clinical category (RCC) improvement at six months. There were no serious adverse events related to the device.
“Today, we have insufficient data for effective lesion revascularisation in BTK arteries. Based on published plain balloon angioplasty data, especially in calcified lesions, more than 40% of the cases result in complex dissections and significant recoil phenomenon. This ultimately leads to scaffold implantation to stabilise the lumen and prevent diminished outflow. This revascularisation strategy is associated with poor patency outcomes,” stated Lichtenberg.
“The PRELUDE study clearly proved the hypothesis, that haemodynamic and morphologic success in BTK revascularisation is strongly associated with vessel compliance improvement. We need to concentrate first on this aspect, before we can discuss the need for longer-term restenosis prevention with antiproliferative substances. We know that dissections are directly associated with loss of patency and impaired wound healing. Prevention of dissections within a rigid, non-compliant vessel, along with luminal gain can only be successful with a vessel wall modification device that applies low atmospheres. The PRELUDE-BTK study clearly showed that the mechanism of action works well enough that it does not even need additional antiproliferative treatment, as CD-TLR was only 2.3% after six months,” continued Lichtenberg.
The Serranator product offering for the infrapopliteal indication is available in 2.5, 3, and 3.5mm balloon diameters and 40, 80, and 120mm balloon lengths. The company has initiated US and EU sales and plans to expand its commercial efforts later this year.
BD today announced that new clinical data have found robust evidence that using a vascular care solution can help improve outcomes for patients requiring peripheral intravenous catheters (PIVCs).
Results of the CLEAN3 trial, published in The Lancet Infectious Diseases, showed that use of the BD vascular care solution resulted in fewer PIVC failures compared with the standard group (34.8% vs. 47.5%, respectively) and extended the median time between catheter insertion and failure (50.4 hours vs. 30 hours, respectively). PIVC failure was defined as any premature removal of PIVC before end of treatment—other than for routine replacement—and included phlebitis, infiltration, occlusion, dislodgment, local infection and catheter-related bloodstream infection (whichever occurred first).
The CLEAN3 trial also evaluated skin antiseptics with 2% chlorhexidine-gluconate (CHG) 70% isopropyl alcohol (IPA) single use, sterile applicator versus 5% povidone iodine (PVI) 69% ethanol applied with sterile gauze in preventing infectious complications related to the use of PIVCs (catheter colonisation: 0.9% vs. 16.9%, respectively; local infection: 0% vs. 1.2%, respectively).
The trial, which involved approximately 1,000 patients from nine different medical wards within a single university hospital (Poitiers University Hospital, France), evaluated PIVC failure rates by comparing the BD vascular care solution for PIVCs, which included an integrated PIVC (BD Nexiva), a positive displacement needle-free connector (BD MaxZero), a disinfecting cap (BD PureHub) and a sterile prefilled flush syringe (BD PosiFlush)—compared with a standard group, which included a straight safety PIVC (BD Insyte Autoguard BC Winged), extension set three-way stopcock; the PIVCs were continuously infused with saline or polyionic solution, by gravity.
“The findings of the CLEAN3 trial support the use of an integrated solution as the best practice standard when peripheral IV catheter dwell time is expected to exceed 24 hours,” said Olivier Mimoz (Poitiers University Hospital, Poitiers, France), principal investigator of the CLEAN3 trial. “Furthermore, the study shows that the use of 2% CHG-70% IPA single use, sterile applicator should become the first-line antiseptic for skin disinfection prior to PIVC insertion. We believe that the results can be extrapolated to all adult patients admitted to a medical ward requiring a PIVC placement and, by extrapolation, to those admitted to a surgical ward.”
Recent data from the investigator-initiated, randomised controlled trial (RCT), BIOLUX AV, showed that the treatment of patients with dysfunctional haemodialysis access with BIOTRONIK‘s Passeo-18 Lux drug-coated balloon (DCB), is safe and effectively prevents access failure.
Patients (n=120) with dysfunctional haemodialysis access underwent initial high-pressure balloon angioplasty and were randomly assigned for a second angioplasty using either the Passeo-18 Lux DCB or a plain percutaneous transluminal angioplasty (PTA) balloon. Patients were initially followed-up for one year, and quantitative angiography was performed six months after angioplasty.
The one-year data, presented by Eric Therasse (Centre Hospitalier de l’Université de Montréal, Montréal, Canada) at LINC 2021 (The Leipzig Interventional Course, 25–29 January, online) and published in the Journal of Vascular and Interventional Radiology, showed that, in comparison with uncoated balloon PTA, DCB angioplasty was associated with a significantly lower haemodialysis access failure rate and need for reintervention.
Serious adverse events related to HA were less frequent after DCB treatment than after plain PTA. The study principal investigator also stressed that this study, as with previous ones using DCBs in haemodialysis access lesions, did not demonstrate a significant increase in mortality in the DCB group.
Key results from the BIOLUX AV trial publication:
“DCBs with paclitaxel have demonstrated variable results to prevent haemodialysis access restenosis in a few RCTs, and, until recently, their effectiveness was unclear,” explained Therasse, BIOLUX AV principal investigator. The study investigators hypothesised that differences in paclitaxel dosages and excipients of DCBs may be responsible for these variable results and that, in comparison to plain PTA, the paclitaxel-coated balloon technology used in the Passeo-18 Lux would significantly decrease the haemodialysis access restenosis rate at the treated site.
“Our results show the clinical benefit of DCBs to prevent haemodialysis access failure. Both haemodialysis access circuit and haemodialysis access target lesion failures were significantly reduced in the DCB group,” summarised Therasse.
Forge Medical has announced the publication of results of an investigator-initiated randomised trial comparing its VasoStat haemostasis device to the TR Band (Terumo Medical) among patients undergoing radial artery coronary and peripheral procedures with planned same-day discharge.
Published in the Journal of Invasive Cardiology, the study authored by Robert L Minor Jr (Billings Clinic, Missoula, USA), the study involved 40 patients without prior radial access undergoing elective coronary, endovascular diagnostic or interventional procedures, who were randomised to receive either VasoStat or TR Band.
The study’s primary outcome was time to haemostasis enabling radial artery compression device (RCD) removal. Minor Jr and colleagues reported significantly shorter times to haemostasis, higher patient satisfaction and fewer device manipulations needed by nursing personnel among the VasoStat group.
All patients were able to be discharged the same day as their procedure, the study reports, adding that Doppler perfusion imaging follow-up within 60 days in all study patients confirmed radial artery patency with no events of radial artery occlusion (RAO) or pseudoaneurysm.
Commenting on the study’s results, Ty Schlander, CEO of Forge Medical, said: “Same-day discharge among elective PCI [percutaneous coronary intervention] and peripheral vascular patients is being used more often by clinicians, hospitals and health systems around the country, with ever higher adoption since the pandemic. We are proud to provide an innovative haemostasis device for radial artery applications differentiated from balloon/band-type devices that enables faster hemostasis and higher patient satisfaction, in alignment with national trends using same-day discharge.”
Forge Medical has announced the publication of results of an investigator-initiated randomised trial comparing its VasoStat haemostasis device to the TR Band (Terumo Medical) among patients undergoing radial artery coronary and peripheral procedures with planned same-day discharge.
Published in the Journal of Invasive Cardiology, the study authored by Robert L Minor Jr (Billings Clinic, Missoula, USA), the study involved 40 patients without prior radial access undergoing elective coronary, endovascular diagnostic or interventional procedures, who were randomised to receive either VasoStat or TR Band.
The study’s primary outcome was time to haemostasis enabling radial artery compression device (RCD) removal. Minor Jr and colleagues reported significantly shorter times to haemostasis, higher patient satisfaction and fewer device manipulations needed by nursing personnel among the VasoStat group.
All patients were able to be discharged the same day as their procedure, the study reports, adding that Doppler perfusion imaging follow-up within 60 days in all study patients confirmed radial artery patency with no events of radial artery occlusion (RAO) or pseudoaneurysm.
Commenting on the study’s results, Ty Schlander, CEO of Forge Medical, said: “Same-day discharge among elective PCI [percutaneous coronary intervention] and peripheral vascular patients is being used more often by clinicians, hospitals and health systems around the country, with ever higher adoption since the pandemic. We are proud to provide an innovative haemostasis device for radial artery applications differentiated from balloon/band-type devices that enables faster hemostasis and higher patient satisfaction, in alignment with national trends using same-day discharge.”
“Practicing ethical inquiry and reflection may mitigate the moral distress that can arise from ethical dilemmas,” write Michelle Shnayder-Adams, Eric J Keller, and Mina S Makary—and there have certainly been a number of emotionally-challenging ethical dilemmas for healthcare providers treating patients against the backdrop of the COVID-19 pandemic. The authors discuss the intersection of medical ethics and interventional radiology (IR) amidst this crisis, and propose a framework interventionalists can use to enable decision-making when faced with multiple, conflicting moral obligations, which they say can cause stress and uncertainty.
In stressful times, challenges associated with making ethical and honourable decisions become more apparent. The COVID-19 pandemic has placed an immense amount of strain on the medical community, and interventional radiologists are not exempt from this pressure. When ethical norms are disrupted, we have an even greater responsibility as a specialty to bring ethical decision-making to the forefront. This article will highlight: 1) how ethics and IR intersect, 2) how ethical issues have been heightened during the COVID-19 pandemic, and 3) how to apply a framework to ethical decisions pertaining to IR care.
The discipline of ethics helps us to decide how we ought to behave as a standard of behaviour.1 To some, it may not seem obvious to discuss and practice ethical decision-making in medicine as it appears innate. After all, physicians pledge the Hippocratic Oath and vow to “do no harm”. However, conflict arises when ethical principles clash. The COVID-19 pandemic has challenged a number of ethical values, including duty to care, equity, autonomy, and individual liberty. As we continue to practice in a new societal norm filled with personal risk, limited resources, and limited physical contact, we must continue to reflect on our ideals and ethical identities during patient care delivery.
The Society of Interventional Radiology (SIR) Code of Ethics offers guiding principles for IR physicians on societal ethical expectations.2 Respect for human dignity, respect for human rights, and respect for the law are all included. However, these guidelines are not always sufficient when faced with practical matters. Are you obligated to place a central venous catheter in a patient with COVID-19 at a time when personal protective equipment is limited, and other departments have the means to perform this service? Some may argue that a pandemic qualifies as a state of emergency in which physicians must act on the best interest of society. However, in practice, it is much more challenging to jeopardise your own health and the health of your family and colleagues for the sake of professional duty. Physicians have a responsibility to care for patients, but this responsibility must be balanced with a duty to one’s health and one’s family.3,4 We must also resist the urge to deflect risk onto others and should view patient care as a collective responsibility. With thoughtful reflection and support from institutions to ease the moral burden of these difficult choices, IR physicians can weigh their competing responsibilities and come to a solution that balances all the ethical and practical issues at play.5
With the development of the COVID-19 vaccine, resource allocation concerns have shifted from intensive care unit (ICU) bed provision to vaccination distribution priority. How do we decide on a fair system of vaccine distribution? Whether you are a healthcare leader responsible for the development of a vaccine rollout plan or a frustrated IR practitioner awaiting a vaccine, resource allocation and equity affects all healthcare providers. The Center for Disease Control (CDC) has advocated to minimise morbidity and mortality and preserve societal functions.6 With these priorities in mind, some vaccination algorithms have prioritised age over exposure frequency. Without transparency from leaders about their chosen ethical approach, it is reasonable for younger practitioners with frequent exposures to feel betrayed when they observe vaccine prioritisation of older practitioners with lesser patient interaction. There is no absolute right answer when it comes to prioritisation in the setting of scarce resources, but as these ethical dilemmas unfold, it is crucial for healthcare leaders to maintain transparency and robust discussion with their communities to reach more optimal solutions.
Imagine you are running a busy consult service and you are tasked with acquiring consent for a gastrostomy tube placement in a non-English speaking patient with COVID-19 who has been delirious the last few nights. Her son is her power of attorney. Would you risk exposure, call a translator, and attempt to assess the patient’s decision-making capacity, or just call the patient’s son to get consent? From an ethical standpoint, many IR physicians may agree that they would advocate for explaining the procedure and its risks to the patient despite the extra risk, time, and logistic challenges. From a practical standpoint, respecting a patient’s autonomy, while paramount, can be often inconvenient, especially during a pandemic. Despite the challenges, we must keep in mind that assessing a patient’s decision-making capacity is one of our responsibilities as IR physicians, and if needed, there are resources and other departments in the hospital to help with capacity assessments.
Despite being accountable to our individual patients, IR physicians also have a responsibility to the general public. These two obligations may lead to internal turmoil and conflict. Visitor restrictions limit disease exposure for patients, providers, and hospital staff but at the expense of some individual liberty. Limiting a patient’s number of visitors may support a public effort to reduce spread of disease, but the social isolation of patients can lead to psychological distress and worse patient outcomes. 7–9 In balancing these opposing priorities and accepting the restriction of some individual liberties for the betterment of society, interventional radiologists may find that going beyond their usual levels of communication with patients and families may be necessary to preserve the patient-doctor-family relationship during a pandemic.
The COVID-19 pandemic has forced medical professionals, including interventional radiologists, to deal with ethically-ambivalent decisions every day. Many frameworks have been developed to aid in the ethical decision-making process. 1,5,10–12 One such approach is as follows: 1) recognise an ethical dilemma, 2) gather relevant information from all parties involved, 3) scrutinise possible options using various ethical theories, 4) decide how to act, and 5) reflect on the outcome. For example, this framework may be applied to triaging patients. First, we recognise that triaging with limited resources is an ethical issue. Second, we may gather information about the acuity of all patients involved and consider occupancy capacity at nearby facilities. Third, question the correct course of action under a utilitarian, rights, justice, common good, and virtue approach. For instance, under the justice approach, consider which options treats people equally—making sure not to succumb to bias and favouritism. Fourth, decide which patient to treat, and, fifth, consider how your decision impacted those involved. Practicing ethical inquiry and reflection may mitigate the moral distress that can arise from ethical dilemmas.13
Interventional radiologists have started to recognise the importance of ethical discussion in our field. We have an Applied Ethics Committee supported by the Society of Interventional Oncology (SIO) and SIR, and we have growing literature on ethical topics in IR including: complications,14 conflicts of interest,15 research ethics,16 and futility.17–19 The COVID-19 pandemic has highlighted the need for these discussions, and we must continue to provide platforms to discuss how best to act in ethically challenging situations.
Michelle M Shnayder-Adams is an interventional radiology resident at the University of Michigan Hospital, Ann Arbor, USA. @MMShnayderMD on Twitter.
Eric J Keller is an interventional radiology resident at the Stanford University Medical Center, Stanford, USA. @IR_Ethics on Twitter.
Mina S Makary is an assistant professor, interventional radiologist, and the director of scholarly activity and research at the Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, USA. @MinaMakaryMD on Twitter.
References
Personalised treatment selection and planning based on controlled dosimetry will lead to improvements in treatment accuracy. This is the conclusion presented by Marnix Lam (University Medical Center Utrecht, Utrecht, The Netherlands) at ECIO Virtual (27 January, online), a series of afternoon webinars that the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) is hosting in lieu of the 2020 European Conference on Interventional Oncology (ECIO). Lam spoke on the differences between Yttrium-90 (Y-90) and Holmium-166 (Ho-166) radioembolization, and told delegates that it was “very important” to ensure interventionalists conduct a “good” scout procedure with control over selection and planning.
Currently, there are three microspheres available for radioembolization treatment in Europe: TheraSphere (Boston Scientific), SIR-Spheres (Sirtex), and Quiremspheres (Terumo). Lam began his talk by highlighting several differences between these microspheres. “Firstly,” he said, “the isotope. This is Y-90 for TheraSphere and SIR-Spheres, and Ho-166 for Quiremspheres.”
Importantly, he said, the different isotopes have different characteristics. Relative embolic effect is lowest for TheraSphere, middling for Quiremspheres, and highest of the three for SIR-Spheres. This is because the number of particles that are injected differs for each microsphere brand: five million for TheraSphere, 50 million for SIR-Spheres, and 20 million for Quiremspheres.
Lam explained: “Typically for Theraspheres, there is a low embolic effect, because we only administer around five million particles. With SIR-Spheres, there is a higher embolic effect, because we administer up to 50 million particles, ten times the number of particles as with TheraSphere. With Quiremspheres, we are somewhere in between, with a medium embolic effect, as we administer around 20 million particles. This means that the specific activity of TheraSphere is much higher: so, the activity per sphere is much higher for Therasphere than it is for SIR-Spheres, and Quiremspheres is again somewhere in between.”
He cited the specific activity for each microsphere as: 1,250–2,500Bq/microsphere for TheraSphere, 50Bq/microsphere for SIR-Spheres, and 200–400Bq/microspheres for Quiremspheres.
“What does this mean?” Lam asked rhetorically. “This is really important to understand”. Pre-clinical work by Alexander Pasciak (Johns Hopkins University, Baltimore, USA) et al in pig livers investigated the use of different numbers of microspheres over the same overall radiation activity (i.e., the same Gy in total; so, when few microspheres were used, they each have a high specific activity, and when large numbers of microspheres were used, they each had a low specific activity). When relatively few microspheres were injected, there was a very heterogeneous distribution pattern. In contrast, when a large number of microspheres were injected into the liver, each with a low specific activity, the distribution pattern was much more homogenous across the organ.
Liver tolerance of the same radiation activity (as measured in Gy), the same absorbed dose, is therefore greater when fewer particles are injected, each with a higher specific activity. The more homogenous distribution of radiation in the high-number-of-microspheres-injected model means that there is a much more limited area of unaffected liver. As Lam explained at ECIO Virtual, in the low-number-of-microspheres group, certain areas of the liver are “super dead”—have a very concentrated radiation dose—and a large swathe of the liver is unscathed.
“This is exactly the difference between TheraSphere [low particle count] and SIR-Spheres [high particle count],” he said. QuiremSpheres are in between.
Expanding on what this means in terms of tolerability, Lam informed listeners that for glass microspheres, a 100Gy radiation dose to the liver results in a 50% chance of toxicity. The same toxicity risk is attained at a 50Gy radiation dose when using resin microspheres, “so half the absorbed dose to the liver, same chance of toxicity, because the distribution is more homogeneous”. The dose thresholds used for treatment planning therefore vary depending on what type of microsphere is used.
Lam commented that this “is a very important message”, and advised the audience “to be very careful when comparing doses between products”.
Interventionalists utilise different imaging modalities for different microspheres
Turning to imaging, Lam explained how, due to differing microsphere characteristics, the imaging modality used for each also varies. Expanding on the clinical implications of this, Lam explained: “The idea of using Ho-166 instead of Y-90 is that Ho-166 has a therapeutic effect very similar to Y-90, but on top of that the element Holmium, like Gadolinium, is chemically a lanthanide, so it is paramagnetic and may be visualised and quantified using MRI [magnetic resonance imaging]. Holmium also emits gamma radiation, that may be used for quantitative SPECT [single photon emission computed tomography] imaging.”
While Y-90 can be imaged using SPECT or positron emission tomography (PET), Lam told ECIO Virtual attendees that the former modality is limited by resolution, and the latter by sensitivity. However, Ho-166 can be imaged at low quantities by MRI or SPECT, meaning that with Quiremspheres, the same particles can be used for the scout dose as for the treatment dose, unlike with Theraspheres and SIR-Spheres. Lam went on to explain the clinical significance of this characteristic of Ho-166.
Typically, ahead of a radioembolization procedure, he explained, the interventionalist will conduct a work-up or scout procedure using Tc-99m MAA (macroaggregated albumin).
The 2017 SARAH trial, an open-label, randomised controlled phase 3 trial investigating the efficacy and safety of selective internal radiotherapy (SIRT) with Y-90 resin microspheres compared with sorafenib in hepatocellular carcinoma (HCC) patients, found no significant difference in survival between the two treatments. In a more recent post-hoc analysis of the SARAH trial, published in Radiology in 2000, Ann-Laure Hermann (Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France) et al showed that when the tumour-absorbed dose is at least 100Gy, there is a clear difference in survival between resin microspheres and SIRT. “I think there is quite a spectacular result when you compare groups over 100Gy tumour-absorbed dose or below 100Gy tumour-absorbed dose,” Lam noted.
“However,” he continued, the same study also demonstrated that the correlation between the Tc-MAA distribution and the post-treatment Y-90 distribution was “good in 53% of patients only”. In 20% of patients, there was a medium correlation, and in “as much as 27% of patients”, a correlation between Tc-MAA and Y-90 distribution was poor.
“This means if we use Tc-MAA for treatment planning, in only 53% of patients the predicted value of Tc-MAA versus post-treatment Y-90 is sufficient for treatment planning. So, this is quite poor,” Lam said. “What we learn from this study is that of course, number one, we have to select patients who will benefit: patients where we can reach a 100Gy absorbed dose, and of course we should plan our treatment accordingly, to make sure we reach that tumour-absorbed dose.
“But what we also learn from this study is that we gain control by having an improved scout procedure, where the work-up is predictive of the final outcome. I believe this is where Holmium steps in, because instead of Tc-MAA, we use the exact same particles for work-up as we use for the treatment procedure. What we gain is control—over the lung-shunt calculation, and also over the intra-hepatic distribution.”
Tomorrow’s treatment planning method: Individualised patient care
Looking to the future, Lam enthused about personalised treatment planning. “Today, we use single compartment modelling at best,” he said, “aiming for an average absorbed dose within a certain perfused volume, but we really want to go towards multi-compartment modelling, differentiating between a tumour-absorbed dose and a normal-liver-absorbed dose in each individual patient. personalised
“We can use the scout dose procedure, the imaging that we gain, by selecting our patients based on a safe normal-liver-absorbed dose and a sufficient tumour-absorbed dose. If we are not able to reach that, we should seek an alternative treatment; so, selection comes first, and, secondly, we should plan our treatment accordingly. This is very important.” personalised personalised personalised personalised personalised personalised personalised personalised
“I consider intravascular ultrasound (IVUS) to be essential equipment in venous interventions,” Rick de Graaf (Clinic of Friedrichshafen, Friedrichshafen, Germany) told viewers of LINC 2021 (The Leipzig Interventional Course; 25–29 January, online). De Graaf was speaking during a session on endovascular procedures for the deep venous system, aiming to answer the question, ‘Is IVUS a fancy tool, or relevant for clinical outcomes?’
“It is hard to say that [IVUS] is fancy,” de Graaf began, noting that this is technology is essentially “just an ultrasound probe on a catheter”. In venous interventions, he noted, the technology is mainly used to indicate stenosis, determine a healthy stent landing zone, to evaluate after stenting, and evaluate after thrombectomy to see if there is any residual thrombus.
Regarding data, de Graaf detailed that there are a number of papers on using IVUS for diagnosis and procedural planning, as well as recent data from the Arnsberg registry, headed by Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany), that showed IVUS to be an effective option to reduce radiation during deep venous obstruction (DVO) interventions.
De Graaf then summarised the benefits of IVUS in venous procedures, detailing that the technology can identify “subtle yet significant” pathology—even more so than magnetic resonance (MR)-venography, in his view—gives “instant and accurate” three-dimensional (3D) representation, reduces radiation, as different angulations are not necessary and the imaging is more efficient, and reduces contrast.
Moving on to when and how to use IVUS in venous practice, de Graaf expressed his belief that to not use it at all would be “dangerously close to malpractice”. He elaborated: “Sooner or later you are going to miss something, and the patient will suffer.”
De Graaf told the audience that he has IVUS present in all venous cases, because “you never know what you are going to miss,” he said. De Graaf noted that some physicians state they only use IVUS when they need it, but likened this to only wearing a seatbelt when it is needed.
In terms of experience, de Graaf detailed that he started performing venous procedures in 2009 without IVUS, due to the cost. However, he became convinced of its importance after several stent occlusions proved to be related to the lack of IVUS. “I now use IVUS in every venous case,” he reiterated.
De Graaf outlined a specific venous case in which IVUS was crucial. A patient presented with iliac vein thrombosis, but also a distal vena cava thrombosis, he explained. While the speaker noted that he cleared out the iliac vein and stented it, IVUS then showed that there was still thrombus in the inferior vena cava (IVC), which could not be left. “I tried thrombectomy and suction with a large sheath, but I did not get it out,” he relayed. De Graaf then decided to use live imaging with IVUS and was able to remove the thrombus successfully under IVUS guidance.
“IVUS obviously has significant value guiding venous interventions, and real-time IVUS offers further possibilities,” de Graaf concluded.
A key theme among the late-breaking trial data presented at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online) was the emergence of long-term data on paclitaxel devices in the femoropopliteal segment. Results out to five years shows good efficacy and safety.
Thomas Zeller (University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany) presented five-year outcomes of the IN.PACT Global trial, assessing the IN.PACT Admiral drug-coated balloon (DCB; Medtronic), followed by Young-Guk Ko (Yonsei University College of Medicine, Seoul, Korea), who announced results from the IN.PACT Global Asian cohort. Also presenting data out to five years, Marianne Brodmann (University of Graz, Graz, Austria) detailed new findings from the ILLUMENATE randomised controlled trials (RCTs) of the Stellarex DCB (Philips).
The EffPac study of the Luminor DCB (iVascular) now has data out to three and a half years, which Dierk Scheinert (University of Leipzig, Leipzig, Germany) shared with the LINC audience. Finally, Michael Lichtenberg (Karolinen Hospital, Arnsberg, Germany) relayed three-year data from the first-in-human KANSHAS 1 study of the novel Kanshas DCB (Terumo).
“Robust, real-world data”: IN.PACT Global five-year outcomes
First to present was Zeller, who informed LINC viewers that the IN.PACT Global study, “remains the largest and only reported real-world DCB study with independent Clinical Events Committee (CEC) adjudication through five years”. The results demonstrate the sustained efficacy of the IN.PACT Admiral DCB through five years and show evidence of long-term safety.
Zeller noted that patients with complex lesions are usually excluded from randomised controlled trials (RCTs), however, they are reflected in real-world studies. “RCTs and global registries have demonstrated the superiority of DCBs over percutaneous transluminal angioplasty (PTA) for the treatment of peripheral arterial disease (PAD) in real-world patients,” he remarked, adding, however, that long-term evidence in complex real-world patients is limited.
The IN.PACT Global study is a real-world, prospective, multicentre, single-arm, independently-adjudicated femoropopliteal study. A total of 1,416 patients were included across 64 sites in the EU, Middle-East, Latin America, and Asia.
In terms of efficacy, Zeller reported that the five-year freedom from clinically-driven target lesion revascularisation (CD-TLR) rate was 69.4%. He compared this to the rates at one, two, three and four years: 92.%, 83.3%, 76.9%, and 73.4%, respectively. Considering additional efficacy outcomes, Zeller noted that the rate of CD-TRL was 30.6% and that the rate of any TLR was 31.3%.
Regarding the primary safety composite endpoint—which consists of freedom from device- and procedure-related deaths out to 30 days, freedom from major target limb amputation within 60 months, and freedom from clinically-driven target vessel revascularisation (CD-TVR) within 60 months—the rate was 67.4% at five years.
In addition, there was a 78.9% rate of freedom from all-cause mortality out to five years, and 96.4% follow-up was achieved with vital status collection.
Zeller concluded: “Robust, real-world data continue to demonstrate durable results, indicating the IN.PACT Admiral DCB as a viable solution for the treatment of femoropopliteal disease.”
IN.PACT Admiral demonstrates “consistent treatment effect” in complex geographic subset
Honing in on the Asian subset of the IN.PACT Global study, Ko revealed that this subgroup showed more complex baseline clinical and lesion characteristics than the global clinical cohort. However, he also informed the audience that the Asian subset showed a consistently lower CD-TLR rate of 22.9% at five years for complex femoropopliteal lesions, with a mean length of 17.4±12.4cm and 51.4% total occlusions.
“These results demonstrate a consistent treatment effect with the IN.PACT Admiral DCB across IN.PACT studies, including this complex geographic subset,” he concluded.
Five-year ILLUMENATE outcomes show continued efficacy and safety of Stellarex DCB
Brodmann announced the final, five-year results of two RCTs that show no difference in all-cause mortality between patients treated with the Stellarex DCB and those treated with PTA, the current standard of care. Moreover, the studies showed no difference in mortality between the Stellarex DCB and PTA at every 12-month endpoint over the course of the study.
The ILLUMENATE EU RCT and ILLUMENATE Pivotal RCT together comprised approximately 600 patients in Europe and the USA. After five years, the ILLUMENATE EU RCT showed 19.3% mortality among patients treated with the Stellarex DCB compared to 19.4% mortality for those treated with PTA.
The five-year results for the ILLUMENATE Pivotal study also show no statistically significant difference among patients treated with the Stellarex DCB (21.2%) compared to those treated with PTA (20.2%). Both studies had a high vital status follow-up compliance, with the status of over 90% of patients known.
“The five-year final results show favourable overall safety of the Stellarex low-dose paclitaxel DCB, and are applicable within an extensive patient cohort,” said Brodmann. “Every year, the Stellarex programme has demonstrated low mortality rates with no difference in rates between the two patient cohorts.”
Luminor DCB results in “significant haemodynamic improvement” out to 3.5 years in EffPac study
Presenting new findings from the EffPac trial, Scheinert outlined 3.5-year outcomes with the Luminor-35 DCB (iVascular). A total of 166 patients were included in this study; 82 were treated with the Luminor DCB, while 84 were treated with PTA.
He concluded that at the 3.5-year timepoint, DCB angioplasty with the Luminor-35 DCB of medium length superficial femoral and popliteal artery lesions results in a, “significant haemodynamic improvement from baseline,” with a lower TLR rate, and an all-cause mortality rate similar to PTA.
Three-year findings of the first-in-human KANSHAS 1 study demonstrates “good safety and efficacy” of novel Kanshas device
Finally, Lichtenberg presented results of the first-in-human KANSHAS study of the novel Kanshas DCB (Terumo), for which there are results for 31 patients.
The speaker concluded: “Angioplasty using the novel Kanshas DCB for the treatment of de novo femoropopliteal artery lesions displays good safety and efficacy throughout the period of 36-month follow-up.” In addition, he noted that haemodynamic and clinical improvement was maintained in the majority of patients, and that no sign of an abnormal late mortality signal was observed in the studied population, with only a few TLRs noted.
New data presented for the first time at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online) are positive for the IN.PACT AV drug-coated balloon (DCB) and the Ellipsys vascular access system (both Medtronic). The IN.PACT AV Access study investigated the use of DCB angioplasty versus percutaneous transluminal angioplasty (PTA) for the treatment of dysfunctional arteriovenous fistulas (AVFs). In a second presentation at the virtual congress, delegates were treated to a comparison of surgically-created versus percutaneously-created AVFs.
One-year results from the IN.PACT AV Access study demonstrate superior target lesion primary patency outcomes for DCB angioplasty compared to percutaneous transluminal angioplasty (PTA) for the treatment of de novo or restenotic obstructive lesions of native arteriovenous fistulae (AVF) in the upper extremity. So said Andrew Holden (Auckland Hospital, Auckland, New Zealand), addressing attendees virtually.
In a comparison of surgical and percutaneous AVF creation, Robert Shahverdyan (Asklepios Clinic Barmbek, Hamburg, Germany) told LINC 2021 attendees that whilst surgical AVFs have a higher primary patency and fewer re-interventions, percutaneous AVFs with the Ellipsys vascular access system have a higher technical success rate, faster procedure times, higher assisted, secondary patency and maturation rates, faster cannulation times, and fewer abandonments.
Superior target lesion primary patency at 12 months with the IN.PACT AV DCB versus standard angioplasty, new data show
In addition to Holden, Robert Lookstein (Ichan School of Medicine at Mount Sinai, New York, USA) and Hiroaki Haruguchi (Haruguchi Vascular Access Clinic, Tokyo, Japan) are principal investigators of the IN.PACT AV Access investigational device exemption (IDE) study, which evaluated the IN.PACT AV DCB versus PTA.
They conducted a global, prospective, 29-centre, 1:1 randomised, single-blinded study evaluating the safety and effectiveness of DCB angioplasty versus PTA in dysfunctional AVF, following 330 patients out to five years. Each patient enrolled in the study had lesions up to 10cm in length in the native AVF.
The primary safety outcome was measured by the serious adverse event rate involving the AVF access within 30 days of the procedure. The primary effectiveness outcome was defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or access circuit thrombosis, measured through six months post-procedure.
One year after intervention, target lesion primary patency was 65.3% in the DCB group, and 46.3% in the standard PTA group (p<0.001). Access circuit primary patency was also higher amongst the IN.PACT AV DCB cohort: 55.1% versus 35% (p<0.001).
The subset outcomes of the IN.PACT AV Access trial through 12-months were presented for the first time. Assessing the 12-month data by lesion type, Holden informed the virtual LINC audience that the IN.PACT AV DCB arm demonstrated superior patency in both de novo and restenotic lesions compared to the standard PTA arm. Target lesion primary patency was achieved in 77.5% of de novo lesions treated with the IN.PACT AV DCB (31 of 40), compared to in 61.9% of de novo lesions treated with standard PTA (26 of 42); confidence interval (CI), -4–35.2%. In restenotic lesions, target lesion primary patency was also higher in the DCB group than the standard angioplasty one: 58.4% (59 of 101) versus 35.7% (35 of 98); CI, 9.2–36.2%
Looking at the data by type of AVF type, the IN.PACT AV DCB group achieved better target lesion primary patency at 12-months for all subgroups: radiocephalic (64.5% vs. 47.2%; CI, 1.5–33%), brachiocephalic (63.8% vs. 41.2%; CI, 3.4–41.9%), and brachiobasilic (61.5% vs. 45.4%; CI, -23.5–55.6%). Commenting on these results, Holden told delegates: “Fewer reinterventions are needed to maintain target lesion primary patency in the DCB group compared to the PTA group. We saw a 56% reduction in reinterventions at six months, and a 35.4% reduction in reinterventions at 12 months.
“Through 12 months, sustained superior target lesion primary patency was achieved with DCB in restenotic lesions, and both forearm and upper arm AVF types. Subset analysis of lesion location showed a patency advantage for INPACT AV DCB over standard PTA for all lesion locations in the access circuit but particularly at the arterial inflow, anastomosis and cephalic arch.”
One-year data consistent with positive six-month results
These 12-month data concur with the six-month results of the IN.PACT AV Access study, published in The New England Journal of Medicine (NEJM) in August 2020, which also showed that DCB angioplasty is superior to standard angioplasty for the treatment of stenotic lesions in dysfunctional haemodialysis AVFs. Furthermore, it was found to be non-inferior with respect to access circuit-related serious adverse events within 30 days.
The investigators noted last summer that long-term outcomes for standard PTA—the current recommended treatment for dysfunctional haemodialysis fistulas—are poor. They suggested that DCBs delivering the antirestonotic agent paclitaxel may improve outcomes, as evidenced in the present study.
Speaking to Vascular News at the time, Lookstein commented on the clinical implications of the study: “We now have Level 1 evidence of a simple technology that is proven to be safe and effective at improving outcomes for patients with end-stage renal disease [ESKD] on haemodialysis.
“This is the first US Food and Drug Administration [FDA]-approved paclitaxel-based device since the controversy last year, which is a testament not only to the incredible results seen in this trial, but also the significant needs of this population.”
Percutaneous AVF creation with Ellipsys faster, and “easier to salvage” than surgically-created AVFs
In a comparison of surgical and percutaneous AVF creation, Shahverdyan told LINC 2021 attendees that whilst surgically-created AVFs have a higher primary patency and fewer re-interventions, percutaneously-created AVFs with the Ellipsys vascular access system have a higher technical success rate, faster procedure times, higher assisted, secondary patency and maturation rates, faster cannulation times, and fewer abandonments.
Currently, there are two systems available on the market for the percutaneous creation of AVF: the Ellipsys vascular access system and the WavelinQ 4F endoAVF system from BD.
Comparing these two endovascular AVF options with the surgical Gracz technique, the investigators have created over 500 new vascular accesses during the study period in total, from which Ellipsys was used in 116 patients, WavelinQ 4F in 41 patients, and Gracz surgical AVF creation was performed in 90 patients.
Technical success was 100% in the Ellipsys and surgical Gracz groups, and 92.7% in the WavelinQ group.
“Anastomosis is very important,” Shahverdyan said, before sharing that 100% of anastomoses were radial in the Ellipsys group, while 61% were radial in the WavelinQ groups (a further 34.1% were ulnar), and 37% were radial in the Gracz group (an additional 12% were ulnar, and 51% were brachial). Commenting on the fact that half of surgical AVFs were brachial, Shahverdyan noted: “Anastomosis [location] is not only important for the flow, but also after a failed endoAVF, you could still create a brachial artery based anastomosis [surgically]”.
The procedure time was significantly shorter when using the Ellipsys, with a median time of 13 minutes versus 62 minutes in the WavelinQ arm and 69 minutes in the Gracz arm.
“This is where it gets interesting,” Shahverdyan enthused. He shared that maturation at four weeks “is similarly high for Ellipsys and Gracz” (78.4% and 80%, respectively), and that they observed total maturation in 88% of patients for both these groups. Time to cannulation in dialysis patients was shorter for Ellipsys procedures (52 days vs. 69 days in the surgical cohort), and, although there were more interventions in the endoAVF groups, fewer Ellipsys AVFs were abandoned or converted to another fistula (12.3% vs. 36.6% in the WavelinQ group and 15.6% in the surgical group).
At six months, one year, and two years, primary patency was highest in the surgical Gracz group (68%, 53%, and 42%, respectively). The Ellipsys had the second highest primary patency at all time points (50%, 34%, and 27%, respectively), whilst primary patency with WavelinQ was lowest (35%, 27%, and 23%, respectively). However, assisted patency rates at six months, one year, and two years were similarly high for Ellipsys (83%, 77%, and 77%, respectively) and Gracz (84%, 80%, and 78%, respectively) groups, and secondary patency rates were slightly, but not significantly, higher for Ellipsys-group (89%, 87% and 87%) versus Gracz-group (855, 82% and 82%).
“To conclude,” Shahverdyan said, “Ellipsys demonstrates high technical success and faster procedural times compared with both surgical and WavelinQ procedures. It shows similarly high assisted and secondary patency and maturation rates as the Gracz fistula, and especially if you compare it to the proximal radial artery based Gracz AVF, it shows significantly higher secondary patency rates. There are fast cannulation times for Ellipsys AVF, and although there are fewer re-interventions for the Gracz AVF [than with Ellipsys], there are fewer abandonments for Ellipsys percutaneous AVF, so it is easier to salvage.
“Therefore, Ellipsys percutaneous AVF expands the options for a valid, long-term AVF creation in our patients.”
Twelve-month results from the PRESTIGE below-the-knee (BTK) study have been presented as a late-breaking trial at LINC 2021 (25–29 January, virtual). The objective of this clinical investigation has been to evaluate safety and performance outcomes of SELUTION SLR, MedAlliance’s novel sirolimus-eluting balloon, for the treatment of long tibial occlusive lesions (TASC C and D) in patients with chronic limb-threatening ischaemia (CLTI).
The primary patency rate was 78% and the rate of wound healing was 81%. Freedom from target lesion revascularisation (TLR) was exhibited by 93% of patients and 84% demonstrated amputation free survival (AFS). All these figures have been sustained from the six-month data.
PRESTIGE is a prospective, single-centre, physician-initiated clinical study, run at the Singapore General Hospital (SGH) by Tze Tec Chong and Tjun Yip Tang, who are both senior consultants at the Hospital’s Department of Vascular Surgery. Twenty-five patients were enrolled with an average age of 64. Eighty-eight per cent had diabetes mellitus and 44% had end stage renal failure. No patients required bailout stenting. Clinical follow-up was at one, three, six, and 12 months.
“We have observed minimal slow-flow phenomena and some cases of fast wound healing with SELUTION SLR. It is also easy to track and deliver. We are looking forward to gaining further clinical experience with this device,” commented Chong.
Singapore has a high percentage of diabetics in its population and CLTI therefore constitutes a major challenge among patients seen with peripheral arterial disease (PAD). SGH performs over 1,000 interventional procedures a year on patients suffering from CLTI.
In February 2020 MedAlliance received CE mark approval for SELUTION SLR in the treatment of peripheral arterial disease. Both the STEP Pedal Arch study and SUCCESS PTA, a large post-marketing clinical study in PAD, will commence enrolment soon. In the US, SELUTION SLR has received US Food and Drug Administration (FDA) Breakthrough Device Designation Status for a drug-eluting balloon (DEB) in the treatment of peripheral below-the-knee lesions.
Artio Medical recently announced that it has successfully completed the first human use of its Amplifi vein dilation system. The first clinical procedure was performed by Adrian Ebner, head of the Cardiovascular Department at Sanatorio Italiano Hospital in Asuncion, Paraguay.
“Vascular access is a constant challenge for end stage renal disease patients who depend on haemodialysis treatment. Most patients are plagued with interrupted or delayed care due to repeated access site failures and require additional procedures and surgeries to maintain vascular access,” commented Ebner.
“Many also frequently experience access site complications, often resulting in hospitalisation and the need for additional care. I am pleased to be a part of the first human use for the Amplifi system. This is the first technology that seeks to address these challenges by proactively preparing patient’s veins for AVF creation.”
Artio Medical’s Amplifi vein dilation system is designed to stimulate arm vein enlargement in haemodialysis patients using rapid, non-pulsatile blood flow. The innovative system is designed for percutaneous placement and includes a wearable, external blood pump, inflow and outflow catheters, and a controller. The Amplifi system is used for seven to 10 days and removed completely during AVF creation.
“I believe this device has the potential to change the standard of care for haemodialysis patients, allowing more patients to be eligible for AVF surgery and reducing the risk of AVF failure and abandonment,” continued Ebner. “The degree of vein dilation we observed during the treatment period for the first patient was remarkable, and the AVF made with the treated vein matured very rapidly.”
Artio Medical acquired the first-of-its-kind vein dilation technology through the acquisition of Flow Forward Medical in June 2020. The Amplifi vein dilation system aims to address common issues related to vascular access site creation and maintenance for the 2.3 million patients worldwide with end-stage renal disease who require haemodialysis. Artio expects to complete the first-in-human clinical study in the first half of 2021.
VentureMed Group announced today that data from three studies evaluating the use of its Flex Vessel Prep (VP) system were presented during LINC 2021 (Leipzig Interventional Course; 25–29 January, virtual). The Flex VP system is designed to modify plaque and prepare vessels with complex femoropopliteal arterial disease, including in-stent restenotic (ISR) lesions, prior to delivery of the definitive therapy.
“Individually and collectively, these three studies report compelling data,” said J Robert Paulson, Jr, president and chief executive officer of VentureMed. “The data demonstrate that longitudinal, circumferential micro-incisions delivered by the Flex Vessel Prep system safely and consistently modify plaque to improve vessel compliance and increase luminal gain, with minimal trauma to the vessel, which may reduce the need for stenting and facilitate the delivery of drug therapies into the vessel wall. The Flex Vessel Prep system allows physicians to modify plaque and prepare diseased vessels of any length to optimise their choice of definitive revascularisation therapy.”
The following are summaries of the three studies presented at LINC 2021:
12-month results of micro-incision Vessel Prep system showing acute and long-term benefit in superficial femoral and popliteal arteries
This single-centre study assessed the impact of vessel preparation with Flex VP longitudinal, controlled-depth, micro-incisions prior to drug-coated balloon (DCB) angioplasty or percutaneous transluminal angioplasty (PTA) therapy, acutely, and at six and 12 months.
Study findings:
Patterns and number of dissections with atherectomy versus Flex VP: An IVUS assessment
This single-centre, comparative, prospective study was based on published data demonstrating that dissection, not plaque compression, is what opens the lumen of obstructed vessels post-PTA. Published clinical data also has demonstrated that severe dissections per NHLBI classifications (Type C and higher) and dissections involving the adventitia are likely to be associated with worse outcomes after definitive PTA therapy. This study evaluated the differences in dissections between atherectomy and the Flex VP system in femoropopliteal arteries and included de novo and restenotic lesions using intravascular ultrasound.
Study findings:
Lesion modification with a micro-incision Vessel Preparation system enhances balloon-based drug delivery in complex porcine restenotic lesions
This study examined if and how a vessel preparation system delivering micro-incisions could enhance in vivo paclitaxel (delivered from a DCB) retention in a complex porcine ISR lesion model design. Optical coherence tomography (OCT) images of the baseline ISR images confirmed barriers to delivery of DCB therapy. The animals were either (a) imaged by OCT and treated with a DCB and then re-imaged, or (b) imaged by OCT, re-imaged after micro-incisions were delivered by the Flex VP system, treated with DCB and then re-imaged again. The animals were survived to one, 15 or 30 days and the treated arteries then were processed to measure retention of paclitaxel concentrations.
Study findings:
Data from two head-to-head trials on drug-eluting technologies in femoral artery treatment were presented during a late-breaking session at LINC 2021 (Leipzig Interventional Course; 25–29 January, virtual)—one-year TRANSCEND and two-year COMPARE results. Both studies point to the non-inferiority of lower-dose paclitaxel devices, prompting discussion on whether these results will see a trend towards using lower-dose devices in practice. Although these results are promising, the panel agreed that more data are needed.
Kenneth Rosenfield (Massachusetts General Hospital, Boston, USA) presented one-year results of the TRANSCEND study, a non-inferiority randomised trial comparing the efficacy and safety of the SurVeil drug-coated balloon (DCB; Surmodics) versus the IN.PACT Admiral DCB (Medtronic), and Sabine Steiner (University of Leipzig, Leipzig, Germany) presented two-year results from the COMPARE trial, assessing the Ranger DCB (Boston Scientific) compared to the IN.PACT device.
All DCBs assessed utilise the anti-proliferative drug paclitaxel. The SurVeil and Ranger DCBs both have a low dose of paclitaxel (2µg/mm²) compared the the IN.PACT Admiral DCB, which has a higher dose of 3.5μg/mm².
TRANSCEND one-year results: SurVeil demonstrates non-inferior efficacy and safety versus IN.PACT Admiral
Rosenfield announced that primary results of TRANSCEND demonstrate the non-inferiority of the SurVeil DCB compared to the IN.PACT Admiral DCB with regards to both safety and efficacy, while delivering a substantially lower drug dose.
In the TRANSCEND trial, the SurVeil DCB was found to be non-inferior to the IN.PACT Admiral DCB in both the primary safety and primary efficacy endpoints. The SurVeil DCB cohort (n=222) exhibited a strong safety profile with 91.7% of subjects demonstrating freedom from device- or procedure-related death within 30 days and freedom from above-ankle amputation or clinically-driven target vessel revascularisation (CD-TVR) within 12 months, compared to 89.6% of subjects treated with the IN.PACT Admiral DCB (n=224).
The SurVeil DCB group also met its efficacy endpoint of primary patency of 81.7% as compared to 85.9% of the IN.PACT Admiral DCB arm. In addition, the number of reinterventions deemed clinically necessary by physicians did not differ between the products.
COMPARE two-year results: Ranger continues to demonstrate similar patency rate to IN.PACT
Two-year results from COMPARE, the first head-to-head comparison of two DCBs with different paclitaxel dosages and coating technologies for femoropopliteal interventions, were also presented.
The study compared the lower paclitaxel dose Ranger DCB to the higher paclitaxel dose IN.PACT Admiral DCB. One-year results of COMPARE were presented for the first time during LINC 2020 (Leipzig Interventional Course; 28–31 January, Leipzig, Germany) and published concomitantly in the European Heart Journal.
At two years, the Ranger DCB, which has a significantly lower drug dose density of paclitaxel continued to demonstrate a similar primary patency rate to the higher-dose IN.PACT DCB with a freedom from restenosis rate of 70.6% for the Ranger DCB (n=207) compared to the 71.4% observed with the IN.PACT DCB (n=207), according to Kaplan-Meier estimate (log-rank p=0.96).
No significant differences were observed for other secondary two-year outcomes, Steiner informed the LINC audience, detailing low all-cause mortality rates at two-years with 3.6% for the Ranger DCB vs. 2.2% for the IN.PACT DCB (p=0.6).
In addition, there was a low clinically-driven target lesion revascularisation (CD-TLR) rate through two years—17.8% for the Ranger DCB vs. 13% for the IN.PACT DCB (p=0.3).
Results for low-dose devices “reassuring,” but more data needed
Subsequent discussion focused on the significance of these results, with moderator Dierk Scheinert (University of Leipzig, Leipzig, Germany) posing the question: “Are low-dose balloons the way to go in the future?”
Rosenfield responded: “I think that this new generation of balloons is going to be better, and the safety data are comparable. If you are going to use multiple balloons in a given patient, I would certainly feel a lot more comfortable using a lower-dose balloon with better transmission of the drug and with less particulates downstream. I believe that this is going to be the way to go. Also, the technology is constantly improving.”
Steiner was in agreement, noting that the results are “reassuring”. While the data from both TRANSCEND and COMPARE point in a similar direction, Scheinert was curious to know if there are any key differences between the datasets. “COMPARE included longer lesions, up to 30cm,” Steiner began, adding that it also included more chronic total occlusions (≈40% CTOs). However, the speaker noted this design came at a price, referring to a much higher bailout stenting rate than TRANSCEND. Steiner also remarked that with the “more typical” design of TRANSCEND, with lesions of up to 18cm only, non-inferiority for a low-dose versus a high-dose balloon was also evident.
Both TRANSCEND and COMPARE assessed low-dose devices to the high-dose IN.PACT Admiral DCB. In the same late-breaking session, Thomas Zeller (Universitäts-Herzzentrum, Bad Krozingen, Germany) had presented long-term data on this device. Scheinert asked for his opinion on the results.
“We have to wait for longer-term follow-up data in order to see whether there will be a difference in terms of future safety endpoints,” Zeller remarked. “However, it is interesting to see that all the data with the first-generation DCB [IN.PACT Admiral] are more or less in line, independently of whether the maker of this device has conducted the trial, or if this balloon was used as a control,” he added, highlighting the strong data available for the device.
In terms of whether this should herald a move towards low-dose devices, Zeller was unconvinced: “I do not see a reason to switch, and I do not know whether it is really necessary.”
Panellist Marianne Brodmann (University of Graz, Graz, Austria) also commented, echoing Rosenfield: “If a low-dose device is as safe and as efficient in the long term as a high-dose device, I think a lot of physicians might feel more comfortable to use a low-dose device.” However, she also stressed that more data on these low-dose devices are needed.
The US Food and Drug Administration (FDA) has granted Pedra Technology a breakthrough device designation for the periprocedural use of the company’s Pedra Xauron perfusion system in the treatment of critical limb-threatening ischaemia (CLTI).
CLTI is a severe form of peripheral arterial disease (PAD) that is defined as ischemic rest pain, tissue loss, or gangrene (tissue death) that develops as a result of chronically poor blood flow to the lower limbs. If left untreated, CLTI can lead to limb amputation or death. The one-year mortality rate of CLTI patients without amputation is 30.3%, and with amputation is 40.4%. At five-years post-CLTI diagnosis, the mortality rate exceeds 50%, which is worse than most cancers.
The breakthrough devices programme at the FDA aims to provide patients and providers with timely access to medical devices that offer for more effective treatment and diagnosis of severe diseases, including a prioritised review of market approval regulatory submissions.
Paul Hayes, vascular surgeon and CMO of Pedra Technology, comments: “With the Xauron device, physicians can at last see real-time perfusion changes during an interventional procedure in the angiographic suite. I am excited about building on our early clinical data and demonstrating that Xauron will save patient lives and limbs.”
Hayes spoke to this newspaper last year at LINC 2020 (Leipzig Interventional Course; 28–31 January 2020, Leipzig, Germany) about the challenges of wound care, in particular assessing the success or failure of endovascular treatment of peripheral arterial disease. At the time, he described Pedra as a novel, portable, tissue-monitoring device that uses laser, and that provides real-time quantitative feedback in the angiosuite about whether the proceduralist has truly achieved improved blood flow to the microcirculation in the foot. Hayes noted that the device does not interfere with the workflow in the cath lab. The full interview can be seen here.“This breakthrough device designation recognises the compelling need for real-time tissue perfusion monitoring during lower limb revascularisation procedures for the treatment of CLTI. To my knowledge, this is the first perfusion monitor for CLTI that has received this designation,” comments Kareen Looi, CEO of PEDRA Technology. “An improvement in microvascular perfusion at the tissue level is necessary for elimination of rest pain, healing of chronic wounds, and for limb salvage. We look forward to developing this important new technology and working closely with the FDA to develop the appropriate clinical programme for market approval.”
Royal Philips has announced the final, five-year results of two randomised controlled trials (RCTs) that show no difference in all-cause mortality between patients treated with the Stellarex drug-coated balloon (DCB) and those treated with percutaneous transluminal angioplasty (PTA), the current standard of care. Moreover, the studies showed no difference in mortality between the Stellarex DCB and PTA at every 12-month endpoint over the course of the study. Results from the two RCTs were presented at LINC 2021 (Leipzig Interventional Course; 25–29 January, virtual).
The ILLUMENATE EU RCT and ILLUMENATE Pivotal RCT together comprised approximately 600 patients in Europe and the USA. After five years, the ILLUMENATE EU RCT showed 19.3% mortality among patients treated with the Stellarex DCB compared to 19.4% mortality for those treated with PTA.
The five-year results for the ILLUMENATE Pivotal study also show no statistically significant difference among patients treated with the Stellarex DCB (21.2%) compared to those treated with PTA (20.2%). Both studies had a high vital status follow-up compliance, with the status of over 90% of patients known.
“The five-year final results show favourable overall safety of the Stellarex low-dose paclitaxel DCB, and are applicable within an extensive patient cohort,” said Marianne Brodmann (Medical University of Graz, Graz, Austria), primary investigator for both trials and a paid consultant to Philips. “Every year, the Stellarex programme has demonstrated low mortality rates with no difference in rates between the two patient cohorts.”
“These study results build on the robust, consistent long-term data of the Stellarex program and confirm the safety and performance of our unique DCB,” said Chris Landon, senior vice president and general manager Image Guided Therapy Devices at Philips. “The Stellarex DCB, with its low drug dose and unique drug coating composition, continues to be an important treatment choice for healthcare providers treating patients with peripheral arterial disease.”
The journal CVIR Endovascular launched its own podcast in December 2020, to discuss endovascular and interventional interventions, and to promote the Cardiovascular and Interventional Radiological Society of Europe (CIRSE)’s open access journal. The podcast, hosted by editor-in-chief Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands), takes place every other month, and highlights articles published in CVIR Endovascular, as well as features interviews with contributing authors.
Interventional News discusses the new podcast with Reekers, and how he believes it will transform communication and education within interventional radiology through a broadening of the discursive channels available.
Why is it timely to launch a podcast now, and what are your hopes for this platform?
CVIR Endovascular is a platform for interventional radiology (IR) publications, but also for ideas and discussions. Since the postponement of many meetings due to the pandemic, we need a new way to communicate and to exchange our IR narratives, as narratives have always been an important part of this unique and innovative medical specialty. Podcasts are a great way to get our message out, especially to millennials, as you can listen a podcast when you want, and wherever you want.
How will the podcast and the journal complement each other?
They will be complementary in the sense that the podcast will enrich the journal and the publications with additional background information. It will create a community of young interventional radiologists around the journal.
What is it about the medium of a podcast that appeals/ what benefits are there to this format beyond the journal?
Narratives through podcasts are a relaxed way to communicate a message; it does not have the in-your-face nature of social media, you can consume it at your own pace. You can listen whenever you want, commuting, doing the dishes, cooking, just when you want. A podcast is like a friend and not like an aggressive salesperson, it does not speak in headlines. It is thoughtful and contemplative, something we all need in this complex world.
What sort of content can your audience expect from the podcast, and what in the next few months are you specifically excited to discuss with guests?
The podcast will highlight articles published in the journal, as well as hot topics, via interviews with many of our authors and a number of leaders in the field of endovascular interventions. CVIR Endovascular is a journal that promotes directions and ideas through editorials and is therefore a forerunner. The podcast will do exactly the same—it will make you think and sharpen your mind.
What developments in endovascular and vascular interventions are underreported/ explored, and how is CVIR Endovascular giving a platform to these topics?
Endovascular interventions are driven by the hype of the day, for example with all the drug-eluting technologies and the amazing technical skills, but the real core of IR is being a good and thoughtful doctor for your patients. A podcast does away with the dominant visual factor of current IR communications; as such, having a concurrent CVIR Endovascular podcast episode alongside an article will enrich the paper.
What can listeners expect in the future?
Our newest podcast episode is about our special issue of paediatric interventional radiology. I think it is important to become a friend of the CVIR Endovascular Podcast, to reset your mindset, and to step out of the IR roller coaster when you listen.
Please subscribe to the CVIR Endovascular Podcast on Apple Podcasts and Spotify, and visit our website for more information https://www.cvirendovascular.org/podcast/.
Bart Dolmatch (Portola Valley, USA) talks to Vascular News about some of the key data highlights from the 24-month AVeNEW trial, which compared the safety and efficacy of the Covera™ Vascular covered stent (BD) against percutaneous transluminal angioplasty (PTA) for the treatment of stenotic lesions in the upper extremity venous outflow of the arteriovenous access circuit.
The data, which was presented at CIRSE 2020, are “very compelling”, says Dolmatch, who notes that that the primary endpoints of safety at one-month and durability at six-months were “superior” for the covered stent compared to angioplasty alone. These results “hold up” at 24-months, he adds, with a greater target lesion primary patency for the covered stent group (N=69) compared to the PTA group (N=25), 41.8% vs. 10.4% respectively – highlighting a “dramatic improvement” at the target lesion site.
He also discusses the importance of circuit patency when treating hemodialysis patients, stating that there is now “robust data” to show that the use of the Covera™ Vascular covered stent is a “great strategy” for cephalic vein arch stenosis. Further sub-analyses showed that the Covera™ Vascular covered stent performed better regardless of the type of arteriovenous fistula, lesion location, de novo or recurrent lesions, concluded Dolmatch.
This video is sponsored by BD
Indication For Use: The Covera™ Vascular Covered Stent is indicated for use in hemodialysis patients for the treatment of stenoses in the venous outflow of an arterio-venous (AV) fistula and at the venous anastomosis of an ePTFE or other synthetic AV graft.
Warnings: DO NOT use in patients with known hypersensitivity to nickel-titanium or tantalum. · Placing a covered stent across a vessel side branch may impede blood flow and hinder or prevent future procedures. · DO NOT place a flared covered stent with the flared end in a straight vessel segment since this may lead to flow turbulences. · Covered stent placement beyond the ostium of the cephalic vein into the axillary/subclavian vein may hinder or prevent future access.
Potential Complications and Adverse Events: Complications and Adverse Events associated with the use of the Covera™ Vascular Covered Stent may include the usual complications associated with endovascular stent and covered stent placement and dialysis shunt revisions.
Please consult product labels and package inserts for indications, contraindications, hazards, warnings, cautions, and information for use.
A recent analysis by finds an association between depression and non-home discharge after revascularisation for chronic limb-threatening ischaemia (CLTI). Authors Joel L Ramirez, James C Iannuzzi (University of California, San Francisco, San Francisco, USA) and colleagues write in an online Journal of Vascular Surgery (JVS) article that these results “provide further evidence of the negative impact that comorbid depression has on patients undergoing revascularisation for CLTI,” and propose that future studies should examine whether treating depression can improve outcomes in this patient population.
“Recent evidence suggests that depression in patients with peripheral arterial disease (PAD) is associated with increased postoperative complications,” the authors begin, noting that problems can include decreased primary and secondary patency after revascularisation and increased risk of major amputation and mortality.
Ramirez et al note that the impact of depression on non-home discharge after vascular surgery remains unexplored, despite this being “an important outcome” for patients. They hypothesised that depression would be associated with an increased risk for non-home discharge following revascularisation for CLTI.
The investigators identified endovascular, open, and hybrid cases of revascularisation for CLTI from the 2012–2014 National (Nationwide) Inpatient Sample, which they explain is “a patient-level administrative claims database that is published annually by the Agency for Healthcare Research and Quality and represents approximately 20% of discharges from US hospitals”.
They write that a hierarchical multivariable binary logistic regression controlling for hospital level variation examined the association between depression and non-home discharge and controlled for confounders meeting p<0.01 on bivariate analysis.
Ramirez and colleagues identified 64,817 cases, of which 5,472 (8.4%) were diagnosed with depression, and 16,524 (25.5%) required non-home discharge. They relay that patients with depression were younger, more likely to be women, white, have multiple comorbidities, a non-elective admission, and experience a postoperative complication (p<0.05).
The authors report that, on unadjusted analyses, patients with depression had a 7% absolute increased risk of requiring non-hospital discharge (32.1% vs. 24.9%, p<0.001). On multivariable analysis, they found that patients with depression had an adjusted 50% increased odds for non-hospital discharge (odds ratio [OR]=1.5; 95% confidence interval [CI]=1.4–1.61; c-statistic, 0.81) compared to those without depression.
After stratification by operative approach, Ramirez et al identified that depression had a larger effect estimate in endovascular revascularisation (OR=1.57; CI=1.42–1.74) compared to open (OR=1.45; 95% CI=1.3–1.62).
Finally, the authors write in JVS that a test for interaction between depression and gender showed that men with depression had higher odds of non-hospital discharge compared to women with depression (OR=1.68; 95% CI=1.51–1.88 vs. OR=1.37; 95% CI=1.25–1.51; interaction p<0.01).
In the discussion of their findings, Ramirez and colleagues recognise that the present study is limited by certain factors. For example, they note that their investigation was based on a large national administrative database, in which all diagnoses are determined based upon billing codes. They acknowledge that use of this particular source “may introduce bias and be susceptible to under-reporting of certain comorbidities”.
The authors summarise that this study found a novel association between depression and non-hospital discharge after revascularisation for CLTI. Considering the wider impact of their findings, they write: “These results provide further evidence that an increased awareness about mental health is fundamental to care for vascular surgery patients and to understand postoperative pathways.”
Data from the EXRACT-PE trial, published online first in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions, found that the Indigo Aspiration system (Penumbra) met its predefined safety and efficacy endpoints for the treatment of pulmonary embolism (PE). In this multicentre, prospective study, the Indigo aspiration system was associated with a significant reduction in the right ventricular-to-left ventricular (RV/LV) ratio and a low major adverse event rate in submassive PE patients. Intraprocedural thrombolytic drugs were avoided in 98.3% of patients.
EXTRACT-PE stands for Evaluating the Safety and Efficacy of the Indigo aspiration system in Acute Pulmonary Embolism. It is a single-arm investigational device exemption (IDE) trial that enrolled 119 patients at 22 US sites, and is sponsored by Penumbra. Patients with signs and symptoms of acute PE for ≤14 days, computed tomography angiography (CTA) evidence of PE, systolic blood pressure ≥90 mm/Hg with evidence of dilated RV (RV/LV ratio >0.9), and who were 18 years of age or older were eligible for enrollment.
Patients were treated for acute PE with the Indigo aspiration system at each investigational sites. According to Penumbra, the Indigo system is designed to remove clots from arteries and veins in the peripheral vasculature. It was introduced in 2014, and received clearance for the PE indication in January 2020.
The primary efficacy endpoint analysis was the difference between the baseline and the 48-hour RV/LV diameter ratio; it was met if the lower bound of the confidence interval (CI) was >0.2.
The primary safety endpoint was the rate of major adverse events at the 48-hour mark, a composite of device-related death, major bleeding, and device-related serious AEs (SAEs). The primary safety endpoint was met if the upper bound of the CI was <40%. Device-related SAEs were a composite of clinical deterioration, pulmonary vascular injury, and cardiac injury. Secondary safety endpoints at 48 hours included rates of device-related death, major bleeding, clinical deterioration, pulmonary vascular injury, and cardiac injury. Additional secondary safety endpoints were 30-day rates of any-cause mortality, device-related SAEs, and symptomatic recurrence of PE.
Detailing their results, lead author Akhilesh K Sista (NYU Grossman School of Medicine, New York, USA) and colleagues write: “In this prospective study of the Indigo Aspiration device for submassive PE, we found a statistically significant reduction in RV/LV ratio (0.43; 95% CI: 0.38–0.47; p<0.0001), an average reduction in systolic pulmonary artery pressure of 7.9%, and a low major adverse event rate (1.7%) following use of the device. This was achieved with 98.3% of patients receiving no procedural tissue type plasminogen activator (tPA). The rate of major bleeding was 1.7%, and there were no haemorrhagic strokes. Of note, 89.6% (n=103 of 115) of patients had a reduction in RV/LV ratio without an adverse event related to the device, major bleeding, PE-related death, or clinical deterioration.”
This led them to conclude that the Indigo Aspiration system “may be considered by endovascular physicians for use in intermediate risk PE”, and to express the opinion that future prospective studies and randomised trials should focus on which patients (including high-risk PE patients and those with thrombolytic drug contraindications) derive the greatest benefit from aspiration thrombectomy.
Sista first presented these results at the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA).
New single-centre clinical study data published in the Journal of Neuroradiology claims to support Anaconda Neurovascular Access (ANA) catheter system for the treatment of ischaemic stroke.
Investigators at Hospital Vall d’Hebron, Barcelona, Spain, are participating in the multi-center SOLONDA (“SOL”itaire in combination with the ANA Catheter system manufactured by Anac”ONDA”) clinical trial, a 125-patient, prospective study that will assess system safety and reperfusion measured using the modified treatment in cerebral infarction (mTICI) score.
Hospital Vall d’Hebron investigators followed 35 consecutive patients, with published results as follows:
“The ANA device showed promising high rates of first-pass complete recanalisation,” Alejandro Tomasello (Hospital Vall d’Hebron, Barcelona, Spain), lead author and principal investigator of this study. “We hope that the device completes the regulatory process soon.”
According to a company press release, Anaconda’s investigational ANA catheter system consists of a funnel-shaped delivery and aspiration catheters to be used in combination with a stent retriever. When deployed, the funnel self-expands and directly conforms to the artery diameter up to 5mm. It is designed to locally restrict flow and allow full thrombus extraction without fragmentation. The SOLONDA study aims to validate earlier testing that achieved statistically significant improvement in revascularisation rates at both first and third pass.
“Vall D’Hebron’s early results are fulfilling our expectations for the safety and efficacy of the ANA System,” said Francois Salmon (Barcelona, Spain), CEO of Anaconda Biomed. “Its performance in this study, which was designed with great clinical rigour, is a testament to the system’s potential to benefit physicians and patients.”
Nephrology Associates of Northern Illinois and Indiana (NANI), the largest nephrology group in the USA, is the first practice in Illinois to adopt the Ellipsys vascular access system (Avenu Medical, now part of Medtronic), a technology for patients with end-stage renal disease (ESRD) who require haemodialysis treatments.
In May 2020, interventional nephrologist Gautam Bhanushali first used the Ellipsys system to create an endovascular fistula at NANI Vascular’s Willow Springs Surgery Center in Justice, USA. He has completed nearly a dozen Ellipsys procedures to date, and NANI plans to implement the Ellipsys technology at its other five outpatient vascular access centres in the near future.
“It is a very safe procedure, and research shows that fistulas created with Ellipsys can be used for dialysis sooner than surgically-created ones and that they also work for much longer periods of time,” said Bhanushali. “Patients find this new process much more appealing. Not only are they coming in for a procedure that has a higher likelihood of success, but it requires only a single needle stick instead of surgery, so they walk out with just a band aid on their arm. Our goal is to make the lives of dialysis patients easier, and that is exactly what Ellipsys does.”
For NANI, the use of the Ellipsys System will be a key part of the practice’s participation in the Kidney Care First (KCF) model, part of the federal government’s Advancing American Kidney Care initiative, according to chief executive officer Brian O’Dea. The initiative is designed to improve kidney patient health and quality of life, a large part of which is having ESRD patients begin dialysis with fistulas instead of central venous catheters (CVCs).
“Having a well-informed patient start dialysis with a functional fistula, under the care of a nephrologist, is invaluable,” said O’Dea. “That is what is being incentivised under these programmes, and we are pleased that the Ellipsys technology helps us comply with their guidelines and make a difference for our patients.”
New single-centre clinical study data published in the Journal of Neuroradiology claims to support Anaconda Neurovascular Access (ANA) catheter system for the treatment of ischaemic stroke.
Investigators at Hospital Vall d’Hebron, Barcelona, Spain, are participating in the multi-center SOLONDA (“SOL”itaire in combination with the ANA Catheter system manufactured by Anac”ONDA”) clinical trial, a 125-patient, prospective study that will assess system safety and reperfusion measured using the modified treatment in cerebral infarction (mTICI) score.
Hospital Vall d’Hebron investigators followed 35 consecutive patients, with published results as follows:
“The ANA device showed promising high rates of first-pass complete recanalisation,” Alejandro Tomasello (Hospital Vall d’Hebron, Barcelona, Spain), lead author and principal investigator of this study. “We hope that the device completes the regulatory process soon.”
According to a press release from the company, Anaconda’s investigational ANA catheter system consists of a funnel-shaped delivery and aspiration catheters to be used in combination with a stent retriever. When deployed, the funnel self-expands and directly conforms to the artery diameter up to 5mm. It is designed to locally restrict flow and allow full thrombus extraction without fragmentation. The SOLONDA study aims to validate earlier testing that achieved statistically significant improvement in revascularisation rates at both first and third pass.
“Vall D’Hebron’s early results are fulfilling our expectations for the safety and efficacy of the ANA System,” said Francois Salmon (Barcelona, Spain), CEO of Anaconda Biomed. “Its performance in this study, which was designed with great clinical rigour, is a testament to the system’s potential to benefit physicians and patients.”
Reflow Medical introduces the low-profile Spex LP 0.014 and 0.018-inch reinforced support catheters.
According to the company, the Spex LP is designed with a low-profile tip for accessing and crossing the “tightest and most complex lesions” with a supportive system. The customisable tip can be shaped to the desired angle and is compatible with the physician’s choice of guidewire and procedural technique. The device also features three radiopaque markers that enhance visibility on imaging. Additionally, the Spex LP can be combined with Reflow’s Spex 35 for more robust support, the company notes.
“Using the new Spex LP with the Spex 35 creates a telescoping action for extra support,” comments S Jay Mathews (Bradenton Cardiology Center, Bradenton, USA), one of the first physicians to use the Spex LP, in the company’s press release.
Jihad A Mustapha (Advanced Cardiac & Vascular Centers for Amputation Prevention, Grand Rapids, USA) adds: “The Spex LP has an extremely low lesion-entry profile and provides unmatched flexibility and trackability, especially in difficult cases.”
The US Food and Drug Administration (FDA) has granted premarket approval (PMA) for the Woven EndoBridge (WEB) 17 system from MicroVention, a US-based subsidiary of Terumo. This is a new addition to the WEB aneurysm embolization system for the treatment of intracranial wide-neck bifurcation aneurysms.
According to the company, the WEB 17 system is designed with microbraid technology, features a lower-profile delivery system compatible with the Via 17 microcatheter, and includes additional device configurations.
“The excellent clinical results we can achieve with intrasaccular flow disruption technology has changed the way we approach the treatment of wide-neck bifurcation aneurysms, and the WEB 17 system expands upon that,” comments Adam Arthur (Semmes Murphey Neurologic & Spine Institute and the University of Tennessee, Memphis, USA), principal investigator of the WEB-IT pivotal trial. “Now, we can deliver WEB devices using a low-profile system, similar to those used for standard coil embolization.”
In April 2019, Arthur et al published the final 12-month results of the WEB-IT trial in Journal of NeuroInterventional Surgery.
MicroVention stated that when placed inside the aneurysm sac, the WEB device’s microbraid technology bridges the aneurysm neck (disrupting blood flow) and creates a scaffold for long-lasting treatment. The WEB system received its first FDA approval in late 2018.
The WEB aneurysm embolization system is indicated for use at the middle cerebral artery bifurcation, internal carotid artery terminus, anterior communicating artery complex, or basilar artery apex for the endovascular treatment of adult patients with saccular, wide neck, bifurcation intracranial aneurysms with dome diameter from 3 to 10mm, and either neck size ≥4 mm or dome-to-neck ratio >1 and <2, advised MicroVention.
The UK Royal College of Radiologists (RCR) has partnered with the Apollo Radiology International (ARI) Academy to create a new exam centre in India.
The move means radiologists in India and surrounding countries will soon be able to sit RCR Fellowship (FRCR) exams locally, reducing travel and expense for candidates and with the aim of expanding RCR exam capacity across the region.
An RCR press release states that, as RCR Fellowship is “an internationally recognised benchmark of excellence”, there is high demand for FRCR exams in India. The press release also notes that RCR Fellowship status makes it easier for overseas doctors to register with the General Medical Council.
Currently, many Indian candidates travel to the UK or to centres in Hong Kong and Singapore to access the exam.
The new venue, which is currently being adapted and equipped with exam stations, is based in the south Indian city of Hyderabad.
Initially, it will host the Final FRCR Part B exam, before rolling out the First FRCR and Final FRCR Part A elements. Capacity will be subject to logistics and scaled up as the centre becomes established. However, the ARI Academy hopes to hold sittings for up to 150 candidates in future.
The RCR and ARI Academy had hoped to host the first Hyderabad exams in spring 2021; however, timelines are now under ongoing review due to the knock on impact of COVID-19 restrictions and logistical challenges.
Welcoming news of the joint agreement to launch the exam centre, RCR Overseas Ambassador for India Venkat Sudigali says: “It is a great initiative from the RCR to establish overseas exams centre in India.
“This exciting development will be of great benefit to many radiologists in India who are keen to attempt the FRCR exam to add to their qualifications, and also for those who potentially want to work in the UK in future, to learn new skills, and gain experience in the NHS.”
The new exam venue builds on recent collaborative work between the RCR and ARI, who worked with education and training partners in 2019 to create a scheme providing three-year placements for Indian radiologists looking to develop their skills working in the UK’s National Health Service (NHS).
Commenting on the Hyderabad exam venue, Sreenivasa Raju Kalidindi, ARI CEO and director of the ARI Academy, says: “It is a privilege to partner with the RCR in working towards a common vision of making FRCR exams more accessible and affordable to radiologists in India and other countries in this region.
“This initiative will set new benchmarks and empower large numbers of radiologists with the knowledge required to achieve higher standards in their practice.”
The RCR and ARI will release more information on the official launch of the centre and first exam bookings as soon as possible.
A trio of vascular experts including Raphaël Coscas (Paris, France), Alexandros Mallios (Paris, France) and Kate Steiner (Stevenage, UK) discuss the key findings of the IN.PACT™ AV Access trial–which was recently published in the New England Journal of Medicine (NEJM)–and what impact its data might have on patients and in clinical practice.
Mallios believes the data is “groundbreaking”, with all physicians agreeing that publication in the NEJM shows that it is a “high-quality” trial. The data itself highlighted a “significant” improvement in patency of the target lesion primary patency with the IN.PACT DCB compared to plain balloon angioplasty.
The experts further delve into what the findings mean for the quality of life of patients, and their own daily practices, with Coscas noting that the benefit of fewer reinterventions and hospitalisations is “huge”. Mallios adds that the data has shown improvement of the entire fistula, not just the primary patency, with the IN.PACT DCB which, for him, is “the most important and most relevant characteristic of this paper”. Concluding, Steiner notes that the IN.PACT AV Access data “adds weight” to the use of DCBs in her clinical practice.
This video is sponsored by Medtronic.
There are several covered stents on the market that are used in an off-label setting as bridging stents for fenestrated and branched endovascular aneurysm repair (F/BEVAR). Currently, there is no consensus on when to use what—no gold standard, no proof, no evidence. According to three experts in the field, however, this is about to change. As trials take place and data begin to emerge, Vascular News speaks to Stéphan Haulon (Hôpital Marie Lannelongue, GHPSJ, Paris, France), Eric Verhoeven (Klinikum Nuremburg, Nuremberg Germany), and Tim Resch (Copenhagen Aortic Center, Rigshospitalet, Denmark), who express their views on the past, present, and future of bridging stents in FEVAR and BEVAR.
Considering the origins of bridging stents in these indications, Haulon explains that they have been used “for years”, but in an off-label sense. Nowadays, however, he relays that specific devices are being developed, and that trials are beginning to specifically evaluate bridging stents for FEVAR and BEVAR.
“I think it is important to stress that bridging stents for fenestrated endografts have different features to bridging stents for branched devices,” Haulon says. “The main difference is that we use bridging stents to connect the fenestration to the target vessel, but usually the fenestration is adjacent or close to the origin of the target vessel, so the bridging stent does not need to cross a large gap or a large aneurysm sac before going into the target vessel. In addition, it needs to be locked to the fenestration […] so there is a flaring process, whereas in branches, you have a long overlap between the bridging stent and the branch, and you have a long gap in most cases to bridge the aortic device to the target vessel,” he explains.
Resch elaborates: “In many cases of fenestrated repair for pathologies such as juxtarenal and pararenal aneurysms, where you have wall apposition of the main body of the device, the fenestrated or branched stent per se is not much for seal, but for direction, to keep patency in these vessels.”
“It means that [the] stent is much shorter and less subjected to difference forces, whereas oftentimes in a branch repair, you are actually traversing an aneurysmal space. It needs to create a whole different seal between the main body of the endograft and the target vessel and traverse a lot of space in between, so those stents are typically longer and need to display more varied properties. They have to be strong and flexible and to withstand forces of a different magnitude than bridging stents in fenestrated grafts,” he adds.
Within this context, Verhoeven highlights the fact that fenestrated and branched procedures require different types of stents. “In fenestrated grafts, or in grafts with fenestrations only, we use balloon-expandable covered stents that we can flare, while in branched grafts, we can use either self-expandable covered stents or balloon-expandable covered stents,” he states, adding that the next step in the branched setting is to have more flexible balloon-expandable covered stents to accommodate the angles between the branches and the target vessel.
Past: Expanding clinical goals and the changing role of industry
Historically, physicians did not have much choice about which stent to use, Verhoeven stresses. Resch echoes this lack of choice, recalling his experience from 15–20 years ago: “It was all about getting a graft in place, so we took whatever device we could regarding trackability and profile, and tried to get it in place.”
Nowadays, they emphasise that the aim is more focused on long-term outcomes. He explains: “Over the years, we have obtained more experience and data on what actually makes the device last, so our aim today is not just to get a device in place and get an aneurysm excluded, but to keep that aneurysm excluded over a long period of time.”
Regarding industry, Verhoeven notes that there used to be only a few companies who had the desire to develop these devices as it was a small market, but that this market has “continuously grown”.
Speaking on this changing role, Haulon remarks that, given the off-label use of these devices, the only way to get better was to combine experiences in order to try and find out which stent worked best in which indication, with little input from industry. “What is changing is that now industry is coming up with dedicated bridging stents and launching trials, so we will have real evidence,” he explains.
More specifically, Verhoeven details which devices he currently uses in his practice. “In fenestrations, we currently use the BeGraft [Bentley], which is a dedicated balloon-expandable covered stent for fenestrations, and we also use the Advanta V12/iCast [Getinge], which we have been using for years. We use both as the ‘new’ Begraft provides all the diameters and lengths we require. For branches, our first covered stent is the balloon-expandable BeGraft Plus [Bentley]. As a bailout with regard to length, we also use the VBX [Gore], because that is the only balloon-expandable covered stent that comes in a length of 79mm.”
Present: Crucially different demands of FEVAR and BEVAR highlight need for trials
The interviewed physicians are keen to stress the importance of differentiating between FEVAR and BEVAR. Recognising the unique demands of the two procedures is “crucial,” according to Resch. “There is still some confusion with regards to that in the marketplace and among users, which sometimes leads to disastrous outcomes,” he explains, using the example of BeGraft (for fenestrations) and the BeGraft Plus (for branches) as examples, stressing that they are “two totally different devices that we use for two totally different things”.
In his consideration of why the two are confused, Haulon underlines the need for data and dedicated stents: “I think the main reason is that we do not have approved bridging stents for the technology. They are being used off-label and that is why we urgently need specific trials.” He elaborates that Bentley is currently actively supporting both a FEVAR and a BEVAR physician-initiated trial with the BeGraft and the BeGraft PLUS as bridging stents that he hopes will bring the data needed to support which stents works well for which indication.
Future: The journey from off-label to on-label continues
Resch sees the gathering of data for these indications as part of an essential part of a wider project. “We have worked on main body stent graft development for many years, and it feels like the mating stents were left a bit behind, so we are very happy now that we are finally taking on the whole package, because the repair itself and its durability is really dependent on the whole graft,” he comments.
“It has been a very long journey,” Haulon adds, noting that it “felt bad” to be using stents off label for so many years. “There was a huge learning curve for everyone, and it was a niche for companies for many years,” he recalls, but adds that the need for data is evident.
“We are moving from pioneering times to a mature technology,” Haulon concluded.
In an effort to raise the profile of paediatric interventional radiology (PIR), CVIR Endovascular Editor-in-Chief Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands) has invited Alex Barnacle (Great Ormond Street Hospital, London, UK) and Anne Marie Cahill (The Children’s Hospital of Philadelphia, Philadelphia, USA) to guest edit the journal’s first thematic series on the topic.
Barnacle and Cahill commissioned four review articles, which they say “detail the latest evidence for a range of complex interventions in children, demonstrating current best practices in this highly specialised field”.
Musing in an editorial about the lessons learned from these articles, Barnacle and Cahill write: “These reviews illustrate that many of the latest advances in adult IR are applicable in children, despite the concerns of many adult IR practitioners that such interventions may be too risky or perhaps futile. Each paper, however, also highlights the frustrations common to every paediatric interventional radiologist. These include the limited evidence base available to date, the lack of paediatric-sized equipment, and the challenges of developing and maintaining IR competencies with small caseloads, often focussed in only a few specialised centres.”
Whilst they acknowledge these challenges to PIR, they also note that the specialty has come a long way since the early 1980s, when the first paediatric papers were published in the interventional radiology space. According to Barnacle and Cahill, the first PIR workforce survey in 2007 identified “just 110 PIRs practising worldwide, rising to 177 in a follow-up survey 10 years later”. However, in 2020, more than 600 delegates from 22 countries registered for the Society for Pediatric Interventional Radiology (SPIR) annual congress. The editorialists suggest that this is “in part due to the advantages of new online conference accessibility during the COVID-19 pandemic”, but that this “groundswell of interest may be influenced by increasing visibility of the speciality through the work of publications such as this [CVIR Endovascular] and organisations such as SPIR, but we believe it also speaks to a growing interest in a speciality that brings great rewards for those searching for greater meaning in their work. There is immense satisfaction in giving a family real hope for their child and providing care that often means accompanying a child throughout their journey to adulthood.”
They conclude their editorial with a call to action: “It is imperative that we strive to eliminate the inequality that means the vast majority of children even in developed countries are denied modern, minimally-invasive, safe, and highly effective IR procedures that are routinely offered to adults. Significant progress has been made in recent years by a small, highly dedicated PIR workforce, but there is still much more to be done.”
Interventional News spoke with Barnacle about the publication of the CVIR Endovascular guest editorial, to gain insights into the urgency and nature of future PIR work.
What is the significance of having the first CVIR Endovascular thematic series be dedicated to paediatric interventional radiology (PIR)?
This is a real honour for our sub-specialty. This series highlights the breadth and depth of PIR. We hope it will give readers cause to stop and think, and consider what they could perhaps apply in their practice.
What have been the pivotal developments in PIR research and clinical practice since its inception in the early 1980s?
Over time, we have shown that there is far more that is possible in small children than even we could have imagined. PIR has changed the management of a number of diseases and provided minimally invasive options for thousands of children who would otherwise not have been offered treatment or would have undergone far more invasive surgery.
What areas of PIR do you feel are particularly under-researched/ demand greater attention?
It is a real challenge to trial interventional oncology (IO) treatments in children because almost all patients are on protocols that do not include IO options. PIR is where adult IR was 20 or 30 years ago, only being given access to patients who have failed most other interventions. This means that the data are sketchy and our patient cohorts are skewed. In time, we hope to see the oncology organisations show greater confidence in the aims we are pursuing.
What are the biggest challenges to PIR currently, and how can these be overcome?
The biggest hurdle outside of North America is getting hospitals to recognise what PIR can do when it is a fully resourced service. Most centres are not aware of what we can deliver or the benefits we bring. We need more training schemes, more consultant posts, and the commitment to building PIR in several centres in each country, so that children everywhere have access to minimally-invasive, effective IR treatment options.
What message do you want to give to those considering a career in PIR?
PIR is such a rewarding career! Contact a PIR centre near you and ask to visit—you will be amazed by what our departments offer and may be inspired to join us in growing this speciality together.
You can read the full PIR series on CVIR Endovascular here.
The full list of articles can be found below:
Mermaid Medical Group recently announced US commercial availability of the D-Clot HD rotational thrombectomy system. As of 12 January, the company reports 25 successful human cases.
‘‘I am extremely pleased to see dialysis patients who are heavily involved with the healthcare system benefits from the release of D-Clot HD.’’ said Lars Vinther, CEO of Mermaid Medical Group.
A multicentre limited market release evaluation demonstrated the system’s ability to restore flow effectively and safely with no reported complications. The data derives from several institutions where numerous users applied the technology to patients and showed effectiveness across variations in vessel size, access type, and thrombus morphology.
“Today marks a major milestone for the company as we are transitioning to full commercialisation of the product in the USA,’’ stated Lars Vinther. The D-Clot HD will provide an added mechanical thrombectomy option for physicians involved in arteriovenous (AV) access flow restoration.
A recent study concludes that arterial diameter may influence arteriovenous fistula (AVF) aneurysm progression and the interval to surgical revision. “Patients with larger arterial diameters should be monitored closely and referred early after aneurysm development,” authors Alexis M Cahalane (Massachusetts General Hospital, Boston, USA) and colleagues write in an online article in The Journal of Vascular Access (JVA).
Another key finding from the study was that radiocephalic AVFs are more resistant to aneurysm development, and “should be considered the first access option for ESRD [end stage renal disease] patients, especially younger patients,” the authors communicate.
This study included all patients who underwent fistula surgical revisions due to aneurysms between 1 January 2014 and 30 July 2016. From this data pool, the investigators collected patients’ demographics and AVF dimensions based on fistulograms. They identified a control group with non-aneurysmal AVFs who had undergone serial fistulograms between 2013 and 2016.
In this retrospective study, Cahalane and colleagues identified 45 eligible patients in the AVF aneurysm group and 24 in the control group, with the mean age of AVF creation being older in the control group (61.8 vs. 53 years, p=0.03).
Writing in JVA, they report that the mean interval between AVF creation and first fistulogram in the study group was 1,464±282 days, compared to an interval of 263±101 days in the control group (p=0.003). Cahalane et al added that the arterial diameter on first fistulogram (r=0.6, p=0.03) predicted maximum aneurysm diameter on the last fistulogram (r=0.6,p=0.03) as well as the interval between first fistulogram and surgical revision (r=-0.33, p=0.03).
In the discussion of their findings, the authors list some limitations of the present study. They note, for example, that the study group contains only a small number of patients with heterogeneous distribution of AVFs in terms of laterality and location. They explain the reasons behind this: “The overall five-year survival rate for ESRD patients receiving haemodialysis was recently found to be 42%, and aneurysms are a late complication of access, with the average follow-up in our study being 1,324 days. Thus, a small number of patients met the study criteria.”
Keith M Hume has joined the Society of Interventional Radiology (SIR) today as the organisation’s new executive director.
In this role, Hume will advance SIR’s advocacy, education and policy mission to strengthen and support the practice of interventional radiology and ensure patient access to minimally invasive, image-guided therapies, an SIR press release states.
“I am honoured to join SIR at this exciting time as interventional radiology continues to cement its status as a primary specialty and build a brighter future for patients through minimally invasive medicine,” comments Hume. “Today’s changing healthcare environment presents a variety of new opportunities. I look forward to working with SIR’s physician-volunteers, members, and staff to advance the interventional radiology specialty by transforming the way SIR educates its members and patients, fostering scientific research and innovation, and increasing cross-specialty collaboration.”
Hume previously served as SIR Foundation’s executive director from 2003–2008. He has nearly two decades of executive experience in the healthcare association sector driving strategic program development, regulatory advocacy, organisational growth, and creating sustaining strategic partnerships with healthcare stakeholders, the society state. Hume rejoins SIR following 13 years at the American Society of Plastic Surgeons and the Plastic Surgery Foundation.
“We are thrilled to welcome Keith Hume back to SIR,” says SIR president Michael D Dake (University of Arizona Health Sciences, Tucson, USA). “His understanding of interventional radiology, coupled with his passion for research, quality, and education, will take SIR to new heights as we look forward to transforming IR education, launching our new VIRTEX registry, and growing our research grants and quality improvement programs.”
Hume holds a Bachelor of Science degree from the College of William and Mary (Williamsburg, USA) and a Master of Arts degree, where he focused on autonomic and cardiovascular regulation from the University of Georgia (Athens, USA).
The first fully remote, online-proctored European Board of Interventional Radiology (EBIR) examination took place on 13 January, 2021, with a 113 participants from 25 countries sitting the test.
EBIR is a voluntary supplemental examination designed to evaluate interventional radiologists’ clinical and technical knowledge, and was first released in 2010 in Valencia, Spain.
According to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), by taking this examination, “interventional radiologists can certify their expertise and demonstrate their ongoing commitment to pursuing a career in this rapidly evolving discipline”.
“If you are thinking about taking the exam, the CIRSE Library offers hundreds of lectures ideally suited to EBIR preparation,” CIRSE shared on Twitter.
The next EBIR examination will take place on 3 March 2021, and will also be conducted remotely.
In addition to submitting their CV and filling out a competency checklist, applicants for the EBIR examination must also have completed national radiology training. The applicant and the responsible authority listed in the document are also required to confirm that two years of interventional radiology training have been completed or will be completed within a specific time frame. At least one year of this training must be completed after national radiology training.
Applicants must also verify that they have experience as the first operator, performing at least 250 interventional radiology procedures, 150 of which have to be interventions according to chapter 2.2.1 Vascular Diagnosis and Intervention and/or chapter 2.2.5.2 Vascular Interventional Oncology in the European Curriculum and Syllabus for Interventional Radiology.
Following the publication of the SWEDEPAD interim analysis, Andrew Farb, Misti Malone, and William H Maisel, representatives of the Center for Devices and Radiological Health, US Food and Drug Administration (FDA), have authored a perspective piece in the New England Journal of Medicine (NEJM), titled, “Drug-coated devices for peripheral arterial disease [PAD]”.
“Percutaneous revascularisation procedures can improve claudication symptoms, and devices coated with antiproliferative drugs (drug-coated balloons and stents) reduce neointimal proliferation after revascularisation procedures. Pivotal randomised, controlled trials (RCTs) of paclitaxel-coated devices [PCDs] in patients with femoropopliteal PAD reveal significantly reduced repeat-revascularisation rates as compared with use of uncoated devices. Reasonable assurance of device safety and effectiveness at one year has led the FDA to approve six PCDs to date, and their use has become common in symptomatic patients,” they write in NEJM.
“The results of the SWEDEPAD interim analysis provide important and reassuring information on PCDs used to treat femoropopliteal disease,” say Farb et al. “Furthermore, recent analyses of additional data from nonrandomised studies have not identified an increased mortality risk associated with PCDs.”
However, they also add that these newer analyses, “though comforting, are limited by the duration of follow-up”.
“Because of the demonstrated short-term benefits of the devices and the limitations of the available data, the FDA believes that clinical studies of these devices should continue and should collect long-term mortality data. Similarly, the FDA now routinely reviews longer-term data for PCDs for which market authorisation is being sought when they are intended to treat patients with PAD, and the agency requests that trials capture information on adjunctive antithrombotic therapy and medications indicated for patients with atherosclerosis,” they conclude.
VasQ, a high haemocompatibility biosynthetic vascular device from Laminate Medical Technologies, could be protective against the haemodynamic modifications that occur during arteriovenous fistulae (AVF) creation, a recent article in The Journal of Vascular Access reports. Roberto Palumbo (Saint Eugenio Hospital, Rome, Italy) and co-authors caution that their results, which derive from their clinical experience and are thus representative of a “real-life setting”, should be considered preliminary. They call for further research of the VasQ device in AVF creation, and say that “further effective treatments are needed to prevent or treat AVF failure”.
According to Palumbo et al, the VasQ device was designed “to improve the outcome of AVF [creation] by optimising the haemodynamics of the flow in the juxta-anastomotic region of the AVFs through tailored external support”. They continue: “The rationale for supporting the implantation of [the] VasQ device is based on the reduction of the turbulent blood flow through the anastomotic site and of the radial stretching of their venous wall, allowing a potential attenuation of hyperplasia and stenosis consequences and, finally, improving AVF-outcomes in haemodialysis patients.”
AVFs are the current gold standard for vascular access during the treatment of optimal chronic haemodialysis patients, due to their prolonged patency and durability, and thanks to their low complication profile. However, there is a high non-maturation rate of native fistulas. The study authors note that a prolonged maturation time, neointimal hyperplasia at the anastomotic site, and a high rate of abandonment are disadvantages associated with AVFs, and state that AVF creation “may cause significant haemodynamic modification in cardiovascular parameters”, potentially leading to adverse cardiac outcomes, such as progressive heart failure.
To establish if the use of the VasQ device would help reduce these haemodynamic modifications, the investigators compared patients who underwent native radio-cephalic AVF creation with and without implantation of the device at their institution between May and September 2019 (15 individuals in each group). Haemodynamic parameters were evaluated pre-operatively, and at one, three, and six months follow-up. The patency and complication rate were also evaluated.
At baseline, there was no significant difference between the treatment group and the control group in terms of mean preoperative arterial flow, vein diameter, preoperative ejection fraction, and cardiac output. Arterial diameter was greater in the treatment group (those where the VasQ device was deployed) at baseline (3.4±0.8mm vs. 2.8±0.5mm), but Palumbo and colleagues dismiss this, writing: “Although the vessel radius is considered a major determinant of the vessel flow, this finding may have reflected only marginally in the clinical results achieved in the VASQ device implanted [in] patients”.
While at one-month follow-up, there was no difference in mean arterial flow between the two cohorts, a significant difference was observed at three months (645±143mL/min in the VasQ group vs. 824±211mL/min in the control group; p=0.02) and six months (714±146mL/min vs. 810±194mL/min; p=0.05).
At six months follow-up, the cardiac output flow was lower in the cohort of patients implanted with the VasQ device: 4,458±928ml/min versus 5,599±1,355mL/min (p=0.05). Palumbo et al suggest that this could mean that the VasQ device “may provide a potential benefit in preventing haemodynamic modifications of the cardiovascular system and preventing the overload of the left ventricle by reducing the altered high cardiac output of haemodialysis patients associated with AVF creation”.
“Of note, no VasQ device complications were recorded,” the authors write. “The VasQ has been well tolerated by the patients, and no patient had poor subcutaneous tissues at the anastomotic site. During surgery, no technical complication occurred.”
At six months, primary patency was 73% in the treatment group and 80% in the control group, respectively. Cumulative patency was 80% and 86%, respectively, in implanted VasQ device patients compared to those in the control group.
“Although our experience is limited to a small group of patients with a relatively short follow-up”, Palumbo and colleagues write, “we confirmed the substantial safety and utility of [the] VasQ device in AVF creation. […] Our experience outlined that the implantation of [the] VasQ device during AVF creation compared to those [who underwent the] standard technique may allow a stabilisation of the high cardiac output of haemodialysis patients.”
Revisions to current procedural terminology (CPT) codes in the USA for 2021 overhaul the evaluation and management section, reducing documentation requirements and introducing new rules determining the level of coding. These changes will affect interventional radiologists and radiation oncologists more than they will impact the day-to-day work of diagnostic radiologists, according to Erin Stephens, a senior client manager in education at Healthcare Administrative Partners.
There are also several other non-evaluation and management code changes affecting interventional radiology for 2021.
Changes to the evaluation and management services section
Under the revised evaluation and management coding structure, physicians may elect to document a visit based either on time spent or on medical decision-making. Level 1 (99201) for new patients has been eliminated, leaving four levels of billing for new patients and five levels for established patients.
Until now, the level of coding has been determined by time spent face-to-face with the patient and by evaluating the three components of an exam:
The new system that begins in 2021 will be based only on the following:
For an established patient, a level 1 visit (CPT 99211) might not require a physician to be involved. This could be a nurse visit or blood pressure check. There is minimal medical decision-making and no prescribed time element.
Medicare has approved a new code, G2212, to be used for encounters that exceed the maximum time for a level 5 (99205/99215) visit. Its description is “Prolonged office or other outpatient evaluation and management services (beyond the total time of the primary procedure which has been selected using total time), requiring total time with or without direct patient contact beyond the usual service, on the date of the primary service; each 15 minutes.” This mirrors the language of CPT code 99417 that might be approved by payers other than Medicare.
Other changes: Lung biopsy
The code 32405, “Biopsy, lung or mediastinum, percutaneous needle,” has been replaced by a new code 32408, “Core needle biopsy, lung or mediastinum, percutaneous, including imaging guidance, when performed.” Accordingly, imaging guidance may no longer be billed separately. When more than one core needle biopsy of the lung or mediastinum is performed on separate lesions during the same session on the same day, then 32408 is billed once for each additional lesion along with modifier -59.
Ventricular assist device (VAD) insertion
The coding of these procedures was revised to differentiate between left- and right-heart procedures, encompassing either initial placement or replacement of a percutaneous VAD.
Other changes: Endovascular venous arterialisation
Coding has been available for endovascular revascularisation (37228-37231 and 0505T), but not for arterialisation. A new code (0620T) has been created as follows:
“Endovascular venous arterialisation, tibial or peroneal vein, with transcatheter placement of intravascular stent graft(s) and closure by any method, including:
Other changes: Ultrasound ablation of pulmonary arteries
A new code (0632T) has been created as follows:
“Percutaneous transcatheter ultrasound ablation of nerves innervating the pulmonary arteries, including:
A recent network meta-analysis shows that, in failing arteriovenous fistulas (AVFs) with outflow stenosis, drug-coated balloon (DCB) angioplasty is “significantly superior” to plain balloon angioplasty, presenting an improved six-month failure rate. However, Gregory Tripsianis (Democritus University, Alexandroupolis, Greece) and colleagues stress that the effectiveness of DCB angioplasty in the long term “deserves further investigation”.
While the 2018 European Society for Vascular Surgery (ESVS) vascular access clinical practice guidelines recommend balloon angioplasty for the treatment of venous outflow stenosis to extend the use of AVFs, the authors note that its effectiveness compared to other endovascular modalities “remains unclear”. In fact, they state more generally that “there is currently uncertainty regarding the ideal treatment to salvage failing AVFs”.
Writing in an online Journal of Vascular Surgery (JVS) article, Tripsianis et al note that it was their intention in this study to investigate the comparative effectiveness of the different endovascular treatments in patients with failing autogenous AVFs with outflow vein stenosis.
The investigators detail that they searched Medline/PubMed and SCOPUS databases for studies that fit the criteria of being randomised controlled trials (RCTs), compared endovascular treatments of autogenous AVF stenosis—including plain balloon angioplasty, cutting balloon angioplasty, and DCB angioplasty—and provided six-month and/or one-year patency data for each group at follow-up.
Inclusion criteria were venous outflow, anastomotic or swing area stenosis, either de novo or recurrent, and exclusion criteria were central vein stenosis or RCTs including open surgical repair or stent/stent graft arms.
Following the literature search, Tripsianis and colleagues performed a systematic review and network meta-analysis of RCTs investigating the effectiveness of plain balloon angioplasty, cutting balloon angioplasty, and DCB angioplasty in autogenous AVFs vein stenosis. They write that they included eleven RCTS in the study, reporting a total of 814 patients, of whom 395 underwent plain balloon angioplasty.
According to the authors, their network meta-analysis showed that DCB angioplasty at six months was “significantly more effective” than plain balloon angioplasty (odds ratio [OR]: 0.39, confidence intervals [CI]: 0.18–0.81) and ranked as the best treatment option, but without having statistically significant difference when compared with cutting balloon angioplasty (OR: 0.65, CI: 0.2–2.12).
Writing in JVS, the investigators also report that statistical significance was not achieved at one year among treatments, and that additional conventional pair-wise meta-analyses did not find significant differences at one year.
Tripsianis et al stress that the results of this review “should be interpreted with caution” due to some limitations. Firstly, they acknowledge that the network geometry did not provide any closed loops and write that “no direct comparison between DCB angioplasty and cutting balloon angioplasty existed, thus it was impossible to assess inconsistency between direct and indirect evidence”.
In addition, they note that there was “a considerable degree of heterogeneity” among the included RCTs and that confounding factors were present. They detail: “There was blending of various AVF configurations, de novo lesions with recurrent ones, high-pressure balloon use in a variable number, different brands of DCBs and paclitaxel dose, differences in patency reports (target lesion versus circuit patency), and difference in methodology of angioplasty regarding predilatation or post-dilatation following DCB angioplasty”.
Finally, they recognise that there was “a high risk of bias” among the included studies, especially those comparing plain balloon angioplasty with cutting balloon angioplasty. Tripsianis et al detail that most of the trials suffered from the “inherently high risk in the domain of blinding,” specifying that all but one of the included studies suffered from bias in blinding or personnel, as this is “almost impossible” in endovascular procedures. However, they note that there was some blinding of the outcome assessment in six studies.
Speaking to Vascular News, Miltos Lazarides (Democritus University, Alexandroupolis, Greece), one of the study’s senior authors, considered the present study in its wider context. He noted that a recently-published RCT had similar findings to those presented here. In the New England Journal of Medicine, Robert Lookstein (Ichan School of Medicine at Mount Sinai, New York, USA) et al found that DCB is superior to plain balloon angioplasty at six months, based on data from 330 patients.
Rapid Medical has announced its Drivewire novel guidewire with a steerable distal top, has received US Food and Drug Administration (FDA) clearance. According to a company press release, Drivewire is the first neurovascular guidewire with a controllable distal end that can change course and shape on-demand for more precise navigation.
Rapid Medical states that, with Drivewire, physicians control the direction and shape of the guidewire’s tip while it is inside the vessel, precisely navigating the neuro and peripheral vasculature. Rapid Medical add that this intravascular steering provides access to difficult anatomical locations, increasing the physician’s ability to treat vascular diseases with less invasive interventional approaches.
The press release states that guidewires are key components for treating intravascular diseases such as ischaemic and haemorrhagic strokes. Rapid Medical claims that currently physicians do not have direct control over the guidewire tip and often remove the guidewire several times to reshape it before reaching the desired location.
Erez Nossek, (NYU Langone, New York, USA), commented: “The development of Drivewire has been an exciting collaboration. I can now easily navigate through complex anatomies by varying the shape of the wire tip inside the vessel, something that cannot be performed with the current neurovascular guidewires.
“I expect this first-of-its-kind technology to benefit patients with challenging anatomies and increase the interventional treatment options available to them.”
Outside of the US the device is named Columbus.
The European Trainee Forum of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Residents, Fellows, and Students section of the Society of Interventional Radiology (SIR), the Society of African Interventional Radiology & Endovascular Therapy (SAFIRE), and Road2IR—a collaborative effort between several partner institutions aiming to build self-sustaining interventional radiology (IR) training programmes in East Africa—have published an open letter to the World Health Organisation (WHO) in CVIR Endovascular, calling for an increase in the efforts to understand the needs of low income countries regarding image-guided therapies.
In what participants hope marks “the beginning of a great collaboration between the WHO and the IR community”, several letter signatories first met with Adriana Velazquez Berumen, group lead for medical devices and in vitro diagnostics at WHO, online on 23 October to discuss IR and service development in low income countries. Interventional News understands that these remote conversations are ongoing, and that an online petition is in the pipeline “to continue raising awareness and increase the pressure on the WHO to do something about this [lack of IR provision in low-income countries]”.
First author of the CVIR Endovascular letter Yi Yang (Aventura Hospital and Medical Center, Aventura, USA) and colleagues say that the intent of the address is “to initiate a discussion on and collaboration in addressing the dramatic lack of interventional radiology services in low income countries and the lack of associated data”.
The letter is also approved and supported by Andrew Kesselman (RAD-AID International), Susan Jackson (Western Angiographic and Interventional Society), Kartik Ganga and Sreenivasa Raju (both Indian Society of Vascular and Interventional Radiology), Gerard Goh (Interventional Radiology Society of Australasia), Murray Asch and Kevin Shixiao He (Canadian Association for Interventional Radiology), and Karin Euler (Canadian African Health Care Alliance—Tanzania).
The authors write: “Prompt publication of countless dedicated research articles, public education through news outlets and social media on preventive measures, and initiation of vaccine development within weeks of the COVID-19 outbreak highlight the many benefits of global connectivity and collaboration. Yet, these times of fear and stress reveal the persistent chasm of racial inequality, healthcare inequity, and social injustice that have plagued humanity for centuries. These inequalities extend into almost every facet of medicine, but nowhere is the disparity more extreme than in minimally invasive treatment options available to patients in high-income countries and the near-complete lack thereof in most low- and middle-income countries (LMICs).
“[…] There are several hurdles to the implementation of IR in LMICs, including the sparsity of baseline data, limited access to equipment, and lack of training. In order to facilitate effective IR training and adequate supply of IR equipment, there is a critical need for improving and updating the ‘WHO Global Atlas of Medical Devices’.”
Speaking to Interventional News about the significance of a collaboration between the WHO and the IR community, immediate past chair of CIRSE’s European Trainee Forum and past chair of the British Society of Interventional Radiology (BSIR) trainee committee, Gregory Makris (Guy’s and St Thomas’ NHS Foundation Trust, London, UK), a senior author of the open letter, comments: “This letter is part of an effort to increase awareness around this very important issue. During the last five years there has been significant effort in increasing the presence of IR in Africa, but we now need more structured support to take these efforts to the next level. We have to make people understand that even standard life-saving procedures like a nephrostomy insertion or a drain of a liver abscess are currently not possible due to the luck of expertise and kit. The scale of the problem, as well as its significance, is massive, and that is why it is important to have a collaboration between international IR societies, the WHO, and the medical devices industry to address the various issues in lack of training, manpower, and supply chain/kit. We are planning to start an online petition within 2021 in order to reach even more people and get people interested in our cause. Introducing IR in Africa can have a major impact in raising health care standards given the multidisciplinary nature of our specialty. We hope for your support.”
Updating the WHO Global Atlas of Medical Devices
The WHO Global Atlas of Medical Devices, the most recent iteration of which was published in 2017, is a report presenting the global status of national medical device policies and the availability of medical device information, regulations, assessments, procurement, and donation guidelines, as well as the density of high cost medical equipment and guidance documents available at country level.
Its authors say that the aim of the publication is “to raise awareness and bring evidence of the indispensable safe and good use of appropriate, affordable, and quality medical devices in health care delivery to achieve better health outcomes”.
Data included in the WHO Global Atlas of Medical Devices come from a 2013 Baseline Country Survey on Medical Devices (to which 177 countries responded), a 2015 global health technology assessment survey (conducted by government or national institutes), and a 2016 study analysing medical devices regulatory frameworks. The information collected by the surveys and studies was then processed into a comprehensive database that includes statistical analyses of more than 100 aspects related to medical devices evaluated with respect to welfare indicators, such as World Bank income groups, health expenditure, Human Development Index and WHO regions.
However, signatories of the recent CVIR Endovascular letter point out that the WHO document does not assess several medical device and equipment categories “that are integral for diagnosis, treatment, and follow-up of patients by minimally invasive means”. Specifically, they request the following be included in future versions of the WHO Global Atlas of Medical Devices:
“1. Ultrasound: As a non-ionising imaging modality, ultrasound is the ideal first-line imaging tool in obstetrics, paediatrics, trauma triage, and is essential for breast cancer diagnosis, biopsy, and follow-up. Ultrasound is used in over 90% of IR procedures to guide percutaneous biopsies, vascular access, and drainage procedures.
“2. Fluoroscopy: As a dynamic, X-ray based, real-time imaging modality, fluoroscopy is the other most essential imaging tool used in IR. With fluoroscopy, interventional radiologists can navigate wires and catheters to almost any place in the body in order to perform embolizations in the setting of haemorrhage, limb salvage from peripheral arterial disease, extract clot in the setting of stroke or pulmonary emboli, and administer radio- and chemotherapy locally. These procedures are often life-saving and significantly less invasive than their surgical alternatives.
“3. Systems for Reviewing Imaging: Determining the availability of PACS (Picture Archiving and Communication System), EMR (Electronic Medical Record), and/or access to a viewing box or written medical records which are paramount for initial evaluation and follow-up of the patient’s medical history, management planning, and disease status over time.”
They expand: “The availability of these data measures will clarify the global distribution of diagnostic and therapeutic imaging and procedural devices. This will allow IR societies, academic institutions, researchers, educators, and non-governmental organisations to strategise and prioritise where and how to best extend and implement minimally-invasive life-saving procedures in LMICs. Additionally, these data will facilitate industry growth and partnerships within the unique context of the LMIC setting.
“We believe that increasing the robustness of the ‘WHO Global Atlas of Medical Devices’ will contribute to increasing access to minimally-invasive procedures in LMICs. We want to be actively involved in this process to support the efforts of the WHO in this matter. For example, as trainees, we can assist with facilitating coordination with consultants and suppliers and lead research efforts in evaluating and guiding implementation. We appreciate your efforts in leading equity in global health and look forward to moving forward in our collective commitment to providing all patients with the care that they need and deserve.”
Exercise can play an important role in treating peripheral arterial disease (PAD), a recent review from Amy Harwood (Centre for Sport and Exercise Life Sciences, Coventry University, Coventry, and the Faculty of Health Sciences, University of Hull, Hull, UK) et al, published in the British Medical Journal (BMJ) Open Sport and Exercise Medicine, shows. The review concluded that, for people with PAD, exercise programmes may help improve walking ability and quality of life by relieving symptoms of leg pain, cramps, and fatigue.
PAD affects 236 million people across the world. While some people with this disease experience no symptoms, approximately 30% experience pain, cramps, numbness, and intermittent claudication. Intermittent claudication is more common in adults over 50, men, and people who smoke.
Currently, PAD treatments focus on managing symptoms and preventing atherosclerotic narrowing of the arteries, which will also reduce the risk of heart disease and stroke. Medications may also be prescribed to reduce cholesterol or treat high blood pressure, which are both risk factors for developing PAD.
Managing intermittent claudication is especially important as people who have it are at a higher risk of other cardiovascular diseases, such as heart disease and stroke. On top of this, the leg pain they experience means people often cannot walk very far. This could lead to lower fitness levels and reduced quality of life. It may also cause depression, as people are no longer as independent as they would like to be in their daily life.
But exercise programmes may offer another treatment approach for people with intermittent claudication, Harwood and colleagues claim. Evidence from their latest review shows exercise can help increase the distance patients can walk pain-free, and may reduce the risk of heart disease and stroke. “We also uncovered what it takes for an exercise programme to be successful,” they write in a press release.
“We found that for people with intermittent claudication, a supervised, walking-based exercise programme is most likely to improve their symptoms. This programme should ideally be done at least three times per week for a minimum of three months. Patients should try to walk at a challenging pace (meaning it causes them to experience strong leg pain) for three to five minutes before resting until the pain goes away. The walk-rest pattern should be repeated for about 30 to 60 minutes.”
This type of exercise programme was shown to significantly improve claudication symptoms, as indicated by an increase in the distance a person can walk without pain. It also increases quality of life and overall fitness levels.
“Revascularisation or drug treatment options should only be considered in patients if exercise training provides insufficient symptomatic relief,” Harwood and co-authors conclude.
For those who cannot access a supervised walking programme, the authors say that exercise can still be done independently, and should also be carried out at least three times a week for 30 to 60 minutes each time. The reviewers recommend people start walking regularly for exercise at their own pace, building up their walking speed and time gradually. “Monitoring how far you walk with an app or smartwatch may be helpful,” they say.
The review also found that resistance exercise (such as lifting weights) can help to improve muscle strength in patients with intermittent claudication. Resistance exercises can be used alongside a walking programme and can be done two to three times per week with each session including exercises for the main muscles of the upper and lower body.
“It is worth noting that people with intermittent claudication should not worry about walking with leg pain, because this pain does not equate to harm being caused,” Harwood et al write. “Claudication pain is thought to be a result of insufficient blood flow to the exercising muscle. Walking while experiencing claudication pain could, over time, stimulate the growth of new blood vessels in the legs and improve symptoms.”
Patients are advised not to exercise if they feel unwell and to seek medical advice if they experience any concerning symptoms when they do exercise—such as chest pain, dizziness, or sickness.
“Our review shows exercise can help manage claudication pain, and may limit the progression of atherosclerotic disease throughout the body. Regular exercise may improve claudication pain in several ways, including improving the way blood vessels work and helping the leg muscles use oxygen more efficiently. Not only can this exercise be done alone or as part of a supervised programme, but it may also have other benefits, including improving cardiovascular health, mood, and sleep.”
The excimer laser sheath technique is safe and effective for removing embedded inferior vena cava (IVC) filters refractory to high-force retrieval, the investigators of a first-in-human escalation trial conclude in the Journal of the American Heart Association (JAHA). “This technique may allow cessation of filter-related anticoagulation and can be used to prevent and alleviate filter-related morbidity,” they write.
This is the largest study to date supporting a new indication for endovascular laser use to remove a variety of embedded IVC filters, regardless of implantation length.
Contextualising this research, lead author William T Kuo (Stanford University School of Medicine, Stanford, USA) and colleagues note that chronic indwelling IVC filters are associated with many potential risks, including non-thrombotic injury, thrombotic events, and the potential need for lifelong anticoagulation. While the US Food and Drug Administration (FDA) recommends that filters be promptly removed once the risk of acute pulmonary embolism has subsided, many filters remain chronically implanted and become refractory to standard retrieval methods. More advanced retrieval techniques (defined as any method other than standard snaring and sheathing) may be effective, but can induce major procedure-related complications due to the use of excessive force. This first-in-human study reports that these complications can be avoided with the use of the excimer laser sheath technique.
Over an 8.5-year period, 500 patients were prospectively enrolled into the study. There were 225 men and 275 women (mean age, 49 years; range, 15–90 years). Indications for retrieval included symptomatic acute inferior vena cava thrombosis, chronic inferior vena cava occlusion, and/or pain from filter penetration. Retrieval was also offered to prevent risks from prolonged implantation and potentially to eliminate the need for lifelong anticoagulation. In total, there were 140 physically symptomatic patients (28%; 140 of 500) with filter-related morbidity, 360 physically asymptomatic patients with filter-related anxiety (72%; 360 of 500), and 78 patients (16%; 78 of 500) receiving filter-related anticoagulation with no underlying thrombophilia.
After retrieval failed using standard retrieval force (6–7lb via digital gauge), treatment escalation was initiated by placing a laser sheath (Spectranetics) connected to a 308-nm XeCl excimer laser generator (CVX-300, Spectranetics), to attempt fibrotic tissue ablation. “We hypothesised that the laser-assisted technique would allow retrieval of more than 95% of embedded filters with less than 5% risk of major complications and with lower force,” Kuo et al put in their abstract.
The three primary study end points were: successful filter retrieval (complete filter detachment from the caval wall and removal from the body, excluding extravascular filter fragments) versus failure; presence versus absence of major procedure-related complications; and the difference in force applied to a patient’s filter both with and without laser assistance during attempted filter removal. Secondary end points were defined as follows: resolution of symptoms in patients with filter-related morbidity, resolution of filter-related anxiety, and further need for filter-related anticoagulation. The primary outcome was successful filter retrieval, and the primary safety outcome was any major procedure-related complication as defined by established guidelines.
Laser-assisted retrieval was successful in 99.4% (497 of 500; 95% CI, 98.3–99.9%). This was significantly higher than the 95% hypothesised by Kuo et al ahead of the study’s initiation (p<0.0001). Three cases that failed retrieval did so because of bulky calcified thrombus (refractory to thrombectomy) within cylindrical-shaped filter components, creating a volume that was too large to be captured within the bore of the existing laser sheath apparatus, the authors explain.
The mean filter dwell time was 1,528 days (4.2 years; range, 37–10,047 days [>27.5 years]), and the median dwell time was 569 days (interquartile range, 260–2,348 days). Successful filter retrieval alleviated filter-related morbidity in 98.5% of cases (138 of 140; 95% CI, 96.5–100%) and allowed cessation of anticoagulation in 98.7% of cases (77 of 78; 95% CI, 93.1–100.0%).
Furthermore, the major complication rate was low: 2% (in 10 of 500 patients; 95% CI, 1–3.6%), with only 0.6% complications from laser. This is significantly less than the 5% threshold (p<0.0005). All complications were successfully treated with either medical management and/or percutaneous endovascular therapy without the need for open surgery.
Discussing the ten complications observed over the study period, Kuo et al say: “As a specialised centre that accepts complex filter cases, our patients were often referred after failed retrieval attempts or when other centres refused to attempt filter removal because of high procedural risks. Indeed, we noted increased variety and complexity of cases encountered throughout the study period. We believe this helps to explain why 10 different combinations of major complications and causes were encountered without duplication. For instance, we accepted cases involving severe filter fractures and penetrations that increased the risk of injury to the IVC and/or adjacent arteries during filter removal. In attempting these cases, we learned that severe filter fractures may lead to asymmetric lasing of fibrous tissue along the vessel wall causing major venous haemorrhage. We also learned that filter components may penetrate through the cava and into adjacent arteries predisposing to organ infarction, major arterial haemorrhage, and arteriovenous fistula formation during filter removal.”
In addition to perhaps seeing more complex cases, another consequence of conducting this study at a single centre specialised in advanced filter removal is that “It is unclear whether the overall safety and efficacy of removing embedded filters as described here [in JAHA] would translate into similar outcomes when performed elsewhere,” as the authors put it. They list this as a limitation of the study, alongside the fact that, although all patients with anxiety reported relief of this symptom, the investigators did not obtain formal psychiatric evaluations or use scoring systems to quantify their anxiety relief post procedure.
Kuo et al also call for a cost analysis study, musing that, although the laser sheath apparatus carries additional device cost, successful filter removal in a single session may decrease overall expense by eliminating the high cost of multiple failed procedures routinely observed before successful laser retrieval.
The laser sheath apparatus is currently not FDA-approved for IVC filter removal; this is an experimental protocol—albeit one that has now been validated in a large cohort of patients.
Corindus has announced today global launch of a new set of automated robotic movements in the technIQ Series designed for the CorPath GRX system. The company received 510(k) clearance from the US Food and Drug Administration (FDA) for new software automation that provides predictable and consistent movements to aid in advanced device manipulation during complex coronary and peripheral procedures.
Jean Fajadet, the co-director of interventional cardiology at Clinique Pasteur, Toulouse, France, performed the first-in-human coronary procedures using the new automated movements, which replicate manual techniques of interventionalists. The procedures demonstrated how the new movements can help to reduce procedure time associated with wire and device manipulation and drive standardisation in quality of care by offering advanced techniques to all physicians.
“This new software algorithm gives the operator new possibilities to advance and facilitate treatment, especially with complex lesions,” said Fajadet. “I am pleased with the success of using the automated moves and am honored to play a role in the advancement of robotic technology that will make interventional procedures more efficient and safer for our patients.”
In 2018, Corindus received CE mark and FDA clearance for an automated technique called Rotate on Retract (RoR). RoR was the first automated robotic movement in the technIQ Series and has demonstrated the potential to significantly reduce wiring time. The latest global introduction and FDA clearance for the technIQ Series provides physicians with four additional automated robotic movements that aid with complex tasks such as crossing lesions, navigating tortuosity, and precisely measuring the anatomy for appropriate device size selection.
“The new technIQ movements mark the next phase in the evolution of robotic-assisted intervention and a vital step toward the advancement of our technology,” said Wayne Markowitz, executive vice president and head of Corindus. “Automating more movements used in cardiovascular intervention will allow physicians to focus their attention on overall case strategy while equipping them with advanced techniques for navigating the vasculature.”
Corindus is a Siemens Healthineers company, following a merger in 2019.
Compared with doxorubicin-loaded drug-eluting embolic transarterial chemoembolization (DEE-TACE), conventional transarterial chemoembolization (cTACE) yielded a higher number of quality-adjusted life years (QALY) at a lower cost, making it the more cost-effective of the two modalities. This is the conclusion reached by a cost-effectiveness analysis published in the Journal of Vascular and Interventional Radiology (JVIR) by Xiao Wu (Yale School of Medicine, New Haven, USA), senior author Nishita Kothary (Stanford University Medical Center, Stanford, USA), and colleagues.
The investigators set out to compare the cost-effectiveness of DEE-TACE versus that of cTACE for patients with unresectable hepatocellular carcinoma (HCC).
They constructed a decision-analysis model that spanned a payer’s entire life; the model simulated the clinical course, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death, of patients with unresectable HCC. Describing their methodology, Wu et al explain: “All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way sensitivity analyses were performed.”
Conventional TACE yielded a health benefit of 2.11 QALYs at a cost of US$125,324, whereas DEE-TACE yielded 1.71 QALYs for US$144,816. In 10,000 Monte Carlo simulations, a mathematical technique used to estimate outcomes of an event, cTACE continued to be a more cost-effective strategy.
The authors report that cTACE was cost-effective when the complication risks for both the procedures were simultaneously varied from 0–30%. DEE-TACE became cost-effective if the cTACE mortality exceeded that of DEE-TACE by 17% in absolute values. The two-way sensitivity analyses demonstrated that cTACE was cost-effective until the risk of disease progression was >0.4% of that for DEE-TACE in absolute values.
“Our analysis showed that DEE-TACE would be more cost-effective if it offered >2.5% higher overall survival benefit than cTACE in absolute values,” Wu and colleagues summarise.
Replying to this journal article as posted on Twitter, Aaron Maxwell (The Warren Alpert Medical School of Brown University, Providence, USA) asked: “If cost effectiveness is being discussed, why not bland embolization alone? No chemotherapy to pay for, and RCT [randomised controlled trial] data with equivalent outcomes to TACE from 2016.”
Responding, study co-author Julius Chapiro (also Yale School of Medicine, New Haven, USA) wrote on Twitter: “Excellent point! While there is some doubt as to the standard of care for the control arm in the JCO paper (DEB-protocol), I am not at all convinced that chemo adds value to beads. Our experimental studies prove the point, too. We must really think about it in depth.”
He posted a figure from a previous JVIR paper authored by the same team, writing: “Even with smaller calibre beads, the drug (heat map) barely covers the entire tumour. Primarily embolic effect. I will say that my journey so far has really made me doubt the value of chemo.
“We now need to understand the immunological effect of the different materials we introduce and how they may or may not affect the tumour microenvironment and immune response (especially + checkpoint inhibitors). I do not see clear striking evidence for DEBs re outcome. None.”
This prompted Maxwell to reply: “Terrific work. I think it is incumbent upon the IR [interventional radiology] research community to aggressively expand our understanding of the tumour microenvironment if we are to optimise outcomes for catheter-directed locoregional liver therapies.”
Chapiro agreed, exclaiming: “We simply have to aggressively expand our science and transform our therapies to be directed to and tailored for the individual tumour microenvironment!”
Speaking directly to Interventional News, Kothary added: “Data on bland embolization are limited, precluding a robust carcinoembryonic antigen (CEA) test. “DEE-TACE is also associated with a higher need for pain control due to its true embolic nature (I would guess that bland embolization is similar), and pain control often requires overnight hospitalisation that would impact a CEA.”
Guerbet has been granted approval for an indication extension in the UK, where Lipiodol Ultra Fluid is the only oil-based contrast medium indicated for hysterosalpingography (HSG) in women undergoing infertility workup. New clinical evidence showing that an HSG with Lipiodol Ultra Fluid enhances pregnancy rates has been recognised by the UK’s Medicines and Healthcare products Regulatory Authority (MHRA). MHRA’s endorsement of evidence-based clinical practice confirms the benefit of Lipiodol Ultra Fluid in fertility management, a Guerbet press release claims.
One in seven couples face fertility issues in the UK. The fertility workup, during which HSG is performed, is a key step in patient care management.
The technique involves the slow infusion of Lipiodol Ultra Fluid into the uterus, using X-ray monitoring to assess the uterine cavity and tubes.
More importantly, women who underwent an HSG with Lipiodol Ultra Fluid had enhanced pregnancy outcomes:
“This is great news for UK patients experiencing difficulties conceiving, as it brings them additional hope by enhancing their chances of falling pregnant at an early stage of their fertility journey. As with any procedure, patients should be aware of any associated risks,” says Gwenda Burns, chief executive of Fertility Network UK.
“Our clinical experience of Lipiodol Ultra Fluid has showed us that its use is similar to water-based contrast media and does not alter the patient experience during the exam. However, it is noteworthy that long term follow-up studies showed that performing an HSG with Lipiodol Ultra Fluid reduces the median time to pregnancy by around four months, as compared to an HSG with the reference contrast media,” comments Colin Duncan (Royal Infirmary Edinburgh, Edinburgh, UK; chair of the Society for Reproduction and Fertility).
“At Imperial College Healthcare NHS Trust, we have performed more than 10,000 HSGs over the last few decades. The evidence-based results from the H2Oil study encouraged our HSG and fertility teams to use Lipiodol Ultra Fluid for HSG in selected patients. After several months of use, we can confirm that an HSG with Lipiodol Ultra Fluid is an exciting and valuable technique in the management of patients being investigated for fertility issues in our centre. Our teams at Imperial College Healthcare NHS Trust will soon to be involved as investigators in on-going randomised controlled clinical trials evaluating the performance of Lipiodol Ultra Fluid for HSG in extended populations undergoing fertility workup,” adds Anne Hemingway (Imperial College Healthcare NHS Trust, London, UK).
The UK is the sixth European country to grant approval for HSG in women undergoing infertility workup after Ireland, Hungary, The Netherlands, the Czech Republic, and Denmark. Lipiodol Ultra Fluid is also currently approved for HSG in ten additional countries (the USA, including Puerto Rico, Canada, Argentina, Turkey, South Africa, Japan, Taiwan, Thailand, Australia and New Zealand).
In 2016, the Guerbet Group launched its Women’s Health franchise with the ambition to improve the quality of infertility management and breast cancer surgery.
“Not everything that is published is true or important” and “always be critical, but not cynical,” urges Jim Reekers, editor-in-chief of CVIR Endovascular, as he talks about filters that operate in the world of scientific and medical publishing that favour the publication and spread of positive news. He particularly warns against the “silent and very dangerous” trend of unscrutinised, non-peer reviewed papers that are presented as pre-prints with a Digital Object Identifier (DOI) number, enabling the creation of a parallel publishing universe.
“Nobody knows what the truth is anymore, and I think that this the biggest threat to medical science,” he states.
Reekers delivered the 2020 BSIR Wattie Fletcher Lecture on similar themes titled “Extra extra read all about it”.
An unplanned interim analysis of the registry-based SWEDEPAD clinical trial, in which patients with peripheral arterial disease received treatment with paclitaxel-coated (drug-coated balloons or drug-eluting stents) or uncoated endovascular devices, “did not show a difference between the groups in the incidence of death” during one to four years of follow-up. This conclusion was published today by Mårten Falkenberg, Joakim Nordanstig (Gothenburg University, Gothenburg, Sweden) and colleagues in the New England Journal of Medicine (NEJM).
Falkenberg et al conducted the analysis against a backdrop of “concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral arterial disease”. They relay that data for the analysis was from the multicentre, randomised, open-label, registry-based SWEDEPAD (Swedish drug elution trial in peripheral arterial disease) clinical trial.
At the time of their analysis, the authors detail, 2,289 patients had been randomly assigned to treatment with either drug-coated devices (the drug-coated device group, 1,149 patients) or treatment with uncoated devices (the uncoated device group, 1,140). They state that paclitaxel was used as the coating agent for all the drug-coated devices.
Falkenberg et al detail that randomisation was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischaemia (1,480 patients) or intermittent claudication (809 patients), and that the single endpoint for this interim analysis was all-cause mortality.
Writing in NEJM, the authors communicate that no patients were lost in the mean 2.49-year follow-up period, during which 574 patients died, including 293 patients (25.5%) in the drug-coated device group and 281 patients (24.6%) in the uncoated device group (hazard ratio, 1.06; 95% confidence interval, 0.92–1.22).
At one year, Falkenberg and colleagues write that all-cause mortality was 10.2% (117 patients) in the drug-coated device group and 9.9% (113 patients) in the uncoated device group. During the entire follow-up period, they found that there was “no significant difference in the incidence of death between the treatment groups” among patients with chronic limb-threatening ischaemia (33.4% [249 patients] in the drug-coated device group and 33.1% [243 patients] in the uncoated device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).
In the discussion of their findings, the authors acknowledge that this interim analysis “was not a prespecified part of the trial protocol”. They respond to this limitation by noting a twofold rationale behind publishing these total mortality data ahead of completion of the trial: “First, we sought to reduce patients’ and physicians’ concerns regarding the safety of paclitaxel-coated devices, and second, we considered the data to be important to support completion of ongoing trials investigating the efficacy of such devices in peripheral arterial disease.” They add that this analysis was recommended by an independent data and safety monitoring committee “in order to alleviate patients’ and physicians’ concerns” surrounding paclitaxel safety.
Falkenberg and colleagues recognise a number of other limitations to their unplanned interim analysis, including the fact that the open-label design “could have the potential to introduce bias”. However, they point out that the endpoint of all-cause mortality used “is less sensitive to this particular limitation than more subjective outcomes”.
Another drawback the authors recognise relates to the fact that there were few deaths among patients with intermittent claudication, resulting in the confidence interval for that particular group of patients being wide (ranging from 0.72 to 1.93). As a result of this, the investigators write that they “cannot completely exclude the possibility of a difference in mortality in this subgroup”.
Falkenberg et al identify the use of ‘low-dose’ (rather than ‘high-dose’) paclitaxel-coated devices being “relatively common” in the trial as another limitation, which “may have influenced” their results.
In addition, they note that there was variation in the treatment effect among centres, although they write that it “seems likely that this variation is due to chance rather than to variation in centre characteristics”.
Finally, they highlight that no analysis of the efficacy of paclitaxel-coated devices is included in this interim report. They write: “These data are planned to be provided in the final clinical trial report after formal completion of the trial”.
At the end of their discussion, Falkenberg and colleagues stress that the SWEDEPAD trial “was not primarily intended for analysis of total mortality,” pointing out that the main purpose was “to determine whether drug-coating technology ultimately improves the lives of patients with symptomatic peripheral arterial disease by preventing amputation and improving health-related quality of life”.
Because this interim analysis “does not show a significantly higher incidence of death resulting from the use of paclitaxel-coated devices,” the authors conclude with their belief that “equipoise remains,” detailing that recruitment has been resumed with enrolment of patients in both the chronic limb-threatening ischaemia cohort and the intermittent claudication cohort.
The authors write that the trial is funded by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, and Region Västra Götaland. They also communicate that “all the companies that provide drug-coated balloons and drug-coated stents for patients in Sweden with peripheral arterial disease are supporting the trial by providing price discounts on their devices”.
Sirtex Medical (Sirtex) has announced a strategic investment in BlackSwan Vascular (BlackSwan), a private company developing therapies in endovascular embolization. The investment provides resources for further development of BlackSwan Lava, a liquid embolic system specifically tailored for peripheral vascular target indications.
According to Sirtex, Lava has the potential to be the first liquid embolic for peripheral vascular applications to receive approval in the USA. Its key differentiators, which include optimised radiopacity, availability in two viscosities, reduced preparation time and controlled delivery, can enable treatment of a wide array of peripheral vascular diseases, a press release reads.
“Our investment in BlackSwan marks an important step in Sirtex’s commitment to expand product offerings to the endovascular field and to interventionalists addressing unmet medical needs,” said Mark A Turco, global chief medical officer and executive vice president, research and development of Sirtex. “We look forward to partnering with BlackSwan on its clinical journey and future opportunities to innovate patient care worldwide.”
Under the collaboration, Sirtex made a significant equity investment in exchange for preferred shares in BlackSwan as well as an option to purchase the remaining shares of the company at an agreed price. In addition, Sirtex will appoint an observer member to the Board of Directors.
“We strive to provide the interventional community with the tools they need that drive safe, effective and value-based treatments,” said Suresh Pai, CEO of BlackSwan. “We are excited to partner with Sirtex, a leader in targeted oncology, as an investor and collaborator as we advance our clinical programme and bring much-needed therapy options to patients.”
Hypercoagulability in COVID-19 patients leads to an increase in the malfunction rate of temporary haemodialysis catheters—but heparin locking of the catheters is linked to decreased malfunction rates.
Those are among the main findings of a study recently published in the Journal of Vascular Surgery.
The research sought to address the subset of COVID-19 patients with acute kidney injury who require haemodialysis. With temporary catheters being the mainstay in their treatment and up to 96% of COVID-19 patients experiencing dialysis circuit clotting, the investigators identified a “paucity” of data and guidelines to address the problem.
John J Kanitra, MD (Ascension St John Hospital, Detroit, USA) and colleagues carried out a retrospective cohort study via chart review at their institution—a large urban hospital. The study included patients who needed a temporary catheter placed between 1 February and 30 April, with follow-up for outcomes continued between 1 May 12 May.
A total of 48 patients with a mortality rate of 71% were identified. Malfunction occurred in 31.3% of patients. Thirty-seven patients (77.1%) received heparin locking, 22 (45.8%) received systemic anticoagulation and 38 (79.1%) received venous thromboembolism prophylaxis. The overall rate of malfunction was lower at a trend level of significance with heparin versus saline locking (24.3% vs. 54.6%; p=0.058), Kanitra at al found.
Meanwhile, systemic anticoagulation did not affect temporary catheter malfunction rate (p=0.240). Higher D-dimer levels were related to greater mortality (hazard ratio [HR] 3.28, 95% confidence interval [CI] 1.16–9.28; p=0.025), but were not significantly associated with temporary catheter malfunction (HR 1.79, 95% CI 0.42–7.71; p=0.434).
“The high malfunction rate is likely a result of the hypercoagulability that has been suggested in COVID-19 patients,” the authors write. “Reports describe COVID-19 patients without predisposing factors developing thromboembolic events. The aetiology of this is thought to be endothelial damage driven by the cytokine storm, leading to excess thrombin formation in addition to increased blood viscosity from hypoxaemia.”
The authors noted the need for prospective, randomised studies in order to confirm their findings—chiefly so that locking the temporary catheters with heparin in COVID-19 patients can be recommended. “Increased [venous thromboembolism] prophylaxis suggested a possible association with improved [temporary haemodialysis catheter] patency, though the comparison lacked sufficient statistical power,” they write. “Additionally, the current study found an 71% mortality rate in COVID-19 patients requiring acute haemodialysis, which has important implications for planning and resource delegation for future coronaviral infections.”
Felipe Nasser (São Paulo, Brazil) talks to Interventional News about his experience of the COVID-19 pandemic after contracting the SARS-CoV-2 virus himself, saying that the infection and period of isolation “made me think a lot about my life.” “We are now prepared” and “know how to face a situation like this” in the future, he says, speaking of the capabilities and competencies of his own institution, as well as that of the global medical community as a whole, to responding to public health crises of this scale.
Nasser explains that the rise of the virus has led to a reduction in the number of patients being treated in the oncology department of the São Paulo hospital where he works. “We replaced our normal work with COVID-19 patients”, he says, adding that he has not just been treating oncology patients, but also those with vascular disease.
He goes on to highlight some of the practical modifications his institution has adopted, including the use of an N95 respirator when treating any patient, the separation of catheter labs—there is a specific cathether lab dedicated to COVID-19 patients —and the use of a negative pressure air filtration system. Physicians also now use impermeable scrubs and face shields, and the number of physicians in the room at any one time has been reduced to just one physician and one Fellow.
B Braun has revealed that 12-month results from the LOCOMOTIVE EXTENDED study of the company’s Multi-Loc multiple stent delivery system have been published in Vasa: European Journal of Medicine. The study authors, Klaus Amendt (Diakonissenkrankenhaus Mannheim, Mannheim, Germany) and colleagues conclude that the Multi-Loc “provides promising results concerning target lesions revascularisation and primary patency at 12 months”.
They add that use of the Multi-Loc stent system is both safe and effective for provisional repair of flow-limiting dissections or recoil following plain balloon angioplasty and drug-coated balloon angioplasty of the femoropopliteal artery.
The LOCOMOTIVE EXTENDED (Multi-Loc for flow-limiting outcomes after plain old balloon angioplasty and/or drug-coated balloon treatment in the infrainguinal position with the objective to implant multiple stent segments) study is a prospective, single-arm, multicentre observational study, in which B Braun’s Multi-Loc multiple stent delivery system was used for provisional stenting of the femoropopliteal artery.
Amendt et al enrolled 357 patients with 449 femoropopliteal lesions and a mean age of 71±10 years. The mean lesion length was 16±9.7cm; 44.5% of which were TASC II C/D lesions and 31.4% were chronic total occlusions.
At six and 12 months, the authors report that freedom from clinically-driven target lesion revascularisation was 95.5% and 88.7% and the primary patency rates were 88.7% and 82.3%, respectively.
At 12 months, significant improvements were noted in Rutherford categories and ankle-brachial indices, and in multiple regression analyses, both diabetes mellitus and no distal run-off vessel showed a trend toward worse target lesion revascularisation, while other factors such as drug-coated balloon predilection or the lesion length were not predictive.
Considering future research, Amendt and colleagues write: “Randomised controlled trials are needed to compare the focal stenting strategy to conventional interventions with long stents. Possibly, the efficacy of spot stenting could be further increased by combining it with additional preparation techniques, such as vessel scoring or debulking.”
The European Conference on Interventional Oncology (ECIO) will be held as an online-only event in 2021, and will take place 10–13 April.
Writing to potential attendees, ECIO scientific programme committee (SPC) chairperson Alban Denys and ECIO SPC deputy chairperson Philippe L Pereira write:
“Dear colleagues,
“As 2020 comes to an end, we are hopeful that the promising vaccines developed by various manufacturers will soon provide relief from the pandemic. However, it will take a while until things return to normal and we will once again be able to travel and attend in-person meetings.
“This is why the ECIO leadership has decided to hold ECIO as an online congress from Saturday to Wednesday April 10–13, providing the same high-quality sessions and global platform for research exchange you have all come to expect of our annual meeting in a reliable and safe way.
“The scientific programme committee has been working diligently to create an expansive programme covering the entirety of the interventional oncology spectrum in a convenient, interactive format. Topics will range from clinical subjects and well-established therapies all the way to experimental approaches and the latest study results.”
Pua Uei (Singapore) talks to Interventional News about how Singapore’s interventional radiologists (IRs) in Tan Tock Seng Hospital and National Centre for Infectious Disease (NCID) dealt with the ongoing COVID-19 crisis. Singapore was one of the first countries to register a case outside of China, notes Uei, who adds that as the NCID had previously been on the frontline of the 2003 Severe Acute Respiratory Syndrome (SARS) virus, “preparing for outbreaks was nothing really new to us”.
The “challenge for interventional radiology”, says Uei, was community spread of the virus, which meant that it was no longer possible to effectively identify and segregate COVID-positive and COVID-negative patients. “From past experiences with SARS, it is vital to put a mask on any patient undergoing a procedure to reduce the risk of unprotected contact”, Uei states, adding that such a move was made in Singapore “before masks were made mandatory”.
The second thing that “threw a spanner in the works” early on in the pandemic, as medical facilities were preparing their response to the viral threat, was the existence of asymptomatic spreaders. “We have had to be very responsive,” Uei reflects. “Every time we learn something new about the virus, we have to react to it and put in measures to protect patients”.
He outlines how vital resources were managed: “The moment we knew it was coming, we had stoppages of leave and vacation, and we cancelled academic teaching. As a result there was more manpower than ever. “We were very judicious with regards to the preservation of personal protective equipment (PPE) due to the global supply chain disruption; we had rules on how long you could use a surgical mask and how many times you should reuse an N95 (respirator).”
Uei also touches on the mental health toll caused by the COVID-19 public health crisis, and the fatigue felt by healthcare workers on the frontline. He notes that it is important that experienced physicians, such as those who worked through the SARS epidemic, help provide perspective and support to their more junior colleagues.
Mo Hamady discusses developments in aortic stent grafts in recent years, and offers a contemplation on the complications associated with endovascular aneurysm repair (EVAR). Despite advances in stent graft technology, operator knowledge, and physician experience in recent years, he writes that the overall long-term survival remains stable, prompting him to encourage interventional radiologists and vascular surgeons to consider the most durable and cost-effective intervention and modality when selecting patients for aortic aneurysm repair.
Aortic stent grafts have been through significant developments over the years in terms of mechanical features and material properties.
These changes have refined the performance of stent grafts such as global deformation, profile, navigability, and conformability. The biggest leap in technology was demonstrated mainly between the first- and second-generation grafts.
Have technological changes influenced clinical outcome?
A large retrospective study, published in the Journal of Endovascular Therapy (JEVT) in 2014, comparing the outcomes of old versus new generation stent grafts, showed lower reintervention rates at five and seven years; 86.6% and 83.6% versus 80.3% and 74.2% (p=0.015) in favour of new stent grafts. Similarly, newer stent grafts had better freedom from late conversion and sac growth >5mm (p=0.0001 and p=0.022, respectively). Lower type 1 endoleak (p>0.07) and less grafts migration (p>0.02) were noted in another study featured in the Journal of Vascular Surgery in 2017, assessing the performance of Endurant and Talent stent grafts (Medtronic).
A French Registry of 176 patients reported on the performance of the second-generation Anaconda EVAR (Terumo Aortic) over five years. Although one third of the studied cohort had hostile neck anatomy, there was higher freedom from aneurysm related re-intervention when compared with the reported results of the Dutch DREAM trial: 78% versus 70%. The Italian Registry for the new generation C3 Gore Excluder stent graft of more than 460 patients, all followed for 10 years and treated as per the instructions for use (IFU), showed quite high freedom from reintervention (80%) and freedom from stent-related complications (88%).
The improvement in cloth material and refinement in stent structure have influenced the durability outcomes. Type III endoleak was studied in a large retrospective study of more than 900 patients, published by in the Journal of Vascular Surgery in 2017. Almost 50% reduction of this serious endoleak was noted in the third generation grafts when compared to the first and second generations.
This technological development has been accompanied by a growth in operator knowledge and experience. There is consistent observation in the literature that the use of stent grafts within IFU is accompanied by reduction in early type 1 endoleak, early reinterventions, and late death. In one retrospective study of more than 600 patients, among several other studies, published in the Journal of the American College Surgery in 2016, it was documented that early and late type 1 endoleak, early reintervention, and late death were all significantly higher in the cohort of patients treated outside IFU, despite very high initial technical success. It is alarming that this kind of practice is still widespread and there is a real possibility that the reported results are actually undermining the technological development in this field.
The concept of relation between neck diameter and durability is gathering momentum. Several studies have shown that the smaller the neck diameter, the better the overall results are. The GREAT registry collects data from real life patients treated with C3 Gore stent graft. A study of more than 1,600 patients published in 2018 in the Journal of Vascular and Endovascular Surgery showed that neck diameter of ³25mm was significantly associated with lower freedom from type 1A endoleak, lower freedom from aortic reintervention, and lower freedom from primary composite end point at five years. It is however inconsistent in the literature what the diameter threshold is that defines the desired neck.
Despite the great investment in this technology, the overall long-term survival remains stable regardless of the technology or stent manufacturer. This is perhaps an expected finding in a pathology that frequently presents with several other co-morbidities. This observation should prompt interventional radiologists and vascular surgeons, when selecting patients and/or treatment modality, to consider the most durable and cost-effective intervention.
Future developments
Several outstanding issues are yet to be studied. The new stent designs and new adjuncts such as endostaples should be properly appraised. The optimum neck diameter, together with ideal length (fenestration versus standard EVAR), should be included in the long-term risk-benefit assessment. A reliable and sensitive follow up tool, beyond CT and ultrasound, will be welcomed for the life-long needed surveillance.
Mo Hamady is a consultant interventional radiologist at Imperial College, London, UK, the training programme director for Interventional Radiology at London Health Education England (HEE), and is secretary of the British Society of Interventional Radiology (BSIR). EVAR
“Artificial intelligence [AI] is changing the face of healthcare for all stakeholders, from consumers to providers,” Stephen Hunt (University of Pennsylvania, Philadelphia, USA; co-founder of the Penn Image-guided Interventions Laboratory) told attendees of the virtual 2020 annual scientific meeting of the British Society of Interventional Radiology (BSIR; 1–3 December, online). Speaking during a “State of the Art” session on the future of interventional oncology (IO), Hunt spoke on how “the era of AI” will expand the horizons of interventional oncology.
According to Hunt, the growth of US Food and Drug Administration-approved AI tools in the coming decade “will be exponential”. He urges interventional radiologists to stay abreast of the developments by integrating AI concepts into medical education: “Users must be educated not only on the proper application of these AI tools and on their limitations,” he said, “but on the mechanisms for validating their efficacy. Foundational concepts in statistics and bioinformatics are critical to responsible adoption and use of AI. Collaboration with developers of these tools will improve their clinical relevance and usability to interventional radiology. IO educators and faculty should incorporate AI topics into their curricula and research.”
He defines AI simply: “Really, it is just using computers and software to perform tasks that normally require human intelligence to accomplish. That seems like a very broad definition, and it is—it is somewhat vague on purpose, because it encompasses such a large field.”
Machine learning is a concept integral to AI: it describes the process of a computer learning from experience as it goes through data sets. A machine learning algorithm will learn to make connections between data points or perform some sort of classifier task, such as image recognition, when fed data, and gets better at its designated job the more input it is fed.
“The real breakthroughs for interventional oncology will require assembling and curating larger datasets,” Hunt therefore explained to delegates.
In addition to a large amount of data and a machine learning algorithm (or another tool designed to perform sophisticated calculations, such as a neural network), AI also requires some technical expertise, he continued. The end user has to be able to interpret the output generated by the AI software in order to apply the information to clinical practice.
Hunt provided some examples of AI use in the interventional oncology space.
Intraprocedural spatial localisation
Firstly, he talked the BSIR audience through an example where an interventionalist brings in a patient with a gastrointestinal (GI) bleed. Whilst the imagined patient is lying on the angiography table, the interventional radiologist needs to identify the location of the bleed on a CT scan in order to then stop the blood flow. Hunt suggested that an algorithm could be used in image registration and segmentation: this would enable the fluoroscopy unit to automatically identify the area where it predicts the bleed would appear.
“This kind of technology already exists, it has just not been put to use in clinical practice,” Hunt said. “It has not really been deployed that way.
“In addition, you could take those images [from prior GI bleed angiography studies] and train an AI with them—we have done this in our lab, and other labs have done this too—so automatically you have a classifier that will show you where the bleed is on the image. It is able to learn from some prior database that we made of GI bleed images, and then we can try it on new cases.”
Clarifying this point specifically to Interventional News, Hunt elucidates: “The point is for your angio suite to automatically detect the bleed during angiography and ‘circle it’ or otherwise provide a target sign to point it out to your eye. That way the interventionalist can go to that spot to drop a coil.
“I think within the next five years you are going to see a lot of these tools from the larger venders, like Siemens and Philips.”
CT perfusion imaging during TACE
Giving another example, Hunt next discussed AI in CT perfusion imaging during transarterial chemoembolization (TACE).
“We always have this problem of, during a TACE, how do you know you have full treatment of the tumour? One of the ways would be to do CT perfusion on that patient at the time of TACE. We have one of these image hybrid rooms, we have all the technology there, we have CT perfusion on that CT scanner, which is in the hybrid room of the fluoroscopy CT unit, but it has not been integrated into the workflow, the technicians do not know how to use it—it is these kinds of problems that we have not yet worked out. This is an example where you can have that real-time critical feedback, [as the AI] tells you ‘hey, there is an area of tumour that you have missed’. The CT perfusion would give you that information.
Intraprocedural Augmented reality
Turning to an example he said is more in the research and development phase, Hunt then discussed the use of augmented reality intraprocedurally. The HoloLens, from Microsoft, is a set of goggles that the interventionalist could wear that allows them to see virtual projections superimposed over the real world.
There are various methods of registration when it comes to correctly superimposing the projected image on to a patient, which utilises AI. Hunt described how the physician could select a point on the patient’s skin, and a point in the tumour on the projection, and the HoloLens will allow the user to visualise a path that will give them an angle to register their ablation probes. This can be combined with the breathing cycle and cardiac gating, so probe advancement only takes place at the correct time in the cycle. Hunt highlighted work that IMACTIS and XACT are doing in this space, and encouraged listeners to look into these companies.
Thermal lung ablation (TLA) is an effective treatment, resulting in good overall survival with good local control, attendees were told at the 2020 annual scientific meeting of the British Society of Interventional Radiology (BSIR; 1–3 December, online). Elfadil Elmahdi (Royal Liverpool University Hospital, Liverpool, UK) presented his ten-year experience of the non-invasive alternative to surgical resection at a tertiary hospital.
Elfadil and colleagues conducted a retrospective, observational review to evaluate local tumour control, overall survival, and complications of TLA in their centre between 2009 and 2019. While 128 patients in total were treated with TLA during this period, five were excluded from the study for disease progression prior to TLA and no follow-up data. Between the 123 patients analysed in the study, 321 nodules were ablated.
Technical success was achieved in 301 nodules (93.8%). Of the 20 unsuccessful procedures, 14 nodules underwent a repeat ablation.
Showing a Kaplan-Meier graph depicting local recurrence, Elfadil informed his audience that the mean number of years before local recurrence was 10.5 years (±0.234; confidence interval [CI]: 10.07–10.99), with one-, two-, and three-year survival without local recurrence being 90%, 87.5%, and 86%, respectively. A second Kaplan-Meier graph, this time depicting new pulmonary recurrence, showed that the mean time before new tumours developed again was 5.8 years (±0.414; CI: 4.95–6.57), with the one-, two-, and three-year survival rate with no new pulmonary occurrence being 85%, 72%, and 60%, respectively.
Median overall survival was 3.16 years (±0.305; CI: 2.56–3.76). One-, two-, and three-year overall survival was 98%, 82%, and 56%, respectively. These survival rates are comparable to other TLA studies, Elfadil said, “if not slightly better”.
A pneumothorax requiring a chest drain was seen in 50.7% of patients—again, Elfadil told delegates that this was similar to that reported in the literature.
Addressing the limitations of the presented study, he went on to say that the investigators assumed that TLA practice in the Royal Liverpool University Hospital was homogenous between operators over time, co-morbidities that may influence survival were not taken into account, and no correlation was made with the grades of the primary tumour. In addition, there are reservations to what can be achieved with a retrospective study design using data from a single institution. lung ablation
Based on the findings of their first-in-human feasibility study, Joost van Herwaarden (Utrecht University Medical Centre, Utrecht, The Netherlands) and colleagues write in the European Journal of Vascular and Endovascular Surgery (EJVES) that Philips’ Fiber Optic RealShape (FORS) technology “has the potential to improve intraoperative imaging”. Their results show that real-time navigation using FORS technology is safe and feasible in abdominal and peripheral endovascular procedures.
Van Herwaarden and colleagues detail that endovascular procedures are conventionally conducted using 2D fluoroscopy. However, a new technology platform, FORS, has recently been introduced, which allows “real-time, 3D visualisation of endovascular devices using fibreoptic technology,” they explain. This technology functions as an “add on” to conventional fluoroscopy and “may facilitate endovascular procedures”. The present first-in-human study assessed the feasibility of FORS in clinical practice.
The researchers performed a prospective cohort feasibility study between July and December 2018, recruiting patients undergoing either regular or complex endovascular aneurysm repair (EVAR) or endovascular peripheral lesion repair.
Van Herwaarden et al used FORS guidance exclusively during navigational tasks, such as target vessel catheterisation or crossing of stenotic lesions. In EJVES, they write that three types of FORS-enabled devices were available: a flexible guidewire, a Cobra-2 catheter, and a Berenstein catheter. They note that devices were chosen at the physician’s discretion and could comprise any combination of FORS and non-FORS devices.
The primary study endpoint was technical success of the navigational tasks using FORS-enabled devices, and secondary endpoints were user experience and fluoroscopy time.
The authors note that they enrolled 22 patients in the study, comprising 14 EVAR and eight endovascular peripheral lesion repair patients. They detail that, owing to a technical issue during start up, the FORS system could not be used in one EVAR. However, they report that the remaining 21 procedures went ahead without device- or technology-related complications and involved 66 navigational tasks.
Van Herwaarden and colleagues add that in 60 tasks (90.9%), technical success was achieved using at least one FORS-enabled device. In terms of user experience, operators graded FORS-based image guidance “better than standard guidance” in 16 of 21 and “equal to standard guidance” in five of 21 procedures. Finally, regarding fluoroscopy time, the authors report that this ranged from 0 to 52.2 minutes, adding that several tasks were completed without or with only minimal X-ray use.
The authors acknowledge some limitations of the present study. For example, they communicate that, although the operators had experience with the system in preclinical studies, they went through a learning curve during clinical use. Van Herwaarden et al write: “The optimal visualisation settings (regarding viewing angle, magnification, mono- or biplane mode, and optimal overlay) had to be identified for the different types of procedure.”
In addition, they note that workflow improvements, like the optimal positioning of the system, to work from both the groin and the arm, had to be learned during the study. “In this first study, the technical success would probably have been higher if more than two differently shaped catheters had been available,” they posit.
Van Herwaarden and colleagues list a few more limitations for clinical use, including the limited working length of the catheters and guidewire available for this study and also the inability to backload the guidewires. “These issues will be addressed in future releases of the system,” they state.
Finally, they relay that there were technical issues with the FORS equipment during this study. The technology could not be used in one patient, they detail, and using two FORS devices at the same time was impossible in on other patient. They note that these factors “probably affected study results”.
The authors conclude that this exploratory study “demonstrates the feasibility and potential of this technology in clinical practice and forms a foundation for future clinical research.” However, they recognise that comparative studies are needed to “prove and quantify” the benefits and potential radiation reduction for all types of endovascular procedures.
A combination of liquid biopsy and whole-body magnetic resonance imaging (WB-MRI) could revolutionise cancer diagnostics and monitoring, write Bruno Damascelli, Vladimira Tichà, Gianluigi Patelli, and Giuseppe Petralia. Here, they detail the potential advantages of these non-invasive techniques: “The combination of magnetic resonance and liquid biopsy may potentially solve some diagnostic conflicts and guide new treatments based on molecular diagnosis and its variations as the cancer evolves”.
Modern cancer diagnostics aim to provide improved sensitivity, specificity, and disease localisation, without any risk of biological harm. Liquid biopsy and whole-body magnetic resonance imaging (WB-MRI) are both in an accelerated phase of development as promising, non-invasive methods for early cancer diagnosis and monitoring. A combination of the two methods could prove advantageous.
The genetic profile of a tumour extracted from a blood sample seemed to be the end point for cancer diagnosis, disease monitoring, and selection of targeted molecular treatments. However, liquid biopsy results are not easily reproducible at present because tumours release minimal amounts of fragmented DNA into the circulation in an unpredictable manner. Molecular diagnosis based on biological liquids is complementary to tissue biopsy and cannot replace it. Yet liquid biopsy has unique advantages, such as the ability to demonstrate changes in the heterogeneity of the cancer genome and to detect circulating tumour cells (CTC) with intact DNA, which are prognostically significant.
The most widely used imaging methods in oncology are based on ionising rays, making it undesirable to resort to these methods for screening and for frequent disease monitoring, especially in young patients and women of fertile age. Since its introduction, magnetic resonance imaging has developed surprising abilities to distinguish between normal and tumour tissue without unwanted effects. Diffusion sequences reflect the restricted mobility of water protons that occurs in some tumours because of their greater cell density. The consequent increase in contrast between tumour and normal tissue allows spatial localisation of the cancer. The increased sensitivity and specificity of diffusion-weighted WB-MRI has been demonstrated in cancer patients, but the data on healthy subjects are still preliminary. The possibility of diagnosing cancer in the 1–2% of asymptomatic subjects who undergo screening DWB-MRI makes this test interesting, although findings calling for further investigation may be produced in as many as 30% of those screened, according to published data.
Similarly, liquid biopsy, as conventionally applied in patients without a cancer diagnosis, is unable to provide direct topographical information, although identification of a tumour-related mutation in the blood is of considerable diagnostic significance.
For liquid biopsy, tumour DNA extraction can be improved through enrichment methods currently being developed and through detection of other tumour markers, such as new-generation protein biomarkers, and cancer metabolites identifiable by mass spectrometry. We endeavour to improve the sensitivity of liquid biopsy through selective venous sampling from the vessels draining the district or various districts affected by the tumour, thus reducing the impact of the dilution of fragmented DNA that occurs in the total blood volume.
Case 1
A 46-year-old male with no personal or family history of cancer underwent diffusion-weighted WB-MRI in the context of clinical screening, which revealed enlarged lymph nodes in the left iliac chain. The remaining lymph nodes, spleen, and bone marrow were unremarkable. Given the difficult access for instrumental biopsy, liquid biopsy with selective venous catheterisation was suggested. Only the sample from the left internal iliac vein was positive for the FGFR3 gene mutation, related to lymphoma. Subsequent percutaneous CT-guided biopsy and a video-laparoscopic procedure were both non-diagnostic. Blood tests were normal, while an 18F-FDG PET scan showed positive uptake coinciding with the MRI finding. No progression was seen at follow-up.
Case 2
A 50-year-old male presented with persistent thrombocytopenia. Liquid biopsy performed as a preliminary test showed BRAF gene mutation in selective venous samples as well as in peripheral blood. This mutation is related to lymphoma in 2.23% of cases. Low-grade lymphoma was confirmed by bone marrow biopsy. Chemotherapy led to the disappearance of the mutation in liquid biopsy samples, whereas a repeat bone marrow biopsy confirmed minimal disease. Diffusion-weighted WB-MRI revealed diffuse discrete lesions in the bone marrow, mainly in the spine and pelvis.
Case 3
Liquid biopsy was performed in a 77-year-old asymptomatic female with a close family history of ovarian cancer. The peripheral sample was negative, whereas blood obtained from the inferior vena cava showed the PTEN gene mutation. This mutation is related to ovarian cancer in 3.5% of cases. On DWB-MRI, a right supraclavicular lymph node was enlarged with respect to a previous chest CT scan performed for other reasons. Lymph node biopsy was negative for epithelial cells or lymphoproliferative disease. Gynaecologic examination, transvaginal ultrasound, and abdominal CT scan were all negative. In this case, the liquid biopsy result may be the expression of a tumour clone not destined to develop into progressive ovarian cancer. The finding of the mutation in the sample collected from the blood draining the pelvis nonetheless reinforces the ovarian origin of pathological DNA. Follow-up over time is recommended.
Diffusion-weighted WB-MRI has already earned its place in cancer diagnostics for staging of multiple myeloma and malignant lymphomas, thanks to its ability to depict the bone marrow and skeletal lesions due to solid tumour metastases. In any case, the high contrast resolution of MRI makes it an important alternative for other difficult evaluations, such as peritoneal cancer seeding, for example. The potential value of this imaging method in asymptomatic patients remains to be established. Likewise, liquid biopsy can hardly be accepted as the sole initial diagnostic method in asymptomatic patients and those with no previous history of cancer because tumour-related mutations, which are defined as transient, do not necessarily mean that cancer will develop in that person’s lifetime. On the other hand, the diagnostic and prognostic significance changes when a diagnosis of minimal residual disease or recurrence of disease cannot otherwise be obtained at sites inaccessible to conventional instrumental biopsies. The combination of magnetic resonance and liquid biopsy may potentially solve some diagnostic conflicts and guide new treatments based on molecular diagnosis and its variations as the cancer evolves.
Bruno Damascelli and Vladimira Tichà are interventional radiologists in the department of Interventional Oncology, Emo GVM Centrocuore Columbus, Milan, Italy.
Gianluigi Patelli is the chief of the Radiology Department at Seriate Hospital, Seriate (BG), Italy.
Giuseppe Petralia is director of the Precision Imaging and Research Unit, IEO European Institute of Oncology, IRCSS, Milan, Italy, and is an interventional radiologist in the department of Oncology and Haematology, University of Milan, Milan, Italy, and at Advanced Screening Centers, ASC Italia, Castelli Calepio, Bergamo, Italy.
This work is sponsored by the Falciani Foundation. The authors report no disclosures pertaining to this article.
The Royal College of Radiologists (RCR) and the British Society of Interventional Radiology (BSIR) have created a “myth busting” guide to encourage more women to train as interventional radiologists.
While more than half of medical graduates are female, women are under-represented in interventional radiology (IR).
The RCR’s most recent radiologist census revealed that only one in ten consultant interventional radiologists are women (11%), compared with four in 10 consultant diagnostic radiologists (41%). A 2018 survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) found that exposure to radiation, particularly during reproductive years, and the perceived lack of work-life balance has made the subspecialty less attractive to prospective radiology trainees.
To encourage and support more women training in IR, the RCR and BSIR have created “Women in Interventional Radiology: Insights into the Subspecialty”, aimed at interested undergraduates, foundation doctors, and trainee radiologists.
The leaflet features commentary from women in IR working across the UK and at various stages in their careers, addressing common myths and queries about IR training, such as access to flexible training, radiation exposure risks, and working in what has been a traditionally male-dominated medical sub-specialty.
The contributors also give general advice about getting into the subspecialty and the professional satisfaction they have experienced through a career in IR.
Rosemina Ahmad, chair of the BSIR Women and Diversity Committee and one of the guide authors, says: “This is a landmark document in terms of providing a clear focus on and for women in IR.
“The support from the RCR and BSIR has been invaluable in highlighting the importance of recruiting women into IR, so that we have the very best talent and provide doctors that reflect our local communities.
“Role models are incredibly important in shaping career choices and I hope the experiences of women in IR are both motivating and inspiring to readers and highlight that women can and do succeed in this rapidly advancing field of image-guided surgery.”
There is no evidence of a benefit from additional paclitaxel-coated balloon use compared to standard balloon angioplasty alone in the context of preserving arteriovenous (AV) fistula patency for haemodialysis, the multicentre, randomised controlled PAVE (Paclitaxel-coated balloons and angioplasty of AV fistulas) trial finds. Speaking during the “Trial update” session of the 2020 annual scientific meeting of the British Society of Interventional Radiology (BSIR; 1–3 December, online), Michael Robson (Guy’s and St Thomas’ Hospital and King’s College London, London, UK) informed livestream attendees that there was no indication of an early treatment effect, and that all primary and secondary outcome measures of their trial demonstrated this same conclusion. Robson reported no disclosures relating to the PAVE trial, but noted that BD provided the balloons used. BD played no other role in the investigation, he reported.
Contextualising the PAVE trial, Robson told BSIR attendees: “A fistuloplasty is a good treatment for a blocked arteriovenous fistula before haemodialysis; however, the benefits may be short-term, and a stenosis often occurs. In retrospective series, the post intervention primary patency rate is around 60–70% at six months, going down to 40–50% at one year.”
Drug-coated balloons (DCB) have “a fairly established role” in the peripheral arterial setting and may provide some improvement in patency rates, Robson and colleagues hypothesised. Several small, single-centre studies have suggested a benefit for the use of local paclitaxel delivery in dialysis access, leading the PAVE triallists to design a study that would assess the efficacy of additional paclitaxel-coated balloon angioplasty compared to high-pressure balloon angioplasty only to preserve the patency of AV fistulas used for haemodialysis.
They conducted a double-blind, multicentre randomised controlled trial. Patients were unaware of treatment allocation, as were the majority of the clinical and research team. “It was not possible to blind the radiologists,” Robson explained, “because of the different appearances of the drug-coated balloon and the control balloon.” In total, 212 patients from 20 centres across the UK were recruited, randomised in a 1:1 ratio into the paclitaxel-coated balloon group or the control group, and followed up for a minimum of one year—the trial ended when the last recruited patient had completed one-year follow-up.
There was no statistically significant difference in time to end of target lesion primary patency, the study’s primary endpoint, between the two groups. Time to end of target lesion primary patency was measured when any of the following occurred: a clinically driven reintervention of the treatment segment; thrombotic occlusion that includes the treatment segment; surgical intervention that excludes the treatment segment from the access circuit; abandonment of the AV fistula due to an inability to re-treat the treatment segment.
“We also looked at competing risks, so conducted a sensitivity analysis, and, again, this did not suggest a difference [between the DCB and control arms],” Robson said.
Time to end of access circuit primary patency, one of the study’s secondary endpoints, also was not statistically significantly different between the paclitaxel-coated cohort and the control group.
Time to end of access circuit cumulative patency—when the fistula was abandoned—another secondary endpoint, was again not meaningfully different between the groups.
Continuing the pattern, “there was no suggestion of a difference between groups” when the triallists looked at the angiographic secondary outcomes, late lumen loss and rate of binary restenosis.
Procedural success was “good” in both cohorts, according to Robson said, with no difference between the treatment and control arms of the PAVE trial. There was no difference between the two groups in terms of the number of adverse events.
Lutonix AV clinical trial and IN.PACT AV access study: Randomised controlled trials prior to PAVE
In 2017, data from the first large-scale, randomised controlled trial investigating the clinical use and safety of a DCB catheter (Lutonix 035 AV; BD) for the treatment of dysfunctional AV fistulas and grafts were presented at the Leipzig Interventional Course (LINC; 24–27 January, Leipzig, Germany) and published in the Journal of Vascular and Interventional Radiology (JVIR). The eight-month data presented by Scott Trerotola (Perelman School of Medicine of the University of Pennsylvania, Philadelphia, USA) at the time showed that the drug-coated balloon is linked with a significantly higher target lesion patency and far fewer reinterventions to maintain the opening in a wide variety of failing AV fistulas than standard angioplasty. Two-year data, also published in JVIR in 2020, corroborated this finding.
However, the 180-day target lesion primary patency was not significantly different between the two treatment groups (p=0.06). As this was the primary endpoint, Trerotola noted that it was not met, but clarified at the time that this was a “statistical blip” as the curves continue to clearly diverge by the 240-day mark.
In August 2020, the New England Journal of Medicine published the six-month results of a second large, randomised controlled trial—the IN.PACT AV access study, which used the IN.PACT AV balloon from Medtronic for the treatment of stenotic lesions in dysfunctional haemodialysis AV fistulas. In this study, DCB use was found to be superior to standard balloon angioplasty, and this difference was statistically significant: target lesion primary patency was 82.2% in the former group (n=170), and 59.5% in the latter (n=160; p<0.001).
“So why have we not shown a difference in the PAVE trial, whereas the IN.PACT AV access study did show a difference [at six months]?” Robson asked. “I have not got an obvious answer to that.
“I guess all I can say about the PAVE trial,” he continued, “is that we tried to deliver as robust a trial as we could. We did everything that we could to preserve blinding amongst participants and the research team. Clinically-driven reintervention was called by a different radiologist wherever possible.”
Difference between PAVE trial and IN.PACT AV
There were several differences between the PAVE trial and IN.PACT AV access study: only patients with a single lesion or with tandem lesions that could be treated with a single drug-coated balloon were included in the PAVE trial, whereas IN.PACT analysed data from patients with multiple lesions; AV fistulas with previous thrombosis were included in the PAVE trial, but not IN.PACT; more patients in PAVE were Caucasian, and fewer had had previous revascularisations.
“Whether these explain the differing results I do not know,” Robson said.
Robert Morgan (St George’s Hospital NH Foundation Trust, London, UK) was awarded the British Society of Interventional Radiology (BSIR) Gold Medal for distinguished service to the specialty and to the society at the BSIR 2020 annual scientific meeting (1–3 December, online).
“It gives me great pleasure to accept this honour on behalf of the society,” Morgan said. He thanked the BSIR council and officers for volunteering him for the award, saying he is “deeply honoured” for the recognition. He also thanked BSIR members for their support, and his interventional radiology (IR) colleagues at St George’s, saying: “without whom this would not have been possible”.
Speaking in a pre-recorded video, Lakshmi Ratnam (St George’s Hospital, London, UK), chair of the BSIR scientific programme committee, said: “Unfortunately, due to COVID, we are unable to do this [present the Gold Medal at a physical meeting] as we usually would, surrounded by colleagues, peers, and family. I am therefore very grateful today to be joined by the chief medical director of St George’s Hospital in London, Richard Jennings, who will present the Gold Medal to this year’s distinguished recipient, Robert Morgan.”
Keeping a distance of 2m as per COVID-19 regulations in the UK, Jennings presented Morgan with his award by placing it on a bench for the recipient to collect. “He is an exceedingly valued clinical leader here at St George’s,” Jennings said, before thanking Morgan for his work. “All of his colleagues think extremely highly of him, and we are very proud to have him working with us.”
Describing her “colleague, mentor, and friend”, Ratnam said of Morgan: “Robert has had an extremely distinguished career in interventional radiology, and has been an IR consultant here at St George’s for 21 years. He has served the BSIR as a member and chair of multiple committees, and has been a secretary of the society. He has represented UK radiology as a member and chair of multiple committees in the Cardiovascular and Interventional Radiological Society of Europe [CIRSE], finally culminating in the prestigious role of president of CIRSE in 2017. Robert is current Past President of CIRSE and is a member of the CIRSE Executive Board. Robert is an officer of the BSIR and is the BSIR council lead for strategy and international relations. He has also held several other roles in national and international societies including the Royal College of Radiologists (RCR), the European Congress of Radiology (ECR), the Society of Interventional Radiology (SIR), the UK Endovascular Forum, and the British Society of Endovascular Therapy.
“His main interest within IR has been in vascular disease, both in the role of endografting for diseases of the thoracic and abdominal aorta, and the role of IR in the management of arterial occlusive disease. During his career, he has been at the forefront of many emerging vascular techniques, and has been a great mentor and teacher to many generations of interventional radiologists, myself included.”
She continued: “Despite his countless and impressive achievements, Rob has always remained approachable, and generous with his knowledge and skills. The growth and achievements of the department here at St George’s are a testimony to the ethos that he has been key to building. He continually champions IR as a subspecialty, and is a great role model for future generations of aspiring interventional radiologists.”
Medical background
BSIR vice president Phillip Haslam (Freeman Hospital Newcastle, Newcastle upon Tyne, UK) introduced Morgan to congress attendees, recounting his education background: Morgan trained at Bristol University Medical School (Bristol, UK), before heading to Plymouth, UK, for three years of radiology training, and then to St George’s Hospital in London, UK, for a further two years. He next completed a Fellowship at the University of Texas (Austin, USA) under Eric Van Sonneberg, specialising in hepatobiliary and vascular interventions. Returning to the UK, Morgan was a Fellow under Andreas ‘Andy’ Adams (Guys’ and St Thomas’ NHS Foundation Trust, London, UK) for 18 months, before becoming a consultant at St Mary’s Hospital, London, UK, between 1996 and 1999. He ultimately returned to St George’s Hospital, where he remains as a consultant interventional radiologist and the clinical director for Diagnostics.
The immediate past president of CIRSE, Morgan was instrumental in the development of the European Board of Interventional Radiology (EBIR), a voluntary supplemental examination designed to evaluate interventional radiologists’ clinical and technical knowledge, first released in 2010 in Valencia, Spain.
“He has a long history of involvement with the BSIR,” Haslam continued, “and is currently a co-opted council member”.
Morgan has written over 160 peer-reviewed articles, authored more than 45 book chapters, and edited multiple textbooks, as well as delivered above 300 lectures to international audiences (including the 2017 BSIR Wattie Fletcher Lecture). His main research interests lie in the endovascular treatment of the aorta and peripheral vascular disease, as well as the use of embolization to control haemorrhage, and the treatment of visceral aneurysms. He is the deputy editor-in-chief of Cardiovascular and Interventional Radiology (CVIR) Endovascular, and has organised many teaching courses throughout his career.
Following the rapid reconfiguration of healthcare practices in response to the COVID-19 pandemic in early 2020, Narayan Karunanithy reflects on the position of interventional radiology (IR) services going into 2021. Citing data demonstrating that the reduction in IR activity during the first national lockdown was far less than that seen in other procedure-centred specialties, such as vascular surgery, urology, and endoscopy, Karunanithy argues that formal incorporation of IR treatments into patient pathways would result in more efficient care. As many IR procedures can be performed as a day case or in an ambulatory care unit, he writes that interventional radiologists can “hugely support emergency preparedness plans”, which will likely continue to be vital in 2021.
The challenge for healthcare organisations to deliver on the “triple aims” of health system performance has been made many magnitudes more complex in 2020 due to the COVID-19 pandemic (see Table 1).1 The scope and nature of interventional radiology (IR) practice, however, is unusually well-placed to meet these aims, and looks well set to play a more central role in delivery of high quality, safe healthcare in 2021 and beyond.
At the time of writing, we find ourselves in the midst of the second COVID-19 pandemic wave in the UK, and sadly we are once again already seeing both high infection and mortality rates. The recent promising vaccine results have provided a much-needed glimmer of hope. Whilst vaccines are considered at present our best hope, uncertainty still remains regarding the effectiveness, availability, and impact of those vaccines. Hence, the healthcare strategy—at least for the foreseeable future—will need to incorporate the ability to treat those with COVID-19 and continue to provide timely, safe, effective, and cost-efficient care for everyone with non-COVID related illnesses.
During the first wave, it was impressive and inspiring to see so many IR departments demonstrate a willingness to reconfigure working practice and be available to provide much-needed acute services. One of the models that worked extremely well during the summer/autumn of 2020 was the spatial segregation of services into “low-risk” and “high-risk” sites. This was, in large part, created through partnerships forged with private sector hospitals which enabled IR to maintain access to important treatments such as tumour ablation and uterine fibroid and prostate artery embolization in “low-risk” environments. In parallel, comprehensive cover was provided at “hot” sites for the spectrum of COVID and non-COVID emergencies like embolization, thrombectomy, complex venous access, and percutaneous drainage of obstructed kidneys, bile ducts, and abscesses.2 Published activity data bear this out and have shown that the reduction in IR activity during the first wave of lockdown, by 41% and 25% in outpatient and inpatient volumes respectively, was far less than that seen in other procedure-centred specialties like vascular surgery, urology, and endoscopy.3
Even prior to the pandemic, it was estimated that approximately one in 10 in-patients were treated by IR during their hospital stay, underlining the key importance of IR in the day-to-day functioning of hospitals.4 Formal incorporation of IR treatments into patient pathways and access to IR expertise through ward rounds and clinics would allow far more efficient and streamlined care for those requiring it. Across the spectrum of clinical practice, minimally invasive IR treatments result in quicker recovery, lower morbidity, and shorter hospital stays. Crucially in these times, these procedures can often be performed in a day case or ambulatory care unit. The availability of such units can hugely support emergency preparedness plans. This was illustrated in the first wave of the pandemic, when most endoscopy services ceased and IR stepped in to perform many more radiologically inserted gastrostomies rather than percutaneous endoscopic gastrostomies.
An additional benefit of high-volume IR day case units is the efficient utilisation of resources and an increase in financial income for the organisation. Increasingly, organisations within the UK have come to recognise these clinical and financial benefits, and many centres have invested in such facilities. However, these are not universally available, as highlighted in the recently published Radiology GIRFT [Get It Right First Time] report.5 Alongside this, there is a need for robust workforce planning to ensure there are adequate numbers of IR doctors, nurses, radiographers, and administrative staff to sustain IR services. The skillset that IR staff possess is extremely versatile, and there were many reports of IR supporting the frontline response during the first wave of the pandemic. This included redeploying staff in the critical care setting with the goal of providing bed-side procedures like difficult venous access and ultrasound guided drainage procedures.
Whilst the months ahead will be challenging, there is an opportunity to establish IR practice firmly at the very core of clinical practice through proactive planning and delivery of innovative, effective, and safe care for the benefit of our patients.
I would like to acknowledge the guidance and support from Ian McCafferty (President, British Society of Interventional Radiology [BSIR]) in the preparation of this article.
Stay safe everyone.
Narayan Karunanithy is a member of the Communications Committee, British Society of Interventional Radiology, and is a consultant interventional radiologist at Guy’s & St Thomas’ NHS Foundation Trust, London, UK.
References
On the opening day of BSIR 2020 (1–3 December, virtual), Lakshmi Ratnam (London, UK), chair of the scientific programme committee, moderates a special Interventional News panel with BSIR president, Ian McCafferty (Birmingham, UK), and vice-president, Philip Haslam (Newcastle, UK).
McCafferty outlines some of the highlights from this year’s programme, which he notes contains a “nice balance between vascular and non-vascular interventional oncology subjects”, adding that he is particularly excited about the lymphatic session.
McCafferty discusses how interventional radiology (IR) has “risen to the challenge” of COVID-19 with the strong message that interventional radiologists have “helped maintain activities in the hospital more than any other group” during the COVID-19 pandemic. He points out that the BSIR has worked closely with the Royal College of Radiologists (RCR), so that interventional radiology could continue to perform procedures throughout lockdown, while the majority of surgery was put on pause. Those interventional radiology departments with their own day case units were the most efficient, he notes, making the point that quick outpatient-style treatment by interventional radiologists is really possible, extremely cost-effective, [generally has] low-morbidity, and is often preferred by patients. Indeed, vitally, it can be carried out in “cold” COVID-free environments outside of the hospital setting.
Haslam, commenting on the symbiotic relationship that industry and many device-using specialties share, states that the BSIR has continued to work closely and collaborate with industry partners to bring about a high-quality virtual event with impactful and useful education. Haslam hopes that COVID-19 will soon “be a thing of the dim and distant past”, which will allow for “a brilliant face-to-face meeting” in Glasgow for BSIR 2021.
Boston Scientific has announced that it has entered into a definitive agreement with Stark International and SERB SAS, affiliates of the European specialty pharmaceutical group SERB, to sell its BTG Specialty Pharmaceuticals business for US$800 million in cash.
Boston acquired BTG in August 2019, an acquisition covering BTG’s three business segments, including an interventional medicine portfolio encompassing interventional oncology therapeutic technologies for patients with liver and kidney cancers, as well as a vascular portfolio for treatment of deep vein thrombosis, pulmonary embolism, deep venous obstruction and superficial venous disease.
The transaction announced today will see Boston divest the pharmaceuticals segment of the business, which develops, manufactures and commercialises antidotes used in hospitals and emergency care settings, including the CroFab, DigiFab, and Voraxaze products. The three franchises are expected to generate approximately US$210 million in revenue for the full year 2020.
SERB, backed by private equity firm Charterhouse Capital Partners since 2017, owns a diversified portfolio of prescription medicines focused on rare and life-threatening diseases.
“This transaction will help the BTG Specialty Pharmaceuticals business enhance its potential as a fully integrated specialty pharmaceuticals platform,” said Anthony Higham, president, BTG, Specialty Pharmaceuticals. “We believe our capabilities and portfolio strongly complement those of SERB, and we look forward to this next chapter as we continue to positively impact the lives of patients and the people who care for them.”
“After acquiring BTG in 2019 for approximately US$3.7 billion net of cash on hand, and following the close of this transaction, we will have divested the two BTG non-medical device portions—Pharmaceutical Licensing royalties in the fourth quarter of 2019 and Specialty Pharmaceuticals announced today—for more than US$1 billion in net proceeds,” said Jeff Mirviss, executive vice president and president, Peripheral Interventions, Boston Scientific. “We continue to be very pleased with the performance of the core Interventional Medicines business, the primary driver of the BTG acquisition, which has delivered strong growth and is expected to exceed our original goal of US$175 million in synergies.”
The Society of Interventional Radiology (SIR) and the American Medical Association (AMA) have sent a letter to the Centers for Medicare and Medicaid Services (CMS) urging them to implement and pay for Current Procedural Terminology (CPT) code 99072 to compensate practices for the additional supplies and new staff activities required to provide safe patient care during the COVID-19 pandemic.
The medical societies of each of the 50 states of America, plus the Medical Society of the District of Columbia, are also signatories, in addition to 76 societies and associations representing different medical specialities at the national level—such as the Society for Vascular Surgery, the American Urological Association, and the Spine Intervention Society. Altogether, hundreds of thousands of physicians are represented by the undersigned organisations.
Addressed to CMS administrator Seema Verna, the letter states that the COVID-19 public health emergency “has placed unprecedented strain on our [the signatories’] physician members, including ongoing threats to their financial viability due to months of lost revenue from practice closures and/or operating at reduced capacity”. According to the letter, in July and August 2020, an AMA survey of 3,500 physicians who provided at least 20 hours of patient care per week prior to the pandemic found that 81% of respondents reported that revenue was still lower than pre-pandemic times, with the average revenue drop being 32%. Compounding the financial stress of lost revenue, practices are also incurring additional costs for heightened infection control protocols and personal protective equipment (PPE).
The letter writers continue: “We recognise and appreciate the significant support and flexibility CMS has provided to physician practices. However, it is imperative that CMS specifically compensate physicians for the additional expenses involved in treating patients during the public health emergency. Practices incur significant costs in implementing the increased infection control measures required to provide safe care during the COVID-19 pandemic. These costs include additional supplies (such as cleaning products and facial masks for both staff and patients), clinical staff time for activities such as pre-visit instructions and symptom checks upon arrival, and implementation of office redesign measures to ensure social distancing.”
The AMA survey from the summer of 2020 describes how practice owners reported an average increase in PPE spending of 57% from February 2020, with 25% of owners saying that PPE expenses have risen at least 75%. Nearly all (99%) surveyed physicians have implemented infection control protocols, such as pre-visit screening phone calls, screening for COVID-19 symptoms/exposure and checking patient temperatures upon office arrival, and limiting the number of patients in the waiting room.
Detailing CMS’ actions, the letter claims that, in order to address the financial impact of these new protocols related to the COVID-19 pandemic, “the CPT Editorial Panel approved CPT code 99072 on 8 September 8 2020. According to CPT guidance, 99072 is used to report the additional supplies, materials, and clinical staff time over and above the practice expense(s) included in an office visit or other non-facility service(s) when performed during a public health emergency, as defined by law, due to respiratory-transmitted infectious disease.”
“Our organisations advocate for CMS to immediately implement and pay for CPT code 99072 with no patient cost-sharing during the public health emergency,” the societies write. “Payment for these additional costs should be fully funded and not be subject to budget neutrality. CMS could use remaining money from the CARES Act funding to pay physicians for these costs and/or recognise the decreased expenditures during the early months of the pandemic to waive budget neutrality. Your support will ensure that physicians receive the critical financial resources needed to maintain intensive infection control measures during the COVID-19 public health emergency.”
Prostate artery embolization (PAE) is a good treatment option for patients with benign prostatic hyperplasia (BPH) with minimal complications, according to the 24-month results of the STREAM (Prostatic artery embolization for the treatment of benign prostatic hyperplasia) trial, which affirms the place of the minimally invasive procedure in interventional radiologists’ arsenal.
This MRI-based study looked to examine factors important in predicting successful PAE using MRI over a two-year follow-up period. The triallists report that while adenomatous BPH does particularly well in the short term when treated with PAE, stromal BPH demonstrates better results at two years. In addition, they conclude that patients with median lobe hypertrophy (MLH) do as well as those without MLH up to 24 months, and that initial prostate volume does not appear to be significant in predicting outcome at two years.
“This study has provided valuable information and allowed a better understanding of which glands respond and how they will respond to PAE,” Charles Tapping (Churchill Hospital, Oxford, UK) and co-authors write in Cardiovascular and Interventional Radiology (CVIR). “It also allows clinicians to provide more information to patients exploring treatment for their BPH. MLH responded as well as non-MLH BPH disease, suggesting this technique may be valuable in treating patients with MLH, especially if some of the other minimally invasive techniques are limited if significant MLH is present.”
STREAM trial data at two years proves the technical and clinical success of PAE
“PAE has established itself as one of the alternative minimally invasive treatments for BPH, and is now accepted as safe and effective,” Tapping et al write. They go on to say that while performing PAE can be technically challenging, with a significant learning curve to perform the technique successfully, it is important to ascertain factors that may aid in predicting which patients would benefit most from PAE. They note that this is a particular imperative for interventional radiologists as there are “a number of robust minimally invasive techniques to treat BPH, such as the Urolift system and water vapour thermal therapy (REZUM)”.
They therefore conducted a prospective cohort study of 50 patients with BPH who were treated with PAE at a single institution. Patients had moderate to severe symptoms of BPH refractory to medical management for at least six months prior to enrolment in STREAM. Patients were imaged with multiparametric MRI imaging pre-PAE, and at three months, 12 months, and 24 months post-procedure. Clinical success was measured with international prostate symptom score (IPSS), international index of erectile function (IIEF), and validated quality of life (QoL) EQ-5D-5L questionnaires.
The technical success rate was 96%—no prostate arteries could be identified intraprocedurally in two of the 50 patients. The study authors report only minor complications arising from PAE: two cases of acute urinary retention and one case of uncomplicated urinary tract infection. While these are positive data for PAE, the authors state that, “Unfortunately, as there was no comparison group or control group in this study, it is not possible to make direct comparisons between different minimally invasive methods for treating BPH.”
Clinical outcomes of the STREAM trial were also positive. The mean IPSS score dropped from a baseline score of 21.1 (range: 16–36) to 7.2 at 12 months, and 8.1 at 24 months. Meanwhile, results from the EQ-5D-5L quality of life questionnaire demonstrated an increased quality of life at three, 12, and 24 months post-procedure. Results from the IIEF showed no significant change in erectile function over the two-year study following PAE. The prostate volume as measured on MRI imaging was significantly reduced from baseline to three months post-PAE. There was then a non-significant volume reduction at 12 and 24 months when compared to baseline.
Greatest improvement in IPSS score seen in patients with adenomatous BPH
“An interesting analysis of the results showed that while adenomatous BPH had an initial greater reduction in their IPSS score, improvement in quality of life, and symptoms (at three and 12 months compared to stromal group), the stromal group had better results at 24 months,” Tapping and colleagues say.
“In fact”, they write, “there was a continued decline in IPSS score in the stromal group over the 24-month study period, with a slight increase in IPSS score in the adenomatous group from 12 to 24 months.”
While the stromal prostate gland volume decreased compared to baseline size at three, 12, and 24 months post-PAE, the adenomatous glands at first rapidly reduced in size, maintained this small volume out to 12 months, and then increased in size again, with a larger volume reported at 24 months.
Discussing this finding, the triallists say: “This adds to the previously perceived literature that suggests adenomatous BPH patients had a better outcome. Angiography of adenomatous masses within the prostate demonstrates that these are highly vascular structures and the more rapid reduction in symptoms and IPSS score can be accounted for by infarction of the adenoma and rapid reduction in pressure on the transition zone of the prostate. Moreover, the more gradual improvement in the stromal group corresponds to typically a less vascular pattern on angiography.”
Patients with median lobe hypertrophy do just as well post-PAE as those without median lobe hypertrophy
No significant difference in IPSS score was observed at any time point between the 19 patients with MLH and those without MLH, according to the STREAM trial findings.
“Typically,” Tapping and co-authors muse, “it has been considered that patients with MLH would not do as well with PAE. However, patients in this cohort did as well as those without MLH. PAE may therefore be a good option for patients with MLH that cannot have alternative minimally invasive forms of treatment for their BPH.”
In addition, there was no significant correlation between initial prostatic volume and the IPSS score at 12 and 24 months post-PAE (p=0.05), the authors note. While previous investigators have suggested that prostate size is associated with clinical success following PAE, Tapping et al consider that in their study, MRI provided extra detail of the internal prostate architecture, meaning that “factors such as adenomatous predominant and stromal dominant disease became more useful”.
They conclude that further studies are needed in order to determine who the most appropriate patients for each minimally invasive BPH treatment are, and to overcome the limitation imposed on this trial by its small sample size.
In their recent systematic review and meta-analysis, Venkata Sai Jasty (University of Arizona, Tuscon, USA) and colleagues found that the risk of ischaemic steal syndrome, “one of the most feared complications in vascular access,” and patency rate are comparable for both tapered and non-tapered prosthetic arteriovenous grafts (AVGs) in dialysis access.
Writing in The Journal of Vascular Access (JVA), Jasty et al detail that end-stage renal disease (ESRD) “remains one of the leading causes of mortality and morbidity”. They note that there are currently three treatment options for ESRD—haemodialysis, peritoneal dialysis, and organ transplantation—but mention that a shortage of organ supply for a rising need has led to “a continued and increased call” for haemodialysis.
Upper extremity arteriovenous access “remains the preferred vascular access for haemodialysis in ESRD patients,” the authors relay, detailing that an arteriovenous fistula (AVF) or AVG are generally favoured over a central venous catheter, “due to lower rates of infection, hospitalisation, cardiovascular events, and all-cause mortality rate”.
They write that prior guidelines recommended AVFs as the initial choice for haemodialysis access due to more durability, higher patency rates, and lower morbidity and mortality compared to AVGs. However, “due to high failure rates of AVF from inadequate maturation and interventions required to achieve and maintain a functional AVF,” they stress that the latest guidelines from the National Kidney Foundation Kidney Disease Quality Outcomes Initiative (NKF KDQOI) “challenge the use of AVFs on certain populations” and recommend AVGs as the “preferable option” for haemodialysis.
Jasty and colleagues note that one of the biggest complications of vascular access placement is ischaemic steal syndrome, where blood is diverted from the hand to the graft, leading to hand ischaemia. To mitigate this problem, they detail that tapered grafts were created. These grafts have a smaller diameter at the arterial anastomosis, they write “which leads to decreased blood flow from the artery to the graft, thus lowering the risk of ischaemic steal”.
“It is unclear whether tapered AVGs are superior to non-tapered AVGs when it comes to preventing upper extremity ischaemic steal syndrome,” Jasty and colleagues state, noting that this gap in the literature led them to evaluate the outcomes of both graft types using a systematic review and meta-analysis.
The investigators performed a literature search in order to identify all English language publications from 1999 to 2019 that directly compared the outcomes of upper extremity tapered and non-tapered AVGs. They evaluated primary patency at one year (number of studies [n]=4), secondary patency at one year (n=3), and risk of ischaemic steal (n=5) and infection (n=4).
Of 5,808 studies screened, Jasty et al identified a total of five studies involving 4,397 patients that met the inclusion criteria and were therefore included in the analysis. They write in JVA that the meta-analyses revealed no significant difference for the risk of ischaemic steal syndrome (pooled odds ratio [OR] 0.92, 95% confidence interval [CI] 0.29–2.91, p=0.12, I2=48%) between the tapered and non-tapered upper extremity AVG.
In addition, they report that the primary patency (OR 1.33, 95% CI 0.93–1.9, p=0.12, I2=10%) and secondary patency at one year (OR 1.49, 95% CI 0.84–2.63, p=0.17, I2=13%), and rate of infection (OR 0.62, 95% CI 0.3–1.27, p=0.19, I2=29%) were also similar between the tapered and non-tapered AVGs.
The authors acknowledge certain limitations of this meta-analysis, including a low number of studies, unknown reasons for surgeons’ preference for one graft over the other, and a low number of patient samples and short follow-up (usually up to one year only) in the included studies.
Jasty and colleagues conclude: “This meta-analysis does not support the routine use of tapered graft over non-tapered graft to prevent ischaemic steal syndrome in upper extremity access”. However, due to the small number of studies and sample sizes, as well as limited stratification of outcomes based on risk factors, they stress, “Future studies should take such limitations into account while designing more robust protocols to elucidate this issue”.
MedAlliance has announced completion of patient enrolment in the ISABELLA clinical trial with the Selution SLR 018 drug-eluting balloon (DEB) for the treatment of dysfunctional arteriovenous (AV) fistulas in end-stage renal failure patients undergoing haemodialysis.
Selution SLR (sustained limus release) is a novel sirolimus-eluting balloon that provides a controlled sustained release of drug, similar to a drug-eluting stent (DES).
ISABELLA (Intervention with Selution SLR agent balloon for endovascular latent limus therapy for failing AV fistulas) is a prospective, single-centre, multi-investigator, non-blinded, single-arm trial investigating the safety and feasibility of the Selution SLR 018 DEB for the treatment of failing AV fistulas in 40 haemodialysis patients.
The objective of this study is to determine the safety and efficacy of the Selution SLR 018 DEB in the treatment of dysfunctional AV fistulas in end-stage renal failure patients undergoing haemodialysis. The anticipated clinical benefit is to improve the target lesion primary patency and reduce the number of reinterventions in stenotic AV fistulas of haemodialysis patients and hence morbidity in this frail patient population compared to conventional balloon angioplasty.
The efficacy endpoint of interest is six-month target lesion primary patency and the safety endpoint is freedom from localised or systemic serious adverse events through 30 days that reasonably suggest the involvement of the AV fistula circuit. The study has recently completed its 40-patient recruitment and will follow them up for a period of two years at Singapore General Hospital (SGH), which performs over 3,000 access salvage procedures annually.
“We are very excited at SGH and eagerly await the results from ISABELLA, which will be the first study to report clinical safety and efficacy data of sirolimus-eluting balloon (SEB) angioplasty using the Selution SLR DEB catheter combined with high pressure conventional balloon angioplasty vessel preparation, for dysfunctional AVF circuits in Asian haemodialysis patients”, said lead principal investigator associate professor Tjun Tang, senior consultant vascular and endovascular surgeon at SGH.
“SEBs are a natural evolution of the current gold standard treatment option of conventional balloon angioplasty for salvaging failing and stenotic AV fistula circuits. Paclitaxel drug-coated balloons have been used with limited success and the data are far from conclusive. The Selution SLR DEB provides therapeutic concentrations of drug within the vessel wall for at least 90 days post-angioplasty, which is a major advantage over other drug-coated balloons in dealing with the extended nature of the NIH [National Institutes of Health] process. Our plan is to follow up patients to two years to define the effectiveness of the studied therapy in the medium term.”
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A novel embolization device in the interventional oncology space—the GPX embolic device (Fluidx Medical Technology)—has successfully been used in a patient to therapeutically devascularise a tumour for the first time.
“We are impressed with the GPX embolic,” comments Andrew Holden (Auckland City Hospital, Auckland, New Zealand). “We delivered GPX through a long 150cm 2.4F (0.022inch inner diameter) microcatheter from the patient’s radial artery. GPX was easy to use, precise, and occluded the tumour well. We look forward to using GPX across a broad range of applications to improve patient care.”
The GPX embolic device is an innovative embolic designed to combine the benefits of other embolics like coils, particles, and liquids with simplified preparation, delivery, precision, and control leading to durable, long-term occlusions. The GPX technology is a low viscosity, aqueous-based solution in a syringe that solidifies into a durable embolic material upon delivery, without polymerisation or dimethyl-sulfoxide (DMSO) precipitation associated with other embolics.
According to a company press release, GPX is packaged ready-to-use in a syringe, requires less than one minute of tableside preparation by the clinician, and may be delivered through standard catheters or microcatheters.
“GPX is easy to prepare, deliver, and control,” says Ryan O’Hara (University of Utah, Salt Lake City, Utah USA). “GPX is responsive to the physician and layers well in the vessel during delivery, resulting in improved targeting and control. I see potential for this embolic in interventional oncology and other peripheral vascular and neurovascular uses.”
Therapeutic, super-selective embolization is a high-growth procedure used for minimally invasive, targeted treatment of internal bleeds, tumours, aneurysms, vascular malformations, uterine fibroids, varicose veins, and other uses. A variety of embolic devices (coils, particles, plugs, liquids) are used for these procedures, however many can have issues in terms of ease of use, and controlled, consistent delivery. Some embolics also require specialised catheters and solutions as well as complex and lengthy preparation processes.
“This is a significant milestone for the Company,” adds Libble Ginster, CEO of Fluidx Medical Technology. “GPX is an advanced embolic technology that overcomes the challenges associated with other embolic devices. GPX can be used effectively for distal penetration and occlusion of vessel networks, as well as proximal ‘one-and-done’ use of GPX in conjunction with coiling. We look forward to GPX’s use to help a variety of peripheral and neurovascular patients.”
The GPX embolic device is not available for sale in the USA, and is for investigational use only.
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Penumbra today announced US Food and Drug Administration (FDA) 510(k) clearance for expanded indication of the latest iteration of the Indigo aspiration system, Lightning 12.
As part of the Indigo aspiration system, Lightning 12 (Indigo system CAT 12 aspiration catheter with lightning intelligent aspiration) and Separator 12 are now indicated for the removal of fresh, soft emboli and thrombi from vessels of the peripheral arterial and venous systems as well as for the treatment of pulmonary embolism (PE).
“Penumbra continues to strive to bring innovative therapies to the medical community, and this is another important milestone that will help advance pulmonary embolism intervention,” said Adam Elsesser, president and chief executive officer, Penumbra. “COVID has increased the awareness of the need for therapies that remove blood clots, and we are thrilled with the FDA clearance of the PE treatment indication for Lightning 12.”
The Indigo System Lightning 12 is the company’s newest generation aspiration system for peripheral thrombectomy. Lightning 12 combines the Indigo System CAT12 aspiration catheter with lightning intelligent aspiration, enabling physicians to focus on optimising thrombus removal using the system’s unique clot detection mechanism.
CAT12 is a large-lumen aspiration catheter that incorporates novel laser-cut hypotube-based catheter engineering to provide deliverability and torqueability within the body. According to a press release, this combination of intelligent aspiration and large-lumen catheter engineering makes Lightning 12 Penumbra’s most advanced clot removal technology for the treatment of PE.
A novel outpatient procedure—cooled radiofrequency ablation (c-RFA)—offers lasting pain relief for patients suffering from moderate to severe arthritis in their hip and shoulder joints, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA; 29 November–5 December, online). Researchers said the procedure could help reduce reliance on addictive opiates.
People with moderate to severe pain related to osteoarthritis face limited treatment options. Common approaches like injections of anaesthetic and corticosteroids into the affected joints grow less effective as the arthritis progresses and worsens.
“Usually, over time patients become less responsive to these injections,” says Felix M Gonzalez (Emory University School of Medicine, Atlanta, USA). “The first anaesthetic-corticosteroid injection may provide six months of pain relief, the second may last three months, and the third may last only a month. Gradually, the degree of pain relief becomes non-significant.”
Without pain relief, patients face the possibility of joint replacement surgery. Many patients are ineligible for surgery because of health reasons, whereas many others choose not to go through such a major operation. For those patients, the only other viable option may be opiate painkillers, which carry the risk of addiction.
Gonzalez and colleagues have been studying the application of a novel interventional radiology treatment, c-RFA, to achieve pain relief in the setting of advanced degenerative arthritis. The procedure involves the placement of needles where the main sensory nerves exist around the shoulder and hip joints. The nerves are then treated with a low-grade current known as radiofrequency that “stuns” them, slowing the transmission of pain to the brain.
For the new study, 23 people with osteoarthritis underwent treatment, including 12 with shoulder pain and 11 with hip pain that had become unresponsive to anti-inflammatory pain control and intra-articular lidocaine-steroid injections. Treatment was performed two to three weeks after the patients received diagnostic anaesthetic nerve blocks. The patients then completed surveys to measure their function, range of motion, and degree of pain before and at three months after the ablation procedures.
There were no procedure-related complications, and both the hip and shoulder pain groups reported a statistically significant decrease in the degree of pain, with a corresponding increase in dynamic function after the treatment.
“In our study, the results were very impressive and promising,” Gonzalez enthuses. “The patients with shoulder pain had a decrease in pain of 85%, and an increase in function of approximately 74%. In patients with hip pain, there was a 70% reduction in pain, and a gain in function of approximately 66%.”
The procedure offers a new alternative for patients who are facing the prospect of surgery. In addition, it can decrease the risk of opiate addiction.
“This procedure is a last resort for patients who are unable to be physically active and may develop a narcotic addiction,” Gonzalez comments. “Until recently, there was no other alternative for the treatment of patients at the end of the arthritis pathway who do not qualify for surgery or are unwilling to undergo a surgical procedure.”
At last year’s RSNA annual meeting, Gonzalez presented similarly encouraging results from a study of a similar procedure for the treatment of knee arthritis. Together, the knee, shoulder, and hip articulations account for approximately 95% of all arthritis cases.
The procedure could have numerous applications outside of treating arthritic pain, Gonzalez explains. Potential uses include treating pain related to diseases like cancer and sickle cell anaemia-related pain syndrome, for example.
“We are just scratching the surface here,” Gonzalez says. “We would like to explore efficacy of the treatment on patients in other settings like trauma, amputations, and especially in cancer patients with metastatic disease.”
This year’s Vascular Interventional Advances annual meeting (VIVA 2020; 6–8 November, online) opened with a session on controversial hot topics and advanced multidisciplinary approaches to vascular disease. Looking back on the paclitaxel “debacle”, Peter Schneider (University of California San Francisco, San Francisco, USA) detailed key learnings from the last year and a half, pointed to forthcoming data that will help add further clarity, and praised the combined and ongoing efforts of researchers, societies, and regulatory bodies.
Schneider began by stressing the patency of paclitaxel in the femoropopliteal segment. At 12 months, the four randomised controlled trials (RCTs) of paclitaxel drug-coated balloons (DCBs) and drug-eluting stents (DESs) versus percutaneous transluminal angioplasty (PTA) that are currently approved in the USA—ILLUMENATE, IN.PACT SFA, Zilver PTX, and LEVANT—show a “significant improvement” in patency with DCB/DES use compared to PTA, he noted. Speaking to Interventional News, Schneider noted that, since then, the Eluvia DES and the Ranger DCB (both Boston Scientific), have also shown “excellent” results and been approved by the US Food and Drug Administration (FDA).
In December 2018, a meta-analysis of summary-level data was published, “which we all know about,” remarked Schneider, that suggested an increased risk of death with paclitaxel use in the femoropopliteal segment at two and five years. Here Schneider was referencing the 2018 Journal of the American Heart Association (JAHA) paper by Konstantinos Katsanos (University of Patras, Patras, Greece) and colleagues.
Highlighting the instant and enduring impact of this publication, Schneider commented: “Overnight, the use of paclitaxel-delivering devices diminished substantially, which means that overnight the value of our field diminished substantially, because now it takes so many more repeat revascularisations in order to keep our patients whole and to keep these arteries open.”
The meta-analysis relied upon three RCTs—Zilver PTX, THUNDER, and IN.PACT SFA—that were followed up to four or five years and encompassed “a little over 800 patients,” Schneider remarked. Delving into the characteristics of the trials included, he noted that they were all powered for one-year patency, not long-term mortality, and that small control groups were used, leading to “unstable estimates”.
Key learnings: No dose effect, no clustering of deaths as to cause, and “substantial geographic variation” in mortality signal
As the meta-analysis pointed to causality between paclitaxel and mortality, Schneider stressed that it was necessary to assess whether or not there was a dose response. In the meta-analysis, dose was calculated as dose multiplied by time. Supposing a continuous, linear, and increasing exposure to paclitaxel over time is “quite an assumption,” said Schneider, detailing that tissue paclitaxel in pre-clinical models decreased over six months to nearly non-detectable levels and that time is disproportionately available for studies with longer-term follow-up.
When the FDA looked at dose response on mortality, Schneider recalled that “they found none,” specifying that the FDA included the LEVANT II, Zilver PTX, ILLUMENATE, and IN.PACT IDE trials in their assessment. Similarly, there was no dose relationship found in either the IN.PACT investigational device exemption (IDE) and Japan trials, or in the VIVA/North American Science Associates (NAMSA) individual patient data project, Schneider added.
The presenter stated that, along with dose response, it was also crucial to assess whether there was a clustering of deaths, as this would suggest a biological mechanism.
In the FDA analysis, Schneider relayed, there was no clustering of deaths. He elaborated: “There was an increase in deaths in the patients that had paclitaxel, but these were spread across numerous causes, really questioning the availability of a biological mechanism”. This led the FDA to issue a letter on 7 August 2019, stating that there was “no clear evidence of a paclitaxel dose effect on mortality, and no identified pathophysiologic mechanism for the late deaths”.
“We know that these trials were powered for one-year patency, so what about the five-year mortality?” Schneider wondered, stressing that many of the paclitaxel RCTs had a considerable number of patients lost to follow-up or who had withdrawn by this time point.
Through a “Herculean effort” by both the clinical sites and by the study sponsors, “a dramatic number” of these patients were identified, located, and their vital status ascertainment found, Schneider detailed. He noted that a five-year point estimate by the FDA developed a risk of 1.72, which after vital status ascertainment was 1.57, showing a decrease of 21%. The same happened in the IN.PACT IDE and Japan trials, he added, where the hazard ratio decreased by 38%, from 1.63 to 1.39 after vital status follow-up.
The third key point that Schneider addressed was the inconsistency of the mortality signal. In the IN.PACT SFA and the LEVANT II trials that were performed in both the USA and the European Union (EU), there was a “significant difference” in how the patients in the USA versus how those in the EU fared, with no apparent difference in mortality outside the USA, Schneider explained. “Why would this agent be more dangerous in one geography than another?” he asked.
“DCB and PTA patients are treated differently,” Schneider observed, adding that the difference in treatment is greater in the USA than in other geographies. Furthermore, he noted that the IN.PACT IDE and Japan trials, which were performed across different geographies using the same device, not only reveal this difference, but also show that PTA patients were more likely to follow up, with the biggest difference observed in the USA. “This really suggests that there may have been a treatment bias involved,” Schneider opined.
“When you include studies conducted outside the USA—ILLUMENATE EU, IN.PACT Japan, LEVANT I, and Lutonix Japan, for example—along with studies conducted on the same devices inside the USA—ILLUMENATE RCT, IN.PACT SFA, LEVANT II, and Zilver PTX—what you see is a significant drop in the hazard ratio,” he revealed.
Looking ahead: More data, continued collaboration, and trial design improvements
Summarising, Schneider noted that while paclitaxel is consistently efficacious, the mortality signal is not consistent. “There is no dose response and no biological mechanism, and the signal is not apparent so far in real-world data,” he communicated.
In addition, he told the VIVA audience that the signal is not consistent in the RCTs. The signal diminished with vital status ascertainment, and also when patients from outside the USA—where the signal was primarily observed—were included, he précised. “There is a possibility of treatment bias associated with trial design or practice patterns, which may help explain inconsistency of signal,” Schneider speculated.
The paclitaxel debacle is “crystalising,” the presenter concluded, pointing to an increasing volume of new data, with more to follow. Over the next five years, he revealed that 29 studies will yield randomised data on over 11,000 patients, including ILLUMENATE, IMPERIAL, TRANSCEND, VOYAGER, BEST, and SWEDEPAD.
Looking forward, Schneider pointed out that trial design improvements will be made with regards to the size, quality of follow-up, veracity of medical management, and vital status ascertainment.
Indeed, Schneider detailed how the VOYAGER trial sets an example for paclitaxel trials of the future. He commented: “One of the key things about VOYAGER, although it was not paclitaxel versus non-paclitaxel, is that it was a prospective randomised controlled trial in which they had excellent ascertainment, where they followed up more than 99% of the patients.” In addition, he mentioned that VOYAGER had “excellent control of medications”, which is “something that we did not do in the prospective randomised trials”.
At the end of his presentation, Schneider commended the continued collaboration of researchers, societies, manufacturers, and regulatory agencies “across specialties and countries” in the interest of moving things forward.
In relation to the role of the FDA specifically, an audience member asked what the agency has learned from the ongoing paclitaxel debate and how they will change things. “The FDA are in a challenging situation,” Schneider acknowledged. “Obviously they are there to protect the public health, but also to facilitate the ability for us to use the tools we need.”
He continued: “It is not clear to me what and how the FDA will use all the new information that is coming out, but there has been a massive amount of information. I did not go into the extensive amount of real-world data that we have but there is a tremendous amount, so I am sure the FDA is continually reconsidering this, but really the question is not the amount of data, but what is the threshold for them to act, for them to change the guidance that they gave us in August of 2019. Nobody knows that, and I do not know that they have even decided what that would look like.”
Schneider noted that the FDA has approved two paclitaxel devices since the paclitaxel situation began—the Ranger DCB from Boston Scientific and the IN.PACT AV Access balloon from Medtronic—which is “really the key”. He ended with the comment that “if [the FDA] felt there was a strong danger at this point, I do not believe they would approve new devices”.
The Infinity Angioplasty Balloon Company announced today that its angioplasty balloon platform—the Infinity angioplasty balloon catheter—has successfully completed a first-in-human clinical trial.
The platform was recently cleared by the US Food and Drug Administration (FDA) for percutaneous transluminal angioplasty (PTA) treatment of peripheral arterial disease.
“The Infinity catheter represents a game changing innovation in percutaneous angioplasty balloon design and utility,” states founder and vascular surgeon, John Pigott.
John A Phillips, an interventional cardiologist at OhioHealth Riverside Methodist in Columbus, USA, performed the first-in-human Infinity procedure. “I am extremely pleased with the catheter delivery and to-the-mm sizing of the balloon length to the lesion, particularly in this very challenging case,” commented Phillips. “The patient was a 60-year-old woman with highly angulated aortic bifurcation and a 78mm chronic total occlusion in the distal superficial femoral artery.”
According to a press release, the Infinity platform is the first and only therapy to provide Precision Angioplasty, to-the-mm sizing of balloon length to the lesion. Adopting the platform significantly reduces inventory needs and costs from dozens of stock keeping units and it reduces shelf space requirements, inventory management time, and trunk stock; while delivering the assurance that the right balloon size will always be on the shelf.
“Infinity is a highly differentiated product,” reports CEO Gary Smith. “This is an ideal product for both office-based labs and hospitals.” While initially launching the Infinity angioplasty balloon catheter, the company intends to follow quickly with the Infinity Defender, a drug-coated balloon (DCB) platform of similar design that will assure precise delivery of drug to the lesion site and minimise downstream and systematic effects.
Sinomed has announced the presentation of data from its inter-continental PIONEER III study comparing the safety and efficacy of the Supreme HT (healing-targeted) drug-eluting stent (DES), to the Xience (Abbott) or Promus durable polymer stent (Boston Scientific). One-year results were presented during a late-breaking trial session at the American Heart Association 2020 scientific sessions (AHA 2020, 13–17 November, virtual). The data showed equivalent clinical performance of the Supreme HT to the market-leading DES and will be used to support US Food and Drug Administration (FDA) and Japanese regulatory approvals.
The PIONEER III study enrolled 1,629 patients (randomised 2:1 experimental to control) from North America, Europe and Japan and had a primary composite endpoint of target lesion failure (TLF) at one-year. The TLF outcomes showed that the Supreme HT met the non-inferiority endpoint at 5.4% compared to 5.1% from the durable polymer DES (p=0.002). A grouped analysis of secondary endpoints showed a numerically better result for Supreme HT in cardiac death or target-vessel myocardial infarction (TV MI) with 3.5% in the Supreme HT arm compared to 4.6% in the control arm (p=0.27). Lower late stent thrombosis data (Supreme HT 0.1% compared to DP DES 0.4%, p=0.22) also suggested exceptional safety for the HT DES. A powered, landmark TLF analysis evaluating the healing superiority of Supreme HT between one and five years is ongoing.
“I am very pleased that Japanese patients will benefit from the most advanced DES in the US, Europe and Japan,” said Shigeru Saito, Shonan Kamakura General, Kamakura, Japan and primary investigator of the Japanese cohort of the PIONEER III study . “The results combined with the safety measurement of cardiac death, target vessel MI and late stent thrombosis favour the Supreme HT, supporting the early endothelial healing concept.”
The Supreme HT development was based on the “wound-healing window” concept originally proposed in 2013 and represents a novel class of DES that highlight the importance of early, timely healing, Sinomed said in a press release.
“We are very grateful to the extraordinary group of medical professionals and all the patients who have endured through this difficult pandemic and completed this study milestone in such a timely and professional manor,” said Jianhua Sun, chairman & chief executive officer of Sinomed. “The results have been extremely encouraging and if we reach superiority in the landmark analysis, we could revolutionise the understanding of healing and the future of implantable devices.”
Sean Lyden (Cleveland, USA), current VIVA Board president, speaks to Vascular News about his two years at the helm, which began with the “controversy on paclitaxel” and has led right up to COVID-19 and the first virtual VIVA meeting. Ten “amazing” late-breaking trials, two of which “brought increased clarity to the paclitaxel controversy”, were among the highlights of VIVA 2020, notes Lyden.
He goes on discuss the findings of a four-year meta-analysis from two major randomised controlled trials–ILLUMENATE EU and ILLUMENATE Pivotal– and explains why these results are so important. There was no significant difference in survival among patients treated with the low-dose Stellarex paclitaxel-coated balloon (85.7%) compared to those treated with percutaneous angioplasty (85.6%), notes Lyden.
More generally, Lyden brings attention to some of the current hot topics in the field of vascular medicine, including the continued vetting of the use of paclitaxel, the advent of new devices for the tibial section and the treatment of pulmonary embolism, which he states has been an “amazing breakthrough area”.
Moderate-to-severe calcification in peripheral arteries is an “ongoing battle” in in the endovascular treatment of complex lesions, William Gray (Philadelphia, USA), tells Vascular News.
Gray explains that there are a number of tools deployed to win the acute battle, but notes frankly that they have never been tested meaningfully in a randomised setting. In the longer-term patency war, when drug-coated balloons are employed as treatment options, interventionalists could use some “reinforcements”. he says.
It is in this context that the acute 30-days results from the DISRUPT PAD III data, billed as the largest-ever randomised clinical trial of severely calcified peripheral lesions, demonstrate superior outcomes with the use of intravascular lithotripsy (Shockwave) over percutaneous transluminal angioplasty.
“2020 has changed so much. But the need for IO education remains the same.” Cued to music and set against a backdrop of footage from previous conferences, lone individuals on laptops, and graphics of the now instantly-recognisable SARS-CoV-19 virus, this is the text that appears on the promotional video for the Symposium on Clinical Interventional Oncology (CIO), which took place virtually for the first time ever this year, with sessions livestreamed on each Tuesday in October 2020. “Undeterred by setbacks,” it continues, “this is your year to learn differently. Meet differently. See IO… differently.” At the time of writing, CIO 2020 is the most recent conference in the interventional radiology (IR) space to deliver education and networking opportunities online. As interventional radiologists look ahead to 2021, Interventional News speaks with thought leaders from IR societies across the world to capture their reflections on how the COVID-19 pandemic is impacting medical education.
“I do not think the pandemic is the end of the in-person meeting, rather the beginning of offering meetings accessible to all,” Erica Holland, interim executive director of the Society of Interventional Radiology (SIR), says. “SIR’s meetings, especially the annual scientific meeting, always feel like a family reunion, and we are looking forward to reuniting with our IR family as soon as it is safe to do so.”
Originally slated to be an in-person meeting in Seattle, USA, on 28 March–2 April 2020, the SIR annual scientific meeting was amongst the first events to be cancelled due to the COVID-19 pandemic. Constantino Peña (Miami Cardiac & Vascular Institute, Miami, USA), SIR 2020 programme chair, tells this newspaper this was “a disappointment”: “The annual meeting committee had spent so many months planning the programme, the awards ceremonies, and the networking events, and was excited to share them with our peers. We knew many of the researchers were eager to share their science with their colleagues and hear the feedback that is so important to expanding their work.
“But we were confident at the time that we made the right decision and that has been proven by how the spring unfolded. As a medical society, we knew we needed to lead by example during this public health emergency and ensure we were protecting our patients, colleagues, families, and communities by not creating a potential to spread the virus further. Interventional radiologists are data-driven, and the data we were presented at the time was unmistakable. There was community spread in the Seattle area, then the epicentre of America’s outbreak. There was a call from local officials, the Centers for Disease Control and Prevention [CDC] and the World Health Organisation [WHO] to limit social interactions and avoid large groups to stop the spread. There was the information from our members telling us their institutions were limiting travel to flatten the curve and ready to respond to the inevitable outbreaks in their hometowns. The team came together, and absorbed and analysed data quickly to make a correct and timely decision.”
The annual meeting of the Chinese College of Interventionalists (CCI), initially scheduled for April 2020, was postponed due to the pandemic. Whilst SIR 2020 took place as a fully virtual event 13–14 June, CCI 2020 was rescheduled for 27–30 August as a hybrid virtual/ in-person meeting in Nanjing, China.
“Although this new meeting mode brings a unique attendee experience for CCI meetings, it also presents a big challenge in terms of planning, in order to ensure audience satisfaction,” Gao-Jun Teng, CCI president, says, thinking back to the months of preparation that went into the 2020 event. Seven host venues were used in total; a “main” venue in Nanjing, and six “branch venues” across the country, which CCI say “were to let more IR professionals easily get involved”. In total, there were over 16,000 registered participants, who were able to access 153 scientific and workshop sessions, 796 lectures, and 76 live demonstrations of IR procedures.
“I am proud to conclude CCI 2020 a big success,” Teng told virtual and in-person attendees of the meeting’s closing ceremony, “and [declare] it a ‘sweet marriage’ between the virtual and physical meeting settings. Except for the completely online English- speaking sessions, almost all lectures were delivered in physical meeting rooms in Nanjing and the other six cities, while most audiences could just stay at home. This has no doubt brought attendees great convenience to participate with minimum travel and cost. Most importantly, it also broke territorial boundaries to allow more attendees to engage in and more citizens to appreciate this fairly new but strongly developing, medical specialty.” Indeed, following the strength of the hybrid model’s success at CCI 2020, the college is continuing with this format in 2021.
These boons of increased attendance and accessibility facilitated by the virtual meeting have been echoed by other IR societies. President of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Afshin Gangi (University Hospital of Strasbourg, Strasbourg, France) weighs in: “While I do believe that the virtual model brought a lot to the table in terms of accessibility, I strongly believe that the major congresses will go back to an in-person format after the pandemic. This, however, will not mean in-person only. We at CIRSE plan to also further develop a strong virtual component of our physical congresses; a hybrid model if you will. Medical education in general will of course require both in-person courses and congresses, as well as online learning opportunities. I believe for IR in particular, it is vital for professionals to be able to physically come together to meet, discuss important data, and interact with the latest technology. Virtual-only will not be the future.”
Speaking on behalf of SIR, Holland muses: “One of the interesting benefits of being all virtual is the fact that it has allowed us to expand access to our offerings to our members. We often hear that attendance at the annual scientific meeting is staggered in practices to ensure coverage at the home institutions, meaning some interventional radiologists attending may not be able to stay for the whole meeting, if they are able to attend at all. That is not generally an issue for virtual meetings as you can log on when you are available and absorb the discussion and even watch it on demand later on, depending on the meeting.
“Post-pandemic, I think you will see a pent-up demand for meeting again in person. Networking and community are a huge part of SIR’s meetings and part of the value of an in-person meeting are the sidebar conversations that happen after a presentation or when you bump into colleagues on your way to plenary session or expo hall. Those are impossible to replicate in the virtual space.
“At the same time, not everyone will be ready or able to attend our events in person, so we may see a hybrid model emerge that live streams what is happening on site for those who cannot be there in person.
“In addition, some of the virtual networking opportunities SIR created to fill the gaps while meeting sizes are still restricted, like our new virtual angio club series, are specifically designed to stay in the long term. Many of our members work in areas that do not have local angio clubs where they can regularly meet with their peers, learn, and exchange ideas. While SIR’s virtual club was born out of the necessity presented by the pandemic, it uncovered an important, longstanding need in our community, and we are excited to have this series continue in the long term to support interventional radiologists in their practice no matter where they are.”
When asked if she believed the future of medical conferences would follow a virtual, live, or hybrid model, Jena Eberly Stack, executive director of Society of Interventional Oncology (SIO), commented: “This is the million-dollar question! While I do not have a crystal ball, I can say that there are wonderful, unexpected benefits of virtual learning experiences, and there are also cherished, deeply missed aspects of in-person learning experiences. I am sure we will see a mix of both once we are able to safely meet in person again, offering tailored opportunities based on the type of information and education being shared.”
Unlike the annual scientific meetings originally scheduled in the springtime, CIRSE had several months to anticipate the possibility of hosting a virtual meeting, something Gangi says was “essential […] to ensure everything went smoothly online”. Commenting on the event, held 12–15 September 2020, he adds: “We received overwhelmingly positive feedback from our stakeholders regarding the high calibre of educational content, interactive learning, and networking opportunities, and first-rate organisation. While of course we missed the opportunity of physically meeting together as in previous years, the CIRSE 2020 Summit was able to ensure an equally high level of educational content with our top-notch faculty streaming in from around the world, giving over 1,000 presentations, and also provide ample networking opportunities through the interactive presentation formats and chat functions available at every level of the platform.”
In total, there were 18,000 active users on the CIRSE 2020 Summit platform, the society claim, with almost 5,000 attendees from 115 different countries logging in and creating more than 20,000 chat messages over the course of the four live event days. While Gangi says these figures paint a positive picture of intra-conference communication, he adds this caveat: “I think the quality of interaction and collective creativity that is achievable online is not the same as we usually have at a physical congress. I therefore strongly hope that we will be able to meet again in-person at the CIRSE annual congress in 2021 in Lisbon, Portugal.” At the time of writing, this meeting is scheduled for 25–29 September 2021.
When questioned on his event expectations for 2021, Gangi said: “We are in the same spot as everyone else at the moment: waiting for a vaccine and hoping the situation will improve. While we hope and plan for in-person meetings, we are prepared to host the meetings in any format we can, and that might be online or in a hybrid format. One thing is certain—all CIRSE events in 2021, including the European Congress on Interventional Oncology (ECIO), the European Conference on Embolotherapy (ET), and the CIRSE annual scientific meeting will take place.”
Gearing up for SIO 2021, which will be held virtually 5–8 February 2021, Stack reflect on the 12 months’ experience the society has had to prepare for a potential online meeting (the society’s annual scientific meeting was one of the few IR congresses able to take place in person this year, 31 January–3 February 2020, New Orleans, USA). “The world certainly looks different today than it did a year ago, and our preparations for SIO 2021 reflect this shift in our landscape,” she says.
“We have held and observed several virtual events over the last seven months, and the learnings from those activities have provided feedback we are incorporating into our planning process for SIO 2021. Providing timely programming, valuable avenues to skill-build, and quality networking opportunities remain our commitment to our attendees, and we are achieving this through thoughtful programme development. SIO 2021 will be an interactive experience—not just a series of webinars—designed to mimic the best parts of an in-person event and capitalise on the unique opportunities a virtual event has to offer.”
SIR 2021 will also be held online. Peña assures readers that this “will be a completely different experience from any previous SIR meeting, including the SIR 2020 virtual offering”. He elaborates: “Given the uncertainty of the landscape, the unique nature of our specialty, and the need for members to stay safe and healthy to deliver patient care, we decided to postpone the in-person portion of our programming now so that we have adequate time to plan for and deliver an all virtual format that provides the same cutting-edge, high-quality programming that our members expect from the annual scientific meeting.
“Unlike SIR 2020’s virtual offering, which was deployed as a standard webinar platform, for 2021 we will replicate the feel of an in-person event as closely as possible through an interactive platform complete with meeting rooms, plenary sessions, an interactive expo hall, and on-demand offerings. We are also exploring ways to deliver the important networking opportunities, committee meetings, and our awards ceremonies honouring those who have greatly contributed to the advance of the specialty. […] We are confident that SIR members will find this online learning experience a not-to-be-missed event.”
Indeed, Holland believes the switch to all virtual education this year, which she says “is spurring SIR to move forward with a total reimagining” of their educational offerings, was actually already a part of the society’s strategic plan. “The pandemic has been a catalyst for us to take things down to the brass tacks and rebuild it anew in a way that is as agile as IR,” she surmises. The consensus amongst the international IR community is that conferences with at least a virtual component are here to stay. hybrid hybrid hybrid hybrid hybrid hybrid hybrid
According to a press release, Transit Scientific’s XO Score system has been successfully used to dilate multiple challenging fibrotic and calcific lesions in haemodialysis patients with stenotic and occluded fistulas. Richard Saxon (Tri City Medical Center Medical Center, Oceanside, USA) performed the first procedures using the XO Score. Treatment of all the lesions proved successful.
“The XO device performed well and demonstrated effective lesion dilatation at low pressures with a variety of our standard angioplasty balloons,” said Saxon. “The rotating scoring struts appeared to be effective against a mix of fibrous and calcified lesions which tend to be highly resistant to plain old angioplasty.”
Specialty scoring and cutting angioplasty balloons are manufactured with integrated struts, wires, or blades to reduce vessel dissection, dilation pressure, and assist with vessel preparation for atherectomy and/or stenting. However, scoring and cutting balloons also add profile, bulk, expense, inventory, and complexity.
The XO Score is different, a press release states, detailing that XO Score technology allows users to convert basic angioplasty balloons in the hospital’s existing inventory into sophisticated scoring, cutting, and infusion/delivery devices.
“One of the procedures required five separate inflations at various points along the native fistula and outflow vein, all of which were accomplished using the same XO Score device,” continued Saxon. “The ability to achieve a more predictable result at a lower and potentially safer pressure in resistant lesions could prove important in achieving the best possible PTA outcomes and thereby help in fistula maintenance. The fact that you can take quick angiograms through the XO Score and around the PTA balloon was a nice additional feature.”
During an XO Score procedure, clinicians insert a basic angioplasty balloon into the ultra-thin XO Score sheath and advance the combined balloon and XO sheath to the stenosis. When the balloon is inflated, up to 22 evenly spaced XO Score struts expand with the balloon and rotate 900 to score and cut the narrowed vessel. When the balloon is deflated, the struts rotate 900 back to an atraumatic position to assist balloon rewrap and removal.
“We are thrilled to see the XO Score contribute to patient care,” said Greg Method, president and CEO of Transit Scientific. “These procedures demonstrate XO Score effectiveness against a variety of lesion types. We look forward to growing the platform to treat complex peripheral arterial disease (PAD), critical limb ischaemia (CLI), along with haemodialysis access patients.”
The XO Score system has been cleared by the US Food and Drug Administration (FDA) to dilate stenotic material in iliac, femoral, iliofemoral, popliteal, infrapopliteal, and renal arteries and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistula.
AngioDynamics has announced the safety and efficacy results from the RAPID (Registry of AngioVac system procedures in detail) database. Results were shared by principal investigator John Moriarty (University of California Los Angeles [UCLA], Los Angeles, USA), at this year’s Vascular Interventional Advances meeting (VIVA 2020; 6–8 November, virtual).
The registry was designed to evaluate the patterns of use, safety, and efficacy of the AngioVac system in the bulk removal of undesirable intravascular material. The registry enrolled 234 patients across 21 sites, surpassing its 200-patient enrolment goal. Among enrolled patients, 48.3% had a mass in the right heart, 35.9% had caval thromboemboli, 8.5% had catheter related thrombi, 1.7% had a pulmonary embolism, and 5.6% had a combination of the above.
“RAPID represents the largest catheter-based thromboaspiration study completed to date, and we are pleased to share its positive findings,” said Scott Centea, AngioDynamics senior vice president and general manager, VIT/PAD. “A growing number of providers are recognising the AngioVac system as a critically important tool in the treatment and removal of thrombi and emboli. The overwhelmingly positive results from the RAPID registry demonstrate that the AngioVac system is appropriate for use by a wide range of providers treating thrombus, clot, and vegetations in both peripheral deep vein thrombosis (DVT) and the right heart.”
Findings from the RAPID registry have been accepted for publication in the Journal of Vascular and Interventional Radiology.
The primary objective of the registry was to capture data on the use of the AngioVac system for various anatomic locations. Greater than 70% of clot/mass removal was achieved in a majority of the patient population. Overall, the study confirmed the AngioVac system to be versatile, safe, and effective for the removal of vascular thrombi and cardiac masses across a broad range of patient populations.
“Our goal threshold was to remove over 70% of the clot, which we felt was clinically relevant, and each of the three main groups—the caval group, the right heart group, and the catheter associated clot group—were associated with very high rates of clot removal,” commented Moriarty. “In the first two years of the registry, there were more caval thrombectomies than right heart mass procedures, and that flipped in the latter two years. If we were to extrapolate our trajectory, we would say that close to 70% of all procedures are being performed in the right heart. Additionally, the AngioVac system was successfully tested by a number of different practitioners, including cardiologists, EP cardiologists, cardiac surgeons, vascular surgeons, and interventional radiologists. Ultimately, the diversity of providers, combined with the efficacy and safety results, demonstrates the unique and versatile nature of the AngioVac system.”
Efthymios Avgerinos (Pittsburgh, USA) speaks to Interventional News about the SUNSET sPE trial, the one-year results of which he presented at VIVA 2020 (Vascular International Advances; 6–8 November, virtual), and which compared ultrasound-assisted thrombolysis (USAT) to standard catheter-directed thrombolysis (SCDT) in patients with submassive pulmonary embolism.
The primary endpoint was thrombus reduction and secondary endpoints included RV/LV ratio improvement, intensive care unit (ICU) stay, bleeding, and other serious adverse events. Participants were randomised 1:1 to a USAT catheter (EKOS System) or a SCDT catheter (Unifuse, Cragg-McNamara).
In the context of “cost-conscious health systems”, Avgerinos, who was one of the principal investigators of the trial, explains the importance of studying the financial viability of these two interventions. He outlines the key aims of the trial, whose findings showed that although a USAT catheter is “10 times more expensive” than a SCDT catheter, there was no significant difference in mean thrombus score reduction between the two groups (p=0.76) despite a similar average tPA dose and average lysis time.
In the USAT group (n=39), the mean raw pulmonary thrombus score was reduced from 31±4 at baseline to 22±7 (p<0.001). In the SCDT group (n=41), the score was reduced from 33±4 to 23±7 (p<0.001).
Avgerinos states that thrombolytic techniques are, in general, “safe and effective” and are “here to stay”, before concluding that despite this “we need to learn more and that is what we are doing”.
The Absorb bioresorbable vascular scaffold (BVS; Abbott Vascular) can be used for the treatment of chronic limb-threatening ischaemia (CLTI) patients in infrapopliteal arteries with no safety concerns and favourable patency, rates of reinterventions, and amputations at a mid-term follow-up of two years. This was the conclusion presented by Steven Kum (Changi General Hospital, Singapore) during a late-breaking data session at this year’s Vascular Interventional Advances annual meeting (VIVA 2020; 6–8 November, virtual).
CLTI continues to plague many patients worldwide and is associated with complex comorbidities, poor vessel patency, and major lower extremity amputations. Plain balloon angioplasty is still the mainstay of treatment although metallic drug-eluting stents have shown promise. This multicentre pooled analysis investigates the mid-term outcomes of a drug-eluting BVS in the treatment of CLTI.
Consecutive patients with de novo infrapopliteal lesions were treated with Absorb BVS at three centres (in Singapore, Chicago, and Sydney) between August 2012 and May 2017. Restenosis was defined on colour-flow Doppler examination with a sensitive peak systolic velocity (PSV) ratio >2 or PSV >2m/s (equivalent to >50% stenosis).
A total of 121 patients with 161 lesions were treated with 189 Absorb BVS in 126 limbs.
The mean age of the patients was 73 years. Fifty-seven per cent of patients had diabetes and 75% had tissue loss. Of the 161 lesions treated, 63% were calcified and 22% were occlusions. Median lesion length was 21mm (4–88mm). Successful deployment was achieved with all scaffolds.
Kum reported that there was no mortality in 30 days. Primary patency was 90.3% and 86.6%, and freedom from clinically driven target lesion revascularisation (CD-TLR) was 97.2% and 96.6% at one and two years, respectively. Major amputation occurred in 1.6% of the limbs and overall survival was 85.8% at two years.
Looking forward, Kum announced that the current LIFE-BTK randomised multicentre trial with the novel Esprit BTK drug-eluting resorbable scaffold (DRS) will help further assess the significance of these findings.
The Royal College of Radiologists (RCR) has welcomed the Getting It Right First Time (GIRFT) report into imaging services in England, released 10 November. One of the key recommendations of the report is for radiology departments to have dedicated provision of interventional radiology (IR) facilities.
The GIRFT radiology team, led by consultant radiologist Katharine ‘Kath’ Halliday (Nottingham University Hospitals NHS Trust, Nottingham, UK), and supported by RCR past-president Giles Maskell (Royal Cornwall Hospitals NHS Trust, UK) and radiology service experts Elaine Quick (Salford Royal NHS Foundation Trust, UK) and Lucy Beeley (Mid Yorkshire Hospitals NHS Trust, UK), spent more than two years investigating variation across National Health Service (NHS) imaging services, analysing data and visiting hundreds of hospital radiology departments. The team also consulted with the RCR and the wider radiology community.
The primary stated aim of the GIRFT radiology national specialty report is to make radiology services more patient-centric and accessible. Major themes include the need for standardised, streamlined radiology pathways and systems, and efficiencies in workload and workforce management.
The report covers the impact of COVID-19 on services and builds on issues highlighted in previous radiology investigations, such as the Care Quality Commission’s 2018 Radiology Review and a recent entitled “Diagnostics: Recovery and Renewal”, as well as various RCR publications.
Key patient-focussed recommendations include the ongoing creation of community-based diagnostic hubs recently promised by NHS England/Improvement (NHSE/I), online booking and extended hours to suit outpatient appointments, and dedicated provision of IR facilities.
The GIRFT team’s remit was to identify how imaging services can reduce variation and look to free up capacity and maximise existing resources.
However, the report authors emphasise that NHS imaging cannot provide the best possible service for patients or clinicians without more staff and resources.
They state: “Unless there is investment in increasing staff numbers overall, it will not be possible to provide the quality of service that patients expect, that other departments require, and that radiology teams wish to deliver.”
Welcoming the report’s publication, RCR vice president for clinical radiology William Ramsden (Leeds Children’s Hospital, Leeds, UK) says: “The GIRFT report is truly comprehensive, clearly stating the pivotal role of imaging in patient care, alongside the complex and significant pressures facing departments, and making positive recommendations to improve diagnostic and IR provision across England.
“As well as backing the RCR’s calls for increased investment in departmental space, equipment, and staffing, and the ongoing creation of imaging networks, the authors detail insightful suggestions for optimising imaging pathways and the use of resources and data. All of this will make NHS radiology more patient-focussed, accessible, and efficient, and we strongly endorse the team’s recommendations.”
The report makes 20 headline recommendations, with more than 50 supporting actions to be undertaken by trusts, the GIRFT team, NHSE/I, the RCR, and imaging community stakeholders.
Short-term and ongoing GIRFT recommendations include:
Medium- and long-term recommendations include:
Commenting further on the GIRFT recommendations, Ramsden adds: “Despite being under-resourced, we know IR expertise saves lives and saves the NHS money. We particularly applaud the GIRFT team’s moves to boost recognition of IR via calls to expand IR day-case capacity on a national scale and improve monitoring.
“We agree there is scope to maximise existing diagnostic and interventional capacity through improved oversight and understanding of radiologists’ workloads, as well as enabling appropriate role extension for allied health professionals. We have started project work on those recommendation areas, alongside the SoR and other stakeholders. Trusts must also take seriously the report’s recommendation to assess workforce needs, and the RCR can help services here by sharing our comprehensive radiologist census data.
“However, given the ongoing crisis in imaging department staffing, we must again stress that these efficiency solutions will still only take us so far without the substantial workforce increases that NHS radiology desperately needs.
“On reporting targets, we previously welcomed the premise of national standards for the reporting of imaging, stating targets could be phased in to help benchmarking, and we appreciate GIRFT supporting a soft approach to any implementation.
“We are pleased to see GIRFT recommend standardised radiology IT solutions and the use of referral software. These are ‘quick win’ systematic improvements for helping to manage demand and have long been championed by the RCR. The suggested creation of real-time workflow management dashboards for both diagnostic and IR activities also has exciting potential.
“There are already many inspirational examples of local service innovation, as demonstrated by the host of departmental case studies featured throughout the GIRFT report, and the community as a whole is engaging with national initiatives such as the creation of imaging networks and guiding artificial intelligence tools in development.
“It is now essential that NHS leaders and providers engage with the GIRFT radiology programme as it progresses, supporting radiology teams to upskill, adapt and adopt best practice.
“The recommendations are ambitious but achievable, and we look forward to working with the GIRFT team, trusts, and other national bodies to see them realised.”
Surmodics recently announced that six-month data from the AVESS first-in-human (FIH) study of the company’s Avess arteriovenous fistula (AVF) drug-coated balloon (DCB) was shared at this year’s Vascular Interventional Advances virtual conference (VIVA 2020; 6–8 November, virtual).
The AVESS study is a prospective, multicentre, single-arm study to assess the safety and performance of the Avess DCB when used in the treatment of subjects with obstructive lesions of AVFs for haemodialysis.
Six-month data from the study show that target lesion patency at 30 days and six months was 100% and 90.9%, respectively. A single reintervention was required within six months, with no AVFs thrombosed. The study’s primary safety endpoints reported no mortality and no device or procedure related adverse events at 30 days, and all patients maintained functional AVFs for haemodialysis.
“This first-in-human study demonstrates that the Avess DCB is a safe and promising treatment for AVF stenosis, which can lead to vascular access dysfunction, thrombosis and loss,” said Ramon L Varcoe, associate professor of vascular surgery at Prince of Wales Hospital (Sydney, Australia) and co-lead investigator for the AVESS FIH clinical study.
“Previous AVF studies have demonstrated that DCBs effectively reduce rates of restenosis after percutaneous angioplasty,” added Andrew Holden, associate professor, director of Interventional Radiology at Auckland City Hospital (Auckland, New Zealand) and co-lead investigator for the AVESS FIH clinical trial. “The Avess DCB is a next-generation DCB that may provide further clinical benefits while minimising systemic paclitaxel exposure.”
Data presented include six-month results from 12 patients treated with an Avess DCB between December 2018 and August 2019. The majority of AVFs were radiocephalic (10/12, 83.3%) with the stenosis located in the juxta-anastomosis (7/12, 58.3%), cannulation zone (2/12, 16.7%), and outflow (3/12, 25%). All patients completed follow-up at or beyond six months.
“Our goal with all of our DCB platforms has been to advance the technology to improve drug transfer and distribution effect on the arterial wall offering the opportunity to use a lower drug dose,” said Gary Maharaj, president and CEO of Surmodics. “We are quite pleased with the AVESS first-in-human study results, which provide vital safety data on the Avess DCB and directional data on its effectiveness. This FIH data strengthens our believe that the Avess DCB could be a safe and promising treatment that improves patient outcomes while reducing the number of interventions needed to maintain patency.”
The first person to perform a transjugular intrahepatic portosystemic shunt procedure (TIPS) in Greece, Adam Hatzidakis discusses his career-long love affair with the hepato-biliary-pancreatic system, and describes the delights and difficulties of being a trailblazer in the interventional radiology (IR) space. Speaking seven months after the SARS-CoV-2 virus first caused multiple governments to impose national lockdowns and resulted in widespread international travel bans, Hatzidakis also hopes that the shift to digital conferences is here to stay, at least in part, “so that more colleagues may benefit from the international educational opportunities on offer”.
I was initially attracted to radiology because I loved imaging and trying to find the “pathological hidden in the physiological”. Then I discovered interventional radiology, where I had the possibility to “clean” the physiological from the pathological.
Yes, several. To start, my first professor, Nicholas Gourtsoyiannis, in Heraklion, Crete. He taught us the importance of becoming clinical radiologists, and how to have a presence on the international stage. Together with my tutor and friend Spyros Karampekios, we performed the first IR procedures in Heraklion, back in 1993.
Next, my IR teacher, Panos Galis, at the AirForce Hospital in Athens, Greece. He was a Greek pioneer in vascular IR, and I learned many tricks from his experience.
Another three titans of IR who have been personally important: Plinio Rossi from Rome, Italy; Rolf Guenther from Aachen, Germany; and Andreas “Andy” Adam from London, UK. Beside great IR teaching, in London I learned how to manage, in Aachen how to organise, and in Rome how to improvise. All experiences were of great value.
In the era of magnetic resonance cholangiopancreatography (MRCP), endoscopists have fewer possibilities to practice so many endoscopic retrograde cholangiopancreatographies (ERCPs), with the result that new doctors are less well trained. So, radiologists usually have more to do. Biliary IR is delicate work, offering you a lot of challenging cases. Performing malignant cases is good training for tough benign cases.
That was my passport to the future. The case went well, although the patient was not able to survive for a long time. Performing this case helped to create a lot of respect for my work and IR more generally, but the expectations others have from you can become a very heavy burden. I learned that I had to constantly perform at a high level, and try to be involved in novel procedures, so that everybody could benefit from this. I think one can feel that they have to fulfil the obligation to continue working at a high scientific level in order to show the younger generation of interventional radiologists their way to the top.
This is the reason why I like working in University Hospitals. Patients and other medical specialties can trust you more easily when it comes to new methods and techniques. Of course, you have to perform the procedures well and safely, with nice results to keep a good and trustful name. Sometimes this is not enough, because other specialties do not want to move to new methods and lose control of their patients, or stop performing what is common practice to them in favour of IR methods. The same happened in the old days with oncologists who did not want to stop chemotherapy protocols and send patients to radiofrequency ablation (RFA) in order to calculate total survival rates. The same thing still happens now with other IR techniques such as vertebroplasty, varicocele and fibroid embolization, and I am afraid it will also happen with prostatic artery embolization.
Yes, definitely the first TIPS procedure done in Greece. I was still a last year radiology resident and I was asked to try to performed it. There were five university professors outside the angiography suite, and I needed five hours to complete the case. I would of course never have managed it without their trust and the good help of two senior radiologists who were my teachers and the backbone of our department.
Providing medical education has become difficult due to travelling restrictions. But this problem has convinced international medical societies to transition to a digital education format. Our last CIRSE Summit (12–15 September, virtual) is such an example. The set-up we managed to create in such a short time and the transformation of the programme from a live event to a digital one was a big challenge.
I am confident that this shift to online learning has come to stay. The future will be full of hybrid congresses with both live and distant participation. I hope during the next two years that we will be able to go back to face-to-face events, as these are very important for communication between doctors and industry, but also maintain some remote-learning capabilities, so that more colleagues may benefit from the international educational opportunities on offer.
It was a hard time for everybody. Our University Hospital in Thessaloniki closed for almost every other activity. We were asked to perform only emergency cases. But due to the fact that the surgical departments also decreased their activities, we managed to keep a decreased but adequate number of cases to continue our clinical work. I am confident that the role of IR departments will come out of this crisis more powerful than before, because we provide minimally invasive solutions without need for intensive care unit (ICU) beds.
Be aware of COVID-positive patients, treat them carefully, and keep your staff safe.
Greek interventional radiologists try hard to maintain a high level of medical services, and to convince patients and other physicians about the possibilities our treatments can offer. Research has always been a tough task in our country, usually due to a lack of financial resources. Nevertheless, there are Centres of Excellence like in Patras, where a lot of research work is conducted in the peripheral vascular disease space and in arteriovenous fistula creation. Athens also has a couple of centres working on interventional oncology therapies in the thorax, abdomen, and musculoskeletal systems. We in Thessaloniki are trying to create a Centre of Excellence for primary and secondary liver tumours, in good cooperation with a local transplant centre. I am pretty confident that this cooperation will be fruitful in the future.
HCC patients are quite complex. Experienced hepatologists, together with surgical oncology and transplant colleagues, are needed to decide how to treat every case. The cooperation of hospital tumour boards demonstrates the importance of being a clinical radiologist; being treated as an equal is the best reward for your work.
I love traveling and learning about other cultures. I am a big fan of various sports, especially soccer, basketball, and tennis, which I also played myself. I enjoy good company with my beautiful family and many good friends, which I am blessed to have. Hatzidakis Hatzidakis Hatzidakis Hatzidakis Hatzidakis Hatzidakis Hatzidakis
In a comparison of the regenerative capacity of portal vein embolization (PVE) before major hepatectomies with two different embolic materials, N-butyl-cyanoacrylate (NBCA) with lipiodol was shown to be superior to polyvinyl-alcohol (PVA) particles plus coils. Speaking during the virtual European Conference of Interventional Oncology (ECIO; 4 November 2020, online), José Hugo Luz (Curry Cabral Hospital and Nova Medical School, Lisbon, Portugal) presented the results of the randomised, controlled BestFLR (Best future liver remnant) trial.
Liver regeneration strategies, such as PVE, are crucial in enabling patients to undergo major hepatectomies, Luz informed delegates. Contextualising the BestFLR trial, he went on to explain that PVE has gained acceptance as the standard of care for inducing liver growth in the last few decades. However, the optimal embolic material for PVE has not yet been established. “There are some suggestions in the literature that NBCA glue (Glubran, GEM) with Lipiodol (Guerbet) might generate more liver hypertrophy,” he said.
The BestFLR investigators therefore set out to determine which embolic material, NBCA-Lipiodol or PVA plus coils, produces the highest healthy liver growth during PVE. In order to be enrolled in the study, the future liver remnant (FLR)—the volume of healthy liver that will remain with the patient after surgery—had to be 25% or less of the total liver volume in healthy liver patients, 35% or less in colorectal patients, and 40 to 45% or less in patients with cirrhosis or cholestatic liver disease.
The 60 patients enrolled in the trial were randomly assigned to receive PVE with either NBCA-lipiodol or PVA plus coils (30 in each group). Baseline characteristics, such as age, sex, comorbidities, weight, height, and presence of cirrhosis, were equivalent amongst the two cohorts. The most common tumour types included in the study were colorectal metastases (45%) and cholangiocarcinoma (35%).
Detailing the embolization technique used by the triallists, Luz recounted: “We injected PVA particles of increasing size until [we reached] flow stasis, followed by proximal coils (6–12mm in diameter) to achieve complete venous occlusion”. For NBCA-Lipiodol, they injected a solution of different concentrations depending on the approach used: when injecting from the contralateral side, a 1:3 dilution was used, and when obtaining ipsilateral access to the liver, they used a 1:5 dilution through a microcatheter.
The primary outcome of the BestFLR trial was liver regeneration 14 and 28 days after PVE, assessed by computed tomography (CT) volumetry. The specific endpoints measured were FLR degree of hypertrophy, FLR absolute hypertrophy, and kinetic growth rate (KGR). Secondary outcomes included the occurrence of post-hepatectomy liver failure, intraoperative incidents, blood loss, transfusions, surgery duration and hospital stay, PVE contrast volume used, fluoroscopy and total procedure time, as well as the rate of minor and major complications after PVE. All patients gave voluntary informed consent to participate in the trial, which is registered in a World Health Organisation (WHO) registry network.
Triallists encourage earlier assessment of patients for hepatectomy in light of positive results at 14 days post-embolization with NBCA-lipiodol.
After 14 and 28 days, all volumetric parameters were superior for PVE with NBCA-Lipiodol compared to PVE with PVA plus coils, such as greater absolute liver hypertrophy of 46.4 versus 29.6, p<0.001 and 57.0 versus 36.7, p<0.001, respectively.
“An interesting finding that we had in this study is that patients were ready for surgery after just 14 days,” Luz said. In the NBCA-Lipiodol cohort, 87% of patients had a sufficient FLR ratio for liver surgery after 14 days. This was higher than amongst the PVA plus coils cohort, where 55% of patients were eligible for surgery after the same time period (p=0.008).
“These data encourage us to assess patients earlier,” Luz told the ECIO audience, “14 days after PVE if we are using NBCA-lipiodol, which we are now after the Trial. This shorter waiting period to enable patients to undergo curative hepatectomy might decrease tumour progression, which is the main cause of precluding liver surgery.”
Addressing patient outcomes, he shared that 24 patients (80%) in the NBCA-lipiodol group underwent a successful hepatectomy after PVE, compared to 23 (76%) in the PVA plus coils group (p=0.32). Three patients in the NBCA-lipiodol cohort (12%) and seven patients in the PVA plus coils cohort (27%) had clinically-relevant liver failure (p=0.27).
Fluoroscopy and total PVE time were also significantly lower for NBCA-lipiodol versus PVA plus coils (16 minutes vs. 25 minutes, p<0.001, and 60 minutes vs. 80 minutes, p=0.0023, respectively).
At the time of writing, the results of the BestFLR trial are under submission for publication.
During a late-breaking data session at this year’s Vascular Interventional Advances annual meeting (VIVA 2020; 6–8 November, virtual), Ehrin Armstrong (University of Colorado, Denver, USA) presented two-year outcomes from the DETOUR I trial for percutaneous femoropopliteal bypass. He reported a 96% clinical success rate, with 83% of patients at Rutherford class 0 at two years, which “shows excellent functional improvement in a patient population facing severely debilitating PAD [peripheral arterial disease]”.
The DETOUR I trial was designed to evaluate the safety and effectiveness of the Detour system for percutaneous femoropopliteal bypass, which recently received US Food and Drug Administration (FDA) breakthrough device designation.
Using the novel PQ crossing device and a series of specially designed Torus stent grafts, the Detour procedure was created to route blood flow around severe lesions caused by complex peripheral arterial disease found in the superficial femoral artery. The procedure uses the femoral vein as a pathway for a Torus stent graft conduit and travels from the artery to the vein and back into the artery.
Now reporting two-year data, the trial enrolled a complex patient cohort with an average lesion length of 371mm; 96% of lesions had a confirmed chronic total occlusion, and 80% had evidence of moderate to severe calcification. At one and two years’ post-procedure, the study is reporting an 81% and 79% primary patency rate, respectively, as well as a rate of freedom from major adverse events of 83.7% and 82.1% at one and two years, respectively.
Armstrong also announced that, with FDA breakthrough designation and recent enrolment completion, DETOUR II is “on track to provide results earlier than expected”.
Concept Medical has announced the enrolment of the first patient in the SirPAD (Sirolimus in peripheral arterial disease) trial. According to a press release, SirPAD is the first all-comer randomised controlled clinical trial (RCT) investigating major adverse limb events in PAD patients with lesions below the inguinal ligament.
SirPAD is an investigator-initiated, single-centre, randomised, non-inferiority, open-label clinical trial investigating whether the use of MagicTouch PTA sirolimus-coated balloon catheters in patients with peripheral arterial disease of the femoropopliteal or below-the-knee segment is not inferior to that of uncoated balloon catheters for major clinical outcomes (unplanned major amputation, target limb revascularisation).
A total of 1,132 patients (1,200 after factoring for a 5% drop-out rate) are to be randomised 1:1 (566 [600 after factoring drop-out rate] patients per treatment group).
The primary objective is to evaluate whether the use of sirolimus-coated balloon catheters (MagicTouch PTA) is non-inferior to uncoated balloon catheters in infra-inguinal angioplasty to prevent one-year major adverse limb events (MALE), including unplanned major amputation of the target limb and target lesion revascularisation for critical limb ischaemia, in a representative population of patients with PAD (‘all-comers’).
If the criterion for non-inferiority is confirmed, the study will test whether sirolimus-coated catheters (MagicTouch PTA) are superior to uncoated catheters for important secondary outcomes and for the primary outcome itself according to pre-specified criteria for hierarchical analysis.
The index patient was successfully enrolled on 3 November 2020 at University Hospital Zurich (Zurich, Switzerland). The study was initiated by Nils Kucher (also the principal investigator) in charge of the Clinic of Angiology at University Hospital Zurich.
Kucher was excited to initiate the study and said, “Over the past decade, a few RCTs have compared the efficacy and safety of drug-coated (mainly paclitaxel-coated) devices versus that of uncoated ones, and demonstrated a significant reduction in restenosis rates, late lumen loss, and incidence of target lesion revascularisation. However, the size of these trials was often too small to draw firm conclusions concerning major clinical outcomes. Moreover, substantial heterogeneity of the study populations and too restrictive eligibility criteria limited their external validity, leading to a difficult interpretation of the results of meta-analyses. Indeed, these trials adopted as the primary outcome surrogate (and rather subjective) outcomes, such as vessel patency and target limb revascularisation, which may be difficult to objectively adjudicate in the setting of an open-label trial, rather than ‘hard’ objective clinical endpoints, such as major amputation or urgent revascularisation due to critical limb ischaemia.
“The aim of the SirPAD trial is to compare the efficacy, as defined by a composite of clinically relevant non-subjective ‘hard’ outcomes (major amputation and target lesion revascularisation for critical limb ischaemia), of sirolimus-coated versus uncoated balloon angioplasty for peripheral arterial disease.”
LimFlow SA has announced the presentation of one-year data from the full patient cohort in its PROMISE I study of the LimFlow percutaneous deep vein arterialisation system, showing sustained positive outcomes for both amputation-free survival and complete wound healing. Results were presented in the a late-breaking data session at this year’s Vascular Interventional Advances meeting (VIVA 2020; 6–8 November, virtual) conference by Daniel Clair (University of South Carolina [USC] and Prisma Health-USC Medical Group, Columbia, USA).
The one-year results from the PROMISE I study show that 70% of patients achieved major amputation-free survival, similar to what was seen at six months, following treatment with the LimFlow system. The patients in the trial also had 75% of their wounds classified as healed or healing one year after treatment. Technical success was reported at 97%.
“One-year outcomes demonstrate that the benefits from treatment with the LimFlow system are durable,” said Clair. “One of the greatest challenges in the treatment of CLTI [chronic limb-threatening ischaemia] is to achieve long-lasting outcomes due to disease progression. In this study, the vast majority of patients who would otherwise be facing major amputation were able to avoid it and, at the same time, heal their previously non-healing wounds. This type of lasting result in such a challenging, no-option patient population offers tremendous hope to CLTI patients and the physicians who treat them.”
PROMISE I is a multicentre, prospective, single-arm study of the LimFlow system conducted at seven US centres encompassing 32 end-stage—or “no option”—CLTI patients, 100% of whom had non-healing wounds on the target foot, 69% of whom had diabetes and 34% of whom had renal insufficiency. The minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated blood back into the foot via the veins in CLTI patients who are facing major amputation and have exhausted all other therapeutic options.
The pivotal PROMISE II clinical trial of the LimFlow system is currently enrolling patients at centres across the USA.
Efthymios Avgerinos (University of Pittsburgh, Pittsburgh, USA) presented results from the SUNSET sPE trial during a late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual). His concluded that catheter thrombolysis is safe and effective in tertiary expert centres and can achieve quick thrombus and right to left ventricular (RV/LV) ratio reduction, and that ultrasound-assisted thrombolysis may not confer additional benefits to standard catheter thrombolytic techniques.
The SUNSET sPE trial is a multicentre randomised trial that investigated whether ultrasound-assisted (USAT) is superior to standard-catheter (SCDT) thrombolysis in pulmonary arterial thrombus reduction.
Adults with sPE were randomised 1:1 to a USAT catheter (EKOS system, BTG) or a SCDT catheter. Thrombolysis dose and duration were left to the operators’ discretion. The primary outcome was 48-hour clearance of pulmonary thrombus assessed by pre- and post-procedure computed tomography angiography (CTA) using a refined Miller score. Secondary outcomes included RV/LV ratio improvement, intensive care unit (ICU), bleeding, and other serious adverse events.
Eighty-one patients with acute sPE were randomised and were available for analysis. The mean total dose of alteplase for USAT was 19±7mg and 18±7mg in SCDT (p=0.53) infused over 14±6 hours and 14±5 hours, respectively (p=0.99).
Addressing the VIVA audience, Avgerinos reported that in the USAT group (n=39), the mean raw pulmonary thrombus score was reduced from 31±4 at baseline to 22±7 (p<0.001). In the SCDT group (n=41), the score was reduced from 33±4 to 23±7 (p<0.001). There was no significant difference in mean thrombus score reduction between the two groups (p=0.76), and the obstruction index reduction was also similar between groups: 21% and 22% for USAT and SCDT, respectively (p=0.77). The mean difference in RV/LV ratio from baseline (1.54±0.30 for USAT, 1.69±.44 for SCDT) to 48 hours was 0.37±0.34 in USAT vs. 0.59±0.42 in SCDT (p=0.01). In five USAT and three SCDT patients there was no RV/LV ratio improvement.
He added that major bleeding (one stroke with hemianopia and one vaginal bleed requiring transfusion) occurred in two patients both in the USAT group. The average ICU stay for the entire cohort was 3.2±6.3, similar between groups.
Avgerinos summarised that in the SUNSET sPE trial, patients undergoing USAT had similar pulmonary arterial thrombus reduction compared to SCDT, using comparable mean lytic dose and duration of lysis.
In a late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual) Thomas Zeller (University Heart Center Freiburg, Bad Krozingen, Germany) presented new data from the IN.PACT Global study. Safety and efficacy of Medtronic’s IN.PACT Admiral drug-coated balloon (DCB) has been sustained out to five years, Zeller revealed, adding that these results support use of the device for the management of real-world patients, including those with complex femoropopliteal artery lesions.
The IN.PACT Global study was a large, prospective, multicentre, single-arm study conducted at 64 international sites. Subjects with bilateral disease, multiple lesions (de novo or restenotic), TASC A, B, C, and D, in-stent restenosis, long lesions (≥15 cm) and chronic total occlusions (≥5cm) were enrolled.
The 1,406 intention-to-treat subjects with 1,774 target lesions were treated with the IN.PACT Admiral DCB and analysed as a part of the consecutively enrolled clinical cohort with safety and revascularisation events reviewed by an independent Clinical Events Committee. Assessments through five years using the Kaplan-Meier (K-M) method included freedom from clinically-driven target lesion revascularisation (CD-TLR), a safety composite (freedom from device- and procedure-related mortality through 30 days, freedom from major target limb amputation through five years, and clinically-driven target vessel revascularisation through five years), and all-cause death.
The mean lesion length in this clinical cohort was 12.1±9.54cm, with 18% in-stent restenosis, 35.5% total occlusions, and 68.7% calcification. The K-M estimate of freedom from CD-TLR through five years was 69.4%, and the K-M estimated primary safety composite endpoint was 67.4% with a low major target limb amputation K-M cumulative incidence of 1.7%, through five years. The K-M estimate of freedom from all-cause death was 78.9%. This all-cause death rate was calculated after 96.4% vital status follow-up and was collected through five years.
Results of the VIVO clinical study support the safety and effectiveness of Cook Medical’s recently FDA-cleared Zilver Vena venous stent for the treatment of symptomatic iliofemoral venous outflow obstruction, Anthony Comerota (Inova Fairfax Hospital, Alexandria, USA) revealed in a late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual).
In addition, Comerota reported that VIVO study patients were “consistent with those in previous literature reports and reflective of a real-world population, including acute and chronic disease, and thrombotic and non-thrombotic lesions”.
Patients with symptomatic obstruction (CEAP clinical classification ≥3 or VCSS pain score ≥2) of one iliofemoral venous segment were included. The primary safety endpoint was 30-day freedom from major adverse events (MAE): procedural bleeding requiring transfusion, procedure- or device-related death, clinically-driven reintervention (reintervention with recurrent symptoms of venous outflow obstruction of the target lesion and a minimum lumen diameter [MLD] ≤50% of the immediate post-procedure MLD by venography), clinical migration, new symptomatic pulmonary embolism, or procedure-related perforation requiring open surgical repair or flow limiting dissection of the target vessel.
The primary effectiveness endpoint was 12-month rate of primary quantitative patency (intervention-free, MLD >50% of the immediate post-procedure MLD by venography). The secondary endpoint was the change in VCSS from baseline to 1 month and 12 months.
Comerota reported that 243 patients were enrolled (53±15 years; 70% female). Iliac vein compression by the iliac artery (n=191; 78.6%) was the primary indication for stent placement. The mean lesion length at baseline was 98.6±69.8mm. Technical success (ability to deliver and place stent in intended location) was achieved for 97.3% of stents. The 30-day freedom from MAE rate was 96.7%, exceeding the performance goal of 87% (95% confidence interval [CI]: 93.5–98.6%, p<0.0001). The 12-month primary quantitative patency rate was 89.9%, exceeding the performance goal of 76% (95% CI: 85.1–93.4%, p<0.0001). Clinical improvement was demonstrated by the improvement in VCSS from baseline: -3.0 (95% CI: -3.5 to -2.6, p<0.0001) at one month and -4.2 (95% CI: -4.7 to -3.7, p<0.0001) at 12 months.
Following Comerota’s presentation, panel member Kenneth Cavanaugh (US Food and Drug Administration [FDA] Office for Cardiovascular Devices, Silver Spring, USA) was interested in the potential value of adding a comparator into these studies now that there are other stents on the market.
Comerota responded by highlighting that certain factors would need to be taken into account in any head-to-head comparison of venous stents, including the potential for lesion length to vary widely. “If you were to choose an ideal lesion it would be short, it would be limited to the iliac segment, and it would be a stenosis, not an occlusion” he said, noting that in the VIVO study one-third of the patients had their stents extended to below the inguinal ligament, representing a “real challenge”.
A vessel preparation treatment strategy of directional atherectomy prior to drug-coated balloon angioplasty with Medtronic’s IN.PACT Admiral drug-coated balloon (DCB) in long, calcified femoropoliteal lesions is effective out to one year, with an acceptable safety profile. This was the conclusion of Krishna-Rocha Singh (Prairie Heart Institute, Springfield, USA) in a late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual), presenting new data from the REALITY study.
REALITY (Directional atherectomy plus drug-coated balloon to treat long, calcifIed femoropopliteal artery lesions) prospectively enrolled subjects at 13 multinational centres with 8–36cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with directional atherectomy prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and Clinical Events Committee (CEC)-adjudicated events.
The study enrolled 102 subjects; one lesion was treated per subject. The mean lesion length was 17.9±8.1cm; 39% were chronic total occlusions (mean lesion length 22.6±8.6cm); and, 86% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 9% (9/102) of patients. Twelve-month primary patency rate was 77% (66/86) and freedom from clinically-driven target lesion revascularisation (CD-TLR) rate was 93% (87/94). No device- or procedure-related deaths were reported; one index-limb major amputation was reported.
Rocha-Singh concluded that plaque excision with directional atherectomy in patients with symptomatic severely calcified femoropopliteal arterial disease prior to IN.PACT Admiral DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.
Commenting on the importance of these results, Rocha-Singh told Vascular News: “VIVA REALITY I think sets a new benchmark for the assessment of claudicants with severe femoropopliteal disease characterised by excessive lesion lengths […] and significant bilateral calcification, and suggests that the use of directional atherocath is very efficient in removing atheroma and that that is reflected in the primary safety and effectiveness endpoints at 12 months with a very compelling from CD-TLR and primary patency.”
However, he cautioned against generalisation: “Until another company steps forward, with the type of data that was presented with REALITY, with three core labs, specifically an angiographic core lab, a duplex Doppler core lab, a histology core lab, with all clinical advance adjudicated by a CEC, we cannot and must not equate the results of REALITY with any other combinations of atherectomy devices and drug-eluting balloons.”
Given the absence of a safety signal in data from the VOYAGER PAD trial, a new analysis examined the potential benefit of drug-coated device versus non-drug-coated device treatment for reducing limb outcomes. Connie Hess (University of Colorado, Aurora, USA) presented the most recent findings in a late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual), reporting no excess mortality and improved limb outcomes with drug-coated device use in peripheral arterial disease (PAD).
Hess noted that patency remains a challenge, and that drug-coated devices are associated with a reduction in clinically-driven unplanned index limb revascularisation. However, she relayed that rivaroxaban 2.5mg twice daily plus aspirin reduces this risk, in addition to reducing major adverse events of the heart, limb, and brain, irrespective of device type. “These observations suggest that a ‘pharmaco-invasive’ approach combining innovative devices with effective medical therapy may optimise outcomes in PAD,” she told the VIVA audience.
The co-primary outcomes for this analysis were unplanned index limb revascularisation and major adverse limb events (MALE), defined as acute limb ischemia or major amputation of vascular cause. As drug-coated use was not randomised, inverse probability treatment weighting was used to account for known confounders.
Hess detailed that use of a drug-coated device was associated with a significant 16% reduction in relative risk of clinically-driven unplanned index limb revascularisation (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.76–0.92) but was not associated with a reduction in MALE (HR 1.08, 95% CI 0.9–1.3).
The DISRUPT PAD III randomised controlled trial (RCT) provides the largest level one evidence for the treatment of heavily calcified femoropopliteal arteries, noted William Gray (Main Line Health, Philadelphia, USA) during the second and final late-breaking data session at this year’s Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual). Gray reported that Shockwave’s intravascular lithotripsy (IVL) was superior to percutaneous transluminal angioplasty (PTA) in acute procedural success out to 30 days.
In addition, Gray informed the VIVA audience that IVL demonstrated atraumatic treatment, characterised by a reduction in percentage diameter stenosis prior to drug-coated balloon or stent placement, lower maximum inflation pressure, reduction in frequency and severity of dissections, and lower post-dilatation and stent implantation rate. He stressed that these RCT outcomes are similar to the PAD III registry in multiple vessel beds, highlighting the consistency of IVL treatment in complex anatomy.
Endovascular treatment of calcified peripheral artery lesions may be associated with suboptimal vessel expansion, increased complication risk, and reduced long-term patency. Single-arm studies have reported promising results with IVL in the presence of moderate and severe calcium, yet comparative evidence from randomised trials is lacking.
The purpose of this study is to compare acute outcomes in patients receiving vessel preparation with IVL or PTA prior to drug-coated balloon (DCB) treatment for peripheral arterial disease (PAD) in calcified femoropopliteal arteries. The DISRUPT PAD III RCT enrolled PAD patients with moderate and severe calcification in a femoropopliteal artery who underwent vessel preparation with IVL or PTA. The primary effectiveness endpoint was procedural success, defined as core-lab adjudicated residual stenosis ≤30% without flow-limiting dissection prior to DCB or stenting. Secondary endpoints evaluated at 30 days included major adverse events (MAE) and clinically-driven target lesion revascularisation (CD-TLR).
Gray detailed that in patients receiving IVL (n=153) or PTA (n=153), the primary effectiveness endpoint of procedural success was significantly greater in the IVL group (65.8% vs. 50.4%, p=0.007). Post-treatment balloon dilatation (measured prior to DCB) residual diameter stenosis (27.3±11.5% vs. 30.5±13.9%, p=0.04), freedom from any dissection (81.5% vs.67.7%, p=0.009), flow-limiting dissection (1.4% vs. 6.8%, p=0.03), and provisional stent placement (4.6% vs. 18.3%, p<0.001) were also significantly lower in the IVL group. Secondary outcomes, including rates of MAE and CD-TLR at 30 days, were comparable between groups.
Royal Philips today announced the results of a patient-level meta-analysis that confirms the safety profile of its Stellarex drug-coated balloon (DCB) at four years. Including data from two major randomised controlled trials (RCTs), the results show no difference in mortality between patients treated with the Stellarex DCB and those treated with percutaneous angioplasty (PTA), the current standard of care. The meta-analysis was presented at the 2020 Vascular Interventional Advances conference (VIVA 2020; 6–8 November, virtual).
The meta-analysis found that over four years, there was no significant difference in survival among patients treated with the Stellarex DCB (85.7%) compared to those treated with PTA (85.6%). The data includes two Stellarex RCTs: the ILLUMENATE EU RCT and the ILLUMENATE Pivotal RCT, comprised of 589 patients in the USA and Europe followed up to four years with a high compliance on vital status data.
“The meta-analysis reinforces previously presented results from the ILLUMENATE RCTs, demonstrating low mortality rates each year through four years, with no difference in rates between the two patient cohorts,” said Sean Lyden (Cleveland Clinic, Cleveland, USA), who presented the data. Lyden is also co-primary Investigator for the ILLUMENATE Pivotal trial, one of the two RCTs included in the meta-analysis, and a paid consultant to Philips. “This independent, patient-level meta-analysis continues to provide consistent, long-term data for a large group of patients.”
In addition to demonstrating no significant difference in all-cause mortality between patients treated with the Stellarex DCB and those treated with PTA (14.3% vs. 14.4%), the results of the meta-analysis also show no difference in cardiovascular mortality (3.6% vs. 4%) and non-cardiovascular mortality (10.8% vs. 10.9%).
“The results of this study confirm the safety and performance of our unique Stellarex low-dose drug-coated balloon,” said Chris Landon, senior vice president and general manager Image Guided Therapy Devices at Philips. “We are committed to providing healthcare providers with accurate and transparent data in order to help them make an informed decision on the optimal treatment for each patient with peripheral arterial disease. Stellarex, with its low drug dose and unique drug coating composition, is a logical choice for those who require this option.”
Boston Scientific announced it has received US Food and Drug Administration (FDA) approval of the Ranger drug-coated balloon (DCB), developed for the treatment of patients with peripheral arterial disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal artery (PPA).
According to a press release, the Ranger DCB was designed with a low therapeutic drug dose and proprietary coating which efficiently transfers the drug into the tissue, resulting in high primary patency rates and low systemic drug exposure for patients.
“This approval allows us to bring more treatment options with exceptional outcomes and proven safety to US physicians and their patients who are facing this challenging disease,” said Jeff Mirviss, president, Peripheral Interventions, Boston Scientific. “Adding the Ranger DCB to our drug-eluting portfolio, which also includes our Eluvia drug-eluting vascular stent system, reinforces our commitment to providing differentiated technology with strong clinical evidence that supports data-driven treatment decisions for millions of patients suffering from PAD worldwide.”
The FDA approval is based on results from the RANGER II SFA pivotal trial, which evaluated the safety and effectiveness of the Ranger DCB versus standard percutaneous transluminal angioplasty (PTA) for the treatment of patients with PAD in the SFA and PPA. In the randomised controlled trial, both primary endpoints were met:
“The Ranger DCB eases deliverability for a wide range of lesion complexities via a low profile platform that is compatible with smaller diameter guidewires and has shown consistent results in multiple randomised controlled trials,” said Ravish Sachar, physician-in-chief for Heart and Vascular services at UNC Rex Hospital (Raleigh, USA) and principal investigator of the RANGER II SFA trial. “For physicians seeking to limit systemic drug loss without compromising outcomes, data demonstrate the Ranger DCB is a safe and effective treatment option.”
The Ranger DCB also demonstrated nearly 90% primary patency in the investigator-sponsored COMPARE trial—the first head-to-head prospective, randomised controlled trial to compare two different DCBs. In the trial, the Ranger DCB demonstrated a similar primary patency rate of 88.4% to that of the 89.4% observed with IN.PACT Admiral drug-coated balloon (Medtronic) by Kaplan-Meier estimate (p=0.81), with a significantly lower drug dose density (2µg/mm2 paclitaxel vs. 3.5µg/mm2 paclitaxel, respectively).
Boston Scientific expects to initiate a registry of the Ranger DCB and the Eluvia stent in the coming months to gather additional real-world evidence, which will add to the breadth of clinical data collected on these devices to date. The registry is expected to include five years of patient follow-up with an emphasis on enrolling patient populations who have been historically underrepresented in clinical trials studying treatments for PAD.
The company announced CE Mark for the Ranger DCB in 2014 and plans to immediately launch the device in the USA.
A new case report published in the Journal of Vascular Surgery (JVS) provides one of the first known opportunities to directly visualise the anastomosis that is created with Avenu Medical’s Ellipsys vascular access system, a press release reveals.
“This is the first published report of direct visualisation of a matured pAVF [percutaneous arteriovenous fistula] created with the Ellipsys System,” said lead author Alexandros Mallios (Paris Saint-Joseph Hospital, Paris, France). “It was an amazing opportunity that provided first hand proof of the permanent, fused vessel anastomosis made possible by this revolutionary technology.”
The subject of the case report was an 80-year-old male diabetic end-stage renal disease (ESRD) patient who had a pAVF created with the Ellipsys system six months prior. He was evaluated for decreasing blood flow (unrelated to his fistula) and required surgical intervention, which provided the opportunity to visualise the matured Ellipsys pAVF up close. According to Mallios, the lack of sutures or other foreign bodies made the fusion look “remarkably natural.”
Mallios has published numerous studies showing the ability of the Ellipsys system to easily and safely create durable vascular access for ESRD patients. In July 2020, he reported one-year follow-up results of 234 Ellipsys patients. Published in JVS, the study reported no adverse events and 96 percent of patients still had fully functioning fistulas with strong blood flow after a year. That “patency rate” is higher than published rates for surgically created fistulas, which average about 60% after one year.
In April 2020, JVS published a case report by Mallios that featured a 3D rendering of the Ellipsys pAVF on the cover of the publication. Mallios also co-authored two recent papers in the Journal of Vascular Access that discussed patient eligibility for Ellipsys and the similarities between an Ellipsys pAVF and a surgical AVF, the current standard of care.
Recently published long-term Ellipsys data showed a functional patency rate of 92% at two years. The study also found high levels of patient satisfaction with the procedure.
Medtronic recently announced its plan to acquire Avenu Medical for the Ellipsys percutaneous fistula creation technology. Terms of the deal were not disclosed.
Preclinical and clinical studies show that local, intra-tumoural injection of immunomodulatory agents can result in the shrinking of tumours distant from the site of inoculation. Furthermore, when chemotherapy drugs are used as the immunomodulator, it may circumnavigate the need for systemic chemotherapy delivery. These are the conclusions presented by Thierry de Baere (Institut Gustave Roussy Université Paris-Saclay, Villejuif, France) at the 2020 Symposium on Clinical Interventional Oncology (CIO; every Tuesday of October 2020, online). “Because this is a new field, there are a lot of open questions,” he said. “What is the best target, how should I access the target, is it safe, is it the correct organ, how should I deliver [the drugs], what dose, which regimen, can I monitor the delivery of the drugs?”
“This is a very new, exciting field, and there is a space for interventional radiologists,” he told viewers. Showing a graph depicting the number of new intratumoural immunotherapy trials conducted each year since 1992, de Baere demonstrated the rapid growth of research in this space: from a low of one trial in 1992, to a high of 40 trials in 2016.
When injecting immunostimulatory agents into the tumour, interventionalists hope to achieve local priming, de Baere explained. “We want to trigger a tumour-specific immune response, but we also hope that this [local] response will result in distant effects,” he continued. The idea underpinning human intra-tumoural injections in cancer care is that these “distant effects”—known as abscopal effects—will confer systematic anti-tumour immunity at non-injected tumour sites.
Many different compounds can be used as immunostimulatory agents, and can be used at different stages of tumour immunity. De Baere expanded: “We use products that will release tumour antigens—could be peptides, could be viruses. We want to activate antigen presentation, we want to stimulate cytotoxic cells on site, and we want to deplete or block regulatory T cells [Tregs].”
Providing a more granular breakdown of the agents currently under investigation for drug delivery, de Baere detailed potential combinations for in situ priming of anti-tumour immunity. At every stage of the immune response to cancer, different products are available. For the recruitment of antigen presenting cells, the stimulation of phagocytosis, and the triggering of tumour antigen presentation, interventionalists could consider using toll-like receptor agonists, STING (stimulator of interferon genes) agonists, RIG-I agonists, or anti-C040 agonists. To activate local immunogenic cancer cell death, there are a variety of options, including: the injection of oncolytic viruses, radiotherapy, transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and cryoablation. Anti-PD-I or Anti-PD-LI could be deployed to activate cytotoxic cells, and anti-CTLA-4 could be used to deplete Treg numbers.
Addressing CIO attendees, de Baere said: “Of note, in most of the studies, you are injecting the drug locally, but there is also some intravenous [IV] drugs. Most of the time, you have a PD-LI inhibitor as an IV-combo with drug delivery.”
After detailing the procedural details of intra-tumoural injection, which involve many technical decisions, de Baere stated: “Of course we should be part of this journey, because I think nobody can deliver better local treatment than interventional radiologists.”
A systemic response from a local treatment
De Baere and other interested interventionalists hoping for confirmation of abscopal effects from local intra-tumoural injection are eagerly awaiting the results of ILLUMINATE 301, a randomised, phase III study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy. Tilsotolimod is a toll-like receptor agonist with potent immunostimulating activity, as described in the literature. In a presentation given by Adi Diab (The University of Texas MD Anderson Cancer Center, Houston, USA) at the European Society of Molecular Oncology (ESMO) annual meeting back in October 2018, the intra-tumoural injection of tilsotolimod combined with ipilimumab resulted in a decrease in the size of an off-target melanoma tumour—one that was not injected with any drugs. Committing this finding to the collective medical memory, Diab and colleagues describe in Annals of Oncology how, in the phase I/II ILLUMINATE 301 study, intratumoural tilsotolimod with ipilimumab was “well-tolerated, demonstrating durable responses (including complete response >21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in responders, and an abscopal effect”. At the time of writing, phase III results from ILLUMINATE 301 are anticipated in the first fiscal quarter of 2021.
Offering a personal example, de Baere showed the CIO audience a case performed at his own institution. The patient had a single injection of ipilimumab into a liver metastasis, as well as systemic treatment with nivolumab. “You can see we had an overall response from all of the tumours, despite [the fact that] only one tumour was injected.
Intra-tumoural injection potentially most suitable in neoadjuvant disease
Looking at the full spectrum of cancer development, from neo-adjuvant to metastatic disease, de Baere related how he believed that localised, intra-tumoural injections of chemotherapy drugs may be most successful in neo-adjuvant tumours. The interventionalist would inject immunomodulatory agents into a specific tumour, wait a few days or a few weeks to allow for the patient’s immune system to fight the cancer, and then perform surgery. “The reason for that is to prevent distant, metastatic disease to improve the overall survival,” he explained, “and maybe to improve the rate of R0 resection”. R0 resection indicates a cure or complete remission.
Data exist that supports this treatment approach. Presented at ESMO 2019, results of a phase 2, multicentre, randomised, open-label trial of efficacy and safety for neoadjuvant treatment plus surgery versus surgery alone in patients with resectable melanoma found that the combined treatment had improved overall survival and resection-free survival at two years (88.9% vs. 77.4%, p=0.050 and 50.5% vs. 30.2%, p=0.038, respectively). Results from the same dataset presented at the American Society of Clinical Oncology (ASCO) 2019 meeting also report an increased rate of R0 surgical resections.
As this is a new field of study, de Baere stressed the importance of collecting data and following up patients treated via an intratumoural injection of immunotherapeutic agents. “It is important that we use a specific way of looking at the tumour response,” he said. “We need to create a waterfall plots both of the tumours that have been injected, and a waterfall plot of the tumours that have not been injected.” Referencing a Journal of Clinical Oncology (JCO) paper from May 2020, de Baere told viewers that they should follow the intratumoural immunotherapy Response Evaluation Criteria in Solid Tumours (itRECIST) protocol when capturing data from their patients in order to assess any local and systemic responses in a standardised fashion.
Raul Uppot (Massachusetts General Hospital, Boston, USA) speaks to Interventional News about the evolution of hepatic ablation, following his talk on the same topic at the recent Symposium on Clinical Interventional Oncology (CIO).
He says: “What I want people to know is that liver ablation started off as a small trial: can we kill a tumour with a small needle? Over the past 30 years, we have shown that that is possible. It is exciting that, using a small probe, you can insert it into the liver and impact care—completely treat large tumours, multiple tumours, and yet the patient goes home as an outpatient with just a band-aid. The ability to do great oncological care and work with a small needle is exciting about ablation.”
You can read a report of the full interview here.
RaFeVA (Rapid Femoral Vein Assessment), a new protocol, is a rapid and effective tool for the systematic ultrasound evaluation of the veins in the inguinal area and at mid-thigh, conclude Fabrizio Brescia (Unit of Anesthesia and Intensive Care Medicine, Vascular Access Team, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano, Italy) et al in The Journal of Vascular Access (JVA). Describing this new protocol step-by-step, the study authors say it is designed to evaluate patency and calibre of the common and superficial femoral veins and to help interventionalists choose the best venipuncture site before insertion of a femorally-inserted central catheter (FICC).
“In recent years, many factors have contributed to improving the practice of central venous access,” write Brescia and colleagues, enumerating: “adoption of biocompatible and high-pressure resistant materials, institution of multi-professional, multi-disciplinary teams focused on vascular access, and so on.” They go on to say that, “probably, the most important novelty of the 21st century in the field of venous access has been the adoption of ultrasound technology for minimising the costs and the complications associated with placement of central venous devices.”
Systemic and standardised approaches for the preliminary ultrasound evaluation before centrally-inserted central catheter (CICC) and peripherally-inserted central catheter (PICC) insertion have previously been developed, the authors state. The rapid central vein assessment—the RaCeVA protocol—is a systematic protocol of ultrasound evaluation of the veins of the neck and of the supra/infra-clavicular area before CICC insertion. According to Brescia and his co-authors, this protocol is “useful for teaching the different ultrasound-guided approaches to the central veins, for helping the operator to consider systematically all possible venous options, and for guiding the operator in choosing the most appropriate vein to be accessed, on a rational and well-informed basis”. The rapid peripheral vein assessment—RaPeVA—is the protocol developed in order to collect relevant anatomical information before positioning a PICC.
Rapid femoral vein assessment: RaFeVA
Brescia et al describe RaFeVA as “a clinical tool to evaluate different approaches to the veins of the groin and mid-thigh region, to provide operators with a systematic sequence for ultrasound evaluation of all the veins in the region with the aim of choosing the most appropriate vein for a tunnelled or non-tunnelled FICC”. It consists of seven steps, corresponding to seven different positions of the probe, and is always performed bilaterally. The seven steps of the RaFeVA protocol take into account the different possible visualisations of the vessels (along the short, long, or oblique axes), and propose different venipuncture techniques (out-of-plane and in-plane).
In brief, the seven steps go thus:
Brescia and colleagues elaborate on why standardising the approach to preliminary ultrasound evaluation ahead of FICC insertion is beneficial: “As for the choice of the venous approach and the technique of venipuncture, the preference or the personal experience of the operator should not be regarded any longer as an appropriate criterion,” they opine. “The venous approach that is more ‘comfortable’ for the operator is not necessarily the venous approach associated with the maximal safety for the patient. A rational choice of the venous approach should be based on objective anatomical criteria, verified in the specific patient who is candidate to the procedure. This rational, objective evaluation of the anatomic characteristics of the vasculature of each patient is possible by adopting systematically a pre-procedural ultrasound scan of the anatomic area where the central venous access device will be inserted. The inappropriate, ‘automatic’ choice of a venous access based only on the habits of the operator is potentially associated with repeated punctures, waste of time, poor clinical outcomes and/or puncture-related complications, due to the lack of knowledge of the possible anatomical variations or pathologic abnormalities of the local veins or the lack of identification of the surrounding structures (arteries, nerve bundles, and organs).”
They conclude that, in all phases of venous cannulation procedures—from preliminary assessment to the early identification of puncture-related complications—a correct use of ultrasound improves performance, “making them safer, faster, and more effective”. As the RaFeVA protocol provides a detailed anatomical assessment in advance of the venous cannulation procedure, they claim, it enables optimisation of the manoeuvre through the reduction of cannulation time and of number of attempts, and the avoidance of surrounding structures that could be accidentally damaged during the venous catheterisation.
Speaking during a livestreamed session dedicated to state-of-the-art liver therapy hosted by the Symposium on Clinical Interventional Oncology (CIO) on Tuesday 6 October, Raul Uppot (Massachusetts General Hospital, Boston, USA) discussed the evolution of liver ablation, from the first procedure in November 1986—where the patient was injected with alcohol into liver tumours—to the potential of this treatment modality to offer systemic, curative cancer care, possibly even without inserting a single needle. Here, he shares his thoughts on the past, present, and future of ablation with Interventional News.
What are the benefits of ablation of the liver, and are there any downsides?
The beauty of ablation is that, in a very minimally invasive way, you can treat tumours. In the past, when we were just doing biopsies, it was amazing to us that you could put a needle directly into the target to sample it for diagnostic purposes. Since the late 1980s, we have moved towards being able to treat tumours in a similarly minimally invasive fashion. The ability to use CT or ultrasound to put a small needle into something, to completely treat a tumour that previously would have required surgery, pull the needle out, put a band aid on, and send the patient home—that is what is unique about ablation.
Ablation allows you to treat tumours in a minimally invasively fashion, and we now have the data to show that the ability to do that has long-term impacts on our patients. As with any procedure that we do, there are risks. There are the same risks that you would have with any procedure: bleeding, infection, injury to adjacent organs.
How has the use of hepatic ablation changed over time?
The first hepatic ablation involved the insertion of a small needle into a tumour that was then injected with alcohol. People realised that alcohol could destroy tissue, so thought ‘Why not kill tumours by injecting alcohol into them?’ Since then, we have developed more advanced equipment that can burn or freeze tumours.
The applications have evolved as well. We initially treated primary hepatocellular tumours, and, over many studies, we have shown that [ablation] is very successful at local control and improving overall survival in patients. But we have also evolved into other tumours, such as treating metastatic disease. I think an exciting part of interventional radiology (IR) now is the ability to treat metastatic disease: colorectal cancer, pancreatic cancer, breast cancer metastases to the liver. Management of all of these tumours are based on a background knowledge from the surgical literature. For example, if you were able to surgically debulk disease in the liver for certain cancers (such as colorectal cancer), then you could improve survival. The same data is now being applied to IR, where, if you can debulk as much of the tumour in the liver, then you can potentially improve overall survival.
What is the evidence for ablation in the treatment of liver metastases?
I think the biggest trial out there that we are excited about is the COLLISION trial—this is a trial that will compare the treatment of colorectal cancer metastases with ablation versus surgery. The trial started in 2017, is expected to recruit 600 or so patients, and has a planned end date of 2022. The strength of this trial is that it is a multicentre, randomised controlled trial that will try to answer the question: is ablation as good or better than surgical resection, the current gold standard?
Given our historical data on ablation, especially for the treatment of hepatocellular cancer, we know that we can treat tumours with a good margin, so the expectation is that, in much the same way as surgery has improved survival in terms of debulking metastases disease to the liver, ablation could probably do the same thing, but with lower costs, less hospitalisation time, and with an equivalent survival to surgically treated patients.
What does the future of ablation look like?
When ablation first started, our goals were really just to provide a good option for locally controlling liver tumours. I do not think that the first time an ablation was done, there was ever any belief that we would treat widespread, systemic disease with a single probe. So it is very exciting now to learn that certain tools we now have, such as irreversible electroporation (IRE) and cryoablation, can potentially incite systemic effects. There are now a lot of trials going on exploring the combination of immunotherapy drugs and ablation.
I think where ablation fits into this whole paradigm is that, by destroying the tumour, you are able to release antigens; the release of these antigens, combined with immunotherapy drugs, could potentially affect overall systemic disease. I personally have had a few patients where treating a single tumour in the adrenal glands or the kidneys has ultimately resulted in a decrease in size of metastatic tumours in other parts of the body. This was accidental—we call it an abscopal effect. I think this has happened enough times that people have realised there is a way to study this, there is a way to learn how this could potentially be occurring, and control it, and use immunotherapy drugs to help it, so it is exciting, because I think for the first time it is a whole new world for IR. The ability to put a needle into one lesion, treat that, yet somehow affect systemic tumour control everywhere else, and improve overall survival in the patient.
What is the key message you would like your IR colleagues to take home from your CIO presentation on liver ablation?
What I want people to know is that liver ablation started off as a small trial: can we kill a tumour with a small needle? Over the past 30 years, we have shown that that is possible. It is exciting that, using a small probe, you can insert it into the liver and impact care: completely treat large tumours, multiple tumours, and yet the patient goes home as an outpatient with just a band-aid. The ability to do great oncological care and work with a small needle is exciting about ablation.
The other thing I am very excited about is that, over time, there has been a constant evolution in the technology [for ablation]. We started off with alcohol, but we evolved to radiofrequency ablation (RFA), cryoablation, microwave ablation, and IRE. There is a constant evolution in these technologies: we are constantly moving towards smaller and lighter probes that are more efficient in what they can destroy. There are new technologies on the horizon, such as histotripsy, that allow one to treat a tumour without inserting a needle. The ability to use ultrasound waves to kill tumour [cells] is what is coming down the pipeline. It is very exciting, the notion that a person could come in with a large liver tumour and one could treat it in a very minimally invasive fashion and, ultimately, improve the patient’s survival.
Medtronic today announced it has received US Food and Drug Administration (FDA) approval for the Abre venous self-expanding stent system. This device is indicated for use in the iliofemoral veins in patients with symptomatic iliofemoral venous outflow obstruction.
The FDA approval is based on 12-month results from the ABRE clinical study, presented at the 2020 Charing Cross Symposium. The ABRE study assessed the safety and effectiveness of the investigational Abre stent in 200 patients with iliofemoral venous outflow obstruction across the spectrum of deep venous obstruction including those with post thrombotic syndrome, non-thrombotic iliac vein lesions (NIVL), and those who presented with an acute deep vein thrombosis (aDVT).
The study also included a challenging patient population, 44% (88/200) of whom required stents that extended below the inguinal ligament into the common femoral vein (CFV). The study met its primary safety endpoint with a 2% (4/200) rate of major adverse events (MAEs) within 30 days. The study also met its 12-month primary effectiveness endpoint with an overall primary patency rate of 88% (162/184). Despite the challenging patient population, no stent fractures and no stent migrations were reported in the study.
“Patients with deep venous obstruction are often younger, therefore it’s critical to have a venous stent that is not only safe and effective, but also strong and flexible,” said Erin Murphy, global principal investigator for the ABRE clinical study and director of Atrium Health Sanger Heart & Vascular Institute’s Venous and Lymphatic Program in Charlotte, USA. “With FDA approval, we now have this important tool in our arsenal to treat patients with even the most challenging of deep venous lesions.”
A self-expanding stent system, Abre is intended for permanent implant and utilises an open-cell design with three off-set connection points to enable flexibility and stability during deployment. Based on data presented at the Leipzig Interventional Course (LINC) 2020 annual meeting by Stephen Black, consultant and vascular surgeon, Guy’s, and St Thomas’ Hospital and Kings College in London, UK, the Abre stent system demonstrated a 0% fracture rate in bench testing simulated out to 50 years.
“With Abre, our goal was to create a dedicated venous stent that combined a balance of the key characteristics necessary to treat patients with a broad spectrum of deep venous obstruction,” said Carolyn Sleeth, vice president and general manager of the endoVenous business, which is part of the Cardiac and Vascular Group at Medtronic. “We are excited to bring Abre to the US market, which we believe will provide both physicians and patients with a new option backed by clinical evidence to treat this disease safely and effectively.”
Abre received CE mark approval in April of 2017 and is also intended for use in the iliofemoral veins for treatment of symptomatic venous outflow obstruction.
The Janssen Pharmaceutical Companies of Johnson & Johnson announced today it has submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for a new indication to expand the use of Xarelto (rivaroxaban) in patients with peripheral arterial disease (PAD).
If approved, this new indication for the Xarelto vascular dose (2.5mg twice daily plus aspirin 75–100mg once daily) would include reducing the risk of major thrombotic vascular events such as heart attack, stroke, and amputation in patients after recent lower extremity revascularisation.
The application is based on data from the VOYAGER PAD study, which showed Xarelto (2.5mg twice daily) plus aspirin (100mg once daily) was superior to aspirin alone in reducing the risk of major cardiovascular and limb events, with similar rates of thrombolysis in myocardial infarction (TIMI) major bleeding.
“Various antithrombotic regimens have been evaluated for short- and long-term prevention of major vascular events in patients with PAD, but only rivaroxaban in combination with aspirin has demonstrated a significant benefit over aspirin alone,” said James List, global therapeutic area head, Cardiovascular & Metabolism, Janssen Research & Development.
“Data from the VOYAGER PAD trial were the first in 20 years to show clinical benefit with an antithrombotic therapy in the symptomatic PAD population after lower-extremity revascularisation, which speaks to the need for a new treatment in this space. We look forward to discussing these data with the FDA.”
Janssen and its development partner Bayer have conducted two major Phase 3 trials, VOYAGER PAD and COMPASS, that evaluated the use of dual antithrombotic pathway inhibition with Xarelto plus aspirin in patients with PAD. Xarelto, in combination with aspirin, was approved by the FDA in 2018 to reduce the risk of major cardiovascular events in patients with chronic PAD and coronary artery disease—the only direct oral anticoagulant (DOAC) approved for use in these populations.
As presented at the Global Embolization Oncology Symposium Technologies (GEST) 2020 meeting (4–6 September, virtual), Robert Lewandowski discusses the evolution of radioembolization with Yttrium-90 (Y-90) over the past decade. Initially a lobar therapy, Y-90 can today be performed via a segmental delivery of microspheres to hepatocellular carcinoma (HCC) patients at earlier stages in their disease, and multiple tumours can be targeted in a same-day session. Furthermore, Lewandowski recounts how threshold dosimetry is now allowing for curative-intent therapy, and explains that the most recent data suggest this personalised dosimetry approach can be applied to a more advanced HCC population.
The historical role of radioembolization with Y-90 for patients with HCC is in the salvage setting; radioembolization has been employed to treat patients considered poor candidates for trans-arterial chemoembolization (TACE) or those that failed TACE. In contradistinction to the selective approach of TACE, radioembolization has been performed in a lobar (or sequential lobar) fashion. Despite these differences in patient selection and technique, evidence has supported the application of radioembolization over TACE in intermediate staged HCC patients because of improved quality of life metrics and longer time to progression. The median overall survival (OS) for patients with intermediate-stage HCC treated with Y-90 is 25 months.
A serendipitous observation following uni-lobar radioembolization was the development of an atrophy-hypertrophy complex; the treated hepatic lobe and targeted tumour decrease in size, with resultant hypertrophy in the contralateral lobe. For patients who would be candidates for surgical resection but present with an inadequate future liver remnant (FLR), radiation lobectomy was developed as a new paradigm to facilitate hepatic resection. With standard dosimetry, FLR hypertrophy is a time-dependent process with approximately 10% hypertrophy from baseline at one-month post Y-90, and 45% by nine-months post Y-90. More recently, modified radiation lobectomy techniques have been developed to increase the rate of hypertrophy and to deliver more effective cancer therapy.
The application of radioembolization is evolving from its lobar therapy origins; radioembolization is increasingly utilised in a segmental fashion to treat earlier stage disease. The results of the PREMIERE trial, a prospective, randomised trial for patients with unresectable tumours not amendable to ablation, revealed significantly improved outcomes for segmental radioembolization versus segmental TACE (time-to-progression >26 months vs. 6.8 months, respectively). These results have been corroborated by other US sites, including the University of Washington in Seattle, Mt Sinai Hospital in New York City, and the Mayo Clinic in Jacksonville. The true potential of segmental radioembolization, however, is in its ablative potential. Radiology-pathology correlative studies have revealed that complete pathologic necrosis at explant is best obtained when the volumes of perfusion are targeted with glass microsphere dosimetry >190 Gray. A recent multi-centre analysis has reset this threshold dose for segmental radioembolization. In this analysis, all tumours treated with a segmental radiation dose >400 Gray achieved complete pathologic necrosis at explant.
High tumour response rates on imaging, long time to tumour progression, and meaningful complete pathologic response rates have made radiation segmentectomy a versatile therapy, allowing for down-staging to liver transplant, bridging to liver transplant, or as a potentially definitive curative-intent therapy for early stage HCC. Median overall survival outcomes for Child-Pugh A patients with solitary HCC <5cm appear consistent with those for other curative therapies (i.e., ablation, surgical resection, liver transplant): 6.7 years from date of Y-90.
The evolution of radioembolization from a lobar therapy to a segmental therapy includes technical modifications beyond threshold dosimetry to achieve complete pathologic necrosis. Many of these techniques have been developed for TACE over the past several decades. The first concept is that of same-day radioembolization: the planning angiogram, macro-aggregated albumin (MAA) administration to determine lung shunt fraction (LSF), and Y-90 administration can be performed in a single session. This is particularly appealing for patients with early stage disease amenable to radiation segmentectomy. Same-day radioembolization might further be streamlined by eliminating the requirement for the MAA administration in patients with limited disease burden. Recent data support this concept by confirming low LSF for those HCC patients within Milan criteria. The second concept is that of performing radioembolization to extra-hepatic tumour perfusing branches. There is no established optimal embolic device to treat tumours via parasitised extra-hepatic arteries; there are now published reports describing the delivery of Y-90 via the inferior phrenic arteries, the adrenal artery, and the cystic artery. The final concept is that of segmental administration of Y-90 to multi-focal disease. With segmental radioembolization, multi-focal disease can be targeted in a single session through separate selective arterial catheterisations and dose vial administrations.
In conclusion, radioembolization with Y-90 has evolved over the past 10 years, morphing from a lobar therapy for patients with HCC advanced beyond being amendable to TACE into a versatile treatment option for patients across the Barcelona Clinic Liver Cancer staging paradigm. This evolution has allowed for radioembolization to be performed in a similar fashion to TACE: segmental/selective delivery of Y-90 microspheres to HCC patients at earlier stages in their disease, targeting multiple tumours as well as extra-hepatic tumour-perfusing branches, often in a same-day session. Most importantly, threshold dosimetry is now allowing for curative-intent therapy, supported by explant data. This concept of threshold, or personalised, dosimetry has more recently been expanded and applied to the advanced HCC population (DOSISPHERE-01 TRIAL), accepted for publication in the Lancet Gastroenterology & Hepatology.
Robert J Lewandowski is a professor of Radiology, Medicine, and Surgery, and the director of Interventional Oncology at the Northwestern University Feinberg School of Medicine, Chicago, USA
Canon Medical Systems has launched its Aquilion Exceed LB (pending 510(k) clearance), a CT scanner dedicated to radiation therapy planning, at this week’s American Society for Radiation Oncology (ASTRO) virtual meeting (23–29 October). At 90cm, the new scanner sports what Canon believes to be the largest bore in the industry, and features a 90cm edge-to-edge extended field-of-view reconstruction and a wide detector coverage of 4cm.
The system also uses Canon’s Advanced intelligent Clear-IQ Engine (AiCE) Deep Learning Reconstruction (DLR) technology, pioneered on the company’s diagnostic radiology CT line.
“Accurate simulation across even the most challenging treatment plans is imperative during radiation therapy planning,” comments Erin Angel, managing director, CT Business Unit, Canon Medical Systems USA. “At Canon Medical, we deliver solutions that meet providers’ needs but also push the boundaries of traditional simulation. With the Aquilion Exceed LB, we brought deep learning reconstruction to the CT simulation space. This will revolutionise care for cancer patients and give the radiation oncology team the confidence and precision they need for accurate planning across patients.”
While the Aquilion Exceed LB is pending 510(k) clearance, international shipments outside the USA are ready to start now, the company said.
The Royal College of Radiologists (RCR) and the British Society of Interventional Radiology (BSIR) have called for a UK-wide clinical registry for ureteric stents, following the release of a report investigating delayed removal of the devices.
The Healthcare Safety Investigation Branch (HSIB) released a report on 22 October titled, “Unplanned delayed removal of ureteric stents”, highlighting the need for better clinical communication and monitoring standards around ureteric stent use.
The new HSIB report was instigated following a reference case involving a patient who was fitted with a stent following surgery for kidney stones. Removal of the stent was delayed, and the device became encrusted, causing ongoing urinary infections before it was eventually removed.
England-wide themes considered by HSIB include the different processes used for stent logging and tracking, varying communications between hospital teams and GPs, and the need for standardised advice for patients.
HSIB recommends the creation of national standards to support paper and electronic logging systems, enhanced patient information and guidance for clinicians, and for stent status and further information to be included on all hospital discharge letters and other communications sent to GPs.
The RCR and BSIR welcome the report and agree with its findings, but also argue that stent monitoring could be further centralised and given clear clinical incentives.
Ian McCafferty, BSIR president and member of the RCR’s Interventional Radiology Committee, says: “Interventional radiology (IR) plays a significant role in stent insertion and removal across specialties, including ureteric stenting. Radiology workload is also only increasing here, particularly as ‘COVID-secure’ IR services have picked up more cases during the pandemic. As a result, IR consultants and their teams are implicated in ensuring these devices are flagged and tracked.
“The RCR and BSIR fully agree stents should be removed at replaced at appropriate timescales, with a robust tracing system for their use.
“HSIB recommends more professional standards to support ureteric stent monitoring. However, ideally we believe there needs to be an open-access, UK-wide stent registry. In addition, tariff reimbursement should be linked to registration, to ensure all devices are properly registered and therefore monitored.
“Providers would also need to appoint leads to support clinicians logging the devices and to ensure local data is kept up-to-date.”
In a recently-published study, Jeremy Crane (Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK) and colleagues conclude that a 3mm-long arteriotomy may be routinely utilised for brachiocephalic fistula creation in an attempt to limit the incidence of steal syndrome, while maintaining clinical patency outcomes. According to the authors, this is the first ever series in the literature of a 3mm arteriotomy.
“The arteriovenous fistula [AVF] is the modality of choice for long-term haemodialysis access,” the Journal of Vascular Access (JVA) paper begins. The authors cite lower rates of access-related infection and improved patient and access survival when compared to other modalities such as arteriovenous grafts or longstanding tunnelled central venous catheters as the reasons behind why the AVF is the most popular modality for haemodialysis access.
However, AVF formation is “not to be taken lightly,” Crane and colleagues warn, noting that dialysis access-associated steal syndrome (DASS) as an “important” and “potentially limb threatening” complication. They explain that the hallmarks of steal syndrome are symptoms and signs of peripheral vascular insufficiency within the limb distal to the AVF, which are often detected through a thorough clinical history and examination.
They go on to describe the feasibility of routinely fashioning a brachiocephalic fistula utilising a 3mm-long arteriotomy in an attempt to reduce the incidence of symptomatic steal syndrome, while maintaining clinical patency outcomes.
Crane and colleagues describe the study as a retrospective analysis of prospectively collected clinical data from a single surgeon. They detail that they included all patients who underwent brachiocephalic fistula formation using a routine 3mm-long arteriotomy within Hammersmith Hospital between January 2017 and March 2018 in the study. They note that primary outcomes included primary failure, failure of maturation, secondary patency, and steal syndrome.
Writing in JVA, Crane et al relay that 68 brachiocephalic AVFs were fashioned utilising a 3mm arteriotomy during study period, adding that the mean age was 60.5 years with 59% having a history of diabetes mellitus. The mean follow-up was 368 days, the authors write.
The authors report that primary failure occured in 10 (14.7%) of patients, and that cannulation was achieved in 67.3% of remaining fistulae within three months, rising to 87.3% by six months.
In terms of primary patency, Crane and colleagues note that this was 76% and 69% at six and 12 months, respectively. Secondary patency at the same time points was 91% and 94%, respectively. Finally, the authors detail that dialysis access steal syndrome was clinically apparent in three (4.4%) patients, with all cases being managed conservatively.
The authors acknowledge that the present study has certain limitations. Firstly, they recognise that steal syndrome is multifactorial in origin and not purely related to anastomosis calibre. In addition, “follow-up among the patients included in the study is limited,” Crane and colleagues write, adding that late presentations of DASS due to ongoing arterial and venous remodelling and subsequent increase in fistula flow may subsequently occur. They suggest that a randomised trial with clear documentation of venous and arterial diameter along with postoperative duplex ultrasound and haemodialysis access flow assessment would be useful.
Crane et al posit that comparison alongside other techniques such as the proximal radial artery AVF, particularly among patients deemed at higher risk of steal syndrome would be of interest. Nevertheless, they emphasise that a shorter length arteriotomy of 3mm “appears sufficient” to maintain fistula patency, while potentially minimising the risk of steal phenomena.
Different risk factors affect patency between vascular access construction and the first percutaneous transluminal angioplasty, Mahoko Yoshida (Hiroshima University Hospital, Hiroshima, Japan) and colleagues conclude in The Journal of Vascular Access. Their results indicate that a poor patency rate is commonly associated with advanced age and diabetes mellitus.
“These findings suggest that older patients and those with diabetes mellitus are more likely to experience vascular access problems after both vascular access construction and percutaneous transluminal angioplasty [PTA], and that different risk factors should be taken into account when managing patients undergoing haemodialysis after vascular access construction and PTA,” the study authors write. “Understanding the risk factors that contribute to vascular access problems may lead to better surveillance and focused care in high-risk patients, resulting in more effective management of vascular access.”
Dialysis: “A global health concern”
The number of patients undergoing dialysis worldwide has been increasing each year, the study authors write, and is considered a global health concern. The majority of dialysis patients receive haemodialysis, and are known to suffer from various complications, including cardiovascular disease and infections. The most frequent issue relates to problems with vascular access: stenosis, thrombosis, aneurysm, and infection. “In fact,” Yoshida et al say, “the medical expenses for vascular access-related complications is estimated at JPY 10,953,310,000/year”. The investigators therefore surmise that “recognition of risk factors for vascular access failure is needed not only to improve the quality of life of patients undergoing haemodialysis, but also to reduce medical expenditure”.
They conducted a multicentre, prospective, observational study of 611 patients who had started haemodialysis between 1 April 2012 and 31 March 2018, and investigated the primary and secondary patency rates after construction of a radiocephalic arteriovenous fistula (AVF) and arteriovenous graft (AVG). Primary patency was defined as the period from vascular access construction to percutaneous transluminal angioplasty or surgical revision within 24 months; secondary patency was defined as the period from vascular access construction to the date of vascular access abandonment. The study also examined the patency rate following percutaneous transluminal angioplasty (PTA)—defined as the period from the first PTA to the next PTA or surgical revision within 12 months—as well as the clinical factors that contributed to the development of restenosis. All patients were followed-up until December 2018.
Post-PTA patency unaffected by vascular access form in older patients
The study results reveal that radiocephalic AVF exhibited better 24-month primary and secondary patency rates than AVG in patients who started haemodialysis: 54.5% and 91.6% versus 25.1% and 70.3%. The authors note that these 24-month primary and secondary patency rates after vascular access construction are higher than those reported in the literature by researchers investigating patients outside of Japan. They postulate that the higher patency rates seen in Japanese patients could be due to the fact that they undergo haemodialysis with lower blood flow, which they suggest may enable the vascular access to be used for longer periods.
While the patency rates after vascular access construction between the two vascular access forms (radiocephalic AVF and AVG) was not significantly different in the multivariate analysis, they did show a significant difference in the log-rank test. “With respect to the post-PTA patency rate, although radiocephalic AVF appeared to result in a better patency rate than that of AVG, the difference was not statistically significant in either the log-rank test or Cox proportional hazard model,” Yoshida and colleagues discuss. “A previous study reported that AVF exhibited a better patency rate after both vascular access construction and PTA than AVG. Notably, another study showed that the patency rate of AVF did not differ from that of AVG in advanced-age patients undergoing haemodialysis, especially those aged >65 years. In the present study, the median age of the patients was 70 years, suggesting that rather than the vascular access form, the background of the patients may be more strongly associated with the patency rate.”
Risk factors for vascular access complications
A Cox proportional hazard model demonstrated that aging, female sex, diabetes mellitus, low serum albumin, and use of an erythropoietin-stimulating agent were associated with poor primary patency after vascular access construction in this study. Of these identified risk factors, aging, diabetes mellitus, and low serum albumin may be indicative of a patient’s poor general condition, the study authors muse, while female sex has reportedly been associated with smaller vascular diameter, which can increase the number of vascular access problems. “Taken together these results indicate that vascular access patency might be improved if modifiable risk factors identified in the present study are well controlled,” Yoshida et al write.
Furthermore, aging, diabetes mellitus, polycystic kidney disease, initiation of haemodialysis with the use of a temporary catheter, and a shorter period from vascular access construction to use were associated with poor patency after the first PTA. These results led the study investigators to conclude that patients need to start haemodialysis “urgently”.
“These findings suggest that with the exception of aging and diabetes mellitus, different risk factors contribute to the incidence of vascular access problems after surgical construction of vascular access and restenosis after PTA,” the authors conclude.
“Our data showed that stenosis accounted for 92% of vascular access problems. […] These findings suggest that the presence or absence of procedure-induced stimulation may cause differences in the risk factors that influence the patency rates after vascular access construction and that after PTA.”
Findings from a series of late-breaking trials in the endovascular field were presented recently at TCT Connect (14–18 October, virtual), the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). Sahil A Parikh (Columbia University Medical Center, New York, USA) and Frank Veith (New York University Medical Center, New York, USA) moderated the session, with Marc Bonaca (University of Colorado, Aurora, USA) and Robert A Lookstein (Mount Sinai Health System, New York, USA) on the panel.
First on the virtual podium was Connie N Hess (University of Colorado, Aurora, USA), who presented results of a large subgroup analysis of the VOYAGER PAD randomised clinical trial. This showed neither a mortality risk nor benefit associated with the use of paclitaxel drug-coated devices in the treatment of peripheral arterial disease (PAD). The study also found that the benefit of rivaroxaban use on reducing ischaemic limb and cardiovascular outcomes was consistent regardless of whether a drug-coated device was used.
This analysis examined the long-term safety of drug-coated devices and evaluated whether rivaroxaban 2.5mg twice daily plus low dose aspirin versus low dose aspirin alone on the primary efficacy endpoint was consistent with versus without drug-coated device (DCD) use.
During the qualifying endovascular lower extremity revascularisation, DCD was used for 31% (n=1,358) of patients. Patients receiving DCD more frequently had prior endovascular lower extremity revascularisation, had higher baseline use of dual antiplatelet therapy and statins, and were more often treated for claudication than non-DCD patients.
In the unweighted analysis, lower associated mortality was observed among patients receiving DCD versus non-DCD (2.9 vs. 3.9 per 100 patient-years; 3.5-year Kaplan-Meier cumulative incidence of 10.2% vs.13.8%). After weighting, there was no association between DCD use and mortality (3.5-year cumulative incidence 12.1% vs. 12.6%, HR 0.95, 95% CI 0.83-1.09, p=0.49). The benefit of rivaroxaban 2.5mg twice daily with aspirin compared to aspirin alone on reducing ischaemic limb and cardiovascular outcomes was also consistent regardless of whether a DCD was used.
The VOYAGER PAD trial was funded by research grants to CPC Clinical Research from Bayer and Janssen.
IN.PACT 0.014 DCB may offer a clinical benefit in patients with CLI
Antonio Micari (University of Messina, Messina, Italy) presented first-ever results from Medtronic’s IN.PACT BTK study, a feasibility study assessing the safety and effectiveness of the company’s IN.PACT 0.014 drug-coated balloon (DCB) in critical limb ischaemia (CLI) subjects with chronic total occlusion (CTO) in the infrapopliteal arteries.
The IN.PACT BTK study is a prospective, multicentre, 1:1, randomised feasibility study assessing the safety and effectiveness of the IN.PACT 0.014 DCB, a 3.5 μg/mm2 dose paclitaxel-coated balloon, versus conventional percutaneous transluminal angioplasty (PTA) for the treatment of CTOs in the infrapopliteal arteries. The study enrolled 50 subjects at nine sites in Europe.
At nine months, subjects in the DCB group experienced a reduction in sub-segmental late lumen loss compared to those in the PTA control group (0.59±0.94mm versus 1.26±0.81mm, respectively, p=0.017), a 53% lower late lumen loss than the PTA control group. Using the classic late lumen loss method, subjects in the DCB group experienced lower late lumen loss compared to those in the PTA control group at nine months (0.89±0.77mm versus 1.31±0.72mm respectively, p=0.07 ), a 32% lower late lumen loss than the PTA control group.
Historically, there has not been a DCB technology that has demonstrated effectiveness in this vessel bed. According to a Medtronic press release, the data presented at TCT demonstrate that IN.PACT 0.014 may offer a clinical benefit in patients with CLI.
The IN.PACT 0.014 DCB is an investigational device that is being evaluated in Europe. This device is not currently being evaluated in the USA.
ILLUMENATE Global: Four-year results support durable long-term outcomes with the Stellarex DCB
Andrew Holden (Auckland City Hospital, Auckland, New Zealand) reported on late safety and efficacy outcomes for the low-dose Stellarex DCB (Philips) in de novo and restenotic femoropopliteal lesions from a large cohort.
He revealed that four-year data from the trial show favourable safety and efficacy outcomes consistent with the ILLUMENATE randomised controlled trials, and also demonstrate similar efficacy in prespecified cohorts including different gender groups and diabetics.
ILLUMENATE Global is a prospective, single-arm, multicentre study conducted in the EU. The patient population included those with Rutherford Clinical Classification (RCC) of 2–4 indicated for treatment of the superficial femoral artery (SFA) and/or popliteal artery for de novo or restenotic lesions. Follow-up office visits were at one, six, 12, 24, and 36-months post-procedure and included clinical, haemodynamic, and functional outcomes.
At four years, the rate of major target limb amputation was 0.8% and that of all-cause mortality was 8.1%. Clinically-driven target lesion revascularisation through four years was 75.6% at day 1,460 and the subgroup analysis revealed no difference in prespecified cohorts.
“The ILLUMENATE Global study supports durable long-term outcomes with the Stellarex DCB and is applicable to a complex population,” Holden told the TCT audience.
Bullfrog device shows promise in TANGO Registry
Ehrin J Armstrong (UCHealth Heart and Vascular Center, Aurora, USA) presented results of the TANGO Registry. This Phase 2 study aimed to assess the six-month efficacy and safety of the Bullfrog micro-infusion device (Mercator MedSystems) adventitial deposition of two escalating doses of temsirolimus in reducing angiographic neointimal hyperplasia and target lesion failure after revascularisation of below-the-knee (BTK) arteries.
This prospective, multicentre, dose-escalation, comparative, double-blinded study enrolled 61 patients undergoing endovascular revascularisation of ≥1 angiographically significant BTK lesions. Treatment was applied after completion of artery revascularisation, and divided into control (saline; 0.25–0.5mL/cm of lesion length), low-dose temsirolimus (0.1mg/mL; 0.025–0.05mg/cm of lesion length) or high-dose temsirolimus (0.4mg/mL; 0.1–0.2mg/cm of lesion length) groups in a dual-blinded, randomised fashion.
Primary and secondary efficacy endpoints were transverse-view vessel area loss percentage (TVAL%) of the target lesion and clinically relevant target lesion failure (CR-TLF) at six months, respectively. Primary safety endpoint was freedom from a major adverse limb event or perioperative death (MALE+POD) at 30 days.
Armstrong reported that superior primary efficacy of the treatment arm was apparent in the per protocol (PP) and PP-TASC B-D (excluding 15 subjects with TASC A lesions) subgroups, and that TVAL% reductions of 13.9% and 22.3% were seen in the PP and PP-TASC B-D subgroups at six months, respectively.
In addition, freedom from CR-TLF rates were substantially higher in those patients treated with temsirolimus, and differences between treatment and control for freedom from CR-TLF at six months were 27.1% and 39.2% in the PP and PP TASC B-D subgroups, respectively. Freedom from composite of 30-day MALE+POD was 100% in all groups.
“Findings suggest that adventitial deposition of temsirolimus using the Bullfrog micro-infusion device improves six-month vessel patency when applied to BTK arteries after successful endovascular revascularisation,” Armstrong concluded.
FLASH Registry: Acute haemodynamic improvement with percutaneous mechanical thrombectomy in a real-world pulmonary embolism population
Catalin Toma (University of Pittsburgh, Pittsburgh, USA) presented results from the FLASH Registry. FLASH is a 500-patient prospective, multicentre registry study to evaluate real-world outcomes after treatment of patients with intermediate and high risk PE with FlowTriever (Inari Medical).
Toma reported that mortality through 48 hours was 0% and that just three patients out of 320 (1.3%) experienced major adverse events—all of which were major bleeds.
Ablation of peri-arterial nerves in ARA should result in an additional blood pressure reduction
Yu Sato (CVPath Institute, Gaithersburg, USA) gave the final presentation of the session, on the anatomy of the human accessory renal artery peri-arterial renal sympathetic nerve for renal denervation.
Sato began by detailing that accessory renal arteries (ARAs) have been reported in about 30% of patients. Some renal denervation clinical trials excluded patients with ARAs, while others included such patients but excluded those with ARAs less than 3 or 4mm in diameter. Moreover, some studies have suggested that renal denervation for ARAs may have an additional advantage of blood pressure reduction. The aim of this study was to evaluate the anatomic distribution of peri-arterial nerves in human ARAs.
Sato concluded that ARAs have two-thirds the number of nerves as compared to dominant renal arteries, and that the number of nerves around the ARAs is dependent on the size of the renal arteries.
“Our results suggest that ablation of peri-arterial nerves in ARA should result in an additional blood pressure reduction,” he remarked, adding that future renal denervation clinical trials should consider including ablation of peri-arterial nerves in ARAs.
Cook Medical today announced that the Zilver Vena received US Food and Drug Administration (FDA) premarket approval (PMA) in the USA. The product is expected to be commercially available to physicians in the USA in Q4 2020.
Zilver Vena is a self-expanding stent approved to treat patients suffering from iliofemoral venous disease. When implanted in a patient with venous disease, Zilver Vena expands to keep blood flowing through narrow or blocked veins.
To receive this FDA premarket approval, Cook Medical had to provide scientific evidence that the device is safe and effective for its intended use in treating venous outflow obstruction.
According to a press release, the stent was designed to balance flexibility and strength: it is flexible so that it can conform to a patient’s unique anatomy while it provides sufficient lumen expansion to open blocked veins.
“We are only in the early stages of understanding this complex disease, but Cook is committed to driving venous therapy development,” said Mark Breedlove, vice president of Cook Medical’s Vascular division. “We are engaged and committed to working alongside physicians and investing in thorough internal training, physician education, building clinical evidence, and more.”
Ra Medical Systems has announced enrolment of the tenth subject in its pivotal clinical trial to evaluate the safety and effectiveness of the Dabra excimer laser system as an atherectomy device for the treatment of peripheral arterial disease (PAD).
“Patient screening and enrolment have recently increased with five clinical sites now cleared to enrol subjects as we pursue an atherectomy indication for Dabra,” said Will McGuire, Ra Medical Systems CEO. “Earlier this year enrolment in this trial had stalled due to the COVID-19 pandemic, which also impacted our ability to activate new clinical sites. We are pleased that nine subjects have been enrolled in the past two months at our clinical study sites, all of which are operating via applicable COVID-19 protocols.”
The open-label pivotal atherectomy clinical trial can enrol up to 100 patients with symptoms of PAD (Rutherford Class 2–5) at up to 10 sites. Outcome measures include safety, acute technical success, and clinical success. The trial’s primary efficacy endpoint is the mean reduction in percent diameter stenosis in each patient’s primary lesion as measured by angiography immediately following treatment with Dabra, before any adjunctive treatment.
The trial’s safety and clinical success endpoints are major adverse events at 30 days and incidence of primary target lesion revascularisation at six months. Dabra received US Food and Drug Administration (FDA) 510(k) clearance in May 2017 for use in ablating a channel in occlusive peripheral vascular disease.
Ushering in “the era of IO”, Brad Wood calls for interventional oncologists to learn the language of immuno-oncology—“the other IO”—in order to improve care for cancer patients. Discussing the “speculative but huge potential impact” of combining interventional radiology (IR) approaches with an understanding of immune-oncology, Wood warns readers that this is not merely an exciting opportunity to increase the scope of interventional oncologists’ work, but a necessary step in ensuring the discipline stays at the vanguard of oncologic treatment. immuno-oncology
It has been known for decades that local-regional therapies like ablation and embolization can stimulate a tumour-specific systemic immune response, or even, on some occasions, tumour regression remote from the treated area. What is not known is who, what, where, when, and how to make it happen more often. Enter the era of IO, which to most people means immuno-oncology (IO), and not interventional oncology (IO). Bridging the gap (between IO and the other IO) requires learning the language and themes of cancer immunology. Interventional radiology (IR) has several hammers to pull out of our big IO toolbox. However, we need to determine whether to freeze, fry, shake, shock, zap, or choke a tumour—that is, whether to use cryoablation, radiofrequency ablation (RFA), microwave ablation (MWA), irreversible electroporation (IRE), high-intensity focused ultrasound (HIFU), histotripsy, transarterial chemoembolization [TACE], or Yttrium-90 (Y-90) radioembolization. We also need to determine which histology to treat, at what stage, alongside what IO drug, and in what sequence. Where in the cancer immunity cycle do the IO tools immuno-modulate? How do we balance pro-immune versus pro-metastatic pathways? The window of opportunity remains open for answering the many questions in a rational way.
Checkpoint inhibition takes the brakes off our natural immune response to tumours. Although revolutionary and Nobel-prize worthy, checkpoint inhibitors usually fail as monotherapy, are costly, and are not without side effects. Enter IR/IO. Local IO therapies alongside of checkpoint inhibition can convert an “immune-cold” tumour into an “immune-hot” tumour, potentially turning local into systemic. Immunomodulatory mechanisms boil down to enhancement of: 1) antigen release and presentation, 2) antigen-presenting cell (APC) maturation, 3) T-cell priming proliferation and trafficking, and, 4) reduction of immune tolerance and immune resistance. The molecular tumour micro-environment and the dynamic immune compartments (blood vessels, lymph nodes, target tumour, and remote tumours) also merit consideration.
Initial clinical experience with checkpoint inhibition drugs plus ablation or embolization for advanced hepatocellular carcinoma (HCC) was first reported over five years ago in a National Institute of Health (NIH) study.1, 2 This showed disease stabilisation in the bulk of patients with advanced and heavily pre-treated HCC via this combination approach, often with intentional subtotal treatment of the target tumours. This study also has strong blood and tissue evidence for an immune mechanism when looking at responders versus non-responders. For cholangiocarcinoma, a similar approach with subtotal ablation can be taken.3 Human tissue and survival data convince more medical oncologists at a multidisciplinary tumour board meeting than curing mice in 1,000 lab studies. In this setting, the local or regional therapy is meant to boost the immune system, deposit antigens, promote APC and T-cell maturation, broaden the T-cell receptor response, and tip the balance of immune-regulation away from immune tolerance and towards tumour-specific T-cell activation. More recently, Bevacizumab plus Atezolizumab was approved by the US Food and Drug Administration (FDA) for locally-advanced HCC,4 and ongoing clinical trials will hopefully address whether and when local ablation or embolization add value. The therapeutic options are evolving fast, so IR needs to organise a clinical trial infrastructure, so we can ask hypothesis-driven questions in a standardised fashion. Team science wins.
Emerging data support aggressive local-regional therapies when immunotherapy fails locally in established tumors (versus new widespread metastases). Specifically, when stratified by patterns of failure, local therapy has been shown to be particularly effective after failed checkpoint inhibition, supporting an aggressive re-treatment approach, when progression is confined to established tumours (rather than new breakthrough metastases).5 Like ablation, drug-eluting bead TACE (DEB-TACE) and Y-90 radioembolization reduce regulatory T-cells (good) and expand T-cell responses in HCC. Doxorubicin potentiates immunogenic cell death and enhances cross-priming, but ischaemia cascades turn on damage/pathogen-associated molecular patterns (DAMPS/PAMPS), HIF1a, and cell stress pathways. IRE may leave vessel highways intact for APC and T-cell trafficking, which may explain why IRE (shock) may be better for immunomodulation than RFA (heat) or cryoablation (freeze) for T-cell activation. Histotripsy may be better than heat when combined with checkpoint inhibition.6 Both IRE and cryoablation release more proteins than heat. Yet RFA heat may have a favourable impact upon immunosuppressive T-regs than cryoablation. Cryoablation may have the most inflammation and cell stress signals. Any ablation might recruit more good macrophages than bad, when the margin interacts with the tumour (thus leaves tumour behind). Yet colorectal metastases may explode when partially treated and exposed to the hypoxia of partial treatment.
Clearly, we need to biopsy more after IO therapies. We need to learn more about the tools to measure immune effects (such as immunohistochemistry, flow cytometry, and sequencing). It is a great time to have coffee with an expert from another discipline!
So when you freeze, fry, shake, shock, zap, or choke the tumor—treat the patient, not the picture. Do not be a technical robot and just treat geometric spots in the liver. Think before ablating. Create the proper tumour micro-environment via timing, sequence, and delivery of rational IO plus IO immunomodulation. This is a one-time opportunity, with speculative but huge potential impact. New immuno-oncology trials with checkpoint inhibitor drug combinations have exploded in the past two years.7 Where is IR? We need to be at the table and not on the menu.
Brad Wood is an interventional oncologist at the National Institutes of Health (NIH) Center for Interventional Oncology, Bethesda, USA.
References:
A new survey among vascular access (VA) and emergency department (ED) clinicians has revealed significant levels of variation in ultrasound-guided peripheral IV (UGPIV) practices and supply use across hospitals and alternate care settings. Published in the September issue of the Journal of the Association for Vascular Access, the findings carry critical implications for patient safety.
A total of 1,475 VA and ED practitioners responded to the survey, which was designed to gain better insight into clinicians’ current practices regarding UGPIV insertion. The survey also identified inconsistencies in supply use across hospital departments. The survey was conducted by Nancy Moureau (Griffith University, Brisbane, Australia) an internationally recognised expert and consultant in vascular access and CEO of PICC Excellence.
“Identifying gaps and variations in clinical practice forms the basis of quality initiatives intended to improve patient safety. This survey revealed clinically meaningful differences in all variables for UGPIV procedures and supplies,” said Moureau. “Aseptic technique is essential for minimising contamination, but its effectiveness is diminished if it is not done in a consistent manner. Often inconsistencies in supply usage point to variation in policy application and the potential for substandard practices. The survey results suggest a need for clinical education on the application of UGPIV guidelines, and for greater scrutiny over supplies and techniques in order to promote standardisation.”
The lack of consistency revealed by the survey is apparent in respondents’ varied use of transducer protection and gel. To minimise contamination during UGPIV insertions, current guidelines—such as those from the American College of Emergency Physicians and the American Institute of Ultrasound in Medicine—recommend use of a transducer cover and single-use gel packets (sterile or non-sterile). According to the survey, however, just 59% of VA clinicians and 11% of ED clinicians always use a sterile probe cover during UGPIV procedures, and only 64% of VA personnel and 13% of ED personnel use sterile gel. In addition, more than 22% of respondents stated that they vary between multi-use gel bottles and single-use gel packets, both sterile and non-sterile.
The survey results also highlight issues resulting from the presence of gel in the area of the sterile insertion site. Among the respondents, 41% of VA clinicians and 51% of ED clinicians reported instances of inadequate gel removal, which results in securement and dressing adherence issues. Poor adherence of dressings can lead to catheter failure and accidental dislodgement. Over half of all VA personnel (52%) said they felt that aseptic technique is often compromised by post-procedure gel clean-up.
PIV insertion is the most commonly performed invasive medical procedure among hospitalised patients. Over 70% of acute care patients require IV access at some point during their stay. According to Moureau, up to 60% of those patients may be considered to have difficult vascular access (DiVA). These patients frequently require ultrasound guidance in order to successfully achieve peripheral access and receive necessary treatments.
“This study confirms that the lack of consistent, evidence-based guidelines regarding ultrasound-guidance for PIV insertions has led to a great deal of fragmentation, and shows that clinicians are confused over when and how to use this technology in a way that protects patient safety,” said emergency vascular access expert Jon Bell (St Joseph Hospital, Bangor, USA). “There needs to be an objective standard for identifying difficult access patients, as well as a multidisciplinary effort to conduct research to determine the best practices that will minimise harm to the patient.”
The use of ultrasound may increase the risk of contamination during PIV insertions if certain guidelines are not followed to maintain a sterile insertion site and use the appropriate supplies (gel and transducer protection). According to Moureau, a specialty gel-free insertion dressing that separates the transducer and gel from the insertion site (UltraDrape, Parker Labs) may address and even mitigate many of these issues while reducing the cost of performing UGPIV insertions. In this study, 9% of survey respondents reported use of this gel separation safety dressing.
The survey results align with recent concerns from the healthcare quality and safety organisation, ECRI (Plymouth Meeting, PA). The non-profit technology assessment group addressed the issue of standardisation in its list of top patient safety concerns for 2020, writing that “policies and education must align across care settings to ensure patient safety.”
ECRI also included the use of point-of-care ultrasound in its briefing on 2020 Top 10 Health Technology Hazards, and noted that the rapid adoption of this technology across various care settings has left many organisations struggling to keep up with appropriate safety measures.
MedAlliance has announced enrolment of the first two patients in the PRISTINE registry with Selution sustained limus release (SLR) 018 drug-eluting balloon (DEB) for the treatment of patients with below-the-knee disease. This is the first DEB accepted by the US Food and Drug Administration (FDA) for its breakthrough programme.
The PRISTINE registry is a follow up to the encouraging results seen in the PRESTIGE clinical trial (below the knee, chronic limb threatening ischaemia [CLTI]) at six months.
PRISTINE is a prospective registry to investigate the safety and efficacy of treatment with Selution SLR sirolimus drug-coated balloon in TASC C and D athero-occlusive infrainguinal disease in patients with CLTI from Singapore.
The objective of the registry is to evaluate over 12 months safety and performance outcomes in 75 patients, with Selution SLR DEB in the treatment of infrainguinal occlusive lesions (TASC C and D) in patients with CLTI at Singapore General Hospital.
The clinical primary safety endpoint of the registry is freedom from major adverse events through 30 days and the performance primary endpoint is freedom from cd-TLR within six months. The secondary endpoints are primary patency at six and 12 months follow-up, freedom from cd-TLR at 12 months, clinical success at follow-up in Rutherford score by one class or more, wound healing at six months, and freedom from major target limb amputation within six and 12 months post index procedure.
“We are excited about the commencement of this large single-centre prospective study focusing on patients with chronic limb threatening ischemia receiving the novel sirolimus drug-eluting balloon (Selution SLR DEB) from MedAlliance”, said associate professor Chong Tze Tec, head and senior consultant, Department of Vascular Surgery, Singapore General Hospital. “We believe this registry will give us detailed insight into the efficacy and safety of this new balloon technology which will benefit this challenging group of patients.”
“We are delighted to report enrolment of the first two patients in the exciting PRISTINE registry”, added associate professor Tjun Tang, lead Investigator and a senior consultant in the Department of Vascular Surgery, Singapore General Hospital. “CLTI represents the worse part of the spectrum of peripheral artery disease and patients are at an increased risk of limb loss and mortality. The incidence is likely to increase in Singapore because of the rising trend in diabetes and end stage renal disease in the country and these patients are a challenging and frail population of patients.
“We currently do far too many major lower limb amputations: in fact the rate in Singapore is two to three times higher than in western countries. We seriously need to address this issue. One of the cornerstones of treatment is to re-establish pulsatile blood flow to the foot to promote wound healing and although percutaneous lower limb angioplasty has become the favoured option of revascularization, its Achilles heel is vessel recoil and restenosis from neointimal hyperplasia”.
“Singapore General Hospital performs over 900 lower limb salvage revascularisation procedures per year and has established multi-disciplinary wound management protocols and we are highly encouraged by the pilot data we have found using this technology so far and PRISTINE will offer further insight, leveraging on our experience with PRESTIGE, whether this sirolimus coated balloon will become an established device in our angioplasty armamentarium in the future”, concluded Tang.
The Surfacer Inside-Out access catheter system device (Bluegrass Vascular) is safe and effective for patients with thoracic central venous obstruction requiring central venous access. That is conclusion of the prospective, multicentre SAVE (Surfacer system to facilitate access in venous occlusions) registry, published today in the Journal of Vascular and Interventional Radiology (JVIR).
Central venous catheters were successfully placed in 29 of 30 patients (96.7%) with no device-related adverse events or intra- or postprocedural complications reported.
“The SAVE registry achieved its desired objective of confirming the safety and effectiveness of the Surfacer system to gain central venous access in patients with central venous occlusions,” comments Vladimir Matoussevitch, head of Vascular Access Unit University of Cologne (Cologne, Germany) and co-lead author for the paper.
“The publication of the results of the SAVE registry expands and strengthens the clinical evidence confirming the role the Surfacer system has in helping to establish central venous access in patients with venous obstructions,” states Maurizio Gallieni, director of Nephrology and Dialysis at the University of Milan (Milan, Italy), who was the other co-lead author.
Watch the JVIR press release video here.
President-elect of the Society of Interventional Oncology (SIO), Matthew Callstrom discusses his journey into cancer care, and how advances in percutaneous ablation have shaped the procedure’s integration into first-line therapy. “If we [interventional oncologists around the world] can work together to achieve common standards, we will be able to develop evidence to support interventional oncology [IO] procedures in guidelines at an earlier point in a patient’s care,” he says.
The opportunity to improve the care of patients through interventional radiology and IO by offering minimally invasive treatments that reduce pain and morbidity and also improve survival continues to motivate me. I strongly believe that what we offer patients is often a significant improvement over surgery and other treatment options.
I was fortunate to have mentors that were advancing the care of patients in the very earliest days of IO. Both Bill Charboneau and Luigi Solbiati were great role models for driving improved care of patients with new, innovative technology and supporting the advancement through scholarship. They were instrumental in promoting an international approach to sharing lessons learned and advancing the care of patients with cancer.
The primary goal over the next year will be to work with the SIO leadership and membership to help advance the clinical evidence that demonstrates the value of IO for patient care. The SIO is focused on advancing the care of patients through supporting both investigator-initiated feasibility studies but also through pivotal clinical trials, industry partnership, and advocacy for IO. We are also committed to improving the care of patients by advancing IO through guidelines and standards.
The WCIO was a great format for communication of the advances of IO, but it was only a meeting. The transition to a society and SIO was to build the support of education, research, and advocacy that expands the impact of the physicians and industry partners committed to IO. A good example of what SIO has accomplished is the support of teams that update the National Comprehensive Cancer Network (NCCN) guidelines on a regular basis. Another benefit of a society is the support of research efforts that advance the science of IO. If you look back at the history of radiation oncology, the formation of the Radiation Therapy Oncology Group (RTOG) was instrumental in advancing the evidence that supports the use of radiation therapy for patients with cancer. SIO is working to support IO through a similar infrastructure.
I think a good research paper is focused on advancing the care of patients with clear communication of the findings. While early experience of new applications or advances is important, we need to produce evidence that shows how IO is important for patient care. It is important to recognise that decisions at tumour boards are driven by high-quality data with an emphasis on phase II/III studies.
I have been fortunate to be involved in the care of patients that have had improved survival due to the care that we provide in our practice. I was part of the team treating a patient that had metastatic hepatocellular carcinoma (HCC) but survived more than 10 years due to the care we provided. He had more than 10 ablation treatments involving his liver, adrenal, lung, spine, and body wall. Throughout the time that we cared for him, he continued in his medical practice and his son became a teenager. We developed a great friendship and I attended his funeral with his passing, which was difficult, but the celebration of his life at the service was a profound experience for me.
I think we are now at the point in the use of ablation procedures where integration in first-line therapy has an important role. We have established that local control with ablation is complementary and comparable with surgery and radiation therapy for some applications. I think that in the next few years we will demonstrate that ablation procedures offer the advantage of tissue preservation and less morbidity over the course of a patient’s life with cancer. There is also promising research that ablation in combination with immune therapy may provide abscopal response for patients with metastatic disease.
We experienced a continued need for the treatment of patients with cancer throughout this pandemic. We initially reduced our access in order to implement safety measures such as measuring aerosol clearance in our procedural suites and improved standards for personal protection equipment. We learned that we can safely offer cancer treatments with appropriate testing. We learned the necessity of continuing to offer treatment for patients rather than attempting to prioritise only for more acute or semi-acute patients as delayed care is a risk to patients for progression and potentially survival.
The introduction of improved ablation devices has allowed better outcomes for IO treatments. The first heat-based devices we used were underpowered, and getting a complete treatment was often difficult. Percutaneous cryoablation devices have allowed the expansion of treatments that we can offer. I was involved in the use of the intraoperative liquid nitrogen systems many years ago and, although innovative, treatment of renal masses, lung tumours, and musculoskeletal tumours would not be possible. We now treat more than 500 patients a year with this technology. Hybrid rooms are also putting the best imaging methods in the hands of the proceduralists, allowing both CT and fluoroscopy imaging, where they offer the best visualisation and guidance approach.
I believe we need to work together to improve the standard performance and delivery of IO treatments. Many of the procedures that have matured and are helpful for patients are done differently in centres across the world. We have been involved in multicentre clinical trials where we have struggled to gain a common approach in the use of devices and technical performance, and the outcomes have been impacted negatively. Performing procedures with standard approaches and objective outcomes will both advance patient care and elevate the standing of IR/IO in the world. If we can work together to achieve common standards, we will be able to develop evidence to support IO procedures in guidelines at an earlier point in a patient’s care.
Outside of medicine, I am blessed to have a wonderful family, including my wife Brenda and my two boys, Joseph (30) and Peter (27). We also have two golden doodles (Charlie and Lucy) that are our constant companions and treated like children now that we are empty nesters. We spend as much time as we can at our lake cabin that is on the lake that Brenda and I first met and honeymooned—our family and friends often join us, and although there are 10,000 lakes in Minnesota, there is only one as far as our family is concerned. I enjoy making furniture in my wood shop even though there is usually more dust than any final product generated. I also enjoy riding a road bike—on the less travelled roads near our house and cabin, and in the basement on a trainer during the too-long winters in Minnesota.
In a session of the 2020 Cardiovascular and Radiological Society of Europe (CIRSE) meeting (12–15 September, virtual) focused on the hottest news in the endovascular thrombectomy space, Antonin Krajina (University Hospital, Hradec Králové, Czech Republic) shared new devices available for the procedure, and enthused about their potential in stroke management.
First describing his, hypothetical, ideal device for endovascular thrombectomy, Krajina said that it should be “easy to use and have fast access to the clot”. Stent retrievers are assessed by their ability to integrate the clot and to keep hold of it during retrieval; radiopacity of the stent retriever therefore plays an important role, Krajina stated. Additionally, he explained how there is a significant association between first-pass complete reperfusion and favourable clinical outcome, with two to three times higher odds for a favourable clinical outcome compared with complete reperfusion after multiple passes.
Indeed, his key take-home message was that clot integration is a function of delivery technique, duration of device implantation, and clot mechanics. His talk therefore detailed how device design influences these aspects of performance. In addition, he urged his listeners to “use all tricks in the attempt to remove the clot at the first pass (including aspiration via balloon guide), and detailed how the COMPASS trial results provide Level 1 data that an aspiration thrombectomy as first-pass approach is non-inferior to a stent-retriever as a first-line approach for the treatment of selected patients with acute large vessel ischaemic stroke.
The importance of device design
Comparing the Solitaire X device (Medtronic), the CatchView stent retriever (Balt), and the Embotrap III device (Cerenovus), Krajina showcased how each had platinum markers on the proximal and distal ends, explaining that these acted as radiopacity markers.
Turning to the capacity to integrate the clot, he next discussed the relative benefits of using a short (20mm) or a long (30mm) stent retriever: “A longer [stent retriever] may increase the capacity to catch the clot,” he said. This was proven by Gaurav Girdhar (Medtronic, Irvine, USA) et al in their January 2020 publication in Interventional Neurology, which concluded that stent length had a significant effect on first pass success rate (p<0.05). The authors wrote: “Longer stent retrievers may be safe and effective in improving first pass success for fibrin-rich clots in vitro and in vivo models of large vessel occlusion”. However, Krajina added that a longer stent retriever means higher friction, which in turn increases the probability of the device getting stuck and then elongating, resulting in a loss of apposition to the arterial wall. The embolisation risk of the clot is also higher with longer devices, he explained, as longer dwell times affect the likelihood of distal embolization.
“Stent retrieval length should be adjusted to clot extent,” Krajina said, citing a June 2020 paper published in Cerebrovascular Diseases from Hanna Styczen (University Hospital Essen, Essen, Germany) and colleagues. Styczen et al hypothesised that increased stent retriever length may improve the rate of complete angiographic reperfusion and decrease the respective number of attempts, resulting in a better clinical outcome. They conducted a retrospective analysis of 394 patients with large vessel occlusion in the anterior and posterior circulation treated with stent retriever mechanical thrombectomy, sorting patients by propensity matching into two groups: those treated with a short (20mm) device, and those treated with a long (30mm) device. They found that, in the anterior circulation, short stent retrievers had a significantly higher rate of first-pass reperfusion in cases with low clot burden, and in middle cerebral artery occlusions. Higher rates of favourable outcome at discharge and 90 days were observed for the short stent retriever group (p<0.001). This led them to conclude, as Krajina related to the CIRSE audience, that stent retriever length “should be adjusted to clot burden score and vessel occlusion site.” Krajina clarified: “Stents for short occlusion are appropriate if they are 20mm long; for longer occlusions, we need longer stent retrievers.”
“What position of the stent-retriever in relation to the occlusion/ embolus is the most effective?” Krajina asked his listeners rhetorically. “If it [the stent-retriever] is too –proximal and/or only partially engaged into the clot, it is less probable that we can remove the whole clot,” he explained. “If the clot is more proximal to the stent-retriever, the probability that we remove it during first-pass is higher. To verify the relationship of the clot and the stent-retriever position, we perform an angiogram after stent-retriever deployment.”
Next, Krajina discussed how to decide what diameter stent-retriever device to use to increase the probability of successfully removing the clot at first pass, 4mm or 6mm. “If you look at a diameter of the M1 segment in males, it is about 2.5mm, and the diameter of the internal carotid artery is around 3mm,” he informed delegates.
Writing in the Journal of Neurointerventional Surgery in 2018, Mark Davison (Rush University Medical Center, Chicago, USA) and colleagues said: “Compared with males, females consistently fare worse following mechanical thrombectomy for large vessel ischaemic strokes. Understanding why this gender disparity occurs may guide improvements in future treatment strategies.” In their study, they aimed to determine whether gender differences in cerebral arterial diameter correlated with clinical outcomes following stroke thrombectomy. They therefore performed an observational study of 92 consecutive acute ischaemic stroke patients (42 women) undergoing mechanical thrombectomy between June 2013 and August 2016 at a single, urban tertiary care medical centre. Catheter angiographic images were used to manually measure proximal segment arterial diameters in a standardised fashion, and medical record review was used to obtain relevant independent and dependent variables. Internal carotid artery terminus diameters for men and women were 3.08mm and 2.81mm, respectively (p=0.01). M1 segment middle cerebral artery diameters for men and women were 2.47mm and 2.18mm, respectively (p<0.0001). Nearly half (48%) the patients in the upper middle cerebral artery calibre tercile attained a favourable mRS 90-day value compared with 35% in each of the lower and middle terciles (p=0.51). Larger middle cerebral artery diameters correlated with favourable discharge disposition (p=0.21).
This led Davison et al to conclude: “These results provide limited evidence that males have larger cerebral arterial diameters than females and that larger arterial diameters may improve the odds for favourable clinical outcomes. If future studies validate these findings, arterial diameter may become a relevant variable in the design of improved thrombectomy strategies.”
However, Krajina went on to say that “More and more studies are proving that stent-retrievers with larger diameters do not appear to provide clear benefits”. Detailing a 2017 paper published in the American Journal of Neuroradiology, he reported how, in their investigation of the effects of different diameters of Solitaire retrievers on clinical outcomes, Dong Yang (Jinling Hospital, Second Military Medical University, Nanjing, China) and colleagues found “no evidence of a differential effect of intra-arterial therapy based on the size of the stent-retrievers”. Though they also found that, in patients with atherosclerotic disease, favourable reperfusion was associated with deployment of a small stent.
Demonstrating new designs for stent retrievers that he believes are improving interventionalists’ ability to successfully perform endovascular thrombectomy, Krajina introduced the NeVa stent retriever from Vesalio, which has clot pockets oriented at 90 degrees to each other that increase the first-pass effect. The Embotrap III device (Cerenovus) has an inner channel to stabilise the clot during retrieval, and an outer cage to engage and integrate the clot. With this latest re-design, the distal mesh of the Embotrap III device is also denser than previous iterations.
Access and delivery catheters and guidewires
“Besides stent-retrievers, we also need delivery catheters and guidewires,” Krajina said. In his view, the most important aspects to consider for these devices are navigability, pushability, kink resistance, and whether or not they can be assembled as a coaxial set.
A survey of Society of Neurointerventional Surgery (SNIS) neurointerventionalists that received 78 responses (approximately 10% of SNIS membership), published in the Journal of Neurointerventional Surgery, indicated an increase in aggressiveness in pursuing thrombectomy based on selection criteria. Nearly 40% of respondents (39.7%) reported using catheter aspiration thrombectomy as a frontline therapy. A further 28.2% opted for stent-retriever mechanical thrombectomy, and another 28.2% said they adopted a combined approach, utilising stent-retrievers with aspiration.
“Interventional neuroradiologists love to combine access catheters to create coaxial double, triple systems,” Krajina told CIRSE registrants, “sometimes in difficult or tortuous anatomy, referred to as a ‘tower of power’, to have enough support for intracranial catheters.” To create such a set, the length and diameter of the catheter used is important, the CIRSE audience heard: “Ideally one should use the shortest length necessary to do the job.”
Finally, he stressed that interventionalists should use balloon-guiding catheters to stop arterial flow, and to facilitate aspiration via these catheters during clot removal.
Reflow Medical has announced that Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has approved the Wingman chronic total occlusion (CTO) catheter. Reflow Medical has partnered with Century Medical, a medical device distributor based in Tokyo, to introduce the Wingman CTO catheter in Japan.
The Wingman catheter crosses peripheral CTOs using an extendable bevelled tip. The physician controls the advancement and activation of the tip to create a channel to help penetrate, or cross, the occlusion with a guidewire, enabling further treatment of the lesion with therapeutic devices. The catheter is compatible with the physician’s preferred guidewire and procedural technique.
Approval by Japan’s PMDA follows the completion of the Wing-IT CTO clinical trial, a prospective, international, multicentre study that treated 85 patients and followed them for 30 days. The Wingman catheter was able to demonstrate a 90% crossing rate when up to two previous guidewires could not cross the CTOs, meeting its primary safety and efficacy endpoints.
“Reflow Medical focuses their efforts on developing technologies based on physicians’ needs,” said John R Laird (Adventist Heart and Vascular Institute, St Helena, USA). Laird was the principal investigator for the study. “We rely on Reflow for real clinical evidence when utilising the technology.”
Reflow’s Wingman crossing catheter received clearance from the US Food and Drug Administration for the expanded CTO indication for the Wingman crossing catheter in March 2020 after completing the Wing-IT clinical trial.
PQ Bypass has announced enrolment of the final subject in the company’s DETOUR II investigational device exemption (IDE) clinical trial. This milestone occurs only a month after the Detour system entered the US Food and Drug Administration (FDA)’s breakthrough device programme.
DETOUR II is led by national co-principal investigators Sean Lyden (Cleveland Clinic, Cleveland, USA) and Jihad Mustapha (Advanced Cardiac and Vascular Centers, Grand Rapids, USA). Both national co-PIs receive compensation for their duties in this role.
“The speed with which we were able to enroll DETOUR2 in 2020 speaks to the large patient population that exists with long-segment femoropopliteal disease that has sub-optimal endovascular options,” says Lyden.
“If percutaneous fem-pop bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR1 study, it could be a game changer for the way we treat complex, long-segment SFA [superficial femoral artery] disease today,” continues Mustapha.
DETOUR II is a prospective, multicentre trial evaluating the Detour system for percutaneous femoral-popliteal bypass in patients with extremely long, complex lesions in the SFA. The study enrolled 202 patients in 36 sites in the USA and Europe, and is assessing freedom from major adverse events (MAE) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness is primary patency at 12 months.
“After finishing enrolment in DETOUR II and achieving the breakthrough device designation, PQ Bypass is on track to deliver results from this study much earlier than what we originally expected,” says Heather Simonsen, president of PQ Bypass. “We would like to thank the DETOUR II investigational sites for their ongoing contribution to this important research.”
A coalition organised by the CLI Global Society has announced its proposal to distinctly recognise “critical limb ischaemia” (CLI) and “chronic limb-threatening ischaemia” (CLTI) in the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) was approved by the Centers for Disease Control and Prevention (CDC) and went into effect on 1 October 2020.
The ICD-10-CM is a worldwide standard reference set of disease codes used to report medical services provided to patients. The announcement marks a major step forward in tracking patient treatments and outcomes for CLI and CLTI, which affect millions of patients globally.
The CLI Global Society worked in close partnership with the vascular specialist community to develop the proposal. Coalition members include:
The goal of this initiative is to support coding professionals, educators, compliance staff, and physicians to identify and accurately report CLI and CLTI in clinical documentation, electronic medical records, and medical billing in order to track and monitor patient treatments and outcomes in the future.
“This effort is a first step in building awareness of the complexity associated with caring for patients who suffer from CLI within public and commercial payers and the broader healthcare community,” says Barry Katzen, board chair of the CLI Global Society. “These dedicated codes, now newly identified for CLI, are critical in our goal to improve quality of life by preventing amputations and death due to CLI.”
Robert Lookstein, chair of the Vascular Societies Workgroup and CLI Global Society board member, acknowledges the collective effort of his colleagues, “who came together to prioritise the need for a well-defined and accessible method to identify, report, and track CLI for the benefit of patients who suffer from this disease.
“We also look forward to continued partnership as we launch initiatives to educate our membership, our hospitals, and healthcare provider staff regarding these changes,” Lookstein explains. “They have the potential to positively impact the care we provide to these extremely vulnerable patients across the United States and around the world.”
CLI and CLTI are advanced forms of peripheral arterial disease (PAD), a common circulation problem that occurs when arteries that carry blood throughout the body become narrowed or blocked, restricting blood flow to legs and feet. Those who smoke, have diabetes or chronic kidney disease, or suffer from high blood pressure or high cholesterol are susceptible to CLI and its complications. Left untreated, CLI can lead to tissue loss, gangrene, amputations, and eventually death.
“The statistics are grim,” says Jihad Mustapha, founding board member of the CLI Global Society. “We know 60% of patients who receive an amputation due to PAD or CLI die within two years—this is higher than the five-year mortality rate for patients with breast, colon, and prostate cancer.
“In order to fight this deadly disease, we need to have accurate data. This seemingly small change to medical coding will allow us to save countless limbs—and lives.”
Interventionalists are being encouraged to take consideration of a set of talking points about the risks and benefits of paclitaxel-equipped devices—which has developed by a multispecialty panel of medical societies—in discussions with their patients.
The document is the work of the Multi-Specialty and Multi-Society Coalition for Patient Safety With Paclitaxel Technologies, which includes the following societies: the American College of Cardiology (ACC), American College of Radiology (ACR), American Heart Association (AHA), Society for Cardiovascular Angiography and Interventions (SCAI), Society for Vascular Medicine (SVM), the Society of Interventional Radiology (SIR), the Society for Vascular Surgery (SVS), the Vascular and Endovascular Surgery Society (VESS), and the Society for Clinical Vascular Surgery (SCVS).
The US Food and Drug Administration (FDA) tasked the coalition with putting together bullet points that reflect the current evidence around the hot topic of paclitaxel devices.
“The coalition bullet points reflect the current evidence surrounding this complex topic and is designed to help institutions and members to use when discussing increased rate of long-term mortality in patients treated with paclitaxel-coated balloons and paclitaxel-eluting stents,” the coalition stated.
“The statements are intended to summarise the current state of the evidence and to serve as starting points for discussion. We recognise this is a complex issue and the talking points and are not intended to take the place of thoughtful, individualised discussions with patients.
“The ability to effectively communicate risk and benefit of revascularisation is key part of procedure selection. Please consider the following statement in your discussions and informed consent process.” The document follows in full.
Peripheral vascular intervention talking points for informing patients about the paclitaxel safety signal
A recent meta-analysis of randomised trials suggests an increased mortality rate after two years in peripheral artery disease (PAD) patients treated with paclitaxel-coated balloons and paclitaxel-eluting stents for femoropopliteal disease compared to patients treated with uncoated balloons or bare metal stents. The FDA recommends that physicians discuss the risks and benefits of all available treatment options with their PAD patients.
To this end, a Multi-Specialty Paclitaxel Coalition (American College of Cardiology, American College of Radiology, American Heart Association, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine, Society of Interventional Radiology, Society for Vascular Surgery, Vascular and Endovascular Surgery Society, and the Society for Clinical Vascular Surgery), representing the majority of specialists who evaluate and treat patients with PAD, developed the following talking points, which have been reviewed by the FDA, that physicians/providers may consider when discussing PAD treatment options with their patients:
The Multi-Specialty Paclitaxel Coalition is actively working with the FDA, medical device manufacturers, and clinical investigators to advance our understanding of the long-term safety and effectiveness of paclitaxel-coated devices.
On behalf of the Multi-Specialty and Multi-Society Coalition for Patient Safety With Paclitaxel Technologies.
Teleflex has announced it has received 510(k) clearance from the US Food and Drug Administration to expand the indications for use of the Arrow EZ-IO intraosseous vascular access system. This device can be used when intravenous access is difficult or impossible to obtain in emergent, urgent, or medically necessary cases.
The Arrow EZ-IO system is now available with the expanded indication stating use of the device may be extended for up to 48 hours when alternate intravenous access is not available or reliably established in adults, and in paediatric patients 12 years and older.
“Vascular access is one of the most basic, yet critical, components of patient care,” said Michelle Fox, corporate vice president and chief medical officer, Teleflex. “The ability to use the EZ-IO system for a longer dwell time provides clinicians the option to utilise intraosseous (IO) access for the entire duration of therapy in patients with difficult vascular access where therapy is required for up to 48 hours.”
In patients who require longer-term access, the expanded indication gives clinicians additional time to establish vascular access safely, choosing the appropriate device and optimal site of insertion to meet the patient’s clinical needs. “These benefits are of particular importance in a time of constrained resources and patient surge,” said Fox.
Medtronic today announced the planned acquisition of Avenu Medical, a medical device company focused on the endovascular creation of arteriovenous (AV) fistulae for patients with end-stage renal disease (ESRD) undergoing dialysis. Terms of the transaction were not disclosed.
A press release explains that Avenu Medical’s Ellipsys vascular access system is a single-catheter, ultrasound-guided device that inserts a catheter percutaneously into the arm to create a durable AV fistula. The procedure can be performed in the hospital outpatient department, ambulatory surgery center (ASC), or physician’s office.
“AV fistulae are like lifelines to patients undergoing dialysis. Until recently, the only option to create a fistula was through invasive surgery, which is associated with high failure rates,” said Jeffrey Hull (Richmond Vascular Center, Richmond, USA), co-founder of Avenu Medical. “The Ellipsys system has shown durable outcomes out to two-years and has the ability to shorten procedure times and potentially reduce costs. Unlike open surgery, sutures are not required after the procedure and the patient leaves with just an adhesive bandage.”
“Medtronic’s acquisition of Avenu aligns directly with our vision of bringing less invasive, endovascular solutions to patients requiring durable vascular access,” said Mark Ritchart, president and chief executive officer of Avenu Medical. “With Medtronic’s extensive market presence, clinical leadership, and market development expertise, coupled with Avenu’s customer-focused team and innovative technology, we are confident that together, we can drive awareness and adoption of this technology globally.”
“Within the last year, we have seen significant momentum with the launch of the IN.PACT AV drug-coated balloon (DCB) in the USA and primary endpoint results of the IN.PACT AV Access study being published in The New England Journal of Medicine,” said Mark Pacyna, vice president and general manager of the Peripheral Vascular business at Medtronic. “Now with the acquisition of Avenu Medical, we can support procedures across the vascular access care continuum, while continuing to provide innovative endovascular therapies that will ultimately reach even more patients with ESRD around the world.”
The acquisition is expected to close in October, subject to the satisfaction of certain customary closing conditions.
Royal Philips has announced the launch of the QuickClear mechanical thrombectomy system. The single-use system delivers an all-in-one aspiration pump and catheter to remove blood clots from the vessels of the peripheral arterial and venous systems and has received US Food and Drug Administration (FDA) 510(k) clearance.
The system’s design aims to simplify the use of the device and improve procedure times without the need for capital equipment or accessories.
Chris Landon, senior vice president and general manager of image guided therapy devices at Philips claims that “by taking away the high initial capital expenditure costs associated with traditional mechanical thrombectomy systems, QuickClear can help bring cost-effective solutions to both the hospital and outpatient care settings.”
The small footprint of the sterile device allows it to be placed easily on the table next to the patient. The company claims that the system can easily work at maximum aspiration power within seconds and that the consistency of the aspiration power during the procedure supports faster procedure times.
Furthermore, the system’s range of catheters includes a large 10F aspiration catheter which, according to the company’s own in-house data, provides 59% more aspiration volume than 8F aspiration catheters.
Bryan Fisher (Nashville, USA) says that the “QuickClear is a simple and easy to use mechanical thrombectomy system.” He adds that it “is significantly smaller than other systems without compromising aspiration power.
The QuickClear mechanical thrombectomy system is the latest expansion of the company’s portfolio after acquiring Intact Vascular. Philips’ peripheral vascular portfolio already includes advanced interventional imaging systems for precision guidance; intravascular ultrasound (IVUS) catheters to assess the location of the disease and lesion morphology and guide and confirm the treatment; peripheral atherectomy devices to remove blockages; and peripheral therapy devices, such as Philips’ Stellarex drug-coated balloon, to treat lesions.
Midterm results from a study of the largest population of patients with no-option chronic limb-threatening ischaemia (CLTI) treated with percutaneous deep vein arterialisation (pDVA) using the LimFlow device show that, in this complex group of patients, this treatment method is feasible, with a high technical success rate and amputation-free survival at six through to 24 months, coupled with effective wound healing. In selected patients with no-option CLTI, percutaneous deep vein arterialisation could be a recommended treatment to prevent amputation and heal wounds, Costantino Del Giudice (Université de Paris, Paris, France) told delegates attending the online 2020 meeting of the Cardiovascular and Radiological Society of Europe (CIRSE; 12–15 September, virtual).
These results from the ALPS (midterm outcomes of percutaneous deep venous arterialization with a dedicated system for patients with no-option chronic limb-threatening ischemia) multicentre study were published in the Journal of Endovascular Therapy in May this year, and appeared in the August print issue, in addition to being presented at the CIRSE congress. The ALPS registry is the largest study to date of no-option CLTI patients treated with the LimFlow system reporting mid- and long-term results, and is a multicentre, retrospective study conducted at centres in Alkmaar, The Netherlands; Leipzig, Germany; Paris, France; and Singapore encompassing 32 end-stage—or “no-option”—CLTI patients.
The investigators set out to evaluate the midterm results of patients suffering from no-option CLTI treated with a dedicated system (the Limflow system) for percutaneous deep venous arterialisation. Thirty-two consecutive CLTI patients (mean age 67±14 years; 20 men) were treated with this method using the Limflow device at four centres between 11 July 2014 and 11 June 2018 and retrospectively analysed. Of all patients, 21 (66%) had diabetes, eight (25%) were on immunosuppression, four (16%) had dialysis-dependent renal failure, nine (28%) had Rutherford category six ischaemia, and 25 (78%) were deemed at high risk of amputation. The primary outcome was amputation-free survival (AFS) at six months. Secondary outcomes were wound healing, limb salvage, and survival at six, 12, and 24 months.
Technical success was achieved in 31 patients (96.9%). The median follow-up was 34 months (range 16-63). At six, 12, and 24 months, estimates were 83.9%, 71%, and 67.2% for AFS, 86.8%, 79.8%, and 79.8% for limb salvage, and 36.6%, 68.2%, and 72.7% for complete wound healing, respectively. Median time to complete wound healing was 4.9 months (range 0.5–15). The deep vein arterialisation circuit occluded during follow-up in 21 patients; the median time to occlusion was 2.6 months. Reintervention for occlusion was performed in 17 patients: 16 because of unhealed wounds and one for a newly developed ulcer.
Deep vein arterialisation a hope for “no option” patients
“No option” patients are those where no possible endovascular or surgical procedure will help, due to either the absence of a target vessel or thanks to unsuccessful prior interventions. These patients frequently have calcified vessels, diabetes mellitus, dialysis, and/or long-term corticoid therapy. The risk of amputation and persistent wound is 58% when these patients are treated with conservative therapy, and the risk of death at one-year follow-up is 20%.
Deep vein arterialisation aims to improve the blood flow to the foot. “We direct nutritional improvement by reversal of flow through venules,” Del Giudice told the CIRSE audience, describing how deep vein arterialisation works. “This stimulates arteriogenesis, and recruits hibernating collaterals.”
The most important step, he shared, is patient selection. “Patients have to have a good heart function, a good life expectancy, foot arteries not treatable by an endovascular or surgical approach, a Rutherford class 5–6, a Wound, Ischaemia, and Foot Infection (Wifi) score of 3, and no infection,” Del Giudice listed.
According to the speaker, the Limflow technique is the most commonly used method.
The Limflow technique: How it works
Del Giudice talked CIRSE registrants through a case demonstrating the use of the Limflow technique. This first involved performing arteriography and venography scans to aid target vessel selection. Next, the interventionalists advanced the venous and arterial catheters to the target vessel, where the artery and vein were closest, and created an arteriovenous fistula, bridging the two vessels. Then, they advanced the guidewire along the vessel, using it to push the balloon through the arteriovenous fistula to create a passage. Blood flow is diverted from the blocked artery into the vein to salvage the lower leg.
Del Giudice also shared an alternative technique whereby entry in the distal lateral or medial plantar vein from a subintimal channel in the plantar artery can be intentionally pursued as a bailout tactic; this involves pointing the tip of the guidewire opposite to the arterial wall calcifications.
Yet another method is the venous arterialisation simplified technique (VAST). This utilises a low-profile balloon catheter and a snare to facilitate arteriovenous fistula creation during venous arterialisation.
An arteriovenous fistula could also be created using a low-profile balloon catheter and an outback catheter. Del Giudice described a case where he and his team treated a patient using this method, explaining how the patient had occlusion of the popliteal artery. “Without any target vessel in the distal leg,” he said, “we performed subintimal ligation towards the posterior tibial artery, and then we used the outback [catheter] to advance the balloon into the posterior tibial vein, and create the [arteriovenous] fistula, advancing the guidewire. Finally, we performed a valvotomy with a low-profile balloon, and stented the vein from the ankle to the arteriovenous fistula.”
Showing a table comparing the outcomes at six months from these different techniques, Del Giudice was positive: “There is good primary patency, ranging from 40–90% at six months, and good wound healing outcomes, ranging from 40–100%. Major amputations ranged from 0–33.3% at six months follow-up.”
Earlier trials: The Promise I study
PROMISE I study was an early feasibility study launched in mid-2017 to establish the clinical safety of the Limflow technique. It aimed to provide enough data for the investigators to move on to a pivotal trial, to identify and address any operator challenges, and to determine patient characteristics and therapeutic parameters that impact performance. Enrollment was completed in 2019, and the triallists have since reported a 97% technical success rate in the 32 patients treated in the USA as part of this study. Overall survival was 96%, freedom from amputation was 77%, and amputation-free survival was 74%.
“The importance of this study was that it allowed us to understand that not all patients are candidates for this procedure. We need salvageable tissue to obtain some results,” Del Giudice told the CIRSE audience. “Moreover,” he continued, “the results [show that] this is quite different from an arterial canalisation. Deep vein arterialisation requires four to six weeks for tissue granulation to start. Oedema can occur in the treated limb after deep vein arterialisation, but typically resolves within three to four weeks. We need to preserve native arterial perfusion and mange pedal loop outflow during the maturation process. It is also important to monitor changes in foot tissue colour. In terms of wound care, multidisciplinary collaboration is required, and patients may need some minor amputation management, debridement.”
Surmodics has announced receipt of US Food and Drug Administration (FDA) 510(k) clearance for its Pounce thrombus retrieval system.
The company describes the Pounce system as a mechanical thrombectomy device intended for the nonsurgical removal of thrombi and emboli from the peripheral arterial vasculature without the added expense or commitment to additional external capital equipment. The device includes a 5Fr basket delivery catheter, a basket wire assembly, and a trumpet assembly. Its mechanism of action is described as follows: “After the basket wire assembly is delivered distal to the location of the thrombus, two nitinol self-expanding baskets are deployed to collect and entrain the clot into a trumpet-shaped nitinol wire mesh. With the clot entrained, the trumpet assembly is then collapsed into a 7Fr guide sheath through which the clot is withdrawn and removed from the body.”
“The Surmodics team has done an excellent job finalising the product design and advancing the Pounce thrombus retrieval system into a medical device that has the potential to change the treatment algorithm for arterial thrombectomy,” comments Gary Ansel (OhioHealth Heart & Vascular Physicians, Columbus, USA), founder and former chief medical officer of Embolitech, from which Surmodics acquired the technology and intellectual property behind the Pounce thrombus retrieval system. “By providing peripheral interventionalists with an innovative, nonsurgical tool for treating arterial thrombotic occlusions, the Pounce thrombus retrieval system will serve an important clinical need and is a great fit with the company’s focus on advancing therapies for peripheral artery disease.”
Surmodics president and CEO Gary Maharaj adds: “The FDA 510(k) clearance of our Pounce thrombus retrieval system brings us one step closer to providing a technology that offers significant advances over the current treatment of complex, peripheral artery disease.” Maharaj also noted the company’s development efforts in the areas of deep vein thrombosis, pulmonary embolism, and ischaemic stroke. The company recently announced CE Mark for its Surveil drug-coated balloon and FDA clearance of its Sublime radial access 0.014 RX PTA dilatation catheter.
The first patient has been recruited into a trial investigating the BeGraft peripheral plus stent graft system (Bentley InnoMed) as a dedicated bridging stent in branched endovascular aortic repair (BEVAR) for the treatment of complex aortic aneurysms. It is the first study of its kind worldwide.
Martin Austermann (St Franziskus Hospital, and University of Münster, Münster, Germany) is the coordinating investigator of the prospective, single arm, multi-centre clinical study.
“Until now, we have not had a dedicated indicated bridging stent to connect branched endografts with renal and visceral arteries,” says Austermann. “There are many devices that could be used for this, but all in an off-label setting.”
“It is great news that we could start a trial in collaboration with the Foundation for Cardiovascular Research and Education and Bentley for this indication, it has been an unmet need for such a long time,” he adds. “We are very pleased to run this study, which is approved by the German national competent authority BfArM, together with some other colleagues working in high volume centres in Germany. For us, as endovascular specialists, it is key to work as much as possible with medical devices that are indicated for certain procedures.”
Eligible patients are those seeking elective repair of thoracoabdominal aortic aneurysm (TAAA) with BEVAR. The trial aims to carry out 100 BEVAR procedures with an average of 2.5 bridging stents per procedure.
The primary efficacy endpoint is comprised of a measure of technical success defined as the successfully introduction and deployment of the BeGraft Plus implanted as a bridging stent in BEVAR, with bridging stent patency at 12 months (absence of restenosis (≥50% stenosis) or sole target vessel occlusion based on computed tomography (CT) angiography at 12 months. The primary safety endpoint at 12 months relates to the absence of procedure-related complications and bridging stent related endoleaks.
“In one or two years, the trial will provide us with valuable information on occlusions or stent fracture, for example. We will be able to let the patient know what to expect, and it will make the procedure more predictable,” Austermann comments.
The BeGraft Plus combines radial force with flexibility, a Bentley press release states. It consists of two layers of micro-porous expanded polytetrafluoroethylene (ePTFE) tubing based on two cobalt chromium stents and has a sandwich design. The outer ePTFE layer provides fixation of the outer stent and guarantees sealing properties. It also protects the inner ePTFE layer and prevents endoleaks. The inner PTFE layer provides a sealing of the aneurysm and the inner stent supplies fixation of the inner and outer ePTFE layer. Compared to other available bridging stent grafts, Bentley claims it has an up to 3.5 times higher radial force and is kink-resistant.
Gore has announced the US launch of the lower profile, large diameter Gore Viabahn endoprosthesis.
Gore previously received approval from the US Food and Drug Administration (FDA) for the enhanced Gore Viabahn endoprosthesis.
“With broad clinical indications for use and numerous product improvements, the Viabahn device continues to be a dependable choice that demonstrates positive results in patients with complex vascular disease,” comments Amit J Dwivedi, (University of Louisville, Louisville, USA), who has implanted the lower profile device in complex arterial anatomy. “Older patients with co-morbidities such as hypertension, diabetes, and obesity may benefit from a less invasive endoluminal approach versus surgical bypass. These latest enhancements, including a lower profile, provide physicians with additional options for treating these patients.”
This innovative Viabahn device design reduces the delivery profile for larger 9–13mm diameter stent grafts by up to 3Fr, enabling delivery through smaller sheaths. Smaller introducer sheaths have resulted in a lower risk of vascular access complications in select patient populations, a Gore press release states. Additionally, new radiopaque markers on the distal and proximal ends enhance visualisation under fluoroscopy, facilitating positioning and device delivery, as well as precise and predictable placement.
“In addition to the radiopaque markers that facilitate positioning and deployment, the new lower profile enables use of a smaller sheath, potentially reducing the risk of damage at the access site,” says Yevgeniy (Eugene) Rits (Wayne State University; Detroit Medical Center; Harper University Hospital, Detroit, USA). “Combined with the trackability and flexibility I have always trusted with Viabahn devices, this new lower profile offering will become very instrumental in my dialysis access practice.”
Currently, the Viabahn device is indicated for use in superficial femoral artery (SFA) lesions, iliac lesions, in-stent restenosis of SFA lesions, and in stenosis or thrombotic occlusion at the venous anastomosis of synthetic arteriovenous access grafts for haemodialysis.
Outcomes of the BIO4AMB trial demonstrated that ambulatory treatment with 4-French (4F) devices is a valid and safe option for endovascular treatment of lower extremity peripheral arterial disease (PAD), a Biotronik press release reports.
In addition, The 4F compatible products showed similar results to 6-French (6F) devices, with the added benefit of an eliminated need for a vascular closure device. These results were presented at the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).
The BIO4AMB multicentre, controlled trial compared the rate of access site complications and major adverse events in 4F versus 6F femoral access endovascular interventions. The full-cohort analysis of 766 patients showed no significant differences in safety and efficacy between the patient group treated with 6F devices and those treated with Biotronik’s 4F product portfolio.
“Compared to the already well-established 6F devices, 4F compatible devices were shown to be a valid alternative,” summarised co-principal investigator Marianne Brodmann (Medical University of Graz, Graz, Austria). The rate of freedom from access site complications was 97.2% in the 4F arm and 96.8% in the 6F arm (p=0.734).
Brodmann, who presented the data, highlighted a key difference: “Use of 4F sheaths creates 45% smaller puncture holes, which resulted in low rates of access site complications despite not needing vascular closure devices. This may offer a better potential for ambulatory treatment.”
The health economic evaluation of the BIO4AMB study, also presented at CIRSE, investigated the implications on safety, resource use and cost of lower-extremity peripheral treatment using 4F and 6F access in an ambulatory setting. In this analysis, the rate of vascular closure device use was 0% in the 4F arm versus 87.4% in the 6F arm (p<0.05).
“Depending on the country specific reimbursement situation, ambulatory treatment may offer a cost saving option compared to a stationary setting,” concluded co-principal investigator and presenter Jos van den Berg (Regional Hospital of Lugano, Lugano, Switzerland).
Two devices for creating minimally invasive dialysis access—the Ellipsys vascular access system (Avenu Medical) and the WavelinQ 4F system (BD)—demonstrated high rates of technical success and low rates of complications, according to a new study published in the Journal of Vascular and Interventional Radiology. In addition, both technologies enabled patients to start dialysis sooner compared to surgery, offering significant quality-of-life benefits.
For patients with end-stage renal disease (ESRD) who require haemodialysis, the preferred type of vascular access is an arteriovenous fistula (AVF)—a permanent connection between a vein and artery in the arm. Until recently, the only way to create an AVF was through a surgical procedure that subjects patients to discomfort, longer recovery times and delayed dialysis.
Both the Ellipsys and WavelinQ devices offer a nonsurgical alternative by using a minimally invasive approach to create a percutaneous arteriovenous fistula (pAVF). The new single-centre study, led by vascular surgeon Robert Shahverdyan (Vascular Access Center, Hamburg, Germany), compared the outcomes for 100 patients who underwent pAVF procedures (65 Ellipsys and 35 WavelinQ) from December 2017 to December 2019.
The Ellipsys system had a technical success rate of 100%, and only 27.7% of patients required secondary interventions following fistula creation. The WavelinQ system demonstrated similar outcomes, with a technical success rate of 97% and 26.5% of patients requiring secondary interventions. Overall, 79.5% of Ellipsys patients and 58% of WavelinQ patients were able to successfully begin dialysis with their fistula. At 12 months, 82% of Ellipsys fistulas were still functional, compared to 60% of WavelinQ fistulas.
“For every patient, my goal is to create the best possible dialysis access with the fewest possible interventions,” said Shahverdyan. “Our data show that with careful planning, both systems can safely and quickly create percutaneous fistulas with a high rate of success, though the Ellipsys system appears to create more durable access that is also easier to repair if that becomes necessary.”
Compared to surgical fistulas, both devices reduced the time to dialysis (cannulation). The mean time to cannulation for WavelinQ was 90 days, compared to 60 days with Ellipsys. In fact, 75% of Ellipsys fistulas were ready for cannulation at just four weeks, with a small number of patients ready for early cannulation within a few days of fistula creation, Shahverdyan notes.
“This study confirms other newly published data showing how much faster we can start using the Ellipsys percutaneous fistula for dialysis—a finding that has significant patient safety benefits,” said interventional radiologist Jeffrey Hull (Richmond Vascular Center, Richmond, USA). “The sooner a patient can start dialysis with their fistula, the sooner we can get them off such riskier dialysis access methods as central venous catheters, which are associated with much higher rates of infection and other complications.”
Hull is the lead author on a recent study of Ellipsys pAVF that reported an average time to dialysis of 66 days. Vascular surgeon Alexandros Mallios (Hôpital Paris Saint-Joseph, Paris, France), recently published data showing that patients were able to begin using their pAVF for dialysis an average of 4 weeks after creation, with six percent of fistulas becoming functional in as little as 2 weeks.
The studied technologies differ significantly in their design, pAVF creation technique and fistula location. The single-catheter Ellipsys system uses ultrasound guidance and thermal energy to create the fused and permanent connection between the perforating vein and the proximal radial artery; no radiation or contrast media are required. The WavelinQ device is a two-catheter system that uses radio-frequency energy and fluoroscopy to create an aligned slit fistula. Differences between the systems can affect patient eligibility for the procedures based on anatomic constraints.
“Based on our preoperative ultrasound evaluations, we found that 65% of patients were eligible for an Ellipsys pAVF, compared to just 27% with the WavelinQ system,” said Shahverdyan. “By knowing that more than twice as many patients will be able to undergo the procedure, Ellipsys makes it more feasible for a center to offer this endovascular approach to creating dialysis access.”
Cleared by the US Food and Drug Administration (FDA) in 2018 for patients with end-stage renal disease, Ellipsys is the first significant innovation in AVF creation in over 50 years. It transforms a complex surgery into a minimally invasive procedure that can be performed in a hospital outpatient setting, ambulatory surgery center or physician’s office. Since 2015, nearly 3,000 patients worldwide have undergone the Ellipsys procedure. Recently published long-term data show that 92% of Ellipsys fistulas are still functional after two years. The study also found high levels of patient satisfaction with the procedure.
Panagiotis M Kitrou and Nicholas Inston discuss the impact of the COVID-19 pandemic on vascular access services. Despite the disruption caused, they are optimistic that the pandemic should be viewed as a catalyst for change. It is time to “redesign and restructure” vascular access programmes, they tell Vascular News.
The COVID-19 pandemic has resulted in major disruption in the delivery of clinical services on a scale previously unseen. In many countries, rationing of facilities and severely restricted or zero access to operating theatres has been imposed. It has been estimated that 28.4 million surgical procedures have been cancelled globally, with the highest cancellation rates in benign disease.1 The crisis has affected different countries and even different regions of countries variably. In Asia, 47% of healthcare practices suspended elective vascular surgery completely and 23% scaled down activity.2 In the UK, it has been estimated that to clear the backlog of cancelled surgery at 20% extra activity will require 11 months, even if further surgeries are not factored in.
To manage constrained services, many societies issued prioritisation to allow rationing based on clinical risk, mainly based on estimated urgency and need for treatment. These have been classified as 1a. emergency <24 hours; 1b. urgent (up to 72 hours); 2. up to one month; 3. up to three months; and 4. over three months by the Royal Colleges in the UK,3 and by the Society for Vascular Surgery (SVS) as 1. postpone; 2a. consider postponing; 2b. postpone if possible; and 3. do not postpone.4
Provision of vascular access for dialysis “less than ideal” before pandemic
The impact of COVID-19 on dialysis access is not yet known, but it is predicted that the rates of definitive access have been severely affected. Prior to the pandemic, the provision of vascular access for dialysis was already identified as being less than ideal. In the USA, 80% of patients initiate dialyses on a central venous catheter (CVC)5 and international rates of definitive access are highly variable.6
Despite this, benefits of definitive vascular access and avoidance of CVCs are clearly demonstrated, particularly in the younger and less comorbid patients.7,8
The problems encountered during the first peak of the pandemic are likely to have resulted in many patients starting dialysis on a CVC. This is multifactorial. Patients with chronic kidney disease (CKD) stages 4 and 5 require access in preparation for dialysis. These patients who were classed as a vulnerable group have been advised to follow enforced shielding practices. As such, they neither fall into a high priority group for surgery or are advised to attend hospital appointments in person. Assessment for vascular access generally requires ultrasound mapping and this may have been avoided due to patient concerns and/or clinical policies to avoid virus exposure. For the same patients, pre-emptive living donor transplantation, which may have avoided the need for vascular access, may have been suspended.
In patients infected with COVID-19, the requirement for renal replacement therapy was high, particularly in those requiring intensive care. The impact of multiple vascular access attempts on these patients and long-term effects on renal function remain to be seen, but may add a further healthcare need.
For patients with existing access data, is not yet possible to assess whether COVID-19 infection had adverse outcomes. Anecdotally, claims have been made for prothrombotic tendencies, particularly in those severely affected, but data on fistula loss secondary to infection is not yet clear. Dysfunctional access may have been afforded higher priority and performing maintenance procedures may have avoided CVC insertions. It is unclear yet whether patients presented later during the pandemic due to shielding risks, or hospitals operated policies of inserting a CVC to reduce lengthy salvage procedures.
The consequences arising from increased CVC placement and reduced fistula creation and salvage will result in multiple issues. Repeated hospitalisation, bloodstream infections, catheter dysfunction, central venous stenosis, and occlusion are all a product of increased catheter use and as a consequence healthcare costs will increase.9 This significant economic and healthcare burden will not only start to show now, but as renal failure is a chronic disease will have significant effect on health economics in the long term. In addition, CVCs have a negative impact on the quality of life and longevity of haemodialysis patients and constitutes a major deviation from best practice guidelines and a serious setback in the standard of care previously delivered.10
“Robust plans” needed for predicted second wave
Whilst some countries are unfortunately currently dealing with the first wave, others are now preparing for a predicted second wave. The needs of CKD and dialysis patients require robust plans to optimise safe creation, maintenance, and salvage of definitive vascular access and avoidance of the use of CVCs.
These strategies may require local modifications. Ideally cold (green) sites should be used, although dialysis patients’ inability to isolate due to thrice weekly treatment may prohibit pure “clean” pathways. Risk assessments may need specific “renal pathways” to be developed rather than apply standard surgical risk stratification.
Where surgical services are overwhelmed or resources compromised, other strategies should be considered, particularly endovascular approaches to maintenance, salvage, and even creation using percutaneous devices. This may increase the availability of additional operators, (e.g. interventional nephrologists and interventional radiologists) where staff redeployment or sickness is a problem, and also allow procedures to be performed in alternative facilities, avoiding hot sites and potentially freeing up theatres.
In order to recover from the first wave of COVID-19 and prepare for further phases, the provision of the best dialysis access, including peritoneal dialysis, will require close working with the wider multidisciplinary team involved in assessment, creation, cannulation, surveillance, maintenance, and salvage of definitive access.
An opportunity for change in the interest of renal patients
To manage dialysis access appropriately during peaks of COVID-19 will require better identification of those at need with more timely assessment and creation of access.
Early identification of problematic access through skilled clinical examination, timely and appropriate referral for diagnostics, and treatment using optimal technologies and devices by those with expertise should be available. Follow-up and surveillance should be based around dialysis sessions and training of dialysis centre staff to cannulate, examine, and identify problems with liaison and accessibility to expertise made easily available.
The challenges of dialysis access may have been exacerbated by the pandemic, but all these requirements were present before. This is an opportunity for vascular access programmes to redesign and restructure, not only to deal with the pandemic, but to build better programmes suited to the needs of the large global population of renal patients.
Panagiotis M Kitrou is an interventional radiologist at Patras University Hospital, Patras, Greece.
Nicholas Inston is a consultant transplant and vascular access surgeon at the University Hospital Birmingham NHS Trust, Birmingham, UK.
References
Fertility in patients who have had uterine artery embolization (UAE) is still a “hot topic,” Jean-Pierre Pelage (University Hospital and Medical Center, Caen, France) told delegates attending the online meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual). “We have confusing data in the literature—we know fertility after UAE is possible, and that UAE is a valuable alternative to hysterectomy and multiple myomectomy in symptomatic patients, but the role of embolization in the specific subset of women trying to get pregnant remains controversial.”
While some studies have demonstrated a 100% pregnancy rate following UAE, Pelage warned his audience that every patient is different, as is every procedure; there may be technical differences in how an embolization is conducted at different centres, for example. There are some reports in the literature of complications specifically associated with fertility after UAE. In the EMMY trial, the level of follicle-stimulating hormone (FSH)—used as a measure of ovarian impact, with higher values typically seen in patients with a diminished ovarian reserve—was seen to increase after embolization. However, this trend was more strongly observed in women over 45 years of age, and in those with higher FSH levels at baseline.
Complications from UAE include non-target embolization, mainly due to uterine-to-ovarian artery anastomoses, and extensive myometrial and endometrial ischaemic damage, largely due to an aggressive embolization technique. The latter complication can result in hysterectomy, which Pelage said “is obviously a disaster for women trying to get pregnant.” There are also reports of chronic endometriosis, which can also negatively impact fertility.
“There are some studies reporting very low pregnancy rates, including our initial experience: in 66 women offered embolization as a last resort treatment, there is virtually 0% pregnancy,” Pelage commented. He went on to give several examples of studies from other centres that also reported low fertility rates post-embolization.
“All these studies are confusing,” he said, “including the only randomised controlled trial dedicated to fertility [from Michal Mara (General Faculty Hospital and First Medical Faculty of Charles University, Prague, Czech Republic) et al, published in Cardiovascular and Interventional Radiology in 2008]. The pregnancy rate was lower after embolization, and the final term pregnancy rate was also very low.”
However, he did give the CIRSE audience some good news as well, informing them that embolization is known to be effective in the long-term for the treatment of heavy menstrual bleeding and pressure symptoms, and that the procedure leads to fully infarcted fibroids. “We know that you can expect spectacular volume reduction both of fibroids and of the uterus, which is good news for pregnancy. Embolization is a good alternative to myomectomy, which is the reference treatment for pregnancy-seeking women.”
In addition, Pelage’s group reported encouraging hormonal function following UAE, with no side effects of embolization on the ovarian reserve. Some studies have reported high rates of pregnancy: 61% (14 of 23 women) in a paper from Kavous Firouznia (Tehran University of Medical Sciences, Tehran, Iran) and colleagues published in American Journal of Roentgenology in 2009, which also reported no significant complications post-procedurally; and 59.5% (44 of 74 women) in a paper from João Pisco (St Louis Hospital, Lisbon, Portugal) et al, published in Fertility and Sterility in 2011.
Detailing his own institution’s recent experience, Pelage told registrants: “[We had a] 56% pregnancy rate in better-selected women, so younger than in our first cohort.” The 16 women included in this more recent study had an average age of 35 years, and nine of the group were actively trying to conceive. One-year post-embolization, five of the women were pregnant. Most of these pregnancies were not associated with any complications by the time of delivery.
Citing the July 2020 New England Journal of Medicine (NEJM) paper from Isaac Manyonda (St George’s, University of London, London, UK) detailing the results of the FEMME trial, Pelage highlighted the team’s fertility results: “They reported a significant number of pregnancies after embolization, even higher than in the surgery [myomectomy] group. Since it was not the primary objective, I well understand that you cannot draw definitive conclusions based on this paper.”
Attempting to make sense of these myriad results for fertility outcomes following UAE, Pelage summarised: “Pregnancy results are very variable, ranging from 14–61% from one study to another. The same [is true] for the miscarriage rate, obviously with miscarriage being more common in older women.
“From the existing literature, there seems to be an interest on the hormonal function [elevated FSH levels is more frequent after UAE], there seems to be a higher rate of pregnancy after myomectomy compared to embolization, and the rate of miscarriage seems to be higher after embolization. But again, most cases are not treated in a randomised trial, and treated women are older or have more fertility-confounding factors when treated with embolization.”
These summations led him to the conclusion that, “Despite the encouraging results of recent publications, we should still consider embolization with caution in pregnancy-seeking women. In our centre, we always discuss as a group with the referring gynaecologist to decide whether we should offer embolization or myomectomy, and we know that prospective randomised trials are very difficult to conduct in this group of women, especially in 2020, where women are well-aware of the potential interest of embolization as an alternative to surgery.”
Irreversible electroporation (IRE) significantly induces a window of reduced immune suppression two weeks post treatment, allowing the activation of effector T cells that seem to be correlated with improved survival, according to preliminary flow cytometry results of the CROSSFIRE trial (NCT02791503 on clinicaltrials.gov). Speaking during the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual), Bart Geboers (Amsterdam UMC, Amsterdam, The Netherlands) described how his team investigated the immune modulatory effects of IRE and MR-guided stereotactic ablative body radiotherapy (SABR) in patients with locally advanced pancreatic cancer.
Pancreatic cancer is one of the most aggressive cancers, Geboers informed the CIRSE audience, with a five-year overall survival of less than 10%. Thirty percent of all patients present with locally advanced disease, and are not amenable for surgical resection. The median overall survival for patients with locally advanced pancreatic cancer is approximately 12–14 months. “The problem with pancreatic cancer is that it is barely immunogenic, and the tumour cells can escape the immune system,” Geboers explained. “This might explain the disease aggressiveness.”
Describing the pathophysiology of the cancer, he said the low immunogenicity is “probably two-fold”: the cancer suppresses the tumour microenvironment, and is associated with a lack of spontaneous apoptosis.
In terms of suppressing its microenvironment, the tumour releases suppressive cytokines that induce activation and proliferation of specific T cell subsets that are immunosuppressive—regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). In turn, these reduce the activation and proliferation of effector T cells, including Helper T cells (CD4) and cytotoxic T cells (CD8), thereby providing the tumour with a “T cell tolerance”.
The second problem is the rarity of spontaneous tumour cell apoptosis. This means no epitopes are released that can be taken up by dendritic cells and used by the immune system to develop an adaptive response in the lymph nodes.
Altering the immune balance of the tumour microenvironment
Overcoming tumour-induced immune suppression is therefore difficult. Geboers and colleagues hypothesised that ablation can alter the immune balance, changing the microenvironment from an immunosuppressive one to a more immunopermissive one. “We know that ablation results in a reduction in the tumour mass, and so a reduction in suppressive cytokines. This will lead to a reduction in T cell tolerance, and allow the development of effector T cells,” he explained. In addition, ablation induces apoptosis and necrosis, meaning there will be a release of immunogenic epitopes that can be taken up by antigen-presenting cells. Furthermore, “IRE has the advancement of being vessel sparing,” Geboers said, so antigen-presenting cells can transport epitopic antibodies to lymph nodes, where an adaptive immune response can occur.
To test this thinking, the investigators conducted an Immunological side study of the CROSSFIRE trial, where pancreatic cancer patients were prospectively enrolled between January 2016 and February 2020. Patients with locally advanced pancreatic cancer were pre-treated with FOLFIRINOX, before being randomised between IRE or SABR.
Tumour microenvironment shifts to become more immunopermissive two weeks after IRE, but this is lost by three months post-IRE
In order to assess the immune response, Geboers and colleagues took a venous blood sample from each patient before IRE or SABR, two weeks after treatment (to evaluate the immediate response), and three months post-treatment (to evaluate the durable immune response). Flow cytometry analysis was used to detect the type, frequency, and activation status of circulating immune cells.
A T cell analysis of 36 patients (19 treated with IRE, 17 with SABR) revealed that, two weeks after IRE, there was a significant downregulation of the regulatory T cells in the peripheral blood flow, as predicted by Geboers and colleagues. This downregulation returned to baseline three months after IRE. There was a trend for down regulation of the regulatory T cells three months after SABR, though this was not significant.
The investigators next looked at checkpoint expression of CD4 and CD8 T cells (the effector or helper T cells that were suppressed by the tumour’s activities). Two weeks after IRE, there was a significant upregulation of PD1 on the CD4 T cells. All the other checkpoints remained low. None of the checkpoints were significantly upregulated in the SABR group at any time point following ablation. “When looking at the activation status of the CD4 and CD8 T cells, we found that Ki67, which is a marker for T cell activation, was significantly upregulated at two weeks after SABR, in both CD4 and CD8 T cells, but was only significantly upregulated on the CD8 T cells two weeks after IRE ablation,” Geboers shared.
A linear regression model demonstrated that an increase in PD 1, on both CD 4 and CD8 T cells two weeks after IRE, was significantly associated with improved overall survival. No significant correlation was seen between PD 1 upregulation and overall survival in the SABR group.
“We found a significant downregulation of regulatory T cells two weeks after IRE that was simultaneous with a PD 1 upregulation on CD 4 T cells,” Geboers summarised. “The fact that the expression of the other checkpoints remained low argues against T cell exhaustion, but rather indicates that we are looking at a real effector T cell activation that might be amenable for PD 1 blockade with checkpoint inhibitory drugs.”
The CIRSE audience were left with this promising take-home message: transient PD 1 T cell upregulation combined with simultaneous regulatory T cell decrease after IRE is consistent with previously described systemic immune stimulatory effects of IRE, and supports combination with pharmacologic PD 1 checkpoint inhibition.
“These findings warrant further studies, for which we designed the PANFIRE III trial,” Geboers told delegates (NCT04612530 on clinicaltrials.gov). This will be a Phase I trial in which 18 patients with oligometastatic pancreatic cancer will be included. The study has three arms: the first six patients will be treated with Nivolumab (a PD 1 blockade; this is the control); the second six patients will be treated with IRE ablation of the primary tumour followed by Nivolumab; the final six patients will be treated with TLR-9 ligand intra-tumoural injection, followed by incomplete IRE ablation of the primary tumour and Nivolumab.
Concept Medical has announced the enrolment of the first patient in the FUTURE SFA (Randomised controlled trial of first sirolimus coated balloon versus standard balloon angioplasty in the Treatment of superficial femoral artery and popliteal artery disease) study.
The index patient was successfully enrolled on 12 September in Singapore.
FUTURE SFA is a randomised, double blind, placebo-controlled, multicentre trial to determine the effectiveness of the MagicTouch PTA sirolimus drug-coated balloon (DCB) versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal arterial disease.
Sirolimus-coated balloons are considered to be the next new generation of DCBs and the novel MagicTouch PTA sirolimus-coated balloon (SCB), has emerged as one of the most promising transcatheter technologies in preventing restenosis for diseased arteries.
The principal investigator of FUTURE SFA is Edward Choke (Sengkang General Hospital, Singapore), who comments: “I am inspired by the bold, imaginative, and futuristic concepts presented by the Nanolute technology of the MagicTouch PTA sirolimus-coated balloon. In contrast to other contemporary technologies, MagicTouch PTA offers a solution which optimises both the deliverability and the absorption of sirolimus into the vessel wall.”
He adds: “Initial experience with the XTOSI first in man study suggested that MagicTouch PTA can provide an effective way of revascularisation for PAD patients, by keeping the vessels open longer and reducing the need of repeated angioplasty procedures. I look forward to the FUTURE SFA randomised controlled trial, which will test whether the Magic Touch PTA sirolimus-coated balloon can improve the patencies of femoral and popliteal arteries in PAD patients. We hope to establish whether SCB will emerge as the new standard of care which will impact the way we treat PAD.”
The trial will enrol 153 patients with Rutherford class 3 to 6 PAD. These subjects will be randomised in 2:1 fashion to receive either Magic Touch PTA or standard balloon angioplasty.
Primary outcome will be primary patency at six months, defined as duplex peak systolic velocity ratio (PSVR) of 2.4 or less.
The trial is designed to follow a rigorous blinding protocol in order to minimise bias. Patients, care providers, investigators and outcome assessors, including vascular technologists performing the duplex ultrasound, will be blinded to the treatment allocations. The patients will be followed up for two years.
In this supplement:
Symptomatic peripheral arterial disease (PAD) patients undergoing recurrent lower extremity revascularisation have higher rates of ischaemic events, particularly acute limb ischaemia, than those patients who are undergoing their first peripheral revascularisation. This is the conclusion presented by Marc Bonaca (University of Colorado, Aurora, USA) at the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual). Bonaca and colleagues conducted a subgroup analysis from the VOYAGER PAD trial, which examined the efficacy and safety of Rivaroxaban in patients with PAD undergoing recurrent lower extremity revascularisation.
“We know from trials of patients with PAD that a history of a prior peripheral revascularisation is associated with a very high risk of acute limb ischaemia, even long-term years after the intervention was done,” Bonaca told online attendees. “More recent data from the landmark COMPASS trial shows that, in patients with chronic PAD, those who had a prior history of revascularisation are at major heightened risk of major adverse limb events.”
VOYAGER PAD is a trial of 6,564 patients with symptomatic lower extremity PAD undergoing peripheral revascularisation. Patients were randomised 1:1 in a double blind fashion to either the Rivaroxaban group, where they received 2.5mg of the drug twice daily, or a placebo group. The primary efficacy endpoint was a five-point composite of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic stroke, or cardiovascular death. The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.
In an assessment of the primary efficacy endpoint, the rivaroxaban group performed better than the placebo group, with fewer incidences of the five major complications included in the composite measurement. “In spite of best medical therapy in this population [those patients treated with a placebo], the event rate was nearly 20%, which was extremely high—nearly one in five had an event,” Bonaca said. A Kaplan-Meier curve plotting cumulative incidence of the composite measurement of major adverse events against time since randomisation revealed that, at three-years post-treatment initiation, the event rate was 19.9% in the placebo group, and 17.3% in the rivaroxaban arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.76–0.96; p=0.009).
“Rivaroxaban risk-benefit was apparent early, and continued over time,” Bonaca commented, “with an absolute risk reduction of 2.6% at three years, and a number needed to treat of just 39.”
Subhead
Against this backdrop of successful rivaroxaban use in the main VOYAGER PAD trial, Bonaca and colleagues conducted a subanalysis investigating symptomatic PAD patients undergoing recurrent lower extremity revascularisation versus those undergoing their first revascularisation. They hypothesised that repeat revascularisation patients would have a higher rate of acute limb ischaemia, and would derive “even greater benefits with a rivaroxaban plus aspirin strategy versus aspirin alone”.
The presence of known prior revascularisation was reported by investigators at baseline, and was defined as any history of endovascular, hybrid, or surgical lower extremity revascularisation. The primary outcome was the same composite as in the VOYAGER PAD study, and a COX model with interaction terms was used to assess for heterogeneity of efficacy and safety of rivaroxaban by prior lower extremity revascularisation status.
From a comorbidity perspective, the prior revascularisation group had a higher risk profile, Bonaca shared, with more hypertension, diabetes, and hyperlipidaemia. PAD characteristics were similar between the two cohorts, with the prior revascularisation group having a slightly lower risk: “they were more likely to be treated with an endovascular revascularisation, they had less frequently presented with acute limb ischaemia versus claudication, and the [average] ankle-brachial index was a bit higher. […] It is worth noting that they were very well-treated.”
In the placebo cohort, the cumulative event rate for those with no prior lower extremity revascularisation was 17.7%—“very high,” Bonaca pointed out, “even in this very well-treated population.” Nevertheless, those patients who had had a prior revascularisation had a higher cumulative event rate of 23.8%, representing a 6.1% increase in risk.
“When we look at the efficacy of Rivaroxaban, stratified in these two groups [prior revascularisation and no prior revascularisation], we see the benefit is there for both groups,” Bonaca explained.
In the Rivaroxaban cohort, those with no prior revascularisation had a cumulative event rate of 16.9%, while those who had undergone an earlier revascularisation had a cumulative event rate of 18.1%. The impact of prior revascularisation was therefore less in the Rivaroxaban cohort than in the placebo cohort.
Comparing the placebo and rivaroxaban cohorts (Figure 1), Bonaca told delegates: “The benefit [of Rivaroxaban] appears even greater in those who had a prior history of revascularisation, with a HR of 0.73, and a trend towards heterogeneity, meaning there may be an even greater benefit in this high-risk group.”
Wondering what could be driving this difference, Bonaca and colleagues looked at the limb outcomes of acute limb ischaemia and vascular amputation in patients treated with Rivaroxaban with and without prior lower extremity revascularisation. In placebo patients with no prior revascularisation, rates of acute limb ischaemia and vascular amputation were lower at three-years post-randomisation than they were in the group of patients who had had previous revascularisation: 6% versus 10.8%, and 3.4% versus 4.5%, respectively.
As Bonaca put it: “Patients in the prior revascularisation group have a very high risk of acute limb ischaemia, almost 11%, and that is driving this risk-profile, and that benefit for acute limb ischaemia [with Rivaroxaban] is even greater in patients with a prior history of revascularisation. This does look like our hypothesis—that repeat revascularisation patients are at higher risk and would derive a greater benefit of Rivaroxaban—was met in this analysis.
“Rivaroxaban plus aspirin versus aspirin alone reduces irreversible harm events, so the heart, limb, and brain in patients that are undergoing revascularisation, but in this subgroup with prior revascularisation, there is a particularly robust benefit, and really notably in acute limb ischaemia. The current analysis demonstrates that within this population, those with multiple revascularisations are at higher risk than those who have undergone a first revascularisation only, and may derive particularly robust benefit from Rivaroxaban plus aspirin versus aspirin alone. These observations further demonstrate the heterogeneity of risk in the PAD population, and may assist in clinical risk stratification and therapeutic decision-making.”
Stefan Müller-Hülsbeck (Ev Luth Diakonissenanstalt zu Flensburg, Flensburg, Germany) presented attendees of the online meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual) with an update from the IMPERIAL head-to-head randomised trial comparing the Eluvia drug-eluting stent (DES; Boston Scientific) with the Zilver PTX DES (Cook Medical) for the treatment of femoropopliteal artery lesions. reimbursement
“Through 24 months, there was a significantly lower clinically-driven target lesion revascularisation (CD-TLR) rate for the Eluvia DES than for the Zilver PTX [12.7% vs. 20.1%; p=0.0495],” Müller-Hülsbeck told registrants. An “excellent” primary patency rate was sustained with the Eluvia DES (83% from Kaplan-Meier estimates), and both study devices showed a low mortality rate at 24 months: 7.1% for Eluvia, and 8.3% for Zilver PTX.
In addition, Müller-Hülsbeck reported a significant improvement in mobility and pain/discomfort dimensions of health-related quality of life, sustained over 24 months in both treatment arms.
Cost-effectiveness analysis of the US Medicare system and the German health insurance system showed cost savings; on average, US$1,300 per patient was saved when patients were treated with the Eluvia device in the USA, Müller-Hülsbeck said. “This shows, once again, that when we chose Eluvia, we might achieve a high value when treating our patients with this kind of drug-eluting technology, due to the higher TLR rates we might achieve.”
Moderator Fabrizio Fanelli (Careggi University Hospital, Florence, Italy) stated: “I am very curious about how, still after two years, there is a pretty important gap between the ELUVIA DES and the Zilver PTX”. He queried if Müller-Hülsbeck thought this gap would grow larger in the future, or if he believed that outcomes from using these two devices would become more similar in time.
“That is an excellent question, and it is hard to answer!” Müller-Hülsbeck responded. “Probably the results from [using] both stents could differ, but I think there is also a high probability that the curves in terms of target lesion revascularisation might come closer, so we have to see what will happen in five years.
“The five-year data Michael [Dake] presented [during the same FIRST@CIRSE session] with the Zilver PTX are really outstanding. My personal hope for the patient is that, with Eluvia, we might achieve equal or even slightly better data, but this is just a hope. We will have to see what will happen. Once again, I think that with both technologies, the Eluvia stent and the Zilver PTX, we have options to treat our patients adequately, to provide them with drug-eluting technology.”
Fanelli was in agreement, adding: “This is something everyone is watching with a lot of interest.”
Turning tack to discuss the cost-effective analysis, Fanelli next asked if Müller-Hülsbeck thought this could “push the use of Eluvia, or more generally drug-eluting stents” in the future.
“I think yes,” Müller-Hülsbeck replied, “especially in the USA, because there are some major differences. In Germany, I do not know exactly, because the difference there is slightly lower, but it is my hope—as we want to avoid patients coming back for early target lesion revascularisation—that this kind of technology becomes more accepted by insurance companies for reimbursement. I am mentioning that because, at the moment, especially in Germany, we do not receive any reimbursement if we use drug-eluting technology, either the Zilver PTX or the Eluvia stent.”
An ad hoc, two-year analysis of the EffPac study found no signal of increased risk of long-term mortality, nor any adverse events, within two years of drug-coated balloon (DCB) angioplasty using a Luminor-35 device (iVascular). This was the conclusion presented by Ulf Teichgräber (University Hospital Jena, Jean, Germany) at the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).
Teichgräber is the principal investigator of the EffPac trial, a prospective, randomised controlled trial initiated by the federal authorities in Germany, and conducted at eleven study sites, that compares the paclitaxel-coated Luminor balloon with plain balloon angioplasty in the femoropopliteal artery segment of patients with peripheral arterial disease (PAD).
The primary efficacy endpoint of this study was late lumen loss at six months; secondary endpoints included primary patency, freedom from target lesion revascularisation (TLR), Rutherford category, ankle-brachial index, and quality of life score. All-cause mortality and target limb amputation were assessed as the primary safety endpoints.
Just published in Radiology, Teichgräber described to the CIRSE audience how he and his team conducted an ad hoc, two-year review of mortality and morbidity following DCB angioplasty in EffPac patients. The two-year follow-up of the EffPac trial was in fact completed in February 2019, but another study cast its shadow over the results. Konstantinos Katsanos (Patras, Greece) et al published a meta-analysis in the Journal of the American Heart Association (JAHA) in December 2018 that found an increased association between late mortality risk and paclitaxel use in the femoropopliteal arteries. “Numerous public debates about the safety of paclitaxel-coated balloons were triggered”, Teichgräber recalled.
This led the Federal Institute for Drug and Medical Devices in Germany (in German: Bundesinstitut für Arzneimittel und Medizinprodukte; BfArM) to request a formal hearing on mortality of all ongoing studies concerning paclitaxel use in the peripheral arteries.
While the EffPac trial could not confirm a correlation between paclitaxel application and all-cause mortality—there was one death in the DCB arm, out of a total of 82 patients, and seven out of 85 in the plain angioplasty arm—a lot of patients were lost to follow-up.
In total, the EffPac trial randomised 171 patients into two arms: those treated with the Luminor DCB (85 patients), and those who received plain angioplasty (86 patients). At 24 months, 60 patients were left in the DCB group, and 56 in the plain angioplasty group, due to a lack of follow-up in nearly one third of randomised patients. This represented a discontinuation of 25 patients in the DCB arm, and 30 patients in the plain angioplasty arm.
Under entreaty from the BfArM, Teichgräber set out to find those EffPac participants lost to follow-up in order to gain further information on two-year mortality rates with paclitaxel devices.
“Paclitaxel showed a very low [mortality] risk ratio of only 0.15 compared to other trials, meaning there is no correlation of all-cause mortality associated with Luminor balloons,” Teichgräber inferred from their results. “Another interesting aspect [to look at] is cause of death,” he said. “The only case of death in the DCB group was due to multiple comorbidities, which were hardly associated with the application of paclitaxel.” Patients in the plain balloon angioplasty cohort died of heart failure, sepsis, cholangiocarcinoma, respiratory failure, and suicide. “A correlation between paclitaxel and cause of death is [therefore] quite unlikely,” Teichgräber concluded.
The total number of adverse events per patient was higher in the DCB group than in the plain balloon angioplasty group, though this difference was not statistically significant (3.2±2.8 vs. 2.9±2.6; p=0.59). The proportion of patients who experienced any adverse event was slightly higher in the plain angioplasty arm of the study, but again, this difference was not statistically significant (88.5% vs. 86.5%, respectively; p=0.81). “So there is no real difference in adverse events between both groups,” Teichgräber summarised. Except for serious malignancies, there were no significant between-group differences in the incidence of adverse event types.
Summing up, Teichgräber said: “I believe that such an ad hoc analysis on discontinued patients in randomised controlled trials gives us a full picture on all-cause mortality for our follow-up patients.
“As we do not have a class effect between different DCB products, with our ad hoc analysis we can only give information on Luminor balloons, and their coating technology. Therefore, it is important that other trials, with other DCB products, go the same way as we did with EffPac, and assess what happened to their lack-of-follow-up patients, and [see] if they could show equivalent results of all-cause mortality in their full cohort.”
“The SAVER registry reinforces the safety and effectiveness profile for the Stellarex drug-coated balloon (DCB; Philips) in a real-world patient population,” Konstantinos Stavroulakis (St Franziskus Hospital–Vascular Surgery, Munich, Germany) told the live, online audience during the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).
“These real-world registry data provide important outcome information for healthcare providers for the debate on the safety of drug-eluting technology,” he opined.
The Stellarex DCB is a low dose (2µg/mm2) paclitaxel device, with proven effective drug tissue transfer and residency. Compared to competitors, it has limited drug loss, “a very important feature”, in Stavroulakis words.
The SAVER registry
SAVER stands for the Stellarex Vascular e-Registry, a multicentre, European registry with external monitoring and clinical event committee adjudication. Patients are followed up through to three years, and experience a 12-month visit. The aim of the SAVER registry is to assess the safety and efficacy of Stellarex DCB use in the superficial femoral, popliteal, and/or infra-popliteal arteries in a broad, real-world patient population.
The registry is split into two patient cohorts: claudicants, and chronic limb-threatening ischaemia (CLTI) patients.
In the claudicant group—where patients are classified as Rutherford category 2–3—the primary safety endpoints are freedom from 30-day device- and procedure-related death, and freedom from 12-month target limb major amputation and clinically-driven target lesion revascularisation (CD-TLR). The efficacy endpoint for claudicants is freedom from 12-month CD-TLR.
In the CLTI group—where patients are classified as Rutherford category 4–5—the primary safety endpoints are freedom from composite major adverse limb events and perioperative death through 30 days. The efficacy endpoint for CLTI patients is freedom from six-month CD-TLR.
Registry results “robustly” demonstrate safety of the Stellarex DCB
An interim analysis of the first 1,000 claudicant patients revealed a procedural success of 97.9%, and lesion success in 98.5%. “Bailout stenting was required in 24% of the patients, showing that we can treat the majority of these PAD patients effectively, […] with no additional permanent scaffold,” Stavroulakis said.
Regarding complications, there was a 0% periprocedural mortality, and “just” 0.6% significant distal embolization. Target vessel thrombosis was seen in 0.2% of the patient cohort, and emergent surgical revascularisation in 0.1%.
The majority of patients (87.4%; 892 of 1,021) reached the primary safety endpoint, with freedom from device- and procedure-related death through 30 days post-procedure, and freedom from target limb major amputation and CD-TLR through 12 months post-procedure. Giving additional outcomes at one-year, Stavroulakis told the CIRSE audience that all-cause death was 3.2%, and amputation rate was 2.7%, with the major amputation rate 0.8%—“acceptable” outcomes in this real-world population.
Regarding the efficacy endpoint, 87.7% (895 of 1,021) patients had freedom from CD-TLR at 12-months post-procedure, a “robust” finding, according to Stavroulakis. Kaplan-Meier evaluation demonstrated 98.7% freedom from CD-TLR at 30 days, 95% at 180 days, and 88.6% at 365 days.
Recounting the additional secondary outcomes, Stavroulakis told registrants that the majority of patients (87.6%) improved by at least one Rutherford class; 8.9% had no change in Rutherford category, and 3.5% worsened from baseline. There was a significant improvement in walking capacity at 12 months, as measured via the six-minute walk test: at baseline, the mean distance a patient could walk during the test was 52±24.4m; by 12 months, this had risen to 169±123.7m. Quality of life scores and the ankle-brachial index also improved from baseline to 12 months.
These results led Stavroulakis to conclude that there was a low rate of procedural complications when the Stellarex DCB was used in claudicants, and the device had a high safety profile.
Against the backdrop of increasing end-stage renal disease (ESRD) prevalence in the USA, Bart Dolmatch (Portola Valley, USA) presented the 24-month results of the prospective, randomised controlled AVeNEW study at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2020 Symposium (12–15 September, virtual).
This is the first level one trial dedicated solely to assess the safety and efficacy of the Covera (BD) covered stent designed to treat stenosis in the arteriovenous fistula (AVF) access circuit. The two-year results showed statistically superior target lesion primary patency and AVF circuit primary patency with the use of the covered stent compared with angioplasty alone.
Renal replacement is expensive, online attendees of the FIRST@CIRSE session heard, and largely achieved with haemodialysis using an arteriovenous AVF. However, Dolmatch explained how AVF stenosis interferes with efficient haemodialysis, leading physicians to try and find a treatment modality that reduces its occurrence.
“Angioplasty has been our go to for many years,” he said, “but we know that the durability after angioplasty is OK, but the question is, can we improve upon angioplasty durability when treating fistula stenosis?”
Enter the AVeNEW study, a prospective, multicentre, multinational clinical trial of 280 patients with stenotic AVFs and clinical AVF dysfunction. Patients were randomised 1:1 to either the percutaneous transluminal angioplasty (PTA) group, or the angioplasty with Covera covered stent group.
The study met both its primary safety and efficacy endpoints: freedom from a primary safety event out to 30 days, and target lesion primary patency at six months, respectively. There was no significant difference in freedom from a primary safety event out to 30 days between the covered stent cohort and the angioplasty alone cohort (95% and 96.4%, respectively; p=0.002). Target lesion primary patency at six months was “superb” and “statistically superior” in the covered stent group compared to angioplasty (78.7% and 47.9%, respectively; p<0.001).
A 12-month exploratory subgroup analysis of target lesion primary patency revealed that, regardless of certain lesion characteristics, “a preferential, better outcome using the covered stent compared to angioplasty alone. A Kaplan-Meier plot showed that the freedom from loss of target lesion primary patency was superior shortly after implantation of the covered stent compared to angioplasty, and remained statistically better at all time points, with more than a 30% better patency at 24 months.
Secondary outcomes were also better for the covered stent cohort, Dolmatch related. The index of patency function and mean access circuit reinterventions were both superior in the covered stent group, while secondary patency was the same in both groups (91.4%). “Interestingly, all-cause death was lower in the covered stent group than the angioplasty group,” Dolmatch continued. “I am not sure if this is statistically significant, we have not done that analysis yet, but it is a curious finding.”
Looking specifically at freedom from loss of access circuit primary patency, he commented: “Access circuit patency for an AVF drops off regardless of which group you are in, and yet, at 24 months, there is a statistically superior outcome of circuit patency for the covered stent group compared to the angioplasty group [p=0.02].”
The AVeNEW trial is still ongoing, with one more year of data collection and analysis ahead, to bring its total duration to three years.
“Please feel free to utilise this in your practice,” Michael Dake (University of Arizona Health Sciences, Tucson, USA) urged on the first day of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2020 Symposium (12–15 September, virtual). Speaking during a FIRST@CIRSE session, he presented a new, interactive, web-based tool built to predict patients’ freedom from target lesion revascularisation (TLR) following treatment with the Zilver PTX (Cook Medical) drug-eluting stent (DES).
Dake and colleagues used patient and lesion factors from five global clinical studies from Cook Medical to develop a prediction model for freedom from target lesion revascularisation (TLR) following use of Zilver PTX. These clinical studies studied both pre-market and post-market outcomes with the Zilver PTX stent in patients with femoropopliteal disease. In total, they collated data came from 2,374 patients, and included 15 risk factors in their creation of the model.
“It is note-worthy that over 50% of the patients included in the model had over five-year follow-up. In fact, this is the first prediction model to estimate the impact of patient and lesion characteristics on freedom from TLR through five years for patients with PAD,” Dake enthused. “Based on unique patient profiles, the model provides expected patient outcomes following treatment with the Zilver PTX DES, and may assist in defining algorithms for patients as the value of population management is increasingly recognised.”
Turning to the freedom from TLR results, Dake informed the CIRSE audience that 94% of the complete dataset (2,227 cases, with a median follow-up time of two years) was used to generate the model. Freedom from TLR was 90.5% at one-year, and 75.2% at five years.
Describing the model more closely, Dake next related the 15 risk factors that were considered when the tool was under construction: sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, dexamethasone, popliteal involvement, total occlusion, calcification, prior interventions, and the number of patient runoff vessels. “Most all of these have been in the past implicated as being high-risk for TLR in studies performed over the last two decades,” Dake disclosed.
He continued: “Risk factors common in PAD patients collectively contributed to overall prognosis. As expected, chronic limb-threatening ischaemia (CLTI), lesion length, and total occlusion have a significant impact on TLR. Other factors, such as diabetes and calcification, do not have a significant impact on TLR.”
He then talked through three example patient profiles to illustrate how listening physicians could use this predictive model in their own practices. The risk factors any given patient may have are fed into the model, which then churns out an estimation of the risk that patient has of maintaining freedom from TLR out to five years, with a standard error given, when treated with the Zilver PTX. These results also translate into a freedom from TLR Kaplan-Meier curve. The physician can then make an informed treatment decision based on individual risk factors.
The baseline data
Teasing apart the larger dataset to examine trends in baseline patient demographics, Dake said: “Looking a bit closer at some of these individual patient demographics, and how they are distributed within the various trials included in the analysis, you can see some differences. Of note, in the Japan post-market study, [there is] a very high frequency of renal disease, and a higher frequency of CLTI. In terms of diabetes, there was a high frequency in all studies, approaching 50%.”
Appraising the baseline lesion characteristics, Dake informed viewers that 42% of patients had total occlusions, and that there was an increased number of prior interventions in both the single-arm study and the Japan post-market study, as both these trials included in-stent restenosis. “Patients with in-stent restenosis were not allowed to enter the other trials,” he explained.
“This is the first step”
Praising Dake for these results, moderator Stefan Müller-Hülsbeck (Diako Hospital, Flensburg, Germany) commented: “I think you have shown once again that paclitaxel is probably safe, and we meet a new level of security when using these kinds of devices, especially when using this kind of predictability model.” He then asked Dake if the model is already in use, and if so, if he was using it for his patients during his daily practice.
“This is actually the first debut of this model and this website,” Dake responded. “The manuscript will be published in Cardiovascular and Interventional Radiology (CVIR).” He encouraged CIRSE attendees to visit the site themselves and “really get a sense of getting comfortable with how individual risk factors can affect TLR going out through five years”.
Referring to his presentation as the launch of this predictive model, Dake closed the discussion by postulating: “Maybe other device manufacturers will look at this as a model and adopt predictive models as a way to counsel patients and their families in the clinic regarding their individual risk factors, modification of those risk factors, how we can really just predict and have them anticipate what results might be with individual different devices. I think this is the first step. I think this is an outcropping of what we have seen as a result of the Katsanos paper [Konstantinos Katsanos (Patras, Greece) et al published a paper in late 2018 that suggested the existence of an increased mortality risk with paclitaxel devices used in the peripheral arteries]. The next level now is [to evaluate the] efficacy in terms of using paclitaxel in individual patients.”
Biotronik today announced European market release of the Passeo-35 Xeo percutaneous transluminal angioplasty (PTA) balloon catheter. A company press release states that, compared to other available PTA balloons, the device offers physicians improved crossability, excellent trackability, and pushability in a wide range of sizes.
“The new Passeo-35 Xeo balloon handled impressively well, crossing easily even in an occlusive lesion,” comments Gerd Grözinger (University Hospital Tübingen, Tübingen, Germany), after performing the first-in-human procedure with the balloon. “The deflation time was also very fast compared to other balloons, which can save valuable procedure time.”
To aid in challenging lesion crossing, the Passeo-35 Xeo catheter offers a low entry profile, smooth tip taper, and up to 19.5% more pushability compared to competitors, facilitating improved catheter navigation in the peripheral vasculature. Catering to a full range of lesion sizes, the device is available in balloon diameters from 3–12mm and lengths of up to 250mm, with usable catheter lengths of 90, 130 and 170cm. Additionally, the Passeo-35 Xeo catheter is fully 5F compatible for balloon sizes up to 7mm in diameter and 250mm in length.
The Passeo-35 Xeo balloon is indicated to dilate stenosis in the iliac, femoral, popliteal and infrapopliteal arteries and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulae. It is also recommended for post-dilatation of balloon-expandable and self-expanding stents in the peripheral vasculature. Passeo-35 Xeo is the platform for Biotronik’s recently released Dynetic-35 balloon-expandable cobalt chromium stent system.
Uterine artery embolization (UAE) preserved fertility in “at least 75% of patients with acquired uterine arteriovenous malformations,” according to a recent single centre study presented at the virtual 2020 Global Embolization and Cancer Symposium Technologies (GEST) meeting (4–6 September). Dmitry Akinfiev (National Medical Research Center for Obstetrics, Gynecology and Perinatology, Kulakov, Russia) presented the clinical and reproductive findings of his research group to the live, global audience.
“In our work, the clinical effectiveness of UAE in acquired uterine arteriovenous malformations is 86.2%,” he shared.
Akinfiev and his team conducted a retrospective, single centre study involving 29 patients, with a mean age of 29.1 years—“rather low”, in the presenter’s words, with the oldest patient included in the study being 43 years old. “All [patients included in the study] were fertile,” Akinfiev informed delegates. The study investigators performed 34 UAE procedures, and the mean patient follow-up was 2.5 years (range: one to six years).
Uterine arteriovenous malformations are rare, the GEST audience were told. “Speaking of risk factors for acquired uterine arteriovenous malformations,” Akinfiev said, “in 80% of cases, the malformation was associated with curettage [19 patients had curettage following a miscarriage; four patients had a normal pregnancy and underwent curettage; one patient had a diagnostic curettage and no pregnancy]. Also, we had one patient with arteriovenous malformation after vacuum aspiration [following a normal pregnancy].” A further two patients developed uterine arteriovenous malformations due to gestational trophoblastic disease, and two patients acquired malformations for unknown reasons.
The team from Russia used irregular uterine bleeding as the primary indication for embolization. Eight patients (27%) needed a blood transfusion prior to UAE, and 10 procedures of 34 (29%) were emergency UAEs.
All patients underwent ultrasound and computed tomography (CT)-angiography before and after the procedure. “Those were our main diagnostic instruments,” Akinfiev divulged. “Importantly, we performed CT-angio from the diaphragm to the bottom of [the] pelvis.”
Detailing the procedures themselves, Akinfiev told the GEST attendees that 10 of the 34 procedures were expanded by embolizing additional arteries: branches of the internal iliacs, ovarian arteries, and superior mesenteric artery branches. Twenty-seven (80%) of the procedures were performed via the radial approach, and embolizations were performed with gelfoam and non-spherical polyvinyl acetate (PVA) particles under 500µm. “I prefer to use gelfoam in cubes,” Akinfiev opined.
The evaluation parameters for the study were the elimination of abnormal uterine bleeding, and the absence or significant reduction of arteriovenous shunting on CT-angio.
Of the 29 patients, 25 (86%) experienced clinical success after one procedure. Of the four who underwent a second procedure, the clinical success rate was 75%, with one patient having to have a third embolization. This third UAE was a clinical success.
There was a significant correlation between the clinical findings and the diagnostic findings, as presented on CT-angio. Twenty-seven of the 34 procedures were both clinically successful, and diagnostic imaging revealed a reduction or absence of arteriovenous shunting following UAE. In two cases, the interventionalists reported a clinical success, but diagnostic imaging showed the presence of arteriovenous shunting post-procedurally. All five clinical failures showed arteriovenous shunting on CT-angio. “There were no patients with CT-angio success and clinical failure,” Akinfiev said.
Next, he turned to reproductive outcomes. Of the 29 patients included in the study, 12 (41%) desired pregnancy, and 17 (59%) did not. In the desiring pregnancy subgroup, nine (75%) women did become pregnant, and all nine have since given birth, “a rather encouraging result,” according to Akinfiev.
“We had only one patient with a comorbidity during pregnancy,” he continued, “a patient with placental presentation. Our obstetricians had to perform a caesarean section in the 35th week of gestation due to threatening bleeding.”
Fielding a question from the audience concerning pulmonary embolisms, Akinfiev answered: “In this group, we did not see any sign of pulmonary embolism in our patients, but when we performed our procedures, we always tried to use the gelfoam first prior to PVA, as the cubic gelfoam particles are larger, and this way we try to prevent pulmonary embolism. Generally, we did not see any significant complications in this group except for one strange point, I cannot call it a complication, but about half of them demonstrated a very high temperature, higher than 38°C, on the second or third day after the procedure. I think it is because of using gelfoam.”
Another questioner asked if any of the 29 patients were given hormonal drugs prior to UAE, but Akinfiev replied that they did not use any form of systemic therapy ahead of embolization, “so zero,” he replied.
Lymphatic fistulae and/or lymphoceles in the groin following radical lymphadenectomy are frequent, and therapeutic options are needed to avoid severe restrictions for oncologic patients waiting for adjuvant medical therapies. This is the key message Florian Offensperger (General and Interventional Radiology, Stuttgart Clinics, Stuttgart, Germany) wants audience members to take home from the 2020 virtual Global Embolization and Cancer Symposium Technologies (GEST) meeting (4–6 September).
“It is important to say that there are treatment options,” he told attendees of the live event on Friday 4 September, “because we often have excellent patients who have been told that there is no other option but to wait.”
Stuttgart Clinics, where Offensperger works, is one of the largest surgical centres in Germany. Discussing postoperative lymphatic complications following radical inguinal lymphadenectomy in patients with malignant melanoma, Offensperger says: “Where wood is chopped, splinters must fall”. However, his talk offers hope for how best to deal with these splinters—a complication need not spell disaster for a patient.
The basic lymphatic intervention performed at the Stuttgart Clinics for patients with postoperative complications from radical inguinal lymphadenectomy is pedal Lipiodol lymphangiography combined with second-line interventions. “In our opinion,” Offensperger says, this is “the best treatment for these patients”.
He informs the GEST audience that the technical success rate of conventional lymphangiography is 75–100%, and the cure rate of postoperative lymphatic leakage for pedal conventional lymphangiography is 51–70% (time to cure, 2–29 days). “Conventional lymphangiography is safe, feasible, and effective in the management of postoperative lymphatic leakage,” he concludes, showing a pre-recorded video of the procedure to illustrate how it works to his listeners. “Personally, I really like this intervention, because it is a delicate task requiring many interventional techniques,” he shared.
In the present study, Offensperger and colleagues conducted a prospective analysis of their institutional digital databases for melanoma patients. They compared patients who had been treated with lymphatic angiography alone with those who had been treated with lymphatic angiography combined with sclerotherapy.
Between October 2014 and June 2019, 13 patients met the inclusion criteria: nine in the lymphatic angiography alone group, and four in the combined lymphatic angiography and sclerotherapy group. Mean patient age was 66.4 years (range: 46.8–83.4 years), and the interval between radical inguinal lymphadenectomy and lymphatic angiography was 17.8 days (range: seven to 34). The technical success rate for lymphatic angiography was 93%. The amount of Lipiodol used to perform the procedure was 15.4ml (range: six to 22ml), and in the combined group sclerotherapy was applied after an interval of 10 days (range: zero to 23). Sclerotherapy was performed either with 3–5ml ethanol, or with a glue/ Lipiodol 1:5 mixture (6–8ml) under fluoroscopy or computed tomography (CT) guidance.
The clinical success rate was higher in patients treated with lymphatic angiography and sclerotherapy, 100% compared with 78%. However, the interval between intervention and cure was slightly shorter in the cohort treated with lymphatic angiography alone: 23 days (range: four to seven) versus 29 days (range: 24–33). While there were no minor procedure-related complications in the group of patients treated with lymphatic angiography alone, there was one in the combined cohort (representing 25% of the patients treated in this arm of the study), a local infection cured by antibiotic treatment. There were no major procedure-related complications in the study.
These results led Offensperger to conclude that “Lymphatic angiography, with or without sclerotherapy, is an essential tool to cure therapy-refractory lymphatic fistulae after radical inguinal lymphadenectomy in patients with malignant melanoma.
“Lymphatic angiography in combination with sclerotherapy seems to result in higher clinical success rates,” he continued, “but also in higher complication rates when compared with lymphatic angiography alone.” However, he stressed that he wanted to leave GEST attendees with the understanding that lymphatic angiography in combination with sclerotherapy is a safe and effective option.
Boston Scientific announced that the US Centers for Medicare and Medicaid Services (CMS) granted a new technology add-on payment (NTAP) for the Eluvia drug-eluting vascular stent system as part of the 2021 inpatient prospective payment system (IPPS).
The NTAP designation, awarded to new medical devices determined to substantially improve the diagnosis or treatment of Medicare beneficiaries, will be effective on 1 October 1 2020 and will provide eligible hospitals with incremental reimbursement for the Eluvia stent system for up to three years. The Medicare criteria for an NTAP designation is based on newness of the device, cost, and a substantial clinical improvement.
The Eluvia stent system was developed for the treatment of peripheral arterial disease (PAD). The Eluvia stent reopens the blocked artery and restores blood flow, while also utilising a drug-polymer combination to offer a sustained, low-dose release of drug to prevent tissue regrowth within the stented artery.
“The CMS determination is a very positive development for patients with PAD and supports what we have confirmed through our clinical trials—the Eluvia stent offers clinically superior outcomes compared to other peripheral drug-coated technology available to clinicians and their patients,” said Jeff Mirviss, executive vice president and president, Peripheral Interventions, Boston Scientific.
“The decision is particularly important given the level of consideration and evaluation related to the role of paclitaxel in the peripheral vasculature, and we believe this designation reflects the unique attributes of the Eluvia stent, which are clearly differentiated and improve the quality of life for the millions of people suffering from symptoms of PAD.”
The NTAP designation will support access to the Eluvia stent for Medicare beneficiaries in the hospital inpatient setting, making it possible for eligible hospitals to receive NTAP payment in addition to the standard Medicare severity diagnosis related group (MS-DRG) payment.
The US Food and Drug Administration (FDA) approval of the Eluvia stent system in September 2018 was based on findings from the IMPERIAL trial, which exhibited the highest 24-month primary patency reported to date for the treatment of femoropopliteal disease in a US pivotal trial with a drug-coated balloon or drug-eluting stent. Trial data confirmed a statistically significant lower clinically-driven target lesion revascularisation (TLR) rate of 12.7% for patients treated with the Eluvia stent, in contrast to 20.1% observed within the Zilver PTX drug-eluting peripheral stent cohort (p=0.0495), thus reducing the need for repeat procedures at 24 months.
The Ellipsys vascular access system reduces the time before patients with kidney failure can start lifesaving dialysis treatments, while requiring fewer secondary procedures, according to a new study led by interventional radiologist Jeffrey Hull (Richmond Vascular Center, Richmond, USA).
This could have a significant impact on patient safety and healthcare costs by reducing the need for other forms of dialysis access that are associated with higher rates of complications, a press release states.
For patients with end-stage renal disease (ESRD) who require haemodialysis, the preferred type of vascular access is an arteriovenous fistula (AVF), a permanent connection between a vein and artery in the arm.
Until recently, surgery was the only way to create an AVF, but that subjects patients to longer recovery times and, as a result, delayed dialysis. Hull helped develop the Ellipsys system as a non-surgical alternative; the technology uses just a small needle puncture and catheter to create an endovascular AVF (endoAVF).
The prospective study, involving 123 patients at Richmond Vascular Center, evaluated patient selection and best practices for preparing (“maturing”) Ellipsys fistulas for dialysis. The results show that use of the Ellipsys system along with early maturation procedures reduced the average time from fistula creation to dialysis to just 66 days, down from 100 days in the initial US pivotal trial. In the USA, literature reports the time to dialysis with surgical fistulas averages 135 days.
This “rapid maturation” is important because it can potentially reduce or even eliminate the length of time patients require a central venous catheter (CVC) for dialysis. Compared to fistulas, CVCs are associated with significantly higher rates of complications, like infection and even death. Despite these risks, 80% of patients in the USA still start their dialysis with a catheter.
“Catheters are a less than optimal choice for dialysis access and the goal is to always get them out as soon as possible to avoid serious complications,” said Hull. “With Ellipsys, we have the unique ability to create fistulas in the office during the patient’s initial visit, thus avoiding surgery at the hospital and reducing physician visits. This enables us to streamline the dialysis timeline and reduce patients’ total catheter contact by a significant amount—sometimes by as much as four months. This will have a tremendous impact on quality of life for patients.”
Published in a recent issue of the Journal of Vascular and Interventional Radiology (JVIR), Hull’s study demonstrates real-world outpatient use of the Ellipsys endoAVF system. It is also the first US-based study to evaluate the application of best practices for early maturation. These best practices include performing balloon angioplasty during fistula creation to improve blood flow, as well as completing maturation after just four weeks. In addition to shortening the dialysis timeline, this protocol decreased the overall number of secondary maturation procedures required to prepare the fistula for dialysis and reduced the rate of thrombosis, a common complication with fistula creation.
Decreasing the number of procedures a patient must undergo to prepare for dialysis, as well as moving fistula creation from hospitals to outpatient settings, is a particular advantage for both patients and healthcare providers as the USA deals with COVID-19, according to kidney patient advocate Terry Litchfield.
“The ability to create a fistula with a minimally invasive procedure in an outpatient setting preserves limited hospital resources and lowers the risk of exposure for kidney patients, who already have a higher risk of developing complications with the virus,” said Litchfield. “Ellipsys enables physicians to safely create dialysis access, even in the midst of a pandemic, which will make it easier for these vulnerable patients to get the lifesaving dialysis treatments they need.”
PQ Bypass has announced that they received breakthrough device designation from the US Food and Drug Administration (FDA) for the Detour system. The Detour system is the world’s first fully-percutaneous femoral-popliteal bypass device intended to treat extremely long, complex blockages in the superficial femoral artery (SFA).
Physician access to this device can now be expedited as a result of this designation by the FDA breakthrough device programme, which is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide PQ Bypass with priority review and interactive communication regarding device development and clinical trial protocols, during the premarket review process.
“As this is a first-of-its-kind device, we are pleased to have the FDA recognise the novelty and potential of our therapeutic approach in treating severe SFA,” said Heather Simonsen, general manager at PQ Bypass. “We appreciate their collaborative review of our breakthrough device designation request and look forward to a continued productive relationship as we continue towards PMA submission.”
The Detour system is designed to treat patients who are unable to carry out activities of daily living and are unable to enjoy the liberties of free mobility as a result of their advanced symptomology, severe lesion morphology, and multiple comorbidities.
Once peripheral arterial disease (PAD) progresses to debilitating claudication or tissue loss, revascularisation becomes imperative to mitigate the ongoing deterioration and to prevent amputation. Left untreated, these patients are at greater risk for further functional deterioration, major adverse limb events, and mortality.
“This designation is a major milestone for PQ Bypass, and we expect this technology to change the paradigm for complex SFA treatment in the way EVAR [endovascular aneurysm repair] and TAVR [transcatheter aortic valve replacement] changed the paradigm for aortic repair,” said Rich Ferrari, chairman and CEO of PQ Bypass.
“We are nearing enrolment completion in our DETOUR2 and TORUS2 IDE [investigational device exemption] studies, and had new positive data on our technology published in the Journal of Vascular Surgery, making 2020 a momentous year for the company. This is an exciting time for all of us at PQ, with this important designation a credit to such a talented group. We are honoured and proud to be part of this important journey to develop a first-line therapy in the treatment of advanced PAD.”
Sirtex Medical and its shareholders, China Grand Pharmaceutical and Healthcare Holdings Limited (CGP) have been issued a “Notice of Drug Clinical Trial Approval” by the National Medical Products Administration (NMPA) of the People’s Republic of China.
The notice confirms that SIR-Spheres Y-90 resin microspheres meet the relevant requirements for drug registration in China. With this confirmation, Sirtex is approved to file a New Drug Application (NDA) in the country.
“We are grateful to the members of CGP, Sirtex China, and our Global Regulatory, Quality Assurance, Operations, and Medical teams for their dedicated work in achieving this approval from the NMPA and navigating the complex regulatory process,” comments Kevin R Smith, chief executive officer of Sirtex. “This is a critical milestone toward allowing us to provide a valuable treatment option to people with liver cancer in China.”
The announcement marks a step in Sirtex’s journey to gain market entry into China, thanks to the company’s collaboration with its shareholder, CGP.
“We are proud of our team’s accomplishment and work to achieve this goal,” says Weikun Tang, general manager of Sirtex China. “We are excited for the opportunity to work together with CGP to bring SIR-Spheres Y-90 resin microspheres to our country’s patients.”
Royal Philips has announced the next-generation of its Azurion image-guided therapy platform, designed to improve the quality and efficiency of interventional procedures. The Azurion platform has been used in over two million procedures worldwide since its introduction three years ago, according to a company press release.
In the past few decades, clinical practices around the world have evolved to successfully treat more patients and perform more complex procedures in interventional labs, the Philips press release noted, adding that with more staff and technologies involved during these procedures, interventional lab environments can become crowded and cluttered. In order to enhance clinician focus and control during procedures, Philips has integrated all the essential lab systems and tools into the new version of the Azurion platform.
The Azurion image-guided therapy platform now integrates control of imaging, physiology, haemodynamic and informatics applications, as well as intuitive control of the gantry, at the tableside, allowing clinicians to control all compatible applications from a single touch screen while performing procedures. This can eliminate the need for clinicians to leave the sterile field and step into an adjacent control room, as well as supporting faster and better informed decision making, the company said.
Philips is also introducing a new 3D imaging solution called SmartCT, where users are guided through image acquisition and can review and interact with the acquired CT-like 3D images on the tableside touch screen module using 3D visualisation and measurement tools. These tools have been designed to support procedures in a range of clinical domains, including neurology, oncology, and cardiovascular procedures.
“Our aim as an innovation company and global market leader in image-guided therapy is to push the boundaries and set new industry standards for delivering an outstanding experience for clinicians, helping them to deliver superior care to every patient,” said Ronald Tabaksblat, general manager image guided therapy systems at Philips. “This next-generation Azurion makes routine cardiovascular procedures more efficient and supports the development of new minimally-invasive techniques to treat complex diseases such as stroke, lung cancer and spine disorders.”
“The integrated platform enables us to efficiently carry out complex interventions at any time using a wide range of functions such as IVUS and iFR co-registration,” said Alexander Becker, head of the cardiac catheter laboratory at the Robert Bosch Hospital, Stuttgart, Germany, and one of the first hospitals to experience the new platform. “The use of the control panel by the examiner is intuitive, combining different sources of information to make patient evaluation much easier and faster.”
Philips adds that the new Azurion platform allows clinicians to easily switch between imaging, physiology, haemodynamic and informatics applications, including SmartCT and IntraSight—a suite of clinically proven iFR, FFR, IVUS and co-registration modalities.
The new Azurion also includes cybersecurity features, high-definition image display capabilities, and advanced remote and proactive services. The platform is available in three versions: complementing the Azurion 3 and 7 variants, Philips now also offers the Azurion 5 to facilitate tailored solutions to address specific customer needs.
The largest European-wide observational study on the treatment of primary and metastatic liver tumours with SIR-Spheres microspheres (Sirtex) will present its data on safety and overall survival from its 1,027-patient cohort for the first time at the virtual 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (12–15 September).
The study, initiated by CIRSE, collected data on the clinical application of selective internal radiation therapy (SIRT), also known as radioembolization. The data will be presented virtually during a live hot topic symposium: “Research in IR: First results from CIRSE’s observational studies (HTS 1801, Monday 14 September, 14:30–15:30 CEST).
Thomas Helmberger (München Klinik Bogenhausen, Munich, Germany), speaking on behalf of CIRSE as the chairperson of the CIRT Steering Committee, states: “I am extremely proud of all the hard work that my colleagues have put into this study over the last six years. Its success is due to their continuous efforts, and I am very excited to present this data during the upcoming CIRSE 2020 Summit.”
The Society of Interventional Oncology (SIO) National Comprehensive Cancer Network (NCCN) Task Force submitted recommendations to the NCCN for the latest revision of the Neuroendocrine Tumour treatment guidelines. These have been accepted by the national body. According to the society, this is the first time interventional radiology (IR) has been called out as a separate body contributing to the guidelines (see figure 1).
The inverted “U” is the mathematical symbol for intersection; SIO describe this symbol as “a fitting designation for interventional oncology operating at the intersection of cancer therapies”.
For lung neuroendocrine tumours (NETS), ablation was added for treatment of primary tumours, and liver-directed therapy added for liver-dominant metastases.
An entirely new section on “Principles of Liver-Directed Therapy” was added to the guidelines and referenced in the sections on treatment of metastatic gastrointestinal and pancreatic NETS. The principles cover the spectrum of embolotherapies and include thermal ablation as an option, while acknowledging the limited prospective data for ablation. Adding an entirely new section of this name was the first request made from SIO late last year.
Cautions about liver-directed therapies in the setting of a Whipple were modified to include any prior biliary instrumentation.
Ablation was added as an option for malignant adrenal tumours.
A new section on “Principles of Imaging” was created to codify recommendations for anatomical and nuclear imaging.
Rony Avritscher (MD Anderson Cancer Center, Houston, USA), Nick Fidelman (University of California San Francisco, San Francisco, USA), and Etay Ziv (Memorial Sloan Kettering Cancer Center, New York, USA) authored the SIO submission. Their letter, dated 15 October 2019, requested the NCCN Neuroendocrine and Adrenal Tumours guideline panel review data regarding six specific changes to update the role of liver-directed therapies in the clinical practice guidelines in oncology.
In response to the global outcry following the murder of an unarmed black American, George Floyd, by police in Minneapolis in late May of this year, and as a contribution to the continuing conversation on racism in the USA and globally, the Society of Interventional Radiology (SIR) released a statement of commitment in support of diversity within medicine. It promised to “commit to anti-racist efforts, policies, and programmes that aim to increase the numbers of underrepresented minorities and women within our specialty”. Interventional News spoke with Paul J Rochon, chair of the SIR Diversity and Inclusion Advisory Council and a vascular and interventional radiologist at the University of Colorado School of Medicine, Aurora, USA, about the society’s continued anti-racist activities and intentions.
As we outlined in our statement, SIR has a number of activities underway to combat racial inequality. In addition to establishing the Diversity and Inclusiveness (D&I) advisory group and the Women in IR (WIR) section—both of which bring a powerful diverse voice to SIR’s leadership—the society and SIR Foundation offer a variety of grant programmes for medical students from diverse backgrounds to participate in clerkships that fund research by women and underrepresented minorities, and that fund the establishment and validation of programmes that aim to diversify the workforce. We also established a Speakers Bureau to ensure meeting planners have access to IR experts from underrepresented groups.
The formation of active diversity, equity, and inclusion committees and boards in institutions, both academic and private, is the first strategy. All specialties should have these incorporated. As this happens, specialties should come together in their efforts and strategies to recalibrate these systemic imbalances.
One of the biggest challenges facing IR is awareness of the specialty. For years, it was a subspecialty of radiology, and did not have that much exposure outside of radiology rotations. IR’s status as a primary specialty in the USA and its associated residency programmes are fairly new, but it is raising the profile of IR, which will hopefully help us recruit more people of diverse backgrounds into the specialty. The MATCH results are encouraging in that we remain among the most competitive specialties. We have routinely filled more than 98% of slots each year.
To help with recruitment among medical students, SIR’s D&I advisory group’s recruitment committee, in collaboration with SIR’s Residents, Fellows, and Students (RFS), WIR, and Association of Program Directors in Interventional Radiology (APDIR) sections, have been working to plan strategies related to ensuring that female and underrepresented minority medical students and undergraduates are aware of IR as a specialty option.
Through SIR Foundation, and a generous endowment from Alan Matsumoto and his family, we have issued grants to help people from underrepresented backgrounds participate in IR clerkships. The funding is critical to ensuring that those in various underrepresented groups are able to access the networking opportunities clerkships provide and be exposed to IR as a career path.
It will be some years before we train enough new interventional radiologists to build a truly diverse workforce, but in the meantime, we are working hard to raise the voices of those underrepresented in our workforce.
SIR has been collecting member demographic information for over five years; these data include gender and ethnicity, and cover all career stages, from medical student through to attending. The D&I advisory group has been reviewing this data as it relates to overall SIR membership, committee engagement, and speakers at its educational meetings, and is working to ensure that these posts and opportunities are accessible to people of diverse backgrounds.
Additionally, it is part of SIR’s strategic plan to conduct a study on the IR workforce, which will entail an overall look of the workforce trends and include insight on practice types, gender, and underrepresented minorities. This will further help us to tailor programmes to ensure we are effectively including all voices and views in all SIR activities. All in all, it all stems from intentionality. Workplaces need to not check boxes; strategic plans should be in place to recruit diversity in gender and race and ensure inclusion.
Together, the WIR section and D&I advisory group promote diversity of gender, race, and ethnicity within SIR. The two groups collaborate to increase the participation and visibility of women and underrepresented minorities (URM) in SIR, as well as fostering the growth and awareness of women and URM in IR. It is expected that these initiatives will enhance our specialty and strengthen our society.
The success of our mission as a society draws strength not just from the clinical expertise of our physicians, but from the diversity of their backgrounds and experiences as human beings in the world. An innovative, competitive IR workforce requires more than market competencies—it must also carry the power of innate, authentic human connection. As a specialised group of medical practitioners, the diversity of our members and the patients they treat every day is of utmost importance to the overall health of our specialty. SIR’s commitment to these principles must be active and consistent. Having a dedicated D&I advisory group comprised of members and committees that are working across the society helps to ensure that diversity and inclusiveness is an active, living part of SIR’s culture and its work.
SIR and SIR Foundation have launched several programmes to encourage students of diverse backgrounds to enter into IR as their specialty. One of the key programmes, which I alluded to above, is the Grants for Education of Medical Students (GEMS), which was launched in 2019 thanks to the support of Alan Matsumoto and his family, as well as corporate partners. This scholarship programme allows up to 10 applicants from a variety of disadvantaged backgrounds to participate in an away clerkship rotation in IR.
Since its establishment in mid-2019, the GEMS programme has awarded seven medical students with US$10,500 in funding to participate in clerkships, and another US$7,000 in funding for travel to the SIR annual meeting, where they will be able to network with interventional radiologists and learn about the specialty. By the end of this year, we hope to increase that funding to US$16,500 and US$11,000, respectively. Due to the impact of COVID-19, the GEMS programme will be going virtual for a six-week course with a heavy health equity and diversity component. Each scholarship and travel stipend will still be paid out to the students for this year. In addition, the GEMS programme will also be issuing IR textbooks to the recipients and GEMS instructors from its endowment.
By the end of this year, the 2020 GEMS recipients will submit a Journal of Vascular and Interventional Radiology (JVIR) white paper outlining their vision for IR’s role in achieving healthcare and education justice moving forward as part of a group project during their GEMS curriculum.
In addition to this programme, SIR has an SIR Speakers Bureau, which aims to increase the visibility of URM and women nationally. The Speakers Bureau list is used to identify potential speakers for national and regional meetings, as well as invited guest speakers. Grants are available through the diversity and inclusion grant programme to defray the travel costs associated with speaking engagements.
Development of and/or involvement in diversity, equity, and inclusion committees in their own institutions is how SIR members can help promote diversity and inclusivity. The old saying of “it starts at home” cannot be truer for this endeavour.
A national society should balance grassroots activism with a top-down approach by bridging the gap between both. While the grassroots efforts may be involved in producing resources to educate members and increase awareness, leadership of a national society should embrace, advocate, and support, in addition to incorporating them into all aspects of the society, leadership and executive committees not excluded. There needs to be representation at all levels. Pipeline programmes for underrepresented minorities and women should be established to get more representation in leadership and executive committees.
“Unnecessary hysterectomies” could be avoided by involving interventional radiologists at gynaecology multidisciplinary team meetings and in the patient counselling process, Gregory Markris, Saqib Butt, and Tarun Sabharwal (all Guy’s and St Thomas’ Hospital, London, UK) write in a Letter to the Editor in Cardiovascular and Interventional Radiology (CVIR) Endovascular. UAE
Citing a 2019 article by Annefleur de Bruijn (Vrije Universiteit Amsterdam, Amsterdam, The Netherlands) and colleagues that concluded that adding uterine artery embolization (UAE) as a treatment option to the national Dutch guidelines did not change the number of performed UAEs for symptomatic fibroids, Makris et al claim: “Such low UAE rates are not isolated to The Netherlands”. As previously reported in this newspaper, approximately 145 UAEs are performed annually in Spain, a country with a population of over 44 million, and in France, there is an average of 2,000 UAEs performed each year, compared to 40,000 hysterectomies per annum. “This is concerning,” Markris et al opine, “especially in light of trial evidence showing that two thirds of women treated with UAE remain hysterectomy free at 10 years”.
Makris, Butt, and Sabharwall believe that promoting awareness of UAE amongst patients, and closer collaboration between interventional radiologists and gynaecologists, will help to raise the number of UAE patients. They say: “The interventional radiology community must continue to address the injustice of chronic underutilisation of this minimally invasive, safe, clinically and cost-effective procedure. Engaging with relevant stakeholders and lobbying at social and political levels is crucial for the success of this endeavour.”
The results of a randomised controlled trial—the Shunt simulation study—show that a new patient-specific computation model accurately calculated postoperative access flow. As flow is related to maturation, the authors argue that this model may potentially improve arteriovenous fistula (AVF) maturation rates.
Authors Niek Zonnebeld (Maastricht University, Maastricht, The Netherlands) and colleagues— on behalf of the Shunt simulation study group— add that further investigation is needed to improve the predictive power of these simulations in order to render the computational model an adjunct to surgical planning.
Writing in the July edition of the European Journal of Vascular and Endovascular Surgery (EJVES), Zonnebeld et al detail that an AVF needs to mature before it becomes suitable to cannulate for haemodialysis treatment, and that maturation depends on postoperative flow increase.
The authors highlight that AVF maturation remains a permanent issue in vascular access surgery for haemodialysis treatment, with 20–40% of AVFs failing to mature. To address this, they developed a patient-specific computational model that predicts immediate postoperative flow, and hypothesised that providing information from this model for planning of fistula creation might reduce failure rates. Zonnebeld and colleagues conducted a multicentre, randomised controlled trial in nine Dutch hospitals, in which they recruited patients with renal failure who were referred for AVF creation. Using 1:1 randomisation, they assigned patients to the control or computer simulation group. Both groups underwent a work up, with physical and duplex ultrasonography (DUS) examination.
In the simulation group, the data from the DUS examination were used for model simulations, and—based on the immediate postoperative flow prediction—the ideal AVF configuration was recommended.
Zonnebeld et al detail that the primary endpoint was AVF maturation defined as an AVF flow ≥500ml/min and a vein diameter of ≥4mm six weeks postoperatively. The secondary endpoint was model performance (i.e. comparisons between measured and predicted flows, and (multivariable) regression analysis for maturation probability with accompanying area under the receiver operator characteristic curve.
A total of 236 patients were randomly assigned (116 in the control and 120 in the simulation group), of whom 205 (100 and 105, respectively) were analysed for the primary endpoint.
The authors report in EJVES that there was no difference in failure to mature rates between the groups (29% and 32%, respectively). Immediate postoperative flow prediction had an odds ratio [OR] of 1.15 (1.06– 1.26; p<0.001) per 100ml/ min for maturation, and the accompanying operator characteristic curve was 0.67 (0.59–0.75).
Zonnebeld and colleagues recognise that the study has several limitations, including the fact that the primary endpoint was not a clinical one; it does not give any information on the functionality/usability of the AVF. However, they stress that it is an objective measure, and when patients reach the criteria of ≥500ml/min and a vein diameter of 4mm, as defined in this study, there is a 95% likelihood that the AVF will become functional.
Furthermore, to assess the vascular access functionality, the included patients should have initiated dialysis treatment. However, it remains very difficult to predict which and when a predialysis patient will progress to dialysis dependency and start haemodialysis. In the latter group of patients clinical AVF functionality cannot be determined.
Despite these limitations, the authors highlight the generalisable nature of their results, due to the fact that most of the (pre-)haemodialysis patients in need of an AVF were eligible for inclusion, and that the study was designed in such a way that it could be implemented easily in daily practice. In addition, DUS protocols were standardised to comply with the model’s demands. Usually, Dutch hospitals have well-equipped vascular laboratories with trained technicians who routinely perform preoperative DUS examination for AVF surgery.
Zonnebeld et al write that the multicentre design of the present study is a “major strength”, as it shows that the model can be implemented in other clinics. In addition, they note that selection of dialysis facilities for the multicentre study ensured a representative sample of the Dutch dialysis population, comparable with other European populations and studies. Compared with North American studies, however, they recognise that there is a considerably lower percentage of blacks included.
The authors summarise that simulating patient-specific immediate postoperative flows is an “innovative approach” to improve AVF maturation. “Since AVF maturation does not depend on blood flow enhancement through the anastomosed vessels exclusively, the predictive power of a single model was found to be insufficient to support clinical decision-making,” they write.
Looking to the future, the Shunt simulation study group speculate that incorporating the flow predictions in a hybrid model, in which other relevant but non-physical parameters or factors can be incorporated, might be beneficial.
The inaugural CX Aortic Vienna meeting will be livestreamed 8–11 September 2020 to an international, online audience, and will include registrant participation, interaction, and polling.
The programme will focus on all matters aortic—from the aortic valve to the iliac arteries. All known pathologies will be included, and imaging, diagnosis, and therapeutic options—open, endovascular, hybrid, and no intervention—will be applied to the length of the entire aorta, all the while keeping the patient front and centre. On each of the four days, the programme will cover abdominal and thoracic topics.
CX Aortic Vienna 2020 is brought to you with the participation of the Austrian Society of Vascular Surgery (ÖGG), the Italian Society of Vascular and Endovascular Surgery (SICVE), the Swiss Society for Vascular Surgery (SGG), and Aortic Surgery “HOW TO DO IT” (HTDI).
In the abdominal aortic section, there is an enduring fascination with the importance of diagnostic imaging modalities, as well as how to maintain endovascular aneurysm repair (EVAR) results, or instead turn to open repair. There will be dedicated discussion around open and endovascular choices to treat abdominal aortic aneurysm, with a focus on sac size and EVAR follow-up, ultrasound versus CT surveillance after EVAR, and current research into the best imaging modalities for EVAR. There is also a separate session on pathologies of the iliac vessels within the pelvis. In the juxtarenal section, the programme will explore methods to overcome the challenging aortic neck, using all manner of open and endovascular means.
In the thoracic aorta, there will be sections dedicated entirely to the aortic arch, and every aspect of dissecting aortic aneurysm, especially with regard to the timing of intervention. All treatment approaches will be considered and comparisons of open and endovascular methods made in a stepwise, methodical manner.
In the thoracoabdominal section, there remains obvious interest in spinal cord ischaemia and how to reduce the risk of this, with or without cerebrospinal fluid drainage.
In an important collaboration, the ÖGG will be joined by the SGG in the creation of a combined livestreamed programme. The SICVE will also have a livestreamed programme and HDTI will show Aortic Techniques & Technologies.
All about the aorta
Roger Greenhalgh (London, UK), the founding chair, explains the evolution of aortic management, contextualising the need for an aortic-specific educational meeting: “What I would like to know is the pathology behind any problems with the aorta. This might be very different: for example, with the ascending aorta, with the arch of the aorta, the great vessels to the brain and risk of stroke, the descending aorta—four different pathologies there, atherosclerosis, dissection, transection, and ulceration. How do you diagnose those, how do you image those, how do you know which is the best way to treat them in the first place?
“We still live in an era where it is possible for patients to be referred to one hospital and have an open operation for the aorta, and to another hospital and have an endovascular approach. It should not be right for it to dependent upon which hospital or specialist you get sent to, whether a patient should have endovascular or open. The patient should have the right treatment [speakers’ emphasis]. There should be discussions in centres on whether an open or an endovascular approach is best, it should not be a territorial matter. Let us encourage every patient to be considered with all options, and have an open mind about open surgery and endovascular.
A focus on decision-making in the patient’s interest
Roberto Chiesa (Milan, Italy) will be specially filming open and endovascular technical procedures of how to best manage the diseases of the arch of the aorta, considering whether to intervene or not based on the underlying pathology.
He will outline the importance of a forward-thinking, non-biased approach and running daily multidisciplinary meetings in the patient interest to decide which, if any, is the best treatment.
A comprehensive meeting on aortic therapies
Afshin Assadian (Vienna, Austria), the current president of the ÖGG, describes CX Aortic Vienna as a “comprehensive meeting on aortic therapies” taking in contributions from speakers covering a wide range of specialties.
Alexander Zimmermann (Zürich, Switzerland) comments that the livestream format will enable widespread participation, enabling all colleagues interested in vascular medicine “to participate and actively contribute to this event” easily, wherever they are in the world.
In octogenarians with chronic limb-threatening ischaemia (CLTI), researchers found a one-year mortality rate of 32% after revascularisation, which was significantly higher than in non-octogenarians. Amputation rates were comparable between both age groups.
The authors—Lina F Wübbeke (Maastricht University Medical Centre, Maastricht, The Netherlands), Barend ME Mees (Maastricht University Medical Centre, European Vascular Centre, Aachen-Maastricht, Germany, and European Vascular Centre, Maastricht, the Netherlands) and colleagues—comment that this mortality rate is “substantial”.
Writing in the European Journal of Vascular and Endovascular Surgery (EJVES), they remark: “This [outcome] is of major importance to clinical practice to inform patients and colleagues adequately during the decision-making process of any intervention in this fragile patient group.”
The authors do acknowledge, however, that only low-quality evidence could be obtained supporting the results of this meta-analysis, because only observational studies were available for inclusion. Therefore, they stress that the results should be “interpreted with caution”.
Discussing their methods, Wübbeke, Mees, and colleagues detail that two independent researchers searched systematically Medline, Embase, and Cochrane Library databases. Meta-analyses were performed to analyse one-year mortality, one-year major amputation, and one-year amputation-free survival (AFS) after revascularisation.
They specify that pooled outcome estimates were reported as percentages and odds ratio (OR) with 95% confidence intervals (CI). In addition, sensitivity and subgroup analyses were performed and the quality of evidence was determined according to the GRADE system.
Wübbeke, Mees et al write that the review includes 21 observational studies with patients who were treated for CLTI, and that a meta-analysis of 12 studies with a total of 17,118 patients was performed.
Writing in EJVES, the authors report that a mortality rate of 32% was found in octogenarians (95% CI 27–37%), which was almost double the mortality rate in the non-octogenarians (17%, 95% CI 11–22%/OR 2.52, 95% CI 1.93–3.29; GRADE: “low”).
They also state that no significant difference in amputation rate was found (octogenarians 15%, 95% CI 11–18%; non-octogenarians 12%, 95% CI 7–14%; GRADE: “very low”), and that amputation-free survival (AFS) was significantly lower in the octogenarian group (OR 1.55, 95% CI 1.03–2.43; GRADE: “very low”).
In a subgroup analysis differentiating between endovascular and surgical revascularisation, amputation rates were comparable, Wübbeke and colleagues detail. For octogenarians, those treated conservatively had a mortality rate significantly higher than those treated by revascularisation (OR 1.76, 95% CI 1.19–2.6; GRADE: “very low”). No significant difference in mortality rate was found between primary amputation and revascularisation in octogenarians (OR 0.7, 95% CI 0.24–2.03; GRADE: “very low”).
In the discussion of their findings, Wübbeke, Mees et al recognise that their study is limited by the weakness of the available evidence.
“No randomised controlled trials were available for inclusion,” they write, adding that 19 of the 21 studies were retrospective cohort studies, “increasing the risk of information bias”. They add that the current Global Vascular Guidelines on the Management of CLTI also stressed that high-quality data on ‘evidence-based revascularisation’ is limited.
Considering future research, Wübbeke, Mees et al recognise that additional studies are needed “to provide more solid results and to determine the optimal management of octogenarians with CLTI”. Moreover, they write that outcomes after revascularisation have to be compared with outcomes after conservative treatment or primary amputation and standardised study designs and endpoints should be used as promoted by the current Global Vascular Guidelines on the Management of CLTI.
Finally, they state that these results should also be used to develop adequate risk scores, enabling appropriate patient selection, and that quality of life studies should be performed to decide whether revascularisation interventions are always indicated in this group of frail patients.
Concept Medical has announced the enrolment of the first patient in the FUTURE BTK (Randomised controlled trial of first sirolimus coated balloon versus standard balloon angioplasty in the treatment of below-the-knee artery disease) trial. The index patient was successfully enrolled on 26 August 2020 in Singapore.
FUTURE BTK is a randomised, double-blind, placebo-controlled, multicentere trial. It is aimed at determining the effectiveness of MagicTouch PTA sirolimus-coated balloon versus standard balloon angioplasty for the treatment of below the knee arterial disease in chronic limb-threatening ischaemia (CLTI) patients.
Sirolimus-coated balloons are considered to be the next new generation of drug-coated balloons (DCBs), and MagicTouch PTA sirolimus-coated balloon offers a solution which optimises both the deliverability and the absorption of sirolimus into the vessel wall.
Edward Choke (Sengkang General Hospital, Singapore, Singapore), principal investigator of FUTURE-BTK comments: “CLTI is a condition which puts patients at an increased risk of limb amputation and death. Its burden is likely to grow in the coming years given the rising trends in key risk factors such as age and diabetes. Effective revascularisation is the cornerstone of treatment, but this is often hampered by high rates of restenosis and reintervention after conventional balloon angioplasty”.
He adds: “The novel MagicTouch PTA sirolimus-coated balloon has emerged as one of the most promising transcatheter technologies in preventing restenosis for below-the-knee lesions. The earlier data on the efficacy of MagicTouch PTA from small studies are encouraging but these need to be confirmed or refuted. I look forward to the FUTURE BTK randomised controlled trial, which will test whether the MagicTouch PTA sirolimus-coated balloon can improve the patency of below-the-knee arteries in CLTI patients, and this will hopefully bring us closer to our goal of reducing leg amputations”.
The trial will enrol 210 patients with Rutherford class 4 to 6 CLTI. These subjects will be randomised in 2:1 fashion to receive either MagicTouch PTA or standard balloon angioplasty. Primary outcome will be primary patency at six months, defined as duplex peak systolic velocity ratio (PSVR) of 2.4 or less.
The trial is designed to follow a rigorous blinding protocol in order to minimise bias. Patients, care providers, investigators, and outcome assessors, including vascular technologists performing the duplex ultrasound, will be blinded to the treatment allocations. The patients will be followed up for two years.
Royal Philips today announced that it has signed an agreement to acquire Intact Vascular. According to a press release, Intact Vascular will enhance Philips’ image-guided therapy portfolio, combining Philips’ interventional imaging platform and diagnostic and therapeutic devices with Intact Vascular’s unique, specialised implantable device to optimise the treatment of patients with peripheral arterial disease (PAD).
“Acquiring Intact Vascular will expand our portfolio of minimally invasive therapy options for PAD with the Tack endovascular system, a much needed implant that effectively restores blood flow in small limb vessels, promotes healing and preserves limbs,” said Chris Landon, senior vice president and general manager Image Guided Therapy Devices at Philips. “Through the integration of our interventional imaging systems and diagnostic and therapeutic devices, we will be able to provide clinicians with a complete procedural solution to optimise the treatment of patients with this disease.”
Philips’ peripheral vascular portfolio already includes advanced interventional imaging systems for precision guidance; intravascular ultrasound (IVUS) catheters to assess the location of the disease and lesion morphology and guide and confirm the treatment; peripheral atherectomy devices to remove blockages; and peripheral therapy devices, such as Philips’ Stellarex drug-coated balloon, to treat lesions.
Intact Vascular will strengthen this portfolio with the Tack endovascular system, which reinforces standard and drug-coated balloon PAD treatment results. Intact Vascular’s Tack implant is a first-of-its-kind, minimal-metal, dissection repair device that provides precision treatment of peripheral arterial dissections following balloon angioplasty in above-the-knee (ATK) and below-the-knee (BTK) therapeutic interventions. The Tack implant leaves less metal behind compared to stents, preserving future treatment options and ultimately preserving limbs. Moreover, Intact Vascular’s Tack implant offers a solution for repairing dissections and optimising post-angioplasty outcomes in the challenging chronic limb-threatening ischaemia (CLTI) patient population.
“We are excited about the strategic fit between our team, expertise and unique therapeutic device, and Philips’ Image-Guided Therapy business,” said Bruce Shook, president and CEO of Intact Vascular. “We share the same vision of complete procedural solutions to improve existing procedures and expand treatment options. We look forward to completing the transaction and working closely with Philips on a seamless transition.”
The transaction, which is subject to customary closing conditions, is expected to be completed in the third quarter of 2020. Philips will acquire Intact Vascular for an upfront cash consideration of US$275 million, and deferred payments for which the company expects to recognise a provision of US$85 million upon completion of the transaction.
Sirtex Medical reports that enrollment in the US RESiN registry has reached a milestone of 1,650 patients and 12.8 months of follow-up, allowing for a satisfactory number of patients enrolled for meaningful data analysis.
Under the leadership and direction of Daniel Brown and the trial’s executive committee, the registry will close enrollment at the 45 centres and will move to a new phase of data review and evaluation, publication, and presentation. The US RESiN registry, a database of patients eligible for treatment with SIR-Spheres Y-90 resin microspheres (Sirtex), started enrollment in 2015 and represents one of the largest prospective, multicentre, observational studies conducted in interventional radiology and the field of interventional oncology.
The registry should provide robust real-world evidence to characterise the effectiveness, safety, and clinical impact of SIR-Spheres Y-90 resin microspheres, a Sirtex press release states. To date, the RESiN registry has yielded several publications, including oral and poster presentations at international medical oncology and interventional radiology congresses, as well as a recent submission of “Incidence and risk factors for sustained hepatic function toxicity six months after Y-90 radioembolization: Interim analysis of the radiation-emitting SIR-spheres in non-resectable liver tumour (RESIN) registry.”
“I am extremely grateful to Sirtex for their support. Their commitment to developing and maintaining this first-of-its-kind interventional oncology registry has been unwavering over the five years of the study,” comments Brown, vice-chair of Innovation and Clinical Research, and chief of Interventional Oncology at Vanderbilt University Medical Center, Nashville, USA. “As this phase of the project winds down, I am looking forward to future collaborations with Sirtex to advance the data, science, and knowledge around patients treated with SIR-Spheres Y-90 resin microspheres.”
With completed enrollment, Sirtex and Vanderbilt will focus efforts to expand the number of publications arising from this data base and topic areas of interest, such as an assessment of different pre-treatment planning dosimetry methods, orphan tumour outcomes, and specific cohorts of interest.
As of August 2020, corresponding authors from more than 750 German universities and research institutions are able to publish in Cardiovascular and Interventional Radiology (CVIR) Endovascular free of charge thanks to a deal Springer Nature has signed with these German research institutions.
An explanatory statement on the Springer Nature website reads: “If you are a corresponding author affiliated with a German university or research institution, you are entitled to publish open access in our journals with fees covered by the German DEAL agreement.
“More than 900 German institutions are eligible to participate in the agreement between Springer Nature and Projekt DEAL, meaning that corresponding authors affiliated with these institutions are eligible to publish their articles open access without being invoiced by Springer Nature. The agreement includes more than 2,000 hybrid journals across the Springer Nature portfolio (from January 2020) and more than 500 fully OA journals (from August 2020).” CVIR
Sirtex Medical has announced a collaboration with Magle Chemoswed, a Sweden-based contract development and manufacturing organisation.
The development and commercial agreement grants Sirtex global use of Magle Chemoswed’s technology to develop a novel imaging agent for use in interventional oncology. Sirtex will have the exclusive license and commercialisation rights in the defined field of use. Magle Chemoswed maintains rights to its technology platform and to exclusively manufacture the product for supply to Sirtex. The development programme will begin in the third financial quarter of 2020.
“Our partnership with Magle Chemoswed marks an important step in our company growth, portfolio expansion, and investment in patient-centered care worldwide,” says Kevin R Smith, Chief Executive Officer (CEO) of Sirtex. “We are honoured to utilise this technology platform to advance innovative therapies for patients.”
“This is an incredibly exciting collaboration with a recognised global leader in the industry. Sirtex will be able to nimbly move the project from development to regulatory approvals and commercialisation, and we look forward to working closely with their team for optimal success,” says Justin Pierce, Magle Chemoswed’s CEO.
“We are thrilled to begin the collaborative programme with Magle Chemoswed to combine our resources and expertise,” says Mark Turco, Global Chief Medical Officer and EVP, Research and Development of Sirtex. “This technology will open the door to new product development opportunities for optimal patient care.”
The European Conference on Interventional Oncology (ECIO), hosted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) have announced that their November meeting will no longer take place as a physical event. CIRSE says that, in order to provide continuing education in interventional oncology, a series of webinars will be taking place between November 2020 and February 2021.
In full, the letter from ECIO scientific programme committee (SPC) chairperson Alban Denys (CHUV University Hospital, Lausanne, Switzerland) and ECIO SPC deputy chairperson Philippe Pereira (SLK-Kliniken GmbH, Heilbronn, Germany) reads:
“We would like to update you on ECIO and how we are planning to proceed in light of the ongoing COVID-19 pandemic. As you all know, in the spring we had to postpone ECIO 2020 to November. At that time, we were hopeful that we could meet again in the fall to discuss the latest data and share our experience with a community that we have all come to appreciate so much.
“Unfortunately, COVID-19 is still far from being contained and the uncertainty involved in planning a major in-person event at this point has given us no choice but to take the difficult decision that ECIO 2020 will not take place as a physical meeting. It is with heavy hearts that we have to make this announcement, not only as physicians keen to push our specialty, but also as colleagues and friends looking forward to meeting you again soon in person.
“However, we are hopeful that ECIO 2021 will take place as planned from April 11–14 in Stockholm.”
In an entirely new endeavour for Yttrium-90 (Y-90) radioembolization, investigators from Northwestern University, Chicago, USA, have used the technique for the treatment of prostate cancer. “This is a new use for radioembolization, and an entirely new, more targeted treatment for prostate cancer,” Sam Mouli, who is leading the research group, tells Interventional News.
Sandeep Bagla (Prostate Centers USA and Vascular Interventional Partners NOVA, Falls Church, USA), course director of the STREAM meeting, which focuses on research at the vanguard of prostatic artery embolization (PAE) and musculoskeletal embolization, says of this novel use of Y-90: “It is the most cutting edge application of embolization going on right now, with extensive future long-term potential.”
The research team, led by Sam Mouli, set out to examine the potential role of intra-arterial radiotherapy in the setting of a large prostate and prostate cancer. “Radiotherapy has been a cornerstone of treatment for locally advanced prostate cancer for the last 30 years,” Mouli explains. “Despite several advances in the understanding and treatment of prostate cancer over this time, current therapies continue to be limited by significant toxicities, including risks of urinary, bowel, and erectile dysfunction following treatment. Patients continue to seek novel therapies that not only provide oncologic benefit, but also maximise quality of life.
“We posited that we could use our experience with Y-90 radioembolization in the treatment of liver cancer, and adapt it to what we have learned from our PAE programme.”
Prostate gland shrunk in early animal testing
The research team utilised the same canine model that they had initially used to study PAE, this time investigating the potential role of Y-90 radioembolization for the treatment of prostate cancer in a dose escalation study. They specifically looked into radiation changes to the prostatic tissues, as well as the effects of radiation on surrounding organs, such as the bladder and rectum, in addition to the erectile nerves, vasculature, and soft tissues.
Mouli describes the thought processes underpinning this early study: “External beam radiotherapy and transperineal brachytherapy are limited by nontarget radiation delivered to tissues surrounding the prostate, which is the source of the adverse event profile seen with current therapies. We hypothesised that targeted intra-arterial delivery of Y-90 microspheres could mitigate these off-target effects, while still delivering high-dose radiotherapy to the prostatic tissues.”
Utilising the techniques learned from both PAE for benign prostatic hyperplasia (BPH), and Y-90 radioembolization for liver malignancies, half of the prostates of the 14 animals included in the pr-clinical feasibility study were treated with Y-90 radioembolization, while the untreated contralateral sides were used as the control.
In this cohort, imaging follow-up performed at specific time-intervals demonstrated prostate gland size reduction in a dose-dependent fashion starting at two weeks’ post-embolization, continuing to three months post therapy. There were no clinical adverse events throughout the follow-up period. In addition, the investigators report no evidence of nontarget embolization or of any radiation damage to the surrounding bladder, rectum, and erectile tissues on MRI and pathologic analysis.
Expounding on the perceived importance of these early data, Mouli enthuses: “By demonstrating feasibility and safety in this model, we have shown that Y-90 microspheres can be safely delivered to prostatic tissues delivering highly targeted radiation without the off-target damage seen with current approaches. Additionally, given the radio-isotope characteristics of Y-90, this potentially offers a single-stage treatment option for patients. Current radiotherapy often requires multiple treatments over several weeks to deliver radiation safely.
Radioembolization tailored to treat the radiosensitive prostate
Radiation is a standard of care therapy for prostate cancer. However, Mouli says, current radiotherapy approaches are challenged by technical considerations, such as limited dosing due to the proximity of surrounding structures, and difficulty of brachytherapy seed placement in larger glands. He believes that radioembolization can overcome these limitations, while also delivering higher therapeutic doses with minimal off-target effects.
“Our initial results have been incredibly promising,” he comments, “demonstrating both feasibility and safety in an animal model. Of note, explant analysis demonstrated no radiation injury or scarring to adjacent tissue, and validated the initial hypothesis of using radiotherapy delivered trans-arterially: it maximises delivery to the gland and minimises non-target radiation. Our next step would be preparing a clinical study in men with unresectable, locally advanced prostate cancer in 2021. Similar to the current paradigm for Y-90 radioembolization, treatment volume-based dosimetry would be utilised to determine radiation dosing.”
However, Mouli also cautions that investigating new therapeutic options can be challenging: “The bar is very high when comparing to the standard of care,” he says. “Once demonstrating safety and feasibility pre-clinically, clinical translation requires collaboration between various medical specialties as well as industry support. Northwestern University is a highly collaborative enterprise, and we have a strong relationship with Boston Scientific, the sponsors of our Y-90 study. We will work together to move this therapy forward through the next phases of clinical trial testing.”
The future of embolization: “The field is advanced”
Mouli and Bagla belong to a generation of interventional radiologists enthusiastic about the potential of embolization in several guises. Mouli expands: “As interventional radiologists interested in advancing the science, we are always looking for ways to expand areas of clinical success into other organs. What 20 years of radioembolization research has shown is that the traditional dogmatic thinking of radiation dose limits no longer holds when radiotherapy is performed trans-arterially. It turns out that with microcatheter technique, 3D imaging, and proper patient selection, in fact doses much higher than can be delivered externally can be delivered to organs safely, in a single-setting. This is now being demonstrated by our current canine model, has been used in the kidney, spleen and, soon, in the brain. The radioembolization platform is quite simple to use, and when combined with modern imaging and contemporary state-of-the-art techniques, the field is advanced. Ultimately, the patients benefit.”
Julius Chapiro and Lynn Savic claim there is “no need for scepticism” about the recent emergence and growth of immuno-oncology from an interventional oncologists’ perspective. Indeed, they write that interventional oncology (IO) will thrive in this new research environment, and say that combinations of loco-regional therapies and immunotherapies are just now being trialled that may yet transform cancer care whilst centring the skills and clinical expertise of interventional oncologists.
Interventional Oncology (IO) brands itself as the fourth pillar of cancer care alongside medical, surgical, and radiation oncology. Across the board, IO is now the fastest growing sub-specialty in interventional radiology (IR) and certainly understands itself as the flag bearer of our entire field. The vast majority of National Institute of Health (NIH) funding for IR research supports IO science. The presence of an interventional oncologist at interdisciplinary tumour boards in every tertiary care centre has become the new normal. In fact, the rapidly growing IO culture—enhanced by our own society, the Society of Interventional Oncology (SIO)—can be seen as an organising principle among interventional radiologists that strive to abide by Charles Dotter’s everlasting legacy calling upon us to “provide clinical care” rather than practicing as “high-priced plumbers”.
Our dedication to curing cancer minimally invasively—one tumour at a time—and our involvement in patient care as clinicians rather than service providers was reinforced and invigorated during the COVID-19 pandemic. Precisely because of this level of maturity of our profession, there is no need for skepticism or concerns in light of the recent emergence of the “other IO”, immuno-oncology.
Without a doubt, novel immunotherapies transformed the way we approach cancer care. As such, five novel molecular targeted agents and their combinations have become available and US Food and Drug Administration (FDA)-approved for the use in advanced stage primary liver cancer within just roughly three years. While some in our community are overwhelmed and anxious in light of this rapid development, fearing replacement by the “other IO” in our key domain of liver-directed cancer therapies, the overall message remains reassuring: “our IO” will thrive in this new environment.
As the clinical trial data on immunotherapies in liver cancer continues to trickle in, we begin to realise that therapeutic outcomes in immunotherapy have not yet delivered upon the initial promise to make a substantial difference or even provide a cure. In fact, many in our community began to explore combinations of loco-regional and immunotherapy, and, meanwhile, numerous trials have been initiated to study this exciting new option.
While we eagerly await the first results from such prospective clinical trials, we must continue to do our homework in science and education. Historically, basic and translational research has been the Achilles’ heel of IR and this is especially true for the ethos of our professional training. The fellowship training model in IR was naturally focused on rapidly building up procedural hands-on skill in just 12 months of training by means of volume, frequently leaving no room to learn the “language of oncology”. Aware of its shortcomings, the generation before us wisely paved the way for a dedicated IR residency as the new training model. As such, we are now able to recruit trainees from a pool of medical students that have six years to make IR their professional identity, and interventional oncology their sub-specialty.
Therefore, and in order to succeed in this increasingly complex environment of advanced cancer care, we must substantially expand upon interventional oncology education and expect engagement in basic, translational, and clinical research from day one of training. Our interdisciplinary partners in tumour boards should sit across specialised peers with knowledge and profound understanding of tumour biology, disease staging, and clinical trial design when requesting our advice. We must therefore step up in those disciplines and offer more than just technical expertise on whether or not a tumour can be safely reached and targeted under image guidance. Formal oncologic training, increased participation in non-procedural patient care, shared therapeutic decision making, advice on expected outcome, and key opinion leadership in cutting edge research and guidelines must be the new hallmarks of our identity.
Consequently, we must leave behind our anxious heritage as proceduralists and no longer engage in meaningless conversations about “takeover” of our procedures by “competing” specialties. The future of cancer care lies in teamwork and it is time for us to recognise our qualitative edge and expand upon our expertise beyond a set of hands-on skills that can be easily learned by anyone with interest and access to equipment. Thus, we should define new role models in this rapidly evolving field and shift away from reverence and idolisation of procedural prowess as the final endpoint of career development.
Ultimately, the central task of our generation will be to establish formal interventional oncology training as part of the IR residency curriculum, and possibly even offer a formal IO fellowship for sub-specialisation. With that in mind, we will continue to strengthen our role as the fourth pillar of cancer care with content and substance to ensure a bright future of our specialty for the next generation of interventional oncologists.
Julius Chapiro is an assistant professor of Radiology and Biomedical Imaging, co-director of the Yale Interventional Oncology Research Lab, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA. Chapiro declares grants and research support from the Society of Interventional Oncology, Philips Healthcare, Boston Scientific, Guerbet, and the National Institutes of Health.
Lynn Savic is a diagnostic and interventional radiology resident and co-director of the Minimally Invasive Tumor Therapy Research Laboratory at the Charité University Hospital, Berlin, Germany. Savic has no disclosures.
A recent systematic review showed that randomised trials comparing different types of peripheral endovascular arterial intervention have a high level of heterogeneity in their antithrombotic regimens. It also revealed an increasing trend for use of dual antiplatelet therapy post intervention with no clear justification.
Authors Mahim I Qureshi (North Bristol NHS Trust and University of Bristol, Bristol, UK) and colleagues comment that this finding demonstrates a lack of standardisation and poor reporting of antithrombotic therapy in randomised controlled trials of endovascular intervention.
Writing in the July issue of the European Journal of Vascular and Endovascular Surgery (EJVES), they remark that antiplatelet therapy needs to be standardised in trials comparing endovascular technologies in order to reduce potential confounding.
Exploring this potential for confounding, they remark that dual antiplatelet therapy increases the major bleeding risk, which may contribute to late mortality if regimens were continued long term. “This is especially relevant in the current climate,” they comment, highlighting that the trials included in this systematic review contributed to the late mortality results attributed to paclitaxel.
Qureshi and colleagues say that while randomised trials of new devices for peripheral arterial endovascular intervention are published regularly, the evidence for which antiplatelet and/or anticoagulant (antithrombotic) therapy to use after an intervention is lacking.
The aim of this systematic review, therefore, was to examine the antithrombotic regimens in randomised trials for peripheral arterial endovascular intervention to understand choices made and trends with time or type of device.
Qureshi et al sourced information from the Medline, Embase, and Cochrane Library databases. They included randomised trials involving participants with peripheral arterial disease (PAD) undergoing any endovascular arterial intervention.
The investigators assessed trial methods to determine whether an antithrombotic protocol had been specified, its completeness, and the agent(s) prescribed. They classed antithrombotic therapy protocols as periprocedural, immediate post-procedural (up to 30 days following intervention), and maintenance post-procedural (therapy continuing beyond 30 days).
Qureshi and colleagues included 94 trials in the narrative synthesis. They note that study quality was low and that none of the trials justified their therapy protocol. Only 29% had complete periprocedural antithrombotic protocols, and 34% had complete post-procedural protocols.
The authors report in EJVES that antiplatelet monotherapy and unfractionated heparin were the most common regimen choices in the periprocedural setting, and dual antiplatelet therapy (55%) was most commonly utilised post procedure.
They write that over time there has been an increasing tendency to use dual therapy (p<0.001), which corresponds with the introduction of newer technologies and trials focused on below-the-knee interventions.
Qureshi et al’s results show that periprocedurally, aspirin remains the most widely adopted antiplatelet monotherapy, despite randomised evidence favouring clopidogrel. They note that reasons for this were unclear, but speculate that cost may be a factor as clopidogrel has only relatively recently come off patent. “There is the potential to reduce cardiovascular events periprocedurally by using clopidogrel in future trials,” they add.
In the discussion of their findings, the authors comment on potential bias in the randomised trials included in their study. They note that even though a formal meta-analysis could not be not performed, a risk of bias assessment was included as a marker of study quality. This showed a concerning amount of “unclear” bias such as detection bias and attrition bias, which can be compensated for by good trial design and follow-up.
Qureshi et al acknowledge that that their review has some limitations. They detail, for example, that it was impossible to tell whether some trials used antiplatelet agents alone in the periprocedural phase or whether they simply made no statement on heparin/anticoagulant use. They remark: “Because of this lack of clarity, it was impossible to confidently separate antiplatelet and anticoagulant use in these trials, which means some of the periprocedural regimens may not reflect ‘real-life’ practice during procedures.”
They emphasise also the strengths of their review, specifically its “all-encompassing search protocol” and “robust reporting of results,” but stress the need for an independent randomised trial specifically examining antiplatelet therapy following peripheral arterial endovascular intervention.
AngioDynamics has announced the enrolment of the first patient in the PATHFINDER I postmarket registry.
The PATHFINDER I registry is a pilot study to evaluate the safety and efficacy of the Auryon atherectomy system in the real-world treatment of de novo, restenotic, and in-stent restenosis (ISR) lesions in infrainguinal arteries of patients with peripheral arterial disease (PAD).
“We believe that the solid-state laser technology utilised in the Auryon system is the future of atherectomy treatment,” said Jim Clemmer, president and chief executive officer of AngioDynamics. “Providers are showing an eagerness to enrol patients in the study and treat patients with our game-changing technology. Their strong support of the PATHFINDER I registry, along with the enrolment of our first patient, represents a meaningful step toward achieving our shared goal of advancing the standard of care for patients with PAD and related conditions.”
Jason Yoho (Heart and Vascular Institute of Texas, New Braunfels, USA) enrolled the first PATHFINDER I registry patient, a 61-year-old woman with a past medical history of atrial fibrillation, hypertension, hyperlipidaemia, and prior myocardial infarction. She was initially evaluated for severe claudication at rest and was classified as Rutherford 5 (ischaemic ulceration not exceeding ulcers of the digits of the foot). A diagnostic angiography of her right leg revealed severely calcified and diseased anterior and posterior tibial arteries. She was treated with the Auryon atherectomy system.
“Thanks to the successful Auryon laser atherectomy procedure, which was performed in conjunction with balloon angioplasty, there is now excellent, rapid flow restored into the pedal arch. In this case of severely calcified and tortuous anatomy, other devices likely would not have been as successful,” said Yoho.
“Having a passion for CLI [critical limb ischaemia] and limb salvage, my staff and I are eager to advance the body of knowledge around the Auryon atherectomy system through the PATHFINDER I registry. I am excited that AngioDynamics is dedicated to improving upon existing atherectomy technology and increasing the quality of care in the peripheral space. It is critical that we aggressively seek out and support promising new technologies, such as the Auryon system, so that we can provide patients with the best outcomes possible.”
The Auryon system is a proprietary solid state laser technology platform that is US Food and Drug Administration (FDA)-indicated for use in the treatment, including atherectomy, of infrainguinal stenoses and occlusions, including ISR, which is the gradual re-narrowing of the artery after a blockage has been previously treated with a stent. The Auryon system uses a 355nm wavelength laser platform which enables the use of longer wavelengths and shorter pulses to produce the groundbreaking delivery of short UV laser pulses. The Auryon system’s targeted biological reactions address the risk of perforation and preserve the ability to vaporise lesions without thermal damage.
Ten healthcare delivery sites in the USA are expected to participate in the PATHFINDER I registry, each of which is equipped with an Auryon system. Sites are located in Texas, Iowa, Arizona, New Jersey, and Florida. AngioDynamics expects a total of 100 eligible PAD patients to participate in the PATHFINDER I registry, which will track outcomes for patients for 24 months after treatment with the Auryon system.
The PATHFINDER I registry is structured as a prospective, non-randomised, single-arm, multicentre observational study that will evaluate the performance of the Auryon system during procedures and measure clinical outcomes, both intermediate and long-term. Initial findings from the pilot registry study will inform and help shape a subsequent larger registry that is expected to include approximately 1,000 patients.
Just-published six-month results of the IN.PACT AV Access study show that drug-coated balloon (DCB) angioplasty is superior to standard angioplasty for the treatment of stenotic lesions in dysfunctional haemodialysis arteriovenous fistulas (AVFs). Furthermore, it was found to be non-inferior with respect to access circuit-related serious adverse events within 30 days.
These results were published on 19 August in the New England Journal of Medicine (NEJM).
Robert Lookstein (Mount Sinai Health System, New York, USA) and colleagues note that long-term outcomes for standard percutaneous transluminal angioplasty (PTA)—the current recommended treatment for dysfunctional haemodialysis fistulas—are poor. DCBs delivering the antirestonotic agent paclitaxel may improve outcomes, they write.
In this prospective, single-blinded, 1:1 randomised trial, the investigators enrolled 330 participants across 29 sites in the USA, Japan, and New Zealand. Patients with new or restenotic lesions in native upper-extremity AVFs were eligible for participation.
After successful high-pressure PTA, participants were randomly assigned to receive treatment with either the IN.PACT AV drug-coated balloon (Medtronic) or a standard balloon.
Lookstein and colleagues detail that the primary effectiveness endpoint was target-lesion primary patency, defined as freedom from clinically-driven target revascularisation or access-circuit thrombosis during the six months after the index procedure.
They assessed the primary safety endpoint—serious adverse events involving the arteriovenous access circuit within 30 days—in a noninferiority analysis (margin of noninferiority 7.5 percentage points).
Lookstein et al write that a total of 330 participants underwent randomisation, with 170 assigned to receive treatment with a DCB and 160 assigned to receive treatment with a standard balloon.
Writing in NEJM, the authors report that, during the six months after the index procedure, target-lesion primary patency was maintained more often in participants who had been treated with a DCB than in those who had been treated with a standard balloon (82.2% [125/152] vs. 59.5% [88/148]; difference in risk, 22.8 percentage points; 95% confidence interval [CI] 12.8–32.8; p<0.001).
In addition, they found that DCBs were noninferior to standard balloons with respect to the primary safety endpoint (4.2% [7/166] and 4.4% [7/158], respectively; difference in risk, -0.2 percentage points, 95% CI -5.5–5; p=0.002 for noninferiority).
In the NEJM paper, Lookstein et al detail that there has been a wide adoption of continuous haemodialysis through autologous AVFs. However, this has been associated with a high incidence of dysfunction caused by vascular stenosis within the fistula circuit, leading to inadequate haemodialysis.
Lookstein and colleagues acknowledge some limitations of the present study. For example, they note that the DCB has a different appearance than a standard balloon, which made a double-blind trial design “unfeasible”. In addition, the investigators recognise that further studies will be required to evaluate the safety and effectiveness of DCBs for the treatment of central vein obstruction, in-stent restenosis, or arteriovenous graft stenosis, as they investigated only lesions in AVFs.
“Improvements in patency could potentially have significant benefits for patients, leading to longer periods of successful and uninterrupted dialysis, as well as reducing the use of catheter-based dialysis and the substantial incidence of adverse events associated with this type of dialysis.”
Speaking to Vascular News, Lookstein commented on the clinical implications of the study: “We now have Level 1 evidence of a simple technology that is proven to be safe and effective at improving outcomes for patients with end-stage renal disease [ESKD] on haemodialysis.”
He continued: “This is the first US Food and Drug Administration [FDA]-approved paclitaxel-based device since the controversy last year, which is a testament not only to the incredible results seen in this trial, but also the significant needs of this population.”
A new study has found several racial disparities after mechanical thrombectomy for stroke with respect to post-procedure management and outcomes. Vineeth Thirunavu of Northwestern University Feinberg School of Medicine, Chicago, USA, presented the data at the Society of NeuroInterventional Surgery’s (SNIS) 17th Annual Meeting (4–7 August), which detailed key findings from the NVQI-QOD registry.
Specifically, Thirunavu explained that minority groups, including Hispanics, Asians, and African Americans, exhibited worse immediate post-procedural outcomes and a greater length of in-hospital and intensive care unit (ICU) stays.
“Race seems to be implicated in the length of treatment for acute ischaemic stroke,” he told the online audience. However, he said that the registry yielded an “interesting finding” in that in-hospital mortality for African Americans appears to be lower compared to their Caucasian counterparts. “This finding does not necessarily correlate with the findings that you would expect with longer length of stay and more ICU days.”
Discussing this finding further, Thirunavu added that in terms of outcome variables—modified Rankin scale (mRS) score and 90-day mRS—no difference in the rate of favourable outcome between races was observed, when excluding mRS scores of six.
Speculating as to why in-hospital mortality for African Americans was significantly lower, he said: “It could be a cultural thing, or not staying on the support of care, but we really have to do more research to see at what level these disparities are occurring at; is a patient level, a genetic level, or are healthcare providers treating patients differently?”.
Discussing the led the team to initially investigate racial disparities, Thirunavu said that since endovascular therapy has become the standard of care for stroke, research has focused on the disproportionate burden of stroke and cerebrovascular disease on African Americans. “Some studies have also looked into other minority groups […] but that research has focused on differences in the utilisation and access to mechanical thrombectomy; not a lot of research carried out has been on outcomes after mechanical thrombectomy, in terms of mRS scores or National Institutes of Health Stroke Scale [NIHSS] scores,” he added.
Therefore, according to Thirunavu, the current study utilised real-world evidence from the NVQI-QOD registry, enabling the team to study racial disparities in a large group of patients throughout the USA. In total, he reported that 3,261 patients from 23 US centres across 17 states, over a five year time period (January 2015–March 2020), were included.
He pointed to a slide displaying the population breakdown by race. It showed that 2,484 patients were Caucasian, 563 African American, 109 Hispanic, and 105 Asian. He admitted that there might be a slight underrepresentation of Hispanics in the cohort.
“We used a robust set of outcome variables; we were able to look up days to follow-up, and in-hospital mortality. In addition to the initial statistical analysis, we looked at regression models which controlled for demographics, comorbidities, intravenous tPA [tissue plasminogen activator] thrombolysis and pre-stroke functional measures,” Thirunavu explained.
However, he pointed to a particular caveat with the outcome variables, acknowledging that the registry contains some limited data. “Only 33% of patients that are alive at 90 days had mRS scores reported; two-thirds of the data are still up for grabs, and we do not know how those individuals faired,” he told viewers, and further emphasised that mRS, especially at 90-days, is an important outcome variable after mechanical thrombectomy.
In terms of moving forward with these findings, Thirunavu told the SNIS audience that time-to-event analyses need to be carried out. He noted that the NVQI registry has some data on this. “We also need to look into the relationship between sex and race, and think about how we can improve mRS data collection for registries, and have better outcome variables,” he concluded.
For more stories from SNIS 2020, click here.
The European Society of Radiology (ESR) announced attendance was up for its virtual European Congress of Radiology (ECR) 2020, which took place from 15–19 July.
More than 15,000 professional delegates from 130 countries attended the virtual meeting, an increase of 5% compared with attendance at the virtual portion of ECR 2019. In addition, more than 2,000 people tuned in to the Imaging Interpretation Quiz, which was broadcasted live this year from Australia.
Furthermore, 216 companies exhibited at the meeting’s virtual exhibition, the ESR noted. Through the interactive experience, vendors could hold product demonstrations, host webinars, and invite attendees to visit their digital booths.
The meeting featured online educational, scientific, interactive, and industry-specific content, including more than 50 live sessions, and attendees could earn up to 28 continuing education credits. In a 21 July statement, congress president Boris Brkljačić (University of Zagreb School of Medicine, Zagreb, Croatia) deemed the virtual meeting a success.
“When we decided to convert ECR 2020 into an online-only congress, there was a lot of uncertainty about how this would look and whether it would still be possible to capture the magic of ECR in a digital format,” he stated in a press release. “After an incredible congress week, I am extremely pleased to say, there are no longer any doubts.”
Responding to the results of the FEMME (Fibroids with embolization or myomectomy to measure the effect on quality of life) trial, James Spies suggests that uterine artery embolization (UAE) is a favourable treatment option over myomectomy in many patients, as they take into consideration the recovery times and weigh up the benefits of having a minimally invasive procedure versus undergoing an open, operative one. “The important takeaway from the study is that both these treatments are highly effective and they produce comparable outcomes in this population,” he writes.
With the recent publishing of the FEMME trial outcomes in the New England Journal of Medicine,1 we gained additional insight into the outcomes of UAE, this time in a head-to-head comparison with myomectomy. Myomectomy has had growing acceptance in recent years as a first choice among surgical options for fibroids. Where myomectomy used to be limited to those who wished to have children in the future, there is a growing body of data suggesting that outcomes are similar to hysterectomy in women beyond their primary childbearing years,2 and it has been promoted by some in the gynaecology community as a preferred uterine-sparing treatment. It is in this context that we evaluate the FEMME study.
At first glance, some might be disappointed that the primary outcome from this study, the change in the quality of life score from the UFS QOL, showed a modest advantage for myomectomy, about eight points on a scale of 0 to 100. Higher scores on this scale reflect better quality of life. This was the primary conclusion reported in the abstract. However, when one looks closer some important points become clear. First, an eight-point difference is a modest difference at best, not reflecting a clinically important difference. As the authors note, the confidence interval suggests a range from no difference to a moderate 15-point difference.
The second important point is that, despite randomisation, the myomectomy group had lower baseline quality of life scores. This is a statistical aberration but with a direct impact on the primary outcome, which was the change in quality of life score. The final quality of life score was 80 for UAE patients and 84 for myomectomy patients, a minimal difference, below the threshold of what constitutes a clinically-important difference for this questionnaire.
A final point is that the more important measure on this questionnaire is the symptom score, which also showed a small, not clinically-important difference at six months in favor of myomectomy and no statistically significant difference at 12 months and two years. These findings confirm an earlier study using the same questionnaire comparing the outcomes of UAE, myomectomy, and hysterectomy with normal controls,3 in which myomectomy and UAE had similar quality of life and symptom scores.
So, the final scores are comparable, as were the safety and the limited fertility outcomes. The important takeaway from the study is that both these treatments are highly effective and they produce comparable outcomes in this population. When women choose a treatment for fibroids, they take a range of factors into consideration, including the outcomes mentioned, but also the time for recovery and time away from normal activities. In most cases, they will be comparing open operative myomectomy to a minimally invasive procedure, and many women are likely to believe that UAE is a better choice for them.
Having said that, the FEMME trial was not powered to address reproductive outcomes and, despite comparability in the very limited data presented, we cannot conclude that the reproductive outcomes are the same. There has only been one randomised trial reporting on reproductive outcomes of UAE versus myomectomy,4 and it showed an advantage for myomectomy. However, the data were not strong, and this lead the most recent Cochrane Review in 2012 to conclude that there was weak evidence favoring myomectomy over UAE for those seeking to become pregnant—to quote: “There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08–0.84; pregnancy: OR, 0.29; 95% CI, 0.10–0.85, one study, 66 women”.5
The FEMME trial investigators are to be congratulated on completing a randomised trial comparing these two therapies. The study has contributed significantly to our knowledge of these two therapies, demonstrating that the two procedures provide very similar outcomes and, while each patient’s circumstances are different, UAE should be considered whenever myomectomy is proposed.
James B Spies is an interventional radiologist at MedStar Georgetown University Hospital, Washington, DC, USA.
References:
The Australian Medicare Services Advisory Committee (MSAC) has recommended restoring Medicare funding for vertebroplasty in patients with severely painful thoracolumbar fractures of less than three-weeks duration.
The MSAC is an independent, non-statutory committee established by the Australian Government Minister for Health in 1998. The body appraises new medical services proposed for public funding, and provides advice to government on whether a new medical service should be publicly funded (and, if so, under what circumstances) on an assessment of its comparative safety, clinical effectiveness, cost-effectiveness, and total cost, using the best available evidence. Interventional News has been informed by an Australian interventional radiologist that, following the MSAC recommendation, “It is now a formality that parliament will approve a Medicare item number for vertebroplasty”.
The MSAC recommendation comes after the Interventional Radiology Society of Australasia (IRSA) submitted an application to the Department of Health requesting the reinstatement of Medicare Benefits Schedule listing for vertebroplasty for severely painful osteoporotic thoracolumbar vertebral fractures of three-weeks duration or less in Australia, which was discussed at the 78th MSAC Meeting, on 3 April 2020.
MSAC’s advice to the Minister reads: “After considering the strength of the available evidence in relation to its safety, clinical effectiveness and cost-effectiveness, MSAC supported public funding for vertebroplasty for severely painful thoracolumbar osteoporotic fracture of three-weeks duration or less, as suggested during the MSAC Stakeholder Meeting on Vertebroplasty held on 7 June 2019. MSAC also advised that a prospective registry be developed to monitor this listing.”
Lead author of the VAPOUR trial (Vertebroplasty for Acute Painful Osteoporotic fractURes) William Clark (St George Private Hospital, Sydney, Australia) explains how the VAPOUR trial identified a subset of patients who benefit from the minimally invasive procedure, expanding on these ideas in a commentary for this newspaper how the VAPOUR trial results ultimately led to the reinstatement of Medicare funding in Australia.
Vertebroplasty is defined in the MSAC recommendation document as “A procedure in which acrylic cement is injected into a bone of the spine to treat a break (fracture) where the bone was already weakened due to osteoporosis, and where the break has resulted in pain and limited mobility affecting quality of life.”
“MSAC accepted that vertebroplasty has a benefit in a small population of patients by helping them regain their mobility sooner and reducing pain in the short term,” states the consumer summary. “However, MSAC noted that the cost-effectiveness of vertebroplasty is uncertain. MSAC also considered that the procedure might be used in patients for whom there is no evidence of any benefit. Therefore, MSAC advised that the use of vertebroplasty be limited to those patients with recent and severely painful fractures of a certain type and location. The Committee also suggested that this use is monitored through a registry for at least two years, so that information can be collected about who is receiving the treatment and the costs associated with that treatment. This will provide data that MSAC can review in the future to ensure that the procedure is being used appropriately according to these specified criteria.”
Vertebroplasty previously stripped of eligibility for Medicare funding: A timeline of events
Vertebroplasty was previously listed on the Medicare Benefits Schedule from 2005 to 2011 based on recommendation in the 2005 MSAC report. The interim item number was to be reassessed by 2010.
MSAC completed its second review in April 2011 and did not recommend continued public funding based on two randomised controlled trials, published together in the New England Journal of Medicine in 2009, that did not appear to support vertebroplasty.
An application for relisting vertebroplasty for severely painful osteoporotic vertebral fractures of less than six-weeks duration on the Medicare Benefits Schedule was submitted to MSAC after the results of the VAPOUR randomised controlled trial were published in The Lancet in 2016. The six-week limit for facture duration was later modified by consensus between MSAC and IRSA to three-weeks.
MSAC considered this application for relisting vertebroplasty in a November 2018 meeting, but did not support pubic funding for vertebroplasty due to the committee being “uncertain of its clinical significance”. They did, however, acknowledge that there may be “a small clinical benefit” from vertebroplasty.
In March 2019, MSAC again considered the application, but deferred its advice until a stakeholder meeting could be held, as the body believed this would “provide a broader clinical perspective and patient input, [and] could inform the uncertainties in the application”.
The June 2019 stakeholder meeting represented a turning-point for vertebroplasty advocates. In the publicly-available minutes of this meeting, it is noted: “One clinician commented that there is respect among his colleagues for the MSAC process. They feel it is fair and rigorous and prevents adoption of low value practice and wastage of health funding. However, there is some concern that the process is quite arduous, and the difficulty of obtaining the evidence required may discourage people from submitting applications for services that may be beneficial.
“The clinician suggested that MSAC needs to have procedural consistency in dealing with differences of opinion between professional groups. They commented that vertebroplasty is an established technique, and related that clinicians were achieving good results with it when it was previously funded. Clinicians were surprised when the 2009 randomised trials showed no benefit. The clinician commented that the VAPOUR trial compensated for problems in the early trials, and showed that with strict patient selection criteria, results can be positive. They expressed their disappointment that so far results of the VAPOUR trial had been combined with, and effectively ‘drowned out’ by, the other trials. Other clinicians agreed that there is no rationale for combining data from the VAPOUR trial for patients in the acute phase with data from other trials in patients with chronic fractures.”
Following the discussion at the stakeholder meeting, MSAC gave their funding recommendation.
Lead author of the VAPOUR trial (Vertebroplasty for Acute Painful Osteoporotic fractURes) William Clark discusses the recent history of Australian Medicare funding for vertebroplasty, detailing how the 2009 results of two negative trials resulted in the Medicare Services Advisory Committee (MSAC) pulling their financial backing of the procedure. He outlines how the VAPOUR trial identified a subset of patients who benefit from the minimally invasive procedure, and ultimately led to the reinstatement of Medicare funding nationally.
Our application for public funding of vertebroplasty in Australia was based on the VAPOUR trial. Medicare funding for vertebroplasty had been removed after two negative trials were published together in 2009. We felt that these trials had largely excluded the group of patients that we had been treating in Sydney—patients with severe pain and early fractures, especially hospitalised patients. We conducted the VAPOUR trial to gather evidence in this patient group and the trial showed positive benefits from vertebroplasty.
Consistent with the recent history of vertebroplasty debate, the Medicare Services Advisory Committee (MSAC) assessment was shrouded in controversy. The MSAC was torn between the positive evidence of VAPOUR, which was specific for this application, and the negative findings of the Cochrane vertebroplasty review. The situation was complicated by the first author of the Cochrane review being a committee member of the MSAC. Timing of the Cochrane review appeared designed to influence the MSAC assessment.
MSAC initially advised against funding vertebroplasty, citing negative findings of the Cochrane review. The Interventional Radiology Society of Australasia (IRSA) complained to the Australian government that the application had not received an impartial hearing and that the Cochrane review should have been excluded due to conflict of interest. VAPOUR authors have published a criticism that the Cochrane review misrepresented evidence from our trial.1
The MSAC agreed to reconsider the application and summoned a stakeholder meeting for vertebroplasty in June 2019, inviting additional input from a broader range of clinical, epidemiologic, and biostatistical experts. The consensus from this meeting supported public funding of vertebroplasty for a subgroup of patients with uncontrolled pain from acute thoracolumbar vertebral fractures of not more than three-weeks duration. This patient subgroup derived most benefit from vertebroplasty in the VAPOUR trial. It includes most of the patients who are hospitalised with osteoporotic spinal fracture pain.
Early vertebroplasty can reduce pain and the reliance on opiate analgesia, with its attendant negative side-effects (delirium and constipation), which so often complicate management of these patients. It can change the natural history of the fracture by restoring height and preventing further collapse while the fracture is still soft and pliable.
Two randomised trials have assessed vertebroplasty for patients with fractures of three weeks or less. Diamond and colleagues2 published findings of a sub-group analysis from the VAPOUR trial, looking at 93 patients (46 vertebroplasty, 47 placebo) who underwent an intervention within three-weeks of fracture. Yang and colleagues3 published an open label randomised trial of 107 patients (56 vertebroplasty, 51 control) for vertebroplasty performed within three-weeks of fracture. Both trials showed significantly better pain reduction in the vertebroplasty group and worse complications in the control group.
The authors of the VAPOUR trial are proud that we have helped identify a patient group likely to benefit from vertebroplasty. We encourage interventional radiologists to consider offering early vertebroplasty for patients with severe pain or immobility caused by osteoporotic vertebral fractures. Delay can mean missing the window of opportunity to change the natural history of the fracture to benefit these suffering patients.
William Clark is an interventional radiologist at St George Private Hospital, Sydney, Australia.
References
ID3 Medical Belgium has announced the first two enrolments in the SUPERSURG study to investigate the safety and efficacy of Abbott’s Supera peripheral stent system versus surgical endarterectomy in treating patients with common femoral artery disease, with and without femoral bifurcation involvement.
The physician initiated, prospective, multicentre, randomised study is set to enrol 286 patients at 13 centres in four European countries (Belgium, Poland, the Netherlands, and the UK).
Patients will be stratified first based on three criteria: obesity, calcification, and femoral bifurcation involvement. After this stratification, consented patients will be 1:1 randomised in an open surgical or endovascular arm.
In addition to superior safety and non-inferior efficacy of the Supera peripheral stent system arm as primary endpoints, the study will also assess core lab-based angiographical outcomes post common femoral endarterectomy in a subcohort of 40 patients.
The principal investigator of the SUPERSURG study is Koen Deloose, head of the Department of Vascular Surgery at AZ Sint Blasius hospital in Dendermonde, Belgium, who performed the first two procedures (one open and one endo) in the trial.
“My enthusiasm about the use of the Supera peripheral stent system in the common femoral area was initiated by some case experiences at high risk for surgery with great longer-term follow-up,” comments Deloose in ID3 Medical’s announcement.
“Based on these findings, we set up the physician-initiated single-arm VMI-CFA trial,” Deloose continues. “The 12- and 24-months outcomes of this 100-patient cohort, presented at VIVA 2019, confirmed our initial enthusiasm with core lab-based primary patencies of 95% and 93%, respectively, and freedom from target lesion revascularisation (TLR) of 98% at two years (in press). As these results were very close to our surgical data, but with lower complication rates, the idea for a head-to-head randomisation between both treatment strategies, with the same stringent assessment methods was born. With a support grant from Abbott Vascular, we were able to launch this exciting project”.
Looking to the future, Deloose concludes: “Based on the outcome of this trial, I hope to be able to define subgroups of patients who are better treated with surgery, others with a minimal invasive Supera peripheral stent system implantation. I am convinced that there will be a place for both complementary strategies in the vascular future.”
In the EffPac trial, designed to compare a drug-coated and an uncoated balloon in the treatment of vascular occlusion in the femoropopliteal region, the drug-coated device proved to be superior. Additionally, the complete review of the study cohort two years after the intervention showed no increased mortality with the drug-coated balloon.
In cooperation with the Center for Clinical Studies, radiologists at Jena University Hospital, Jena, Germany, initiated an investigation to evaluate the efficiency of the Luminor paclitaxel drug-coated balloon catheter (iVascular) versus an uncoated balloon.
The success of the treatment was measured by the patient’s ability to walk and by ultrasound examinations of the vascular permeability in two follow-up examinations. This prospective, multicentre, randomised controlled trial enrolled a total of 171 participants at 11 centres throughout Germany.
Principal investigator of the EffPac trial Ulf Teichgräber (Jena University Hospital) summarises the result: “Compared to the control group, in the group treated with drug-coated balloon catheters, there was better vascular permeability and less tissue formation at the former constriction two years after the procedure.”
On behalf of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany, the study authors re-checked the complete cohort with respect to morbidity and mortality. The reason for this was a meta-analysis of angioplasty studies published last year that warned of long-term increased mortality associated with paclitaxel-coated devices. This warning triggered discussions amongst experts, since subsequent analyses of patient-level data could not confirm the increased long-term risk.
According to a Jena University Hospital press release, a possible source of error in determining mortality rates is not considering patients who have not completed the entire follow-up programme. “Within the trials considered in the meta-analysis, these patients counted up to a quarter of the subjects. Their data are not included in the study result as if they had not participated at all. However, for mortality assessment, they have to be included. This happened for the first time in the EffPac trial: in the subsequent review, 167 patients were recorded, which represents almost the entire study cohort, thus preventing a misjudgement in comparing the groups,” the press release reads.
The review yielded no difference in the survival after two years between the groups treated with an uncoated balloon or with a paclitaxel-coated balloon. Teichgräber comments: “The mortality risk by drug-coated balloons turned out to be even lower than that shown in the original two-year results recently published. We could confirm angioplasty with paclitaxel-coated balloons to be a long-term successful and safe treatment option for intermittent claudication.”
A recent study, published online on 3 August in the European Journal of Vascular and Endovascular Surgery (EJVES), found that regional anaesthesia alone is reasonable for major lower extremity amputation (LEAMP) in high-risk patients, and may initiate a more efficacious enhanced recovery programme than general anaesthesia.
The authors of this retrospective cohort study—Michael R Hall (The University of North Carolina at Chapel Hill, Chapel Hill, USA) et al—detail that there was no difference in outcomes between regional or general anaesthesia techniques in patients undergoing LEAMP, but add that further studies are needed to establish best practices in LEAMP procedures.
Hall et al emphasise the fact that major limb amputations are psychologically stressful and subject patients to perioperative cardiovascular risk. They note that up to 90% of major LEAMP are being performed under general anaesthesia, despite the fact that regional anaesthesia is an acceptable option in most cases.
The authors state that obtaining a better understanding of who would benefit from regional versus general anaesthesia could reduce complications and help to establish best evidence-based practice, and their hypothesis was that patients undergoing LEAMP with regional anaesthesia would have better postoperative outcomes than patients receiving general anaesthesia.
Hall and colleagues used the Vascular Quality Initiative (VQI) lower extremity amputation module to identify patients aged 18 or over who underwent LEAMP from 2013 to 2018.
They note that outcomes included 30-day incidence of major adverse cardiac events (MACE) and all-cause mortality, and used multivariate logistic regression modules to compute odds ratios (ORs) and 95% confidence intervals (CI). They analysed time to death using standard survival analysis.
Writing in EJVES, Hall et al detail that the final sample included 5,567 patients (median age: 65 years; 67% white, 65% male). They report that only 719 patients, representing 13% of the cohort, received regional anaesthesia. In addition, compared with patients undergoing general anaesthesia, patients in the regional group were older (67 vs. 65 years; p<0.001) and more likely to have diabetes (78% vs. 69%; p<0.001), end stage renal disease (26% vs. 18%; p<0.001), congestive heart failure (33% vs. 27%; p<0.01), and coronary artery disease (35% vs. 30%; p<0.01).
Hall and colleagues add that the overall incidence of MACE, death, and MACE or death was 5%, 6%, and 9%, respectively. In addition, there was no statistically significant difference by anaesthesia groups for MACE (OR 0.98, 95% CI 0.69–1.39) or mortality (hazard ratio [HR] 1.03, 95% CI 0.9–1.17).
According to Hall et al, this is the largest retrospective study analysing the outcomes for LEAMP using either regional or general anaesthesia. They note that other research using the National Surgical Quality Improvement Program (NSQIP) database demonstrated similar results, namely no difference in 30-day mortality or cardiac events, but was limited to above-knee amputations only and the majority of the regional anaesthesia used was spinal anaesthesia. “The present results parallel these studies while including regional nerve block techniques as well as all major LEAMP in the analysis,” they comment, which they add suggests acceptable short-term outcomes for all types of regional anaesthesia.
The authors recognise that physiological stress during and immediately after the major LEAMP operation may drive the postoperative outcomes regardless of anaesthetic approach and state that further study is warranted to determine whether regional anaesthesia can attenuate that stress by reducing the pain response during and after surgery.
Hall et al also acknowledge that the study is observational in nature and so the results do not imply causality, but instead describe the association between anaesthesia type and outcomes.
Commenting further on the study design, they concede that it made controlling for residual confounding impossible. “A randomised trial would be required to address this issue,” they remark.
Hall and colleagues end by stressing the many strengths of the methods they used. “The VQI represents a ‘real-world’ data source that provides a view of current outcomes in a large population of patients undergoing elective limb amputation,” they comment, and the findings “offer a critical insight into this highly complex, highly comorbid, and understudied population”.
The authors conclude that many patients are candidates for regional anaesthesia and this study “has shown that his method of anaesthesia is a reasonable alternative to general anaesthesia”.
A randomised controlled trial has found that clinical and patient-reported outcomes following radiofrequency ablation (RFA) of varicose veins without compression are no worse than with compression. Madu Onwudike (Manchester University NHS Foundation Trust, Manchester, UK) and colleagues conducted the study, which appeared as an Editor’s Choice paper in the July edition of the European Journal of Vascular and Endovascular Surgery (EJVES).
The authors detail that the target vein occlusion rate was not influenced by whether post-procedure compression was worn or not following RFA of varicose veins, where phlebectomies had not been performed adjunctively. Similarly, there was no evidence that quality of life (QoL) scores, patient satisfaction, and complications were inferior in the group that had no post-procedure compression.
Onwudike and colleagues write that post-procedure limb compression, hitherto routine following open varicose vein surgery, has been extended to endovenous procedures. “However,” they comment, “no robust evidence exists to support this practice”. Therefore, the investigators designed the present study to evaluate the clinical and patient-reported outcomes with and without post-procedure leg compression following RFA.
They note a few studies that raise doubts about the necessity for post-procedure compression, including a 2017 Annals of Vascular Surgery study by Ayo et al, which compared seven-day compression versus no compression and reported no difference in clinical (vein obliteration) and patient-reported outcomes (pain, ecchymosis, and QoL) following endovenous ablation. However, Onwudike et al’s study is the first to investigate the role of post-procedure compression where all the veins were exclusively ablated using RFA.
In this single-centre, prospective, non-inferiority randomised controlled trial, the investigators recruited adult patients into two groups: A (RFA with compression stockings for two weeks) and B: (RFA alone). The primary outcome was ultrasound determined target vein obliteration at 12 weeks. Secondary outcome measures included a QoL score (Aberdeen Varicose Vein Severity Score [AVSS] and Revised Venous Clinical Severity Score [RVCSS]), patient satisfaction, pain score, and complications.
In total, the investigators recruited 100 consecutive patients—51 to group A and 49 to group B—classified as clinical class C2–C6 of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification.
Onwudike and colleagues write in EJVES that, at 12 weeks, the occlusion rate of the target vein was similar in both groups at 98% (n=47) and 98% (n=45), respectively (p=1).
They also report that here was no statistically significant different in mean AVSS 6 vs. 5 (mean difference -1, 95% confidence interval [CI] -2–3, p=0.57) and mean RVCSS 3 vs. 4 (mean difference 1, 95% CI -1–2, p=0.46) scores at 12 weeks.
Finally, they observed comparable patient satisfaction scores (p=0.72) and pain score 2 vs. 2 (p=0.92) were achieved in both groups. Two patients in each group developed deep vein thrombosis at two-week follow-up (p=1 for above the knee and p=1 for below the knee).
In the discussion of their findings, Onwudike et al remark that the method of randomisation and the fact that both the chief investigator and the statistician were blinded to the allocated group reduced the risk of bias. In addition, the low dropout rate reduced the risk of type 2 error.
However, they also note some limitations. Firstly, Onwudike and colleagues recognise that the study is from a single centre and it only reports short-term results. “Long-term follow-up analysis may give further insight into differences in success rates based on compression therapy use,” they write.
Overall, while the authors “accept that the place or duration of compression post-RFA is far from settled,” they expect that this study will “contribute to development of the body of knowledge on the subject”.
Onwudike et al elaborate that, while earlier studies concentrated on the duration of compression, the present study and that of Ayo et al have moved the discussion on to answering the question of whether compression is required at all following RFA in situations where phlebectomies have not been performed. “This is consistent with a publication by the UK National Institute for Health and Care Excellent (NICE), which highlighted the knowledge gap in the role of compression following endothermal ablation,” they remark.
Furthermore, they note that this study is also a partial response to the European Society for Vascular Surgery (ESVS) guidelines, which recommend the need for further studies in this area. Onwudike and colleagues state that, if the present findings are confirmed by larger studies, “it is likely that the current recommendation of post-procedural compression for all cases of open surgery and endovenous superficial vein procedures will be revised”.
The authors summarise: “This trial supports the conclusion that the widely practised use of compression after RFA adds no clinical benefit for the patients.” However, they add that a much larger study, “preferably a multicentre trial,” may be required to confirm their findings.
Interventional radiology is “an operational and financial hedge” for hospitals during COVID-19, Mikin Patel (University of Arizona College of Medicine, Tucson, USA) and co-authors claim in Journal of Vascular and Interventional Radiology (JVIR).
“Under normal circumstances, interventional radiology (IR) efficiently cares for both inpatients and outpatients,” the authors note. “In response to the COVID-19 pandemic, IR has taken a more prominent role in the hospital, accounting for an increased share of both procedural volumes and gross charges at two academic medical centres [in the USA], the first with a total of 894 beds in Tucson, Arizona, and the second with 811 beds in Chicago, Illinois. This trend countered the observed, and notably opposite, trend towards a relative decrease in contribution from other prominent procedural services (surgery, cardiac catheterisation lab, and endoscopy).”
The JVIR report used aggregated departmental data from the two institutions studied to investigate procedural volume. At the start of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services gave the recommendation that all elective surgeries, as well as all non-essential medical, surgical, and dental procedures, should be cancelled or delayed during the pandemic. Therefore, at both medical centres evaluated in this study, procedural volumes across the hospital decreased year-over-year (35% and 69%, respectively) in April 2020.
However, IR procedural volumes decreased by a much smaller amount (22% and 35%, respectively). Over the same time-frame, procedural volumes in surgery, cardiac catheterisation lab, and endoscopy decreased by a much larger proportion: -45%, -30%, and -40%, respectively, in the Tucson centre, and -72%, -56%, and -81%, respectively, in the Chicago hospital.
At the medical centre in Tucson, total gross procedural charges for the hospital decreased 40% year-over-year in April 2020, but IR charges had only decreased 20%. For surgery, this decrease was more stark, at 44%. Gross procedural charges in the catheterisation lab declined by 35%, and endoscopy charges were reduced by 43% in the same month.
“The data above demonstrate that, while other procedural services such as surgery, cardiac catheterisation lab, and endoscopy have suffered decreased procedural volume and charges, IR has filled the void,” Patel and colleagues write in their brief research letter. “The resultant increased disparity in work performed and charges generated should be recognised by hospital administration as a source of procedural revenue that is relatively spared. Furthermore, the work performed by IR during the pandemic likely provides value by contributing to patient discharges and length of stay metrics, however the authors acknowledge this would be difficult to quantify.”
They note that the majority of IR procedures took place in the outpatient setting in 2019, while most surgery and catheterisation lab procedures were performed on inpatients (56% and 60%, respectively). As the COVID-19 pandemic led to suspension of non-essential procedures, Patel et al say that resources were diverted towards inpatient care. “Paradoxically, IR pivoted from a predominantly outpatient-based practice to a service focused on hospital in patients, while services that were predominantly treating inpatients in 2019 decreased their role,” they relate.
Speaking to Interventional News, Patel comments: “I do think that interventional radiology’s role in treating hospitalised patients will continue to grow whether or not we are under pandemic conditions. In the short term, the COVID-19 pandemic has exaggerated this trend. In the long term, I am optimistic the ‘new generation’ of interventional radiologists we have been training will push the advantages of IR therapies for patients.
“Ideally, hospitals will recognise the value IR brings in terms of efficacy, quality, and efficiency for patients. From the administrative perspective, it sometimes feels as if IR gets lumped in with the rest of radiology and is treated as a service to be ‘ordered’ by other physicians. It may be time for hospitals to start treating IR more like a surgical subspecialty, recognising the need for things like clinic space, scheduling support, and dedicated coders.”
“IR’s adaptation to the operational shocks of the COVID-19 pandemic was largely the result of two factors: efficiency in reconfiguring workflows and availability to treat patients,” the JVIR authors continue. “At both medical centres included in this report, IR departments promptly prepared for handling of COVID-19 patients by adding negative pressure air handling for IR suites, clearly assigning duties and personal protective equipment for staff, and establishing clear protocols on potentially aerosolising procedures requiring extra precautions. Notably, these changes took effect in IR before they were implemented in the operating rooms.”
In addition, interventional radiologists working at both institutions included in this study noted an increased number of consult requests for procedures which are traditionally areas of considerable overlap in scope of practice (central venous access, gastrostomy, nephrostomies, biopsies, and venous thromboembolism intervention). In many cases, other procedural services had rejected these consultations for lack of medical urgency, and IR was available and ready to treat these patients during the COVID-19 pandemic.
“The flexibility and motivation to accommodate the needs of the hospital are arguably core principles of IR which appear to be common across multiple institutions. During times of stress, these strengths allow IR to serve as an operational and financial hedge for ensuring the continued health of critically ill patients and burdened health systems,” they conclude.
Repeat prostatic artery embolization (PAE) is safe and effective for recurrence of lower urinary tract symptoms (LUTS) or acute urinary retention caused by benign prostatic hyperplasia (BPH), and may be used as a first-line treatment option. However, it has limited impact in patients who did not show a response to the initial embolization procedure. This is the conclusion presented by Nuno Costa (Saint Louis Hospital, Lisbon, Portugal) et al in their recent publication in Journal of Vascular and Interventional Radiology (JVIR).
The study investigators set out to evaluate the safety and efficacy of repeat PAE for LUTS caused by BPH, to define revascularisation patterns, and to establish predictors of outcome in larger cohort of treated patients. Costa and colleagues conducted a single-centre, retrospective study investigating 108 patients with BPH and clinical failure after PAE who then underwent repeat PAE between June 2009 and October 2018. Of these 108, 39 did not show a response to their initial PAE, and 69 had an initially favourable response in the first six months following PAE, but then experienced relapsing symptoms.
Clinical failure after initial PAE, as seen in the 39 non-responders, was defined as improvement in International Prostate Symptom Score (IPSS) after PAE of less than 25%, an IPSS after PAE of more than 15 points, no improvement in quality of life related to LUTS or a quality of life score greater than three points, acute urinary retention after PAE, and need for any additional medical or invasive therapy for LUTS.
The cumulative probability of clinical success at 12 months following repeat PAE was higher for patients who initially responded positively to embolization and were subsequently treated for a recurrence of initial symptoms than for patients who did not show a response at all to initial PAE: 56.7% versus 28.2%.
Indeed, for patients with symptom relapse after initial PAE, the clinical outcomes were comparable to those reported for PAE: mean IPSS improvement of 9.5 points, mean quality of life improvement of 1.3 points, and clinical success rates of 84% at one month, and more than 50% at mid-term and long-term follow-up appointments. Costa et al suggest that “these results may justify repeat PAE”.
They continue: “Of note, the subjective parameters of LUTS (IPSS/ quality of life scores) were not the only improvements noted after repeat PAE. Objective parameters such as prostate volume, postvoid residual volume, peak urinary flow [Qmax], and prostate-specific antigen level also showed significant improvements after repeat PAE.” They point out that the difference between non-responders and relapsers after repeat PAE were only observed in the IPSS/ quality of life analyses.
Speaking to Interventional News, Tiago Bilhim (Saint Louis Hospital, Lisbon, Portugal), a co-author of the JVIR paper, says: “This study is important because it is not uncommon to follow-up patients after PAE that still have residual LUTS and that may need additional treatments. These treatment options include medical management, surgery, and repeat PAE. In order to advise patients that still have LUTS after PAE about the best treatment options, one should have a clear idea on the potential outcomes from repeat PAE. We have previously shown [in a 2016 Radiology paper by Bilhim et al] that patient selection is important to improve outcomes.”
Up to 20% of PAE patients undergo repeat intervention after one year, with a minority of clinical failures occurring in patients who experience symptom relapse after initial improvement (80% of clinical failures never show any improvement post-procedurally, and are in the non-responders category of this study). By demonstrating the safety and efficacy of repeat PAE, the investigators hope that this clinical study sheds some light on the treatment options available for patients who are deemed clinical failures following embolization.
“The present study […] expands on the concept that not all patients respond to PAE the same way, and that patient selection plays a pivotal role in improving clinical outcomes,” the authors note. “Even with a technical success rate of 100% and a unilateral repeat PAE rate lower than 6% (similar between relapsers and non-responders), clinical outcomes in non-responders were inferior to those reported for PAE. Even though as many as 17% of patients who never showed a response to PAE may still exhibit clinical success 24 months after repeat PAE, the vast majority of these patients do not show improvement. Therefore, repeat PAE should probably be avoided in patients who do not show a response to initial PAE.”
Expanding on this idea, Bilhim tells this newspaper: “In this study, we prove once more that patient selection rather than PAE technique has a profound impact on outcomes. PAE is not a ‘perfect fit’ in all patients with LUTS and BPH, with up to 25% of clinical failures despite optimal technique. Correlation of clinical outcomes after PAE with prostate volume reduction are not clear, with many patients improving LUTS with minimum prostate volume reduction and vice-versa. We now know that patient factors play a role. A lot of studies exist nowadays looking at predictors of clinical outcome for PAE.”
Some identified predictors of clinical outcome listed by Bilhim include:
The embolization procedure
Patients were treated in an outpatient setting by a team of experienced interventional radiologists: two with nine years of experience with PAE each, one with four years experience, and one with one years experience. PAE was performed under local anaesthesia by a unilateral or bilateral femoral approach “wherever feasible”, the authors describe, stating that this was “usually through the right femoral artery”. In total, a unilateral femoral approach was used in 101 patients, and a bilateral approach in seven patients.
Embolization was performed with different embolic agents, including: non-spherical polyvinyl alcohol (PVA) particles (100–300μm), spherical PVA particles (Bead Block 100–300μm and 300–500μm; BTG International, London, UK), tris-acryl gelatin microspheres (Embosphere 100–300μm and 300–500μm; Merit Medical), and Polyzene-coated hydrogel microspheres (Embozene 250μm and 400μm; CeloNova, San Antonio, Texas).
Repeat PAE was considered more technically challenging than the initial embolization procedure: at 75 minutes (range: 20–120 minutes), the median procedure time of the repeat embolization was significantly higher versus initial PAE. Microspheres were used more often in repeat PAE procedures than the initial embolization, but Costa et al acknowledge that this “reflects a temporal trend rather than an intended method”.
There were no major complications. Among the 108 patients, 104 (96.3%) were discharged three to six hours after PAE, and the other four (3.7%) spent the night in the hospital and were discharged the next morning (18 hours later) per personal preference.
The endpoint of embolization was occlusion of all vessels to the prostate and reflux toward the prostatic artery. Embolization of at least one prostatic artery was considered a technically successful repeat PAE—repeat PAE was technically successful in all patients.
Endologix recently announced that it has received a CE mark for the Alto abdominal stent graft system.
“We are very excited to receive a CE mark for the Alto system, that has been achieved through a strong partnership and collaboration with our European notified body, NSAI ” commented Matt Thompson, chief medical officer of Endologix. “Alto will provide our physician partners and patients in the EU with a differentiated low profile endovascular treatment option designed to improve durability over traditional EVAR. In addition, with Alto, we anticipate observing improved short-term outcomes relative to the Ovation iX abdominal stent graft system (Ovation iX) as a result of the design and manufacturing changes incorporated into Alto. Lastly, CE mark of the Alto system is yet another critical milestone for Endologix as we seek to introduce a portfolio of devices to address the current unmet needs of endovascular aneurysm repair (EVAR).”
“Alto offers a highly differentiated endovascular treatment option to AAA patients and includes design features that we believe will enhance ease-of-use, improve acute outcomes and preserve the long-term durability associated with patient-specific anatomically adaptive sealing,” commented John Onopchenko, chief executive Officer of Endologix.
“We believe Alto, with its ultra-low profile and 7mm aortic neck length indication, will provide patients and physicians with an endograft capable of treating the highest proportion of patients within the indications for use of the device. As we continue with the global roll-out of the Alto system, which has commenced in the USA, Endologix is committed to investing in the highest levels of clinical evidence by initiating a head-to-head randomised controlled trial versus traditional undifferentiated EVAR grafts, with the intent of proving the superiority of Alto. Finally, with our recent announcement regarding our proposed transition to a private company, we are poised to meet the needs of our customers and the patients we proudly serve and fulfil our company mission.”
Surmodics recently announced it has received US Food and Drug Administration (FDA) 510(k) clearance for its Sublime radial access 0.014 rapid exchange (RX) percutaneous transluminal angioplasty (PTA) dilatation catheter.
According to a press release, the Sublime radial access 0.014 RX PTA catheter allows below-the-knee access through a transradial approach by providing the longest working length (250cm) on the market. Outer balloon diameters range from 2–4mm with balloon lengths between 20mm and 220mm. The product joins the previously cleared Sublime radial guide sheath within the company’s Sublime radial access platform and is designed to facilitate radial access for the treatment of above- or below-the-knee arteries.
“FDA 510(k) approval of the Sublime radial access 0.014 RX PTA dilation catheter is another step forward in our strategy to become a provider of whole-product vascular solutions through the design, development and manufacturing of highly differentiated products,” said Gary Maharaj, Surmodics president and CEO. “The continued expansion of our Sublime radial access platform demonstrates our commitment to developing the transradial peripheral market space through the introduction of longer, lower-profile devices that fill unmet physician and patient needs.”
Radial access offers many benefits relative to femoral access including reduced puncture site bleeding complications, earlier ambulation, reduced length of hospital stay, and lower healthcare costs. Although transradial access has become a mainstream technique in percutaneous coronary interventions (PCI), it has been less widely adopted in peripheral interventions due to the limited availability of purpose-designed access and therapeutic devices.
The Sublime 0.014 RX PTA dilatation catheter is compatible with a 5Fr guide sheath and is designed to provide the performance of an over-the-wire PTA catheter in an RX platform. Its proprietary reinforced shaft technology with flexible, kink-resistant construction and a tapered RX port transition are designed for optimal trackability and push through distal tortuosity.
A new post-market study investigating the effectiveness of the Renzan peripheral stent system (Terumo) in patients with peripheral arterial disease (PAD) has been initiated. PRIZER
The PRIZER (Prospective, multicentre post-market, single-arm study, to confirm the performance of the Renzan peripheral stent system in treating subjects with superficial femoral and/or popliteal artery disease) study plans to enrol 135 patients, in approximately 10 European centres in five countries. Patients will be stratified into two groups: 90 patients with arterial disease in both the femoral and popliteal segments, and 45 patients with isolated popliteal artery disease.
The Renzan peripheral stent system consists of a self-expanding nitinol stent pre-mounted on the distal portion of a rapid exchange (RX) delivery catheter, constructed from two layers of tubular braided nitinol wire mesh.
As well as aiming to confirm the safety and efficacy of the Renzan peripheral stent system in treating patients with superficial femoral and/or popliteal artery disease, the PRIZER study aims to assess the primary patency of the artery evaluated at 12 months, compared to clinical results coming from other clinical trials using similar metallic scaffolds.
“My enthusiasm about the dual layer Roadsaver stent in the carotid field can be investigated in this way in the even more challenging infra-inguinal area”, comments Koen Deloose, head of Department of Vascular Surgery at AZ Sint Blasius Dendermonde hospital in Dendermonde, Belgium, and principal investigator of the PRIZER study. “In current times, where drug-eluting technology is only reserved for high risk patients and where the need for scaffolding post drug-coated balloon treatment is high, a lot of interventionalists are really looking for a ‘daily practice’ modern scaffold that is extremely flexible, well balanced in chronic outward force and radial resistive force, and easy to implant accurately. The new 018″-compatible nitinol braided Renzan stent with dual layer technology over the full length showed in some proof of concept cases to respond extremely well to all my expectations. The PRIZER study offers us the possibility to further investigate the safety and efficacy of the Renzan peripheral stent system for treatment of superficial femoral and/or popliteal artery disease in 135 patients”, Deloose continues.
“We are very proud to contribute to our commitment to physicians and their patients and drive innovation in the field of peripheral artery disease”, says Jim Rushworth, chief commercial officer, Terumo Global. “With this clinical trial, we explore initiatives to increase our footprint in peripheral interventions.”
“This new technology ensures a great flexibility, conformability to the vessel, and fracture resistance”, comments Christophe Giot, chief medical officer, Terumo Europe. “The PRIZER study aims to provide scientific evidence for RENZAN stent in patients suffering from peripheral arterial disease.”
Peripheral arterial disease affects more than 200 million people worldwide
PAD is a progressive disorder caused by atherosclerotic changes in the blood vessel wall, which result in stenosis or occlusion of the arteries outside the heart and brain. The pathology affects more than 200 million people worldwide. In the last decade, the number of PAD-affected individuals increased by 13% in high- and by 29% in low-income countries. The PAD prevalence increases with age, affecting over 20% of octogenarians. Lower extremity PAD is its most common subset. PAD is associated with high morbidity and both cardiovascular and all-cause mortality rates. The pathology causes major personal, medical, and socio-economic burden, increasingly becoming a global healthcare concern.
Cerus Endovascular and AB Medica, a subsidiary of Balt, has announced that they have entered into a strategic distribution agreement providing AB Medica with the exclusive rights to market and sell the newly CE marked Contour Neurovascular System and the Neqstent Coil Assisted Flow Diverter devices in Germany.
“Our partnership with Balt will provide significantly increased awareness and more rapid penetration of both the Contour Neurovascular System and the Neqstent device within Germany, the largest market within the European Union (EU),” stated Stephen Griffin, president of Cerus Endovascular.
“Physicians in Germany have indicated their desire for greater access to our products and have, therefore, been very supportive of our decision to partner locally with AB Medica. We are excited to begin working closely together and eventually, to extending the distribution agreement into other key EU countries.”
Thomas Liebig, professor at the Institute for Diagnostic and Interventional Neuroradiology at Ludwig-Maximillian’s Universität München (LMU) and principal investigator of the CERUS clinical trial of the Contour Neurovascular System, noted, “I am delighted with the progress that Cerus has made thus far in Germany. At LMU, we performed the first case with the system in Germany back in 2018 and have been using the device consistently since CE mark was granted.”
“Balt has a long history of delivering innovative devices to the hands of physicians. With this partnership with Cerus, we are happy to continue with this tradition and look forward to providing two new unique products to physicians in Germany,” said Pascal Girin, CEO of Balt.
A new system designed to deliver Yttrium-90 (Y-90) resin microspheres during targeted liver cancer therapies, SIROS (Sirtex) has launched commercially.
A company press release states: “SIROS offers a visual, intuitive and versatile option for interventional radiologists to deliver SIR-Spheres to patients with liver cancer. With the system’s visually-controlled administration, physicians can determine and adjust the precise quantity and speed of SIR-Spheres microspheres delivery. Additionally, the system is designed to be simple to use yet versatile enough to allow expanded options for patient-tailored delivery.”
SIROS’ design features a peel-and-place tubing set, a proprietary needleless D-Vial specifically designed to suspend SIR-Spheres into a vortex that may allow for a more even distribution, and a locking cover to safely secure the microspheres during delivery. A three-step setup provides quick and simple administration and disposal.
“SIROS brings world-class expertise and innovation together to provide interventional radiologists with the support and technology they need to treat patients with liver cancer,” says Kevin R Smith, chief executive officer of Sirtex.
Siemens Healthineers has announced it has reached an agreement to acquire Varian Medical Systems, a US company active in the area of cancer research and therapy, in an all-cash transaction valued at $16.4 billion.
The combined company will offer an integrated platform of end-to-end oncology solutions to address the entire continuum of cancer care, from screening and diagnosis to care delivery and post-treatment survivorship. By bringing together the diagnostic tools, imaging, radiotherapy and AI capabilities across both companies, Varian and Siemens Healthineers aim to lead the digital transformation of oncology healthcare, to enable more efficient diagnosis, increased treatment quality and access, personalised precision cancer care, the companies said in a press release.
Under the terms of the agreement, Siemens Healthineers will acquire all outstanding shares of Varian for $177.50 per share in cash, representing a premium of approximately 42% to the 30-day volume weighted average closing price of Varian’s common stock as of July 31, 2020, the last trading day prior to the announcement of the transaction, and a premium of approximately 24% to the closing price of Varian’s common stock on July 31, 2020.
“Today’s announcement represents an important milestone in our company’s history,” said Dow Wilson, president and chief executive officer of Varian. “The combination with Siemens Healthineers brings us even closer to realising our transformative vision of a world without fear of cancer.
Bernd Montag, CEO of Siemens Healthineers AG said: “With this combination of two leading companies we make two leaps in one step: A leap in the fight against cancer and a leap in our overall impact on healthcare.”
The transaction is expected to close in the first half of calendar year 2021, subject to approval by Varian shareholders, receipt of regulatory approvals and other customary closing conditions.
Varian expects to continue to operate under the Varian name as an independent company within Siemens Healthineers following the completion of the transaction.
“Decreases in caseload and widespread cancellation of conferences have had significant impact on diagnostic and interventional radiology (DR/IR) training during COVID-19 restrictions,” Ahmed M Gabr (Oregon Health and Science University, Portland, USA; Tanta University, Tanta, Egypt) and colleagues reflect in Academic Radiology. “Whether remote learning can mitigate lost opportunities from in-person interactions remains uncertain. Optimising these strategies will be important for potential future restricted learning paradigms and can also be extrapolated to augment trainee education during unrestricted times.”
The study investigators set out to assess the immediate impact of the COVID-19 pandemic on diagnostic and interventional radiology education, and to propose measures to preserve and augment trainee education during future crises. They reviewed DR and IR procedures at a single tertiary-care teaching institution between 2015 and 2020, dividing DR up by section (body, cardiothoracic, musculoskeletal, neuroradiology, nuclear medicine, paediatrics, women’s imaging) and IR by procedural types (arterial, venous, lymphatic, core, neuro, paediatrics, dialysis, cancer embolization or ablation, non-cancer embolization, portal hypertension, and miscellaneous).
In their review, they note that remote learning technologies with annotated case recording, boards-style case reviews, procedural simulation, and narrated live cases, as well as online lectures and virtual journal clubs, have increased over the last few months.
Highlight findings
Results from a multicentre, randomised controlled trial—FEMME—published today in the New England Journal of Medicine (NEJM) indicate that myomectomy shows superior fibroid-related quality of life at two years compared to uterine artery embolization (UAE) in women with symptomatic uterine fibroids. Several prominent interventional radiologists suggest that while gynaecologists may use this headline finding to cease recommending UAE, the treatment is still a good therapeutic option in patients with symptomatic fibroids. They highlight that informed patient choice is at the heart of personalised fibroid therapy.
Isaac Manyonda (St George’s, University of London, London, UK) and colleagues’ publication coincides with fibroid awareness month. July 2020 has seen healthcare workers, hospitals, and other organisations promoting uterine health, shining a spotlight on an underexposed condition that one in three women will experience in their lifetime.
The triallists set out to compare the effect of UAE and myomectomy on quality of life in women with symptomatic fibroids wishing to avoid hysterectomy. The primary outcome measure of the FEMME trial (Fibroids with embolization or myomectomy to measure the effect on quality of life) was the condition-specific quality of life domain score from the Uterine Fibroid Symptom Quality of Life questionnaire (UFS-QOL). Scores could range from 0–100, with higher numbers indicating a better quality of life.
Average quality of life scores at two years were substantially improved in both groups, but were greater in those assigned to myomectomy (mean-adjusted difference using complete case analysis: eight points; 95% confidence interval [CI], 1.8–14.1; p=0.01; mean-adjusted difference with missing responses imputed: 6.5 points; 95% CI, 1.1–11.9). Mean quality of life score at two years from randomisation was 84.6±21.5 in the myomectomy cohort, versus 80±22 in the UAE group.
In total, 254 patients were recruited from 29 hospitals, and randomly assigned to undergo myomectomy or UAE as the primary procedure in a 1:1 ratio. Women were only eligible for enrolment if they were considered suitable for either procedure.
“The six- to eight-point benefit on average in health-related quality of life scores in the myomectomy group, as compared with the UAE group, is consistent with small to moderate standardised treatment benefit at two years,” the authors write. “However, the 95% confidence interval around these estimates indicates that plausible results range from almost no benefit of myomectomy over embolization to a moderate (15 point) difference.”
Despite the increased quality of life scores in the myomectomy cohort, several interventional radiologists, including two of the study co-authors, have expressed to Interventional News that UAE is still a good option for patients with symptomatic fibroids. Jonathan Moss (University of Glasgow, Glasgow, UK), a co-author of the NEJM study, comments: “Although the quality of life was higher in the myomectomy group and [this difference was] statistically significant, it was only a few points better. Therefore, provided women understand this, then they can choose either procedure.”
Fellow study author Anna-Maria Belli (St George’s University Hospital NHS Foundation Trust, London, UK) echoes this sentiment, telling this newspaper that “The results show a substantial benefit to treatment in both groups with regard to quality of life and symptom severity, even though the results for myomectomy were better than UAE.” However, she adds that she believes “The results do not mean UAE is an inferior treatment to myomectomy.
“With regard to menstrual blood loss, the results in both groups were comparable. This means that women should be offered either treatment and choose for themselves. For some women, avoiding a general anaesthetic, having a shorter hospital stay, and avoiding an open surgical procedure (the majority of myomectomies in FEMME were open abdominal as fibroid and uterine sizes were large) is of paramount importance, in which case UAE would be their preferred option.”
Gerard Goh (The Alfred Hospital, Melbourne, Australia) also enumerates the benefits of UAE: “Individualised medicine, i.e. tailoring treatment to the patient, is an important part of patient care and as interventional radiologists we are able to offer patients an alternative treatment to surgery. Even before the FEMME trial was published, we knew that there were some patients better-suited to myomectomy, and some better-suited to UAE. Some benefits of UAE are its ability to be performed under conscious sedation, as well as a shorter recovery time that may be better-suited to young women with busy family and work commitments.”
Contextualising the investigators’ decision to use UFS-QOL score as the primary outcome measure, Moss explains that quality of life measurements are “included in almost all randomised controlled trials [RCTs]”. Early UAE trials, such as REST and EMMY (from Scotland and The Netherlands, respectively) used the SF36 questionnaire, which Moss describes as a “generic quality of life instrument”.
Weighing in on the primary outcome measure of the FEMME trial, James Spies (MedStar Georgetown University Hospital, Washington, DC, USA) comments: “The primary outcome was the change in quality of life, and the quality of life scores of the myomectomy patients were worse at baseline than the UAE group, despite the randomisation. If one looks at final quality of life scores, they are very comparable within the sensitivity of the questionnaire used, but the study was designed to use the change in scores as the primary outcome [Spies’ emphasis]. Thus, somewhat artefactually, there was a greater improvement in quality of life scores for myomectomy. If one compares final quality of life scores or symptom scores, there would have been no difference.”
The authors acknowledge that the presence of some baseline differences in health-related quality of life and age between the two groups is a limitation of their analysis, but note that prespecified analyses were adjusted for the baseline health-related quality of life, and a post-hoc analysis adjusted for age showed similar findings.
Spies describes FEMME as “an important study, one of the very few randomised trials comparing myomectomy versus UAE. It shows very comparable outcomes of both procedures in terms of symptom control, quality of life, complications, and in the limited fertility outcomes. Overall, I congratulate the authors on completing an outstanding study, which validates UAE as an effective therapy that yields comparable outcomes in this population of patients.”
UAE and myomectomy result in comparable pregnancy rates, but numbers too small to call
In terms of fertility, there were no consistent differences between groups in the FEMME trial with regard to biomarkers of ovarian reserve. Nine women in the UAE group (8%) and five women in the myomectomy group (4%) reported pregnancies within two years of randomisation, resulting in six and four live births, respectively, the authors report. However, they note there are too few pregnancies amongst the trial cohort to inform the effects of the procedures on fertility.
Expounding on the clinical implications of the two-year results, Moss relates: “We found no evidence of ovarian damage using several markers after either procedure. The number of pregnancies was low in both groups. The pregnancy data is difficult to interpret, and the intention to treat (ITT) and per protocol analysis showed no difference [between the UAE and myomectomy groups]. Interestingly, if you look at the women who actually received UAE, there were slightly more pregnancies than in those who actually had myomectomy. However, the numbers are small, and one cannot draw any firm conclusions.”
Belli believes that an “important aspect” of the trial is that the results reveal “no adverse effect on ovarian reserve from UAE, which opens up the potential for further research in younger women wishing to become pregnant”. She notes that the average age was 40 in the trial, “so low pregnancy rates are not so surprising”.
Belli adds: “Also, this trial reflects the real population of women suffering from symptomatic fibroids, with a high proportion of black women and large fibroid uteruses (mean >1,000cc).”
“There is a surprising amount of resistance from the gynaecological community across the world about offering UAE to women who wish to maintain their fertility,” Moss opines. Prior to the FEMME trial, Moss outlines how “several smaller RCTs compared these two techniques, but the numbers were small and results conflicting. Some, such as FUME, had to exclude women wishing to become pregnant. FEMME overcomes most of these problems, even though the number of pregnancies is small, with limited data on that outcome.”
He further informs Interventional News that his research team are currently considering a large trial using pregnancy outcomes as the primary outcome measure, which they believe is needed. “It would have to be a trial of several thousand women, and probably an international effort,” he says.
Other secondary outcome measures similar in both groups
In addition to fertility, other secondary outcomes measures were similar for both myomectomy and UAE: menstrual bleeding scores, peri and postoperative complication rates, and the percentage of patients who would recommend their procedure to a friend.
Specifically, at two years, the percentage of women who would recommend myomectomy to a friend was 93%, versus 84% with UAE, while respective percentages of women who said they would have the procedure again were 78% and 74%.
Peri and postoperative complication rates for both procedures were low, Manyonda et al relate, with one conversion of a myomectomy to a hysterectomy, and one conversion from a laparoscopic to an open myomectomy. At six months post-procedure, 32 of 80 (40%) fibroids treated by embolization were completely infarcted. Peri and postoperative complications from all initial procedures occurred in 34 out of 118 patients (29%) in the myomectomy arm, and in 27 out of 113 patients (24%) in the UAE group (relative risk, 1.2; 95% CI, 0.8–1.9; p=0.4).
Furthermore, a “substantially” greater number of patients in the UAE group underwent additional procedures within two years of follow-up: 18 of the 110 patients with two-year data (16%), versus eight of the 111 women (7%) in the myomectomy cohort. “This observation may be explained in part by the lower quality of life reported in the UAE group,” Manyonda et al muse. “However, more hysterectomies were performed as the initial procedure in the myomectomy group, owing either to patient preference or clinical decision.”
Moss acknowledges that the higher re-intervention rate with UAE was “a little surprising, as both procedures preserve the uterus”.
However, UAE was associated with a shorter length of hospital stay: the median time spent in the hospital for an embolization patient was two days, compared with four days for a myomectomy patient.
Belli articulates her opinion of these findings: “We knew that UAE had a greater repeat treatment rate, but the complication rate is no different between the two treatments, even though the blood transfusion and haemorrhage rate was higher in the myomectomy group. I have always believed that getting rid of the large bulky fibroids [as with myomectomy] is ultimately more satisfying for women than simply returning menstrual function and other fibroid symptoms to normal. My happiest patients were the ones who had the largest reduction in bulk, despite counselling them that this was not the main aim of UAE.”
However, reflecting on the impact of these FEMME trial data, Belli adds: “I hope that the results of this trial will make gynaecologists more accepting of UAE as an alternative, and allow a larger trial to address pregnancy rates and outcomes to go ahead. Unfortunately, I am afraid some gynaecologists might simply read the headline result and use this to confirm their prejudices and not even offer UAE.”
Moss concurs, commenting that “trying to ‘open many closed minds’ was the largest barrier” to running this trial. “At times it felt like trying to persuade someone to change their religion,” he says, “so firmly held are some views. Triallists, however, must never give up, and having a strong team, like we did, is essential.
“My message on the results it that UAE has some advantages, such as avoiding an incision, a general anaesthetic, and more rapid recovery. In my view, it is for fully-informed patients to make their own choice.”
These results will be presented at the 2020 annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe (12–15 September), which will take place online this year for the first time.
C-arm developer Ziehm Imaging has purchased imaging software developer Therenva.
The acquisition comes after two years of work together, Ziehm said. The purchase will allow Ziehm to market Therenva’s EndoSize and EndoNaut intraoperative 3D navigation software for catheterisation procedures via Ziehm’s C-arm distribution network, according to the firm.
Instrumental to the development of interventional oncology in the USA and globally, William (Bill) Rilling tracks how the discipline has grown over the course of his career from a niche area of medicine for the most challenging cases to a subspecialty with its own society dedicated to revolutionising cancer care.
What initially drew you to interventional radiology (IR), and then specifically to cancer care?
My father was an engineer at GE Medical systems working on MR imaging systems and I had a summer job at GE working on MR spectroscopy experiments. This translated into additional research in MRI at UW Madison in undergrad and medical school so I was exposed to the power of rapidly progressing diagnostic imaging at an early age. In medical school, however, I was drawn to the operating room and the intensity of those experiences. I was torn between diagnostic radiology and surgical subspecialty training such as urology, but then I watched John McDermott drain a paraspinal abscess under CT guidance and the decision was made.
The decision to focus on cancer interventions was much more pragmatic. As a junior faculty member at the Medical College of Wisconsin, we were developing a strong multidisciplinary vascular practice but the turf battles with vascular surgery and cardiology were exploding at academic medical centres across the country. Cancer interventions were a blue ocean, with huge potential. I was also drawn to the cancer patient population—to see people face terrible circumstances with courage and grace is truly inspirational.
Who have been important mentors for you throughout your career?
I was fortunate to have wonderful mentors early in my career. During my fellowship at Northwestern University, both Bob Vogelzang and Al Nemcek influenced me greatly. At that time, Bob was spending many hours per week in meetings helping the Society of Interventional Radiology (SIR) construct the component coding system. Al was also doing work in multiple SIR committees and was starting to build some early quality infrastructure in IR. They both taught me that it was not enough to do the work of patient care every day, but that we should be giving back to this wonderful specialty by volunteering our time and expertise to help IR continue to grow. In my clinical practice, we were developing the foundations of a strong multidisciplinary vascular practice that continues to this day. It was my honour to work for 10 years with Jonathan Towne, who was a national leader in vascular surgery, a superb surgeon, and a fantastic and caring physician.
What challenges did you face in the early years of your interventional oncology (IO) practice, and do these differ to those IO faces now?
Initially, the challenges were to introduce the concept of IO techniques to colleagues in medical and surgical oncology. As with much of IR, we started out by treating the “hopeless cases” that had no other options. Once introduced, the power of these interventions were self evident—to see a patient walk out the door the same day after ablation of liver cancer, now cancer free. The integration of transarterial chemoembolization (TACE), radioembolization, and percutaneous ablation into practice patterns then followed, and so did the higher levels of evidence supporting their use.
Currently, the challenges are different. The rapid development of new targeted cancer drugs, and in particular immunotherapy, is revolutionising cancer care. We now have to discuss how and when to integrate IO therapies and systemic regimens and build the data to support such integration. We still have a very powerful case to make from patient quality of life and cost effectiveness perspectives, but we need to prove these as well.
You were involved in running the first ever meetings dedicated to IO back in 2001. How did this come about?
I joined the education committee for SIR as a junior faculty member to start getting involved in SIR. In the early 2000’s, the role of IR/IO in management of hepatocellular carcinoma (HCC) was beginning to blossom. At this time, I met Jeff Geschwind, and we planned and executed the first three stand-alone meetings focusing on multidisciplinary HCC management, beginning in 2001. To my knowledge, these were the first dedicated IO meetings ever organised, but of course, the term “interventional oncology” did not exist at that time.
As education counsellor on the Executive Council for the SIR, you helped develop the APDIR. How did this help improve IR education?
At that time, the IR programme directors met only once per year, for a couple of hours at the SIR annual meeting. The issues being faced by training programmes were becoming more complex, such as turf battles with other specialties, and it was clear we needed a more organised structure. With the support of SIR, we formed the Association of Program Directors in Interventional Radiology (APDIR). The APDIR had a stand alone meeting once per year with staff support from SIR. We started to tackle some urgent issues such as consistent participation in the National Resident Matching Program process and development of a core IR curriculum. Through APDIR, the programme directors were able to coordinate efforts and best practices to deal with the erosion of vascular cases, attracting medical students and residents to IR, and improving non procedural patient care skills.
You were also instrumental to the implementation of the IR residency task force. How did the existence of an IR-specific residency programme come about, and how has it shaped IR as a specialty?
In the early to mid 2000s, it was clear that IR was evolving into a specialty caring for a complex array of patient populations and that direct patient care was necessary to foster the growth of these new areas of practice. Delegation of the patient care aspects and just “doing procedures” was not an option. The complexity and diversity of interventions performed was expanding rapidly and the one year fellowship training pathway was not sufficient to adequately prepare IR trainees for future practice. Knowing that changing the training pathway was a process that would take many years, we formed the Primary Certificate Task Force in 2006 with an initial goal of a obtaining a stand alone IR certificate. I asked John Kaufman to chair the task force and he graciously accepted. As we went to work, it soon became clear that Diagnostic Radiology chairs and the American Board of Radiology and American College of Radiology would not support a pure IR certificate but would support a combined IR/DR certificate.
The ensuing process of navigating the politics, obtaining American Board of Medical Specialties (ABMS) and Accreditation Council for Graduate Medical Education (ACGME) approval, and implementation into the match was exceedingly complex and took over a decade from start to finish. In addition to John Kaufman, there were so many leaders in IR who pushed this to a successful completion, including Jeanne LaBerge, Gary Becker, Anne Roberts, Matt Mauro, Alan Matsumoto, Vicki Marx, Dan Siragusa, and Jan Durham. There have been countless others including my partner, Parag Patel, who have led the complex process of integration of the IR/DR residency into existing training programmes.
The IR/DR certificate was the first new primary specialty approved by ABMS in over two decades. Now, medical students can match direcly into a six year IR/DR programme that will prepare them for modern IR practice, including all the patient care skills necessary to succeed. By some measures, it is the most competitive specialty in American medicine. We are attracting the best and brightest to IR.
Would you describe the thought processes behind the decision to create the Society of Interventional Oncology (SIO) in 2017, and the reaction of the IR community at the time?
The decision to form SIO was made after a very long and thoughtful dialogue that occurred over a few years. The World Conference of Interventional Oncology (WCIO) had been in existence since 2005. WCIO was evolving into much broader activities, including research grants, clinical trial development, and advocacy with various cancer organisations. It was becoming much more than a meeting or conference. We also realised that there would be political ramifications to forming a new society. The last thing we wanted to do was damage or undermine IR as a whole, but felt that a small society focused on IO would have a positive impact on the future of patient care and, ultimately, IO as a subspecialty.
The reactions to forming SIO were varied. Certainly, there were some who feared this would weaken IR and might set a precedent for other subspecialties to “break off.” In my view, the development of subspecialty groups and societies is part of the natural evolution of IR. This process has occurred in many other medical specialties over time and is predictable. IR practice development is significantly driven by those who focus on subspecialty areas of practice, such as prostate artery ebmolization (PAE), venous disease, or women’s health. We need to enable subspecialisation and not fear it.
What has been the highlight of your presidency of the SIO?
For me personally, the highlight is to see forward progress on multiple fronts. We have initiated some simple processes which have the potential to make signifianct impacts on IO practice. We have organised expert panels to provide regular comments to disease specific National Comprehensive Cancer Network (NCCN) guidelines with some early evidence that we have initiated positive changes. We have organised committees working with existing cooperative groups such as Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN) to develop IO trials. SIO has also had success in more complex initiatives. Working with our industry partners, SIO has awarded US$1.5 million in translational research grants, some of which have served as a springboard to larger national grants. We are working with SIR to build IO-CORE, a large and disease specific registry platform for IO. We have multiple clinical trials in development which will help raise the level of evidence for IO in meaningful ways.
How do SIO, CIRSE, and SIR work together?
We are working diligently to coordinate efforts with both the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and SIR. At the end of the day, we all have the same goals: to improve patient care and to advance IR/IO with education and research. SIO leadership is in frequent communication with CIRSE and SIR leaders to try to coordinate our efforts on various fronts, and to hopefully avoid duplicative or competitive activities. As a small society compared to SIR and CIRSE, SIO does not have the resouces for government advocacy, coding and billing initiatives, and some other broad scale IR practice issues that the large societies handle very capably.
As stated above, SIO and SIR are cooperating in building IO-CORE, which will be a registry platform for prospective disease-focused IO data collection with research questions and data elements developed by international expert panels. I believe it is a win for everyone that we do not have parallel or competitive IO registry platforms in development. SIO has had a number of meetings with CIRSE leaders regarding the International Accreditation System for Interventional Oncology Services (IASIOS) initiative, led by Professor Andy Adam. We support the goals of IASIOS to help raise the quality and consistency of IO practice worldwide. We look forward many future cooperative projects with both CIRSE and SIR.
How has SIO adapted during the COVID-19 crisis, and what is the role of medical societies during a pandemic?
SIO has had to change and adapt, similar to all other societies and organisations during this crisis. We now have virtual board meetings, our last in person meeting was in January at the SIO annual meeting. We are planning next year’s annual meeting very aware of uncertainty of future in person meetings—trying to be nimble and have the ability to adjust as circumstances change.
Medical societies provide a very important source of information to members during times like this. I believe that SIO, SIR ,and CIRSE have all done a fantastic job helping to keep members informed of best practices during these rapidly changing circumstances. The webinars regarding patient care during the pandemic hosted by all three societies have been very informative and well attended across the board.
On a personal level, what are the central preoccupations when treating patients with cancer during a global pandemic?
It is a very challenging situation given that cancer patients are vulnerable and have poor outcomes when infected with COVID-19. However, we also know that their cancer needs treatment and that, in most patients, delaying treatment could result in poorer outcomes. So we must balance the risk and benefit and in the majority of cases, we have proceeded with IO treatments as usual. The exceptions have been renal cell cancer ablations and a small number of very small liver tumours that have demonstrated relative stability on imaging. We have worked diligently, as I am certain all IR practices have, to separate inpatient and outpatient flows as much as possible to minimise risk for patients coming in for outpatient treatment.
How do you think this coronavirus pandemic influenced IO, over the short- and long-term?
I think that IR as a specialty has stepped up and shown that we can respond to a public health crisis. Much of our efforts during the pandemic were to support our colleagues in the intensive care unit (ICU), forming teams to perform portable urgent procedures if necessary during the surge of COVID-19 patients in our hospitals.
As stated earlier, much of our IO practice has continued as usual during the pandemic. Globally, I think there has been a shift in some regions toward increased IO treatments, which use fewer hospital resources, PPE, and probably also cause less decrement in the immune system compared to surgery. Over the long term, some of these advantages may result in changes in practice patterns, but it is too early to tell. For example, there has been an increase in overall Y90 treatments in the US during the pandemic—we do not know if this trend will continue.
What are your hobbies and interests outside of medicine?
Outside of medicine, I am blessed to have a wonderful family, including my wife Kate and my three children, Nicholas (24), Gabrielle (20), and Nathaniel (19). Kate has put up with my long hours at the hospital and travel to meetings and my grumpiness at the end of a long day. My children keep me grounded and remind me that there is much to life outside of medicine. I love to spend time with them and to spend time doing just about anything outdoors. I enjoy hiking, skiing, fly fishing, boating, running, and still manage to get up and down the basketball court.
Artio Medical today announced it has acquired Flow Forward Medical, a medical device company developing methods for establishing and maintaining vascular access sites.
This stock-for-stock merger transaction in which Flow Forward merged with and into Artio was approved by the Board of Directors and stockholders of both companies. The transaction closed on 8 June 2020.
“Flow Forward’s venous dilation technology is highly complementary to Artio’s existing peripheral vascular portfolio, with significant overlap in physician call points and procedures,” commented F Nicholas Franano, president and CEO of Artio Medical. “This acquisition provides a unique opportunity to diversify Artio’s endovascular pipeline, which will now include next generation vascular access solutions for kidney failure patients.”
Studies suggest baseline vein diameter may play an important role in achieving and maintaining routine, reliable AVF use. Flow Forward’s Arteriovenous Fistula Eligibility System (AFE System) stimulates flow-mediated vein dilation to expand the initial vein diameter prior to the creation of an AVF. This aims to increase the number of haemodialysis patients eligible for AVF and to enhance the usability and lifespan of newly created AVFs.
“Creating and maintaining reliable access sites is a complex vascular challenge, often resulting in complications, repeat procedures, and increased cost to patients, yet is critical for lifesaving hemodialysis treatment,” commented Paul Muller, chief technology officer and general manager of Flow Forward. “We are very excited Artio recognises the significant potential of our technology and we look forward to leveraging their expertise as we prepare for our first clinical use in the coming months and then move toward commercialisation.”
This advertorial is sponsored by Bentley.
Maria Antonella Ruffino, a vascular interventional radiologist at Azienda Ospedaliera Universitaria Città della Salute e della Scienza in Turin, Italy, tells Vascular News about her team’s growing clinical experience with covered stents as a platform that offer a minimally invasive solution for arterial emergencies. Ruffino gives an insight into the advantages of covered stents in such cases, their potential limitations, and which ones may be a favourable option for emergency treatment.
Arterial emergencies, such as bleeding, pseudoaneurysm, dissection, or fistula are potentially life-threatening conditions. Spontaneous or iatrogenic arterial emergencies require prompt diagnosis and treatment. During the last few decades, the treatment of these lesions has shifted from emergency open surgery to an endovascular approach, and the latter is rapidly becoming part of the treatment algorithm.
What are the advantages of using covered stents in such emergency cases?
The main endovascular approaches include use of covered stents and embolisation. A key advantage of using a covered stent in an emergency case, when compared to embolisation, is that a stent graft guarantees the immediate exclusion of the lesion without the sacrifice of the target vessel, avoiding the risk of non-target embolisation, which can result in ischaemic complications and rebleeding. Preservation of flow is crucial – particularly in districts with a terminal vascularisation, without collaterals, such as the limbs and kidneys. Additionally, this also applies to the liver, where it is uncertain whether extrahepatic arteries provide sufficient collateral circulation in case of hepatic artery occlusion.
What is your clinical experience with covered stents?
At our centre, we started using the BeGraft peripheral stent graft (Bentley, Hechingen, Germany) in June 2015. In the beginning, we used it for iliac procedures in elective cases of severe aortoiliac occlusive disease. Subsequently, we expanded this to include cases of rupture or dissection, and for severe complications that can present when long, calcified iliac occlusions are treated. The availability, wide sizing range, good trackability and conformability of these stent grafts and their low profile (6F compatible up to 8mm diameter) led us to extend their use to other vessels in case of arterial injuries. Since 2018, we have also used the BeGraft aortic stent graft, which has allowed us to treat vessels of larger diameters. Our cardiology colleagues already use the BeGraft coronary stent.
During the last few years, we have treated many emergency cases with the BeGraft stent graft family. These include iliac ruptures or renal pseudoaneurysms – which are quite common – but also more complex cases, like common carotid artery bleeding or penetrating aortic ulcer rupture*. In these last two scenarios, in particular, where we needed a large stent graft (Ø12mm), we have experienced first-hand how a larger diameter BeGraft stent can perform in tortuous anatomies, thanks to its good trackability and low profile, as it can be used with small vascular sheaths (9F in these cases).
Part of our experience, which focused on iatrogenic arterial injuries, has been recently published in Medicine, reporting a technical success of 100% and a clinical success of 88%. No device- or procedure-related deaths, nor major complications were reported. There was no patency loss at mid-term follow-up (average FU 390 +/- 168 days).1
Are there any limitations associated with the use of covered stents for emergency cases?
Almost all arterial lesions can be treated with covered stents, except for those without anatomic suitability, such as very distal lesions, or those without an adequate proximal and distal neck. Similarly, arterial lesions that are located in vessels of a calibre not suitable for stenting cannot be treated with covered stents. Finally, in case of tortuous anatomy or at a joint, when possible, a self-expandable covered stent is the preferred option.
What are your must-have sizes of covered stents for emergencies?
Arterial emergencies can present with a variety of lesions that can be very different in aetiology and characteristics, and located in vessels that can vary significantly in size. This is why we require a wide array of differently sized stent grafts in order to select the most suitable one. It is, therefore, difficult to say which sizes are a “must-have”.
Our experience shows that, in the case of arterial injuries, the proper sizing of the stent graft is essential to achieve technical and clinical success, without complications and recurrences, which further highlights the importance of having a wide range of stent grafts on shelf to treat arterial emergencies, and the BeGraft family has the broadest covered stent platform in the market.
Overall, endovascular treatment with BeGraft covered stents, with preservation of distal flow, is minimally invasive, safe, and effective in the management of arterial injuries and emergencies. Furthermore, all the aforementioned device characteristics allow for the rapid treatment of the lesion, even in case of tortuous anatomy.
*The usage of the BeGraft aortic foot the treatment in the carotid artery or PAU is off-label
References
Case images
MedAlliance’s partner in Japan, MDK Medical, has enrolled the first patient in the clinical study of its novel sirolimus drug-eluting balloon (DEB), SELUTION SLR, for the treatment of peripheral arterial disease (PAD). This follows the acceptance of a Clinical Trial Notification (CTN) by Japan’s Pharmaceutical and Medical Device Agency (PMDA) earlier this month.
The study involves up to 132 patients across a number of centres in Japan. Its objective is to assess the safety and efficacy of SELUTION SLR for the treatment of lesions of superficial femoral arteries and/or popliteal arteries. The study is a prospective, controlled, multicentre, open, single-arm clinical investigation. Its primary endpoint will be the primary patency rate at twelve months. Secondary endpoints will include major adverse events/TLR, primary patency, and the change of Rutherford classification/ABI/WIQ.
“We are extremely pleased with the regulatory and quality expertise demonstrated by our partner MDK, and particularly proud that Japanese patients can now benefit from our unique technology. This is the first sirolimus drug-eluting balloon implanted in Japan, where the current paclitaxel-coated balloon market generates more than US$100M in revenue”, commented MedAlliance chairman and CEO Jeffrey B Jump.
In February 2019, MedAlliance became the first DEB company in the world to receive Breakthrough Device Designation status for a sirolimus DEB from the US Food and Drug Administration (FDA). SELUTION SLR has now achieved three separate FDA Breakthrough Device Designations: for the treatment of AV-Fistula; coronary in-stent restenosis and peripheral below-the-knee lesions. The company announced the enrolment of the first patient in its FDA IDE pivotal coronary trial earlier this month.
In February 2020, MedAlliance announced the award of its first CE mark approval: for SELUTION SLR in the treatment of PAD. In May 2020, the company announced the award of its second CE mark: SELUTION SLR 014 PTCA for the treatment of coronary arterial disease (CAD).
A new study shows significant benefits of the Ellipsys vascular access system (Avenu Medical) in easily and safely creating durable vascular access for end-stage renal disease (ESRD) patients who require haemodialysis.
According to an Avenu Medical press release, the system also offers a standardised process for using the minimally invasive technology that other physicians can follow to reproduce the results, which “will make it easier for more practitioners to adopt this patient-friendly approach to dialysis access,” explained lead author Alexandros Mallios, a vascular surgeon at Institut Mutualiste Montsouris of Paris, France.
Published in the Journal of Vascular Surgery (JVS), this marks the largest study of any percutaneous arteriovenous fistula (pAVF) technique to date. Of the 232 patients who had an Ellipsys pAVF created between May 2017 and July 2019, there were no adverse events and 96% still had fully functioning fistulas with strong blood flow after a year. That “patency rate” is higher than published rates for surgically created fistulas, which average about 60% after one year.
“Vascular access is quite literally the lifeline for dialysis patients,” said Mallios. “The advantages of the percutaneous Ellipsys fistula are that it is a very safe, simple, and reproducible way to create a fistula that will function for a long time with minimal interventions.”
In addition, the study reported that patients were able to begin using their pAVF for dialysis an average of four weeks after creation, with six per cent of fistulas becoming functional (or “mature”) in as little as two weeks. Such rapid maturation can have a significant impact on patient safety, as it avoids the use of a central venous catheter (CVC) if they need to begin dialysis quickly. Compared to fistulas, CVCs are associated with significantly higher rates of complications, including infection and even death.
One of the most important aspects of the study, Mallios added, is that it offers a protocol for fistula creation, maturation and maintenance—which should make it easier for other physicians to adopt the relatively new procedure. For example, the study shows the benefit of adding a new step to the procedure—performing balloon angioplasty immediately after a fistula is created. That improves blood flow and speeds maturation, and could improve patency rates without increasing the need for additional maintenance procedures.
“Dr. Mallios’ results are very exciting, particularly with such a large patient population, as it adds to the growing body of evidence that this approach offers a safe and effective way to quickly create a functional percutaneous fistula,” said Mark Ritchart, president and CEO of Avenu Medical. “He also uses his valuable experience as a guide to enable more widespread use of percutaneous fistulas, which may improve patient safety by reducing reliance on riskier vascular access options.”
In April, JVS published a case report by Mallios that featured a 3D rendering of the Ellipsys pAVF on the cover of the publication. Mallios also co-authored two recent papers in the Journal of Vascular Access that discussed patient eligibility for Ellipsys and the similarities between an Ellipsys pAVF and a surgical AVF, the current standard of care.
In addition, recently published long-term Ellipsys data showed a functional patency rate of 92 percent at two years. The study also found high levels of patient satisfaction with the procedure.
Cleared by the FDA in 2018 for patients with end-stage kidney disease, Ellipsys is the first significant innovation in AVF creation in over 50 years. It transforms a complex surgery into a minimally invasive procedure that can be performed in a hospital outpatient setting or ambulatory surgery center. Since 2015, more than 1,800 patients worldwide have had the Ellipsys procedure.
Jim Reekers (Amsterdam UMC, Amsterdam, The Netherlands), Editor-in-chief of Cardiovascular and Interventional Radiology (CVIR) Endovascular, was awarded the European Society of Radiology (ESR) Gold Medal at this year’s—virtual—European Congress of Radiology (ECR; 15–19 July).
Reekers is a former president of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), and a professor Emeritus of Radiology and Interventional Radiology at the University of Amsterdam.
He has received the ESR Gold Medal in recognition of his achievements in the field of interventional radiology (IR). In a statement on their website, CVIR Endovascular say: “We hope [this award] will increase the visibility of IR and the importance of endovascular procedures”.
“It means a lot,” Reekers tells this newspaper, when asked about the impact of a prominent interventional radiologist receiving the Gold Medal award at the largest European radiology congress. “I think that diagnostic radiology (DR) is the basis for any interventional radiologist. Up to date diagnostic skills—and that means understanding the whole spectrum of diagnostic radiology—is mandatory to be an IR expert. Any medical specialist performing endovascular or interventional oncology procedures without high level diagnostic skills will always stay a craftsman, sometimes useful, but will never be able to make the real difference. Performing IR without up to date diagnostic skills is like driving with your eyes closed, and hoping for the best.”
Writing on Twitter, Reekers’ colleague Rick van Rijn (also Amsterdam UMC, Amsterdam, The Netherlands) wrote: “Proud moment for Dutch Radiology and for a great and inspiring colleague. For several years I have had the pleasure to work with him at the same department at the Amsterdam UMC #welldeserved”.
“I see this as a great honour,” Reekers says, “the golden crown on my career as an interventional radiologist (and trained radiologist), an innovator, a researcher, a mentor, and a teacher. To be only the second Dutch radiologist to receive this honour feels very special to me. This award symbolises to me personally that diagnostic and interventional radiology should always stay one close family. On equal base, with full clinical responsibilities for IR, and permanent cross fertilisation.”
Radiologists Richard FitzGerald (Royal Wolverhampton Hospitals National Health Service [NHS] Trust, Wolverhampton, UK) and Katrine Riklund (Umeå University, Umeå, Sweden) also received Gold Medals at this year’s ECR.
It was recently announced that Veryan Medical will support Walk Vascular in the commercialisation of the Jeti peripheral thrombectomy system in Germany.
Walk Vascular’s Jeti thrombectomy system employs an internal jet, located safely just inside its catheter mouth, capable of engaging large thrombus volumes through a miniature lumen, rapidly clearing peripheral vessels that can often prove challenging for standard aspiration devices.
“By working with Veryan Medical we can hit the ground running” comments David Look, president and CEO of Walk Vascular. “Veryan provides an invaluable catalyst to our commercial efforts, providing access to key opinion leaders in Germany through an experienced sales team with clinical expertise.”
“We are pleased to be working with Walk Vascular and the Jeti technology, a proven solution that safely and effectively restores blood flow in peripheral thrombectomy procedures,” says Nick Yeo, Veryan Medical’s CEO. “We are proud to support innovators like Walk Vascular to provide insights, marketing strategy, and a top-tier salesforce to ensure commercial success and clinical adoption. JETi and Veryan’s novel BioMimics 3D stent are an exciting combination both for our sales team and our customers.”
This advertorial is sponsored by Guerbet. SeQure®
As the leader of an investigator-initiated, Phase 2 study evaluating the safety and efficacy of the SeQure® microcatheter (Guerbet), Francisco Cesar Carnevale here outlines his experience using the device, drawing particular attention to the reduced risk of reflux and non-target embolization. Originally scheduled to be presented at the Society of Interventional Radiology (SIR) Annual Scientific Meeting, this early experience with the SeQure® microcatheter in prostate artery embolization (PAE) is promising, with Carnevale hopeful it will enable the delivery of more therapeutics to the target vessel, while reducing damage to healthy tissue.
PAE is a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) attributed to benign prostate hyperplasia (BPH). Embolization of the prostatic arteries leads to ischaemic shrinkage of the prostate gland and subsequent reduction of LUTS. PAE’s therapeutic effect was first described in a case report in 2000. The first intentional treatment of BPH in humans was reported in 2010, and early cohort studies from around the world soon followed.
As with any new treatment, there is a learning curve. The more cases we perform, the more apparent it becomes to us that making even minor changes to our technique can make a difference to the outcome. One of the main concerns regarding PAE is related to non-target embolization (NTE). This is often due to one of three main causes: (A) reflux of embolic agents around the microcatheter into the main artery that feeds the prostatic artery (types I–V from the University of São Paulo Classification); (B) reflux or flow-direct injection of embolic agents to proximal, non-target branches; and (C) distal injection of embolic agents through intraprostatic shunts. The most common regions to NTE are the bladder, seminal vesical, rectum, penis, and pubic bone. So, having a refined technique and using dedicated microcatheters are key to a good and safe embolization.
With the aim of identifying a microcatheter that reduces the risk of NTE and which could be used as an alternative option, we have initiated the first PAE clinical study using the SeQure® microcatheter at the University of São Paulo Medical School (Prostate Artery Embolization using the SeQure® Microcatheter: A Phase 2 Study Addressing Safety and Efficacy).
The main goals of this microcatheter are to reduce the risk of reflux and NTE, and deliver more therapeutics to the target vessel while reducing damage to healthy tissue. Observations from our early experience—we have performed three procedures—indicate that PAE can be safely and effectively performed with the SeQure® microcatheter, even when navigating distally using the PErFecTED technique.
Case 1
A 70-year-old man with IPSS: 33 (nocturia 4x, weak urinary stream, incomplete voiding, frequency and intermittence). QoL: 6; PSA: 1.40 ng/mL; Qmax: 4.10 mL/sec; prostate volume by MRI: 70 grams; post-void residual volume by US: 40 mL. The patient was refractory to LUTS medication (taken for decades already) and PAE was chosen over surgery to avoid the risk of complications, mainly because of his age. To avoid NTE into the rectal branches—shown by digital subtraction angiography (DSA; Figure 1A) and cone beam computed tomography (CBCT; Figure 1B)—the SeQure® microcatheter was placed distally at the capsular branch, closing the communication with a metallic microcoil (Figure 1C). After injecting the embolic agents from the proximal position (before the bifurcation into the central gland and peripheral zone branches), the SeQure® microcatheter was easily navigated deeply into the central gland branch (Figure 1D) to inject additional particles according to the PErFecTED technique.
Case 2
A 65-year-old man with IPSS: 25 (nocturia 3x, urgency, frequency and weak urinary stream). QoL: 5; PSA: 3.40 ng/mL; Qmax: 6.50 mL/sec; prostate volume by MRI: 46.5 grams; postvoid residual volume by US: 5 mL. Refractory to LUTS medication after taking it for several years; PAE was chosen to avoid the risk of complications, and upon the recommendation of a friend of the patient previously treated with PAE.
During DSA of the right prostatic artery, some bladder branches were identified before the origin of the central gland and the capsular branches (Figure 2A). The SeQure® microcatheter was advanced distally to the bladder branches and positioned before the bifurcation of the central gland and capsular branches for a safer embolization (Figure 2B). One of the risks and consequences when performing this embolization step is the occlusion (NTE) of bladder branches proximal to the prostate resulting in bladder ischaemia. The side slits on the 1 cm distal tip of the SeQure® microcatheter allow the outflow of contrast media without passage of the embolic agent, meaning the bladder branches were saved from NTE (Figure 2C).
We hope that the data obtained from this important study will help bring a new, exciting device to those in the medical community performing this technically challenging procedure. Interventional radiologists should adopt a strategic, multidisciplinary approach to develop pre-clinical and clinical research, and to ultimately transfer current evidence into clinical practice.
Francisco Cesar Carnevale is the director of Vascular Interventional Radiology at the University of São Paulo Medical School, Sao Paulo, Brazil. He has received consulting and speaker honoraria from Guerbet.
Results from case studies are not necessarily predictive of results in other cases. Results in other cases may vary.
Ten-year data published in Radiology show that prostate artery embolization (PAE) is a safe and effective treatment for men with benign prostatic hyperplasia (BPH), which can result in long-term improvements in lower urinary tract symptoms (LUTS) and quality of life. Francisco Carnevale (University of São Paulo Medical School, São Paulo, Brazil) and colleagues note that, prior to their study, long-term experience with PAE for BPH was “limited”. They state that this research is an “important contribution” towards the wider medical community’s understanding of PAE not as an experimental procedure, but “as another alternative for patients suffering from LUTS related to BPH”.
Carnevale and colleagues set out to evaluate the efficacy, safety, and long-term results of PAE for BPH through a retrospective, single-centre study. Between June 2008 and June 2018, a total of 317 men (mean age, 65±8 years) were treated with the minimally-invasive procedure for the alleviation of moderate to severe BPH-related symptoms. PAE was performed with 100–500μm embolic microspheres, and the investigators report a 94% technical success rate for the procedure.
Patient follow-up ranged from three months to 96 months (mean, 27 months). International Prostate Symptom Score (IPSS), quality-of-life score, maximum urinary flow rate, post-void residual volume, prostate-specific antigen (PSA), and prostate volume were all assessed at baseline and during follow-up. Mean maximum improvement was as follows: IPSS, 16±7 points; quality-of-life score, 4±1 points; prostatic volume reduction, 39±39cm3 (39%±29); maximum urinary flow rate, 6±10mL/sec (155%±293); and post-void residual volume, 70±121mL (48% 81) (p<0.05 for all). Early clinical failure occurred in six (1.9%) and symptom recurrence in 72 (23%) men at a median follow-up of 72 months.
Unilateral PAE was associated with higher LUTS recurrence (42% vs. 21%; p=0.04), but the study authors note that the unilateral PAE cohort were on average slightly older than those treated with bilateral PAE (71 years old vs. 65 years old). However, log-rank analysis comparing unilateral and bilateral PAE groups showed no statistically significant difference in the median time to recurrence (48 months and 72 months, respectively; p=0.19).
Embolic particle size did not relate to symptom recurrence, with no difference observed in the median time to recurrence among men treated with microspheres 100–300μm or 300–500μm in diameter.
Baseline PSA was inversely related with recurrence, and was found to be an independent predictor of recurrence outcomes after PAE (hazard ratio [HR], 0.9 per nanograms per millilitre of PSA; 95% confidence interval [CI], 0.8, 0.9; p<0.001).
None of the patients presented with urinary incontinence or erectile dysfunction, an “important finding”, according to Carnevale.
Speaking to Interventional News, Carnevale stresses the significance of this research, the first decade-long dataset to follow-up outcomes in over 300 PAE patients: “It was published in the most reviewed journal with the highest impact factor in the radiology field. Urological societies have been waiting for these long-term data to decide if [they trust that] PAE can be offered as another alternative treatment for patients suffering from LUTS related to BPH. These data consolidate the pioneering, multidisciplinary work done by the Radiology and Urology Departments at the University of São Paulo Medical School. Without this mutual collaboration, this important contribution would not be achieved.
“To bring a new, alternative treatment to the medical community is not an easy assignment,” he continued. “This 10-year experience of using PAE confirms that this minimally invasive procedure is not only an alternative for candidates suffering from LUTS due to BPH-enlarged prostates. Several publications from different centres all over the world have shown that PAE has been accepted with excellent results for patients with urinary retention, for BPH-related bleedings, for patients with contraindications to traditional surgical treatments, and for patients with different prostate sizes (small and huge prostates). Now, PAE can be looked at with different eyes. Over the last decade, we have followed every ethical committee approval (local and national) and have followed several lines of inquiry (including investigating different prostate sizes and symptoms, as well as various embolic agent types and sizes). In this Radiology publication, we have included all patients during our ‘learning curve on PAE’. This means that, among all published patients following different prospective trials, we have tested and learned with every single patient and procedure. We were trying to identify the best way to perform PAE. It was really new and challenging to us.”
PAE excluded from urology guidelines globally
In March 2016, the Conselho Federal de Medicina (CFM), the authority in charge of professional regulation and medical licensing in the country, stated that PAE can be used as a new, alternative treatment for symptomatic patients with BPH. However, the board noted that five-year results should be analysed before a final decision is made on the procedure’s inclusion in the national urology guidelines. “Now, after 12 years of PAE and with this 10-year follow-up data, it is time the CFM gives the final approval for PAE,” comments Carnevale. “With that obtained, we hope the Brazilian Urological Society will include PAE in its guidelines for the treatment of BPH.”
This is a global issue. In 2018, results of the UK ROPE study, which compared embolization to conventional prostate surgery, led the National Institute of Health and Care Excellence (NICE) to determine that the evidence on the safety and efficacy of PAE for BPH was adequate to support the use of this procedure on the National Health Service (NHS). They recommended the procedure “provided that standard arrangements are in place for clinical governance, consent and audit”. NICE added: “This technically demanding procedure should only be done by an interventional radiologist with specific training and expertise in PAE”.
Nevertheless, the European Association of Urology (EAU) guidelines for the diagnosis and treatment of men with LUTS/BPH have not been updated, and remain cautious when describing the potential clinical role of PAE. They state: “A multidisciplinary team approach of urologists and radiologists is mandatory as the basis for future randomised controlled trials of good quality with long-term follow-up in order to integrate this treatment option into the spectrum of efficient, minimally invasive treatment options.” Since then, a 2019 study published in European Urology from Tiago Bilhim (Hôpital Saint-Louis, Lisbon, Portugal) et al has demonstrated that improvements in quality of life measurements and IPSS are “far superior” following PAE than due to any placebo effect.
A US Food and Drug Administration (FDA) review in 2017 concluded that “the probable benefits outweigh the probable risks for this indication”, and in June the same year, the indication of Embosphere microspheres (Merit Medical) was expanded through the FDA’s 513(f)(2) de novo classification to include PAE. In 2018, the product was approved for the same indication by a 510(k) pathway. Embozene microspheres (Boston Scientific) also gained an expanded indication in 2018, with the FDA granting approval for its on-label use in PAE treatment in the USA via the 510(k) pathway. However, PAE is not recommended outside of a clinical trial in the American Urological Association (AUA) guidelines, something many interventional radiologists refute.
Addressing doubters of PAE, Carnevale says: “According to the Hippocratic oath, physicians should ‘Apply dietetic measures for the benefit of the sick according to their ability and judgement’. Interventional radiologists have faced turf battles for decades when aiming to bring new alternative treatments for patients. This happened with peripheral angioplasty, fibroid embolization, and abdominal aortic aneurysm repair, among others, and it will not be any different with PAE. We are not saying that PAE is the only or the best treatment for LUTS related to BPH. We have simply brought another option for patients and physicians to discuss. Each treatment has its indications and contraindications, and it is necessary to understand the patient’s aims and wishes. The publication of these exciting results from our 10-year experience of PAE is a great achievement, and should be considered by the medical community. Its time is now.”
Ahead of the first ever virtual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Thomas Kröncke, chairperson of the CIRSE 2020 scientific programme committee, speaks to Interventional News about the programme highlights, and the logistics of how an online congress will function. He encourages readers to participate, and notes that, for those who register for the event before 30 July, there will be a chance to win free CIRSE registration for life.
Due to the COVID-19 pandemic, this year’s annual CIRSE meeting will take place online. How will the programme look? Which sessions will stay the same as they were, and which will change?
As the CIRSE 2020 congress will be online this year, some of the presentation formats will be adapted, but the content of the congress will remain almost completely as originally planned. All authors of accepted abstracts and all invited speakers will have the opportunity to present their posters and lectures to a worldwide audience.
Part of the on-demand programme will be available online from 1 September, in order to give the interventional community the opportunity to prepare for the large virtual get-together during the four days of the congress. During the CIRSE 2020 Summit from 12–15 September, ten hours of live programming will be offered throughout three channels—the Dotter, Rösche, and Grüntzig auditoriums. On 15 and 15 September, a fourth channel will be added: the IDEAS auditorium. The preliminary programme and registration are already online at www.cirse.org.
During the summit, just as at a physical congress, the focus will be on interactivity and the opportunity to exchange views and ideas. There will be a number of interactive formats for this, such as case-based discussions, expert round tables, workshops, and much more. The participants will always have the opportunity to ask the lecturers questions and to participate in the discussion.
What is the focus for the CIRSE 2020 programme?
A clear focus of this year’s meeting is on the presentation of the latest data and the push for evidence-based practice in interventional radiology. For example, the results of the FEMME study will be presented, in which the quality of life of women after embolization versus myomectomy was examined. The presentation of the first results from two registry studies on transarterial radio- and chemoembolization carried out by CIRSE will also be very exciting. Regarding peripheral endovascular interventions, peripheral arterial disease (PAD) Day and the First @ CIRSE session on Saturday 12 September will certainly be a highlight.
Another important programme focus of the CIRSE Summit is new therapeutic approaches, such as the radiofrequency-based creation of arteriovenous fistulas or fluoroscopy-free 3D imaging.
Are there other programme highlights?
As mentioned, on the first day of the congress we will have a strong focus on peripheral arterial disease in a special PAD track. There will be a session scrutinising the latest study results, as well as an innovation forum in which new therapeutic approaches will be presented and discussed.
On the last two days of the congress the Interdisciplinary Endovascular Aortic Symposium—IDEAS—will again take place. This important format extremely successfully aims at all specialists who deal with the endovascular care of aortic pathologies. In contrast to many other meetings, IDEAS offers a truly interdisciplinary platform through which the pros and cons of all therapeutic approaches are presented and discussed based on evidence.
Another session I would like to highlight is “Women in IR”. With this format, CIRSE deliberately tackles the necessary discussion about a stronger female representation in leadership roles in intervention radiology.
What are the biggest challenges in transforming a physical congress into a virtual one?
Of course, we were disappointed that the physical meeting in Munich, Germany, would not be possible this year. But we soon realised that a virtual congress also offers many opportunities. We can reach a much wider audience online. Many doctors who would not have had the opportunity to travel to Munich will now be able to take part in the CIRSE 2020 Summit.
We are currently working tirelessly to create a virtual format that will further increase interactivity in the sessions. In addition to the opportunities for interaction with the speakers, there will also be break-out rooms where discussions can be continued on a smaller scale.
Our team in Vienna, Austria, has evaluated the best providers and is currently creating a platform through which the meetings, industrial exhibition, and communication between conference participants will be ideally served.
When will the first content be available?
The scientific programme for the CIRSE 2020 Summit is already available at www.cirse.org. The first presentations are expected to be available on the congress portal in early September. In order to stay up-to-date, I invite all those interested to sign up for the CIRSE e-newsletter and to follow our channels on Facebook, Twitter and LinkedIn.
When is registration open for the CIRSE 2020 Summit?
Registration is already open, and a discounted early bird fee is available until 30 July. Registering for CIRSE 2020 will not only give you access to the world’s largest interventional congress, but also exclusive on-demand access to all its scientific content in the six months after the congress. No healthcare professional involved in interventional radiology should miss this opportunity! As a special incentive, everyone who registers before 30 July will be entered for a chance to win free CIRSE registration for life. I warmly invite everyone to sign up!
A new imaging system interface for magnetic resonance imaging (MRI) was presented on the first day of the 2020 European Congress of Radiology (ECR) annual meeting, taking place virtually for the first time from 15–19 July.
The imaging system interface is a joint hardware and software development from Bayer and Siemens Healthineers, and the first injector scanner interface for the MRI suite. It synchronises the MEDRAD MRXperion MR injection system from Bayer and the Siemens Healthineers MR scanner, thereby overcoming significant challenges posed by the complex process used in conventional contrast-enhanced dynamic MRI, which can result in suboptimal imaging, according to a joint company press release. By enabling synchronised injector triggering from the MRI scanner operator console and a more efficient workflow, the imaging system interface allows users to conduct high quality, consistent contrast-enhanced procedures and spend more time focusing on the patient. Bayer and Siemens claim.
In a conventional, manually-controlled setting, radiographers must constantly plan, monitor, and time the various steps on the injector and scanner workstations separately during contrast-enhanced MRI procedures. If the required steps are not optimally-timed and synchronised, poor image quality may be generated, which can delay diagnosis as contrast-enhanced scans then have to be repeated. This can result in additional costs to healthcare systems and may cause unnecessary stress and inconvenience for patients as well as healthcare providers.
“Together with Siemens Healthineers, we were able to design an interface that directly addresses the challenges of conventional contrast-enhanced dynamic MRI workflows and improves both the user and patient experience,” comments Olaf Weber, head of Radiology Research and Development at Bayer.
“This is a very exciting time as we introduce the new technology to our customers that will further improve their experience with our MRXperion injector. We believe that the new interface will assist in allowing the MRI radiographers more time to care for their patients,” says Lynne Collins, country head Radiology at Bayer UK/Ireland.
The imaging system interface recently gained CE mark certification.
Terumo Corporation has announced it has completed the acquisition of Quirem Medical, a Netherlands-based healthcare start-up specialising in the development of next-generation microspheres for selective internal radiation therapy (SIRT), a treatment for liver tumours. Under the terms of the agreement, Terumo acquired 80.1% of the shares of Quirem Medical. This is over and above its current share position of 19.9%, making Quirem Medical now a wholly owned subsidiary of Terumo.
Terumo will make a one-time, up-front payment of US$20 million, with up to US$25 million additional payments based on the achievement of future milestones by 2030. It will be funded through cash on hand and will not significantly impact the company’s financial projections for the current fiscal year ending 31 March 2021.
Quirem Medical has developed and manufactures QuiremSpheres, the only commercially available microspheres containing the radioactive isotope Holmium-166. Recent trials have shown the safety and efficacy of holmium microspheres for the treatment of unresectable liver cancer. To improve patient selection, therapy planning, and treatment verification, QuiremSpheres can be visualised and quantified even in low concentrations by means of single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). This is unique and cannot be done with currently available Yttrium-90 based microspheres.
Furthermore, Quirem Medical also produces QuiremScout, a low dose holmium microsphere that helps evaluate the biodistribution of microspheres prior to therapy, and a dosimetry software package, Q-Suite, which is used to plan QuiremSpheres treatments based on QuiremScout dose imaging. Q-Suite is also able to determine SIRT success immediately after the procedure by converting SPECT and MR imaging into absorbed dose distributions. Together, these three integrated products (QuiremSpheres, QuiremScout, and Q-Suite) make up the full Holmium SIRT Platform. The Holmium Platform equips physicians with the necessary tools to optimise SIRT outcomes through more personalised treatment, a Terumo press release asserts, addressing the individual needs of each patient.
QuiremSpheres, QuiremScout, and Q-Suite are CE-marked and currently available in Europe, the Middle East, and Africa. In the coming years, Terumo intends to launch the Holmium Platform globally as part of the ongoing expansion of its interventional oncology portfolio.
The global interventional oncology market value is more than US$1 billion, which is a rapidly growing field with a compound annual growth rate (CAGR) of 7%. Within this field, SIRT is one of the main treatments that is expected to help to drive this growth year on year.
Terumo has been building its presence in the interventional oncology field, with product offerings such as the micro catheter system (Progreat), compressible microspheres for embolization (HydroPearl), drug-eluting microspheres (LifePearl), and biodegradable drug-eluting microspheres (BioPearl). In 2015, Terumo invested in Quirem Medical and became the exclusive global distributor of their technology.
Medical imaging artificial intelligence (AI) specialist Avicenna.AI has announced it has received 510(k) clearance from the US Food and Drug Administration (FDA) for its CINA Head triage AI solution for neurovascular emergencies. The FDA’s decision covers CINA’s automatic detection capabilities for both intracranial haemorrhage and large vessel occlusion (LVO) from CT-scan imaging.
Stroke is a leading cause of death in the USA, with more than 795,000 strokes resulting in more than 100,000 deaths each year. It is estimated that up to a third of the most common type of stroke are caused by LVO, when a clot blocks the circulation of the blood in the brain. Around one in 10 strokes are thought to be caused by intracranial haemorrhage. Using a combination of deep learning and machine learning technologies, CINA Head automatically detects and prioritises acute intracranial haemorrhage and LVO cases within 20 seconds, seamlessly alerting the radiologist within their existing systems and workflow.
Peter Chang, radiologist and co-founder of Avicenna.AI, says: “When dealing with a stroke, time is of the essence and being able to prioritise effectively is critical to saving lives and improving outcomes. Not only does CINA Head help radiologists to identify pathologies quickly, but also to highlight those that require the most urgent care.”
CINA’s intracranial haemorrhage detection capability was validated using data from 814 cases conducted at more than 250 imaging centres across the USA, with 96% accuracy, 91.4% sensitivity, and 97.5% specificity. The product’s LVO detection capability was validated based on 476 cases, with 97.7% accuracy, 97.9% sensitivity, and 97.6% specificity.
Cyril Di Grandi, co-founder and CEO of Avicenna.AI, comments: “We are excited to have received FDA clearance for CINA Head and are looking forward to working with emergency departments and stroke centres across the USA to help improve detection, decision-making, and patient outcomes. As a triage AI tool that identifies multiple pathologies, we believe that CINA Head delivers more value than AI tools or algorithms that only target a single condition.”
CINA Head is the first in a family of AI tools for emergency radiology being developed by Avicenna.AI. Subsequent products spanning the trauma and vascular fields are expected to be unveiled in the next 12 months.
Dynetic-35, the balloon-expandable cobalt chromium iliac stent system from Biotronik, is now commercially available in Europe. Indicated for the treatment of de novo or restenotic lesions in the iliac arteries, the product is approved for use in Europe and other markets that recognise CE mark certification.
The Dynetic-35 stent size matrix is 6F compatible, including stent diameters of 5–10mm and lengths of 18–78mm, and comes in working lengths of 90, 130, and 170cm, the largest range of iliac stent sizes on the market, a company press release states. Biotronik claim that the thin-strut stent combined with the low crossing profile of the balloon catheter delivery system enhances deliverability.
“The new Dynetic-35 is a true improvement over the previous-generation stainless steel iliac stent. The flexibility, lower profile, and improved deliverability allow direct stenting even in more challenging lesions,” says Michael Lichtenberg (Arnsberg Vascular Center, Arnsberg, Germany). “In my clinical experience with the new stent system, I have been impressed by the smooth placement and deployment for a direct stenting approach, as well as the radial strength of the stent.”
With the 170cm catheter length option, the Dynetic-35 system also enables a radial access approach. “In my practice, I often have the need to use radial access to treat iliac artery disease, which provides more patient comfort and earlier ambulation,” explains Mercedes Guerra-Requena (Guadalajara Hospital, Guadalajara, Spain). “Until now, available options for a radial approach have been limited. Fortunately, the new Dynetic-35 stent’s 170cm length delivery system option and 6F sheath compatibility enables me to comfortably use a radial approach.”
“The next-generation Dynetic-35 is a testament to BIOTRONIK’s continued mission to develop innovative devices that improve the lives of patients,” says Alexander Uhl, president of Vascular Intervention at Biotronik. “We are proud to be able to offer our signature thin-strut stent design in the largest size range on the market while staying 6F compatible for the entire product line.”
The Indigo System Lightning 12 (Penumbra) is now commercially available in the USA, the company has revealed. In addition, Penumbra has announced the appointment of interventional radiologist Corey L Teigen (formerly Sanford Health, Fargo, USA) as chief scientific officer, and interventional radiologist James Benenati (formerly Miami Cardiac & Vascular Institute, Baptist Hospital, Miami, USA) as chief medical officer. Both positions have been newly created.
The Indigo System Lightning 12 is the company’s next generation aspiration system for peripheral thrombectomy. Lightning 12 combines the new Indigo System CAT12 aspiration catheter with Lightning intelligent aspiration, enabling physicians to focus on optimising thrombus removal using the system’s clot detection mechanism. CAT12 is a large-lumen aspiration catheter that incorporates novel laser-cut hypotube-based catheter engineering to provide advanced deliverability and torqueability within the body, a company press release describes. This combination of intelligent aspiration and large-lumen catheter engineering makes Lightning 12 Penumbra’s most advanced clot removal technology.
“Penumbra continues to lead the field of clot management by bringing highly innovative technology to address the challenges that we as physicians face while caring for our patients,” says Frank Arko (Sanger Heart and Vascular Institute, Charlotte, USA). “When dealing with thrombus, we have learned that it is the combination of the catheter along with powered aspiration that yields the most effective results. Lightning 12 with intelligent aspiration is a giant leap forward for the field of thrombectomy, and we have been very impressed with the early results at Sanger.”
“The simplicity of Lightning intelligent aspiration combined with the significant advancements in catheter engineering will enable us as physicians to get closer to our thrombus removal goal in a safe manner, as well as our goal of improving clinical outcomes for our patients,” says Patrick Muck, (Good Samaritan Hospital, Cincinnati, USA).
“Lightning 12 provides physicians with an integrated system that not only removes large amounts of thrombus but also detects and manages clot removal,” comments Jay Mathews (Manatee Memorial Hospital, Bradenton, USA). “This is a very important advancement for the field of thrombus management, and our initial experience at Manatee Memorial with this technology shows us that we are now closer to single-setting care for our patients.”
New leadership appointments
Penumbra also announced appointments for two newly created positions: Corey L Teigen, as chief scientific officer and James F Benenati, as chief medical officer.
Teigen joins immediately as CSO and will contribute his extensive scientific and clinical expertise to ongoing and future research and development efforts.
“In my radiology practice, I have seen first-hand the challenges medical practitioners face while treating difficult medical conditions,” Teigen states. “At Penumbra, I have a profound opportunity to change the course of healthcare delivery for people living with vascular disease. I feel privileged to join Penumbra’s unparalleled group of talented engineers and leaders, and I look forward to contributing my scientific knowledge to help solve challenging medical problems.”
Benenati will join Penumbra on 1 September 2020 as CMO, and will contribute to clinical and medical affairs strategies and advise upon global commercialisation and market development activities.
“I am excited to join Penumbra at this very important time for the company, where it is poised for growth, as it moves into the next generation of intelligent clot removal and expand into rehabilitation with the recent launch of the REAL system,” Benenati says. “Penumbra has changed the landscape of healthcare by providing truly innovative solutions for a wide realm of medical challenges. In this next phase, Penumbra is set to broaden its reach on a global scale, and I am thrilled to join this excellent team and help accelerate the impact of its products.”
“I am thrilled we are bringing Lightning 12, the most advanced technology for aspiration thrombectomy, to the peripheral interventional community,” adds Adam Elsesser, president and chief executive officer, Penumbra. “It is an ideal time for us to welcome Corey and Jim to Penumbra’s leadership team as we progress into our next phase of growth. Their career-long focus on patient care and their innovative mind-set are a perfect fit with our vision and culture, which is dedicated to making a fundamental difference in patients’ lives.”
Barts Health NHS Trust has performed a UK-first operation outside of trial setting that could reduce mortality and risks of infection in patients with dialysis.
Interventional radiologists at The Royal London Hospital (London, UK) have carried out the new minimally invasive arteriovenous fistula (AVF) procedure, WavelinQ EndoAVF (BD Bard).
An endovascular AVF involves fusing a connection between the artery and adjacent vein within the forearm using direct heat which patients can use for dialysis. This procedure is an alternative to the more invasive traditional option of open surgery.
The novel EndoAVF procedure results in a closed circuit that provides adequate blood flow to the superficial veins for dialysis and blood can be withdrawn, cleaned through a dialysis machine, and returned to the body.
With the EndoAVF system—conducted by interventional radiologists Ounali Jaffer, Rashid Akhtar and Rajesh Sivaprakasam at The Royal London Hospital—two thin catheters are inserted into the artery and the vein through small needle punctures.
Magnets help to align the devices and a connection is made between the vein and artery in the forearm without the need for open surgery, which allows clinicians to access the blood stream and gives patients a reliable long-term dialysis AV fistula.
The dual magnetic catheter system is removed from the body once the connection is created and the arm heals without stitches with little or no scarring.
Ounali Jaffer, interventional radiologist at The Royal London Hospital, said:
“This new treatment really enhances our techniques in treating those patients with end stage kidney disease. Avoiding a CVC is imperative and now we have another procedure available to enable timely AVF creation.
“There are only a finite number of options available in creating an AVF, which is the lifeline for the patient. By extending these options, we can maximise the use of these vessels.
“The obvious added benefits are that the procedure is relatively quick and leaves no sign of a procedure, with no visible scar. These are early days, but the innovation is exciting and will hopefully benefit a number of our local population with end-stage kidney disease.”
The Global Embolization and Oncology Symposium Technology (GEST) has announced that it will take place virtually this year. Previously planned to be hosted in New York, USA, on 2–5 September, the event will now be online from 4–6 September 2020.
In an email addressed to the “GEST Community”, the GEST course directors write: “After careful consideration, GEST 2020 will go Virtual to protect the health and safety of our global community.
“GEST Meets Virtual 2020 will include both live interactive virtual sessions and an on-demand e-library. The GEST committees and faculty have been working diligently finalizing the virtual program. Stay tuned over the next week for the updated program!
“Our commitment to global education, innovation, research and improving patient care is stronger than ever. Please join us and take advantage of all the virtual content GEST has to offer.
“Until we ‘meet’ again, we hope you will join us virtually in September.”
The Journal of Vascular and Interventional Radiology‘s (JVIR‘s) impact factor—one measure of a journal’s influence based on the number of article citations compared to the total number of citable articles published—has broken 3 for the first time.
According to the Journal Citation Reports, published by Clarivate Analytics, JVIR‘s Impact Factor jumped 7% to 3.037 in 2019, up from 2.828 in 2018.
“This spectacular leap to the 3 range places JVIR in a distinct new class of peer journals, outdistancing all interventional radiology [IR] specialty journals,” comments Ziv J Haskal, the editor-in-chief of JVIR and a professor of radiology and medical imaging at the University of Virginia School of Medicine in Charlottesville, USA. “This continuing growth trajectory makes JVIR the commanding voice of IR science and the home of the highest-level IR research on its pages. It is a credit to the worldwide IR and endovascular researchers who choose JVIR for their most impactful work. This year’s numbers of submissions are projected to, again, reach record levels.”
Speaking specifically to Interventional News, Haskal adds: “I am incredibly proud that the new JVIR impact factor entered the ‘threes’ at 3.037. I have personally nudged, encouraged, curated, and sometimes ruthlessly edited over 17,000 manuscript drafts at all stages in a decade of living JVIR. The quality of our science has methodically and consistently improved, in JVIR, reflecting the pole position of this specialty in modern medicine. I could not be happier.”
“More than ever, there is a clear need for sound science and strong data to deliver optimal care for patients,” says SIR president Michael D Dake, senior vice president of the University of Arizona Health Sciences in Tucson, USA. “The research published in JVIR provides the support for image-guided therapies that interventional radiologists need to improve the lives of their patients.”
The impact factor, which reflects citations in the previous two years, is often used as a measure of the quality and influence of medical journals within scientific, professional, and academic communities. JVIR citations appeared in radiology, nuclear medicine, medical imaging, and peripheral vascular disease journals.
Patients who crossed over from the sham control arm of the RADIANCE-HTN SOLO trial to the renal denervation arm after 12 months of elevated blood pressure had decreased daytime ambulatory systolic blood pressure at both two and six months following renal denervation. The analysis of the crossover cohort was presented by Ajay J Kirtane (Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, USA) during a late-breaking trial session at the PCR e-Course 2020 (25–27 June).
RADIANCE-HTN SOLO was a multicentre randomised controlled trial that demonstrated the blood pressure lowering effect of endovascular ultrasound based renal denervation (Paradise, ReCor Medical) compared with a sham control. Patients randomised to sham treatment who had daytime systolic ambulatory blood pressure ≥135mmHg or daytime diastolic ambulatory blood pressure ≥85mmHg after 12 months of follow-up were permitted to crossover to receive endovascular ultrasound based renal denervation.
Kirtane explained: “This analysis represents data on the cohort of 31 patients that had crossed-over as of January 2020. Complete two-month ambulatory blood pressure data are available on 31 participants, with complete six-month data available on 25 patients.”
Average age in the crossover population was 54 years, and 39% were female. Average daytime ambulatory blood pressure was 145/90mmHg, with a 24-hour ABP of 138/85mmHg, and office blood pressure of 146/95mmHg. The average number of hypertensive medications at crossover was 1.2±0.7, and the mean time from randomisation to crossover was 23±5 months.
There was 100% procedural success with renal denervation and there were no deaths from any cause.
Kirtane said: “This cohort demonstrated a daytime ambulatory systolic blood pressure change of -11.2mmHg at two months and -12.2mmHg at six months [p<0.001 in comparison to 12-month baseline for both], without an increase in medication burden; through six months, there were no major adverse events following crossover.”
At two months, 71% of patients had a decrease of ≥5mmHg in daytime ambulatory systolic blood pressure; at six months, this was 68%. Among these patients with a response 5mmHg in daytime ambulatory systolic blood pressure, At two and six months, the average daily ambulatory systolic blood pressure reduction was 17.7 and 20.6mmHg, respectively.
Summing up, Kirtane told the online audience: “Control of hypertension represents an unmet need globally, and renal denervation is an ‘adherence-independent’ adjunctive therapy to medications. These results are consistent with the primary SOLO results; however, there was no drug titration protocol between two to six months for crossover patients, so this may provide some added insight into six-month durability after renal denervation.”
He additionally stressed that, because crossover subjects and physicians were unblinded, the data are subject to behavioural and/or medication-related effects and as such these results need to be interpreted first and foremost within the context of the blinded study results. Nonetheless, “these data are further supportive of an adjunctive role of ultrasound-based renal denervation in the treatment of hypertension, especially when considering how many patients with hypertension worldwide are currently uncontrolled”, Kirtane said.
Transcatheter bariatric embolotherapy (TBE) for obesity is safe and leads to clinically significant weight loss in comparison to a sham procedure, a hotline and innovation session at PCR e-Course 2020 (25–27 June) has been told. TBE also demonstrated a greater improvement in quality of life and hunger scores. Vivek Y Reddy (Homolka Hospital, Prague, Czech Republic, and Icahn School of Medicine at Mount Sinai, New York, USA) presented the findings from a pilot, single-blind, sham procedure randomised controlled trial.
Reddy told the online audience: “Bariatric surgery is a highly effective procedure, and improves cardiovascular outcomes as well as mortality, but this invasive surgical procedure has significant morbidity and mortality associated with it, and that limits its utility to those patients who are severely obese, with BMIs [body mass index] almost always over 40. TBE is a novel catheter-based approach. It involves embolisation of microspheres to the left gastric artery [LGA] to cause ischaemia to the gastric submucosa. A number of preclinical studies, as well as clinical case series, have indicated that bariatric embolotherapy promotes weight loss—thought to be due to a mechanism of reducing ghrelin, which is the only known appetite-stimulating hormone in the body, and is secreted largely from the gastric fundus.”
The current study compared TBE to a sham procedure in a first-in-human trial conducted at two centres in Prague, The Czech Republic (PIs: Petr Neuzil MD PhD & Martin Fried MD). The first was a bariatric surgery centre that conducted most aspects of the trial, including patient enrolment, consent, weight counselling, and all of the follow-up. The second centre performed the randomisation and treated patients, either with embolotherapy or the sham procedure.
Key inclusion criteria were a BMI of between 35 and 50, and age 21–60 years. Patients were excluded if they had had prior bariatric surgery, had a history of ulcers, had type 2 diabetes, an active H. Pylori infection, or if they were chronic users of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs).
Randomisation of consenting patients was 1:1 to TBE or a sham procedure. In TBE, femoral arterial access was obtained and a coeliac angiogram using a 6Fr guide was performed. Using an occlusion balloon microcatheter, beads which ranged between 300 µm and 500µm were injected into the LGA to achieve stasis. Injection was performed using a custom robotic manifold designed to inject the beads at the correct pressure. The Sham procedure involved the infiltration of lidocaine into the skin in the femoral area, and propofol was infused for one hour.
The primary efficacy endpoint was total body weight loss compared between TBE and sham therapy. Age, weight, and BMI were similar across the two groups. Patients were analysed in both intention-to-treat (ITT) and per protocol (PP) populations. After six months’ follow-up, crossover was permitted. TBE patients were followed for one year and sham patients for six months. After exclusions and withdrawals, 40 patients were randomised, 20 to each group. Following treatment, analysis of efficacy and safety was performed on 19 patients in the ITT population in the TBE group and on 18 patients in the sham group. The PP analysis of efficacy was performed in 15 patients treated with TBE and 16 with sham procedure.
Mean procedure time for TBE was 82.3 minutes. In 16 patients one vessel was injected, two were injected in two patients, and three in the remaining patient of the original 20 randomised to the procedure (19 treated with TBE).
Reddy announced the outcomes: “On the safety side, there was only mild nausea or vomiting that was self-limited, and minor ulcerations in five patients. All of these ulcers were asymptomatic and were self-limiting, requiring no additional treatment.”
At six months, the primary endpoint of weight loss for the ITT population was 7.4kg in the embolotherapy group versus 3kg in the control group (p=0.034). In the PP population, it was 9.4kg in the TBE cohort compared with 1.9kg for the sham therapy (p=0.0002). A comparison of TBE from baseline to 12 months found a 7.8kg loss in the ITT population (p=0.0011), and a 9.3kg loss in the PP population (p=0.0005). In addition, at both six and 12 months from baseline, TBE treatment led to a greater improvement in quality of life measures than sham treatment for physical function, self-esteem, sexual life, public distress, and work, as well as overall quality of life. Hunger scores also decreased to a greater extent for TBE than sham treatment at both six and 12 months from baseline.
Reddy concluded: “In this randomised pilot trial we established the proof of principle that transcatheter bariatric embolotherapy of the left gastric artery is safe, and it promotes clinically significant weight loss. There was an improvement in the hunger scores, significant weight loss that was maintained out to one year, and this also translated to improvements in quality of life.”
Reddy told Interventional News: “We believe this is an important trial that convincingly demonstrates for the first time that TBE helps promote weight loss. However, there is much additional work that remains to be done—most importantly a large multicentre trial to assess efficacy in the hands of a large number of operators, rare safety events that can only be identified after treating a large number of patients, and corroborating data on hormones (for example, ghrelin). My understanding is that the company that sponsored this pilot study is planning to conduct a large US pivotal FDA trial using a second generation TBE system (micro-infusion catheter and robotic manifold).
Cook Medical recently announced that the Advance Serenity hydrophilic percutaneous transluminal angioplasty (PTA) balloon catheter is now available to physicians in the USA. The catheter is manufactured by Surmodics and distributed by Cook Medical.
According to a press release, Advance Serenity is a hydrophilic-coated angioplasty balloon catheter designed to meet the technical needs of clinicians for treatment of patients who suffer from peripheral artery disease (PAD) which includes below-the- knee disease. The catheter portfolio includes both a 0.014- and an 0.018-inch diameter wire guide platform and will be available in a wide variety of balloon lengths and diameters.
“Now that we have added Advance Serenity to our product portfolio of vascular solutions, physicians have one more tool in their toolbox to help treat patients who have PAD,” said Mark Breedlove, vice president of Cook Medical’s Vascular division.
Cook Medical is working to make Advance Serenity balloon catheters available to physicians in Europe in the coming months.
Royal Philips recently announced the four-year results from the ILLUMENATE European randomised controlled trial (EU RCT). The Stellarex drug-coated balloon (DCB) cohort demonstrated similar all-cause mortality compared with the control arm through four years. This analysis included missing data found post hoc to achieve a follow-up compliance of 93.9%, increasing the robustness of the statistical analysis.
Along with the recently-published data on the ILLUMENATE Pivotal trial, this is the second RCT which has indicated similar mortality rates, further validating the long-term safety profile of Philips’ Stellarex low-dose DCB. The data were presented in the evening of 25 June as part of Vascular Interventional Advances’ (VIVA) first-ever Late-Breaking Clinical Trials Livestream.
The four-year ILLUMENATE EU RCT data are the latest from a series of trials evaluating the safety and efficacy of the Philips Stellarex .035″ DCB in restoring and maintaining blood flow in the superficial femoral artery and popliteal arteries of patients with peripheral arterial disease. The results were evaluated compared to percutaneous transluminal angioplasty (PTA) treatment with uncoated balloons, the current standard of care.
The mortality rate at four years shows no statistical difference between two patient groups, at 17.7% for the Stellarex patient group and 14.1% for the control group. Secondary safety outcomes were also similar across the two groups.
“These latest data from the ILLUMENATE EU RCT study add to the ILLUMENATE Pivotal RCT results and continue to demonstrate no statistical difference in mortality when comparing the DCB and PTA arms of the trial,” said William Gray, president of the Lankenau Heart Institute (Wynnewood, USA), an investigator for the Stellarex clinical trials who presented the results during the livestream.
“The results from the ILLUMENATE EU RCT trial continue to demonstrate durable long-term results at a high rate of follow-up compliance,” said Marianne Brodmann, professor, vascular specialist at the Medical University of Graz (Graz, Austria) and a primary investigator for the trial.
“The ILLUMENATE EU RCT results now establish Stellarex as the only paclitaxel DCB that has shown a consistent lack of statistical difference in mortality compared with PTA at each annual follow-up through four years across two randomised controlled trials,” said Chris Landon, general manager, Image Guided Therapy Devices at Philips. “We continue to proactively communicate relevant clinical findings to ensure physicians can make the best-informed decision for each patient.”
“There is a general misconception that you cannot do interventional radiology (IR) in a resource limited setting,” says Fabian Laage Gaupp, IR resident at Yale School of Medicine (New Haven, USA), and a member of the Yale Radiology Outreach Program. He is outlining his work alongside colleagues to establish a radiology service at the Muhimbili National Hospital campus in Dar es Salaam, Tanzania, East Africa. “From having done this for almost three years, I can say that this is simply not true,” he says, picking up on the earlier statement.
The initiative has seen more than 50 volunteers travel to Tanzania in teams of up to five for two-week placements to provide hands-on training to radiology residents, nurses and technologists. Funded initially through donations and institutional grants, the project has recently been awarded funding through the Radiological Society of North America (RSNA) Derek Harwood-Nash International Education Scholar Grant scheme, which Laage Gaupp says will help to continue the initiative into the immediate future.
The project has grown out of work begun by Yale’s director of neuroradiology MRI and assistant professor of neuroradiology, Frank Minja, who initially sought to implement a Picture Archiving and Communication System (PACS) at the Muhimbili Orthopaedic Institute in Dar Es Salaam in 2014. Since then, Minja has made regular trips to Tanzania—the country of his birth—to support physician training in the country. Minja crossed paths with Laage Gaupp, who joined Yale as a radiology resident in 2016, and, hungry for outreach opportunities within the IR field himself, joined Minja on a trip to Dar es Salaam in 2017.
“In Africa you have around 1.3 billion people currently, and there are really only two countries where IR is established—South Africa and Egypt,” says Laage Gaupp, discussing the demand for IR services across the continent. Tanzania has a population of over 50 million, including over four million in Dar es Salaam, the country’s most populous city and the focal point of the outreach programme. During his first trip to the country, Laage Gaupp armed himself with an Interventional Radiology Readiness Assessment tool to establish the scope for setting up an IR service within the country. In terms of the availability of imaging equipment to support IR work, he found that this could be feasible, but the disposable equipment needed was lacking. Undeterred, he set about designing a training scheme that could bring IR into the country.
“We have followed the same training model that we do in the USA, doing three years of diagnostic radiology, followed by two years of an IR residency. In Tanzania they already have the three years of diagnostic radiology residency, so we essentially just have to add two years of interventional radiology.”
To date, six residents have enrolled over two year groups, with the first group of three residents set to graduate in September 2021. They are undertaking a combination of on-the-job training and lectures delivered by the visiting groups from institutions across the USA and Europe. Visiting groups, who visit for two weeks at a time, comprise at least one physician, nurse, and technologist, reflecting the fact that IR is, in Laage Gaupp’s words, “a team sport”. Groups may also be augmented by medical students and radiology residents. The ultimate aim of the programme is the establishment of a self-sustaining IR residency programme at Muhimbili, with Tanzanian IR faculty training Tanzanian residents. “Our focus has always been on getting them to be able to work independently quickly and we are already starting to see the outcomes of that,” Laage Gaupp comments. “They are already doing a lot of procedures independently, so now on a daily basis they do CT and ultrasound guided core needle biopsies, they do nephrostomy placements, and they do biliary drain placements, which is really considered a technically challenging procedure in many cases. There is no trained IR attending in Tanzania, but they are able to provide these really life-saving procedures, and have great success.”
The course has been designed to begin with teaching residents more basic procedures: “those that are more necessary”, Laage Gaupp says, such as core needle biopsies. “That might not be considered a life-saving procedure, but it is extremely necessary, because until then people were only doing fine needle aspiration, which has a much lower diagnostic yield.
“We felt that is something that would have a really significant impact on patient care because it is going to help you diagnose and help to guide the treatment. At the same time, it is a simple procedure where you can learn [to use] image guidance and you have a lower chance for complications.” Other procedures, including abscess drainage and nephrostomy and biliary drainage, have been prioritised, due to the potential impact these could have on morbidity and mortality compared to surgery. “Just by making those procedures available, that is the highest return in terms of patient outcomes that you can have. Even with those really basic procedures, you are going from a patient dying, to that patient surviving,” he emphasises.
Discussing some of the differences in running an IR service in East Africa, compared to the USA, Laage Gaupp comments that there is a significant difference in the “disease spectrum” of patients using healthcare services in Tanzania, with a high prevalence of parasitic infections, for example, as well as in the stage at which patients present in-hospital for treatment. “People present a lot later in general [in Tanzania],” Laage Gaupp remarks. “In the USA in particular, when people have the slightest headache or stomach ache, they usually go and see a doctor. In Tanzania, the coverage is different. For someone from a rural area to actually present to the national hospital in Dar es Salam takes months or sometimes years. Until they get to the national hospital, those are really the sickest of the sick, people show up with huge tumours, with roaring infections, with anything under the sun.”
Another aspect he notes as being specific to Africa is a higher percentage of paediatric patients. “While paediatric interventional radiology in the USA is considered a bit of a fringe subset of IR, in sub Saharan Africa, paediatric interventional radiology will play a pretty big role because there are so many paediatric patients,” he notes. He also points to a large prevalence of uterine fibroids, which is particularly notable in black women compared to in predominantly white or Asian populations, adding that the introduction of uterine fibroid embolization (UFE) has the potential to have a huge benefit in throughout the region.
“If you look at UFE in particular, and you compare it with hysterectomy, one of the most common procedures worldwide, complication rates in sub Saharan Africa are on average higher than in Europe or the USA,” Laage Gaupp comments. “Now with UFE, the procedural risk is much lower, and second of all you do not need general anaesthesia, so you are taking that risk out. It is such a common problem, even if you said IR was limited only to UFE, that alone would justify bringing IR to sub Saharan Africa.”
The outbreak of COVID-19 has meant that outreach trips have been cancelled until it is safe to travel again. Laage Gaupp hopes that this will be before the end of 2020, but faculty have been able to offer online education through video conferencing. “If there is a positive thing that has come from COVID-19, it is the access to online teaching,” he comments, but notes that there is “no substitute” for hands-on teaching, particularly within IR.
Six-month clinical outcomes of the MERLION trial were presented as part of the VIVA Late-Breaking Clinical Trials Livesteam (25 June), by Tjun Tang (Singapore General Hospital, Singapore).
MERLION is a physician initiated, prospective, non-randomised multicentre trial investigating the safety and efficacy of the treatment with the luminor drug-coated balloon (DCB) and angiolite below-the-knee (BTK) drug-eluting stent (DES) in TASC C and D tibial occlusive disease, in patients with chronic limb-threatening ischaemia (CLTI).
Tang reported a 100% technical success rate, with a 4.5% bailout stenting for severe flow limiting dissection using angiolite BTK, and a primary patency of 78.9%.
Freedom from clinically driven TLR was 91.7% while the amputation free survival (AFS) was 88%, both at six months.
Tang concluded that the “luminor DCB is safe and efficacious, in treating highly complex infra-popliteal atherosclerotic lesions in challenging CLTI patients” and he added that “luminor is associated with highly satisfactory acute technical success, six-month target lesion patency, and AFS.”
The COVID-19 pandemic will have a deep impact on the future of healthcare according to Tan Bien Soo, Singapore General Hospital (Singapore). He tells Interventional News how his institution has prepared for and dealt with the pandemic, including a six step programme for preventing the spread of the SARS-Cov-2 virus, how this response was influenced by Singapore’s experience tackling SARS and how the pandemic will shape healthcare services into the future.
Singapore General Hospital was well-equipped to deal with the COVID-19 outbreak due to previous experience with SARS. Could you expand on this, detailing the similarities and differences between COVID-19 and earlier viral epidemics?
SARS was also a coronavirus spread by droplets, as is the SARS-Cov-2 virus which is the cause of COVID-19. Based on this, we can conclude that the SARS-Cov-2 virus also spreads by droplets. However, beyond this, as it is a novel coronavirus, there is much that we still do not know about. We are now, for example, finding out that patients who are infected can have a pre-symptomatic phase when they can be very infectious. This is unlike SARS. After our experience with SARS, infection control and prevention has become an integral focus for all staff in Singapore General Hospital and we are constantly training and auditing ourselves to prepare for the next big disease outbreak. We have also, over the years, designed our infrastructure to allow for segregation of patients with different infection risks. Thus in Singapore General Hospital, we have different interventional radiology facilities for inpatients and outpatients.
What are the most important steps for interventional radiologists to take when ensuring their departments are ready for COVID-19 patients?
This has been summarised in six steps that we shared in the peer-reviewed journal Cardiovascular and Interventional Radiology. The six steps are:
Elective procedures have been postponed or cancelled to mitigate the chances of coronavirus overwhelming the healthcare service. What counts as an elective procedure for an interventional radiologist, and what procedures are essential? Are elective procedures still cancelled in Singapore, or are you phasing them back in?
At Singapore General Hospital, we prioritise all clinically urgent and all inpatient procedures so that hospital length of stay can be shortened. For outpatient elective procedures, priority is given to patients with cancer who need treatment. Non-cancer related procedures that can be safely deferred, like fibroid embolisation, fallopian tube recanalisation and arteriovenous malformation embolisation have been postponed.
Interventional radiologists have also raised concerns over disposable sterile supplies. What actions did Singapore General Hospital take to conserve these supplies, and was there pressure from regulators to use them? Did you have any issues with your supply?
We quickly reviewed our existing guidelines for personal protective equipment (PPE) to ensure alignment with our institutional practice, and commenced refresher training in infection control. We stressed the need for appropriate use of PPE, and discouraged wastage. We also tracked our PPE stocks daily. That way, we have been able to maintain adequate supply.
On reflection, how do you feel Singapore has handled the COVID-19 outbreak? What lessons can other countries learn from the response in your country? What will the next few months look like?
In my opinion, we have handled the pandemic well. Even though we are now seeing a surge in case numbers, our hospitals are not overwhelmed, and mortality rate remains low. The response is co-ordinated nationally among all stakeholders, and not limited to just the healthcare sector. I feel that this holistic response will be the key to eventually overcoming this pandemic.
In your opinion, how will the COVID-19 pandemic impact the future of healthcare?
This pandemic will have deep impact on the future practice of healthcare. Much like how we in Singapore have learned from SARS which changed our practice and infrastructure to cater for future disease outbreaks. We now have to start thinking about the ‘new clinical practice norm’ in the post COVID-19 era by learning from our current experience.
This pandemic has created a global crisis and brought significant suffering upon millions of people, but I am confident that we will find a way to overcome it and emerge stronger, better and more resilient.
Tan Bien Soo is chairman of the Division of Radiological Sciences, and senior consultant, Department of Vascular and Interventional Radiology at Singapore General Hospital.
iVascular recently announced the launch of its Sergeant peripheral support catheter. Sergeant is a CE marked over-the-wire catheter, indicated for patients with peripheral arterial disease in small vessels or challenging anatomy during diagnostic and interventional procedures.
According to a press release, Sergeant is intended to facilitate, guide, and support guidewires. It also allows guidewire exchanges and provides a conduit for the delivery of saline solutions and diagnostic contrast agents. Sergeant’s guidewire support is possible thanks to its braided catheter that allows “exceptional” pushability and torque.
iVascular’s Hydrax proprietary hydrophilic coating increases the catheter’s trackability, allowing Sergeant to pass through tortuous anatomy. In terms of visibility, Sergeant features four radiopaque markers that asses accurately the catheters position and lesion length.
The device is available with the tip, straight, and 30º angled, and in lengths between 65 and 150cm, while offering compatibility with 0.014”, 0.018” and 0.035” guidewires, all of them being 4F introducer compatible.
Marc Sirvent, angiologist and vascular surgeon specialist at the University Hospital Germans Trias i Pujol in Barcelona, Spain, carried out the first procedures with the product, and notes that the product easily crossed the occlusion in the tibial posterior and plantar arch.
A BIBA MedTech Insights survey (conducted May 2020) indicates a trend towards centres only performing emergency percutaneous peripheral procedures during the COVID-19 pandemic. However, this trend is not seen with stenting/angioplasty for critical limb ischaemia. With critical limb ischaemia, the trend is for at least some elective procedures to still be performed.
BIBA MedTech Insights polled physicians at 238 centres across the globe about how the pandemic has affected clinical practice at their centre. More than half (55.8%) of respondents were vascular surgeons, with the rest of the respondents ranging from interventional radiologists to angiololgists. Furthermore, 46% of respondents came from the top four European countries: Italy, Germany, the UK, and Spain. Therefore, this article reviews the key Western European findings from the survey.
The survey showed that, in Western Europe, for both peripheral embolization and stenting/angioplasty for claudication, the majority of centres were only performing emergency procedures. For example, 69% of respondents reported that they were only performing emergency peripheral embolization and 61% said that they were only performing emergency stenting/angioplasty procedures for claudication. However, this tendency was not seen with critical limb ischaemia procedures. For stenting/angioplasty procedures for critical limb ischaemia, the majority of centres were performing at least some elective procedures: 40% for some procedures and 19% for all procedures versus 41% only performing emergency procedures. See Figure 1.
Furthermore, of those still performing elective procedures for critical limb ischaemia, the tendency was for them to report seeing a reduction of 50% or less in elective procedures rather than a reduction of more than 50%. See Figure 2.
The split between emergency only versus some versus all elective percutaneous procedures, for critical limb ischaemia, did vary depending on the country. For most countries, the majority of the centres were still performing at least some elective procedures. However, in the UK, 52% of centres reported performing emergency only procedures. In Spain, by contrast, only 29% of centres report performing emergency procedures (with 42% performing all procedures). See Figure 3
Given that the survey suggests that elective critical limb ischaemia procedures have continued (albeit at a reduced level) during COVID-19, one may expect centres to “return to normal” relatively quickly once COVID-related restrictions have been lifted. Indeed, the survey does find that the majority of respondents in Western Europe estimate that their centre will go back to performing their usual level of elective critical limb ischaemia procedures within three months. Interestingly, although there is some variation, this trend is seen for all countries including the UK.
In terms of the measures needed to “clear the backlog” of elective procedures, overall, increased operating days, adjusted working practices (such as more frequently using a minimally invasive approach), and increased operating hours were the most common answers. However, of note, 10% felt no extra measures would be necessary.
The cover of June’s edition of the Journal of Hepatology featured a paper on transarterial radioembolization for the treatment of hepatocellular carcinoma (HCC). Publication of the paper, authored by Riad Salem (Department of Radiology, Northwestern University, Chicago, USA) and colleagues, has been described as a “milestone” for interventional radiology (IR) as a specialty and has heralded a call for greater collaboration between interventional radiologists and their Hepatology colleagues.
In the paper, Salem and colleagues investigate lung shunt function (LSF) observed in early HCC, and provide the scientific rationale for eliminating this step from routine practice. Salem and colleagues found that early stage patients, where segmental injections are planned, exhibited low lung shunting, effectively eliminating the risk of radiation pneumonitis. The study team proposed that the lung shunt study be eliminated in this subgroup, leading to fewer procedures, a cost reduction, and improved convenience for patients.
Commenting on the clinical implication of eliminating lung shunt function in early HCC patients from routine practice, Salem tells this newspaper that “this would streamline the Yttrium-90 [Y90] algorithm, decrease the time to treatment, lower costs and minimise unnecessary hospital visits.” He continues: “This is particularly important in the time of COVID-19. Basically, we could take a patient selected for segmental Y90 at tumour board, schedule the procedure, and treat. This model also gets us one step closer to our ultimate goal of the ‘one-hour Y90’ as the standard of care.”
Julius Chapiro, co-director of the Interventional Oncology Research Laboratory at Yale School of Medicine, New Haven, USA, speaks to Interventional News about the publication of the data, and why its publication in one of the preeminent journals for research into the field of hepatology represents a landmark moment in the continuing development of interventional radiology (IR). He argues that the paper could help to forge stronger ties between interventional radiologists and their colleagues in hepatology.
“The importance of publishing such data in the Journal of Hepatology and being featured as the cover story cannot be overstated for all of interventional radiology,” Chapiro comments. He cites the words of IR pioneer Charles Dotter, calling upon the practice to “provide clinical care” and “own” diseases and patients. “If we fail to do so,” Chapiro says, paraphrasing Dotter, “[we] become nothing more than high-priced plumbers”.
According to Chapiro, the manuscript takes these words from Dotter directly to heart. “Those of us who advocate for interventional oncology as the fourth pillar of cancer care must be rooting for Riad Salem’s team and this achievement,” he says. “Such high profile publications are changing clinical paradigms and inform a broad variety of specialists involved in therapy of liver cancer. The Journal of Hepatology is the official outlet of the European Association for the Study of the Liver (EASL) and has the highest impact factor of all journals focusing on liver disease. The publication reaches tens of thousands of people across the globe, including medical and surgical oncologists, both academic and in private practice. Having an IR cover story highlight our entire profession with such prominence legitimises our efforts, advocates for our therapies, establishes unquestionable authority, and protects our specialty.”
Describing the publication process, Salem says: “Once we had selected the prestigious Journal of Hepatology as our target, the manuscript was formatted accordingly and submitted. After receiving generally positive comments, we were encouraged to submit a revision with specific queries addressed. Once it was accepted, their production team sprang into action and enhanced the presentation style and graphics. They are a world-class team that significantly improved the manuscript quality, with the end result of the journal cover.
“The field of Hepatology is supremely competitive. Research groups from all around the world compete for a place in their high impact journals, with the Journal of Hepatology as one of the leaders, with an impact factor of 19. If the research is novel, impactful, and advances the field, the editors are universally fair and provide opportunities for all disciplines to publish in their journal. I have been very fortunate that in my career advancing IR, 26 manuscripts have been published in the highest impact journals of Gastroenterology, Hepatology, Journal of Hepatology and Gut. The editors placing our study on the cover reflects an acknowledgment of our team dedicating years of hard work investigating new concepts and challenging dogma. Our research group is humbled and honoured by this prestigious recognition.”
Discussing the efforts being made to improve teamwork between hepatologists and interventional radiologists, Chapiro comments that interventional radiologists are an integral part of liver tumour boards across most academic institutions, and that there has been a growing appreciation of their role in treating cancers of the liver. “Hepatologists and medical oncologists, who mostly lead those tumour boards in their cancer centres, have come to appreciate interventional oncologists as valuable team members and the spirit of those interactions is usually collaborative, productive, and cordial,” Chapiro states.
However, he argues that one of the most prevalent issues for interventional radiologists during these interactions with hepatology colleagues is the lack of unequivocal data in support of the therapeutic options. “This is especially true for the relative paucity of prospectively collected data from randomised controlled trials (RCTs) that would support the use of Y90, for example, in lieu of chemoembolization or as an option for patients with advanced stage disease.” Although not a randomised controlled trial, the data from Northwestern published in J Hep on the use of Y90 in early stage disease in patients waitlisted for transplant is an extremely valuable piece of information and has huge practical value, Chapiro suggests. “The elimination of shunt studies will make it more likely for transplant hepatologists and medical oncologists to choose this therapy, now that it has the stamp of approval from J Hep. Such data represent an important bridge between IR and other members of the tumour board.”
Exploring this idea further, Chapiro’s abiding message is that “teamwork begins at home”. “Our own institution has a very productive liver centre and interventional radiologists participate as full and associate members in collaborative projects and National Institute of Health [NIH]-funded research,” he says, adding that other avenues to collaborate are certainly through participation in NCCN guidelines, and through active memberships in national and international societies such as the American Association for the Study of the Liver Disease (AASLD), EASL and several Asian societies. Looking ahead at the opportunity for further opportunities to collaborate, he called for interventional radiologists to continue to make their voices heard within hepatology practice. “It is key for us to be present at their annual meetings and invite them to our own platforms such as the Society of Interventional Oncology Annual Meeting. At the end of the day, all we care about are patient outcomes and there is no better glue for us than this shared responsibility.”
The UK Royal College of Radiologists (RCR) has collaborated with the Society of Radiographers to create a leaflet for patients coming to the hospital for imaging and interventional radiology procedures.
The leaflet, “Protecting people attending for imaging tests or interventional radiology procedures,” outlines the new arrangements hospital sites are putting in place to protect visiting patients from COVID-19 so they may feel at ease. For example, patients with COVID-19 are scanned and treated separately, plus all patients coming to hospitals must wear a face covering or mask, it explains.
The leaflet also covers additional safety precautions patients will see, such as being asked about COVID-19, checking their temperature, new access routes, spacing around the imaging department and waiting areas, and staff wearing personal protective equipment.
“We want to reassure anyone visiting a hospital that radiology teams are doing everything they can to keep you safe from the virus,” notes RCR vice president for Clinical Radiology Caroline Rubin. “New protection measures are likely to include assessing you as you arrive, minimising contact in waiting areas, and potentially asking you to wait to be called in, as well as altering entry and exit points within the imaging department to keep people appropriately distanced.”
Intact Vascular announced the positive one-year results from its Tack optimised balloon angioplasty (TOBA) II BTK clinical trial during the 2020 Vascular Interventional Advances (VIVA) Late-Breaking Clinical Trial livestream.
Co-principal investigator Patrick Geraghty, professor of Surgery and Radiology at the Washington University School of Medicine in St Louis, USA, presented the one-year results, which successfully demonstrated sustained improvement in Rutherford category, toe-brachial index (TBI) and quality-of-life metrics following management of patients with post-PTA dissection with the Tack Endovascular System (4F), in conjunction with excellent limb salvage and amputation free survival rates.
“Effective treatment of below-the-knee arterial disease is a critical component of amputation prevention. Now, with Tack implants, we have an on-label treatment for post-angioplasty dissection that provides excellent outcomes through the first year of follow-up,” commented Geraghty. “The Tack device is a valuable treatment option that augments an aggressive approach to endovascular limb salvage.”
Notably the first vascular implant to receive US Food and Drug (FDA) premarket approval for below-the-knee (BTK) interventions, Tack implants impressively demonstrated an 81.3% Kaplan-Meier tacked segment patency and a 78.6% Kaplan-Meier target lesion patency, with an 83.1% Kaplan-Meier freedom from clinically-driven reintervention at one-year. No fractures, embolisation, or migration of the Tack device were observed, confirming the durability of the minimal metal implants.
Additionally, in the critical limb ischaemia (CLI) cohort, a population associated with high rates of amputation and mortality, Tack implants demonstrated remarkable 96.1% Kaplan-Meier target limb salvage and 89% amputation-free survival.
“This unprecedented trial is the first to investigate the safety and efficacy of a permanent vascular implant for repairing dissections in arteries below-the-knee. It enrolled a complex, predominantly CLI patient population that included 100% dissected vessels,” commented Peter Schneider, co-founder and chief medical officer of Intact Vascular. “These excellent one-year data highlight the clinical importance of below-the-knee dissection repair and validate the sustained durability of Tack implants.”
Additional co-principal Investigators for the trial included George Adams, director of Cardiovascular and Peripheral Vascular Research, UNC Rex Hospital, in Raleigh, USA, and Andrej Schmidt, Division of Interventional Angiology, University Hospital Leipzig, Leipzig, Germany.
“We are extremely pleased with the results from TOBA II BTK,” commented Bruce Shook, president and CEO of Intact Vascular. “The data from this clinical study add to the expanding evidence that repairing dissections following angioplasty improves long term outcomes for patients suffering from peripheral arterial disease (PAD). With FDA approval in hand, we are moving forward to address the large unmet need that exists among patients suffering from the most serious form of this disease, critical limb ischaemia.”
In a real-world retrospective analysis, recently published in JACC: Cardiovascular Interventions, the long-term mortality rate was lower after drug-coated balloon (DCB) angioplasty than after plain balloon angioplasty of femoropopliteal lesions. First author Tanja Böhme, senior author Thomas Zeller (both Universitäts-Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany), and colleagues note that known co-morbidities, risk factors, and disease severity were identified as mortality predictors, but not paclitaxel.
Böhme et al cite the continuing debate surrounding the association between paclitaxel and late mortality in femoropopliteal interventions as the principal motivation behind their study.
They note that the conversion was sparked by the December 2018 meta-analysis by Konstantinos Katsanos (University of Patras, Patras, Greece) et al, which suggested an increased long-term mortality risk following femoropopliteal angioplasty using paclitaxel-coated devices.
“It remains unclear whether treatment of femoropopliteal lesions with a paclitaxel-coated DCBs leads to an increase in all-cause mortality in a real-world setting,” Böhme and colleagues note, adding that health insurance data-based analyses even suggest a survival benefit for patients with paclitaxel-coated DCBs, referring specifically to a presentation given by William Schuyler Jones (Duke Heart Center, Durham, USA) at the TransCatherTherapeutics 2018 conference (TCT; 21–25 September) and a paper by Eva Freisinger (University of Münster, Münster, Germany) et al published last year in the European Heart Journal.
The authors of the present study therefore set out to evaluate the long-term mortality after paclitaxel DCB use and plain balloon angioplasty of femoropopliteal lesions in real-world practice.
Böhme et al conducted a retrospective mortality analysis of patients with at least three-year follow-up who underwent balloon-based endovascular therapy of femoropopliteal lesions. Between January 2011 and June 2016, 7,357 patients with femoropopliteal lesions were treated with either a DCB or plain balloon angioplasty; 1,579 fulfilled the study criteria. They detail that 514 patients were treated with plain balloon angioplasty without crossover to a paclitaxel-coated device during follow-up, and 1,065 patients were treated with DCB angioplasty.
The primary endpoint of the study was the difference in all-cause mortality rate after plain balloon and DCB angioplasty. Secondary endpoints included three-year and five-year mortality rates, the relationship between DCB length as a measure of drug concentration and mortality, as well as search for mortality predictors including type of treatment, age, gender, hyperlipidaemia, diabetes mellitus, renal insufficiency, cerebral artery disease, coronary heart disease, and Rutherford-Becker class 1–3 versus 4.
The authors report that mortality incidence at mean follow-up of 52±20.5 months (median 51 months) was 27.8% after plain balloon angioplasty and 16.9% after DCB (p<0.001). Equally, for a cohort excluding patients over 80 years of age, the mortality rate after plain balloon angioplasty treatment was significantly higher (23.6% vs. 12.3%, p<0.001).
In addition, they note that DCB length was not correlated to mortality rate and, after propensity score matching, independent mortality predictors were plain balloon angioplasty treatment (p=0.035), age (p<0.001), stroke (p=0.025), and renal insufficiency (p=0.007).
In the discussion of their findings, the authors remark that, despite including a large number of patients with long-term follow-up in this single-centre study, they were not able to confirm the findings of the Katsanos et al meta-analysis. “In this real-world study, even after adjusting for confounding variables, we found a significant mortality benefit for patients treated with DCB,” they write.
On the subject of mortality, the authors note that death was most common due to cardiovascular events. However, in a significant number of cases, the cause of death remained unknown.
Comparing their results to those of the Katsanos et al meta-analysis, Böhme and colleagues write that the mortality rates of their study are higher, “as expected”. They cite a potential reason for this as being Katsanos et al’s focus on randomised controlled trials, which “usually exclude patients at higher mortality risk, such as patients with end-stage renal disease. In addition, only patients with a certain life expectancy are included—frequently excluding elderly and frail patients results in a selection bias”.
The authors note that the single-centre observational design of their study is a potential limitation but defend the retrospective data analysis, which they state “does not affect the primary study endpoint of all-cause mortality”. They also note that this study design represents strength in terms of excluding potential confounding variables due to a standardised prescription of secondary preventive drugs, such as statins and antiplatelet agents following the intervention. Another limitation they mention is that in almost half of the study population the cause of death could not be determined.
Böhme et al conclude that, in this real-world study, treatment of femoropopliteal lesions with DCB excluding patients with ischaemic wounds resulted in a survival advantage. However, they note that all-comers randomised clinical trials are necessary to prove this long-term survival benefit and to identify the potential cause, such as a mobility benefit resulting in a positive risk profile modification as a result of a patent vessel.
The European Trainee Forum (ETF) Subcommittee of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) has published a report on the status of vascular and interventional radiology training in Europe.
Interviews based on a specially designed questionnaire created to assess the various aspects of interventional radiology (IR) training were conducted with the subcommittee members of the ETF, where recipients gave answers regarding their country of residence. The report includes responses from representatives of 24 European countries.
Contextualising the report, editor-in-chief Gregory Makris (London, UK) writes in the executive summary: “IR is transforming medicine through minimally invasive image-guided procedures. Despite the explosive growth of the specialty and the huge demand for more interventional radiologists, the training pathways across Europe have not all evolved in parallel with the clinical and academic needs of the discipline. Our objective was to map the training pathways across Europe in order to identify potential issues and identify ways for further improvement and development.”
The report reveals that IR has gained subspecialty status in nine of the 24 included countries, though adds that a structured IR training programme is available in 15 (62.5%). Makris and co-authors also note that there is “significant heterogeneity in terms of duration of IR training, with nine countries offering up to one year, 10 countries offering up to two years, and only five offering more than two years”.
An official IR certification examination is awarded following completion of the training programme in just under half of the 24 countries (11). Clinical training is included as part of the IR curriculum in seven countries, and ranges from two to six months of vascular surgery or intensive care.
In addition, the report finds that endovascular training opportunities “vary significantly” at an international level, “with inconsistent levels of exposure for the trainees”.
“Finally”, Makris et al write, “only three national IR societies have trainee subcommittees in their structure”.
There is slow progress in terms of obtaining subspecialty status for IR in European countries, while the duration, structure and certification of IR training remains heterogeneous. Consensus among the European IR leaders is needed in order to achieve a homogenous, well-structured, competitive and clinically orientated IR curriculum in Europe with clear guidelines regarding the required duration and structure of training to achieve competency, especially regarding peripheral arterial and aortic work. More active involvement of the trainees in national and international IR societies is also deemed essential for the future growth of the specialty.
NOTE: This video is ONLY available to watch in selected countries and geographies
Ripal Gandhi (Miami, USA) outlines his initial experiences with the Caterpillar™ Arterial Embolization Device (BD), a product, which he says is easy to utilize, shows good trackability in tortuous vessels and allows for “very accurate placement”.
Gandhi describes the novel device, which consists of both distal and proximal nitinol fiber segments that are designed to promote thrombus formation and limit migration.* There are three versions of the device currently available, which treat varying vessel sizes (1.5-4mm, 3-6mm and 5-7mm), he says.
Gandhi presents a case in which a 46-year-old male with colorectal cancer with metastatic disease to the lung and liver was scheduled for treatment with systemic chemotherapy and concomitant radioembolization. The patient’s right gastric artery measured 3mm in diameter so the decision was made to use the Caterpillar™ Micro Arterial Embolization Device which “tracked quite smoothly along the curvature of this vessel to the desired embolization site”. The subsequent angiogram showed “immediate occlusion” of the right gastric artery.
Concluding, Gandhi states that the device tracked “very nicely through this tortuous anatomy” and notes that the three radio-opaque markers “allow for good visualisation of the device under fluoroscopy.”
This video is sponsored by BD
Indication For Use: The Caterpillar™ and Caterpillar™ Micro Arterial Embolization Devices are indicated for arterial embolization in the peripheral vasculature. The devices are contraindicated for use in vessels subject to cyclic bending, such as locomotive joints or muscle beds.
*Pre-clinical data and bench testing may not be indicative of clinical performance. Different test methods may yield different results. Data on file, Bard Peripheral Vascular, Inc.
For safety information, click here http://www.bardpv.com/eifu/uploads/BAW1444700R1-Caterpillar-IFU.pdf
The Transluminal Biliary Biopsy Forceps Set (BBFS) and a new 40-centimetre delivery system line extension of the existing Zilver 635 Biliary stent (both from Cook Medical) are now commercially available in the USA.
“We are excited to make these products available to physicians to provide more treatment options for biliary duct procedures. This continues our efforts to bring products to physicians that fill the unmet clinical needs for patients,” comments Mike Williams, director of Cook Medical’s vascular programmes.
According to a company press release, the Transluminal Biliary Biopsy Forceps Set is designed to facilitate percutaneous acquisition of accurate tissue samples for biopsy. Cook Medical go on to state that biopsy samples obtained during biliary procedures “must be sufficient and precise to reflect accurate diagnosis”. BBFS was developed to include an introduction system coupled with a “cup and jaw” forceps design to retrieve biopsy specimens. Supporting the use of the BBFS design, a study published in Cardiovascular and Interventional Radiology reported a 94.2% diagnostic accuracy, with appropriate technique, when evaluating malignant biliary strictures using BBFS.
The Zilver 635 Biliary Stent is designed for cases of abnormal constrictions of the biliary tree (biliary neoplasms). The product helps to restore the natural flow of the biliary duct system, Cook Medical claims in a statement on the product launch. The flexible stent is also resistant to shortening, helping to provide precise placement. Having a 40-centimetre long delivery system permits ease of access for placement of the stent in biliary neoplasms.
Rexgenero, a regenerative medicine company developing advanced cell therapies to treat chronic limb-threatening ischaemia (CLTI), has announced the acquisition of all the key assets of aratinga.bio SAS Group, a preclinical-stage immunotherapy biotechnology company based in Paris, France.
The acquisition, which follows the recent approval by the French Commercial Court, includes all patent applications and related intellectual property, the exclusive license agreement for polymeric nanoparticle technology and the bioproduction facilities of aratinga.bio SAS Group, as well as the entire aratinga.bio team.
All assets of aratinga.bio SAS Group will be transferred to a newly created French subsidiary of Rexgenero.
David Horn Solomon, chair of Rexgenero, comments: “The acquisition of the aratinga.bio SAS Group’s assets and intellectual property will enable the creation of an integrated cell and gene therapy platform that combines our innovative late-stage Phase III REX-001 programme for chronic limb-threatening ischaemia with aratinga.bio SAS Group’s potentially transformative in vivo CAR-T platform. In addition, the operating synergies between the two businesses are considerable.”
Renaud Vaillant, chief executive officer of aratinga.bio SAS Group, says: “This unique combination provides the solution we have been looking for, enabling us to continue the development of our breakthrough CAR-T technology to proof of concept in 2020 in preparation for a Phase I/II clinical trial.”
Cécile Bauche, chief scientific officer of aratinga.bio SAS Group, adds: “This acquisition will provide funding for experiments needed to demonstrate proof of concept of our CAR-T therapeutics in vivo.”
The transaction enables aratinga.bio SAS Group to continue the development of its technology, and for the Paris-based team (15 people in Villejuif, close to the Institut Gustave Roussy) to pursue this programme.
The Infinity Angioplasty Balloon Company has announced that its balloon platform—the INFINITY Angioplasty Balloon Catheter—has been cleared by the US Food and Drug Administration (FDA) for percutaneous treatment of peripheral arterial disease.
“The INFINITY catheter represents a game changing innovation in percutaneous angioplasty balloon design and utility,” states founder and vascular surgeon, John Pigott. “A single SKU to treat lesions from 40–250mm in length, is adjustable, to the millimetre, in vivo assuring Precision Angioplasty, while addressing over 95% of real-life clinical cases.”
“Adopting the INFINITY platform reduces inventory needs and costs from dozens of SKU’s to two, it reduces space requirements, inventory management time, and trunk stock, while delivering the assurance that the right balloon size will always be on the shelf—INFINTY is a highly differentiated product,” reports CEO Gary Smith. “This is an ideal product for both office-based labs and hospitals.”
While initially launching an uncoated angioplasty balloon, the company intends to follow quickly with a drug-coated balloon platform of similar design.
Surmodics recently announced it has received CE mark certification in the European Union for its SurVeil drug-coated balloon (DCB).
“I am excited about the potential of the SurVeil DCB to improve the treatment of PAD,” said Professor Marianne Brodmann, interventional cardiologist at Medical University Graz (Graz, Austria) and a principal investigator in TRANSCEND, Surmodics’ pivotal clinical trial for the SurVeil DCB. “Drug-coated balloons have been widely utilised in Europe as a frontline treatment for PAD.”
The SurVeil DCB, a next-generation device that utilises best-in-class technology in the treatment of peripheral artery disease (PAD), includes a proprietary drug-excipient formulation for a durable balloon coating and is manufactured using an innovative process to improve coating uniformity. Preclinical data have shown a more evenly distributed and durable drug effect, and lower incidence of downstream drug particles compared to the control drug-coated balloon.
“This CE mark is a critical milestone and an exciting step forward for Surmodics as we continue to demonstrate industry leadership in the development of pioneering vascular medical devices,” said Gary Maharaj, president and chief executive officer of Surmodics. “The design of the SurVeil DCB reflects our dedication to providing innovative solutions that bring real clinical value—benefitting both clinicians and the patients that they treat. Congratulations go out to the entire Surmodics team on this well-deserved achievement.”
In February 2018, Surmodics entered into an agreement with Abbott that provided Abbott with exclusive worldwide commercialisation rights for the SurVeil DCB. Pursuant to the terms of the agreement, Surmodics received a US$25 million upfront payment and a US$10 million milestone payment for the completion of patient enrolment in the TRANSCEND clinical trial. As a result of CE mark attainment, Surmodics will receive an additional US$10.8 million milestone payment. The company will recognise approximately US$6.5 million as revenue in its fiscal third quarter and could earn up to an additional US$45 million for future product development milestones. Surmodics is not forecasting material revenue from the sale of its SurVeil DCB product over the remainder of its fiscal year ending 30 September 2020.
Under the agreement, Surmodics will be responsible for the manufacture and supply of clinical and commercial quantities of the product and will realise revenue based on initial product sales to Abbott as well as a share of profits resulting from third-party sales. The SurVeil DCB is not available for sale and is for investigational use only in the USA.
Radiofrequency ablation (RFA) is a successful treatment option for patients with painful osteolytic bone metastases, Jason Levy (Northside, Forsyth, and Cherokee Hospitals, Atlanta, USA) and Sandeep Bagla (Vascular Interventional Partners of northern Virginia, Springfield, USA) conclude, discussing the results of the first 100 patients treated in the OPuS One clinical study. In light of the Society of Interventional Radiology (SIR) annual scientific meeting’s cancellation due to the COVID-19 pandemic, Bagla also shared these positive data, which were featured in an abstract presentation for the SIR’s virtual event, on 14 June 2020.
“RFA for musculoskeletal metastases is really significantly underutilised,” Levy notes. This led the OPuS One triallists to embark on the largest-ever prospective RFA study, with the aim of collecting more data on this treatment option. In this post-market study, patients were monitored at baseline, and then followed-up three days, one week, one month, three months, and six months after RFA with the Food and Drug Administration (FDA) cleared OsteoCool device (Medtronic).
At each of these follow-up time points, patient-reported pain scores improved, Levy and Bagla relate: “These patients were seeing significant pain reductions, significant improvement in quality of life and functionality scores, at three days post RFA. In addition, it was seen at every single time point, and it continued to improve over time.”
On a scale of zero to 10, with 10 being the most painful, the mean score for worst pain in the last 24 hours at baseline was 8.2. This fell to 5.6 three days’ post-procedure, and then continue to fall, to 4.7 after one week, 3.9 after one month, 3.7 after three months, and to 3.5 at six months’ follow-up. Enthusing about these results, Bagla says: “That pain improvement, from 8.2 to 5.6, was very rapid in these patients, and that is what is important, and it was durable, even out to six months.”
Function and quality of life scores also showed improvements at each follow-up appointment. The investigators also observed a decrease in transdermal and/or oral narcotic use in 46% of the patients at three months, “which is even more impressive when you take into account that these patients were at end-stage,” Levy opines.
Medtronic sponsored this video and its distribution in association with Interventional News.
In a new field safety notice, the UK Medicines and Healthcare products Regulatory Agency (MHRA) states that a warning and clinical summary section will be added to the instructions for use (IFU) of 12 paclitaxel-coated balloons and paclitaxel-eluting stents used in the treatment of peripheral arterial disease (PAD) of the lower limbs.
The medical devices that will be affected by the changes are BioPath (Biosensors International), ELUVIA (Boston Scientific), IN.PACT Admiral (Medtronic), IN.PACT Pacific (Medtronic), Luminor (iVascular), Lutonix (BD), Passeo-18 Lux (Biotronik), Ranger (Boston Scientific), Ranger SL (Boston Scientific), SeQuent Please OTW (B Braun), Stellarex (Philips), and Zilver PTX (Cook Medical).
The notice states that updates will be made to the IFUs for these devices throughout Europe, including a warning and a summary of the December 2018 meta-analysis by Konstantinos Katsanos (University of Patras, Patras, Greence) et al, which found an increased risk of death at two and five years following the application of paclitaxel-coated balloons and stents in the femoropopliteal artery in the studies analysed.
The notice clarifies that no product batch/lot is being recalled in relation to this field safety notice, noting in its first appendix that “the benefits of paclitaxel-coated devices (e.g. reduced reinterventions) should be considered in individual patients along with potential risks (e.g. late mortality,” and urges physicians to discuss this late mortality signal and the benefits and risks of available treatment options with patients.
Click here to read the full field safety notice.
Guerbet has announced the approval of an additional indication for Lipiodol Ultra-Fluid by the China NMPA (National Medical Products Administration) for use in transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) at intermediate-stage in adult patients in the People’s Republic of China.
HCC is the most common primary liver cancer and the fourth biggest cause of death due to cancer worldwide. China alone represents more than 50% of all primary liver cancers globally since the country has the highest liver cancer prevalence in the world according to the WHO with about 330 000 cases.
“Guerbet is honoured to receive the NMPA approval for this indication for Lipiodol Ultra-Fluid in China. This registration reflects a strong positive endorsement from Chinese interventional oncologists and provides them with an additional NMPA endorsed therapy for managing patients with HCC in China. This is also evidence of our commitment to making cTACE available to as many HCC patients as possible.” commented David Hale, Guerbet’s CEO. “Development of image-guided procedures is a top priority for Guerbet’s Interventional Imaging Business Unit as we work to enhance liver cancer patients’ prognosis and quality of life in China and worldwide.”
Lipiodol Ultra-Fluid is used in interventional oncology for conventional transarterial chemoembolization, a minimally invasive procedure which consists of mixing Lipiodol Ultra-Fluid with an anticancer drug. The mixture is injected trans-arterially in the liver as a locoregional targeted chemotherapy for unresectable liver tumors (HCC). Lipiodol UltraFluid acts as a contrast agent, a drug vehicle, and a dual arterioportal transient embolic.
For interventional oncology procedures, Lipiodol Ultra-Fluid is approved for cTACE indication in EMEA (Austria, Belgium, Czech Republic, Denmark, France, Hungary, Iran, Ireland, Luxembourg, Portugal, Switzerland, the Netherlands, Tunisia, Turkey), in the Americas (Argentina, Colombia, Brazil, Chile, Mexico, Peru, Uruguay) and in Asia-Pacific (Australia, Brunei Darussalam, Cambodia, Hong Kong, India, Mongolia, New Zealand, Philippines, South Korea, Sri Lanka, Taiwan, Thailand, Vietnam).
Lipiodol Ultra-Fluid is approved for Imaging of patients with known HCC in the USA, in Canada and in Germany. Lipiodol Ultra-Fluid is approved for adjustment of Epirubicin hydrochloride for transarterial injection in Japan.
The first patients have been enrolled in the single centre DEPPER LIMUS clinical trial, Reflow Medical has announced. The non-randomised pilot study will evaluate the temporary spur stent system for the treatment of lesions in the infrapopliteal arteries using a limus-base drug-coated balloon.
According to the company, the DEEPER LIMUS study is expected to enrol up to 30 patients for approximately six months at a single centre outside the USA. It will follow primary and secondary endpoints for safety and efficacy.
“This gives us an opportunity to truly understand how differently antirestenotic drugs can treat infrapopliteal disease,” the trial’s principal investigator Marianne Brodmann (Medical University of Graz, Graz, Austria) comments. “The unique design of the spur device may enable the antiproliferative drug to reach the medial layers of the arterial wall, without leaving anything behind, and minimising the need for follow-up procedures.”
The retrievable temporary spur stent system is designed to treat long, diffuse, and severely calcified infrapopliteal disease. The device has a series of radially expandable spikes intended to create multiple pathways to allow the increased uptake of antiproliferative drugs into the vessel wall and facilitate acute luminal gain, without leaving anything behind, state Reflow Medical.
The Advance Serenity Hydrophilic percutaneous transluminal angioplasty (PTA) balloon catheter is now available to physicians in the USA. The catheter is manufactured by Surmodics and distributed by Cook Medical.
Advance Serenity is a hydrophilic-coated angioplasty balloon catheter designed to meet the technical needs of clinicians for treatment of patients who suffer from peripheral arterial disease (PAD) which includes below-the-knee disease. The catheter portfolio includes both a 0.014- and an 0.018-inch diameter wire guide platform and will be available in a wide variety of balloon lengths and diameters.
“Now that we have added Advance Serenity to our product portfolio of vascular solutions, physicians have one more tool in their toolbox to help treat patients who have PAD,” says Mark Breedlove, vice president of Cook Medical’s Vascular division.
Cook Medical has said it is working to make Advance Serenity balloon catheters available to physicians in Europe in the coming months.
Throwback to the 2019 Society of Interventional Radiology annual scientific meeting when Interventional News interviewed Bart Dolmatch (Mountain View, USA) on the early results of the AVeNEW trial – the first Level One trial dedicated solely to assess the safety and efficacy of the Covera (BD) covered stent designed to treat stenosis in the arteriovenous (AV) fistula access circuit.
The early results were “quite compelling” says Dolmatch, who notes that a 71% treatment lesion primary patency was seen at six months, which he notes is a greater than 30% improvement compared to angioplasty alone. The data also shows that “not only are we doing better than angioplasty historically has done” but also “much better than the original stent graft approved for this indication,” he adds.
Dolmatch also discusses some of the interesting developments in regard to vascular access and says that there is currently “a great amount of enthusiasm and excitement” for the use of catheter-based endovascular fistula creation.
The interim findings of the AVeNEW trial were awarded Abstract of the Year at the Society of Interventional Radiology (SIR) 2020 Virtual Sessions (13–14 June).
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A novel treatment for advanced mesothelioma is safe and effective and may improve the quality of life for patients who have few treatment options, according to a research abstract presented during a virtual session of the Society of Interventional Radiology’s 2020 Annual Scientific Meeting (13–14 June). Transarterial chemoperfusion with cisplatin, methotrexate, and gemcitabine every four weeks is a feasible and safe treatment for patients with relapsed unresectable malignant pleural mesothelioma (MPM). It comes with minimal side effects and shows promise for extending the lives of patients who have limited or no remaining treatment options.
Interim results from a phase 2 prospective study were announced at the SIR Virtual Meeting during an Abstract of the Year session. Presenting on behalf of his fellow researchers, Bela Kis (Moffitt Cancer Center, Tampa, USA), principal investigator of the study, said that the treatment shows a promising disease control rate in heavily pre-treated patients with relapsed MPM.
“MPM is a devastating cancer of the pleura, the membranes surrounding the lungs, that is very difficult to treat,” Kis said. “The typical survival rate of patients with stage 3 and 4 MPM is around 12 months from diagnosis; but with this new treatment, we are hoping we might be able to extend patients’ lives beyond that—giving them more time with friends and family.”
He explained that advanced MPM carries a poor prognosis, and that transarterial chemoperfusion treatment selectively delivers a relatively high concentration of chemotherapy to the targeted tissue’s arterial bed, maximising antitumoural effect and minimising systemic side effects. The study is investigating the disease control rate, overall survival and adverse events of the treatment in patients with relapsed unresectable MPM.
In all, 27 patients with MPM —four females and 23 males, mean age 70.8±6.8 years—were enrolled between March 2016 and June 2019. Patients had transarterial chemoperfusion treatment in every four weeks with cisplatin (35mg/m2), methotrexate (100mg/m2), and gemcitabine (1000mg/m2) via the ipsilateral internal mammary artery and/or descending thoracic aorta. All patients had received and progressed on prior chemotherapy. Four patients had also had radiation therapy, and three patients had had pleurectomy. Response rate was evaluated by modified RECIST for mesothelioma.
Transarterial chemoperfusion delivers a relatively high concentration of drugs to diseased tissue in the lining of the lungs to maximise the treatment effect with limited side effects. Unlike other chemotherapy that is delivered intravenously and circulates through the entire body, interventional radiologists inject one-third of the chemotherapy cocktail of cisplatin, methotrexate, and gemcitabine directly into the internal mammary artery that supplies the pleura. The other two-thirds of the drugs are injected into the descending aorta, which reaches the intercostal vessels that also supply the pleura. The treatment is an outpatient procedure and typically lasts an hour, followed by a one-hour recovery.
The interim results of the study show 70.3% disease control rate and median overall survival rate of 8.5 months from the start of the chemoperfusion treatment. The treatment was well-tolerated by patients with a major complication rate of 1.4%. Most side effects were relatively minor, including mild nausea and chest pain.
“We were pleasantly surprised to find that this treatment doesn’t come with the same side effects of traditional intravenous chemotherapy,” said Kis. “To see these promising results with so few side effects means we are able to make a positive impact on quality of life for these patients.”
Currently, surgery is the only truly effective treatment for MPM, but the disease must be diagnosed early. Only 10–20% of patients are candidates for surgery and often experience surgical complications.
The researchers are looking to expand their study to other cancer centres with larger MPM patient populations, since the cancer is so rare. They also hope to add flexibility to the study to allow for increasing the dosage and changing the combination of medications for individual patients to determine whether either approach could further improve outcomes.
Additional information about the clinical trial is available at ClinicalTrials.gov, using the identifier NCT02611037.
The research was originally scheduled to be presented in person at SIR’s Annual Scientific Meeting, 28 March–2 April, in Seattle, USA, before the meeting was cancelled due to COVID-19 concerns. See all our coverage of the virtual event here.
A covered stent provides significantly better target lesion primary patency than percutaneous transluminal angioplasty (PTA) of stenotic lesions in the venous outflow of upper extremity haemodialysis arteriovenous (AV) fistulae, according to interim results from the AVeNEW study announced at the Society of Interventional Radiology (SIR) 2020 Virtual Sessions (13–14 June).
Other findings presented by lead author Bart Dolmatch (Mountain View, USA) in the Abstract of the Year session were that safety was non-inferior with the expanded polytetrafluoroethylene (ePTFE)-covered, self-expanding Covera vascular covered stent (BD) at six months and, at 12 months, target lesion primary patency was statistically better for the covered-stent group, as was access circuit primary patency. In addition, about half as many reinterventions were required to maintain secondary circuit patency in the Covera stent group.
AVeNEW is a prospective, randomised study in 35 centres in the USA, Europe, Australia, and New Zealand, and is the first level-one clinical trial dedicated to the use of a covered stent designed to treat stenoses in AV fistulae.
Researchers randomised 280 patients with stenotic lesions (≥50%) and clinical or haemodynamic evidence of AV fistula dysfunction to either PTA alone (n=138) or PTA followed by covered stent placement (n=142). Primary endpoints were six-month target lesion primary patency and 30-day safety. Secondary measures included target lesion primary patency, access circuit primary patency, index of patency function, and the number of reinterventions needed to maintain patency at 12 months, with ongoing data collection to three years.
It found that safety at 30 days was non-inferior between groups (p=0.002). Target lesion primary patency at 180 days (Kaplan-Meier analysis) was superior for the covered-stent group compared to the PTA group (78.7% vs. 47.9%, respectively, one-sided p<0.001).
Among the 280 participants, 34 died (10.6% covered-stent group, 14.5% PTA group), and 10 patients withdrew or were lost to follow up (4.2% covered-stent group, 2.9% PTA group) prior to 12-month evaluation, leaving 83.9% of patients for follow up. Target lesion primary patency (Kaplan-Meier analysis) was superior for the covered stent group compared to the PTA (57.5% vs. 21.2%, respectively, p<0.001) at one year. Access circuit primary patency was also significantly better for the covered-stent group at 12 months, 28.9% versus 17.7% respectively (p=0.02). The mean number of reinterventions in the access circuit to maintain patency was 0.8+1 for the covered-stent group compared to 1.7+1.3 for the PTA group.
The research was originally scheduled to be presented in person at SIR’s Annual Scientific Meeting, 28 March–2 April, in Seattle, USA, before the meeting was cancelled due to COVID-19 concerns. See all our coverage of the virtual event here.
A new, nonsurgical treatment decreases errant blood flow in the shoulder to quickly reduce pain and improve function in patients with adhesive capsulitis, also known as “frozen shoulder,” according to a research abstract presented during a virtual session of the Society of Interventional Radiology’s 2020 Annual Scientific Meeting on 13 June. Frozen shoulder gradually causes significant pain and stiffness of the shoulder joint in an estimated 200,000 people in the USA each year. The symptoms are often treated with physical therapy or pain medications, until they resolve within one to three years.
“Patients with frozen shoulder are essentially told to tough it out until their symptoms improve, but considering the significant pain and decreased function many experience, we looked to determine if this treatment model of embolization, already in use in other areas of the body, could provide immediate and durable relief,” comments Sandeep Bagla (Vascular Institute at Virginia, Woodbridge, USA), CEO of Vascular Interventional Partners, NOVA, and lead author of the study. “We were shocked at the profound and dramatic improvement patients experienced in pain and use of their shoulder.”
In this Phase II US Food and Drug Administration (FDA)-approved Investigational Device Exemption clinical trial on arterial embolization of the shoulder (AES), interventional radiologists inserted a catheter through a pinhole-sized incision in patients’ wrists that was used to feed microsphere particles into as many as six arteries in the shoulder to reduce inflammation. The treatment was conducted on an outpatient basis and took approximately one hour. Each patient’s pain, disability, and blood flow in the shoulder were measured before and after the treatment using three scales, in addition to MRI imaging to visualise the shoulder joint.
The treatment was successfully completed in 16 patients whose symptoms had not responded to conservative treatment over 30 days. Minor adverse events such as temporary skin discoloration were reported in nine patients. One month later, researchers followed the progress of 11 patients and found that pain significantly decreased after arterial embolization of the shoulder (-57mm on the Visual Analog Scale) and improved physical function in all patients (+28mm on the Single Assessment Numeric Evaluation and +30mm on the American Shoulder and Elbow Surgeons Shoulder Score). Additional progress was reported at the three-month follow up.
“We are early in the investigation of this treatment but are inspired by its effectiveness in reducing pain and range of motion in patients’ shoulders,” Bagla says.
The research was conducted as a collaboration between interventional radiology and orthopaedic surgery to build on international studies of the procedure by adapting the treatment design and embolic agent to be more durable. The team plans to expand the study to additional patients in 2020.
The authors note that this treatment is still investigational and that conservative therapies should still be considered first. Additionally, there are several important limitations of the research, including small sample size and lack of control arm.
Additional information about the clinical trial is available at ClinicalTrials.gov, using the identifier NCT03676829. The trial is funded through Terumo Medical.
The research was originally scheduled to be presented in person at SIR’s Annual Scientific Meeting, 28 March–2 April, in Seattle, USA, before the meeting was cancelled due to COVID-19 concerns. See all our coverage of the virtual event here.
Interventional radiologists participating in a collaborative house call model in rural Indiana, USA, helped reduce emergency department use by 77% and hospital re-admissions by 50% for nearly 1,000 elderly home-bound patients with chronic illnesses, according to a research abstract presented during a virtual session of the Society of Interventional Radiology’s 2020 Annual Scientific Meeting on 13 June. The novel care model brings interventional radiology treatments into patients’ homes to provide more value through in-home advanced specialty care, prevent common complications of chronic diseases, and avoid unnecessary emergency department visits and hospital admissions.
“Older home-bound patients, including those in nursing home settings, have few resources available to receive specialty care and often delay care until preventable issues become urgent and acute,” explains Nazar Golewale, lead author of the study and an interventional radiologist with Modern Vascular & Vein Center (Valparaiso, USA). “By providing image-guided treatments in a patient’s home, we are improving access to care that otherwise would need to be delivered in the hospital.”
Golewale sees more than 900 of the practice’s patients to diagnose and manage their conditions. Through varieties of portable technology, he brings interventional radiology care into patients’ homes that would normally be delivered in clinics, such as ultrasound-guided needle biopsy, paracentesis and thoracentesis, ultrasound-guided joint injections for pain, wound care, and drug infusions. Payments for care are covered by Medicare reimbursement for home-bound patients.
The care partnership was formed to overcome the difficulty of providing specialty care for chronically ill, home-bound patients in Golewale’s rural community. As a result of the programme, patient satisfaction scores increased from 17% to 84% from before and after implementation of the programme. Primary care providers, including internists and nurse practitioners, recruited specialists based on the needs of the patients they serve. In addition to interventional radiology, the house call practice includes providers in internal medicine, podiatry, laboratory services, and wound care.
“Some specialty services are available at our local hospitals, but cost-effective ways of coordinating patients’ transportation and visits remained a significant barrier to care,” says Golewale. “By bringing the hospital care to the patient, we are eliminating these hurdles and providing timely, personalised care.”
The research was originally scheduled to be presented in person at SIR’s Annual Scientific Meeting, 28 March–2 April, in Seattle, USA, before the meeting was cancelled due to COVID-19 concerns. See all our coverage of the virtual event here.
Data from one of the first clinical uses of augmented reality guidance with electromagnetically tracked tools shows that the technology may help doctors quickly, safely, and accurately deliver targeted liver cancer treatments, according to a research abstract presented during a virtual session of the Society of Interventional Radiology’s 2020 Annual Scientific Meeting on 14 June. The technology provides a three-dimensional holographic view inside a patient’s body, allowing interventional radiologists to accurately burn away tumours while navigating to avoid organs and other critical structures.
“Converting traditional two-dimensional imaging into three-dimensional holograms which we can then utilise for guidance using augmented reality helps us to better view a patient’s internal structures as we navigate our way to the point of treatment,” says Gaurav Gadodia, lead author of the study and radiology resident at Cleveland Clinic (Cleveland, USA). “While conventional imaging like ultrasound and CT is safe, effective, and remains the gold-standard of care, augmented reality potentially improves the visualisation of the tumour and surrounding structures, increasing the speed of localisation and improving the treating-physician’s confidence.”
In this initial in-human pilot study, the technology was used to deliver a treatment known as percutaneous thermal ablation of solid liver tumours. To apply this technology, the physicians use multi-phase CT to coordinate markers placed on a patient’s body. This imaging data is added to a software application that allows for segmentation of the tumour and nearby structures within the marked coordinate space. This information is fed into a proprietary augmented reality application, which utilises Microsoft’s HoloLens technology, a virtual reality headset with transparent lenses, to project a segmented hologram of the patient’s imaged anatomy directly onto the patient. The hologram is registered to the coordinate markers to ensure accurate location of the relevant anatomy.
Utilising electromagnetic tracking, instruments including the ablation probe can also be visualised in the augmented reality space during the procedure, thus allowing for true holographic intraprocedural guidance. Interventional radiologists can then use the combination of the holographic images of the patient’s anatomy and tracked tools to find the tumour in the patient’s liver quickly, check for optimal targeting of the tumour by the ablation probe, and avoid key structures.
The study included five patients who were selected for microwave ablation of their liver tumours. For safety during this Institutional Review Board (IRB)-approved study, the gold standard of ultrasound was used for primary clinical decision making and probe guidance, with direct comparison to holographic guidance. Following ablation, images and video from post-procedural sonography, cone beam and multi-detector row CT, and HoloLens recordings were evaluated. In all five cases, intra-procedural holographic guidance was in agreement with the standard ultrasound-based guidance. Post-procedural imaging showed adequate tumour ablation, and no patients experienced tumour recurrence at the three-month follow-up. In this early phase pilot study, the authors anecdotally observed that the speed of tumour localisation was faster with holographic guidance, and that their confidence in optimal ablation and critical structure avoidance was improved over standard imaging guidance. They are further attempting to quantify these findings as they continue to enroll patients in the study.
Beyond its use during treatments, interventional radiologists also see value in using this tool for clinicians’ planning purposes and for improving patient engagement and understanding of the condition and treatment.
“This technique can be used intra-procedurally to check the accuracy and quality of the treatment, as well as pre-procedurally to engage with the patient in their own care,” says Charles Martin, an interventional radiologist at Cleveland Clinic (Cleveland, USA) who is the principal investigator of the IRB and the senior author of the study. “We can change 2D images into holograms of a patient’s distinct anatomy so that both the physician and the patient get a better understanding of the tumour and treatment.”
Researchers continue to test this technology for ablations in the abdominal area with plans to expand to other types of procedures and in other areas of the body. The technology has only been tested for feasibility and therefore cannot yet be used as a standalone method for delivering a treatment.
Additional information about the clinical trial is available at ClinicalTrials.gov, using the identifier NCT03500757. This work was funded through internal enterprise grants from Cleveland Clinic, as well as the Ohio-based biotechnology start-up, MediView.
The research was originally scheduled to be presented in person at SIR’s Annual Scientific Meeting, 28 March–2 April, in Seattle, USA, before the meeting was cancelled due to COVID-19 concerns. See all our coverage of the virtual event here.
The CX 2020 LIVE Vascular Access Consensus session sparked global interest, with chair Nick Inston (Birmingham, UK) and moderator Domenico Valenti (London, UK) taking questions from 17 countries, spanning South America to South East Asia. The session pinpointed the latest developments in this fast-moving field, including cutting-edge technologies such as endovascular arteriovenous fistula (endoAVF) creation, the use of covered stents in dialysis access, and the advantages of external support. Jennifer Hanko (Belfast, UK) opened with the benefits and drawbacks of peritoneal dialysis compared to haemodialysis, stressing the importance of choosing “the right access, for the right patient, at the right time”. Polling revealed that audience members were split on whether endovascular fistula creation is the future, with Inston concluding that the topic is “still up for debate”.
“All modalities must be considered” when planning access, Hanko began, including peritoneal access, haemodialysis, conservative care “as appropriate,” and the patient’s suitability for kidney transplantation.
She suggested that more patients could benefit from peritoneal dialysis if they had it first, but also stressed that this approach is only recommended for certain patients. Indeed, while haemodialysis requires frequent hospitalisation and peritoneal dialysis can be managed at home, the latter does carry with it a risk of infection.
Among the factors that preclude peritoneal dialysis are the presence of cardiovascular disease, low serum albumin, and age greater than 75 years. Furthermore, Hanko noted that there is “no consensus” on when a patient should proceed to both peritoneal dialysis catheter and back-up fistula creation.
Patients with no fistula options “should be encouraged to do peritoneal dialysis if possible,” Hanko advised the CX 2020 LIVE audience.
“Traditionally, we have advocated radiocephalic fistula first.” However, Hanko acknowledged that there are situations in which this may not be appropriate. She pointed out that patient choice is also an important factor, summarising that the approach at the Belfast City Hospital “is no longer fistula first. It is the right access, for the right patient, at the right time”.
Valenti opened the discussion after Hanko’s presentation, asking how patient choice influences her decision-making in fistula creation. “I think it is a partnership,” Hanko replied, adding that “it is about working with [patients] to get to a solution”.
Inston asked whether it is common practice to insert a peritoneal dialysis tube at the same time as creating a fistula, to which Hanko responded that it is not something she would advocate for most patients. But she acknowledged that a “small subset, probably less than 5%” would benefit. “I think we can all testify to the fact that when patients fail peritoneal dialysis, we are not always that great at having their vascular access ready”.
In response to a question from the UK, about what to do if fistula formation is not what the patient wishes, Hanko said she would still strongly recommend it, and get additional education for the patient on the risks versus benefits of a catheter over a fistula. However, she noted that “it is the patient’s choice in the end”.
New era of vascular access must move beyond “fistula first” approach
David Kingsmore (Glasgow, United Kingdom) also advocated a patient-tailored outlook to vascular access, describing in his presentation the “old era” approach of “fistula provision for all”—typified, he said, by European Society for Vascular Surgery (ESVS) 2018 guidelines on vascular access—as being ripe for change, in particular through greater use of early cannulation arteriovenous grafts (ecAVGs).
Kingsmore made the point that while, for some patients, fistulas remain the ideal treatment option, “for half [of patients] they are not”. Likewise, catheters for some patients are ideal, he commented, but for most they are not. “You have to consider what the patient aim is, and how to incorporate transplant with our vascular access planning. Overall, early cannulation grafts are certainly under-utilised and they can be optimised. We have an opportunity for a new era, to integrate and tailor optimal practices to patients’ aims, choices, and needs.”
Following his presentation, Valenti asked Kingsmore whether the “fistula first” approach has contributed to the underutilisation of grafts, to which he replied: “We are victims of looking at procedures rather than patients, [and] not integrating with other services and patient outcomes. Nick [Inston] has talked before about the outcomes and the changing success rate. We have got to bear in mind that dialysis has evolved substantially over the years, and transplant has evolved even more.”
Support for the use of external reinforcement is still limited
Developments in the use of external support devices were outlined by Robert Shahverdyan (Hamburg, Germany), who put forward a mechanical solution for fistula failure.
And, although an online poll of participants found that only 17% are currently using these devices to improve fistula outcomes, Inston was confident that the numbers would grow following Shahverdyan’s presentation on VasQ (Laminate Medical).
“The VasQ device improves the likelihood of an AVF becoming functional by addressing both haemodynamic and mechanical factors of failure. It produces consistent clinical benefits to patients, and also improves outcomes for an individual clinic when adopted as the standard of care for AVF creation.
“Several studies have been performed and more are under way to validate the clinical benefits of VasQ. So far, we are observing consistently high AVF usability and patency outcomes across the studies: 80–90% usability, with roughly 80% primary patency at six months for VasQ. [This] compares favourably with most other published results for standard AVF creations.”
Experience with endoAVF “encouraging,” but more data needed
Robert Jones (Birmingham, UK) provided a technology update on endoAVF, looking at the performance of two catheter systems—Ellipsys (Avenu Medical) and WavelinQ (BD).
One of the major benefits with this approach is the lack of surgical trauma, “therefore potentially less intimal hyperplasia and stenosis formation”. Jones also highlighted: “Both of these catheter systems utilise the forearm vascular anatomy to create an endoAVF, an area that is not typically used for surgical fistula creation”.
He added: “Multiple specialty operators can use both devices to create successful fistulas and this potentially can lead to a decreased waiting time for definitive access. Of utmost importance is patient preference.”
Polling reveals audience split over whether endovascular fistula creation is the way forward
Polling of the online audience revealed that only 46% agreed with the statement: “Endovascular creation of a fistula is the way forward.” However, if a role for durability of the fistula can be established, consensus may be reached. In the discussion that followed the presentation, a participant from Buenos Aires in Argentina raised the issue of the difference in cost between endoAVF formation and a standard surgical procedure. Jones conceded that “the upfront cost of an endoAVF device is higher in most countries than it is for surgical fistula”. But he pointed out: “The evidence to date has demonstrated that these endoAVFs require less reinterventions.” Jones pointed to the potential for longer-term savings, citing an American study published in the Journal of Vascular Access that compared collective WavelinQ data with retrospective Medicare data that “demonstrated that there was a saving to be made in each patient over a period of time. The upfront costs are certainly more expensive with these devices but, overall, in a long period of time, according to the evidence, it suggests there is a cost saving.”
Edited case illustrates endovascular fistula creation with WavelinQ
Panagiotis M Kitrou (Patras, Greece) demonstrated an edited case on the endovascular creation of an arteriovenous fistula using WavelinQ.
The device consists of two rapid change catheters, with the arterial catheter inserted first. Kitrou detailed the steps involved in preparing the patient, as well as the other devices required for the procedure.
The issue of costs associated with endoAVF was raised again in the discussion that followed, with a question from Johannesburg in South Africa. Other queries on time-to-fistula maturation in endoAVF, and whether it is necessary to coil deep veins, were submitted from as far afield as Argentina and Pakistan.
Covered endoprostheses are “the gold standard” for venous anastomosis with prosthetic vascular access
A second edited case was presented by Matteo Tozzi (Varese, Italy) on the use of a self-expanding covered endoprosthesis—Viabahn (Gore)—to treat AVF failure at the venous anastomosis. Tozzi reviewed the case of a 69-year-old male receiving haemodialysis for diabetic nephropathy, starting the dialysis with a tunnelled central venous catheter filter for a bloodstream infection.
Following the edited case, Tozzi then fielded questions from the global audience, including one from India to which Tozzi responded by outlining that “in the cephalic arch, the stent graft is the first option for the stenosis because all other techniques such as drug-coated balloon, plain balloon or high-pressure balloon fail very fast”. In this instance, a covered stent graft is “the gold standard”.
Tozzi added that he “chose this terrible case to demonstrate the ability to maintain patency in the functionality of the early cannulation graft” and following a question from a physician in Malaysia, about the use of cutting or scoring balloons before deploying the stent graft, Tozzi noted that “I prefer scoring balloons for predilatation of arch stenosis like the prosthetic venous anastomosis. I do not use cutting [balloons] because the blade damages the elasticity of the internal lamina of the vessel and therefore increases the intimal hyperplasia.”
In a series of Podium 1st presentations from world-class faculty, CX 2020 LIVE attendees heard the latest data on peripheral arterial disease management and an evaluation of different types of stents, including covered and helical options for challenging lesions. In total, nearly 5,000 people, from 125 countries, have registered for the inaugural, CME-accredited series of 10 sessions. The first CX 2020 LIVE session dedicated to peripheral interventions has been viewed by 3,222 people, tuning in from five continents.
An overwhelming majority of 81% answered “yes” in agreement with the comment “I like relining”. The poll followed three sessions that looked at the concept of “relining”, using covered stents for the management of complex aortoiliac occlusive disease. Livestream attendees heard that the surgical management of complex lesions, which may be heavily calcified, is difficult, and may lead to rupture. Meanwhile, the endovascular approach is gaining ground. Amer Zanabili (Oviedo, Spain) presented an edited case demonstrating the relining of an occluded, long TASC D iliac lesion, showcasing the potential of this technique. The polling results that followed then revealed an enthusiasm for this endovascular approach.
Roger Greenhalgh (London, UK) chaired the discussion, and Gunnar Tepe (Rosenheim, Germany) joined him as moderator for the session.
Covered balloon-expandable stents are effective treatment options for aortoiliac occlusive disease
In the first talk, Jean-Paul de Vries, (Groningen, The Netherlands) reported the key findings from a systematic review (published in the Journal of Vascular Surgery) of covered balloon-expandable stents for the management of aortoiliac occlusive disease. De Vries said: “Covered balloon-expandable stents are effective treatment options for aortoiliac occlusive disease as evidenced by the high rates of technical success and patency in all the stent grafts at one-year follow-up. They are preferred over bare metal stents for complex aortoiliac lesions, based on the documented five-year patency results for Advanta V12 in the COBEST trial.”
Overall, the studies explored five different stents: Advanta V12 (Getinge), Viabahn VBX (Gore), Lifestream (BD), BeGraft (Bentley), and Jostent (Jomed).
De Vries said the rates of technical success and primary patency were both high, adding that that primary patency, at one year, “was 96.6% for Viabahn VBX and that is comparable to the Advanta V12 [83.6–96.4% at one year] and 94.4% for BeGraft [one-year data were not available for Lifestream or Jostent].” He further noted that five-year data were available for Advanta V12, showing a primary patency rate of 74.7% and a freedom from target lesion revascularisation rate of 67.4%.
During the discussion that followed his presentation, de Vries noted that comparative trials were required because, at present, the data are insufficient to provide “any proof that the new-generation devices perform better than the former generation ones”. However, he observed that three-year data for Viabahn VBX had recently been published and these were comparable to three-year results for Advanta V12.
“Excellent” three-year results with Viabahn VBX relate to stent graft’s unique design
Andrew Holden (Auckland, New Zealand), in his talk, further expanded on the three-year data from the VBX FLEX investigational device exemption (IDE) trial. The objective of the study, he explained, was “to evaluate the safety and efficacy of the VBX stent graft [Gore] for the treatment of arterial occlusive disease in patients with de novo or restenotic lesions in the common and/or external iliac arteries”. The primary outcome was a composite of major adverse events at nine months.
Overall, in VBX FLEX, 234 devices were implanted into 213 lesions (134 patients) across 27 sites. Holden said: “The Viabahn VBX is made up of a double polytetrafluoroethylene (PTFE) layer with independent stainless steel rings that give it flexibility and conformability.”
He reported that with the three-year data, freedom from target lesion revascularisation “was a very impressive 91.2%, which improves to 98.1% when we evaluate the clinically-driven target lesion revascularisation.” Furthermore, according to Holden, “a number of clinical parameters remained improved at three years,” including the Rutherford category, resting ankle brachial index, and walking impairment questionnaire scores. “In fact, of the patients who were at Rutherford 0 by three years, 80% had started from a baseline of Rutherford 3 or 4. Overall, 92% of patients improved at least one Rutherford category at three years,” he explained.
“The VBX FLEX clinical study is truly a real-world study, including complex aortoiliac occlusive disease (TASC II C and D lesions, 32.1%), that has shown excellent results. […] These are no doubt due to the unique design of this device,” Holden concluded.
The ensuing discussion emphasised that covered stents have become the first-line treatment for complex aortoiliac disease. “What we have seen, particularly in complex disease, is a real practice shift towards covered stents. I think one could consider using uncovered stents for very simple lesions, but obviously, for more complex cases, I think the standard of care is covered stents. Rupture of iliac arties is potentially catastrophic, but this is really very well managed by covered stents.”
Greenhalgh observed that there was a risk of rupture when implanting a covered stent because calcification meant that there was no elasticity in the artery. “When you start to expand it, surely, occasionally, there are ruptures? [Is the understanding that] the lining is going to take care of the leak?” he questioned.
Holden commented: “That is precisely right. As long as we are trying to optimise lumen diameter, we are going to see significant incidence of rupture. […] With covered stents, you are certainly much more comfortable being aggressive.”
Rivaroxaban reduces risk of comorbidities in patients with peripheral arterial disease
Three-quarters of the CX 2020 LIVE audience agreed with the statement: “I will use rivaroxaban in peripheral arterial disease lower extremity revascularisation”. Polling took place following a talk from Rupert Bauersachs (Darmstadt, Germany) giving the results of the VOYAGER PAD trial.
“After revascularisation, one in five peripheral arterial disease patients will suffer from acute limb ischaemia, major amputation, acute myocardial infarction, ischaemic stroke, or cardiovascular death within three years,” Bauersachs told CX 2020 LIVE delegates. The VOYAGER PAD trial, he went on to relate, therefore set out to evaluate the safety and efficacy of 2.5mg bid rivaroxaban plus aspirin versus aspirin alone to reduce thrombotic vascular events after peripheral revascularisation.
Bauersachs reported: “Rivaroxaban 2.5mg bid on top of aspirin was associated with a significant 15% reduction in major adverse limb events and major adverse cardiac events, with no significant increase in TIMI [thrombolysis in myocardial infarction] major bleeding. Acute limb ischaemia was significantly reduced by 33% compared to current standard of care.”
The study therefore met both its primary efficacy endpoint—a novel outcome measure combining major adverse limb events and major adverse cardiac events—and its primary safety endpoint—TIMI bleeding.
“Dual pathway inhibition treatment is the only antithrombotic regimen proven for significant benefit of the peripheral revascularisation in a large, randomised controlled trial,” Bauersachs concluded.
As questions began to flood in from Europe and Asia, it became clear that many pertained to Bauersachs’ rationale for using such a low dose of rivaroxaban. “It is a very low dose, 2.5mg,” Bauersachs agreed, adding, “the actual dose for treating venous thromboembolism, for example, is 30mg. Because it is such as low dose, it has to be given twice a day.
“As we know, these are high-risk patients, so the objective was, with a low dose of anticoagulants on top of antiplatelets, to reduce those outcomes.”
Responding to a question asking why a low dose of warfarin was not used, Bauersachs said that previous trials had shown “unacceptably high rates of bleeding” and had lacked efficacy.
Lastly, a CX 2020 LIVE viewer from Malaysia queried the recommended length of time for patients to take rivaroxaban plus aspirin, after revascularisation. In agreement with Tepe, Bauersachs said that it would be a lifelong treatment.
“I think the point we are talking about here,” Greenhalgh said in summary, “is that patients with that sort of peripheral arterial disease will have all of these other issues and comorbidities. It is not a standalone condition, it is a marker of arterial disease throughout the body’s vascular system; the more peripheral, the higher the likelihood it will be severe elsewhere in the body.
“So, the use of rivaroxaban enables the complications that come with this complex disease to be reduced, and comorbidities can be handled better.”
MIMICS-2 study three-year results: Swirling flow “is the answer”
Thomas Zeller (Bad Krozingen, Germany) presented the three-year results of a US IDE study, MIMICS-2, for which he is the European principal investigator. The prospective, single-arm, multicentre clinical trial found comparable efficacy and safety results for the helical BioMimics 3D stent (Veryan Medical) and drug-coated balloons or drug-eluting stents available on the market.
The primary endpoint for this study consisted of a safety endpoint, composite of deaths, major amputation, clinically-driven target lesion revascularisation through 30 days, and an effectiveness endpoint defined as primary patency at 12 months. The proportion of chronic total occlusions was 30%, and moderate-to-severe calcification was seen in 46% of lesions.
Both device and technical success was 100%, and the primary safety and primary efficacy endpoints were reached. Zeller told the audience that these results represent “a clear achievement” for the BioMimics 3D stent.
Three-year freedom from clinically-driven target lesion revascularisation was 81% for the entire patient cohort, and there was “only” a decrease by 8% of freedom from reintervention between one and three years, Zeller related.
Describing the device, Zeller said: “The BioMimics 3D stent represents a new bare metal stent, designed with a helical centreline, which imparts a nonplanar curvature to the stented femoropopliteal segment, inducing swirling flow.”
This mimics the natural flow of certain anatomy, Zeller explained. The vessel curvature in the aortic arch and the iliac arteries induces a swirling flow in normal anatomy, known to protect endothelial cells against atherosclerosis and restenosis, he noted. This is based on the lifetime work of Colin Caro (London, UK). Greenhalgh elaborated: “From what you have just told us, we can say Colin [Caro] was right, all along. Swirling flow is the answer.”
Zeller assessed the results of the BioMimics 3D stent from the MIMICS 2 study against those for contemporary devices, including bare metal stents, drug-coated balloons, and drug-eluting stents. “If you compare the BioMimics 3D stent results from the MIMICS 2 study with Supera (Abbott), Zilver PTX (Cook Medical), Eluvia (Boston Scientific), and the IN.PACT Admiral (Medtronic), we can see that freedom from reintervention up to three years is almost comparable,” Zeller said.
Zeller responded to a question from Tepe about the lower event rate seen in the long term, commenting: “It underlines the theory of the basal-protective and endothelial-protective effect of swirling flow. We have the acute phase, where we see the patency failures, which are induced by acute inflammation, resulting in neointimal hyperproliferation and, over time, it evens out regarding the need for reintervention. For me, the most interesting question would be: ‘What is the outcome of combining this sort of long-term protective stent design with acute suppression of neointimal hyperproliferation means with an antiproliferative agent?’ That would be a very interesting study to be seen in the future.”
Following Zeller’s presentation, Greenhalgh commented: “[The BioMimics 3D stent represents] a completely new way. We are hearing about the future here. This is not just practical reconstruction—you have just heard how the future is going to go.
“Caro spent his life analysing normal flow of an artery, and he believed that if the blood swirled, then it would reduce the risk of arterial disease, and we have just heard that that it is possible, and he was right. We have also had a peek into the future, about how the treatment might be.”
Absence of long-term benefit of revascularisation in claudicants, according to five-year data
The session also heard how a liberal strategy of revascularisation in patients with intermittent claudication resulted in a substantial improvement in health-related quality of life for two years, but this benefit was lost at five years. This is the conclusion presented by Joakim Nordanstig (Mölndal, Sweden), after he shared the five-year results from the IRONIC randomised trial.
The IRONIC trial investigators aimed to study the clinical effectiveness and cost-effectiveness of the two most widely offered treatment strategies for patients with intermittent claudication: lower limb revascularisation in combination with best medical treatment and exercise advice, versus best medical treatment and exercise advice only.
Speaking to the fact that the IRONIC trial included femoropopliteal lesions and aortoiliac lesions alike, Greenhalgh commented, “Assessors would say that the expectation of success or reconstruction over five years with the aortoiliac is far better than with the femoropopliteal. Some would argue that you should keep them separate because the expectation is different. They may present with intermittent claudication, so it is one presentation, but a different expectation of natural history.”
“I agree with that comment,” Nordanstig replied, “but for the purpose of this design, it was a real-world design.”
Asked if this would impact his clinical practice of patients with intermittent claudication going forward, Nordanstig said: “In a way, yes,” before elaborating. “It is a staged process, actually, and I try to really carefully inform every patient about the pros and cons with revascularisation. It is not a first line treatment for me, but I will re-evaluate all patients within a few months.”
The session was followed by an Industry Symposium supported by Concept Medical to explore where the field stands in terms of sirolimus devices, with a session titled “Overcoming the limitations of paclitaxel: A new sirolimus-coated balloon for the treatment of peripheral vascular disease”.
Shockwave Medical announced today that the Centers for Medicare & Medicaid Services (CMS) has issued new codes for intravascular lithotripsy (IVL) procedures performed in peripheral arteries in both the hospital outpatient and inpatient settings.
The new Healthcare Common Procedure Coding System (HCPCS) outpatient and International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) inpatient codes will go into effect on 1 July 1 October 1 2020, respectively. Under these new codes, Medicare payment rates for IVL procedures performed in the hospital outpatient and inpatient settings, respectively, are consistent with current payment levels for other similar peripheral artery interventional procedures.
“The decision by CMS to assign codes for peripheral IVL procedures in both outpatient and inpatient settings is an important validation of Shockwave’s technology as a unique and distinct therapy for treating complex calcified disease in the peripheral arteries,” said Doug Godshall, president and chief executive officer of Shockwave Medical.
He continued: “We look forward to continued engagement with CMS as these new codes will now enable the collection of cost data specific to IVL procedures, which is the information the agency utilises when making future adjustments to procedure payment levels. The appreciation for IVL’s unique ability to safely and effectively treat these challenging patients is growing globally and we are grateful that CMS has taken this important first step on the path towards establishing a reimbursement level that appropriately reflects the clinical value delivered by IVL.”
For more information and a complete listing of codes, please go to https://shockwavemedical.com/reimbursement/.
Last week week, the CX 2020 LIVE agenda turned to the technically challenging topic of aortic arch interventions. Through presentations, discussion, and polling, the session—chaired by Roger Greenhalgh (London, UK) and moderated by Stéphan Haulon (Paris, France)—aimed to tackle some vital questions, including how to reduce the risk of stroke in thoracic aortic endovascular procedures, what the best options are for the left subclavian branch, and how best to approach aortic arch aneurysms. The session covered atherosclerosis, dissection, transection and ulcers, and their role in guiding treatment was clearly emphasised, with audience polling revealing that 85% would alter reconstruction in the arch according to the underlying pathology. The session also dealt with the wider debate of open versus endovascular surgery and considered the benefits of a multidisciplinary team. In a boost for the endovascular approach in this difficulty anatomy, 63% of audience members disagreed with the statement “Open is best”.
Gustavo Oderich (Rochester, USA) outlined preliminary experience with a range of device options that would enable the left subclavian artery [LSA] to stay patent. He began with the statistic that “30–60% of thoracic endovascular aortic repair [TEVAR] patients require Zone 2 incorporation with coverage of the LSA”. Considering the implications, he detailed: “We know LSA coverage without revascularisation is associated with more arm ischaemia, posterior circulation events, and spinal cord injury”.
He noted that patient-specific fenestrated stent grafts have been available for over two decades, and added that reports from the Cleveland Clinic and the Hamburg group demonstrate that mortality and stroke can be an issue, particularly if there is misalignment of the stent graft requiring arch manipulations.
Considering options for left subclavian branch incorporation, Oderich began with the Terumo Aortic Scallop stent graft, outlining a Dutch registry of 30 patients showing “excellent outcomes”, with only one Type Ia endoleak, one mortality, and one stroke.
Moving on to the Gore Thoracic Branch Endoprosthesis (TBE), he noted that this is currently under investigation in the USA. “This device has a single retrograde portal and one-side branch stent,” he said, adding that “this is a self-expandable stent, specially designed for the subclavian artery, with flared diameters”.
“It is recommended for these cases to obtain brachiofemoral through-and-through access for better support of the side branch,” he told the CX 2020 LIVE audience, going on to detail his clinical experience: “My preference is to use a small incision to expose the distal brachial artery, obtain retrograde access, and snare the wire in the distal thoracic aorta. The device has been loaded via the aortic wire and the through-and-through brachiofemoral wire”.
Oderich detailed that the feasibility trial results with the Gore TBE were reported in the Annals of Thoracic Surgery, with “excellent outcomes for Zone 2, no mortality, one minor stroke, one late asymptomatic subclavian artery branch occlusion, no Type Ia endoleak, and no late neurological events”.
Going on to discuss the Medtronic Valiant Mona LSA stent graft, Oderich outlined that this was investigated in an early feasibility study of nine patients. “Although technical success was obtained in all patients, there were three minor non-disabling strokes,” he detailed.
The Cook LSA single branch device, which Oderich noted was designed by Stéphan Haulon (Le Plessis-Robinson, France) and colleagues, has a triple-wide scallop that incorporates the left carotid artery and a preloaded catheter. “Following deployment of this stent graft, a sheath is advanced via the preloaded catheter, the subclavian artery is catheterised, and the repair is extended with a bridging stent,” he described.
He concluded: “Zone 2 extension is needed in up to 60% of TEVAR patients, and the preliminary experience with LSA branch devices indicates low morbidity and stroke rates, with high patency rates”.
Global audience seeks expert opinion on LSA branch devices
In the discussion following his presentation, Oderich first addressed a question from Haulon on treatment with an off-the-shelf device. He responded: “We can have an off-the-shelf device for the subclavian artery, because the location of the left subclavian artery in relation to the left carotid artery is quite predictable”.
He continued: “I do think that a lot of these patients currently being treated with coverage will actually have the option of revascularisation. That would include acute cases, like dissection or even transection. In the pivotal trial from Gore, the enrolment has been quite fast for the chronic dissection group. It is quite impressive. They were tentatively trying to enrol 10 patients and they have already included 93. So, I think that there will be a large subset of patients that will benefit from the left subclavian branch”.
An audience member watching from Moldova then asked Oderich, “In what subgroup of patients would either a bypass or transposition be used rather than a branch endograft?” to which Oderich responded that the “obvious” cases would be when the subclavian artery is not suitable for a branch.
Oderich noted that, given the investigational nature of some grafts, surgeons are still “shying away” from treating patients with certain indications, for example a very dominant vertebral artery. That being said, “with increased experience, as we showed, the patency rate is excellent”. He was positive looking forward: “I do think there will be a benefit of a branch over a bypass”.
One limitation of branches may be for the low origin of the left vertebral artery, Oderich revealed in a response to a question from Brighton, UK. In these cases, “we have to consider another device, like a scallop subclavian artery incorporation,” he suggested.
Finally, a question from Singapore asked when you would choose an LSA branch device over a fenestrated one for the LSA. “The issues with fenestration are several-fold,” Oderich responded. “First of all, from the standpoint of industry, it becomes [a] totally patient-specific device for the most part. The nice think about the branches is the ability to deploy the aortic stent graft and commit to that position. You do not have to keep twisting and you can just focus on the branch.
“I would say people are probably going to move away from fenestration towards a branch,” he concluded.
Collaboration needed to respond to aortic arch aneurysms
Roberto Chiesa (Milan, Italy) provided a comprehensive overview of total endovascular, hybrid, open and frozen elephant trunk repair techniques, looking at which is the best strategy to use in different scenarios, and the European Society for Vascular Surgery (ESVS) recommendations for each. He stressed: “The clever surgeon chooses the best option for the patient.”
Chiesa’s key message on aortic arch aneurysms was the need for multidisciplinary decision-making. He revealed that, at his centre, meetings take place every day between vascular and cardiac surgeons to decide on the choice of technique. Chiesa’s message also illustrated the potential that exists for using patient characteristics to choose between endovascular and open reconstruction. This view was reflected in the polling result on whether to alter reconstruction in the arch according to underlying pathology, with which 85% of respondents agreed. “It [the approach chosen] depends on the extent of the disease and the situation of the patient. In a fit patient, also in a young patient … open surgery can represent a good option. Endovascular repair offers possibilities that open surgery cannot offer,” he said.
“Acceptable results in fit patients” can also be achieved using the Frozen Elephant Trunk technique, said Chiesa, describing a hybrid strategy—a combination of both open and endovascular technique—as “a good option in high to moderate-risk patients”, and total endovascular branch repair as providing improving results in anatomically suitable patients. He closed his presentation with the prediction: “I think that will represent the future.”
Chiesa’s colleague, Luca Bertoglio (Milan, Italy), also presented an edited case of a carotid subclavian bypass. He explained that LSA revascularisation is recommended in aortic procedures to reduce the incidence of spinal cord ischaemia and stroke. Bertoglio noted this was the procedure that “we prefer to perform in our centre”.
He outlined how the carotid subclavian bypass is performed, and dealt with common difficulties encountered, including the impact of anatomy on the choice of implant.
A lively discussion followed his presentation, at the end of which Greenhalgh declared himself to have “been extremely entertained”.
Kevin Mani (Uppsala, Sweden) echoed Chiesa’s comments on the need for consultation with cardiothoracic colleagues when he discussed the feasibility of endovascular arch repair for type A dissection. He explained that more than two-thirds of post type A dissection repair patients are technically eligible for endovascular arch repair. He said: “It is not an easy procedure for the surgeon or the patient, so everybody is happy if it can be done endovascularly at the second stage.”
He concluded: “More than two-thirds of post type A dissection repair patients are technically eligible for endovascular arch repair. Future advancements that may increase this number include a greater awareness among cardiovascular surgeons of a sufficient ascending graft length.
“Considering the high rate of eligible patients, it can be expected that the use of endovascular arch repair for type A dissection patients will increase over time and increasingly replace redo sternotomy as the treatment of choice,” Mani speculated.
Silent cerebral lesions study: Clinical stroke incidence small but infarction rate “substantial” on magnetic resonance
Philippe Charbonneau (Paris, France) presented findings from a multicentre study which looked to quantify silent cerebral lesions, evaluate their clinical impact and to identify predictive factors following endovascular arch repair. He noted that TEVAR is the primary repair technique for aneurysms of the descending thoracic aorta but added that “neurological complications from this technique remain a significant concern” with the stroke rate at around 5%.
The study found that a total of 245 silent cerebral infarcts were detected in 45 patients, which represented almost 50% of the cohort. Lesions were multiple in 78% with a “predilection for both hemispheres” (58%) as opposed to isolated hemispheres (33% left and 9% right). When comparing baselines characteristics between patients with and without silent cerebral lesions, “no difference was found on univariate analysis”. An operative analysis of patients with and without new lesions showed that urgent procedure, deployment in Ishimaru zone 0–1, placement of a branch or fenestrated endograft, a proximal stent diameter of more than 40mm and the use of a haemodynamic strategy during the deployment were all “significantly associated with the presence of ischaemic lesions”.
Haulon said the results are “really interesting” and noted that there is “room for improvement” in aortic arch repair procedures. After Charbonneau fielded questions from physicians across the globe, Greenhalgh remarked that “The STEP study was set up for this very reason” and concluded that the “key is to see whether we can modify technique to reduce that [the infarction rate].”
Double fenestrated stent graft associated with low risks of mortality and persistent stroke
During the session, Ludovic Canaud (Paris, France) described the double branch technique as the “gold standard” for endovascular repair of the arch, while acknowledging that it does carry a high risk of mortality, failure, and stroke. An alternative approach is the chimney procedure, Canaud said, noting that while this is associated with high technical success, it has also been known to carry a risk of endoleak that is higher than 20%. Canaud also outlined the current status of in situ fenestration, detailing its high technical success rate on the one hand, but also issues with long-term follow-up on the other, including fabric tears and poor-quality fenestration.
In a boost for vascular education, the CX 2020 LIVE sessions have been granted European Union (EU) and US reciprocal Continuing Medical Education (CME) points in recognition of its highly interactive nature. In awarding this, the European Accreditation Council on CME (EACCME) is taking into account that this is a livestream with speakers performing from a panel and receiving questions from a global audience. On Tuesday, 759 attendees from 79 different countries tuned in. Each audience member could submit their name, country, and a question or point to the speaker in real-time, enabling interaction, discussion, and polling. Roger Greenhalgh (London, UK) chaired the most recent session, with Stephen Black (London, UK) moderating, as participants from five continents learnt about the latest development in superficial venous disease. Panellists fielded questions from 29 different countries, including the USA, Brazil, Ukraine, Kenya, Mexico, Spain, Saudi Arabia, Egypt, Argentina, Moldova, and the Russian Federation.
The first three talks of the session teased forthcoming, as-yet-unpublished guidelines from the European Venous Forum (EVF), the European Society for Vascular Surgery (ESVS), and the American Venous Forum (AVF)/Society for Vascular Surgery (SVS). These presentations were given by Armando Mansilha (Porto, Portugal), Manj Gohel (Cambridge, UK), and Lowell Kabnick (New York, USA), respectively. Additionally, a clinical assessment and work-up of patients with possible pelvic vein incompetence was presented by Aleksandra Jaworucka-Kaczorowska (Gorzów Wielkopolski, Poland), followed by a network meta-analysis on the use of cyanoacrylate glue, from Raghu Kolluri (Columbus, USA), audience polling, and, finally, an edited case from Kathleen Gibson (Bellevue, USA).
Spontaneous superficial vein thrombosis “far from a benign pathology”
Traditionally, superficial vein thrombosis (SVT) was treated with surgical management due to the perceived increased risk of deep vein thrombosis (DVT), which in turn could cause pulmonary embolism (PE), associated with a higher risk of death. Interestingly, it emerged in the CX 2020 LIVE discussion that surgical intervention is no longer mandatory. Instead, venous experts are searching for factors that explain a possible underlying hypercoagulable state that can lead to spontaneous thrombosis. One possible therapeutic option that is emerging for the treatment of SVT is the administration of anticoagulants. SVT is therefore no longer seen as requiring emergency surgery, but is indicative of an underlying condition that can be treated medically.
Manj Gohel (Cambridge, UK) told the CX 2020 LIVE audience that SVT is “far from a benign pathology”, discussing how the latest set of recommendations from the ESVS are set to pave the way for new approaches to treating this specific type of blood clot.
Though acknowledging that venous thrombosis is an “enormously varied topic”, Gohel said the writing committee felt strongly that superficial vein thrombosis should be included in the new guidelines, as it is “largely neglected” in other recommendations worldwide. “It is important to realise,” he added, “that it is significantly more common than deep vein thrombosis [DVT]; at least five times more common [as suggested] in most studies.”
Gohel said: “Anticoagulation, rather than antibiotics, is going to be the mainstay of treatment for most patients”. While he stated that “there will be a role for ablation of superficial venous reflux”, he clarified that he thought that this will probably not play a part in the treatment of sudden spontaneous thrombosis in the superficial vein.
A question posed to Gohel from a CX audience member from Iraq asked: “After treating superficial vein thrombosis, how long do you suggest waiting before treating the varicose vein in absence of any other contraindications?”
In his reply, Gohel highlighted the importance of treating the underlying superficial reflux. “All too often these patients have been treated and seen in thrombosis clinics, they have been told there is no DVT, and almost forgotten about”.
Multidisciplinary team important for managing pelvic vein incompetence
In her talk, Jaworucka-Kaczorowska looked at the clinical assessment and work-up of patients with possible pelvic vein incompetence. She showcased some extreme examples that she has encountered in her work as a gynaecologist, all the while emphasising the importance of drawing upon multiple skillsets in the treatment of these patients.
In particular, Jaworucka-Kaczorowska—noting she was a gynaecological surgeon—stated that she referred patients to a relevant centre with the appropriate radiological experience if they required percutaneous embolisation. Responding to this, Greenhalgh observed: “I think we have learned that when a physician can see a problem, the answer is that it is a multidisciplinary team that they require.”
Cyanoacrylate: A “good technique”, but “not a panacea”
The discussion next turned to the use of cyanoacrylate glue. Delivering his Podium 1st presentation, Kolluri said the VenaSeal closure system (Medtronic), a type of cyanoacrylate glue, is “a promising therapeutic option” with high rates of anatomic success, improved pain scores, and a low occurrence of adverse events compared with alternative treatment modalities. He made this conclusion based on the six-month results of a network meta-analysis published in the May issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, comparing different interventions for chronic venous insufficiency (CVI) management. Following his talk, Gibson provided a step-by-step guide to cyanoacrylate closure using VenaSeal.
The discussion following the two cyanoacrylate-focused talks highlighted that this new technique may be particularly useful in carefully selected patients, but was not suitable for all veins.
When asked: “Are you a fan of cyanoacrylate glue”, 61% of CX 2020 LIVE respondents answered “no”.
Gibson summarised her take-home message: “It is not going to replace endothermal ablation. I think it is an advance; I think there are some situations where it is extremely good. For example, in the elderly population, where they have a very low incidence of hypersensitivity.”
Kolluri concurred, stating that his patients, who benefit from the use of cyanoacrylate glue, have quite severe disease, with multiple comorbidities, and are at high risk of bleeding.
Turning to the other panellists, Greenhalgh invited each to provide their take on the technique. Gohel: “It is not a panacea; it is not going to replace everything”; Kabnick: “Thermal is still the gold standard”; Mansilha: “One more good technique. The strategy is the point”.
Moderator Black concluded the session: “I think like all new techniques, you learn the good and the bad, and this will find a good place in the long term”.
CME accreditation
The 10 livestreams that comprise CX 2020 LIVE are together worth 10 CME points, with one point awarded for each session. Participants can only claim CME points for the sessions that they have watched live.
Transit Scientific has received US Food and Drug Administration (FDA) clearance for the XO Score percutaneous transluminal angioplasty (PTA) scoring sheath platform for use in iliac, ilio-femoral, popliteal, infra-popliteal, and renal arterial plus synthetic and/or native arteriovenous hemodialysis fistula.
Angioplasty is performed with expandable polymer balloon catheters to dilate stenosed, or narrowed, vessels. Calcified, fibrous, and/or resilient stenosis may require special scoring or cutting angioplasty balloons with integrated wires or blades on the balloon. The added features focus and improve dilating force but result in large crossing profiles and limited deliverability while increasing cost and inventory, Transit Scientific said in a press release announcing the regulatory approval.
“XO Score transforms regular PTA balloons into scoring and cutting systems,” said Greg Method, president of Transit Scientific. “Clinicians insert an off-the-shelf PTA balloon into the XO Score tableside and then the system can be used over-the-wire to dilate calcified plaque and prep vessels.”
The XO Score is a patented, low-profile, flexible, metal-alloy exoskeleton with a balloon expandable scoring section. One XO Score sheath can be used with a number of 4–8mm diameter and 20–40mm balloons to save the hospital, outpatient lab, ambulatory surgery centre (ASC), or office-based lab (OBL) money on each scoring or cutting procedure.
“XO Score is a new way to prep the vessel,” said Jihad Mustapha, interventional cardiologist, Advanced Cardiac & Vascular Center, (Grand Rapids, USA). “The low-profile design is smooth for tracking to and from the treatment site. But, during balloon inflation, XO Score struts rotate 90 degrees on edge to score and cut. Upon deflation, the XO Score rewraps back-to-flat for smooth withdraw.”
Competitive scoring/cutting balloons feature 1–5 fixed-depth scoring wires/blades that add bulk, profile, and stiffness. XO Score has up to 22 scoring/cutting struts that lay flat while tracking but rotate 90 degrees during balloon inflation to score and cut 0.25mm (0.010″), 0.35mm (0.014″), or 0.50mm (0.020″) deep. Struts rotate 90 degrees back during deflation.
This FDA clearance covers the 6.3Fr (French) XO Score in 65cm and 125cm working lengths with 0.25mm (0.010″), 0.35mm (0.014″), or 0.50mm (0.020″) scoring or cutting depths to enable precise dilation across a range of lesion types. Future 3Fr, 4Fr, and 5Fr over-the-wire and rapid-exchange XO Score versions are under development for smaller vessel and coronary use.
In May 2020, Transit Scientific received FDA clearance for the XO Cross 2Fr, 2.6Fr, and 3.8Fr low-profile, high-torque, and high-push non-tapered microcatheter platform. Transit Scientific is a private company with more than 26 combined issued and pending patents to commercialise medical devices including the FDA-cleared XO Score and XO Cross platforms.
The US Food and Drug Administration (FDA) has designated Laminate Medical’s VasQ external support for the creation of arteriovenous fistulas (AVF) in haemodialysis patients as a breakthrough device.
According to a press release, the designation was based in part on the breadth of clinical evidence collected so far for VasQ that consistently demonstrates improvement over the standard of care for creating functional AVFs for haemodialysis treatment.
“I have been anxious to get my hands back on VasQ ever since I reached the maximum enrolment for a site in the US clinical study,” said Jason Burgess of the Surgical Specialists of Charlotte (Charlotte, USA). “I am excited that the FDA has recognised the urgency we have as surgeons to improve the woeful outcomes that plague fistula creation.”
VasQ is currently in a US investigational device exemption (IDE) pivotal clinical study that is expected to have completed follow-up for its primary endpoints by August 2020 and will be evaluated by the FDA through the de novo pathway.
As of 4 February 2020, the single-arm study has prospectively enrolled its entire 144 male and female patient cohort from 15 sites across the USA. Both current and pre-dialysis patients referred for fistula creation where included in the study for either a brachiocephalic or radiocephalic fistulas with VasQ.
The patients will be followed for two years with the primary efficacy endpoint of unassisted primary patency to be analysed at six months. The FDA will consider the results from the study as well as the breadth of clinical evidence collected from use of the device around the world in its decision to grant US market clearance.
“This is a significant milestone for VasQ that will enable a faster and smoother regulatory process for the US market as well as support the necessary reimbursement for the use of the device in clinical practice to benefit patients,” stated Orit Yarden, vice president of Clinical and Regulatory Affairs for Laminate.
BD has announced the launch of the Halo One thin-walled guiding sheath, designed to perform as both a guiding sheath and an introducer sheath, for use in peripheral arterial and venous procedures requiring percutaneous introduction of intravascular devices.
According to the company, the device consists of a thin-walled (1-F wall thickness) sheath made from braided single-lumen tubing, fitted with a female luer hub at the proximal end and a formed atraumatic distal tip. The thin-walled design reduces the size of the arteriotomy compared with standard sheaths of equivalent French size to help minimise access-site complications. A stainless-steel braid construction fortifies the design for extra support.
The Halo One thin-walled guiding sheath is available in a broad size range (4, 5, and 6F) with shaft lengths of 10 and 25 cm, as well as shaft lengths of 45, 70, and 90 cm for 4 and 5 F sizes. The device is suitable for distal peripheral intervention as well as for alternative approaches, such as tibiopedal or radial access sites.
“With Halo One thin-walled guiding sheath, we’re focusing on where those interventions begin, at the point of access. It effectively downsizes the access profile of peripheral procedures compared to standard sheaths, making it a valuable complement to our innovative portfolio of peripheral artery disease interventional devices,” said Steve Williamson, worldwide president of BD Peripheral Intervention.
“Access site complications occur in up to 11% of peripheral vascular interventions,” said JD Meler, vice president for medical and clinical affairs at BD. “A low profile guiding sheath that is available in lengths suitable for distal peripheral interventions and with a design that can help to reduce access site complications, which have been shown to increase hospital length of stay and costs, is a meaningful addition to our interventional suite of products.”
Transradial, as opposed to transfemoral access, may be a safer approach for flow diversion procedures to treat cerebral aneurysms at a wide range of locations. This conclusion was reached by Yangchun Li from the University of Miami Miller School of Medicine (Miami, USA) and colleagues, as their retrospective study, published online in the Journal of NeuroInterventional Surgery (JNIS), found that both access site complication rate and overall complication rate were lower for transradial access flow diversion.
The investigators used a large multicentre registry to retrospectively analyse flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with a 95% confidence interval (CI) to account for results from multiple centres. Access site complication rates and overall complication rates were compared between the two approaches.
Of the 2,285 patients included in the study who underwent flow diversion, 135 (5.85%) were treated with transradial access, and 2,151 (94.14%) via transfemoral access. Li and the team reported that the two groups shared similar patient and aneurysm characteristics.
“There were no access site complication in the transradial access group,” highlight the authors. However, they write that the rate of access site complications for the transfemoral approach was 2.48% (95% CI, 2.4–2.57%, vs. 0%; p=0.039). Of note, one death resulted from a femoral access site complication.
The overall complication rate was also higher in the transfemoral group (9.02%; 95% CI, 8.15–9.89%) compared with the transradial group (3.73%; 95% CI, 3.13–4.28%; p=0.035), reported the investigators.
Why the authors are advocating for transradial access
These findings, Li et al say, help alleviate the apparent lack of neurointerventional literature directly comparing complication rates between the two approaches. Whilst the field of cardiology has conducted large randomised trials that have shown lower morbidity and mortality, as well as higher patient preference and cost reduction associated with transradial access, the same depth of investigation has yet to be applied to neuroendovascular medicine.
Moreover, Li and colleagues write: “Reducing access site complications is relevant to flow diversion for two reasons. First, flow diversion employs larger bore access systems, which may increase the likelihood of access arterial injury, bleeding or occlusion. Second, prolonged dual antiplatelet therapy is administered to patients undergoing endovascular flow diversion along with heparin, which increases the risk of access site bleeding. Additionally, the smaller diameter of the radial artery raises the question of whether a transradial access approach is uniformly feasible for flow diverting procedures.”
The investigators state that the current study is “the largest series to date comparing transradial and transfemoral access for this type of neuroendovascular procedure”. Additionally, they argue that the study demonstrates a significant safety benefit with transradial access flow diversion, alongside the feasibility of treating both ruptured and unruptured aneurysms via transradial access at a wide range of locations.
Lastly, the team surmise: “Combining both these findings with other benefits of transradial access, including high patient preferences, elimination of post-procedural bed rest and decreased cost, we continue to advocate for the transition to a radial-first approach for endovascular flow diversion.”
The Society of Interventional Radiology (SIR) president Michael D Dake (University of Arizona Health Sciences, Tucson, USA) and diversity and inclusiveness group chair Paul J Rochon (University of Colorado Hospital, Aurora, USA), have issued the following statement on supporting diversity and combating racial inequality in the USA.
“Humanity has been dealt many challenges this year. While COVID-19 has undoubtedly received much of our attention, we suffer from another pandemic that remains a structural and pernicious threat—racism. The Society of Interventional Radiology (SIR) will not be silent on this issue.
“We denounce any act of hatred and bigotry on the basis of race, ethnicity, religion, sexual orientation, or gender identity. We denounce the long history of hatred and violence against the Black community and support our Black patients, physicians, trainees, nurses, technologists, industry partners, staff and administrators. We need to stand together in strength and work with a common purpose to realise a more diverse, equitable and inclusive organisation.
“We commit to anti-racist efforts, policies, and programmes that aim to increase the numbers of underrepresented minorities and women within our specialty. Our GEMS programme supports diversity in interventional radiology by providing a travel grant for medical students from diverse backgrounds who desire to participate in a visiting clerkship in interventional radiology (IR) outside of their home institution.
“We value a culture of inclusion in which all members of the IR community are accepted, respected, and embraced. The society’s IAmIR campaign has both celebrated and drawn attention to diversity within the specialty. SIR has microgrants that support research performed by female and underrepresented minority scientists and a speakers’ bureau to ensure interventional radiologists of colour are tapped as experts in their field at scientific meetings.
“We strongly support the need to reduce and eliminate health disparities that affect our Black patients and other patients of colour. SIR’s Diversity and Inclusiveness Group Task Force has been working for several years to ensure that these issues are a vital part of our strategic plan.
“We call upon our membership and affiliates to take this time to remember the families and communities of George Floyd, Breonna Taylor, Ahmaud Arbery and many others who have been subject to unconscionable acts of discrimination and hate. We ask that everyone look into his or her heart to understand the overdue need for change in the nation. With our intentional efforts, SIR calls to action the continuing need to develop strategies to ensure justice, diversity, equity and inclusion.”
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Annual Scientific Meeting will be taking place online 12–15 September. Read the full press release from the society below.
“It has been several months since the beginning of the COVID-19 pandemic and although infection numbers in some countries have declined, others are currently in the middle of experiencing the devastating effects of the virus. The situation remains uncertain and as governments struggle to find ways to prevent a second wave of infections, we all have to accept the new situation. Governments have imposed travel bans and strict limits on in-person meetings, which often means that we—at least for the time being—have to change the way we interact with others.
“It is for these reasons that the CIRSE Executive Committee has decided to hold CIRSE 2020 as an online event from September 12–15 instead of the physical meeting originally planned to take place in Munich. By offering a virtual event, CIRSE will provide a safe and reliable platform for knowledge exchange to IRs [interventional radiologists] around the world, regardless of the situation in their country or their ability to travel.
“We look forward to offering the usual high-quality sessions featuring the field’s top experts and the latest research further enhancing the evidence-base of our specialty. We would particularly like to thank our many faculty members for their patience and their unwavering commitment, as well as our corporate partners, who have been very supportive during the pandemic and will of course also form an important part of the CIRSE 2020 Summit.
“We invite all interested parties to access the CIRSE website, sign up for the CIRSE e-newsletters and join the CIRSE social media channels to stay up-to-date as we continue to plan an outstanding CIRSE 2020 Summit.
“We look forward to a lively knowledge exchange at the CIRSE 2020 Summit and to talking to you via its interactive platforms!”
Despite being “perfectly placed” to help meet the increasing demand for stroke thrombectomy, there is not an established training structure for interventional radiologists wishing to perform the procedure in Europe. The findings of a recent online survey conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) on stroke thrombectomy provide, according to the society, a “mandate [for] further European-wide initiatives” to establish such training programmes.
Writing to the Editor of CardioVascular and Interventional Radiology, CIRSE past president Robert Morgan (St George’s University Hospitals NHS Foundation Trust, London, UK) et al state that current barriers to interventional radiologists becoming key players in European stroke management, identified by CIRSE leadership, include “the absence of an established training structure for interventional radiologists performing stroke thrombectomy, a strong dependence on local conditions, limited 24/7 coverage, as well as varying opinions on the desired involvement of interventional radiology [IR] in stroke thrombectomy”. Therefore, to assess the level of interest and involvement by interventional radiologists in the procedure across Europe, CIRSE conducted an anonymous online survey on the current situation of stroke thrombectomy practice among European interventional radiologists.
Stroke thrombectomy was performed in 74.5% of the respondent’s centres, with an expected predominance in university hospitals, tertiary care hospitals and private hospitals, although the procedure was also performed in 52.5% of general hospitals. There was also an increasing tendency for the procedure to be performed in larger hospitals.
In centres where stroke thrombectomy is performed, it was most frequently delivered by interventional radiologists in 70.1% and by neuroradiologists in 48%. Stroke thrombectomy was provided by both interventional radiologists and neuroradiologists in 21% of centres. “Collaboration with other specialties appeared to be good throughout the obtained sample,” the letter says, “as interventional radiologists perform stroke thrombectomies in collaboration with other medical specialties in almost 90% of centres.”
It continues: “Training for stroke thrombectomy by interventional radiologists was either provided by a neuroradiologist at the same centre (47.7%) or was obtained by interventional radiologists independently (46.2%). However, opportunities for training in stroke thrombectomy are relatively limited for interventional radiologists, especially where there was reluctance by neuroradiologists to involve interventional radiologists in the stroke thrombectomy service, and almost a quarter of respondents who perform stroke thrombectomies indicated that they were ‘trained in another way’, indicating a large variety in training modes and options and reconfirming the need for more standardised training pathways and dedicated courses for IR.”
The survey also reported a broad consensus among respondents that “a significant growth in the demand for stroke thrombectomy was expected, due to factors such as improved infrastructure and service availability, increased awareness of this treatment option among referrers, better clinical evidence, and broader inclusion criteria”.
Speaking to Interventional News about the results of this survey, Morgan says: “This survey confirms that in many countries, interventional radiologists already have a significant role in the delivery of intraarterial stroke therapy. This was already known by CIRSE but had not been confirmed previously by a formal survey of CIRSE members.
“We all know that there are not enough interventional neuroradiologists to provide intraarterial stroke therapy in Europe in the volumes that are required by patient demand for this procedure. I would like the future of stroke thrombectomy to be a comprehensive service satisfying the widespread demand by patients and delivered by doctors who have been adequately trained to perform the procedure. Interventional radiologists would be key players in the stroke thrombectomy service, working alongside our colleagues in interventional neuroradiology.
“To bring this about, we need to form even better collaborative working relationships with our interventional neuroradiological colleagues. These improved relationships should be encouraged by our colleagues and not hampered by any counterproductive issues such as turf. Another important requirement is the recognition by leaders of national health systems that interventional radiologists can provide stroke thrombectomy and should be encouraged to do so in their country’s hospitals.”
CIRSE received a total of 601 valid responses, which the society claims is “a very high response rate (11.5%) for a CIRSE member survey”. Of these, 109 came from Germany, 87 from Italy, 68 from the UK, 38 from The Netherlands, 36 from Turkey, 32 from Spain, 28 from Belgium, 26 from Austria, 25 from Greece, and the remaining quarter from other European countries—“the sample was considered to be representative of CIRSE’s European membership in terms of geographical spread, centre type, and level of experience”. However, the letter writers acknowledge a potential bias that interventional radiologists involved in stroke thrombectomy may have been more likely to respond.
Straub Medical has approved a full acquisition by Becton, Dickinson and Company (BD). The acquisition was completed on 20 April 2020. Straub Medical manufactures, develops, and sells medical devices for the treatment of arterial and venous diseases that are used worldwide by vascular surgeons and interventional specialists in radiology, angiology, and surgery.
Gido Karges, CEO of Straub Medical, comments: “BD is the ideal strategic addition to Straub Medical. With its complementary product portfolio and established global sales channels, BD offers treatment solutions for vascular specialists around the world to advance the world of health.”
“With our extensive expertise in endovascular technologies and our strong global infrastructure, BD is the right company to offer Straub Medical products worldwide as an important building block of our modern treatment solutions,” says Steve Williamson, president of BD’s Peripheral Intervention business. “We are committed to improving the quality of life for the more than 200 million people worldwide who are affected by occlusive diseases of the peripheral arteries. We are also committed to providing more instruments for treating venous diseases. The acquisition of Straub Medical makes it possible to help physicians worldwide treat even more affected patients.”
All employees in all branches are taken over by BD.
Data from an unselected, real-world cohort of 64,000 claimants of the German BARMER Health Insurance reveals no signal of increased long-term mortality when paclitaxel-based devices are used in the femoropopliteal arteries, Eva Freisinger (Münster, Germany) told BLearning Peripheral at LINC 2020.
She explained that as German law mandates the mortality of every insurance holder be reported directly to the healthcare insurance provider, the investigators knew the exact date of death for every patient included in the analysis. “This is why we have no loss of follow-up on this important end-point,” Freisinger imparted.
“In 2020, I would consider these devices to not harm patients in the long-term, as was suggested by the Katsanos work,” she concluded, referencing the 2018 meta-analysis by Konstantinos Katsanos (Patras, Greece) et al that reported an increased association with mortality with paclitaxel-based devices in the leg. Freisinger believes these findings should “reassure physicians [that] we do not see an increased long-term mortality signal for paclitaxel-based devices”.
Bolstering the evidence-base for proponents of paclitaxel-based devices, Thomas Zeller (Bad Krozingen, Germany) also reported positive results for drug-coated balloons (DCBs) at LINC.
In an analysis of approximately 1,600 patients at his own institution treated with either a paclitaxel-coated balloon or through a paclitaxel-naïve method (either bare metal stenting, atherectomy, or plain balloon angioplasty), and with a follow-up of at least three years, Zeller and colleagues “found a mortality benefit of around 10% over time favouring the treatment with DCB angioplasty”.
He added that, despite being a single-centre, retrospective study, he believes “this is very high-level scientific data, because we enrolled really all-comers, we did not exclude any patient”. Additionally, an advantage of the single-centre setting is to exclude any confounding variables that may arise if patients are treated at different hospitals.
Based on both large, real-world data sets from insurance companies and this single-centre data analysis, Zeller concluded that his team “could not confirm” the 2018 findings that treatment with paclitaxel-coated devices in the femoropopliteal segment poses a greater risk to long-term mortality.
This video is sponsored by Medtronic
Mentice AB has announced the global introduction of its seventh-generation Vascular Interventional System Trainer (VIST) simulation platform.
According to the company, the VIST G7 includes artificial intelligence guidance, integration to robotics, and big data analytics. The newly redesigned platform of the VIST G7 incorporates the company’s latest advances in sensor and haptic technologies and uses newly developed software solutions.
A premium version of this platform with a higher level of realism is offered as the VIST G7+, which allows doctors to simultaneously manipulate multiple devices while using a single access point for therapies such as bifurcation lesion interventions and branched devices.
In the Mentice announcement, Lars Lönn, from National University Hospital (Copenhagen, Denmark), commented, “In the past, endovascular simulators were challenged to match the haptic feedback a seasoned doctor will experience on a real patient while pinning and advancing microcatheters, making microadjustments, selecting small vessels, and applying certain tricks and techniques acquired over many years of practice. Performing an interventional procedure on the new G7 platform feels incredibly like the real thing, even in intricate cases.”
Khalid Barakat from Queen Mary University, London, UK, added, “This new G7+ platform increases the fidelity of scenarios and is a much-needed addition to our practice, allowing us to simulate challenging bifurcation percutaneous coronary intervention (PCI) cases. Our aspiration is to perform procedure rehearsals for the most complex PCI cases, testing novel bifurcation strategies and devices.”
Merit Medical has received CE mark approval for the Wrapsody endovascular stent graft system from the British Standards Institution. The Wrapsody system is a flexible self-expanding endoprosthesis indicated for use in haemodialysis patients for the treatment of stenosis or occlusion within central veins as well as the dialysis outflow circuit of an arteriovenous (AV) fistula or AV graft.
According to the company, it will introduce the Wrapsody system in Europe as procedures are resumed following the ongoing lockdown due to COVID-19. Additionally, Merit Medical plans to initiate registration activities associated with the system in Australia, Canada, and certain countries in Latin America. The company recently completed enrolment and primary follow-up of its WRAPSODY FIRST study that included 46 patients in Europe.
Moreover, Merit Medical submitted an application for an investigational device exemption (IDE) to the US Food and Drug Administration (FDA) for its review and consideration before the initiation of its WAVE pivotal study. After completion of the WAVE pivotal study, Merit Medical intends to submit a premarket approval application to the FDA, a press release states.
The company intends to offer additional products using this technology platform, subject to additional submissions and review by the US FDA and the European Union notified body. Merit Medical recently received three US FDA breakthrough device designations covering indications and cohorts of the IDE for the Wrapsody system, which have been filed with the US FDA.
Tokai Medical Products announced CE mark approval for its Rescue balloon occlusion catheter, a low-profile device designed for resuscitative endovascular balloon occlusion of the aorta (REBOA).
According to Tokai, REBOA uses a balloon catheter for temporary control of non-compressible torso haemorrhage, as an alternative to traditional thoracotomy. The Rescue balloon is compatible with a 7-F sheath and 0.025-inch guidewire. Its maximum balloon diameter is 40mm. The device also features a radiopaque tip and marker band to facilitate precise positioning under fluoroscopy.
“As REBOA [is] being used more as part of the endovascular resuscitation and trauma management (EVTM) concept worldwide, there is a great need for this excellent tool,” comments Tal Hörer (Örebro University Hospital, Örebro, Sweden) in the company’s press release. He chairs the EVTM society and is Editor-in-Chief of the Journal of Endovascular Resuscitation and Trauma Management.
Hörer continues, “The Rescue balloon has been in use for several years in Japan and other countries. It has been proven clinically to be effective, reliable, and easy to use. The Rescue balloon can be used in trauma and non-trauma cases, and as a vascular surgeon clinically-active on vascular, endovascular, trauma, and resuscitation, I am looking forward to [being] able to use this product for life-saving procedures.”
CX 2020 LIVE came to life online—despite COVID-19—using state-of-the art broadcast technology to bring together more than 1,000 vascular specialists, live, from 95 countries across the world. The first session of the highly interactive conference, designed to deliver global vascular education in the CX style, saw participants from Stockholm to Santiago asking questions and engaging with leading vascular figures on the ongoing investigation into the safety of paclitaxel devices in the treatment of peripheral arterial disease (PAD). The session can now be viewed on demand here.
Roger Greenhalgh (London, UK) chaired the event, with Andrew Holden (Auckland, New Zealand) moderating the panel discussion. Six speakers gave their five-minute presentations, with each talk interceded with five minutes of discussion time.
A historic occasion for vascular education, attendees can earn continuing medical education (CME) points through their presence at this virtual event, taking place every Tuesday and Thursday from 16:00–17:20 BST from 25 May through to 25 June.
Podium first: “Paclitaxel devices are associated with improved survival” in new propensity score-matched analysis of claudicants and CLTI patients
“The debate on the safety and efficacy of paclitaxel continues to rage,” Sapan Desai (Chicago, USA) stated, kicking off the first session of CX 2020 LIVE with his podium 1st presentation on paclitaxel survival results related to drug-coated balloons (DCB) and drug-eluting stents (DES) out to five years. Contrary to the findings of Konstantinos Katsanos (Patras, Greece) et al in late 2018, Desai concluded that “paclitaxel devices are associated with improved survival, starting at nine months”. However, he added the usual caveat that “additional analyses, such as a more detailed subgroup evaluation, and causal inference determination, are urgently needed”.
In this propensity score-matched analysis, Desai and his co-investigators utilised a global healthcare registry to identify patients with femoropopliteal artery disease who subsequently underwent an endovascular intervention between 2010 and 2015. These patients—11,710 of whom underwent drug-coated balloon (DCB) or drug-eluting stent (DES) treatment, and 76,007 of whom underwent routine angioplasty or bare metal stenting—were followed for up to five years. In total, 61.5% of the paclitaxel cohort and 62.7% of the control group had chronic limb-threatening ischaemia (CLTI), respectively.
There was no difference in the rate of periprocedural complications between the paclitaxel-treated group and the control group, the investigators reported. Desai related how patients treated using paclitaxel “have a lower rate of reintervention at one year, with a significant decrease in major amputation rate at five years”.
Additionally, the triallists found that mortality is significantly lower for claudicants, starting at nine months. At five years, 42.9% of paclitaxel-treated patients had died, compared to 59.2% in the control group.
COMPARE trial highlights efficacy of low-dose paclitaxel balloons
Sabine Steiner (Leipzig, Germany) told the CX 2020 LIVE audience that the COMPARE trial, the first head-to head comparison of two paclitaxel-coated DCBs, the COMPARE trial, showed “excellent efficacy” at one year in both arms. There was a similar patency at one year with the low-dose (2µg/mm2) Ranger DCB (Boston Scientific) compared with the higher dose (3.5µg/mm2) IN.PACT Admiral DCB (Medtronic).
While earlier meta-analyses have suggested an association between paclitaxel dose and late mortality risk, Steiner told the CX 2020 LIVE audience that the COMPARE trial results “cannot identify any signal for a relationship between paclitaxel dose and mortality, at one year or beyond”.
The COMPARE trial, published in the European Heart Journal, was a prospective, randomised, non-inferiority trial of high- versus low-dose paclitaxel DCBs for femoropopliteal interventions. All patients enrolled in the study had PAD categorised as Rutherford class 2–4.
The trial met both its primary efficacy (primary patency through 12 months) and primary safety (freedom from major adverse events through 12 months) endpoints. Steiner says that the investigators, led by Dierk Scheinert (Leipzig, Germany), “will follow the patients up to five years by telephone calls in order to gain safety information”.
Focusing on all-cause mortality, Steiner noted that the COMPARE trial data show “an overlapping of Kaplan-Meier curves through four years”, indicating “no signal for any relevant difference [between the two different paclitaxel dosages] with respect to mortality”. She continued: “Actually, death rates are rather low. After two years, where we do have quite a good follow-up, we observe a death rate which is around 3%”.
When looking at individual causes of death, Steiner shared that the research team did not see any “clear signal of an excess rate of a specific cardiovascular or non-cardiovascular death subtype.
“Importantly,” she expanded, “the same holds true, or we see a similar pattern of causes of death, for the six patients who died in the high-dose DCB group. Importantly, no death was considered procedure- or device-related by the clinical events committee.”
Speaking as co-moderator of the session alongside Roger Greenhalgh (London, UK), Andrew Holden (Auckland, New Zealand) praised Steiner for bringing “new information that we are seeing for the first time” to CX 2020 LIVE.
Prompted by a question from Greenhalgh, Steiner clarified that the COMPARE trial was never designed to compare mortality between the Ranger DCB and the IN.PACT Admiral DCB, but rather efficacy. “What I would really like to highlight,” she stressed, “is that we have these meta-analyses showing us a signal that even for efficacy there will be a difference with respect to dose, so a higher dose will be more efficient. This was really the background of the COMPARE trial, that we wanted to have a non-inferiority design with respect to efficacy and primary patency. Here, we did not see a difference, which is really in contrast to the results from the meta-analyses.”
Holden, who was one of the authors of a 2019 paper published in the Journal of Endovascular Therapy (JEVT) refuting the idea of there being a dose-dependent impact of paclitaxel devices, said he “entirely” agreed with Steiner’s conclusions, adding: “I think it [the dose model] is the weakest part of the original [2018, Katsanos et al] meta-analysis.” Addressing Steiner, he said, “You have really shown that a low-dose device is as efficacious [as a high-dose one], and that there is no safety advantage or disadvantage.”
Steiner acknowledged that although she and her colleagues did not observe a signal with respect to mortality, the numbers in the COMPARE trial “are clearly very small in general, so there is a low mortality rate—we are definitely not powered for this question [detecting an association between increased mortality risk and paclitaxel dose].”
Therefore, the COMPARE trial can make “no statement about dose and mortality”, Greenhalgh concluded.
CX 2020 LIVE audience split over importance of dose effect
Polling during the CX 2020 LIVE session asked the audience: “Do you consider paclitaxel dose level to be crucial?” This split the CX audience with 53% of respondents voting “yes” (see Figure 1), sharing their belief that paclitaxel dose levels are crucial.
US FDA assessing “totality of evidence”, calls out specific value of individual patient-level data sets
Providing an update on the paclitaxel late-mortality signal from the US Food and Drug Administration (FDA) perspective, Misti Malone (Centre for Devices and Radiological Health, US FDA) said that the agency is in the “signal discernment/refinement phase” of the ongoing investigation.
Following the FDA Advisory Committee Meeting last summer (19–20 June, Washington, DC, USA), approved paclitaxel devices have remained on the US market with labelling updates that discuss ongoing uncertainties regarding the signal, as well as the conclusions of June’s meeting. At the time, the agency agreed that the mortality signal existed, but that the signal magnitude was uncertain.
“Because patient comorbidities, extent of disease, and lesion characteristics play a role in clinical outcomes, [the] FDA believes it is important for physicians to determine what patients are considered [at] high risk of restenosis, and they have a favourable risk–benefit profile from treatment with paclitaxel-coated devices.”
Clinical trials are continuing with revised informed consent and increased patient follow-up. Additionally, the FDA has also promoted efforts to increase trial robustness, such as attempts to reduce “missingness”. “We continue to collaborate with investigators of observational datasets, and through groups such as RAPID, a multi-stakeholder collaboration made of clinicians, industry members, and regulators aiming to improve the real-world evidence ecosystem, from data collection to analysis,” Malone explained. “These collaborations may provide insights into remaining questions, such as the precise magnitude of the signal, the mechanism for late-term mortality, and the benefit–risk profile in real-world patient populations.”
Malone stressed the importance of collaboration, finishing by saying: “This is a global issue that requires global collaborations.”
Referencing Desai’s earlier presentation on what he described as “another large, population-based study that failed to show a [mortality disadvantage], but in fact showed a mortality advantage of paclitaxel”, moderator Holden said he has found large population-based studies “reassuring”, and asked for the FDA’s thoughts on these types of analyses.
“We value the totality of evidence,” Malone replied, “be it from randomised controlled trials, single-arm trials, or observational datasets. The devil is in the details for many of these trials, in which we identify how many patients have been followed-up to four or five years, which is when the signal was noticed in our data sets. Many of these data sets have up to 50% missingness at this point, and although we may assume missingness accepts some level of randomness, it may not, so we typically need very robust, high-quality data with long follow-up in order to discern this mortality signal. So, we do value these observational datasets, and as part of the RAPID group, we are compiling all of the datasets we are aware of, and looking at the level of evidence and our confidence in the data that has been evaluated.”
Specifically commenting on individual, patient-level analyses, such as the VIVA individual patient-level data (IPD), Malone said: “We find those very valuable because we can dive into the details, we can see how the individual patients are affected, rather than looking at summary data. The higher-level meta-analyses help to guide us to our next step to do a more in-depth analysis.”
“High impact” of VIVA individual patient data analysis
The IPD analysis of the safety of paclitaxel-containing devices conducted by VIVA Physicians, based on the most complete available data set of mortality events from randomised controlled trials, identified an absolute 4.6% increased mortality risk—corresponding to a 38% increased relative mortality risk—associated with their use. This is a weaker mortality signal than that initially reported in December 2018 by Katsanos.
The analysis, based on the most complete available data set of mortality events from randomised controlled trials involving paclitaxel devices, included 2,185 patients (including those whose data were previously lost to follow-up) across eight studies, with a median follow-up of four years.
Presenting these results at CX 2020 LIVE, first published in Circulation, Gary Ansel (Columbus, USA) remarked: “The VIVA IPD has, and will continue to have, [a] high impact due to the richness of the dataset”.
Nearly two-thirds of the CX 2020 LIVE audience believe the VIVA Physicians’ IPD analysis does not provide consensus on the ongoing paclitaxel debate “once and for all”. When asked “Does the VIVA IPD settle this once and for all?”, 63% answered “no” (see Figure 2).
Greenhalgh concluded: “What we have learnt today, from various pieces of data, is that this matter is not settled. What I personally like is that the FDA’s comments have left room for doctors to decide what they consider to be the right thing to do for the patient.”
Recent meta-analyses have contradictory findings in patients with CLTI
Two analyses investigating the alleged increased rate of mortality with the use of paclitaxel-containing devices in the chronic limb-threatening ischaemia (CLTI) population were presented back-to-back during the inaugural CX 2020 LIVE session.
Though Ramon Varcoe (Randwick, Australia) put forward that paclitaxel-coated devices were not associated with increased mortality in patients with CLTI, Katsanos told viewers that paclitaxel-coated balloons seemed to increase the risk of all-cause death, as well as the risk of amputation, in the infrapopliteal segment.
Expounding on the differences between the methodologies used by each research team, Varcoe said: “As I see it, there are four main differences. The first was [that] we had a different primary endpoint. We looked at all-cause mortality, and we did that because we were asking whether paclitaxel was associated with death; it makes sense to look at overall survival, rather than amputation-free survival, which is more of an efficacy endpoint.
“We also looked at paclitaxel use in stents and balloons above and below the knee, so we did not restrict it, and this was a way to replicate the original 2018 meta-analyses. But also, the rationale was if you are exposed to paclitaxel, it should not matter how it was used in the leg or what device.
“We also used only published data. As we know, data change between their presentation at symposium level and the subsequent peer review at publication, so we thought it was important to use locked and verified data in our analysis.
“Most importantly, we included the five-year data from the Medtronic IN.PACT DEEP study. This was the largest study in the meta-analysis, and the longest follow-up, and had the largest number of event rates in terms of mortality. It was the most influential in terms of a meta-analysis, and it really needed to be included, and that is what we did.”
The five-year findings of the IN.PACT DEEP study, which tested a 3.5μg/mm2 device, were not part of the Katsanos meta-analysis, a fact that garnered criticism from CX 2020 LIVE attendees. Justifying this choice to viewers, Katsanos said: “All the other studies have presented six-month to one-year data. It would not be very reasonable to combine that with the five-year data because then it becomes heavily skewed towards this study, as it a lot more events due to the five-year follow-up.”
Greenhalgh summarised: “I think we will accept that six-month data follow-up is limited.”
The discussion continues 28 May 2020
Session Two of CX 2020 LIVE will focus on the durability of EVAR, sac diameter, and the UK National Institute for Health and Care Excellence (NICE) guidelines. To take part in the global conversation and participate in live polling, register here and join us from 16:00 to 17:20 BST on 28 May 2020. Roger Greenhalgh is returning as chair and Ian Loftus (London, UK) will moderate the discussion.
Guerbet has announced the registration of Vectorio, a kit for imaging hepatocellular carcinoma (HCC), in Canada.
The kit consists of a set of Lipiodol-resistant medical devices that includes patented syringes, stopcock and sampling devices.
Vectorio is dedicated to Lipiodol Ultra Fluid Injection for imaging of liver tumours in adults with known HCC during interventional oncology procedures.
HCC is the most common primary liver cancer and is the fourth biggest cause of death due to cancer worldwide.
This medical device:
Designed and manufactured in France, the product was launched commercially in September 2017 in Europe. Today, Vectorio for HCC imaging is registered in Canada and Germany. Vectorio is also registered in 25 countries where conventional transarterial chemoembolization (cTACE) procedures are approved for Lipiodol Ultra Fluid.
LimFlow SA today announced publication of positive two-year data from the ALPS registry of the LimFlow percutaneous deep vein arterialisation (pDVA) system. Results were published online yesterday in the Journal of Endovascular Therapy and will also appear in the August print issue of the journal.
The ALPS Registry is the largest study to date of no-option chronic limb-threatening ischaemia (CLTI) patients treated with the LimFlow system reporting mid- and long-term results.
“In this complex group of patients, pDVA using the LimFlow device has shown to be feasible and safe with high technical success and good amputation-free survival at six months up to 24 months coupled with good wound healing,” said the paper’s lead author, Andrej Schmidt, head of the Angiology CathLab at Leipzig University Hospital, Leipzig, Germany. “In selected patients with no-option CLTI, pDVA is a safe and effective treatment to prevent amputation and heal wounds.”
“Patients with this disease suffer with chronic ulcers, often including gangrene, recurrent pain, and a very poor quality of life. CLTI is associated with poor mid- and long-term survival, and no-option patients often face the worst outcomes,” said Roberto Ferraresi, chief of the Peripheral Interventional Unit at the San Carlo Clinic, Milan, Italy, co-author of the paper, and a pioneer in the interventional treatment of CLTI. “These patients desperately need an option to avoid amputation and improve their life, and LimFlow offers a very promising alternative for them.”
The ALPS Registry is a multicentre, retrospective study conducted at centres in Alkmaar, the Netherlands; Leipzig, Germany; Paris, France; and Singapore encompassing 32 end-stage—or “no-option”—CLTI patients.
All patients had non-healing wounds on the target foot and no arterial target for surgical or endovascular revascularisation. Among them, 66% had diabetes, 53% had renal insufficiency, and 16% were dialysis dependent. The majority of patients had experienced failed prior attempts at revascularisation.
The registry reported major amputation-free survival of 84%, 71%, and 67%, respectively, at six months, one year and two years. Additionally, a positive trend of successful wound healing was demonstrated, with 73% of wounds completely healed at two years. Technical success was 97%.
When all other therapeutic options have been exhausted and a CLTI patient is facing major amputation, the minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated blood back into the foot via the veins. For many patients, restoring perfusion in the lower limbs resolves chronic pain, improves quality of life, enables wound healing and prevents major amputation.
“It is very gratifying to see these durable results being demonstrated by the LimFlow system in a real-world setting with consecutive patients,” said LimFlow CEO Dan Rose. “For these no-option patients, the next intervention for their leg was going to be major amputation, with the associated morbidity and high mortality risk that comes with amputation. Instead, two years later, the vast majority of patients are alive, with almost three-quarters of them experiencing completely healed wounds. This registry adds to the building clinical evidence that LimFlow therapy is an effective solution for no-option patients.”
Click here to view a video of how the LimFlow System works.
Bluegrass Vascular Technologies has announced that the first US commercial cases using the Surfacer Inside-Out access catheter system were completed at Santa Clara Valley Medical Center in San Jose, California.
The procedures were performed by Ehab Sorial and Ajit Nair. Sorial is a clinical associate professor of Surgery in the Division of Vascular Surgery at Stanford University School of Medicine and staff surgeon at Santa Clara Valley Medical Center. Nair is a staff interventional radiologist at Santa Clara Valley Medical Center.
The device was used to obtain venous access in two haemodialysis patients with central venous obstructions, one of which had limited access options. Bluegrass Vascular was granted de novo classification by the US Food and Drug Administration (FDA) for the Surfacer system in February of this year.
“We are excited to be the first programme in the USA to incorporate use of the Surfacer system into our day-to-day clinical practice,” said Nair and Sorial. “The Surfacer system provides us with a safe and effective option for obtaining right-sided central venous access in patients with venous obstructions, enabling us to preserve secondary central veins and avoid alternative access procedures, which are not as effective and have a higher risk of complications.”
“Dr Sorial, Dr Nair and their team at Santa Clara Valley Medical Center played an integral role as one of several clinical sites for the US investigational device exemption (IDE) study, which led to our recent FDA de novo clearance. We are honoured to have Drs Sorial and Nair perform our first US cases,” stated Gabriele Niederauer, CEO and president of Bluegrass Vascular. “We envision US clinical adoption of the Surfacer system mirroring our positive commercial experiences in Europe and look forward to providing this truly novel technology to physicians and their patients across America.”
Getinge recently announced the launch of its Advanta V12 large diameter stent.
According to a press release, Getinge’s Advanta V12 stent has been shown to consistently improve patient outcomes by restoring iliac patency, reducing restenosis and re-intervention rates, improving ankle brachial index (ABIs) and sustaining symptom relief. Strong benchmark data demonstrates superior patency over bare metal stents.
“A clear need from our customers has encouraged us to now introduce a larger diameter size of Advanta V12 which expands from 12 to 16mm,” says Jens Viebke, president Acute Care Therapies at Getinge.
The first in the world implantation of the Advanta V12 large diameter stent, was performed by Franklin Pond, a vascular surgeon at the Western Hospital in Melbourne, Australia. Following the procedure, he reported, “I am delighted to expand the treatment spectrum of patients receiving the new Advanta V12 large diameter stent, and pleased with the excellent angiographic outcome.”
“Backed by long-term clinical data and over 500 publications, the Advanta V12 stent continues to prove itself every day when it comes to treating patients with this severe condition. We are of course excited to introduce this new larger size to help our customers treat a wider range of clinical cases,” says Jens Viebke.
According to Getinge, a unique full polytetrafluoroethylene (PTFE) encapsulation of the Advanta V12 stent provides a smooth flow lumen and offers an effective barrier to neointimal hyperplasia. It expands uniformly and prevents tissue from prolapsing through the expanded stent. 9F compatibility offers versatility and efficient delivery in complex endovascular procedures.
“The trusted design of Advanta V12 is conformable, deliverable and flexible to track through tortuous arteries and flex to accommodate the iliac arteries. It has the ability to post dilate up to 16mm, providing customization to the patients anatomy,” explains Michel Reijnen, professor at the University of Twente in Enschede, the Netherlands.
The larger diameter Advanta V12 balloon expandable covered stent is CE marked and TGA approved for restoring and improving the patency of iliac arteries.
This information is intended for an international audience outside of the USA.
Older age, being male, deprivation, living in a densely populated area, ethnicity, obesity, and chronic kidney disease are associated with a positive test for COVID-19, according to results from 3,802 people tested for SARS-CoV-2 in the UK. The observational study was conducted between 28 January and 4 April using routine electronic health records data from GP practices across England (UK), and results are published in The Lancet Infectious Diseases.
Study author Simon de Lusignan from the University of Oxford (Oxford, UK) and Director of the Royal College of GPs Surveillance Centre, UK, says: “While clear trends have emerged from hospital data for the people with severe symptoms, the risk of infection among the general population remains a grey area. It’s important to know which groups in the wider community are most at risk of infection so that we can better understand SARS-CoV-2 transmission and how to prevent new cases.”
The authors note that other socio-economic factors, which were not measured in this study, may also be linked with SARS-CoV-2 infection, such as employment in high-risk jobs, education, income, and differences in access to healthcare and testing among ethnic groups. Further research is needed to understand these associations.
de Lusignan and colleagues analysed data from 587 people with positive results and 3,215 with negative results, collated by GP practices in England who are part of the Royal College of General Practitioners Research and Surveillance Centre primary care network.
Among adults, those aged 40 to 64 years were at the greatest risk of testing positive for SARS-CoV-2 (18.5% tested positive, 243 out of 1,316 people), compared with children aged up to 17 years (4.6%, 23 of 499). Among 1,612 men, 18.4% (296) tested positive, compared with 13.3% (291/2,190) of women.
The only clinical conditions significantly associated with a positive test were chronic kidney disease and obesity. Of 207 people with chronic kidney disease, 32.9% (68) tested positive, compared with 14.4% (519/3,595) without kidney disease. While 20.9% of people who were obese tested positive (142/680), compared with 13.2% (171/1,296) people of normal weight.
Compared with people of white ethnicity, of whom 15.5% (388 of 2,497) tested positive, the proportion of people of black ethnicity testing positive were much higher, at 62.1% (36 of 58 people). This finding remained significant after adjusting for comorbidities such as high blood pressure and diabetes, the prevalence of which is increased in black ethnic groups. The authors say that these results should be interpreted with caution, as there were small numbers of people from England’s minority ethnic groups in the study.
There was a large difference between people living in the most and least deprived areas. Of 668 people in the most deprived areas, 29.5% (197) tested positive, compared with 7.7% (143 of 1,855) in the least deprived areas. People in urban areas were more at risk than those in rural areas. Of 1,816 people tested in urban areas, 26.2% (476) tested positive, while in rural areas 5.6% tested positive (111 of 1,986).
Co-author Gayatri Amirthalingam, from Public Health England, says: “With each day that passes our knowledge of COVID- 19 improves. This analysis of primary care outcomes of individuals testing positive for virus is an important contribution to our wider understanding of how COVID-19 is affecting people of different demographic groups. This study, which uses data from the Oxford RCGP Research and Surveillance Centre, will also inform Public Heath England’s ongoing review into factors impacting health outcomes from COVID-19 that is to be completed by the end of May, 2020. This review will also analyse hospitalisations and mortality, including excess mortality, to provide further insight on how COVID-19 may be having a disproportionate impact on different groups. It will also determine the impact of occupation (including healthcare workers) where data is available.”
While more than 60% of medical students are female, the number of women in endovascular medicine is low, report Bella Huasen and Agnieszka Solberg. Here, for Interventional News, they discuss the reasons behind this under-representation and consider the importance of creating a global support network to redress the imbalance.
“What hubris it was, he said, that mankind should think to halve the powers of the human race by ignoring the minds and words of the female half of it”—The Clockmaker’s Daughter, Kate Morton.
Charles Dotter’s first superficial femoral artery recanalisation in 1964 began a new era of endovascular medicine, a fairly new and evolving specialty compared to traditional career paths such as surgery or primary care.
The profession is practiced by multiple sub-specialists including interventional radiologists, vascular surgeons, angiologists, and interventional cardiologists. Despite the variation and interests, female trainee and consultants/residents remain under-represented in all of these specialities.
In the USA, fewer than 8% of interventional radiologists are women; in Europe fewer than 10%. The percentages are even more grim for vascular surgery, in the USA <6% and in Europe <8% are women. Despite >50% of medical students identifying as women in the USA and Europe, there is never a line to the ladies’ bathroom at endovascular medicine conferences.
This beautiful lifesaving carer should attract talent irrespective of gender. It is everyone’s responsibility to recognise this issue and encourage female doctors and students into this field. This is not as easy at is seems given the culture of misogyny and sexism engrained in cultures throughout the globe.
Conscious bias still exists in 2020 and trainees are still being told that endovascular medicine is not for them, based solely on the fact that they are women. Most of the time, however, this behaviour is unconscious and, sadly, it is prevalent in both men and women.
Many females have contributed to this field starting with Marie Curie-Sklodowski for the use of X-rays, yet the gender disparity is rife across the globe. When searching congresses, conferences, proctors, panels, and faculty members; the site or inclusion of females is rare if not none-existent.
We have attended multidisciplinary endovascular conferences with hundreds of attendees, but limited women speakers, chairs or panellists. Surely, there are qualified women endovascular specialists who can provide some insight.
Given the benefits of a diverse workforce and the effectiveness of female physicians compared to their male colleagues in respect to mortality rates and other outcomes (Tsugawa et al 2017; Wallis et al 2017), all specialities should be recruiting female physicians to join their teams.
The benefits of a diverse workforce are well known inclusive companies outperform the S&P 500 index, attract top talent rich in creativity and innovation, and can better anticipate a broad range of customer needs (Spalluto 2018).
Since women make over 90% of their family’s healthcare decisions (Spalluto 2018), female doctors have an edge at understanding and meeting the needs and expectations of the female health care consumer. As the minimally invasive options for patients grow to include gynecologic, urologic, gastrointestinal and breast procedures, female patients are likely to more often request a female physician.
One of the ways to increase the number of women in endovascular medicine is to provide trainees with more role models. Representation matters but there is a striking disparity between the genders in leadership positions in medical schools despite more female medical students; women represent a small fraction of medical school deans and full professors.
This is not occurring because women are uninterested in leadership positions; it is occurring because women are not being considered and not being selected for these positions despite having equal or higher qualifications than their male colleagues.
Many organisations have begun women’s sections to help combat biases and improve the representation of women in their societies. The Society of Interventional Radiology, for example, has a very active women-in-IR (WIR) section which meets monthly. There is also dedicated WIR programming at the annual SIR conference.
Multidisciplinary organisations (ISET, OEIS, VIVA, GEST, etc) tend to be smaller and have few, if any, women physicians in planning and execution of the annual event as well as a smaller percentage of women speakers and even attendees.
Grassroots organisations have tried to raise awareness about these discrepancies; however, it is challenging to enact any change without having adequate representation on the boards.
We met through “RadChicks” in interventional radiology and shared a passion for motivating females into interventional radiology. We work hard from both sides of the Atlantic to support and encourage this change as well as offer medical students and junior doctors’ opportunities to discover this fields as well as support those already in training.
Our main focus is twofold: 1. coordinate in our advocacy efforts for women in radiology/endovascular medicine and 2. provide platforms where medical students and student doctors/residents feel supported, including mentorship/sponsorship programs, book clubs/workshops on a myriad of topics, networking events, even anonymous counselling.
When women trainees see strong women in their field, even in another state/county or across the globe, they feel empowered. They are not only empowered to continue in their path, but they feel empowered to help other women and under-represented minorities. This chain reaction becomes a powerful global support network which one day will improve the representation of women in endovascular medicine.
Bella Huasen is a consultant interventional radiologist at Lancashire Teaching Hospitals NHS Foundation Trust in Preston, UK.
Agnieszka Solberg is a vascular and interventional radiologist at CHI St Alexius Health in Bismark, USA.
This week, the first patient has been enrolled in the Dragon trials, investigating the safety and feasibility of a novel, double vein embolization procedure in the treatment of patients with colorectal liver metastases.
Resection of liver metastases from colorectal cancer improves survival compared to chemotherapy alone and may lead to cure in up to 40% of patients. If the volume of the future liver remnant post-resection is too low to carry out the surgery, and liver growth needs to be stimulated to reduce the risk of post-procedural liver failure. Portal vein embolization (PVE) is the current gold standard for inducing liver regeneration prior to resection of liver metastases in patients with colorectal cancer. However, the triallists propose that as embolization of both the portal vein and the hepatic vein on one side of the liver leads to “faster and more extensive” liver growth, it could be an improvement compared to PVE.
To test this hypothesis, the investigators are conducting an international, prospective, multi-centre pre-trial—Dragon 1—to explore the safety and feasibility of the double embolization approach, and to test enrolment capacity. All participating centres have to include three patients. Currently, four centres are fully initiated into the study, nine have ethical approval but are not yet initiated, and a further 27 are awaiting ethics approval. Dragon 1 will then form the basis of a randomised controlled trial comparing PVE with hepatic vein embolization (HVE) to PVE alone—Dragon 2. Dragon 2 is expected to start in 2021.
Describing the combined embolization option, the clinicaltrials.gov page for the two Dragon studies notes: “PVE/HVE combines simultaneous embolization of the portal main branches into the tumour-bearing liver and the hepatic vein draining them. The tissue in the part of the liver treated with PVE/HVE stays viable because the hepatic artery continues to supply the liver deprived of portal and hepatic veins.”
Speaking to Interventional News, Christoph Binkert (Kantonsspital Winterthur, Winterthur, Switzerland), the international coordinating investigator for interventional radiology in the Dragon trials, comments: “The first double vein embolization in the Dragon 1 trial went very well. From our clinical experience, we always treat the right portal vein first in order to have good antegrade flow within the portal vein. We used a mixture of Lipiodol [Guerbet] and Glubran [Gem] as an embolic agent. In the same session, the hepatic veins were embolized with Amplatzer plugs. There were two main right hepatic veins and a prominent vein draining segment six, which was also embolized. The patient tolerated the procedure well and left the hospital the same afternoon.”
Earlier preclinical studies in pigs have demonstrated the feasibility of this method, and human case series show accelerated and increased liver growth.
Binkert enthuses: “The Dragon trial is a true international and interdisciplinary trial researching the potential of double vein embolization. The idea is to reach a faster growth of the future liver remnant without additional risks to the patient. After several months of intensive preparation, it is good to finally get started. I am convinced that soon other centres will also start enrolling.”
Binkert spoke to Interventional News last September at the first Embolotherapy (ET) conference in Valencia, Spain (26–29 June, 2019). You can see the full video interview here.
The Society for Cardiovascular Angiography and Interventions (SCAI) has released guidelines that provide a comprehensive review of comparative effectiveness data for devices used in aortoiliac arterial interventions.
The recommendations aim to provide clinicians with guidance for device selection in patients for whom these devices are intended as definitive therapy.
The document has just been published in SCAI’s official journal, Catheterization and Cardiovascular Interventions and presented during the SCAI 2020 Scientific Sessions Virtual Conference.
“Endovascular device selection in peripheral arterial interventions remains challenging due to paucity of comparative data and a wide spectrum of available devices. In 2018, SCAI developed the first-of-its-kind guidance document to address device selection in femoral-popliteal arterial interventions,” said Dmitriy Feldman, chair of the writing group.
“The purpose of newly released 2020 SCAI guidelines is to provide a comprehensive review of comparative effectiveness data for aortoiliac devices and to arm clinicians with evidence-based recommendations and practical guidance for selection of devices in aortoiliac arterial interventions,” Feldman continued.
The writing group used a modified Delphi panel methodology to form recommendations based on data extracted through a systematic review of available evidence.
The writing group graded recommendations for eleven relevant anatomical scenarios according to strength of the recommendation (magnitude of benefit or harm, including cost of use) and certainty of the evidence (type, quality, and consistency of data).
Micro Medical Solutions has announced the first implantation of the MicroStent vascular stent in the US Food and Drug Administration (FDA) randomised, multicentre pivotal clinical study, STAND (A Clinical Evaluation of the MicroSTent PeripherAl Vascular SteNt in subjects with Arterial Disease Below the Knee). The 25 leading medical institutions and outpatient centres designated across the USA are now enrolling patients in STAND.
The first procedure was performed 25 March 2020 by the study’s lead investigator, Robert E Beasley of Mount Sinai Medical Center in Miami Beach, USA. “With a very successful MicroStent procedure and positive early results from the feasibility study showing a 90.9% patency rate at one year, I am delighted that the STAND study is now underway,” Beasley comments. “MicroStent offers hope for limb salvage, better health and quality of life to patients at risk for below-the-knee amputation, and the clinical trial will bring us closer to offering this new solution to thousands more candidates.”
MicroStent is a vascular stent, with both a 3Fr and 4Fr delivery system that allows for multiple access points, designed to achieve and maintain vessel patency and improve blood flow in order to reduce below-the-knee amputations for patients with critical limb-threatening ischaemia (CLTI) resulting from peripheral arterial disease (PAD). Micro Medical Solutions received Investigational Device Exemption (IDE) approval from the FDA after completing a three-centre, 15-patient feasibility study in which MicroStent met all primary endpoints for both safety and efficacy. When complete, the STAND study will include approximately 177 patients at up to 25 sites across the US. MicroStent has already obtained CE mark approval for use outside the USA.
Micro Medical Solutions CEO, Gregory Sullivan, adds, “Our leadership team and scientific advisory board have worked diligently to design and plan the STAND trial, with encouraging response from the FDA every step of the way. This first case is a source of great pride and inspiration as we continue to work toward FDA approval, which will help save many patients with CLTI from the devastation of below-the-knee amputation.”
Intact Vascular has announced the peer-reviewed publication of its Tack optimised balloon angioplasty (TOBA) III 12-month clinical trial results in the Journal of Vascular Surgery.
The multi-centre, single-arm, prospective study investigated the combination of the Tack endovascular system with Medtronic’s IN.PACT Admiral drug-coated balloon as a treatment in the superficial femoral artery (SFA) and/or proximal popliteal artery (PPA).
The trial results were previously presented as part of the high impact clinical research session during the 2019 Transcatheter Cardiovascular Therapeutics (TCT) conference.
“We are thrilled to have the TOBA III data published in the Journal of Vascular Surgery,” commented Peter Schneider, co-founder and chief medical officer of Intact Vascular. “This peer-reviewed article adds to the strong body of evidence supporting use of the Tack endovascular system for focal dissection repair when treating lesions both above- and below-the-knee.”
The study was conducted in multiple sites across Europe and enrolled 201 patients, including 169 patients with arterial lesions ≤150 mm in length and a subset of 32 patients with long arterial lesions (>150 and ≤250 mm).
All patients suffered from peripheral arterial disease (PAD) and underwent drug-coated balloon angioplasty, consequently experiencing at least one dissection requiring repair.
Results from the 169-patient standard lesion cohort (≤150mm) impressively demonstrated a 95% primary K-M patency with 97.5% K-M freedom from clinically-driven reintervention at 12-months and a 0.6% bailout stent rate.
The observational data from the long lesion subset (>150 and ≤250mm) was analysed separately. Results from these 32 patients notably demonstrated 98.8% complete dissection resolution and 89.3% K-M vessel patency, with 96.8% K-M freedom from clinically-driven reintervention at 12-months and a 0% bailout stent rate.
“The TOBA III trial met all primary endpoints and impressively demonstrated the highest reported rates of safety, patency and freedom from clinically driven reintervention when treating above-the-knee lesions,” commented Marianne Brodmann, head of the Clinical Division of Angiology, Medical University of Graz, Austria and principal investigator of the TOBA III trial.
She continued: “This study is unique in that we enrolled patients with 100% dissected vessels and included a long lesion subset, notoriously a complex cohort. These clinically compelling data further validate Tack implants as safe and effective for PAD interventions.”
Kevin Stadtlander outlines how his institution is benefitting from the “creativity” of interventional radiologists during the coronavirus pandemic, here providing a step-by-step account of a bedside inferior vena cava (IVC) filter placement for a COVID-19-positive patient in intensive care.
A 38-year-old male with past medical history of hypertension, admitted for complications of COVID-19, required mechanical ventilation and extracorporeal membrane oxygenation (ECMO). The patient developed an intracranial parenchymal haemorrhage felt to be related to ECMO, with fluctuating haemodynamics, while on intravenous (IV) heparin protocol. After removal of the ECMO venous cannula from the right groin, the patient was also found to have right iliac vein and femoral deep venous thrombosis (DVT), as well as below-knee DVT. The patient was referred to interventional radiology (IR) for inferior vena cava (IVC) filter placement, with a contraindication to systemic anticoagulation due to his intracranial bleed.
Given the ongoing COVID-19 pandemic, we had already implemented a plan that included having a designated IR procedure room in the department. Our IR plan included the directive to try to do as much as possible at beside in COVID-positive patients. For this IVC filter placement, we quickly mapped out both options, and decided to take the care directly to the patient room.
We located a portable C-arm with digital subtraction angiography (DSA) capability and did a trial in an empty intensive care unit (ICU) room to ensure that the C-arm would fit under the bed, and that images would be clearly visible through the ICU bed. These goals were both accomplished, but it did necessitate maximum ICU bed height to fit the C-arm. The COVID patient room was negative pressure and separated from the hallway (considered dirty) by sliding glass doors. Since no true anteroom was available, we used the empty ICU room as a staging room across the hall. The entire procedure plan was first reviewed in a huddle with all team members. We chose to have one IR physician and two radiology technologists in the room for the procedure. We were also accompanied by IR nurses (outside the COVID room), who helped with staging and acted as buddies for donning and doffing. The sterile procedure tray for the IVC filter was made up in a second empty ICU room and covered. Informed consent was obtained via telephone from a family member.
The IR physician and two technologists donned their personal protective equipment (PPE) and lead aprons in the staging room with the help of the nursing buddies. The C-arm, the C-arm monitor, and the ultrasound unit were covered with a plastic barrier, and then taken into the COVID-positive patient’s room by the “dirty” technologist (who was wearing full PPE, excluding sterile surgical gown and gloves). The second technologist (wearing full PPE and designated as procedure scrub technologist) then wheeled the procedure tray into the room, put on her surgical gown and gloves, and began prepping the patient’s left groin. We chose the left groin due to a thrombus in the right iliac vein, and in order to stay away from the head of the bed. The IR physician then entered the room, put on a sterile gown and gloves over full PPE, and helped to complete patient preparation. Importantly, a step stool (covered in plastic) was used by the physician during the procedure, as bed height necessary for C-arm made this a requirement. Sign in/time out was performed, IVC filter placement was completed in 10 minutes, and sign out was performed. Throughout the procedure, the patient’s ICU nurse monitored the patient and controlled his IV sedation via drips that were outside the room as per COVID protocol.
The surgical scrub gowns and top layer of gloves were removed in the normal fashion in the room and discarded. The procedure tray breakdown was quickly performed, and all items were disposed of in the room trash. Plastic wraps were removed from equipment and discarded in the room as each unit was moved from room to hallway. Each unit was terminally cleaned with X-ray machine bleach wipes. Each of the three caregivers then performed careful doffing of PPE (with our nurse buddies using a checklist) at the door threshold, ultimately leaving only N95 mask and bottom layer eye goggles on as they exited back to the staging room. Lead aprons were removed and wiped down with a lead X-ray apron cleaner disinfectant. N95 mask and goggles were then removed, and caregivers were free to head to the surgical locker room for scrub change and shower. A debrief huddle with all team members was then performed.
This case illustrates how IR creativity allows for procedures to be performed “portably” at the bedside in a manner safe for both caregivers and patients, while having the added benefit of preserving PPE. By way of follow-up, this patient ultimately came off the ventilator, became COVID-negative, and a CT brain has since demonstrated resolution of the intracranial bleed. The patient has been discharged from hospital.
Kevin Stadtlander, MD is an interventional radiologist at the Cleveland Clinic Florida, Weston, USA.
The Charing Cross (CX) Symposium, with its world-class faculty and unique focus on live audience participation, has announced the launch of a not-to-be missed and timely vascular and endovascular education virtual event: CX 2020 LIVE. Mark your calendars for this live digital experience, designed to deliver high-quality vascular education and featuring extensive audience participation, including polling and Techniques & Technologies edited cases, every Tuesday and Thursday over five weeks from 26 May–25 June 2020.
Roger Greenhalgh (London, UK), symposium chair, invites you to CX 2020 LIVE, and outlines the content of the first two sessions. World-leading vascular experts will give short presentations on some of the hottest topics in the field, including the paclitaxel controversy in peripheral arterial interventions, and the UK’s recently published NICE abdominal aortic aneurysm guidelines.
The 10 live sessions, which will feature audience participation, will run from 16:00 BST/11:00 EDT/17:00 CEST, every Tuesday and Thursday, from 26 May until 25 June.
This meeting is a vascular and endovascular calendar special. Register now and read more on the programme here.
An individual patient-level data (IPD) analysis of the safety of paclitaxel-containing devices (PTXD), conducted by VIVA Physicians, identified an absolute 4.6% increased mortality risk associated with PTXD use.
The analysis, based on the most complete available data set of mortality events from PTXD randomised controlled trials, was led by Krishna Rocha-Singh (Prairie Heart Institute, Springfield, USA) and has been published in Circulation.
VIVA’s analysis included 2,185 subjects across 8 studies with a median follow-up of 4 years; ultimately, VIVA’s analysis identifies a weaker mortality signal than was initially reported in December 2018 by Katsanos et al.
VIVA Physicians’ paper, “Mortality and paclitaxel-coated devices: An individual patient data meta-analysis”, also acknowledges no drug-dose relationship was established.
This is VIVA’s second published article on the risk of increased late mortality in the context of PTXD from their independent, patient-level data analysis. The current study includes subjects whose data were previously lost to follow-up.
Manufacturers of US Food and Drug Administration (FDA) approved and commercially available devices in the USA provided de-identified data for VIVA’s independent analysis.
Cox proportional hazards one-stage meta-analysis models using intention-to-treat (ITT) methods were used for the primary analysis. A secondary analysis of additionally recovered missing vital status data was performed.
The impact of control crossover to paclitaxel-coated devices, cause-specific mortality and drug dose-mortality were all assessed. This IPD analysis was completed in collaboration with FDA, leading clinicians, researchers, and statistical analysts.
The paper appears in the May 2020 online edition of Circulation and is available here.
Reviewing the available evidence for below-the-ankle interventions in the treatment of critical limb-threatening ischaemia (CLTI), Srini Tummala proposes that pedal artery intervention “should be an integral part of the armamentarium” when physicians are faced with patients with both below-the-knee and below-the-ankle disease. Although he calls for more data to consolidate this view, he highlights how the existing literature demonstrates a higher rate of wound healing and a shorter time to wound healing when additional pedal artery revascularisation is performed with below-the-knee interventions.
CLTI is the most severe form of peripheral arterial disease (PAD), and is classified by ischaemic rest pain, ulcers, or gangrene in the lower extremities attributed to objectively proven arterial steno-occlusive disease. Diabetes is a major risk factor, resulting in atherosclerosis occurring at a younger age and affecting mostly the infrapopliteal arteries.1 Revascularisation with bypass or endovascular therapy (EVT) is an important treatment to avoid or minimise amputation based on the latest guidelines.2–4 Surgical bypass, however, is not always an option, as many CLTI patients with infrapopliteal disease may not be surgical candidates due to frailty, co-morbidities, advanced age, or poor distal bypass targets. 2–4 EVT for infrapopliteal disease has become commonplace, and studies have shown a comparable limb salvage rate to surgery, but there is still an apparent discrepancy between limb salvage rate and the rate of wound healing.5–10 Delayed wound healing has increased morbidity, lowers quality of life, and also increases medical costs even if limb loss is successfully prevented.6,9,10 Clinical trials have reported that the presence of below-the-ankle disease results in worse wound healing, thus pedal artery revascularisation is of paramount importance to achieve complete wound healing.7,10
About a decade ago, the safety and effectiveness of below-the-ankle angioplasty was unclear, and it was uncertain whether additional below-the-ankle angioplasty after below-the-knee (BTK) angioplasty improved clinical outcomes.11 Since then, new tools have been introduced, and many advanced techniques have been described for pedal artery revascularisation, but the lack of randomised controlled trial data and long-term results, coupled with the potential risks (including dissection, spasm, rupture, and thrombosis), have limited widespread adoption of these interventions.12–18
In 2009, Manzi and colleagues showed that below-the-ankle interventions in CLTI patients were not only feasible, but safe, and that they appeared to provide positive clinical results at both short and mid-term follow-up. In their analysis, they consecutively treated a total of 1,331 patients with BTK disease of which 135 (10.1%) underwent below-the-ankle revascularisation with pedal-plantar loop technique in order to recanalise the pedal arteries. Technical success for the pedal-plantar loop technique was 85%. Clinical improvement and functional status was obtained and maintained after an average of 12 months, with a significant improvement of transcutaneous oxygen tension (TcPO2) after 15 days. TcPO2 was 59+/-16mmHg in the below-the-ankle intervention group when it was successful versus 42+/-12mmHg in patients where patency was achieved in two BTK vessels down to the ankle level with partial out-flow in the foot (p<0.001).18
Shortly thereafter, Kawarada et al described a pedal arch classification system and demonstrated that the status of the pedal arch was an independent predictor of wound healing. Based on data from the RENDEZVOUS registry, Nakama et al demonstrated that the speed and extent of wound healing was improved with below-the-ankle angioplasty.19,20 This registry was multicentre, and included 317 CLTI patients presenting with infrapopliteal arterial disease who underwent EVT at five experienced cardiovascular centers in Japan. Nakama et al retrospectively reviewed 257 of these CLTI patients who presented with de novo infrapopliteal and pedal artery disease. Patients were then divided into two groups according to whether pedal artery angioplasty (PAA) was performed (n=140) or not (n=117). The rate of wound healing was higher in the PAA group (57.5% vs. 37.3%, p=0.003), and the time to wound healing shorter (211 days vs. 365 days; p=0.008).
More recently, in 2019, Huizing et al published a systematic review and meta-analysis of below-the-ankle angioplasty in CLTI patients. Their review included ten articles which reported a total of 478 patients with below-the-ankle angioplasty performed in 524 legs. The pooled 12-month limb salvage rate was 92%, and there was no statistically significant difference found in limb salvage when additional below-the-ankle angioplasty was compared to BTK angioplasty only. The pooled 12-month amputation-free survival was 78% and no statistically significant difference was found in amputation-free survival when additional below-the-ankle angioplasty was compared to BTK angioplasty only. This systematic review and meta-analysis showed that additional below-the-ankle angioplasty is a safe and feasible procedure, with a 92% pooled proportion of limb salvage at 12 months. Although no significant difference was found in limb salvage rates or amputation-free survival rates when BTK angioplasty only was compared to BTK angioplasty plus additional below-the-ankle angioplasty, the wound healing rates were better in the additional below-the-ankle angioplasty group. Specifically, Nakama et al in 2016 and 2017 showed wound healing rates of 93% versus 60%, and 59% versus 38%, respectively, favouring additional below-the-ankle angioplasty. Finally, with more severe pedal artery disease, wound healing results were better in the additional below-the-ankle angioplasty group compared to the BTK angioplasty only group.11
In conclusion, the currently available evidence suggests that pedal artery revascularisation is a safe and feasible procedure. Data also suggest no significant difference in limb salvage rates or amputation-free survival when additional below-the-ankle angioplasty was compared to BTK angioplasty only. However, wound healing rates are higher and time to wound healing shorter when patients undergo additional pedal artery revascularisation. This begs the question—is pedal artery revascularisation ready for prime time? While high-quality research is most certainly needed to clarify the benefits, available evidence suggests pedal artery intervention should be an integral part of the armamentarium to treat CLTI patients when there is BTK and co-existing below-the-ankle disease in cases of wound healing and limb salvage.
Srini Tummala is the director of the Limb Preservation Program, Department of Interventional Radiology at the University of Miami Health System, UM Miller School of Medicine, Miami, USA.
References
Control Medical Technology has announced that the US Food and Drug Administration (FDA) has cleared its Aspire MAX 7 – 11F mechanical thrombectomy platform to remove blood clots from peripheral vessels.
“This FDA clearance quadruples our product offering and improves our ability to help patients,” said Shawn Fojtik, president of Control Medical Technology in Park City, USA. “The Aspire MAX 7 – 11F mechanical thrombectomy system includes (20) new large-lumen, flexible, and kink-resistant catheters w/dilators powered by the Aspire aspirator and/or an electromechanical pump.”
During a procedure, clinicians typically access the femoral artery or vein, track a catheter over a guidewire to the thrombus, and then apply low-performance suction with a basic syringe or pulsed continual high-performance vacuum with an Aspire mechanical aspirator or an electromechanical pump.
“Blood clots range from soft-fresh clots to hard-aged thrombus,” continued Fojtik. “Clinicians need more cost-effective tools to remove blood clots. We plan to introduce more catheter and electromechanical pump innovations for use in peripheral, coronary, and neurovascular procedures.”
The new Aspire MAX 7 – 11F mechanical thrombectomy system includes 7F (0.090″) outer diameter (OD) to 11F (0.140″) OD catheters with flexible dilators for improved tracking. Catheters may be connected to the Aspire aspirator and/or an electromechanical pump for increased speed, force, volume, and control.
Control Medical’s platform also includes the Aspire MAX 5 – 6F mechanical thrombectomy system with over-the-wire catheters for peripheral vasculature and the Aspire RX-LP mechanical thrombectomy system with rapid exchange catheters for peripheral and coronary vasculature.
Data was recently published using the Aspire RX-LP mechanical thrombectomy system’s to remove blood clots from total occlusions during heart attack [Adams G, Cavros N, Tai Z, “Novel mechanical thrombectomy device for treatment of acute myocardial infarction: A retrospective report,” Journal of Invasive Cardiology, 2020;32(4):142-146].
APERTO, Cardionovum’s paclitaxel-coated balloon for arterio-venous access, has received market approval for China, making it the first high pressure drug-coated balloon (DCB) available in China to treat obstructive lesions of native arterio-venous dialysis fistulae (AVF).
The approval was given based on the statistical superiority shown in a clinical study in Chinese populations: APERTO AVF RCT CHINA.
This is the first AVF randomised controlled study to archive statistical superiority of a high pressure DCB versus high-pressure plain balloon angioplasty. In a population of 161 patients, treatment with the device achieved superiority in freedom from restenosis at six months, and better intervention-free survival of both the target lesion and target shunt at 12 months with equivalent safety. Additionally, patients treated with APERTO maintained patency for another three months.
In a recent webinar hosted by GEST (Global Embolization Oncology Symposium Technologies), Kristen Alexa Lee (Singapore General Hospital, Singapore) shares her experience of navigating the COVID-19 pandemic as a pregnant healthcare worker.
Singapore is using the DORSCON risk assessment system, conceptualised following the 2003 SARS (Severe acute respiratory syndrome) epidemic to provide guidance to the public. Currently, the country is at DORSCON orange, which means the disease is severe, spreads easily, but not spread widely, and is being contained. “It has been almost three months since the first COVID-19 case was diagnosed in Singapore, and we have certainly gone through waves of calm and panic,” Lee says.
Detailing the pandemic experience in her country, she explains: “Thanks to aggressive contact tracing and testing, we have [had] a lot of initial success in the containment of the outbreak in the first two months. We actually had our second wave with [the] return of Singapore nationals and other visitors from overseas sometime in February/March, and with progressive quarantine measures and strict travel restrictions, the surge of imported cases has largely ceased.
“Unfortunately, we are actually now tackling a new surge of cases. There are new foreign clusters which are popping up from foreign worker dormitories.” While part of this is due to increased testing, Lee adds that healthcare workers across the country are bracing for a surge of inpatient and intensive care unit (ICU) admissions in the coming weeks.
However, she asserts that the SARS experience in 2003 has “truly created an urgency for early action”. As measures were put in place within hospitals and the community in a timely manner, she adds, “Personally, despite the situation, I have felt safe both at work and outside of work.”
Education on appropriate infection control measures and ensuring compliance to quarantine are among many of the public health initiatives in Singapore that, according to Lee, the government are advocating. “They have largely been focusing on social distancing and protecting the vulnerable, such as the elderly and pregnant women.”
Due to an array of measures taken within the hospital, Lee acknowledges that they are seeing minimal social transmissions and healthcare worker infections. “Compared to SARS in 2003, 41% of the cases were infected healthcare workers. Now, in 2020 for COVID-19, less than 1% of cases are infected healthcare workers, and those are believed to be acquired from the community.”
She explains that early on, protocols were set in place for perimeter control, and screening occurs for all patients on arrival. Guidelines are also in place to identify suspect cases for immediate isolation and evaluation, while compliance to all policies regarding segregation, social distancing, and travel restrictions are strictly enforced. There are clear directives for staff with any respiratory symptoms to seek medical attention at the staff clinic, Lee says, adding that all healthcare workers at her hospital are obliged to take their temperature twice a day to ensure there are no fevers.
Yet, regarding restrictions on work responsibilities for pregnant healthcare workers, Lee comments that there is only one, as the N95 mask has been deemed unsuitable. Therefore, she says all pregnant staff have been reassigned to areas where only surgical masks are needed, and must avoid participating in aerosol-generating procedures.
“As the situation continues to evolve, we have to revise my day-to-day role. My main concern was that I did not want to compromise our man power. But working together with my chief, we are able to find productive ways to scale back my patient-fronting duties.”
Given that the number of outpatient procedures have been reduced, Lee has taken on diagnostic duties, which are usually assigned to interventional radiologists. She also now helps with the management of outpatient requests, and developing systems to triage such patients. “During peacetimes, our list usually runs from anywhere of 40–50 cases per day. For essential outpatient services, it is important to have a detailed and systematic workflow, so patients can still receive the care that they need.”
Pregnant radiographers and nurses have largely continued their duties, Lee affirms, but are taken out of rotation whenever contact with a suspected COVID-positive patient is required.
“Even though we may be tackling different phases of the pandemic around the world, there is no question that this is a very trying time for many healthcare workers. For expecting mothers, the information on pregnancy and COVID-19 is still relatively scarce.”
Addressing staff that are currently pregnant, Lee urges them to “be familiar with your hospitals occupational health policy regarding pregnant healthcare worker, and continue to have open and honest discussions with your departmental leadership, to minimise your risk.
“Continue to protect yourself with strict infection control measures. For some of us, we need to revise as necessary to minimise our patient-fronting activities. Ultimately, it is important to remember that we are all contributing to this fight, and segregation does not mean isolation.”
Maureen Kohi (University of California San Francisco [UCSF], San Francisco, USA), who was co-moderating the webinar discussion with John Kauffman (Oregon Health and Science University, Portland, USA), praised Lee’s work, saying: “All we have done at UCSF [for pregnant woman during the COVID-19 pandemic], we have done because of her [Lee] and her experience, and what she brings to the table.”
Prism Schneider (Cumming School of Medicine, University of Calgary, Calgary, Canada) and others write in a commentary in the Canadian Medical Association Journal—because of an increase in domestic violence during the pandemic—healthcare providers should be aware of the signs of intimate partner violence and learn strategies to safely ask about injuries.
According to the press release announcing the commentary, China, Italy and Spain have reported increases in calls to emergency support lines. Also some areas of the UK and France have had police reports of violence increase by 20% and 30%, respectively; and crisis lines in Canada have seen large jumps in the number of calls. The press release notes that the frequency of domestic violence increased markedly during the economic downturn after Hurricane Katrina, suggesting that those affected will continue to be at risk long after the current phase of the pandemic ends.
In the commentary, the authors write: “Healthcare providers, although facing the need to learn many new skills related to COVID-19, must also maintain awareness of intimate partner violence, seek opportunities for self-education, develop strategies for discussing intimate partner violence and become familiar with currently available local resources for patient referral.”
They add that evidence supports direct questioning by a healthcare provider in a private environment if they suspect injuries from violence, as many women will not offer this information without prompting. Schneider et al note: “The onus is on health practitioners to begin the conversation with patients who may have experienced intimate partner violence.”
Lead author Schneider says: “Measures to minimise the spread of severe acute respiratory syndrome coronavirus 2 reinforce environments that facilitate behaviours that an intimate partner may use to exert power over another to inflict psychological, physical or sexual harm. The stress of confinement, financial uncertainty, attitudes about gender roles and a desire for control during disasters all contribute to an increased risk of intimate partner violence.”
As many physicians have moved to telemedicine consults to maintain physical distancing, Canada has launched a “Safe Word” campaign and a “Signal for Help” campaign for patients to send a silent request for help.
This article is sponsored by Guerbet. immunotherapy
Preliminary evidence suggests that combining conventional transarterial chemoembolization (cTACE) with immunotherapy could be beneficial to patients with unresectable liver cancer, writes Rafael Duran. He highlights the role of Vectorio (Guerbet) in standardising the cTACE technique, which he says “is needed for better reproducibility”, and explains how immunotherapy could be given systematically, through locoregional delivery within the Lipiodol-based emulsion, or injected intratumourally. He urges interventional oncologists to watch this space, as he predicts that combined cTACE and immunotherapy will become an increasingly common treatment approach for hepatocellular carcinoma (HCC) patients.
cTACE is the most widely used treatment for unresectable HCC, and has been increasingly utilised in patients with liver metastases. As opposed to surgery, which completely removes the tumour, cTACE achieves tumor cell death in situ. Thus, cTACE-induced necrosis may unmask to the immune system previously shielded tumour antigens and induce antigenspecific T cell responses. cTACE can trigger a cascade of inflammatory and immune responses, induce systemic changes in the levels of cytokines and chemokines, and, notably, has a profound influence on T cell repertoire.
Ayaru and colleagues demonstrated that cTACE could uncover tumour-associated antigens (TAAs), such as alpha-fetoprotein (AFP), and elicit AFP-specific CD4+ T cell responses. Flecken and colleagues showed that the detection of TAAs by CD8+ cytotoxic T cells was increased following cTACE when compared to treatment-naïve HCC patients. A seminal study was conducted by Mizukoshi et al on immune responses in HCC patients treated with several liver-directed locoregional therapies. All the patients demonstrated an increased frequency of TAA specific T cells post therapy, and, intriguingly, T cells from some patients also exhibited novel recognition of TAA peptides that were not recognised prior to treatment, underscoring the importance of these therapies in inducing and enhancing tumour specific T cell responses.
Upon the application of immune checkpoint inhibitors, not only did the number of TAA-specific T cells significantly increase, but also their production of cytokines, suggesting that a combination with immunotherapy is beneficial. In another study by Liao and colleagues, type 17 helper T cells (Th17) cells, which are known to play an important role in inflammation and autoimmunity, were significantly increased in HCC patients treated with cTACE. Interestingly, this increased frequency of circulating Th17 cells following cTACE was predictive of better patient outcomes (improved survival and longer time to progression). Importantly, cTACE is able to significantly decrease the percentage of regulatory T cells (Tregs), which are known to correlate with disease stage (the more advanced disease stage, the more Tregs) and progression, and worse survival outcomes, as they dampen the effector T cell responses against tumours and promote an immunosuppressive tumour microenvironment (Li et al; Liao et al).
Although preliminary, these data highlight the rationale of combining cTACE with immunotherapy. Many trials are ongoing that combine cTACE with systematically delivered immunotherapies to maximise the anticancer efficacy of both therapies. Immunotherapy could be delivered locoregionally within the Lipiodol-based emulsion (i.e. replacing the chemotherapeutic drug or in combination with it), or injected intratumorally. More studies employing combinatorial approaches of cTACE and immunotherapy are expected, and further standardisation of the cTACE technique is needed for better reproducibility. Vectorio will help in the standardisation of the technique by decreasing the current heterogeneity in practices among interventional radiologists. The preparation of the water-in-oil emulsion is improved, and, thus, should be more densely retained within the tumours than the alternative oil-in-water emulsion. For this, it is crucial to have a volume of Lipiodol that is double the volume of the cytotoxic drug, and to adequately mix the chemotherapy with Lipiodol with at least 20 back and forth pumping movements through the stopcock.
To date, interventional oncology (IO) approaches such as cTACE have been highly effective in treating tumours locoregionally, and the effectiveness of these approaches can be augmented to achieve systemic anti-tumour effects by combining with targeted immunotherapies. Although the convergence of IO and immunotherapy is still in its infancy, it presents multitudinous possibilities to be explored, which will be pivotal in improving the standard of patient care.
Rafael Duran is an interventional radiologist at Lausanne University Hospital, Lausanne, Switzerland.
Workforce shortages in clinical radiology are increasing year-on-year, resulting in delayed diagnoses and lower-quality patient care, according to the latest annual census from the UK Royal College of Radiologists (RCR). Shortages of interventional and breast radiologists are of particular concern, the “Clinical Radiology UK Workforce Census 2019 Report” states.
“The 2019 clinical radiology workforce census findings are grave,” Mark Callaway, lead author of the workforce report and the RCR’s medical director of professional practice for clinical radiology, writes in the forward. “Once again, they highlight the continued growth in demand for diagnostic and interventional radiology (IR) services, alongside further increases in workforce shortages. These are issues we have raised for many years and, worryingly, the continuing workforce shortages are impacting the cost and quality of patient care.
“The 2019 census report demonstrates unequivocally that our current imaging and interventional radiology services are unsustainable; governments and policy makers from across the sector and from all four nations must take action. Otherwise, patients are at risk.”
Costs have risen as radiology departments struggle to meet the demand for complex imaging, and consultant radiologists are feeling overworked and undervalued, noted the report, which was released on 14 April.
The key findings from the 61-page report were as follows:
“The global coronavirus pandemic brings a sustained period of uncertainty and demand for the NHS,” Callaway comments. “Our most recent report underlines how our staffing crisis, which has been evident and escalating for the past five years, is having an undeniable, direct impact on the cost and quality of patient care.”
He hopes politicians and health leaders will seriously consider how the ongoing shortage of radiologists limits patient care and poses a threat to patient safety and commit to improving trainee numbers and focusing on specialty-specific retention measures.
“Due to our consistent 100% completion rate for the workforce census, these powerful but concerning data can be used by the RCR to lobby government, health education bodies, and policy-makers for increased training numbers and improved working practices for clinical radiologists,” Callaway adds.
Questions concerning the provision of IR services in the UK included for the first time
This year’s report is the first to include questions about the provision of IR services across the UK. Minimally invasive therapy is vital for the delivery of safe patient care and avoiding unnecessary surgery, says Callaway, before opining: “The results make disappointing reading from a patient’s perspective; only half of trusts and health boards can provide a comprehensive 24-hour service, and there is a severe shortage of experts to provide both vascular and non-vascular IR procedures.”
The report concludes that IR provision is “patchy and puts patients at unacceptable risk”, explaining that trusts and health boards need a minimum of six whole-time equivalent interventional radiologists to provide an effective and sustainable 24 hour IR service, or that formal transfer arrangements need to be in place 24/7. This was not the case for all trusts. Specifically pertaining to IR service provision, the key findings of the report were:
Generalists versus specialists
In 2019, 73% of consultant radiologists were classified as generalists. Variations were seen across the UK, with generalists being more common in Northern Ireland, Scotland, and Wales (84% to 85% of the consultant workforce) than in England (71% of the consultant workforce).
“The proportion of specialist radiologists in England has increased gradually over the past five years, from 25% of the consultant workforce in 2014 to 29% in 2019. In comparison, there has been no shift from generalists to specialist consultant radiologists in Northern Ireland, Scotland and Wales, where specialist radiologists account for 15% to 16% of the consultant workforce,” the report noted.
Most generalists across the UK have one main area of specialty interest (57%), a third have two (33%), and a small number (10%) have none. The majority of specialists across the UK have one main area of specialty interest (83%), though some (17%) have two or more areas of specialty interest.
The most common specialty areas of practice are musculoskeletal, gastrointestinal, breast, vascular IR, and chest/lung. Together, these account for 53% of all specialty interests.
Breast radiology has slipped from 13% of all specialty interests in 2014 to 11% in 2019. Similarly, vascular IR has dropped from 12% of all specialty interests in 2014 to 10% in 2019. Shortages of breast radiologists and vascular interventional radiologists are an area of concern, the report stated.
There is an “urgent need” to improve specific venous thromboembolism (VTE) diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients. This is the conclusion of a recent study into venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
Behind this conclusion are the investigators’ main findings that a high number of arterial and, in particular, venous thromboembolic events were diagnosed within 24 hours of admission and there was a high rate of positive VTE imaging tests among the few COVID-19 patients tested.
The authors elaborate: “Hospitalised patients with COVID-19 were characterised by substantial in-hospital mortality and a high rate of thromboembolic complications. Rapidly increasing D-dimer levels were observed in non-survivors, reflecting the inflammatory and procoagulant state of COVID-19.”
The study, authored by Corrado Lodigiani (Humanitas Clinical and Research Hospital and Humanitas University, Milan, Italy) and colleagues—on behalf of the Humanitas COVID-19 Task Force—was recently published in Thrombosis Research.
Lodigiani and colleagues note that few data are available on the rate and characteristics of thromboembolic complications in hospitalised patients with COVID-19.
The Humanitas COVID-19 Task Force studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy. They detail that the primary outcome was any thromboembolic complication, including VTE, ischaemic stroke, and acute coronary syndrome/myocardial infarction and that the secondary outcome was overt disseminated intravascular coagulation.
Lodigiani et al report that, of 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]), thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95% CI 5.4–11%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 hours of hospital admission.
Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed at 10 (33% of computed tomography pulmonary angiography). The rate of ischaemic stroke and acute coronary syndrome/myocardial infarction was 2.5% and 1.1%, respectively. Overt disseminated intravascular coagulation was present in eight (2.2%) patients.
The authors acknowledge limitations to the present study. “This was a retrospective analysis conducted at a large university hospital, therefore possibly not reflecting the management strategies and diagnostic facilities at other non-academic institutions,” they note.
Furthermore, the authors address a geographical limitation: “Patients included in this analysis were diagnosed at one of the ‘red zones’ where the European outbreak started. This may have influenced not only patients’ outcome, as no global experience on the disease was available yet, but also the execution and frequency of imaging tests during hospitalisation. From this perspective, we could not confirm whether thromboembolic events contributed substantially to such a dramatic mortality and no autopsies were routinely performed in COVID-19 patients. Indeed, we showed that the D-dimer levels, a marker of inflammation and coagulation activation, rapidly increases in non-survivors during the course of hospitalisation; overt disseminated intravascular coagulation was present in 2% of COVID-19 patients and fatal in almost all cases.”
On 18 March, the Centers for Medicare & Medicaid Services (CMS) recommended “limiting non-essential care and expanding surge capacity into ambulatory surgical centres and other areas” to conserve resources and staff for managing COVID-19 patients. However, in a statement issued on 19 April, it now recognises “at this time, many areas [in the USA] have a low, or relatively low and stable incidence of COVID-19, and that it is important to be flexible and allow facilities to provide care for patients needing non-emergent, non-COVID-19 healthcare”.
The CMS adds that, as states and localities begin to stabilise, “it is important to restart care that is currently being postponed, such as certain procedural care (surgeries and procedures), chronic disease care, and, ultimately, preventive care”. The CMS advises, therefore, that if states or regions have passed the Gating Criteria, they may proceed to Phase I and directs them to the new US Government’s “opening up American again” guidelines.
According to the CMS, “maximum use” of telehealth modalities is “strongly encouraged”. However, for care that cannot be accomplished virtually, the CMS has issued recommendations (the first in a series) to guide “healthcare systems and facilities as they consider resuming in-person care of non-COVID-19 patients in regions with low incidence of COVID-19 disease”.
It says that non-COVID-19 care should be offered to patients “as clinically appropriate and within a state, locality, or facility that has the resources to provide such care and the ability to quickly respond to a surge in COVID-19 cases, if necessary”. The CMS also notes that decisions should “be consistent with public health information and in collaboration with state public health authorities”.
The recommendations review, among others, general considerations, personal protective equipment, workforce availability, facility considerations, and testing capacity. They include creating non-COVID Care (NCC) zones that “would screen all patients [and staff] for symptoms of COVID-19, including temperature checks”. Another recommendation is that such NCC zones should have “have in place steps to reduce risk of COVID-19 exposure and transmission; these areas should be separate from other facilities to the degrees possible (i.e., separate building, or designated rooms or floor with a separate entrance and minimal crossover with COVID-19 areas).”
Full statement, click here.
Terumo Europe today announced that their BioPearl microspheres have received CE mark, providing a new option for patients eligible for locoregional embolization for the treatment of liver cancer. BioPearl microspheres are designed to preserve post-transarterial chemoembolization (TACE) target artery access, opening up the potential for cyclic treatment.
Currently, drug-eluting microsphere TACE (DEM-TACE) and conventional TACE are both used worldwide. According to Terumo, BioPearl microspheres have been designed based upon clinicians’ desire to have controlled drug elution while keeping future treatment options open. BioPearl microspheres could change treatment algorithms and may offer more choices for patients.
“Interventional oncology is not a standalone speciality, and by working with medical oncologists, we will be able to optimise current and future treatments, namely by delivering drugs directly into the tumour. Through such collaboration, we may be able to reduce the dosage and improve the toxicity profile of anticancer drugs, and ultimately improve the field,” says Thierry De Baere (Institute Gustave Roussy, Villejuif, France). “BioPearl drug-eluting microspheres and its degradation profile is a significant next step toward enhancing localised drug delivery and hopefully improving patient outcomes”.
Last week, the Charing Cross (CX) Symposium 2020 would have taken place in London, UK. To mark the occasion virtually, experts from across the globe took part in a wide-ranging informal chat to share the impacts of the COVID-19 pandemic on the vascular community. Chaired by Roger Greenhalgh (London, UK), Enrico Ascher (New York, USA), Michel Makaroun (Pittsburgh, USA), Roberto Chiesa (Milan, Italy), Jürg Schmidli (Bern, Switzerland), Gunnar Tepe (Rosenheim, Germany), and Rebeca Reachi (San Luis Potosí, Mexico) discussed the effect of the virus on their daily practice, compared the differing readiness with which the threat was met by governments across Europe and North America, and deliberated on what healthcare will look like in the aftermath of the deadliest pandemic in living memory.
A key take-home message is that not all healthcare systems have been impacted equally. Those hit first by the virus had the least time to prepare, and are consequently seeing a greater loss of life. Anecdotally, poorer neighbourhoods and countries (such as Brooklyn in the USA and Mexico City, Mexico) also seem to be the most overwhelmed. On a positive note, governments and local authorities exposed to the virus later, such as those in Switzerland and Pittsburgh, USA, seem to have been able to prepare for the pandemic, having learned from those hit first. Schmidli and Makaroun were able to recount how their regions were able to effectively mobilise against the virus early, closing borders to reduce footfall and slowing the spread. This was possible, they related, due to a delay in the virus reaching their communities, providing a window of opportunity to witness the response from medical communities already exposed.
As an additional consequence of the COVID-19 pandemic, the webinar participants reported that the necessary cancellation of elective procedures has resulted in a backlog of surgeries, meaning the current crisis will potentially have ramifications for healthcare for years to come. Indeed, when considering life after the pandemic, the discussants agree that while virtual meetings are no match for face-to-face interaction, they have been an essential part of healthcare provision during government-enforced lockdowns. Chiesa proposed that a return to normality is possible, providing healthcare professionals work together in unity.
The effects of COVID-19 on physician environment and practice
Later hit countries benefit from early preparation
A key takeaway from the webinar is that there is a large geographic disparity in the severity of the virus’ impact. Timing is also crucial. Those vascular specialists practicing in countries or regions with a “head start” on the virus repeatedly reported being able to mobilise earlier and to prepare their wards for the coming influx of coronavirus patients. For those first impacted by COVID-19, this was not the case. Speaking from Milan, Italy, Chiesa relates the difficulties with being amongst the first hit with the COVID-19 pandemic in Europe. “The problem in Italy is that we are the first country to be infected with COVID-19, so other countries have had a one, two, or three-week delay. It was easier for the other countries. For example, for Switzerland, it was easier, after observing what has happened in Italy, to stop everything immediately, to close down everything.”
Schmidli concurred. “We were quite lucky in Switzerland,” he told webinar listeners. “We knew what happened in Italy, and our authorities shut down the country quite fast. Most of the hospitals had about two weeks to prepare for COVID-19 patients,” he relayed.
Providing a US perspective, Ascher said: “Unfortunately, we were hit with this horrible pandemic, and in particular in New York state we have been hit very hard.” Providing some statistics, Ascher shared that, to date, there were more than 130,000 confirmed cases of COVID-19 in the state, with over 35,000 hospitalisations, and more than 9,000 deaths from the virus. “Just in Brooklyn, which is a very endemic area, we had close to 35,000 diagnosed patients. This is double what you have in Manhattan. We have been particularly hit; although we do not have as many institutions in Brooklyn as in Manhattan, we have double the number of cases. Not only have we been doing what we know how to do within our specialty, but [we have] also been expanding our services to particular needs within the hospital.”
Ascher claims that there is a “poverty factor” associated with the differing proliferation of COVID-19 within New York state; when asked directly about why he believes the discrepancy exists between case numbers in Brooklyn and Manhattan, he replied: “I think it is because the average person in Brooklyn is poorer than in Manhattan.”
In neighbouring Pittsburgh, a city in Pennsylvania, USA, Makaroun reported that there have been very few COVID-19 cases. “We have been lucky in Pittsburgh,” he disclosed. “We have had very few cases, and certainly the system has not been overwhelmed.
Relating her experience of COVID-19 in Mexico, Reachi told the other panellists: “The government are not testing everybody. The number of [confirmed] cases right now is only 8,000, but it is estimated that there are over 50,000. […] The main problem for me is there is not enough testing of patients.
“We do not have anything. We do not have N95 masks. I bought one for myself because some public institutions do not have enough equipment. I am in fear of going to work. We do not know if the patient [we are treating] is infected or not because they are not being tested. We have to take our own protection, not to get infected, so that is a problem here.”
Footfall favours viral spread
Chiesa noted that a football game at the San Siro stadium near Milan in February has been attributed to the initial spike in COVID-19 patients in the region. Similarly, although Tepe described Germany as not being too inundated with COVID-19 patients, he acceded that “Bavaria is quite different”, elaborating: “Rosenheim is the number one spot for COVID-19 within Germany. This is because we are close to Italy and Austria, and quite a lot of people have travelled through who had been in ski resorts in the Alps. About 10% of the population of Rosenheim are affected. Our hospital has 600 beds, and 200 of those are COVID-19. So, we are quite heavily affected.”
Closing borders helped to stop the spread
Makaroun noted: “Pennsylvania borders New York, and when the number of cases started increasing, they put a lockdown on all of Pennsylvania. We are a six-hour drive away, so our region was locked down before the big increase in cases.” Greenhalgh noted Makaroun was the first vascular surgeon he had heard report being ready for the COVID-19 crisis. Most healthcare centres around the world were overwhelmed by the virus.
Schmidli concurred: “Only cities close to the border (such as Geneva, Lausanne, or Lugano, which is quite close to Italy) had a lot of novel coronavirus patients from the beginning. But in the Swiss-German part [of the country], we had very few patients.”
Effect of COVID-19 on surgical practice and emergencies: Increase in number of endovascular procedures performed as physicians aim to keep patients out of hospital
Many elective procedures have been delayed or postponed around the world in response to the COVID-19 pandemic. What is elucidated in the CX COVID-19 webinar is that as well as impacting the number of surgeries taking place globally, the virus has also influenced the type of surgery being performed. Chiesa reported seeing more endovascular procedures than normal, citing the lack of beds in the intensive care unit of his hospital as one explanation: “It is very difficult to do open surgery without intensive care on our ward.”
Making incisions brings greater risk of infection. Several vascular surgeons speaking testified to seeing fewer transplants and fewer cancer referrals because of this increased risk. “In our hospital and throughout Germany, emergencies like patients who present with stroke or heart attack have gone down by 50%,” Tepe stated.
“We have got to assume that heart attacks and stroke are still taking place,” Greenhalgh replied. “So, are we making the assumption that this means patients are not coming into the hospital, but they are in trouble somewhere in the community?” Both Tepe and Schmidli agreed, with the latter adding: “We have seen the same thing—we did not have one ruptured aneurysm [in the last few weeks], which is completely unusual.”
Ascher noted that the same story was true in New York: “We have fewer emergencies, much fewer heart attacks coming to the hospital, and the reason I believe this is happening is because patients are afraid of coming to the hospital. They are saying they might as well take an aspirin at home and take a telemedicine. So, I think we have seen fewer of all these patients.” He declared his concern that several of these patients may need more intensive treatment in the future, once the pandemic-induced panic has passed.
Contrary to the other speakers’ experiences, Makaroun shared that his institution has treated six ruptured aneurysms in the last two weeks, and that, although the number of trauma cases were down (which he attributed to fewer cars being on the road meaning fewer traffic accidents), the number of cancer surgeries “has not really stopped”. He expanded: “Elective work, as you have mentioned, is down to almost none, but in general the emergencies have stayed to about the same as where they were before, but we may be privileged in a way in terms of where we were before, not being overwhelmed with COVID-19, and the hospital actually has around 20% empty beds.”
Backlog of elective cases: Catch-up will vary by geography
The necessary deferral of elective procedures has resulted in a backlog of cases across healthcare systems worldwide. During the webinar a geographical disparity in readiness to restart procedures became clear.
Makaroun predicted some logistical problems in starting the catch-up. “How many operating rooms can you reopen? How many nurses are sick and cannot show up?” he asked. Putting the scale of the situation at his centre in perspective, Makaroun detailed: “Normally on our system there are over 2,800 procedures a day, so you can imagine the backlog after about five weeks of doing very little elective work.”
In general, however, Makaroun noted that his hospital still has “a lot of capacity”, so they are now trying to work out how to prioritise patients and provide a framework for the cases to restart with minimal risk. Schmidli anticipated this to be the case in Switzerland as well: “restarting cases will not be a big issue,” he disclosed, as the number of infections has been lower than expected.
In contrast, Reachi outlined that in Mexico, they will not be starting elective cases again any time soon. “I know that we are very far from where we have to be. We are trying to flatten the curve and we are trying to stay at home. The government says this will be the case until the end of May.”
Medical education during the time of COVID-19: Virtual meetings no match for face-to-face interaction
The discussion then moved towards medical education during an era of unprecedented social distancing. Greenhalgh noted that the CX Symposium had been ready to showcase numerous first-to-podium presentations, covering “a lot of new data which is important to communicate”.
The panel agreed that while virtual meetings have enabled communication whilst face-to-face meetings are not an option, they are no match for a live conference.
Makaroun commented on both the necessity and ubiquity of the online meeting at the present time: “I think virtual is something that we have to do. Most of our meetings are now virtual and I am spending more time in front of my computer than I ever did in my entire life.”
Ascher then emphasised the benefits of interacting in person, stating that “nothing will ever replace the live presence of your colleagues at a meeting”. However, he acknowledged that “right now, we are in a situation where we have no other option but to go online.”
Return to status quo desirable, but timeline remains unclear
It was made clear during the conversation that a return to the status quo ante is desired, however the rate at which this can happen will vary by geography.
While Makaroun is hopeful that things will go back to normal, he stressed that it would take time. “Until the science catches up with this virus, I am not sure that we will ever know how we are going to return to normal. I think we have to learn to live with it for the foreseeable future and it may be a year or two, but I hope we will all go back to where we used to be.”
Schmidli believes that until there is a vaccine, things cannot go back to normal. “In the meantime,” he said, “we hope that the second wave does not hit us too hard.”
There was universal consensus about the need to return to normality as soon as responsibly and feasibly possible.
Profession faces specific COVID-19 danger
On the specific risks faced by the medical profession, Tepe pointed out the importance of testing and how his centre is addressing this: “We have to know who is positive and who is negative. Here at our institution we are doing a lot of CT scans. It is quite sensitive and is faster than a test.”
On a personal note, Ascher raised the point of responsibility towards the families of physicians. “I do not think we should overlook the influence on the family of the surgeon or the provider. It is a big deal because you go and spend 12 hours working and when you get home you have small children, you have a wife, you have grandparents. It is a big problem, and this is affecting a lot of us.”
Role of medical students varies widely across the globe
On the topic of responsibility, the conversation then considered whether medical students were prematurely functioning as doctors in order to meet the needs of the COVID-19 pandemic, with answers once again revealing geographical imbalance.
“In Mexico, all the medical students are at home,” Reachi began. “They are not allowed to go to the hospital because they are not prepared and there is not enough equipment to protect them.”
Ascher outlined a contrasting situation in New York: “At NYU [New York University], 50% of our senior class graduated already. Many of them were given jobs as residents and those who were not were hired to help in other ways and paid as residents.”
In Pittsburgh, however, medical students are not required in the hospitals and have instead been providing childcare for healthcare workers who cannot be at home, and volunteering at clinics in disadvantaged areas of the city. “They are stepping up and helping but not necessarily as physicians,” Makaroun commented.
“If only I knew…”: Vascular community reflects on what they would have done differently
Tepe cited testing as a “major issue” at the beginning of the crisis and something he would like to have been better prepared for.
The conversation then turned to equipment, with Ascher commenting: “I would have called the governor and asked him to expedite an order of ventilators”. One a similar note, Reachi stated that she would have bought more equipment for her college. “It is gone. There is no more.”
In Switzerland, “we would not shut down the whole system completely,” said Schmidli, noting that they had overestimated the impact of the virus in their country.
Chiesa ended this part of the discussion by commenting that in Italy the onset was so sudden that “it would have been impossible to do something differently”.
With more forewarning, Chiesa would have implemented a different organisation of the healthcare system in order to better prepare for the crisis. He outlined that he would have created a hub for every type of specialty “as soon as possible”, stressing that this was “very important, because it would allow you to do all emergency or other important cases in one major hospital in the region and use all other hospitals to cure COVID-19 patients”.
Difficult decisions during the COVID-19 crisis
As the conversation came to an end, the panel revealed the most difficult decision they have had to make so far during the COVID-19 crisis.
Chiesa, Schmidli, and Tepe agreed that choosing not to operate on certain patients was their most difficult decision. Chiesa noted, for example, that he was not able to operate on patients with thoracoabdominal aneurysms of up to 10cm.
One of the most difficult decisions for Makaroun related to his responsibility towards his employees. “I had to make sure that most of our employees and personnel are protected by sending them home and making sure their jobs are protected.”
Ascher addressed the decision between loyalties to family on the one hand and to patients on the other, questioning “whether at my age I should put myself in the situation of being on call 24 days a month.”
Reachi also felt that her loyalties were split between her hospital duties and family ties. She cited her most difficult decision as simply going to the hospital, likening it to gambling in its risk and recalled feeling “petrified” when entering her institution, due to the unknown prevalence of the virus and the lack of PPE.
COVID-19 has illuminated stark differences in healthcare systems across the world. Responses to the pandemic have been reflective of the extent and timing of exposure to the virus, and the resultant impact on the vascular community is markedly variable. At the same time, COVID-19 has brought the medical profession together. While the CX Symposium would have assembled vascular specialists from nearly 80 countries this week, this conversation has revealed commonalities within the community during a crisis. The degree of testing, PPE provision, and the timing and suddenness of onset have determined the severity of the impact on healthcare systems. Speaking from one of the hardest-hit countries in the world, Reachi expressed that her enduring dilemma was between her professional and personal duties, something at the forefront of every physician’s mind today.
The European Congress of Radiology (ECR) will not take place onsite in Vienna, Austria, this year. Instead it will be a digital-only event from 15–19 July, the European Society of Radiology (ESR) has announced.
“It is with a heavy heart and much regret that the board of directors of the ESR has decided not to hold an onsite ECR in 2020,” the ESR statement noted. ” As you can imagine,”, the board of directors continue in a letter addressed to ECR participants, “this serious decision was not taken easily. The choice not to hold ECR 2020 onsite presents a significant burden for the European Society of Radiology and will also influence future congresses and endeavours. However, we have a social responsibility to our members, partners, staff, and the general public. In the current crisis, the ESR must lead by example, and it is clear that your safety will always be our number one priority, and we sincerely hope for your understanding and support of our decision.”
The society also noted: “Public health authorities in Austria, as well as much of the rest of the world, have restricted large meetings and enforced travel bans, with no official indication as to when these restrictions will be lifted. As we are currently witnessing, almost all specialty and subspecialty societies and other congress organisers have already, or will shortly, cancel their meetings for 2020.”
The ESR said it made its decision because the COVID-19 outbreak had worsened since the original resolution was made to postpone the conference, with Europe becoming the epicentre of the global pandemic.
The letter closes with a note of gratitude: “We are not only a medical profession, but a family, and helping and protecting one another during moments like these is of the utmost importance. At no time have your services to radiology and healthcare been more important than now and the ESR board of directors would like to thank you, not only for your ongoing contribution to helping fight coronavirus, in whatever form it might take, but also for your support of our congress and society. We sincerely hope that we can rely on a continuation of this support in the future.”
Registration fees and expenses
Registration fees paid by delegates for ECR 2020 will be valid for ECR 2021, due to take place on 3–7 March in Vienna. Also, an ECR 2020 registration will automatically grant free access to the online congress in July 2020, including on-demand access until 31 December 2020.
Any registration queries should go to the ESR staff at [email protected], although the ESR urged registered attendees to be patient.
With respect to flight and accommodation bookings, the ESR suggested people check the provider’s cancellation policy.
“As there is not yet an official statement by the Austrian government regarding travel restrictions, border openings, or the allowance to hold major events in July, you should consider waiting with the cancellation of your booking if you are not eligible for free cancellation now,” the ESR stated.
The ECR 2020 Book of Abstracts has also been published online in the society’s journal, Insights into Imaging.
Intact Vascular has announced the first commercial use of its Tack Endovascular System (4F) in multiple sites across the USA. Notably the first FDA-approved vascular implant for below-the-knee (BTK) post-angioplasty dissection repair, Tack implants are designed to optimise balloon angioplasty outcomes in the challenging critical limb ischaemia (CLI) patient population.
“Effectively treating the small arteries affected in CLI has always been challenging. Over the years, various technologies have attempted to address this unique vasculature, but failed to provide an effective solution,” commented John Rundback, vascular and interventional radiologist and partner at the American Endovascular & Amputation Prevention Services in Clifton, USA, one of the initial implanting sites. “Finally, I have an option that safely and effectively delivers better results below the knee for my CLI patients, and I am thrilled to incorporate this novel peripheral vascular implant into my treatment algorithm going forward.”
Regulatory approval was based on data from Intact Vascular’s Tack optimised balloon angioplasty II BTK (TOBA II BTK) clinical trial, which met all primary endpoints with 100% acute dissection resolution. The TOBA II BTK results were presented at the 2019 VIVA conference and demonstrated 95.7% K-M amputation-free survival, 87.3% K-M target lesion patency with significant improvement in toe-brachial index (TBI) and 92.0% K-M freedom from clinically driven reintervention at six months.
“As a company, Intact Vascular has sponsored multiple large-scale, prospective studies that have generated a solid and robust body of clinical evidence to support post-angioplasty dissection repair with the Tack Endovascular System,” noted S Jay Mathews, interventional cardiologist and endovascular specialist at Bradenton Cardiology Center in Bradenton, USA, another initial implanting site. “I am confident this game-changing technology will elevate the standard of care when performing endovascular procedures.”
“I would like to acknowledge our TOBA II BTK trial investigators for their collaboration and efforts to reach this important milestone,” commented Howard Rosen, vice president of marketing and business development for Intact Vascular. “There has been a long-standing and significant unmet need for a technology that addresses BTK disease. We are thrilled to provide the first FDA-approved peripheral vascular implant offering endovascular operators a novel tool that safely and effectively addresses this challenging condition and improves outcomes for their patients.”
“With coronavirus disease 2019 (COVID-19), the demands and stresses on radiologists and physicians have increased dramatically. Even before this pandemic, the high prevalence of burnout, complex causes, and critical consequences had been widely reported,” write David Fessell and Cary Cherniss in the Journal of the American College of Radiology. “The need for effective strategies and tools [to manage radiologists’ mental health] is only increasing as both individuals and institutions navigate the current anxiety and uncertainty.” Here, Fessell outlines some “micro-practices” physicians can implement in their daily life to help cope with the additional stresses of working amidst a global pandemic.
With increased stress and anxiety comes an increased risk of decreased functioning and potential burnout. “Macro-practices”, including quality sleep, exercise, and nutrition, are essential for well-being. “Micro-practices” may also be helpful in preventing burnout and promoting emotional wellness. Such practices take just a few seconds to a few minutes. In a recent article, Cary Cherniss [Rutgers University, New Brunswick, USA] and I reviewed the evidence for four such practices: a self-wellness “check-in” during handwashing; the practice of “name it to tame it,” for our emotions; using a gratitude journal; and deep breathing for activating the parasympathetic nervous system to promote calmness and relaxation.1
“Micro-practices” can be anchored to already existing activities, such as hand-washing or logging into the PACS [picture archiving and communication system], to help us form healthy habits.2 Almost any recurring event can be a cue for a wellness check in: focusing on your breath and reflecting: am I well hydrated? Hungry? Emotionally or physically exhausted? Such quick and simple micro-practices are potentially possible even for the busiest radiologist. Activities outside our work lives can be cues as well—waiting in line or online, before answering the phone or a text, or even before brushing one’s teeth. Over time, such built-in wellness moments have the potential to shift one’s energy level and the tone of one’s day.
“Name it to tame it,” to paraphrase [neuropsychiatrist and author] Dan Siegel (University of California Los Angeles [UCLA] School of Medicine, Los Angeles, USA), has fMRI research to back it up. Such a practice can help us regulate our emotions, such as frustration and anger, to bring calm and ease.3 There are many helpful resources, including lists of the range of human feelings, which can help facilitate this process.4,5
An additional evidence-based practice that can aid well-being is the simple act of writing down three things one is grateful for several times a week.6,7 Sharing this practice with a “gratitude partner” can help expand the positive feelings and bring support and encouragement. Such practices can be extended to groups by starting meetings with “kudos” for recent achievements. Such group practices can help develop positive and dynamics relationships among team members.
Finally, a simple breathing technique known as diaphragmatic breathing has also shown promise for reducing stress and self-perceived anxiety.8 The practice is simple: inhale deeply by expanding the lungs downward rather than inhalation using the abdomen or ribcage alone. Inhale through the nose, pause and then slowly exhale through the mouth. Silent counting during inhalation and exhalation may be helpful to establish a respiratory rate of six to eight breaths per minute. This kind of slow, deep breathing is thought to increase para-sympathetic activation. Many other breathing techniques exist—explore them, and find one or more that resonates with you.9,10
Throughout one’s day there are likely many opportunities to take a deep breath or three: before the start of a read-out session, between cases, or on a bathroom break. These micro-practices may seem too small and inconsequential to do any good. Small changes are, however, doable and sustainable. Over time, building moments of mindfulness and gratitude, emotional regulation, and deep breathing into one’s day can increase the wellness in one’s life. Try one or more. If you are bringing more calm and peace to your world, it is highly likely your colleagues, family, and friends will benefit as well.
These micro-practices are not treatments for burnout. If you are experiencing burnout, please seek professional help. We need you happy, healthy, and thriving. These micro-practices are meant to complement other individual efforts such as mindfulness-based stress reduction (MBSR) and personal coaching. Having a robust tool box of practices that resonate with you can be an invaluable resource for navigating challenges including COVID-19, and beyond.
David Fessell is a radiologist at the University of Michigan Medical School, Ann Arbor, USA.
References
Inspired by his father, an interventional radiologist who used to shape catheters over the stove at home, Matthew Johnson switched from a residency in surgery to pursue a career in interventional oncology, and began a lifelong love affair with the liver. “There is always more to learn”, he says.
My father. He was a radiologist, radiation oncologist, and interventional radiologist in private practice in Battle Creek, Michigan, USA. He loved his job, and often spoke about his patients, mostly about his cancer patients. I once suggested that it must be difficult treating cancer patients, but he said “No; it is incredibly satisfying. There are two things you can cure in medicine: infection and cancer.” That positivity has always stuck with me. He did the first arteriogram in Battle Creek, but I did not know that until I was in medical school. I remembered that he used to shape catheters over the stove at home, but did not know that was unusual. It is what Dad did. After medical school, I started residency in surgery, following my brother, Mike. My father thought I was crazy. He said that I should be a radiologist. He was right. I switched to Radiology after two years in surgery, always with the intention of becoming an interventional radiologist.
My father and my brother Mike both taught me the importance of doing the work. Both led by example. The adages that “99% of life is showing up” and “do what you say you are going to do” were family mantras. Mike, two years ahead of me in medical school, and still a practicing surgeon, told me that as a resident, no matter how difficult your day was, you should study for an hour. He did that, all the way through his residency. While I was not 100% successful in matching his effort (his drive is unparalleled), I did understand the concept, and tried to adhere to it. I still do, even if sometimes that study is of ancient history rather than of the latest anticoagulant: there is always more to learn.
I have had many, many other mentors, including Rogelio Moncada, Leon Love, Terry Demos, and Richard Cooper at Loyola in Chicago. All were brilliant and all worked hard. They stressed and accepted only excellence, and were the best teachers. Tony Venbrux, part of the faculty at Johns Hopkins during my fellowship, demonstrated not only knowledge and ability, but unequalled empathy and kindness. I continue to strive to be more like Tony. Scott Trerotola, IR section head at IU when I joined and my chief for eight years, taught me how to be a researcher. His refusal to sacrifice his integrity was inspiring. Finally, in an inexhaustive list, and although he would be surprised to hear it (as he was a radiology resident when I joined the faculty at IU), I consider Himanshu Shah, my current chair, as a mentor. His always-positive demeanour, openness to discussion, keen intellect, and indefatigable spirit have made IU Radiology a wonderful department in which to work, one that continues to flourish under his stewardship.
Unquestionably, that as we have matured as a society and embraced the fact that we are now a primary specialty, we have recognised the importance of demonstrating to the world the value of what we provide to patients. That recognition has led to us having a robust strategic plan that includes supporting interventional radiologists in practice, and creating and maintaining a residency that trains excellent clinical physicians, as well as improving understanding by external groups of what IR is. The fourth pillar of that strategic plan excites me most: it is directed toward improving the quality and impact of IR research. We have grown the research infrastructure within SIR by adding staff experience (for example, a new methodologist) and undertaking advanced clinical practice guideline initiatives. The first SIR-sponsored Clinical Practice Guideline on IVC filter use will be published in the next few months, and two others will begin this year. We have also directed ample resources to support the growth of our registries to be used for both quality improvement efforts and original research. I am very excited about the shared commitment by SIR and the SIR Foundation to research, as I think that support is essential to the continuing success of our specialty.
It is important because it will give us the best data we can obtain regarding IVC [inferior vena cava] filter use in the USA. A randomised controlled trial is not really feasible, because of the impossibility of an appropriate control group: if that group is anticoagulated, it does not represent patients for whom filters are indicated; if that group is not anticoagulated, those patients are subjected (we believe) to increased risk of pulmonary embolus (PE). PRESERVE is designed to follow patients with filters until filter removal or for two years. With over 1,400 subjects, we will be able to evaluate real complication risks and incidences of PE before and after filter removal. We will begin evaluation of the results in May 2020, after all patients have completed one-year follow up or have had their filters removed. I hope and believe that PRESERVE will contribute greatly to our understanding of how filters are used, and will help to demonstrate who will benefit most from their use. As follow-up of patients with IVC filters is so important, I am hopeful that the structured follow-up we employed in PRESERVE will serve as a paradigm for such followup in clinical practice. learn
The PRESERVE trial is a collaboration between SIR, the Society for Vascular Surgery (SVS), the US Food and Drug Administration (FDA), and industry partners. I think that that collaboration is one of the major benefits of PRESERVE. The trial was made possible by a shared goal: wanting to do what is best for our patients. We all recognised that the data surrounding venous thromboembolic disease in general, and especially around IVC filters, are limited, that we do not know who will benefit most from filter placement, how long to leave that filter in place, and how to follow it while it is there. PRESERVE has demonstrated that each of the entities involved has unique strengths—including skills, infrastructure, networks, understanding—and that as we work toward our shared goal, the sum of those combined strengths is greater than their components. I hope PRESERVE can serve as a paradigm for other SIR collaborative efforts. learn
There is always something more to learn. History repeatedly demonstrates the need for continuing innovation. Indeed, innovations changed the world: the stirrup changed warfare, the printing press changed thought. Happily, IR has always been immersed in innovation. That that process continues apace demonstrates how much more there is to improve. My clinical focus in the treatment of people with liver tumours led me to investigate ways to improve delivery of bioactive agents to those tumours. Our understanding of locoregional delivery of those agents is in its infancy, which is very exciting. What is the next thing that will really make a difference? I would like to contribute to the creation of that change-maker, to hear of a person whose life was made better by it. learn
Transarterial radioembolization (TARE). Prior to the advent of ARE, my involvement in the treatment of patients with cancer was without much focus. When I considered treating patients with TARE, I thought that in order to provide adequate care to my patients, I would need to devote myself to interventional oncology (IO). So, prior to adding TARE to my practice, I spent a considerable amount of time learning about the treatment of patients with liver tumours. Not just IR treatments, but all possible treatments. It took me a few years to be somewhat comfortable with those treatment algorithms, but it was well worth it. That study made me a much better interventional oncologist, not just when I choose to use TARE for a particular patient, but also when I choose transarterial chemoembolization (TACE) or another locoregional therapy, or when I choose instead to refer to another doctors in our multidisciplinary team. I thank my IR partners at IU, as they allowed me the time to focus on IO. I am very grateful for their unwavering support. learn
Mainly spending time with my family: my wife, Cynthia, and I have four children, all now adults with their own partners, and one grandson, Wesley. My hobbies include cycling, running, and rowing (machine); ancient history, from the beginning of civilisation to the Reformation, focusing primarily on the Roman republic and empire; playing and listening to music: I played piano and cello growing up, still play piano, and I took up guitar when I was 50 (I am not very good), and Cynthia and I very much enjoy going to concerts; and travel, which I very much enjoy when my wife is with me. learn
“Europe, including the European Union (EU) and the leaders of its nation states, needs to prepare better for future pandemics. I think we must develop a Europe-wide contingency plan providing clear guidance on effective measures,” says Afshin Gangi, president of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Speaking with Interventional News, he outlines the society’s response to the coronavirus pandemic, as well as measures taken by his own institution.
What is CIRSE doing currently to support its membership amidst the coronavirus pandemic?
The health of our members, congress goers, and industry partners has always been our top priority. This is why CIRSE reacted quickly following the outbreak of COVID-19 in Europe, moving our spring meetings to later dates in the year. The European Conference on Interventional Oncology (ECIO) 2020, which was planned for 26–29 April, has been moved to 2–5 November, in Nice, France. The European Conference on Embolotherapy (ET) and the International Conference on Complications in Interventional Radiology (ICCIR) were both going to take place in Austria in June, but since the restrictions on travel and gatherings will still be in place then, they have also been postponed. ET 2020 will take place 16–19 December in Vienna, Austria, with ICCIR 2020 running in parallel at the same congress centre from 16–18 December. The courses of the European School of Interventional Radiology (ESIR) are also being moved to autumn and spring 2021, hopefully once again enabling participants from around the world to join us for the comprehensive two-day courses on specific procedures.
With regards to the CIRSE annual congress, we are moving ahead with CIRSE 2020 to take place as planned in Munich, Germany, from 12–16 September.
In addition to these event-related activities, and in order to ensure that the exchange of experiences and medical education does not stop, we have put into action a series of measures to support online information exchange between interventional radiology (IR) professionals. Within a very short timeframe, a CIRSE/Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR) working group put together a joint CIRSE-APSCVIR checklist to prepare IR departments for COVID 19. My special thanks go to main authors Bien Soo Tan and Kiang-Hiong Tay, both from Singapore General Hospital, Singapore, for sharing the knowledge they gained from both the SARS and the COVID-19 pandemics.
As the coronavirus continues to spread, it is key to be prepared to carry out emergency procedures in this new environment and treat possibly infected patients. Our knowledge in this regard is increasing by the day, which is why CIRSE is also planning to offer a series of freely available webinars in which front-line doctors will share their experience. In the first of these webinars, taking place on Monday 20 April at 5pm (CEST), Lorenzo Monfardini and Vittorio Pedicini from Milan, Italy, will talk about bedside procedures IR provides to COVID-19 patients. I encourage everybody to participate and use this unique opportunity to submit questions for this first CIRSE webinar. For more information please visit the CIRSE website at www.cirse.org
In addition, seven fully CME accredited CIRSE Academy courses have been made freely available, as have almost 200 lectures from previous CIRSE congresses via the CIRSE Library. We are confident that by taking these steps, we will be able to continue providing excellent IR education and supporting information exchange by an increased internet offering for the time being, and again in person once the pandemic has subsided.
CIRSE had to pull together a comprehensive resource centre very quickly. How did this come about? What needed to be prioritised, and how did you identify key stakeholders to work with?
In an effort to offer a concise and useful information hub amidst the myriad of online content on the pandemic, the CIRSE publications department has put together a collection of the most relevant links. These include the main stakeholders on an international scale, such as the World Health Organisation and the European Centre for Disease Prevention and Control, as well as articles, webinars, and checklists of particular relevance to interventional radiologists. Many thanks go to the CIRSE team. They really did an excellent job in putting all this together in such a short period of time.
In general, I think the internet is one of the big advantages we have during this pandemic and compared to past outbreaks. Even in comparison to SARS in 2002/2003, today it is so much easier for medical professionals to quickly share information and their experiences with colleagues from around the globe.
Is there a COVID-19 learning you wish to share with the interventional community?
I can only report on my own experiences in Strasbourg. The first major impact of the COVID-19 crisis was the cancellation of many elective interventions. Unfortunately, among the procedures that were classified as “not urgent” were many oncologic interventions, as well as benign pain management interventions. The delay in receiving their scheduled therapies is very stressful for patients and it will be important to start the interventional service again as soon as possible. I really admire how patients have reacted when learning that their therapies have been postponed. At the moment there is a lot of understanding and strong support for the medical community. However, it is not good to put them off from week to week and I hope that this situation will not persist for too long.
I think another important learning was that we are able, in a very short period of time, to change our work flows and patient pathways. Levels of safety and hygiene needed careful scrutiny and refinement to protect non-infected patients and hospital staff. Sadly, even with our immediate measures, it was impossible to avoid that some colleagues got infected and to my deepest regret a few colleagues even lost their lives.
I want to say that the medical and paramedical staff have been remarkable in this crisis, and I have the feeling that we are now even more united than before. In Strasbourg it seems that the peak has been reached and the situation is slowly starting to ease. However, we all know that this pandemic is far from over. We need to be careful not to provoke a second wave until medication, and hopefully a vaccination, against COVID-19 has been developed. Until that time, we will have to get used to our “new normal”.
Another important learning is that we need more of a European focus, not less. Europe, including the European Union (EU) and the leaders of its nation states, needs to prepare better for future pandemics. I think we must develop a Europe-wide contingency plan providing clear guidance on effective measures. Maybe there were good intentions from the EU leadership to introduce such a system after SARS in 2002/2003, but it seems that far too little was put into action. Among the many things that need improvement, I think, is that Europe should rebuild its infrastructure critical to the production of pharmaceuticals and medical equipment. This is essential, and would allow us to be independent and more proactive in the future.
What procedures are interventional radiologists still undertaking in this period?
In my experience, apart from the conventional emergencies such as bleeding, thrombectomies, or abscess drainages, we have of course also noticed more complications in the intensive care units related to COVID-19 patients with epistaxis or vascular damages.
In Strasbourg we also have seen an increase in thrombosis, but not necessarily in thrombectomy cases.
How has your personal daily practice been impacted by the pandemic? What measures has your hospital implemented?
Our department in Strasbourg has six operating rooms; three of them have been put out of function, with the removal of all anaesthesiologic devices and tools. We are fortunately still able to work in two angiography suites and one CT-angiography suite. Unfortunately, we have reduced collaboration with our colleagues from anaesthesiology. Outside of emergencies we currently receive their support only once a week. Additionally, all of our nurses have been assigned to other departments dealing with COVID-19 patients. Also, our medical staff has been temporarily reduced.
We are now preparing for the comeback and will be ready to catch up on the many postponed interventions once a regular IR service will again be possible.
What message would you like to give to the wider medical community at this time?
I think that the exchange of information is crucial. This is the first time that we have been confronted with a pandemic of this scale. We are gathering experience and seeing what works in real time, while at the same time having little to no data available on how exactly the virus works, and how it affects the body. We must therefore share all newly gained knowledge as quickly as possible. Each of us adding a piece of the puzzle on how to respond to and defeat this dreadful disease. It is a great challenge, but I am confident that we will get through this together, emerging stronger as physicians and a community.
Afshin Gangi is an interventional radiologist at the University Hospital of Strasbourg, Strasbourg, France, and is the president of the Cardiovascular and Interventional Radiological Society of Europe.
Medical oncologists Filippo Pietrantonio and Marina Chiara (both Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) have launched a social media campaign called #knowyourstatus to advocate for the “periodical and frequent testing” of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19, in healthcare workers treating patients with cancer.
“Our aim is to guarantee separate and ‘clean’ pathways for patients with cancer,” they write in the Journal of the American Medical Association (JAMA) Oncology. “Even if this objective is failing in front of our very eyes, we will not give up on maintaining the involvement of institutions, patients’ advocacy organisations, and oncologist associations.”
In an opinion piece chronicling the dawning realisation of the severity of the current pandemic in Italy, Pietrantonio and Chiara write: “At this moment, we feel unprotected. Although everyone in the newspapers is praising physicians as heroes, we feel alone, thrown into jeopardy, thrown into an abyss. Our region has left us to fight the cancer battle and the COVID-19 war without true protection, without knowing whether we are infected with the virus. We go to work every day because we love our jobs, and this is the life we have chosen. But we are people, too; we are afraid of getting infected, of going home in the evening, of infecting our children, our parents. […] We live with the absurdity of trying to cure patients of a disease like cancer at the same time potentially being the vehicles for a virus that might kill these very patients.”
They dwell on the lack of personal protective equipment (PPE) available to physicians, and the criticise the low level of testing of healthcare workers in northern Italy. “We were terrified after reading the recent reports on undocumented infections as a crucial source of contagion. We were terrified when we thought about models of transmission when applied to our daily lives here at the hospital. Unfortunately, during the past few days, we have been facing the terrific and very real effects of the lack of prevention of intra-hospital infections. In the Lombardy region, the epicentre of the outbreak in Italy, and in many other regions in Italy, asymptomatic or paucisymptomatic health care workers who had contact with patients confirmed to have COVID-19 are not routinely tested unless they develop severe symptoms. Individual protection devices are often lacking and cannot be used for intermediate-risk scenarios. Some of our colleagues have tested positive and are now at home or, even worse, hospitalised in intensive care units. Some of us have already infected entire families, children, grandparents.”
Describing the initial approach to cancer care at the onset of the pandemic in Italy, Pietrantonio and Chiara say that they had to determine the risk-benefit ratio of using intensified treatments and treatment combinations, maintenance strategies, and later-line treatments for each of their patients. These “hard-to-make decisions” were discussed in multidisciplinary team meetings held over video call, and then communicated with patients. “As physicians of a referral centre facing the lockdown of the whole country, we had to decide what to do for some patients with cancer already enrolled in clinical trials, and the patients who faced travel disruptions and the lack of flights from the south of Italy to our hospital in the north, and the fear these patients with cancer had of being infected with COVID-19 while traveling,” they say.
Their piece also captures the emotional toll the COVID-19 pandemic is taking on physicians in Italy. With frequent mention of the “terror”, “loneliness”, “fear”, and “anger”, Pietrantonio and Chiara recount: “We meet colleagues and patients and even laugh about funny stories, but it is clear to all of us that the level of stress and the risk of burnout that health care professionals are facing is alarming.”
They conclude, however, on a hopeful note, emphasising the importance of international unity in the face of a shared global crisis: “In this time of fear and anger, the most important thing is sharing. We have found ourselves united across borders. We have felt the love of so many people for us and for our country. How do we survive, then? With love for our patients, for our professions, and thanks to the sharing that has been created between us.”
In a brief report in Annals of Internal Medicine, Seongman Bae (Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea) and colleagues report that neither surgical nor cotton masks appear to be an effective approach for preventing the dissemination of SARS-CoV-2 from the coughs of patients with COVID-19. They add that further research is needed to determine the effectiveness of cotton and surgical masks in stopping the spread of the virus from asymptomatic or non-coughing patients.
Bae et al note that previous research has suggested that surgical masks may be equally as effective as N95 masks at preventing the dissemination of the influenza virus, so surgical masks could potentially be used as an alternative to N95 masks during the current pandemic. However, they add: “The SARS-CoV-2 pandemic has contributed to shortages of both N95 and surgical masks, and cotton masks have gained interest as a substitute.” Therefore, the aim of their study was to evaluate the effectiveness of both surgical and cotton masks in preventing the dissemination of virus particles.
The authors asked four COVID-19 patients, while in a negative pressure isolation room, to cough five times into a petri dish while not wearing a mask. They were then asked to repeat this process while wearing a surgical mask, and then again while wearing a cotton mask (each time coughing into a different petri dish). “Mask surfaces were swabbed with aseptic Dacron swabs in the following sequence: outer surface of surgical mask, inner surface of surgical mask, outer surface of cotton mask, and inner surface of cotton mask,” Bae et al explain.
They report that the median viral loads after coughs without a mask, with a surgical mask, and with a cotton mask were 2.56 log copies/mL, 2.42 log copies/mL, and 1.85 log copies/ml, respectively. Furthermore, regardless of the type of mask (surgical or cotton), all swabs on the outside of the mask tested positive for SARS-CoV-2, but most swabs on the inside did not. According to Bae et al, these findings suggest that surgical or cotton masks do not adequately filter SARS-CoV-2 during coughs by infected patients.
The authors comment that while the size and concentrations of SARS-CoV-2 in aerosols generated through coughing are unknown, SARS-CoV particles from the 2002–2004 epidemic were estimated to be 0.08 to 0.014μm in diameter. They explain that a previous study found that surgical masks did not provide adequate filter performance against aerosols measuring 0.9, 2, and 3.1μm. “Assuming that SARS-CoV-2 has a similar size [to the 2002–2004 outbreak], surgical masks are unlikely to effectively filter this virus,” Bae et al note.
As to why there was SARS-CoV-2 on the outer surface of the masks but not the inner surface, the authors speculate that this could relate to the “aerodynamic features” of the masks. “Alternatively, the small aerosols of SARS-CoV-2 generated through a high-velocity cough might penetrate the masks,” they say. Whatever the reason for the finding, Bae et al state: “These observations support the importance of hand hygiene after touching the outer surface of a mask.”
Looking to the future, the authors say that further studies are needed to review whether face masks “decrease transmission of virus from asymptomatic individuals or those with suspected COVID-19 who are not coughing”. Another unknown is whether masks shorten the distance of droplets during coughing.
Study author Sung-Han Kim (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) told Cardiovascular News that their findings did not mean that surgical or cotton had “no role” to play in stopping the spread of the virus. He explained: “Based on empirical evidence, masks might shorten the distance of aerosol containing virus and redirect the turbulent jets in less harmful directions (outward protection)—although the targeted studies using SARS-CoV-2 are unavailable. Furthermore, the inhaled air might have different aerodynamics in terms of low velocity particles with adherence of masks to face by depressurising. So, the ineffectiveness of outward protection of surgical or cotton masks in coughing COVID-19 patients do not mean ineffective inward protection of these masks. We recommend wearing any kind of masks in public settings with hand hygiene.”
Intact Vascular has received US Food and Drug Administration (FDA) approval for the Tack Endovascular System (4F), a novel, minimal metal implant for precision dissection repair in the mid/distal popliteal, tibial and/or peroneal arteries.
Regulatory approval was based on data from Intact Vascular’s Tack Optimised Balloon Angioplasty II BTK (TOBA II BTK) clinical trial, the first study to enrol patients with advanced disease below-the-knee and with 100% dissected vessels. The TOBA II BTK study enrolled patients suffering from critical limb-threatening ischemia (CLTI), a condition associated with high rates of amputation and mortality. Data from the trial were presented in a late-breaking scientific session at the 2019 Vascular and Interventional Advances conference (VIVA; 4–7 November 2019, Las Vegas, USA).
“Patients who have progressed to a CLTI diagnosis frequently endure debilitating pain, even at rest, infected foot ulcers, and are at an increased risk for amputation,” comments George Adams (UNC Rex Hospital, Raleigh, USA), co-principal investigator of the TOBA II BTK trial. “This is a complex patient population that historically had limited treatment options. The Tack implants deliver a much-needed solution that effectively restores blood flow, promotes healing, and preserves limbs.”
The prospective, multicentre, single-arm TOBA II BTK study met all primary endpoints with 100% acute dissection resolution and 73.8% of wounds healed or improved at six months. Results demonstrated 95.7% Kaplan-Meier amputation-free survival, 87.3% Kaplan-Meier target lesion patency with significant improvement in toe-brachial index, and 92% Kaplan-Meier freedom from clinically-driven reintervention.
Low-dose chest computed tomography (CT) has been an effective screening tool for COVID-19, writes Amir Davarpanah, outlining a novel screening and triage strategy successfully used in Iran to diagnose patients. “This strategy was valuable at the peak of the outbreak in Iran,” he says, “and added a new angle to the important role of radiologists and teleconsultation during a global health crisis”.
Healthcare systems across the world are facing a sudden surge in COVID-19 cases and thoracic radiologists are on the front-line of diagnosis in countries with limited supply of polymerase chain reaction (PCR) testing kits for definitive diagnosis. Due to the nature of the emergency in Iran at the peak of the outbreak and the reported low sensitivity and short supply of PCR testing, we temporarily used chest CT criteria of COVID-19 pneumonia as a surrogate for PCR testing. In our case study, published in the Journal of the American College of Radiology, we described the implementation of a novel triage strategy using humanitarian teleradiology service for the screening of symptomatic patients. The patients with early clinical and laboratory findings suspicious for COVID-19 underwent low-dose chest CT and categorised into two groups according to presence or absence of imaging features of viral lung infection.
Aiming to address the shortage of subspecialty-trained thoracic radiologists in Iran, we created a smartphone-based solution using a social media platform, WhatsApp, to provide expert interpretation of CT scans. Our goal was the early identification and isolation of infected patients to minimise disease transmission. Patients with CT finings suggestive of viral pneumonia were followed by PCR testing for confirmation and were isolated. Patients testing positive were transferred to designated hospitals. Patients with findings inconsistent with viral pneumonia on chest CT were treated according to alternative diagnosis and followed clinically.
Since radiographic findings of COVID-19 infection on chest CT are nonspecific and largely overlap with other viral infections, implementation of screening chest CT will result in a higher number of false-positive cases compared to PCR testing. Nonetheless, CT could be a valuable screening tool due to higher sensitivity, specifically in epidemic areas where there is a high pretest probability for disease. In addition, our priority was to identify the majority of suspicious cases and to use PCR testing in a more selective fashion to minimise resource drain.
Other important issues to consider are the cost and availability of CT scanners, the availability of thoracic radiology expertise, and the fact that at the time of crisis, referrals to major hospitals should be limited to decrease risk of exposure in the healthcare setting. A potential solution is using outpatient imaging centers and teleradiology, which eliminates the need to send patients to overpopulated hospitals and provides near-real time consultation from experts located around the world.
There are other certain downsides for using chest CT for triage, one of which is radiation exposure. We used low dose chest CT, which uses about 25–30% of regular chest CT dose, to minimise radiation exposure. Another concern for imaging centres is the possibility of becoming the new COVID-19 hot spots. In order to address this concern and limit the exposure of healthcare workers, employees, and patients, deep cleaning and disinfection of the room and scanner was performed after each patient, and staff wore personal protective equipment when handling these patients. The downside is the delay generated by the prolonged closure of CT scanning equipment for deep cleaning.
In spite of these limitations, this strategy has been valuable at the time of the outbreak in Iran, and has added a new angle to the important role of radiologists and teleconsultation during a global health crisis. The decision to implement a similar CT screening programme depends on the prevalence of infection in any given country or region, the availability of PCR testing, and the availability of CT scanners. Performing a cost-effectiveness analysis by regional healthcare authority is crucial before making the decision to use chest CT as a screening tool for COVID-19.
Amir H Davarpanah is an abdominal and cardiothoracic radiologist working in the Department of Radiology and Imaging Sciences at the Emory University School of Medicine, Atlanta, USA.
MedAlliance has announced enrolment of the first patient in the SAVE (Use of the Selution sirolimus-eluting balloon for dysfunctional AV access treatment indications) study utilising their novel sirolimus-eluting balloon, for the treatment of failed arteriovenous (AV) fistulae in renal dialysis patients.
The objectives of this prospective, randomised, single-blind multicentre study are to demonstrate the safety and efficacy of SELUTION SLR in the treatment of failed AV fistulae in patients undergoing renal dialysis. This study will also qualify for EU MDR approval.
Eighty-four subjects are being randomised to either SELUTION SLR or plain balloon angioplasty. To qualify for inclusion they must be aged 18–90, have a dialysis access that has performed at least one successful dialysis session, and a stenosis of more than 50% at the outflow vein.
“We are excited to study this novel sustained release of sirolimus in our dialysis patients with a malfunctioning fistula”, said Konstantinos Katsanos, consultant in Interventional Radiology at the University of Patras in Patras, Greece. “We truly look forward to the outcomes”.
The primary efficacy endpoint of the study will be primary patency of the treated lesion and of the treated circuit at six months post-intervention. The primary safety endpoint will be freedom from any serious adverse events involving the AV access circuit or the patient at 30 days.
“MedAlliance is honoured to initiate this important study with Dr Katsanos”, added chairman and CEO Jeffrey B Jump. “It will hopefully demonstrate extended life for AV Fistula patients around the world”.
SELUTION SLR’s technology involves unique Microreservoirs made from biodegradable polymer intermixed with the anti-restenotic drug sirolimus. These microreservoirs provide controlled and sustained release of the drug. Extended release of sirolimus from stents has been demonstrated highly efficacious in both coronary and peripheral vasculatures. MedAlliance’s proprietary CAT (Cell Adherent Technology) enables the microreservoirs to be coated onto balloons and adhered to the vessel lumen when delivered via an angioplasty balloon.
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) has made seven of ts Academy courses free to access online.
On its website, the society states: “While much of our regular routines have come to a halt as a result of the current crisis, your IR [interventional radiology] education should not have to. In an effort to support our community during these challenging times, CIRSE has now made seven CIRSE Academy courses free to access. This offer is only available for a limited time, so do not wait up! Find the courses that interest you, add them to your cart and check out—you will be enrolled at no cost!
“In addition, CIRSE has made more than 190 lectures from CIRSE congresses of the past year, including ECIO, ET, and CIRSE 2019 available free of charge.”
The seven online current courses currently available are:
Completing each course earns the participant CME (continuing medical education) credits.
In the midst of the COVID-19 pandemic, CIRSE and the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR) have jointly published a checklist for interventional radiologists to use when preparing their department for COVID-19 patients.
The Radiological Society of North America (RSNA) has launched a web page to help radiology professionals amid the ongoing COVID-19 outbreak.
The COVID-19 Resources webpage includes guidance, research, and a collection of images to help radiologists and other professionals. At time of publication, the page was last updated the page on 1 April, and the organisation will continue to post regular updates and advice.
The society state: “RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources.
“Stay in the know. Get COVID-19 updates sent directly to your inbox. We will send you the most important announcements and useful resources to help you manage the COVID-19 public health crisis.”
RSNA COVID-19 imaging data sharing survey
RSNA is also planning an open data repository “for international COVID-19 imaging research and education efforts”. In order to do this, the society has posted a form in its online resource centre where physicians can express their willingness to share their institution’s COVID-19 data for research purposed.
The society write at the start of the form: “The Radiological Society of North America (RSNA) has received numerous inquiries seeking access to COVID-19 related imaging data, both from radiology sites interested in sharing such data for use in research and education and from researchers.
“RSNA is committed to accelerating open source collaborative research on the uses of medical imaging in addressing the COVID-19 pandemic, including the use of new tools like artificial intelligence (AI). This form will enable institutions with COVID-19 data to express interest in participating in a planned open data repository for international COVID-19 imaging research and education efforts. Please complete this form if your institution has COVID-19 data that you may be willing and able to share for research purposes.
“Completing this brief survey does not represent a final commitment to collaborate with us or to share your data. RSNA staff will communicate directly with respondents in the next several days with further information about the next steps for organizations willing to participate in the RSNA COVID related research and education efforts.”
Organisations interested in participating are requested to respond to the survey by 15 April 2020.
Royal Philips has announced that the US government and Philips agreed to team up to increase the production of hospital ventilators in its manufacturing sites in the USA.
Philips plans to double the production by May 2020 and achieve a four-fold increase by the third quarter of 2020 for supply to the US and global markets. Such ventilators are critical for the treatment of patients with the new coronavirus disease (COVID-19). Philips will invest several tens of millions in its ventilator manufacturing sites in the USA.
“We are actively collaborating with the US government to help save lives in the USA and across the globe,” said Frans van Houten, CEO of Royal Philips. “There is an unprecedented global demand for medical equipment to help diagnose and treat patients with COVID-19. We welcome the support of the US government in our efforts to aggressively increase the production of hospital ventilators.”
He continued: “We believe in fair allocation of scarce medical equipment to those who need it the most, and we are ramping up to deliver 43,000 units to the most critical regions in the U.S. in the coming weeks and months through December 2020.”
In line with the recent call to action by the International Chamber of Commerce (ICC) and World Health Organization (WHO), Philips and the US government have agreed to work together to accelerate access to critical materials and components, expedite logistics and regulatory approvals, in order to rapidly increase the production of ventilators.
In the first three months of this year, Philips already delivered several thousand ventilators to US hospitals. As a result of its production ramp up, Philips was able to deliver an additional batch of ventilators to one of New York’s hospitals, to help provide immediate relief to the surge of COVID-19 patients within the city.
Philips believes that critical medical equipment, such as hospital ventilators, should be made available across the world using a fair and ethical approach to allocate supply to acute patient demands based on data such as the COVID-19 statistics per country/region (e.g. provided by the WHO and Johns Hopkins Coronavirus Resource Center) and the available critical care capacity. Philips may divide orders into batches to be delivered in phases, so that the company can simultaneously serve multiple countries/regions in need.
VIVA Physicians recently hosted a virtual roundtable to address COVID-19. Tony Das (Connected Cardiovascular Care Associates, Dallas and BSW Heart Hospital, Plano, USA), one of the VIVA Board Directors, lead the discussion, addressing topics such as resource management, triage, and telemedicine.
Das was joined by four other specialists—Niten Singh (University of Washington, Seattle, USA), Saher Sabri (MedStar Washington Hospital Center, Washington, DC, USA), Raghu Kolluri (OhioHealth Riverside Methodist Hospital, Columbus, USA), and John Rundback (Holy Name Medical Center, Teaneck, USA).
Das opened the virtual roundtable, available to watch on the VIVA Physicians website, by noting that Singh would have been one of the first to encounter COVID-19 in the USA in his centre in Seattle.
Singh went on to describe the fast-changing situation in the east coast city, noting that what is required is a “mentality change”. He noted in particular the importance of conserving resources. “In big systems, we all have to contribute,” he commented, pointing to the fact that elective vascular surgeries would have to be suspended so that enough resources would be available to cope with an increasing number of COVID-19 patients.
Singh also pointed to the issue of vascular patients being exposed to the virus whilst in hospital. “Our patients are generally in that age group where they are the most vulnerable to exposure and having a bad outcome with the contraction of COVID-19,” he remarked.
“Nobody stays in the hospital,” Singh added, elaborating that “if consultations can be managed telephonically, we do that.”
Singh also pointed out that, aside from clinical obligations, “fellows and residents still need teaching”. In this case, remote medicine is playing an important role.
Next to speak was Sabri, who mentioned that vascular surgeons and interventionalists are facing difficult decisions about who to treat and who not to treat, adding that “the triage process gets tighter” the more serious the COVID-19 situation becomes.
With regards to PPE [personal protective equipment], Sabri noted that, in his centre, they have started rationing their supply.
“We have to be vigilant,” said Sabri, urging fellow physicians to “think ahead”.
Raghu Kolluri (OhioHealth Riverside Methodist Hospital, Columbus, USA) was next to speak. He began by pointing out that his centre has not yet experienced a large number of cases but that they are expecting a surge in the near future.
The vascular lab “needs to be prepared,” he commented. He pointed out that it is a priority for him to be supportive of sonographers at this time—both from a triaging perspective and emotionally.
Last to speak was John Rundback (Holy Name Medical Center, Teaneck, USA), who is recovering from COVID-19.
He details that he likely contracted the virus in early March from a patient during regular office hours. “We have to assume we are getting infected by every patient walking in,” he said, adding that healthcare professionals are being “exposed in ways we cannot possibly anticipate”.
In terms of his practice, Rundback outlines that he has been “busy at home calling every single patient and triaging them appropriately,” stressing the importance of communication during this time, especially with elderly patients—making up the majority of vascular cases—who may have difficulty accessing telemedicine.
Rundback ended by emphasising that “CLI is not an elective thing,” noting that there are 300 amputations every day in the USA. “This is a serious matter.”
“The practice can adapt”
Das concluded the roundtable discussion on a positive note. “There is always good that comes out of these tragedies,” he began, elaborating that “untethering patients from hospitals and from offices is the reality of where this system is going”.
“The practice can adapt,” he continued. “This pandemic is creating an environment where I think everyone will say ‘I am not just going to do telemedicine right now, I am going to actually start to understand the infrastructure and the tools that are out there to be able to implement those in the future.’”
Considering the long-term impact of telemedicine, he gave the example that “CLI patients deserve more of a check-in than every six months”.
The newly established International Accreditation System for Interventional Oncology Services (IASIOS) gives medical facilities the opportunity to receive credentials for their interventional oncology (IO) service line. Developed by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), IASIOS focuses on the entire patient pathway, and as such has been heralded as a way of recognising that interventional oncologists are “clinicians, not just technicians”. Andreas ‘Andy’ Adam (Guy’s and St Thomas’ NHS Foundation Trust, London, UK) tells Interventional News that the project “will help establish IO as a mainstream clinical discipline, so is very important to IO as a whole”.
IASIOS is built on the standards outlined in the Standards of quality assurance in interventional oncology document, published in 2018 by CIRSE’s oncology alliance subcommittee, which is chaired by Adam. The idea of a global quality assurance scheme for IO goes back even further, to 2012, when radiation oncologist Lizbeth ‘Liz’ Kenny (Royal Brisbane and Women’s Hospital, Brisbane, Australia) delivered a talk at CIRSE’s annual congress on the interventional oncologist’s place in a multidisciplinary cancer care team.
Kenny emphasised the importance of recognising interventional oncologists as “clinicians, not just technicians”. She recalls: “I thought I was being very provocative, but CIRSE was very supportive. Since then [2012], I have been involved with the oncology alliance subcommittee, and have pushed the importance of standards of practice. In the world of radiation oncology, the stakes are very high, so quality assurance is built into every single step of all we do. I could see that with IO, we either needed to bring it into the mainstream, or it would disappear. IASIOS brings IO into the mainstream—by having a really serious quality assurance and standards programme underpinning the discipline, IO is in a great place to offer high benefit care to patients, and to fully integrate interventional oncologists into the multidisciplinary cancer care team.”
Establishing quality assurance standards in interventional oncology
In 2015, the CIRSE oncology alliance subcommittee—Adam, Kenny, Afshin Gangi (University Hospital Strasbourg, Strasbourg, France), Thierry de Baère (Institut Gustave Roussy, Villejuif, France), José Ignacio Bilbao (Clinica Universidad de Navarra, Pamplona, Spain), Thomas Helmberger (Klinikum Bogenhausen, Munich, Germany), Riccardo Lencioni (Pisa University School of Medicine, Pisa, Italy), and Philippe Pereira (Minimally Invasive Therapies and Nuclear Medicine Heilbronn, Heilbronn, Germany)—worked with interventional oncologist Shahzad Ilyas and former chief medical physicist Keith Ison (both Guy’s and St Thomas’ Hospital, London, UK) to adapt the Standards for Radiation Oncology developed and published by the Royal Australian and New Zealand College of Radiologists (RANZCR), the Australian Institute of Radiography, and the Australasian College of Physicists, Scientists and Engineers in Medicine. The group had to make these standards fit for purpose in the IO environment.
“This was a monumental effort,” Kenny describes. The standards went through 30 iterations over three years prior to publication. “The real complexity was to make the standards simple, understandable, and truly relevant to patients and care providers. This is not a tick box exercise. The standards describe what great care looks like, which then facilitates discussion between interventional oncologists and hospital management over necessary infrastructure, equipment, and patient pathways.”
Following the structure of the Australian and New Zealand Standards for Radiation Oncology, CIRSE’s Standards of Quality Assurance in Interventional Oncology document is split into three sections. These are: staff and facilities, treatment planning and delivery, and safety and quality. The IASIOS accreditation system is based on these standards. Between the three sections, there is a total of 52 criteria, 27 of which are “core”. After paying the enrolment fee, an institution can achieve accreditation if it meets all 27 core criteria. The IASIOS process is interactive: once an IO facility has applied for accreditation, a dialogue begins between it and the IASIOS team in the CIRSE office, which offers advice and guidance on how to improve the service, and is independent from the oncology alliance subcommittee. This conversation continues until accreditation is achieved. In exceptional cases, an institution may be awarded a “centre of excellence” accreditation if it fulfils the remaining 25 criteria.
Guy’s and St Thomas’ NHS Foundation Trust, London, UK, is the first in the world to be accredited through IASIOS. The centre gained accredited status in September 2019.
IASIOS is currently in a pilot phase, with eight centres across Europe, Asia, and Australasia enrolled in the programme to date. Two US centres are poised for potential future participation. CIRSE is working in collaboration with the Society of Interventional Oncology (SIO) to create a version of the IO standards appropriate to the pattern of practice in the USA.
While in this pilot phase of the programme, the IASIOS committee at CIRSE, chaired by Jean Palussière (l’Institut de cancérologie Bergonié, Bordeaux, France), is listening to feedback on the scheme from the enrolled institutions, and making any necessary modifications. Maria Weren, head of the department for certification and accreditation at CIRSE, expands: “I do not expect there to be too many changes at this stage. What I do foresee is some fine-tuning of our assessment process, and possibly to our application forms—so largely modifications to technical details. Any obstacles centres are repeatedly running into our expert group will of course also review.” The official, global launch of IASIOS is planned for early 2021.
Building a global IO network
Kenny is enthusiastic about the potential of the IASIOS scheme to build an international network of interventional oncologists. She tells this newspaper: “In due course, we anticipate building a network of centres that have achieved accreditation. I see this as ultimately an interconnected system of institutions offering support, encouragement, and advice for the betterment of all. IASIOS will uplift the whole of IO.”
There is no precedent for this type of international interconnectivity, Kenny explains: “There is no other movement that does what IASIOS does. The standards define the infrastructure, staffing, and safety requirements to bring IO into mainstream cancer care. If IO is to survive and flourish, it cannot just be a technical specialty under the direction of surgeons or medical and radiation oncologists. Interventional oncologists need to be considered a genuine partner in cancer care, and that is what IASIOS does.”
In Weren’s eyes, too, the IASIOS programme will bring increased recognition to the discipline, through giving interventional oncologists greater control of the entire patient pathway and a louder voice at interdisciplinary meetings. “IASIOS benefits not just patients, but also interventional oncologists,” she opines.
“It is an initiative by interventional oncologists, for interventional oncologists, because the standards look at the whole patient pathway. The standards will introduce systemic preprocedural assessment and patient follow-up by interventional oncologists, which I anticipate will provide greater visibility to IO. Interventional oncologists are ready to assume the role and responsibilities of a specialty, but they need to have a voice and they need to have a fixed place in the multidisciplinary cancer care team. This will enrich the discussion and widen the perspective for the patient.”
The European Commission (EC) has adopted a proposal to postpone by one year the date of application of the new Medical Devices Regulation (MDR), which was due to come into force on 26 May this year. The postponement, a press release reports, is to allow Member States, health institutions and economic operators to prioritise “the fight against the coronavirus pandemic”. As previously reported, the announcement follows the EC college (video) meeting on 25 March in which EC spokesperson Stefan de Keersmaecker stated that the commission were looking to delay the “entry into force” of the new MDR because of the global coronavirus pandemic.
According to the press release, the decision to delay “takes into account the unprecedented challenges of the coronavirus pandemic and the need for an increased availability of vitally important medical devices across the EU while continuing to ensure patient health and safety until the new legislation becomes applicable”. The proposal, therefore, delays the application of the MDR by one year (until 26 May 2021).
Additionally, the proposal also ensures that Member States and the Commission can address potential shortages of vitally important medical devices in the EU in a more effective manner through EU wide derogations. However, the press release notes that the proposal would need the full support of the European Parliament and the Council through an accelerated co-decision procedure.
Vice-president for Promoting our European Way of Life, Margaritis Schinas, says: “Shortages or delays in getting key medical devices certified and on the market are not an option right now. The Commission is, therefore, taking a pragmatic approach and delaying the entry into application of new EU rules on medical devices, so we can have our medical industries pouring all their energy into what we need them to be doing: helping fight the pandemic.”
Stella Kyriakides, commissioner for Health and Food Safety, adds: “Our priority is to support Member States to address the coronavirus crisis and protect public health as powerfully as possible—by all means necessary. Any potential market disruptions regarding the availability of safe and essential medical devices must and will be avoided.”
The Society of Interventional Radiology (SIR) has created a free online COVID-19 resource centre for physicians to access via their website.
The site states: “SIR has created this COVID-19 page to keep members apprised of interventional radiology (IR)-specific resources and information to help you, your practice, and your patients.
“Members are also encouraged to participate in the SIR Connect Open Forum for real-time sharing of knowledge, information and ideas among the IR community.”
The page is being continuously updated, but at time of publication includes two clinical notifications, a toolkit, webinars, and federal guidance.
The first clinical notification, effective from 18 March and updated on 19 March, lists SIR recommendations in response to statements from the Surgeon General and the Centers for Medicare and Medicaid Services (CMS) on elective surgeries as well as interim guidance from the Centers for Disease Control and Prevention (CDC).
The second clinical notification in the SIR resource centre, dated 26 March, provides medical decision-making guidance on how to perform aerosol-generating procedures (AGP) safely in the IR suite, following emerging data that indicates SARS-CoV-2 (the virus that causes COVID-19) is primarily spread via respiratory droplets produced when an infected person coughs or sneezes and has a “significant association with AGPs.”
If you have been affected or have any information, we’d like to hear from you. You can get in touch by emailing the editor at [email protected] and one of our journalists may contact you to discuss further.
This advertorial is sponsored by TriSalus Life Sciences.
NOTE: This article is intended only for healthcare professionals in the USA.
The Medicare Transitional Pass-Through Payment (TPT) programme is designed to foster innovation and increase access to cutting-edge treatments that benefit patients. The Centers for Medicare and Medicaid Services (CMS) believes the programme is important for hospitals to receive TPT payment for products that offer substantial clinical improvement. One goal of the programme is to target TPT payments for those devices where cost considerations might be most likely to interfere with Medicare patient access.
Patient access is at the heart of the TPT programme. CMS understands that relentless innovation is a crucial driver in creating value across all industries. Seema Verna, CMS administrator, remarks: “Innovation is the fuel that powers the engine of progress and creativity. […] We are committed to removing government barriers and modernising regulations around new technologies to ensure safe and effective treatments are readily accessible to beneficiaries without delaying patient care.”1
To facilitate beneficiary access to innovative medical devices, drugs, and biologicals, Congress established the TPT payment programme to prevent inadequate payment when used in an appropriate outpatient setting. CMS provides the TPT payment so as not to prevent use of new technologies due to cost concerns. The programme allows Medicare to collect data, and impacts CMS’ ability to establish appropriate permanent rates that are not described by existing categories. By addressing financial risk for outpatient facilities and mitigating the financial deterrent to innovative product utilisation, Medicare patients are more likely to gain access to new products through this programme.2
Historically, very few devices have qualified for TPT. In the last four years, only six device applications (out of 26) have been approved for the TPT programme. While TPT status has been in place for 20 years, only a very limited number of products have been approved because the programme requirements are so narrow. CMS reviews eligible device applications based on a demonstration of the following criteria:
TriNav™ Infusion System—one of five device TPT approvals granted this year
The TriNav Infusion System, which CMS approved TPT status for in November 2019, is the only TPT-approved device specifically designed for interventional radiology (IR) procedures. TriNav is designed to help overcome the infusion barriers that limit therapeutic uptake. In the Medicare hospital outpatient prospective payment system (OPPS) and ambulatory surgical center (ASC) payment system 2020 final rule, CMS stated that TriNav meets the criteria for device pass-through payment including newness, cost, and substantial clinical improvement. For those devices granted TPT status effective 1 January 2020, pass-through payments will mostly likely remain available until 31 December 2022.
A novel drug-delivery mechanism
Fundamental to TriNav is the Pressure-Enabled Drug Delivery™ (PEDD™) approach with SmartValve™ technology. To overcome pressure barriers that limit flow, PEDD with SmartValve creates a high-pressure gradient that improves delivery and penetration of therapeutic agents.3–7 The porous expandable SmartValve is a first-of-kind proprietary technology shown to modulate pressure and flow for optimal therapy delivery and deeper penetration into the vasculature while protecting heathy tissue.3, 5, 7
New HCPCS code information
Medicare’s transitional pass-through payment programme is designed to benefit patients who receive treatment with certain products in hospital outpatient departments (HOPDs) and ASCs. Medicare makes the additional TPT payment for devices where cost considerations might be most likely to interfere with patient access. It allows for CMS to collect necessary data and assign appropriate permanent codes and rates, paving the way for routine Medicare reimbursement later.
CMS assigned the TriNav Infusion System to the Health Care Common Procedure Coding System (HCPCS) code C1982 (catheter, pressure-generating, one-way valve, intermittently occlusive). When the device is used, CMS has stated it should always be billed with 37243 (vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumours, organ ischaemia, or infarction).
While most payers usually follow suit with Medicare B coverage policy, the reimbursement methodologies and amounts may vary. Facilities are encouraged to contact payers prior to using a product on TPT status to confirm coverage and reimbursement policies. For more information on TriNav, visit www.trinavinfusion.com, or call +1-888-321-5212.
None of the above statements are intended to imply a CMS endorsement of TriNav or any other product. The coding information provided is gathered from various resources, is general in nature, and is subject to change without notice. The provider is responsible for determining the appropriate health care setting and submitting accurate claims for products and services rendered. Providers should contact third-party payers for specific information on their coding, coverage, and payment policies. The TriNav Infusion System is available for sale in the USA. This product has not been approved for sale outside the USA. Contraindications: TriNav™ is not intended for use in the vasculature of the central nervous system (including the neurovasculature) or central circulatory system (including the coronary vasculature). Intended Use: The TriNav™ Infusion System is intended for use in angiographic procedures. It delivers radiopaque media and therapeutic agents to selected sites in the peripheral vascular system.9
References
1. Remarks of Centers for Medicare & Medicaid Services (CMS) Administrator Seema Verma to the Medical Device Manufacturers Association (MDMA) Annual Meeting (5/2/2019).
2. Gustafson, TA. ASC Focus. 2015 Sept:8-9.
3. Titano JJ, et al. Cardiovasc Intervent Radiol. 2019;42:560-568. * Study design: A retrospective, single-centre study included 88 treatment-naive patients with solitary HCC tumours <6.5cm who underwent treatment utilising either PEDD™ (n=18) or standard EH microcatheters (n=70). Twenty-three patients (five PEDD™, 18 EH) received a liver transplant during the study, with one PEDD™ and six EH patients excluded from the tumour necrosis analysis for receiving subsequent therapies prior to transplant. A pathologist performed a blinded review of the liver explant specimens to assess tumour necrosis and treatment distribution. Percentage necrosis was defined as the volume of necrotic areas divided by the total tumour volume.
4. Pasciak AS, et al. J Vasc Interv Radiol. 2015;26:660-669. *Study design: Sequential lobar infusion of 99mTc MAA in nine patients prior to 90Y treatment with PEDD™ and conventional microcatheter.
5. Durham ED, et al. J Vasc Interv Radiol. 2015;26:e54 (Poster 18).
6. Kim AY, et al. PloS One. 2017;12(9):e0183861. DOI: 10.1371/
journal.pone.0183861.
7. O’Hara R. Poster presented at: European Conference on Interventional Oncology (ECIO); April 22-25, 2018; Vienna, Austria.
8. Data on file (510K). TriSalus Life Sciences, 2019.
9. TriSalus TriNav™ Infusion System, Instructions for Use. None
In a new statement published on 2 April 2020, all 45 societies represented by the US Council of Medical Specialty Societies (CMSS)—over 800,000 physicians—emphatically declare their belief that all frontline healthcare professionals must have access to personal protective equipment (PPE) and be able to speak publicly about the lack of PPE without retribution while pushing for adequate supply and distribution.
This statement comes days after reports emerged in mainstream media outlets of threats made to hospital staff who have spoken publicly about the difficulties they are confronting on the frontlines of the COVID-19 pandemic. Among other cases, the story emerged of a Washington state emergency room physician who is said to have been fired after giving an interview to a newspaper on claims he had made about inadequate equipment and testing on his Facebook page, according to a report carried by Bloomberg News.
Susan E Sedory, executive director of the Society of Interventional Radiology (SIR), one of the 45 CMSS societies, says: “All physicians and health care professionals on the frontlines of the COVID-19 battle must be adequately protected to ensure they stay healthy and can continue to provide the care so urgently needed. Yet, the inadequate supply and distribution of PPE is magnifying the crisis here.
“Through CMSS, we can instead magnify the voice of nearly all of America’s specialty societies to send a clear and urgent message to policymakers and ensure that all frontline physician fighters have the protection they need. We are proud to advocate for interventional radiologists so they can continue to stay safe and care for patients in their communities.”
In full, the new CMSS statement reads:
“With more than 800,000 physicians across 45 specialties, the Council of Medical Specialty Societies (CMSS) strongly urges action to ensure safer working conditions for physicians and other healthcare professionals on the frontline of direct patient care.
“CMSS and its member societies believe that adequate personal protective equipment (PPE) should be a fundamental expectation for all frontline healthcare professionals:
“CMSS and its member societies urge federal, state and local authorities to ensure an adequate supply and distribution of PPE for every frontline healthcare professional in the United States. Physicians and other healthcare professionals can and should expect their institutions to provide appropriate means to limit occupational exposure.
“Physicians and other healthcare professionals should be allowed to bring their own PPE to protect themselves, colleagues, and patients when these items are in short supply at their institutions. CMSS supports the Joint Commission statement allowing the use of private PPE, but this option does not obviate an institution’s responsibility to provide adequate PPE to all healthcare personnel.
“The United States needs a simple, uniform mechanism for all healthcare facilities to report their PPE needs and other medical supply needs to help guide optimal distribution of supplies across the country.
“Physicians and other healthcare professionals should not be at risk of having their employment terminated, or be otherwise disciplined, for speaking out, within their health care systems or publicly, on conditions and practices related to care of COVID-19 patients (including lack of PPE) that the physician and other healthcare professional has direct knowledge of and deems to be in conflict with the health and safety of patients, themselves, and others involved in providing care to patients.
“CMSS supports the American Medical Association (AMA) statement that “no employer should restrict physicians’ freedom to advocate for the best interest of their patients.” Physicians and other healthcare professionals may appropriately decide that going public (including to the news media and on social media) with their concerns is necessary to achieve needed change for the health and safety of patients and clinicians, both within the healthcare facility and more broadly.”
Full list of CMSS societies
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The European Society of Radiology (ESR) has created a playlist on their YouTube channel dedicated to events and news related to the COVID-19 pandemic.
Currently, the playlist offers three videos. The first is a special report about radiology’s role in fighting the virus. Nicola Sverzellati (University of Parma, Parma, Italy) shares his experiences of working with patients and image management in Europe’s most affected area. He also discusses the challenges Italian radiology departments face and the diagnostic flowchart his team has developed since the outbreak.
The second video showcases geneticist and immunologist Josef Penninger (Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria), who discusses angiotensin-converting enzyme 2 (ACE2) as a potential treatment for the disease, as well as its relationship to the renin-angiotensin system (RAS) in instances of lung injury.
The third video again features Sverzellati, as well as Francesco Sardanelli (University of Milan, Milan, Italy). The two discuss the ongoing Italian response to the pandemic, and, chaired by Adrian Brady (Mercy University Hospital, Cork, Ireland), answer questions posed by audience members from the previous two broadcasts on the myecr YouTube channel.
If you have been affected or have any information, we’d like to hear from you. You can get in touch by emailing the editor at [email protected] and one of our journalists may contact you to discuss further.
The Society of NeuroInterventional Surgery (SNIS) has published a set of recommendations for the care of emergent neurointerventional patients during the COVID-19 pandemic.
“Acute ischaemic stroke patients are a high-risk patient cohort,” the authors write, adding that patients with a history of ischaemic stroke and/or its risk factors are “particularly at risk” for the severe form of the coronavirus. The recommendations also acknowledge evidence that the disease can cause neurological signs, which have been reported in the brains of humans and in animal models.
Pointing to a study documenting neurological manifestations of hospitalised patients with COVID-19 in Wuhan, China, the society writes: “36.4% of SARS-CoV-2 [severe-acute respiratory syndrome-coronavirus 2] respiratory distress patients demonstrated neurological symptoms, with 4.5% of severe patients suffering ischaemic stroke.”
Given this evidence, the SNIS recommendations state that in this setting, neurointerventionalists should expect to be involved in the care of COVID-19-positive patients, as well as those whose status is unknown.
The document specifically advises on the criteria for mechanical thrombectomy: “The presence of COVID-19 as a public health issue should not alter the inclusion and exclusion criteria for mechanical thrombectomy […] denial of this treatment likely creates a greater drain on healthcare resources.”
However, the authors urge that maximum safety precautions should be taken when a patient with COVID-19 positive documentation requires treatment. If a patient’s COVID status is unknown, SNIS recommends that patients be treated as high risk for COVID-positive, provided institutional resources are available.
The document also details guidance on post-thrombectomy principals during the pandemic. The society recommends transferring uncomplicated post-thrombectomy patient’s out of the intensive care unit (ICU) “as soon as possible”, to maximise availability of ICU beds. Further, it advocates for COVID-19 testing of all acute ischaemic stroke patients on admission, if available, to allow preservation of personal protective equipment (PPE), and to “separate true COVID-19 positive patients to prevent nosocomial transmission.”
Due to how the cleaning of angiography equipment and suites will impact on the readiness of additional cases, SNIS advises that elective and non-urgent cerebrovascular cases be postponed until the pandemic’s peak has been reduced. Lastly, the society encourages the shift-based allocation of staff and physicians, to separate individuals with overlapping skillsets.
Given the number of identified COVID-19 patients is expected to increase, the authors underline the importance of safe delivery of care for both patients and providers. “If we fail to protect physicians, nursing staff, and ancillary providers, we will fail to meet the needs of future patients.
“The successful care of future COVID-19 patients will depend on the effective safety and prevention strategies for healthcare workers.”
As the COVID-19 pandemic continues to unfold, SNIS will consider revisiting these recommendations to match up-to-date information. Any such revisions will be provided as updates on the SNIS web page, the society advised.
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Michael Dake (University of Arizona Health Sciences, Tucson, USA) has become the new president of the Society of Interventional Radiology (SIR).
He officially assumed his new responsibilities after the annual members’ business meeting of the society, which was held this year via a webinar. Other officers of SIR’s 2020-2021 executive council include:
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR) have jointly published a checklist for interventional radiologists to use when preparing their department for COVID-19 patients.
The full checklist, as well as other COVID-19 resources collated by CIRSE, is available here.
First author Bien Soo Tan (Singapore General Hospital, Singapore) and colleagues from South Korea, France, Switzerland, the UK, Germany, and New Zealand write: “The primary consideration in preparing the IR [interventional radiology] service for COVID-19 is prevention of intra hospital transmission so as to protect patients and health care workers from being contaminated or infected, while providing safe IR care for patients.”
Addressing the international IR community, CIRSE president Afshin Gangi stressed the importance of a rapid and coordinated IR response to the current coronavirus outbreak. He said: “The spreading COVID-19 pandemic has forced all of us to adjust to a new reality. While IR departments are trying to delay most non-emergency procedures until after the crisis, some interventions cannot be postponed. It is therefore adamant for interventional radiologists to adapt their departments accordingly, from the set-up of a COVID-19 task force to implementing infection prevention protocols and dedicated workflows.
“I am convinced that weathering this storm can only be done together, and when it has finally subsided, we will be stronger for it, as physicians, individuals and as a community.”
Outline of checklist
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The American College of Surgeons (ACS) today leapt to the defense of healthcare workers who are heading to work in the face of increasing concerns over personal protective equipment (PPE) shortages as the COVID-19 pandemic cuts trails across the country.
The association released a statement in support of stretched surgeons, nurses and other key medical personnel as reports emerged in mainstream media outlets of threats made to staff who speak publicly about the difficulties they are confronting on the frontlines.
Among other cases, the story emerged of a Washington state emergency room physician who is said to have been fired after giving an interview to a newspaper on claims he’d made about inadequate equipment and testing on his Facebook page, according to a report carried by Bloomberg News.
The ACS outlined the picture confronting the medical field at large: Many healthcare facilities, it said, face shortages in PPE, including face masks, gowns and respirators.
However, the College’s statement went on to say: “The ACS believes it is essential that surgeons, nurses, anesthesiologists, and other healthcare personnel be able to speak freely, without fear of retribution, as they seek to find a solution to accessing PPE.
“We advise surgeons to speak with their institutional leadership on these matters and to be able to direct any concerns to the ACS, with the goal of protecting themselves and their colleagues.”
The ACS pointed out that the Joint Commission—which accredits and certifies more than 22,000 healthcare organisations and programs in the United States, including hospitals—had released a statement supporting the use of face masks and respirators provided from home when facilities are not able to provide access to PPE that matches the risk surrounding healthcare workers amid the COVID-19 pandemic.
The Joint Commission stepped forward with its statement yesterday, saying: “The Joint Commission supports allowing staff to bring their own standard face masks or respirators to wear at work when their healthcare organisations cannot routinely provide access to protective equipment that is commensurate with the risk to which they are exposed.”
Meanwhile, the ACS continued: “Where masks or respirators are recommended, the ACS maintains that surgeons should have access to and latitude to wear these masks at their sole discretion. The Centers for Disease Control and Prevention (CDC) also has released a document that offers a series of strategies or options to optimise supplies of disposable N95 filtering facepiece respirators.
“The ACS strongly supports the ability of surgeons to use their own masks or PPE, but this option does not obviate the hospital’s responsibility to provide adequate PPE to all their health care workers. In these extraordinary times, the ACS encourages institutions to adapt and be flexible so that health care personnel continue to feel safe; the Joint Commission guidelines are a reasonable starting point.”
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This piece is one in a series of articles covering the GEST webinar. For dispatches from the frontlines of the COVID-19 pandemic, and the pertinent takeaways for interventional radiologists, click here.
“What have we learnt in the last month? We have to try to reduce or stop our activity—in the beginning, we thought we could continue to work as in standard life, but we realised that there is a high risk of infection, as the patient or operator could be a virus carrier. You have to really reduce your activity to only emergency cases.” So said Roberto Iezzi (Catholic University A Gemelli Hospital, Rome, Italy), speaking during the GEST (Global Embolization Oncology Technologies Symposium)-hosted webinar on 25 March, where an international group of interventional radiologists discussed the global response to the COVID-19 pandemic.
The first cluster of coronavirus patients was reported in Lombardy, a region of northern Italy, on 21 February. “It is just one month ago, but it feels like a year”, Iezzi stated. Sharing the key takeaways from the last five weeks’ experience, Iezzi summarised:
Speaking specifically of his institution, the Catholic University A Gemelli Hospital in Rome, Iezzi described the changes made to its usual running. “With COVID, everything changed,” he said.
On 9 March, all IR cases were stopped, except for emergency cases or a few oncological treatments for patients that could not wait until the present pandemic passes. This freed up beds for potential COVID-19 patients, and reduced the risk of infection. In total, the A Gemelli Hospital now has six dedicated COVID-19 wards, one dedicated resuscitation ward, and three wards specifically for suspected COVID-19 patients. A smaller hospital nearby was translated into a COVID-19 only hospital, with 59 beds in its intensive care unit, and a further 80 standard beds.
“We should be ready for COVID patients,” Iezzi said of interventional radiologists, “because we know that COVID patients are [generally] older patients with multiple comorbidities, and they may need interventional treatment, such as a drainage.”
In order to limit the risk of infection, the nine interventional radiologists based at the A Gemelli Hospital (five neuro specialists and four “body” specialists) significantly reduced their case load. Two of the three angiosuites remain open: one is dedicated solely for COVID-19 patients, and the other is open for just six hours a day, the remaining 18 hours of each day being on-call. Usually, Iezzi’s institution has three slots a week for CT-guided procedures and two slots a week for ultrasound (US)-guided procedures; this is now down to one slot a week for CT-guided activity, and no dedicated slot for US-guided activity.
In addition, visitors, students, and external colleagues and specialists have been denied access to the hospital, to limit the number of people present. Operators also have reduced access: at any moment, one operator is on-call, and one is taking up an “active slot” in the hospital scheduling. Residents are only granted access to the IR section of the hospital if needed, and patients are being offered video consultations to limit person-to-person contact.
“We tried to determine which transport routes [to use] in the hospital to minimise exposure for staff and other patients,” Iezzi shared. This measure was also taken by healthcare workers in Singapore.
Furthermore, Iezzi recommended implementing additional precautions. “All patients should wear a medical mask,” he advised, “and for COVID-positive or COVID-suspected patients, try to avoid moving and transporting them out of their room or area. Where possible, you should perform bedside US-guided procedures.
“If we have to use general anaesthesia, for example when performing a stroke thrombectomy, we try to perform induction outside the angiosuite in order to reduce the risk for airborne contamination,” he continued. “We try to avoid or reduce waiting time in preoperative holding areas. It is also very important that we use adequate personal protective equipment (PPE).”
However, he said “there is an issue”, in Italy and in other European countries, notably Spain, with access to adequate PPE. Therefore, Iezzi highlighted the importance of setting up robust guidelines for when PPE is necessary, so as not to waste any protective gear. He recommended stratifying patients based on risk when deciding on what qualifies as appropriate PPE. Low risk patients are defined as those with no fever or respiratory tract symptoms, no loose contact with confirmed or suspected cases of COVID-19, and no residence in or travel to areas or attendance at events where widespread community transmission has been reported. Intermediate risk patients are those with fever and/or respiratory symptoms, but with no close contact with a confirmed or suspected case of COVID-19, and with no residence in or travel to areas or attendance at events where widespread community transmission has been reported. High risk patients have a fever and/or respiratory tract symptoms, and in the past 14 days have either been in close contact with a confirmed COVID-19 sufferer, and/or have lived in, travelled to, or attended an event where widespread community transmission has been reported.
Regardless of risk, Iezzi strongly advised that all patients wear a disposable surgical mask. Physicians should wear PPE appropriate for “contact and droplet precaution” when dealing with low risk patients, and PPE appropriate for “airborne precaution” when treating intermediate or high risk patients (see table 1).
Additionally, Iezzi recommended keeping doors closed when treating suspected or positive COVID-19 patients to reduce the potential for cross-contamination. Similarly, he urged those listening to adjust the team organisation in their own institutions when working with coronavirus patients. “We as interventional radiologists, our problem is devices,” he explained. “We need different devices, and we cannot have everything in the room [at the same time]. So we have a nurse in the room with three pairs of gloves in order to remove one, give the device to the interventional radiologist without touching it, and another nurse is outside. If we need something that we do not have in, they can bring it near the door to the angiosuite. The nurse inside can put on a new pair of gloves and can pick up the device, not touching anything else. This is very important.”
At the end of a procedure, any equipment in the angiosuite must be cleaned and disinfected, Iezzi explained, adding that the doors should remain closed during cleaning. “The IR area should then remain closed for 30 minutes,” he said.
Globally, Italy has experienced the highest death toll due to the coronavirus pandemic. On 9 March, the Italian government implemented a nation-wide quarantine, and on 21 March, they imposed a “significant lockdown” on the country, forcing the shut-down of all businesses and industries deemed “not necessary”.
If you have been affected or have any information, we’d like to hear from you. You can get in touch by emailing the editor at [email protected] and one of our journalists may contact you to discuss further.
This is the first in a series of articles covering the GEST webinar. For dispatches from the frontlines of the COVID-19 pandemic, and the pertinent takeaways for interventional radiologists, click here.
Interventional radiologists must play their part in protecting patients and healthcare workers during the coronavirus pandemic, urge physicians fighting the COVID-19 outbreak in Singapore. Speaking in a webinar hosted by GEST (Global Embolization Oncology Symposium Technologies) on 25 March, Kiang Hiong Tay (Singapore General Hospital, Singapore) told the over 500 virtual attendees: “COVID-19 has exploded around the world. It took 67 days to reach the first 100,000 patients, but the last 100,000 were diagnosed in just the last two days. Europe is now the epicentre. In Italy and Spain, the death toll has exceeded that of China, and I think very soon, the USA will be the next epicentre for the epidemic.”
Singapore is no stranger to viral outbreaks. The 2003 epidemic of severe acute respiratory syndrome (SARS) had a disproportionately high mortality rate in the country compared to the worldwide average, with 14% of the 238 cases proving fatal. Recalling this experience, Tay said he believe it has led to the healthcare service in Singapore being relatively well-prepared for the current eruption in coronavirus cases, commenting: “For many years after SARS, our country has been slowly building up capacity to address big outbreaks such as this.”
He said that “the key principle is to try and prevent hospital transmission: you want to prevent cross transmission between different groups of people, and the way to do this is strict adherence to infection prevention measures. Social distance is another important strategy, especially in preventing healthcare [worker] to healthcare [worker] transmission.”
The crucial takeaways from his experience preventing viral transmission in Singapore that Tay wishes to impress on the international physician community are summarised below:
Protect patients
Protect staff
Prevent cross-transmission
Detailed workflow for COVID-19 patients
Chow Wei Too (Singapore General Hospital, Singapore) next talked listeners through the workflow for COVID-19 patients. “The objective is to provide vascular IR care for COVID-19 patients, whether they are suspected or confirmed, while practicing the highest level of infection control.
“We want to be part of the solution, and really not part of the problem,” he said, referencing an article published in Bloomberg where surgeons operating on patients without proper protection or testing was in part responsible for the rising death toll amongst physicians in Italy. He directed listeners to the Singaporean Ministry of Health website, where a 2017 document outlines the national infection prevention and control guidelines for acute healthcare facilities. The World Health Organisation (WHO) also have a document outlining the five “moments” when physicians should wash their hands. “This is also very important,” Too stressed.
Like Tay, Too mentioned the importance of minimising the movement of patients. Physicians seeing their patients at the bedside “is best”, he said, and if this is not possible, “we go to a designated operating theatre, which we share with other procedures, where we are guided by a C-arm, and for procedures like stroke [thrombectomy] or other things that involve CT scanning, we go to the IR centre”.
Bedside procedure
“For all of our procedures, we put up charts of who is involved, and we label them [extensively], so every staff member knows what to do,” Tay informed his listeners. He showcased an example of a procedure sheet, which included columns for staff members’ initials, the staff needed (for example controller and scrub nurse), the role they would play (for example “maintains command and control of the entire event and to coordinate with various external parties” and “scrubs for procedure”), the attire necessary (such as “N95/ eye protection” or “Full PPE”), and any additional remarks (such as “Walkie Talkie in breast pocket” or “Stays at corridor”). Staff are also given a schematic diagram of the procedure, for clarity.
Between the corridor and the isolation room or intensive care unit, where the patient is, there is an anteroom or air-locked lobby, which provides a barrier against loss of pressurisation, and allows for the transfer of equipment and staff, as well as the removal of PPE.
The workflow is as follows:
Interventional radiology suite procedure
Tay talks through a stroke thrombectomy procedure at the Singapore General Hospital for a suspected COVID-19 patient.
“The staffing here is a lot more elaborate,” he recounted. “We want separation of the procedural and the support teams. Reduce multi-tasking and assign clear roles for individuals. Very important here is the role of the controller. We found that with the creation of this role, of a controller, everyone is much calmer and much happier.”
The second floor of Singapore General Hospital, which is the IR centre, has been divided into seven suites operating across two levels. The hospital has set up a specific PPE removal and donning area, and has a clear traffic control policy in its corridors. A traffic nurse is in charge of directing people between rooms.
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The Imperial College Network of Excellence in Vascular Science at Imperial College London (UK) is to run a COVID-19 Cardiovascular Conference as a live webinar on Thursday 2 April for all healthcare professionals battling COVID-19.
The webinar aims to share current knowledge and key experiences of managing COVID-19 related cardiovascular manifestations, as well as critical issues in team preparedness, prevention, and command and control. Among the topics to be covered are:
Included among the presentations are Ajay Kirtane (Columbia University Irving Medical Centre/NewYork-Presbyterian Hospital, New York, USA) discussing his experience from New York, and Richard Schilling (St Bartholomew’s and the Royal London NHS Trust, London UK) sharing details of the establishment of an emergency field hospital, the Nightingale Excel, in London’s docklands. Other highlights are Simon Ray from the British Cardiology Society, who will outline a UK perspective on safe working in cardiology, and Sukh Nijjer and Ahran Arnold looking at IT measures to reduce COVID-19 infections.
The webinar will run from 14.00–18.00 BST.
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The American Board of Radiology (ABR) has announced that its Core Exam for diagnostic radiology (DR) and interventional radiology (IR/DR) will be held in November.
The ABR originally had the Core Exam scheduled for May and June, but it was forced to postpone the tests due to the novel coronavirus outbreak. The new dates for the DR and IR/DR exams will be 5–6 November and 9–10 November, respectively, in Chicago and Tucson, USA. Eligible candidates for the exam will receive invitations no later than 24 August.
At the same time, the ABR said it is making progress toward scheduling the Medical Physics and Radiation Oncology oral exams in Tucson, USA. The organisation has identified new dates and is waiting for confirmation from the hotel where the exams will take place.
The American Board of Radiology also said the Medical Physics and Radiation Oncology initial qualifying exams are scheduled to take place as planned in July and August.
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“More bleeding with background clopidogrel, even if not severe by adjudication, may be associated with broad consequences, including discontinuation of therapies. In the absence of clear benefit, clopidogrel exposure along with aspirin and rivaroxaban should be minimised or avoided to reduce this risk,” concluded William R Hiatt (University of Colorado Anschutz School of Medicine, Aurora, USA), presenting a subgroup analysis of the VOYAGER-PAD trial during the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual)—originally scheduled to take place on 28–30 March in Chicago, USA.
Hiatt detailed that VOYAGER-PAD aimed to assess the benefit and risk of rivaroxaban plus aspirin in patients with peripheral arterial disease (PAD) after lower extremity revascularisation with and without concomitant clopidogrel.
This subgroup analysis evaluated further the efficacy and safety of concomitant clopidogrel use at baseline. More specifically, the investigators aimed to determine if, in symptomatic PAD patients undergoing lower extremity revascularisation randomised to rivaroxaban 2.5mg twice daily with aspirin versus aspirin alone, the efficacy and safety of rivaroxaban were consistent regardless of background clopidogrel use, and to explore temporal patterns of bleeding in relation to exposure and duration of clopidogrel.
Hiatt said: “In patients with symptomatic PAD undergoing revascularisation, the benefit of dual antiplatelet therapy (DAPT) is uncertain, with the only randomised controlled trial in surgical bypass showing no benefit and significantly increasing bleeding.”
He continued: “Rivaroxaban added to aspirin significantly reduces limb and cardiovascular risk with consistent benefits regardless of clopidogrel; the safety and risk/benefit of rivaroxaban plus aspirin are consistent regardless of background clopidogrel; and, in patients receiving rivaroxaban, the addition of clopidogrel as a third agent, is associated with higher rates of bleeding during exposure”.
Background
The VOYAGER-PAD trial found that treatment with aspirin plus rivaroxaban following lower extremity revascularisation in patients with peripheral arterial disease (PAD) leads to a 15% reduction in the risk of major adverse limb and cardiovascular events when compared with aspirin alone. This conclusion was presented yesterday at ACC.20/WCC Virtual by Marc Bonaca (University of Colorado Anschutz School of Medicine) and simultaneously published in the New England Journal of Medicine (NEJM).
The trial found that a twice daily dose of 2.5mg rivaroxaban plus low dose aspirin is associated with significantly lower incidence of the composite primary efficacy outcome of acute limb ischaemia, major vascular amputation, myocardial infarction, ischaemic stroke, or death from cardiovascular causes than aspirin alone.
On the principal safety outcome of Thrombolysis in Myocardial Infarction (TIMI) major bleeding there was no significant difference between the therapies. However, rivaroxaban plus aspirin was associated with a significantly higher incidence for the secondary safety outcome of International Society on Thrombosis and Haemostasis (ISTH) major bleeding.
A total of 6,564 patients were randomised into VOYAGER-PAD and followed for a median of approximately three years with complete accrual of primary events through September 2019.
Three months after undergoing renal denervation, patients with untreated high blood pressure had statistically significant reductions in average blood pressure over 24 hours compared with patients who underwent a sham procedure according to results from the SPYRAL-HTN OFF MED pivotal trial presented at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual).
Further, these patients experienced no major device- or procedure-related safety events through three months, data from an international, prospective, single-blinded, sham-controlled trial that enrolled at 46 global study sites shows. The findings were also published online on 29 March in The Lancet.
The SPYRAL HTN-OFF MED pivotal trial builds upon a previous pilot study and is powered to evaluate the efficacy of catheter-based renal denervation in the absence of medications. “These results show that renal denervation offers an effective alternative approach to traditional medications that require patient adherence for reducing blood pressure,” comments Michael Böhm (Saarland University Medical Center, Hamburg, Germany) and lead author of the study, in a press release from the ACC.
“Furthermore, the findings show that renal denervation lowers blood pressure not just during the day but also through the night and [in the] early morning periods when risk is highest for [adverse] clinical events and the effect of some medications on blood pressure is reduced,” Bohm adds.
Böhm and colleagues report in The Lancet: “Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications.”
The study enrolled 331 patients whose average systolic blood pressure over 24 hours was between 140 and 170mmHg. Their average age was 53 years, and 67% were men. Most had obesity, with an average body mass index of 31. Around 5% also had type 2 diabetes. A condition of enrolment was that patients either had not been taking any blood pressure-reducing medications or had discontinued those medications at least three weeks before their blood pressure was measured at study entry.
Patients were randomly assigned to receive either renal denervation or a sham procedure in which a catheter was inserted and only an angiography was performed. A total of 166 patients were assigned to renal denervation and 165 to the sham procedure.
At the end of three months, the primary efficacy endpoint was the change in average 24-hour systolic blood pressure, adjusted for systolic blood pressure at study entry. The secondary efficacy endpoint was the change in average blood pressure measured in the doctor’s office at three months, adjusted for office blood pressure at study entry. Major adverse safety events were also assessed at three months, including rates of death, stroke, changes in kidney function or any injury to the arteries surrounding the kidney.
For the primary and secondary efficacy endpoints, the difference between groups was –3.9mmHg for 24-hour systolic blood pressure and –6.5mmHg for office systolic blood pressure, both favouring the renal denervation group, with a 99.9% probability that renal denervation was superior to the sham procedure.
No deaths, strokes or changes in kidney function occurred during the three-month follow-up period, Böhm says. He added that these results may not demonstrate the total decrease in blood pressure achieved with renal denervation given the short follow-up period due to ethical and safety concerns that patients needed to be restarted on antihypertensive medications. In other studies of renal denervation, however, patients’ blood pressure has continued to decline at six months or more after the procedure, he states.
“This study establishes renal denervation as an additional option beyond exercise or lifestyle modification for patients with high blood pressure who are unwilling to take or cannot tolerate medication,” Böhm says, adding that the study results will be included in an application for FDA approval of the renal denervation device used in the trial for the treatment of patients who are not taking blood pressure-reducing medication. Currently there are no renal denervation devices approved for use in the USA.
Results from a companion study, the SPYRAL-HTN ON MED trial, which is testing the safety and effectiveness of renal denervation in patients who are taking up to three blood pressure-reducing medications, are expected in about 18 months. The results of that study will also be included in the application for FDA approval of the renal denervation device, Böhm said.
In stable atherosclerosis, a combination of aspirin plus rivaroxaban provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral endpoints in patients with and without diabetes, a prespecified analysis of the COMPASS trial has shown. It also noted that, given their higher baseline risk, the absolute benefits appeared greater in those with diabetes, including a three-fold greater reduction in all-cause mortality.
The findings were outlined in a virtual presentation by Deepak L Bhatt (Brigham and Women’s Hospital Heart and Vascular Center, and Harvard Medical School, Boston, USA) at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual) which was originally scheduled to take place 28–30 March in Chicago, USA. The data were also simultaneously published online in Circulation.
“Diabetes with atherosclerosis either with or without ischaemic events is associated with an extremely high rate of cardiovascular death, myocardial infarction or stroke over just four years. One potential way to address this cardiovascular risk, this residual risk, is with dual pathway inhibition—that is, combining antiplatelet therapy with anticoagulation,” Bhatt explained on a video link. “This concept was tested in the COMPASS trial.”
The main COMPASS (Cardiovascular outcomes for people using anticoagulation strategies) trial demonstrated that aspirin plus rivaroxaban 2.5mg twice daily was superior to aspirin plus rivaroxaban placebo in reducing ischaemic events in 27,395 patients with coronary artery disease (CAD) and/or peripheral arterial disease (PAD). The study found a significant reduction in cardiovascular death with dual pathway inhibition, as well as lower all-cause mortality.
In the present prespecified analysis of COMPASS, investigators analysed the results of rivaroxaban plus aspirin versus aspirin alone in the subgroups of patients with or without diabetes mellitus at baseline.
The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction , or stroke. Secondary endpoints included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events including amputation). The primary safety endpoint was a modification of the International Society on Thrombosis and Haemostasis (ISTH) criteria for major bleeding. There was also a prespecified net clinical benefit of cardiovascular death, myocardial infarction, stroke, fatal bleeding, and symptomatic bleeding into a critical organ.
In the overall trial, there were 10,341 patients with diabetes and 17,054 without diabetes. The COMPASS diabetes subanalysis found a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin (n=9,152) versus placebo plus aspirin (n=9,126) in patients both with (n=6,922) and without (n=11,356) diabetes for the primary efficacy endpoint (hazard ratio [HR] 0.74, p=0.002, and HR 0.77, p=0.005, respectively, pinteraction=0.77) and all-cause mortality (HR 0.81, p=0.05 and HR 0.84, p=0.09, respectively, pinteraction=0.82). Although the absolute risk reductions (ARR) appeared numerically larger in patients with versus without diabetes, both subgroups derived similar benefit (2.3% vs. 1.4% for the primary efficacy endpoint at three years, pinteraction<0.0001; 1.9% vs. 0.6% for all-cause mortality, pinteraction=0.02, 2.7% vs. 1.7% for major vascular events, pinteraction<0.0001). Because the bleeding hazards were similar among patients with and without diabetes, the prespecified net benefit for rivaroxaban appeared particularly favourable among patients with diabetes (2.7% vs. 1.0%, pinteraction=0.001).
Bhatt also outlined that the findings on the primary outcome of cardiovascular death death, myocardial infarction or stroke in those with and without diabetes, either with or without prior ischaemic events or with or without revascularisation “demonstrated a consistent benefit across all these subgroups of subgroups, with interaction p values that are not significant, suggesting that the benefits of dual pathway inhibition are not predicated on a history of prior ischaemic events or revascularisation, per se, but rather on the presence of atherosclerosis”.
He acknowledged that the diabetes subgroup was not specifically powered to efficacy or safety, but pointed out that the analysis was prespecified “with sufficient power to show a significant reduction in the primary endpoint in the overall trial in [those] with or without diabetes”.
He also pointed that because the trial was stopped early by the data safety monitoring board (DSMB), subgroup analyses were further limited; however, he said: “The independent DSMB felt that the trial needed to be stopped due to overwhelming efficacy, including a reduction in all-cause mortality in the overall trial.”
In conclusion, Bhatt told the online audience: “Low-dose rivaroxaban plus aspirin reduced major adverse cardiovascular events in stable atherosclerosis, irrespective of the presence or absence of diabetes, although the absolute risk reductions were numerically larger with diabetes, including a three-fold greater reduction in all-cause mortality. As in the overall [COMPASS] trial, there was a significant increase in major bleeding, but not in fatal or intracranial bleeding. The net clinical benefit when examining irreversible outcomes appeared numerically greater in those with diabetes. Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients, such as those with diabetes.”
Treatment with aspirin plus rivaroxaban following lower extremity revascularisation in patients with peripheral arterial disease (PAD) leads to a 15% reduction in the risk of major adverse limb and cardiovascular events when compared with aspirin alone.
The VOYAGER PAD study was presented at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual)—originally scheduled to take place 28–30 March in Chicago, USA—and simultaneously published in the New England Journal of Medicine (NEJM). It found that a twice daily dose of 2.5mg rivaroxaban plus low dose aspirin is associated with significantly lower incidence of the composite primary efficacy outcome of acute limb ischaemia, major vascular amputation, myocardial infarction, ischaemic stroke, or death from cardiovascular causes than aspirin alone. On the principal safety outcome of Thrombolysis in Myocardial Infarction (TIMI) major bleeding there was no significant difference between the therapies. However, rivaroxaban plus aspirin was associated with a significantly higher incidence for the secondary safety outcome of International Society on Thrombosis and Haemostasis (ISTH) major bleeding.
Marc P Bonaca (University of Colorado Anschutz School of Medicine, Aurora, USA) outlined the findings for the virtual conference as part of a late-breaking session. He explained that the risks of major adverse limb and cardiovascular events are high in patients with PAD who have lower extremity revascularisation, but there is uncertainty about how effective and safe rivaroxaban is in this context. “In spite of this risk,” he said, “there are no proven antithrombotic strategies to reduce the risk of limb and cardiovascular outcomes after revascularisation. VOYAGER PAD was designed to address this gap.”
The double blind trial randomised 6,564 patients with PAD who had undergone revascularisation to receive either rivaroxaban 2.5mg twice daily plus aspirin (n=3,286) or placebo plus aspirin (n=3,278).
Baseline characteristics were well balanced across the two groups, with median age 67 years, and 26% of patients were female. Risk factors were common: 40% of patients had diabetes mellitus, 20% had an estimated glomerular filtration rate less than 60ml per minute per 1.73 m2 of body-surface area, and 35% were active smokers at randomisation. Less than one third of patients (31%) had known coronary artery disease, and 11% had previous myocardial infarction. The majority of patients (96%) had a history of claudication, and the median ankle–brachial index was 0.56. Bonaca described participants as “a sick population”.
The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and 584 patients in the placebo group. Three-year Kaplan-Meier estimates of the incidence were 17.3% in the rivaroxaban arm and 19.9% in the placebo arm (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.76–0.96, p=0.009).
The incidences of the first five secondary outcomes in the testing hierarchy were all significantly lower in the rivaroxaban group than in the placebo group, including the incidence of unplanned index limb revascularisation for recurrent ischaemia (HR 0.88, 95% CI 0.79–0.99, p=0.03). All-cause mortality was not lower in the rivaroxaban group than in the placebo group (HR 1.08, 95% CI 0.92–1.27, p=0.34). Therefore, the researchers write in the NEJM: “In accordance with the prespecified hierarchical testing procedure, the assessment of the last secondary outcome (venous thromboembolism) was considered exploratory.”
There was no heterogeneity in the efficacy of rivaroxaban plus aspirin as compared with aspirin alone for the primary outcome across major subgroups, including those based on age, sex, and cardiovascular risk factors. Similarly, there was no heterogeneity on the basis of qualifying symptoms, type of intervention, ankle–brachial index at screening, or the presence of critical limb ischaemia at index revascularisation.
TIMI major bleeding occurred in 62 (2.65%) patients in the rivaroxaban group and 44 (1.87%) patients in the placebo group (HR 1.43, 95% CI 0.97-2.1, p=0.07.). Intracranial haemorrhage occurred in 13 patients in the rivaroxaban group and in 17 patients in the placebo group (hazard ratio, 0.78; 95% CI, 0.38 to 1.61). Fatal bleeding occurred in 6 patients in each group.
The second safety outcome of ISTH major bleeding occurred in 140 patients on rivaroxaban versus 100 patients in the placebo group (5.94% and 4.06%, respectively, HR 1.42, 95% CI 1.1–1.84, p=0.007).
Bonaca told the online audience: “To put these results into context, in patients with PAD requiring revascularisation, for 10,000 patients treated for one year with rivaroxaban 2.5mg twice daily with aspirin versus aspirin alone there would be the prevention of 181 first ischaemic events with the components of [the primary efficacy outcome events]. The cost of this would be 29 TIMI major bleeds without any excess in intracranial haemorrhage or fatal bleeding.”
Summing up he said: “In symptomatic peripheral arterial disease after revascularisation … in this population and in this setting, rivaroxaban 2.5mg twice daily with aspirin compared to aspirin alone significantly reduces this risk. The benefits appear early and continued over time, with consistent benefit across subgroups including those with critical limb ischaemia and broad benefits included reductions in the need for unplanned index limb revascularisation. It does increase bleeding and with VOYAGER PAD there was a numerical increase in TIMI major bleeding and statistically significant increase in ISTH major bleeding with no excess in intracranial or fatal bleeding, and putting them together there is about a six-fold increase in the number of ischaemic events prevented relative to bleeds caused.”
During a Q&A section of a European Commission (EC) college meeting on 25 March, EC spokesperson Stefan de Keersmaecker stated that the commission were looking to delay the “entry into force” of the new European medical device regulations (MDR) because of the global coronavirus pandemic.
de Keersmaecker, who spoke via video, said: “The EC is working on a proposal to postpone the entry into force of the new MDR for one year. We are working hard to submit this proposal by early April.” He added that he and his colleagues were calling on the European council and parliament to adopt the proposal (once complete) “quickly” given that the new MDR is due to come into force on 26 May this year. The delay, de Keersmaecker noted, “will relieve pressure from national authorities and industry and it will allow them to focus fully on urgent priorities related to the coronavirus”.
However, even before pandemic, there were calls to delay or revise the new MDR. In a commentary written last year (October 2019), Jeffrey Jump (chairman and CEO of MedAlliance), said: “My belief—one that is shared with others in the industry—is that the MDR could become the most disruptive factor to hit the European healthcare market since the start of the Second World War. For a start, around a half of the estimated 500,000 products currently available in Europe simply will not be re-approved, due to the time, cost and administrative input required.”
He added: “I believe that—even at this relatively late stage—the MDR can still be changed to make it more workable, and some of these changes are very simple. The first and most fundamental is to extend the deadline for the implementation of MDR until at least 20 notified bodies have been accredited.”
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Interventional radiologists from Singapore have shared their strategies for the preparation of IR services to cope with COVID-19 patients, emphasising the need for clear planning and cross-departmental working to tackle the spread of the virus.
Lessons from Singapore’s healthcare system were shared by Kiang Hiong Tay, head of the Department of Vascular and Interventional Radiology at Singapore General Hospital and Chow Wei Too, director of IR Ops at the hospital’s Division of Radiological Services, alongside Farah Irani, director for IR at Seng Kang Hospital, as part of a webinar organised by the Society of Interventional Radiologists (SIR), “Is your IR service ready for COVID-19?”.
The webinar is a part of a suite of resources available to the IR community aimed at assisting in the response to the COVID-19 outbreak. SIR has released a toolkit featuring best practice guidance and recommendations for approaching the virus while the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) is also working on a number of initiatives to share information, including a resource centre on the CIRSE website with useful articles, checklists and webinars.
Rajesh Shah, (Stanford Healthcare, Palo Alto, USA) urged IR teams to adopt the recommendations, warning that the USA is “just at the beginning” of its battle against COVID-19. “You don’t want to be implementing these [recommendations] when COVID-19 patients are coming through your door, you need to be implementing these much earlier. In some places that might be too late, but you have to start right away.”
Speaking during the webinar, Tay explained that Singapore’s response to the 2020 COVID-19 outbreak has largely been informed by lessons learned from the 2003 outbreak of Severe Acute Respiratory Syndrome (SARS), which resulted in around 33 deaths, including those of two healthcare workers. “Because of this incident in Singapore, we have undertaken a number of changes to our system, to prepare ourselves for the next outbreak,” Tay explained. Significant post-SARS developments have included an increase in the number of negative pressure isolation rooms throughout Singapore’s public health system, as well as the establishment of a purpose-built National Centre for Infectious Disease, which itself has 330 negative pressure rooms.
Additionally, Tay explained, all public hospitals now have segregated inpatient and outpatient facilities, including in radiology departments, while the country also began a national stockpiling programme for personal protective equipment (PPE), including N95 respirator and surgical masks, to ensure it has adequate supplies to tackle future outbreaks. Singapore has also developed strong contact tracing capabilities, Tay said, which includes involvement of the police and criminal investigation bodies. “We also have a National Health Staff Surveillance System (S3) where we could survey the temperatures of all healthcare workers nationally. This would help pick up early fever clusters, before they spread out,” he added. “Importantly, we also had a major investment in biomedical science, with a significant focus in building expertise in infectious diseases.”
The strategy for tackling COVID-19 in Singapore has been one of containment, Tay noted, in order to ensure that the healthcare system can prevent itself from being overwhelmed by the number of cases coming in. “The key is to break the chain of transmission, and in Singapore we try to leave no stone unturned and with every single case, isolate them, and have rigorous contact tracing, and quarantining of the contacts,” he explained. Social distancing policies have also been introduced, and the Singapore government has emphasised the social responsibility for residents to remain in their homes, particularly if they begin to show symptoms of COVID-19.
At an institutional level, Tay commented that formation of a taskforce across departments is an important step in coordinating the response to an outbreak. “We meet daily to sort out any COVID-19 related issues. We review our manpower status, the sick leave and the temperature surveillance. We have an app that can easily enter this and staff are required to do this two times a day and this can be easily monitored,” Tay said. Other areas to be overseen by the taskforce include logistical issues, include monitoring PPE stocks, and ensuring that infection control practices are maintained on the ground.
Establishing segregated teams, comprising members of different sub specialities should also be considered, Tay suggested, so that essential functions can continue even if specialist staff are required to be quarantined, while elective cases should also be reduced. “For IR, the lessons learned from SARS are still relevant,” Tay remarked. “The concept is actually quite simple: you need to protect your patients, protect your staff and prevent intra-hospital transmission. Underbuilding all of this is strict adherence to infection control measures. We need to have business continuity plans because the likelihood of getting quarantined from exposure is high.”
Following Tay, Too Chow Wei outlined Singapore General Hospital’s approach from an IR operations perspective, noting that the institution had instigated a six-point plan for dealing with the virus.
The first step is patient segregation, Wei explained, with in- and outpatients separated into different areas or by time slots, so that there is no cross contamination between patients. “Here at Singapore General Hospital we have seven rooms separated into two levels, so that we can do an upstairs/downstairs space segregation. If you can’t, do it by time, finish [the] outpatient list in the morning before you are getting your inpatients in.” Reducing the workload of the hospital is also important, he noted. “Arbitrarily at the start of the infection we said that we wanted to reduce workload by about 50%. In reality it is probably closer to about 30–40%. We want fewer patients in the hospital as it is less likely they can overwhelm the system.”
The second part of the chain is staff segregation. Wei said that within Singapore General Hospital, the IR team has been split into two functional teams of doctors, nurses and radiographers, to keep certain functions running in case specialists need to be quarantined. A policy of social distancing, and staggered meal times has also been employed, to reduce the amount of social contact between staff, and potentially reduce the likelihood of infection. The institution has adopted a further policy of vetting and prioritising cases that are handled. “Non-urgent procedures have been given long waiting times,” Wei explained.
In addition, the hospital has sought to minimise the movement of isolated patients. “If we can treat by the bedside, we should do it by the bedside,” he said. This has necessitated the introduction of enhanced workflows, described by Wei as one of the most important parts of the strategy. “We reached out to our colleagues in anaesthesia, security, infection controls and we developed workflows. This is really a juggling act,” Wei said. The process involves ensuring that as a COVID-19 positive, or suspected patient leaves a ward en route to the IR centre, the area is cordoned off by security, so that a path can be found that minimises contact with other staff and patients. As the patient is moved, environmental services will clean down surfaces. “We need to bring everybody together just for transfer of the patients. We have simulations, rehearsals and after action reviews and we constantly improve our workflows,” Wei commented.
Alongside this, the IR room is prepared for the receipt of the patients. All equipment that is unnecessary for the procedure is removed, and the remaining equipment is wrapped in plastic sheeting. At the end of the procedure there is a wipe down of the equipment, with a disinfectant wipe, after which the walls and floor and other areas are cleaned with sodium hypochlorite solution at 1,000ppm. After this the room is then disinfected, either with ultraviolet c treatment or hydrogen peroxide vapour.
Offering his advice on putting a strong strategy in place for tackling the COVID-19 outbreak from an IR perspective, Wei posited: “You need to talk to different stakeholders in the hospital. Change has become the new constant. New workflows will need to be established, documented, rehearsed, reviewed and improved. Everybody plays a role, we really need to talk about infection controls. This is a labour intensive process, but training will pay off.”
Speaking after Wei, Irani outlined the Seng Kang General Hospital experience in having dealt with COVID-19 cases. Similar to the processes described by Wei, she sketched out the procedure for the movement of patients at Seng Kang, which seeks to minimise the risk of the spread of infection. This involves a similar level of coordination between departments, and within the IR department itself. Each member of the team has a defined role in handling the patient, and prepping the facilities for use.
After the patient has been moved on, there is a strict procedure for the removal and sterilisation of clothing and equipment. Safe removal of equipment is one area highlighted by Irani as being particularly important part of the process to prevent the spread of infection. “Doffing is more important than donning,” she said. “We always are very careful when we put on the equipment, but the time we will get infected is when we take off the equipment, and that is when we need to be really careful.”
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A viewpoint in the Journal of the American Medical Association (JAMA) has offered potential solutions to modifying ongoing randomised clinical trials during the COVID-19 pandemic. It aims to “minimise disruption and preserve integrity”, while still ensuring participant health and safety.
Authors Mary M McDermott (deputy editor of JAMA, and Jeremiah Stamler Professor of Northwestern University, Chicago, USA) and Anne B Newman (University of Pittsburgh Graduate School of Public Health, Pittsburgh, USA) advise “creativity and persistence”. They point out: “Mitigation efforts interfere with all aspects of a successful clinical trial: efficient accrual and randomisation, intervention adherence and delivery, and outcome collection. Those most susceptible to severe consequences of coronavirus, older individuals and those with chronic disease, are commonly included in randomised trials designed to improve health in these vulnerable populations.”
They observe that, although one approach is to discontinue randomised trials that do not provide an immediate clear benefit to enrolled participants, the benefits of ongoing trials are unknown until the trial is completed, and discontinuing ongoing trials wastes previously invested resources, as well as the time and effort of those who have already completed the trial.
“In contrast, sustaining ongoing trials could help millions of people realise substantial, durable health benefits that will be important once the coronavirus pandemic ends. Therefore, efforts and resources should be dedicated to support continuing randomised trials using creative and thoughtful methods and proactive planning. Adapting protocols to facilitate continued intervention adherence, outcome measurement, and some aspects of recruitment for trials already underway is likely to have the greatest benefit for the most people.”
Among the modifications they recommend are changes to how outcome data are collected, and how interventions are delivered and monitored.
McDermott and Newman suggest prioritising outcomes, with the primary outcome given highest priority: “Outcomes that are exploratory or not prespecified are more appropriate to eliminate temporarily. Alternative methods for measuring primary outcomes that cannot be collected in-person should be prepared and protocols modified to facilitate collection of alternative self-reported or medical record data that can be adjudicated as a surrogate for the primary outcome.”
Those that can be collected remotely, such as self-administered outcomes or those collected by telephone or online, should be continued.
Safety and feasibility must be emphasised when considering the delivery of interventions, they say. Interventions that can be safely adhered to without leaving home should be continued, and it may be appropriate to continue some interventions, such as medications, beyond the originally intended stop date. Others may need modification—for example, those that require participants to attend behavioural interventions requiring group visits or exercise sessions at a gym could be temporarily converted to a home-based session with remote monitoring.
The authors also urge consideration of how an intervention might interact with coronavirus infection, and whether a study drug should be continued if a participant becomes ill with symptoms of coronavirus. “Conceivably,” they point out, “some interventions could improve outcomes. For example, a trial testing efficacy of a therapy such as a statin might mitigate the cardiovascular consequences of an acute inflammatory state. If continuing the intervention becomes untenable, intention-to-treat methods are essential for understanding risks and protective factors for infection, illness, or recovery.”
However, McDermott and Newman conclude, investigators should consider scaling back or placing selected studies on hold, if doing so does not substantially harm the trials, allowing research personnel to switch to work on urgent trials of interventions to address the coronavirus pandemic.
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The 2020 Charing Cross (CX) Symposium that was due to take place next month in London, UK, has been cancelled due to COVID-19.
In full, the statement from the CX Symposium team, reads:
“The CX Symposium team has made the difficult but necessary decision to cancel the Charing Cross Symposium 2020 that was scheduled to take place from 21 to 24 April in London, UK. We will be refunding in full all the registration fees incurred by delegates and will work with our Faculty members to assist with their travel cancellations.
“With the unprecedented spread of COVID-19, it has become clear that the CX Symposium could not take place in its usual format. Some alternatives were considered, including a digital symposium to be made available during the dates of CX, but even this would not be possible in these challenging times. The medical profession has a frontline role in the fight against the virus and we are committed to supporting our friends and colleagues in the vascular community at this difficult time.
“The CX and BIBA Medical teams will continue to work hard on the media and digital front to bring you useful and key educational learnings on how medical teams from all over the world are responding to the growing number of COVID-19 patients.
“In addition, when the time seems right, we are planning for some of the carefully selected CX programme presentations to be transformed into a free online educational resource for the vascular community.
“Finally, a copy of the CX Book, containing the high-quality contribution by some of our Faculty, will be made available free of charge on the CX website.”
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The US Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) has written to the medical device industry to outline its response to the COVID-19 public health emergency in its day-to-day operations with industry.
The letter from the agency details that it aims to “prioritise work that advances the nation’s response during this national emergency”. Among the steps it has taken are converting in-person meetings to teleconferences, and changes to its processing of incoming documents, as well as extending response due dates for marketing applications that are currently on hold.
Meetings with industry scheduled up to 30 April are being switched to a teleconference to be held at the same date and time. The agency says it will continue to assess whether any in-person meetings arranged beyond that date should be converted to teleconferences, and promises to provide periodic updates.
The CDRH also indicates that although the Document Control Center continues to receive and process incoming documents it is “generally unable to accept incoming submissions via email”, and it is looking into other electronic options.
Marketing applications that were on hold as of 16 March with a response due date on or before 30 April have had their response due dates extended by 60 days. The extension relates to Premarket Notifications (510[k]s), Premarket Approval (PMA) applications (original and supplements), Humanitarian Device Exemption (HDE) applications (original and supplements) and De Novo classification requests. The agency says this will occur automatically, without the need to submit a request. In cases of additional submission types where a response or report is due (for example, Post Approval or 522 Study reports, Investigational Device Exemption annual reports, PMA reports), the CDRH encourages that the response or report be submitted when possible.
The Postmarket and Compliance Activities at the CDRH will continue to process and work on mission critical post-market and compliance activities. “Medical devices play an essential role in advancing public health in the response to the COVID-19 national emergency. As such, our work in supporting the availability of critically-needed medical devices is our highest priority,” states the organisation.
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Straub Medical (United States), the US direct-sales subsidiary of Straub Medical AG (Switzerland), has announced the launch and first intervention performed with the Rotarex S atherectomy device designed for treating (OPVD).
Baljeet Uppal (Pinnacle Vein and Vascular Center, Suncity, USA), who was the first physician to treat a US patient with Rotarex S commented, “This 70-year-old patient had a 5cm long, calcified, chronic total occlusion (CTO) of the popliteal artery.”
Discussing the case, he stated “The Rotarex S device performed flawlessly in opening the occlusion and restoring flow. It was simple to operate with a relatively short procedure time and no complications. The patient was able to go home just a few hours after the intervention.
Summarising the experience, he stated “In a field crowded by atherectomy devices, Rotarex S provides revascularisation of the lower extremities in virtually all lesion types, be it thrombus, soft or calcified plaque. In the process it has minimised distal embolisation. I see it becoming our tool of choice in the coming times.”
Intended for use as an atherectomy device and to break up and remove thrombus from upper and lower extremity peripheral arteries, Rotarex S is available in both 6F and 8F configurations and compatible with 0.018” guidewire. The device is intended to treat vessels of diameter 3–8mm.
Rotarex S is a hybrid device that removes both atheroma and thrombus at the same time. Straub Medical uses the acronym MATH to describe this process, meaning Mechanical Atherectomy plus Thrombectomy. Many similar devices are only able to remove one or other component, or to only treat stenosis. Use of the device is not restricted by the nature of the occluding material, nor by the length of the occlusion.
Scientific literature published on the device supports the safety of its use and the clinical benefit provided to patients.
Gido Karges, Straub Medical Group CEO, commented, “I am proud we finally can bring this proven technology to the USA. It is safe, fast, and produces reliable and lasting results. While we do not have specific US data in that regard yet, we expect it to have a positive effect on overall treatment cost and thus US OPVD health economics, too.”
He went on to explain, “Clinically proven in terms of safety, efficacy and clinical success, this multifunctional tool from Switzerland is sure to be welcomed by US physicians to increase their versatility and efficiency when treating their patients.” With a wink, he added, “Do the MATH!”
Mike Napack, national director sales and marketing at Straub Medical (United States), emphasised: “This device has been used successfully outside the USA for many years, and we have been eagerly waiting for it to be commercialised here. With the introduction of Rotarex S in the USA, today marks a milestone in the treatment of US patients with occlusive peripheral vascular disease.”
The Straub Medical Group has been marketing Rotarex S outside of the USA for more than two decades, with patients in more than 50 countries benefiting from its uniquely designed and safe operating mechanism.
Larry Scher (New York, USA) interviews John Aruny (Orangeburg, USA) and Stephen Hohmann (Dallas, USA) for VEITHtv at the VEITHsymposium (19–23 November, New York, USA) about the role of percutaneous AV fistulas in contemporary haemodialysis practice.
Aruny says physicians are “on the brink of a whole new paradigm in technology” in regards to creating AV fistulas for haemodialysis patients – who will be the “most impacted” by these procedures. He and Hohmann also discuss patient selection and exclusion criteria for the procedure.
Scher, for his part, says he remains sceptical about the new technology that allows AV fistulas to be inserted percutaneously rather than with open surgical procedures. He is also sceptical about non-surgeons using this technology when surgery may be a better option and goes on to emphasise the importance of a multidisciplinary approach to adopting this new technology.
However, Hohmann addresses these concerns and says that he believes this new technology expands physicians’ capabilities, rather than limiting them; adding that in most cases, physicians are “not sacrificing” but rather “expanding” the options available.
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Edward Choke (Singapore) talks to BLearning Peripheral at LINC 2020 (Leipzig Interventional Course; 28–31 January 2020, Leipzig, Germany) about the first-in-man clinical study—XTOSI—which looked at the safety and efficacy of a sirolimus drug-coated balloon (DCB) in the treatment of peripheral arterial disease. interim
The interim findings showed that primary patency at six months in the XTOSI below-the-knee (BTK) patients was 74%. This, notes Choke, is “highly promising”, particularly when compared to a recent study by separate investigators which looked at a paclitaxel DCB in BTK patients and showed patency of just 40% at six months. Choke outlines some of the challenges with the critical limb ischaemia (CLI) patient cohort, including the strong prevalence of diabetes (90% of patients) and the “complexity of the lesions themselves”.
He concludes by discussing the next steps, including the need to gather level one data from a larger population of patients and also highlights two upcoming randomised controlled trials, FUTURE-SFA and FUTURE-BTK.
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The 2020 European Conference on Embolotherapy (ET), run by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), has been postponed until 16–19 December due to the coronavirus pandemic.
In full, the statement from CIRSE president Afshin Gangi (University Hospital Strasbourg, Strasbourg, France), ET chairperson Christoph Binkert (Institute of Radiology and Nuclear Medicine Kantonsspital, Winterthur, Switzerland), and ET deputy chairperson Patrick Haage (HELIOS Universitätsklinikum, Wuppetal, Germany) reads:
“After careful consideration of the conditions surrounding the continuing spread of the COVID-19 epidemic throughout Europe and the uncertainty regarding the severity and duration of restrictions on travel and gatherings in Austria and globally, the CIRSE leadership has had to take the difficult decision of postponing ET 2020 in Vienna, Austria, to December 16-19.
“We are very grateful for the understanding and support we have received from our community in these challenging times and look forward to welcoming you to another engaging ET in December!”
The American Journal of Kidney Diseases (AJKD) has published the National Kidney Foundation’s KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update, a completely revamped set of 26 individual guidelines for clinicians that focuses on dialysis access choices tailored to individual patients’ goals and preferences, as well as clinical outcomes.
It is the third time the Kidney Disease Outcomes Quality Initiative (KDOQI) team has developed a vascular access guideline and the first time the guideline has been updated since 2006. About 500,000 patients in the USA receive dialysis treatment and in 2016 alone, nearly 125,000 people started treatment for end-stage kidney disease (ESKD).
This comprehensive update was developed due to the significant growth in the evidentiary database for vascular access. Haemodialysis access issues are managed by a multidisciplinary team of medical professionals, thus the working group that developed this update includes members representing not only clinical and academic-based adult and pediatric nephrologists, but also interventional nephrologists, radiologists, surgeons, and vascular access nurses.
“It is gratifying to see how much progress has been made in understanding how to place and maintain the various types of vascular access to maximise the effectiveness and reduce complications,” said NKF chief scientific officer Kerry Willis. “One of KDOQI’s most important contributions to improving outcomes for dialysis patients has been the stimulation of new research such as the studies used in creating this groundbreaking update.”
An important new approach introduced in this guideline is an individualised and comprehensive map for dialysis modalities for the lifetime of the patient called the “ESKD Life-Plan,” achieved by creating a “P-L-A-N” for each patient that considers the Patient’s Life-Plan and corresponding Access Needs. For each access, the “Access Needs” part of the P-L-A-N includes designing and documenting the patient’s access creation plan, contingency plan, succession plan and underlying vessel preservation plan. The end-result is a comprehensive vascular access management plan that will best suit the patient throughout his or her time with end stage kidney disease.
The Evidence Review Team from the University of Minnesota reviewed more than 4,600 peer-reviewed publications, of which 286 were included in the evidence tables. These evidence tables were used by the workgroup, chaired by Charmaine Lok from the University of Toronto, to develop this fresh and more patient-focused approach to vascular access care that takes into consideration each patient’s needs and preferences.
“The new guideline will have many benefits for patients on dialysis, including to help preserve vessels needed for successful future access creation and to minimise unnecessary access-related procedures and complications,” said KDOQI chair Michael Rocco.
NKF has produced clinical practice guidelines through KDOQI on all stages of kidney disease and related complications since 1997. Recognised around the world for improving the diagnosis and treatment of kidney disease, the KDOQI guidelines have changed the practices of numerous specialties and disciplines and improved the lives of thousands of kidney patients. All KDOQI guidelines and commentaries are published in AJKD.
“These Guidelines emphasise an integrated, individualised approach to patient care that promotes optimal dialysis access management based on the best available evidence,” said Guideline Chair Charmaine Lok. “It recognises the need for further research, data, and timely revision that incorporates evolving practices, innovation, and new advances in vascular access. We are excited for clinicians to start using these Guidelines to help get the right access in the right patient at the right time for the right reasons.”
The guidelines will appear in the National Kidney Foundation’s AJKD today. AJKD is the leading kidney disease journal. It reaches thousands of healthcare professionals each month. To read more about the authors and to read the commentary, please visit: https://www.ajkd.org/issue/S0272-6386(20)X0004-7.
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Geert Maleux (Leuven, Belgium), one of the first users of the SeQure® reflux control microcatheter (Guerbet) in Europe, shares his experience with the new device. He tells BLearning IR that the current challenges of embolotherapy include incomplete devascularisation, which can occur in some cases of liver chemoembolisation procedures, as well as non-target embolisation.
Maleux shares that he was drawn to using the SeQure® microcatheter because it is a novel device that is designed to help reduce the risk of non-target embolization. “[.] I have also the impression that we can deliver more microparticles into the targeted areas, for instance in cases of liver chemoembolization, into the tumour,” he adds.
Guerbet sponsored this video and its distribution in association with Interventional News.
A review of data from Veteran Health Administration shows that there was a temporal increase in the use of revascularisations for the management of critical limb-threatening ischaemia (CLTI) between 2005 and 2014. This increase correlated with a reduction in both mortality and major amputation during the same time period. However, contrary to data for non-veteran association patients, the new data did not indicate a shift towards endovascular revascularisation strategies.
Amgad Mentias (University of Iowa Carver College of Medicine, Iowa City, USA) and others write in Circulation: Cardiovascular Interventions that prior studies of non-veteran patients have already shown a temporal increase in both the use of revascularisation and the use of statin therapy for the management of critical limb ischaemia, and these trends have been linked to a reduction in mortality. “However, contemporary studies of critical limb ischaemia incidence, clinical management, and outcomes among veterans remain limited,” the authors report. The senior study author Saket Girotra (University of Iowa Carver College of Medicine, Iowa City, USA) told BIBA Briefings via email that there is a general lack of research on peripheral arterial disease among veterans. He noted that “we do not know with any degree of certainty how common peripheral arterial disease is among veterans”. “How does peripheral arterial disease affect veterans’ health status and quality of life both in the short-term and the long-term? And are veterans with this condition being appropriately managed? If not, what are the barriers and how can we improve care?” he adds.
Therefore, the team reviewed data from the Veterans Health Administration to provide further information in critical limb ischemia, which represents an advanced stage of peripheral arterial disease. They identified data for 20,938 patients (mean age 67.8 years; range 40–100 years) who were admitted to a Veterans Affairs (VA) facility with a diagnosis of critical limb ischaemia between 2005 and 2014 (fiscal years). Overall, the incidence of critical limb ischaemia was 0.25 per 1,000 enrolees. The authors report that across the study period, there was a “modest” decrease in the incidence of critical limb ischaemia: 0.3 per 1,000 enrolees to 0.24 per 1,000 enrolees (p<0.01).
The authors note: “There was a significant temporal increase in the overall use of revascularisation at 90 days (41.4% in 2005 vs. 57.9% in 2014; p<0.01 for trend) and this trend was consistent across all modalities [surgery, endovascular, and hybrid] as well as revascularisation during hospital stay.” Furthermore, between 2005 and 2014, risk-adjusted 90-day mortality decreased: 11.8% in 2005 and 9.4% in 2014 (p<0.01). Both revascularisation and statin use (which also increased) were strongly associated with a lower risk of 90-day mortality; revascularisation was also associated with reduced rates of major amputation at 90 days.
The authors found that surgery was the primary method of revascularisation: 25.4% vs. 14.9% for endovascular vs. 9.2% for the hybrid approach. They note that although the ongoing BEST-CLI trial is evaluating the optimal revascularisation approach, “endovascular techniques provide a lower risk option for revascularisation in patients with critical limb ischaemia”. Furthermore, they observe their findings are in “sharp contrast” to non-VA studies that have “demonstrated a general shift in revascularisation towards an endovascular approach”. Girotra comments: “The suitability of treatment depends on several factors such as the extent and complexity of vascular disease, the availability of conduits, potential for wound healing, patient preference as well as availability of appropriate expertise. Our study did not capture these data to inform us about the reasons for this divergent pattern of care. There is currently equipoise between endovascular therapy and surgical revascularisation as treatment options for critical limb ischaemia and, thus, the result of BEST-CLI are eagerly awaited.”
The study also found more than four-fold variation in the use of revascularisation across the sites and differences in patient factors could only account for less than 10% of this variation. The authors comment that they could not determine, with the current analysis, if these differences were because of differences in speciality expertise or in the number of available operators. Therefore, future studies are needed. “Given the strong association of revascularisation with patient outcomes, the findings highlight an urgent need to develop processes for ensuring that patients with critical limb ischaemia receive care from specialists with expertise in critical limb ischaemia management,” they say.
The authors conclude: “Further studies are needed to examine the reason of low use of endovascular revascularisation in VA hospitals compared with surgical revascularisation.”
An ahead-of-print article in the April issue of the American Journal of Roentgenology (AJR) reviewing various techniques and clinical management paradigms to treat severe frostbite injuries—relevant for interventional radiologists, especially—shows promising results using both intra-arterial (IA) and intravenous (IV) tissue plasminogen activator (tPA) to reduce amputation.
“Severe frostbite injuries can lead to devastating outcomes with loss of limbs and digits,” write radiologists Mikhail Higgins and John Lee (both Boston Medical Center, Boston, USA). Speaking specifically to this newspaper, they add: “In an era where the clinical paradigm for management of frostbite injuries has been primarily tissue rewarming, prolonged watchful waiting, and often delayed amputation, it is particularly exciting to have a meta-analysis that supports and validates a promising endovascular therapy performed by interventional radiologists that can significantly mitigate digit loss.”
Elaborating to Interventional News, Higgins and Lee comment: “The management of frostbite injury has been limited to conservative management and supportive care until now, mainly due to lack of studies on additional treatment options. Patients with severe frostbite injuries have often had bad outcomes—including amputations—due to the lack of reliable treatment options in the acute setting. Our meta-analysis shows promising results of intra-arterial and intravenous tPA therapy in the acute management of severe frostbite involving thrombosis of the digital arteries.”
A search of the literature by Lee and Higgins yielded 157 citations. After manually screening for inclusion criteria of case reports, case series, cohort studies, and randomised prospective studies that reported the use of tPA to treat severe frostbite injuries, 16 qualified for review.
Higgins and Lee analysed series included 209 patients with 1,109 digits at risk of amputation treated with IA or IV tPA—116 and 77 patients, respectively. A total 926 at-risk digits were treated with IA tPA and resulted in amputation of 222 digits, for a salvage rate of 76%. Twenty-four of 63 patients underwent amputation after IV tPA, resulting in a 62% salvage rate.
Both digital subtraction angiography (DSA) and triple-phase bone scan were utilised for initial imaging evaluation of patients with severe frostbite injuries.
Additional concurrent treatment included therapeutic heparin at 500U/h, warfarin with target international normalised ratio of 2:3, nonsteroidal anti-inflammatory drugs, pain management, and light dressings with topical antimicrobial agents.
Interventional radiologists are well-placed to be offering this digit-saving treatment, they add. “Not only are we interventional radiologists trained in catheter and guidewire manipulation skills to successfully navigate the arterial anatomy, but we are also clinically facile with managing patients’ unique endovascular needs with tPA therapy, given our deep experience with its use in catheter-directed thrombolytic therapy of other pathologies, such as pulmonary thromboembolism and thrombosed arteriovenous fistulas and grafts. In addition, the skill of diagnostic angiography, particularly of micro-arterial anatomy, that is needed to quickly and accurately diagnose frostbite-related thrombosis of the digital arteries as well as during post treatment evaluation is a long-held point of expertise by the clinically trained interventional radiologist.”
“For many years,” Higgins and Lee concluded, “the axiom ‘frostbite in January, amputate in July’ was an accurate description of the common outcome in frostbite injuries. Through a meta-analysis of thrombolytic therapy in the management of severe frostbite, this article provides a useful guideline for interventional radiologists, including a suggested protocol, inclusion and exclusion criteria, and potential complications.”
The author’s recommendation is based off the multidisciplinary care protocol that they co-implemented at their own institution, Boston Medical Center. Higgins and Lee say this “begins with an objective evaluation of the affected digits, including grading post-rapid rewarming in the emergency department.” This might then include collaborative clinical triaging of severe frostbite injury patients to intravenous or intra-arterial thrombolytic management with conservative management for low grade injuries, with contributions from emergency medicine, trauma surgery, podiatry, orthopaedics, internal medicine, diagnostic and interventional radiology.
“It is important to note,” they add, “that such multidisciplinary efforts reliably and reproducibly support early and accurate diagnosis and triaging of patients with frostbite injuries and are vital in providing appropriate management and oversight of these patients, particularly during thrombolytic therapy.”
When asked how this research will impact clinical practice, Higgins emphasises the importance of promoting these procedures: “Publicity on the use of thrombolytic therapy in treating acute severe frostbite is vital to ensure that frostbite patients are afforded the most efficacious management option to preserve their digits in the unfortunate event of an acute frostbite injury. With global warming as a real though daunting consideration, who knows which city or hospital might experience a rush of frostbite cases amenable to this important digit-salvaging therapy, and when? Knowing how to protect our patients from digit loss should such events occur is now a critical consideration for the forward-thinking, patient-centric interventional radiologists that we all aspire to be. In that vein, I would consider encouraging periodic efforts to inform healthcare providers about thrombolytic management of severe frostbite, especially during each winter season.”
Higgins and Lee hope to see the results of randomised trials in comparing the effectiveness and complications of intra-arterial and intravenous thrombolytic therapy. “With these results,” they determine, “we will be able to provide more effective and safe digit-saving care for patients with acute severe frostbite injuries.”
The Society of Interventional Radiology (SIR) has cancelled its upcoming conference due to the coronavirus outbreak. The conference was to be held in Seattle, USA, from 28 March–2 April.
The cancellation comes in the wake of a Seattle and King County Public Health Department recommendation on 4 March that requested organisers of large public gatherings consider postponing these events.
“Based on these recommendations, US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) information, and numerous travel restrictions issued by companies and medical institutions, SIR and SIR Foundation leadership have made the difficult, but necessary and responsible, decision to cancel the SIR 2020 Annual Scientific Meeting in Seattle,” the society said.
SIR plans to refund attendees’ and exhibitors’ registration fees and will cancel any hotel reservations made through its official hotel block, it said. It will not refund individual travel costs. Exhibitors’ space rental fees will be refunded upon written request.
The society plans to explore other meeting options.
“In the coming weeks, we will tap into the innovative and agile spirit of [our] specialty to explore virtual meeting options that deliver world-class education, spotlight interventional radiologists’ ingenuity, and celebrate the many achievements we had planned to recognize in Seattle,” SIR said.
In addition, the European Society of Radiology (ESR) announced last week that is has postponed its annual meeting, the European Congress of Radiology (ECR), originally scheduled for 11–15 March in Vienna, Austria. This will now be held on 15–19 July.
Boris Brkljačić, ESR president, comments on the society’s website: “After careful evaluation of the spreading coronavirus epidemic, and considering the recent statements issued by the World Health Organization (WHO) and the European Centre for Disease Prevention (ECDP), and the related evolving world-wide restrictions and crisis, the ESR was forced to make this decision. Above all, we have analysed the recommendations from the Austrian health authorities for large-scale events and came to the conclusion that we are not in a position to fulfil their requirements and guarantee a safe congress for our participants and industry partners at this time. The safety, health and well-being of our delegates and partners will always be the highest priority for the ESR.”
Okami Medical has announced the successful completion of the first cases with the Lobo vascular occlusion system. The first offering in the company’s product portfolio, Lobo-3, recently received 510(k) clearance from the US Food and Drug Administration (FDA) for the occlusion of peripheral arteries.
The Lobo (Low-profile braided occluder) system is uniquely designed to provide interventional physicians with a single-device, one-and-done solution for the occlusion of various arterial targets without the need for multiple embolic devices. The Lobo system combines a patented design with proprietary Hdbraid technology to create a highly occlusive pore structure that substantially reduces blood flow and accelerates vessel closure. The Lobo-3 occluder is intended for use in 1.5–3mm diameter vessels.
Ripal Gandhi, interventional radiologist, Miami Cardiac and Vascular Institute, performed the first Lobo-3 implant. “We have successfully utilised the Lobo-3 occluder to embolise several small vessels via a microcatheter. The device has resulted in immediate occlusion of the target vessels. The device tracks well and deploys precisely at the desired location. The Lobo-3 occluder is a great addition to the embolic armamentarium for the occlusion of small vessels,” said Gandhi.
“Guided by world-class physician collaborators, Okami is committed to addressing numerous challenging aspects of peripheral vascular occlusion,” said Bob Rosenbluth, president and CEO of Okami Medical. “We are very pleased with the clinical performance of the Lobo-3 occluder in the initial cases. The device is in clinical use at key centres and we look forward to expanding our launch in 2020.”
Medtronic has issued an urgent field safety notice to warn on specific production lots of its Pipeline Flex embolization devices due to the potential for device fracture.
The company initiated verbal communication about the issue last month after identifying the potential for device fracture at the distal section during use, due to a weakened bond in a subset of recently manufactured devices.
Use of the affected product could result in unintended separation, where the distal portion of the device delivery system remains in the patient, which could cause significant patient injury, including a prolonged procedure, ischaemic stroke, intracranial haemorrhage, neurological deficit and/or death.
Medtronic has not received complaints related to the issue within the affected population, but the company is recalling the affected products due to the increased potential for fracture, according to the field safety notice.
If a Pipeline Flex embolization device was already successfully implanted, there is no increased risk to patients due to the issue, and those patients can continue with their normal course of treatment. The affected lots include devices with a “use-before” date on or after 21 October 2022.
The company urged those affected by the issue to cease the use of any affected products and to remove and quarantine all unused devices in their inventory before returning them to Medtronic.
Pipeline Flex is designed for the endovascular treatment of adults with large or giant wide-necked intracranial aneurysms from the petrous to the superior hypophyseal segments. In February 2019, it won expanded US Food and Drug Administration (FDA) indication for patients with small or medium wide-necked brain aneurysms in the territory from the petrous to the terminus of the internal carotid artery.
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Andrew Holden (Auckland, New Zealand), Alexandros Mallios (Paris, France), Robert Lookstein (New York, USA) and Tobias Steinke (Dusseldorf, Germany) talk to BLearning Peripheral about the 12-month results of the IN.PACT AV Access randomised controlled trial (RCT) which compared drug-coated balloon (DCB) angioplasty to plain balloon angioplasty.
Holden, who presented the 12-month primary patency data for the first time at LINC 2020 (Leipzig Interventional Course; 28–31 January, Leipzig, Germany), explains that the data showed a “highly significant difference in patency” in the paclitaxel DCB arm (63.8%) when compared with the plain balloon arm (43.6%). He also highlights other key data including a 35.4% reduction in the number of reinterventions in the DCB group, which he notes “really resonates with clinicians as well as patients”.
Mallios notes that the six-month data was not only sustainable but improved and claims that another important point is that, regarding the risk of mortality, “apparently there is no evidence supporting this risk for arteriovenous access”. He discusses the clinical importance of the data which he believes is “very reassuring” and provides a “better quality of life for the patient”.
Lookstein for his part discusses the Economic Impact Model of the German and American healthcare systems which he says provided “a very telling argument” that the technology should be used in the “broadest population possible”. He goes on to look at how these “impressive” datasets, including both the 12-month data and the Economic Impact Model—which showed a DCB cost benefit—have led him to think “even more about using DCBs in AV access patients”.
Finally, Steinke gives his view on the 12-month IN.PACT AV Access data which he says was “really impressive”, noting that this was the first time that “significant results” were seen over this length of observation.
This video is sponsored by Medtronic
Reflow Medical has announced that they have received US Food and Drug Administration (FDA) clearance for an expanded indication for the Wingman crossing catheter after completing the Wing-IT clinical trial. The Wingman catheter crosses peripheral chronic total occlusions (CTOs) using an extendable bevelled tip that creates a channel to help penetrate, or cross, the occlusion with a guidewire, enabling further treatment of the lesion with therapeutic devices.
The Wing-IT CTO clinical trial was a prospective, international, multicentre study that treated 85 patients and followed them for 30 days. The Wingman catheter was able to demonstrate a 90% crossing rate when up to two previous guidewires could not cross these challenging lesions, meeting its primary safety and efficacy endpoints. These clinical trial results have garnered positive feedback in the physician community.
“With this expanded indication, physicians gain the ability to cross [CTOs] in peripheral lesions with a simple and very effective device,” according to John R Laird (Adventist Heart and Vascular Institute, St Helena, USA). Laird was the principal investigator for the study.
S Jay Mathews (Bradenton Cardiology Center, Bradenton, USA), who performed initial patient enrolments, said, “Reflow goes the extra mile to provide physicians with real clinical evidence for utilising their technology, including this new indication for the Wingman.”
Company co-founder and CEO Isa Rizk noted, “We are extremely grateful to the physician investigators, patients, research staff and employees who helped us conduct this very important and compelling clinical study that supported this expanded treatment option for crossing peripheral CTOs.”
On average in France, 2,000 uterine artery embolizations (UAEs) are performed each year. In contrast, 40,000 patients have hysterectomies annually. This has led French interventional radiologists to protest the high number of “unnecessary” surgeries, and spurred the development of a nation-wide public awareness campaign. However, this is not just a French issue.
James Spies (Georgetown University Hospital, Washington, DC, USA) reports that, “despite some progress in reducing the number of hysterectomies for benign conditions such as fibroids, with about a 10% reduction in the past decade, there are still eight to 10 times the number of hysterectomies as UAEs for fibroids in the USA.”
A 2017 report by the Society of Interventional Radiology (SIR), The Fibroid Fix: What women need to know, provided insights into the lack of awareness. SIR commissioned a Harris Poll in June 2017 that surveyed 1,176 US women ages 18 and over. The poll found 62% of respondents had never heard of UAE and that 20% believed hysterectomy was the only treatment option for fibroids. Even those who were diagnosed with fibroids reported a lack of awareness, with 44% saying they had not heard of UAE. Of those who had, 75% said they did not learn about it from a gynaecologist.
“Our numbers for UAE are ridiculous,” José Urbano (Ramon y Cajal University Hospital, Madrid, Spain) says of Spain. According to the Spanish Society of Vascular and Interventional Radiology (SERVEI), 120–150 UAE are performed each year in the country, which has a population of 44 million. These experiences are echoed in Central America. Speaking at SIR’s annual meeting last year (23–28 March, Austin, USA), the only interventional radiologist in El Salvador, Ethel Rivas Zuleta (Universidad Dr José Matías Delgado, San Salvador, El Salvador), told delegates: “We face the same problems in our region”. Fibroids are the leading indication for hysterectomy in El Salvador. In 2018, 746 hysterectomies were performed in Zuleta’s institution, mostly in women between 30 and 50 years of age. Six women were treated with UAE. Zuleta noted that none of these six patients were referred by an obstetrician or gynaecologist: four were either doctors themselves, or related to one, and two had found out about UAE themselves online.
On the other side of the world, Gerard Goh (The Alfred Hospital, Melbourne, Australia) and colleagues recently analysed Australian Medicare data, and found a “huge disparity” between the number of hysterectomies performed each year compared with the number of UAEs. The data showed that, on average over the last five years, 30,332 uterine surgeries are performed each year. According to Goh, you would expect four to five thousand of these (approximately 30%) to be treatment for fibroids. Fewer than 145 UAEs were performed on average per year. “Based on the suggestion that 20% of hysterectomies in Australia are for fibroid-related disease, this estimates 6,066 fibroid-related surgeries per year,” Goh comments.
He adds that he thinks it is “interesting” that a procedure which has been proven to be efficacious has such a poor take-up globally. A major reason for this, he posits, is the lack of “patient and referrer awareness”. To tackle this issue, he believes interventional radiologists from across the world need to “come together” and work with societies to help educate patients and referrers, because currently “a lot of women are really missing out on uterus-sparing surgery for fibroids”.
Speaking specifically of the US population, Spies expands on his thoughts for the causes of the discrepancy between hysterectomy patient numbers and UAE patient numbers: “I believe that there are a range of factors, which could include economic considerations, but also persisting scepticism among gynaecologists about UAE. Despite considerable evidence of excellent outcomes after UAE, UAE patients are more likely to need additional interventions than those that have hysterectomy and many gynaecologists seem convinced that a definitive treatment like hysterectomy is best. [However, we must take into account] women’s desire to avoid hysterectomy.
“In the USA, we have made efforts for years to raise the profile of UAE, with some success. Still, it is an effort of decades that will cause change. Currently, SIR is engaged in a multi-disciplinary creation of practice guidelines for the procedure.”
These guidelines, which are expected to be published in early 2021, are being developed by physicians from the specialties of gynaecology, body imaging, and IR. “The guidelines will amplify SIR’s past awareness and education efforts by providing physicians and patients with evidence-based recommendations for the optimum care of patients with symptomatic fibroids,” SIR president Laura Findeiss (Grady Memorial Hospital, Emory University School of Medicine, Atlanta, USA) comments.
In addition to SIR, the participating societies are Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Fédération Internationale de Gynécologie et d’Obstétrique (FIGO), the American Association of Gynaecologic Laparoscopists (AAGL), the American Society for Reproductive Medicine (ASRM), and the Society for Advanced Body Imaging (SABI).
To attract a Medicare rebate for UAE in Australia, the patient must be referred by an obstetrician/gynaecologist, which Goh says “brings up potential referral bias”. However, he notes that the low UAE rate in Australia is “likely multifactorial”, and that IR can only fulfil its potential in terms of treating the appropriate number of eligible patients when interventional radiologists “take greater clinical ownership of their patients”. To Goh, this looks like preprocedural consultations with patients, postprocedural care, and having an inpatient bed card. He also stresses that gynaecologists and interventional radiologists alike should have an understanding of the pros and cons of both embolization and surgical options, to allow patients to make an informed decision about their fibroid treatment.
Urbano concurs with Goh’s assessment that there are numerous reasons for the underutilisation of UAE globally, and particularly in Spain. “Of course, like in France, gynaecologists actively block this treatment because they fear losing patients,” he says. “Furthermore, when obtaining informed consent for hysterectomy, it is mandatory to notify the patient that UAE is offered as an alternative, but it is often not even mentioned. Gynaecology tends to be a speciality that does not participate in multidisciplinary work. They have countless patients, they do their own diagnostic tests, and their patient management is routine.
“Interventional radiologists have too much work in Spanish public hospitals, so UAE is not an important focus for them. In addition, while they are experts at doing the procedure, they are not always involved in the diagnosis, pain management, and patient follow-up. Interventional radiologists are only fully involved in the UAE process in private practice and some public hospitals. Less than 50% of IR services in Spain have a clinic and beds. In my experience, this is crucial for us to do all those type of procedures in which IR competes with other specialties.”
Zuleta argues the same in El Salvador. She says the underutilisation of UAE is due to “a lack of knowledge by other specialties, the usage of old protocols and guidelines, and highly unequal access to healthcare for women. We do have access to technology: we have angiosuites, CTs, ultrasounds, MRI, but what we lack is education. We at SIDI [Sociedad Iberoamericana De Intervencionismo] believe that supporting education in our countries is the best way to improve the management of patients, especially in IR.”
In the USA, SIR is running its own campaign—the Vision to Heal, Together, launched in September 2019—to bring IR procedures to the forefront of the public consciousness. According to an SIR press release, this aims to “build stronger partnerships with referring physicians and to empower patients to ask about IR as a treatment option.” The campaign is not specific to UAE, it is focused more broadly on vascular disease, cancer, and men’s health conditions, which includes uterine fibroids. SIR is using a combination of radio, digital, and social media advertising in four pilot US markets (Washington, DC; Rochester; Little Rock; Portland) to spread its messaging.
The campaign was inspired in part by SIR’s 2017 report finding the lack of awareness among patients and the lack of information from referring physicians. “By educating both groups, we hope to not just reduce the knowledge gap, but to build trust among the specialties so that patients are presented with all of their treatment options up front,” says Findeiss.
The Vision to Heal, Together campaign ran through to the end of March 2020. SIR reports positive engagement and social media posts. “We have seen friends sharing information with friends in need and others simply commenting to vouch for the life-saving and quality-of-life improving power of interventional radiology,” Findeiss comments. “There is a real desire and need for more information about minimally invasive treatments across the board.”
In Australia, the wording of the Medicare item for UAE is under review, which Goh hopes will change to improve patient access to the procedure. The Interventional Radiology Society of Australasia (IRSA), of which Goh is president, is “working on the UAE issue.” Goh says: “We are working with some other stakeholders to increase public awareness online, and via print and social media.” IRSA is updating its website to list practitioners who can perform UAE, and is leading a global position statement to help further increase awareness.
In Spain, Urbano stresses that the key lesson from the French action is that it is patient-focused. “SERVEI’s position is not to start turf battles,” he says. “We have lost too much time and energy in the past with no-way fights. Our policy is to show what IR work is, and to demonstrate he advantages of our treatments to patients.”
French interventional radiologists are protesting the high number of “unnecessary” surgeries taking place nationwide, stressing that there are minimally invasive alternatives with fewer complications available. The Federation de Radiologie Interventionnelle (FRI), has launched a public awareness campaign to educate potential patients about interventional radiology (IR) procedures, with a specific emphasis on uterine artery embolization (UAE), which it claims is an underutilised, safe, and effective option for patients who do not want a hysterectomy. To read about this issue on an international stage, read the full coverage here.
“I think gynaecologists have a real scepticism of the effectiveness of UAE,” FRI president Hélène Vernhet-Kovacsik (Arnaud de Villeneuve Hospital and Montpellier University, Montpellier, France) tells Interventional News. “They do not trust this technique, which they do not practice.”
The French guidelines for the therapeutic management of uterine fibroid tumours, published in the European Journal of Obstetrics and Gynecology and Reproductive Biology and last updated in 2012, state that “Because UAE is an effective treatment with low long-term morbidity, it is an option for symptomatic fibroids in women who do not want to become pregnant, and a validated alternative to myomectomy and hysterectomy that must be offered to patients.” However, Vernhet-Kovacsik says that though UAE is in the guidelines, and “should be offered as an alternative to hysterectomy for all patients”, it is not. On average 2,000 UAEs are performed a year in France. In contrast, 40,000 patients have hysterectomies annually.
When first elected president of the FRI, Vernhet-Kovacsik set up specific working groups within the society. The communications working group, headed by Vincent Vidal (Hôpital de la Timone, Marseille, France), have launched a public awareness campaign in an effort to educate the public about UAE and other minimally-invasive options. With a focus on pelvic interventional radiology (IR) in 2020, the society’s edifying efforts are dedicated to UAE, haemorrhoids, and prostate artery embolization (PAE). As a world-leading advocate of the “emborrhoid” technique—the embolization of the superior rectal arteries—and the lead author of the 2015 study demonstrating the procedure’s efficacy, Vidal is a global specialist on haemorrhoids. PAE is the principle purview of Marc Sapoval (Georges Pompidou European Hospital, Paris, France, and founder of the GEST Symposium), who is a prominent member of FRI. UAE was chosen for more political reasons: in Vernhet-Kovacsik’s words, the lack of referrals and general awareness “seemed to us very stigmatising and unfair. How is it that a technique recognised as effective and less morbid than hysterectomy, cited in the gynaecology guidelines [and] with long established scientific evidence, remains as little used?”
The communications working group organised a press conference with French media on 23 January at the Georges Pompidou European Hospital in Paris. This resulted in a double page spread appearing in the non-specialist daily newspaper Le Parisien, featuring patient testimonials in favour of UAE, and interviews with Vernhet-Kovacsik, Sapoval, and other French interventional radiologists with private practices explaining technical details of the procedure, as well as describing how and why it is underutilised. The article cited a lack of information provided to the patient from interventional radiologists’ medical colleagues leading to a low referral rate.
Following this, Vernhet-Kovacsik recounts how Sapoval appeared on French radio to discuss embolization. “[He] brilliantly exposed the clinical and economic effectiveness of all the IR treatments, and presented emerging techniques,” she enthuses. Following the success of these media engagements, FRI produced a press kit summarising current scientific data on pelvic IR, which can be used to inform future media opportunities, in France or abroad.
“We also wanted to communicate [the impact on] quality of life,” Vernhet-Kovacsik says of the FRI media strategy, “because it has become a major concern for patients, and is an advantage of IR procedures, which have very low morbidity and require very short hospitalisations in comparison with alternative surgical techniques. This also made it possible for us to directly address patients by proposing solutions to symptoms that are not always recognised as pathological, but [are] handicapping in everyday life, such as pelvic pain or urinary discomfort.”
FRI has taken a multimodal approach to disseminating their message. The society made a short animated film about pelvic IR, which is freely available on their YouTube channel. This also hosts video coverage of radiology congresses and the preprocedural film shown to patients in waiting rooms. Additionally, Sapoval is working on a patient-facing website, to launch 13 June this year. “We are testing and finalising it now,” Sapoval tells Interventional News, “then we will be launching it nationwide. The website will inform patients of treatments for fibroids other than hysterectomy, so they can be aware that they may not need one.” FRI also plans to use Facebook to engage the online community through question and answer sessions, mediated by specialised health publications, designed to offer patients a chance to speak directly with an interventional radiologist.
This direct engagement is part of a trend Vernhet-Kovacsik has identified. “The patient-doctor relationship is changing—it is no longer directive, but participative. The dissemination of information on the web via social media and the creation of user groups should be [a step] in the right direction.” Following the increased interest in UAE that succeeded the Le Parisien article, FRI set up an online directory of pelvic IR centres in France, allowing patients to find these services more easily.
Sapoval believes this increasingly participative relationship is important because patients will have to lead the charge in advocating for UAE. “We have a very unethical situation in France where women get hysterectomies instead of embolizations because the obstetricians/ gynaecologists are operating on patients instead of referring them to interventional radiologists. This is one of the interventions where we have strong, level one evidence, and despite a lot of effort, we have not seen a lot of movement in the last few years. This is the case in many other countries as well, so we wanted to take the lead and raise the flag for UAE.”
When questioned about why he thinks the discrepancy between hysterectomy and UAE numbers exists, Sapoval is categorical: “There is some resistance. Some [obstetricians/ gynaecologists] do not know about UAE, and some do know, but do not want to refer patients because they are paid to perform hysterectomies.”
Vernhet-Kovacsik proposes another reason for the low referral rate: “In my opinion, this goes beyond simple corporatist considerations. Women have a doctor who has looked after them for years, has helped them give birth to their children, knows their intimate problems. A recognition has been created and it is difficult for patients to dare to express desire for a treatment different to the one proposed by the gynaecologist! However, it is shocking to offer a firstline technique (hysterectomy) which has twice as many serious complications as embolization, sometimes requires transfusions, and always prolongs work stoppage. Gynaecologists’ main argument is the increased risk of embolization versus myomectomy regarding fertility, but the vast majority of patients are over 43 years old, are not keen on pregnancy, and are treated by hysterectomy and not myomectomy: so why not perform an embolization? I think our target must be this population precisely!”
The EFUZEN study, conducted in 2017 by Vernhet-Kovacsik, Sapoval, and others from the French Society of Interventional and Cardiovascular Imaging (SFICV) research group, evaluated sexual function before and one year after UAE. The authors concluded that at one-year post-embolization, UAE significantly improves all aspects of sexual function and quality of life. Vernhet-Kovacsik stresses the pertinence of this finding: patient’s quality of life and sexual function “are rarely addressed by gynaecologists”, she says, adding that “there is a close link between fibroids and their treatment, and these aspects of life.
“The uterus is not only used for reproduction; preserving bodily integrity is also a current demand,” she comments. “I think we should all take advantage of the ‘me too’ phenomenon and, as interventional radiologists, speak out and encourage women to dare to ask for fair treatment when it comes to preserving their femininity and their quality of life. We could certainly work together: interventional radiologists, gynaecologists, and patients. I am less concerned about the future of PAE, however technically more difficult, because the importance of preserving sexual function in men will never be questioned!”
The US Food and Drug Administration (FDA) is hosting a public workshop entitled “Medical Extended Reality: Toward Best Evaluation Practices for Virtual and Augmented Reality in Medicine”. According to the agency’s website, the purpose of the public workshop is “to discuss evaluation techniques for hardware, standards development, and assessment challenges for applications of Extended Reality (XR) in medicine. The goal is to identify critical gaps that may impede medical XR device development, innovation, and to advance the evaluation of medical XR devices and applications, thus accelerating the development of safe and effective medical XR devices benefiting patients and healthcare.” Follow for live updates from Interventional News here.
13:41 GMT
Edward Margerrison (director, Office of Science and Engineering Labs, Center for Devices and Radiological Health, FDA) welcomes attendees. “I want to set the scene a bit, and explain why the FDA is involved,” he says. “We have representatives here from industry, from academia, we have healthcare professionals, and we have members of government as well. So we really have the whole community here.
“Much of the technology has been developed outside of healthcare, outside of medical devices, and is beginning to come into FDA to be regulated. It is a very interesting area for us, because companies are developing products that haven’t previously been in a regulated environment. Now is the time to get everyone on the same page, to have real discussions about how we are going to develop these technologies, and stimulate innovation.
“We are looking in a pre-competitive space. […] The technologies and products of the future should compete on how good they are for the customer. […] Being the FDA, a lot of people look to us as leaders. I anticipate a lot of people asking today, is this the end of the beginning, or the beginning of the end? We think it really is the end of the beginning. Particularly the AR/ VR space (augmented reality/ virtual reality), we know it is coming, but what are the things that we do not know yet? We want you to explain so we do not become a barrier.”
13:49 GMT
Technical session begins.
“At the end of the day, at around 4pm [ET], we will need to come up with ideas for how to move forward, and we want those ideas to come from you,” Aldo Badano (deputy director, DIDSR, OSEL, CDRH, FDA) says, encouraging attendees to “be bold” and come up to the microphone to ask questions and air opinions.
“With the exception of our keynote speaker, we do not want to focus on the hype or what would be possible if we had infinite amount of time and resources, but rather what are the current challenges that are impeding the application of these technologies in the medical field.”
13:55 GMT
General trauma surgeon Rafael Grossmann (Maine, USA), the first surgeon to use Google Glass, starts his keynote lecture.
Talking of VR, Grossmann enthuses: “It blows my mind, what the technologies allows you [to do] today. What you can see through s VR headset is incredible, and this is just the beginning. The future of this technology is to become more ergonomic, more economically viable, and, ultimately, much more common.
“We are going to see a paradigm cost in the cost, weight, size of these devices that will transform the way we do health care.”
He shares BrainLab, a company he claims is “revolutionising how we educate patients and providers in regards to surgery and planning”. A representative from BrainLab will speak later. Grossman stresses the importance of haptic feedback when using VR or AR in surgery, and says that BrainLab is a “pioneer” in this field.
Grossman is currently not using VR headsets clinically, but for teaching purposes. “This is not a matter of sterility, there is no infectious concern, but we have not found the right combination of this technology and procedure in the operating room. We are still waiting on regulations.”
14:23 GMT
Bernard Kress, an optical engineer at Microsoft, takes to the podium to present on advances in mixed reality devices and new evaluation challenges.
He says HoloLens is not advertised for general consumers, but is specifically for healthcare providers. The legal team at Microsoft requested Kress read the following disclaimer ahead of his talk: “HoloLens is not intended to be a medical or surgical device, but our clients say it can be effectively used in medical imaging and image assistant surgical planning.”
Several companies, including Philips, are already using HoloLens in the medical space, Kress comments. Atul Gupta will speak on behalf of Philips later in the programme.
“Everything that we do is centred on the human,” Kress explains. “The first pillar of mixed reality is immersion. Immersion has to be matched with what the human can actually sense. This is very difficult. You do not want to over-design your system; it has to fit what the actual human can see. You have to match the optical resolution and the field of view with that of the human eye.”
The second “pillar” is comfort. “This is especially important if the surgeon has to wear the headset for multiple hours”. There are four types of comfort Microsoft take into account: wearable comfort (taking into account size, weight, temperature, centre of gravity), vestibular comfort (the device has to be physically untethered, and a large, transparent, unobtrusive peripheral see-through is required so wearers are aware of their surroundings), visual comfort (having non-conflicting 3D cues and the shortest “motion to photon” latency possible), and social comfort (need to be able to make eye contact with nurses and technicians in the room, and not put off the patient).
“So where are we today with MR hardware?” Kress asks. “There is still a long way to go to provide full comfort to surgeons and medical professionals to allow for a revolutionary imaging and augmentation tool which will change forever the medical imaging field. This is just the tip of the ice berg.”
When asked by an audience member when the cost of MR headsets will go down (“Like VR headsets, which can be very cheap”), Kress says “It will take a long time. There is no AR market today for consumers, so we are not even looking at a consumer price point. For industry, right now, I think the device is around US$3,500. This will go down, but we are not constrained by consumer requirements.
“However, this ecosystem of companies that are trying to reduce the cost of these very complicated optics are emerging, so in five to ten years I think you will see a price decline of a degree of magnitude.”
14:52 GMT
Hiroshi Mukawa, of Sony, speaks on “Emerging technologies for addressing performance limitations in extended reality devices, such as motion-to-photon latency compensation, and retinal scan displays”.
15:09 GMT
Vinay Narayan, from HTC, delivers his talk, “Advances in virtual reality devices and characterization methods”.
“We started off in VR,” he says, “but the ability to build products that can scale in a meaningful time frame really made us switch our priorities to the VR space.” Echoing Kress, Narayan stresses that one of the key differences between AR and VR when thinking about commercialisation is that VR products are available for general consumers.
17:05 GMT
John Penczek, from NIST, takes to the podium to discuss progress in standards for extended reality devices. Providing a review of the International Organization for Standardization (ISO), he outlines how the standard-setting body has robust, specific guidance for consumer requirements for finding eye point, but that there is still more work to be done, in particular in the realm of eye tracking and direct retinal tracking.
18:45 GMT
Atul Gupta, from Philips, outlines the opportunities and challenges for extended reality devices in medicine.
Andrea Kahlberg (Milan, Italy) talks to BLearning Peripheral at LINC 2020 (Leipzig Interventional Course; 28–31 January 2020, Leipzig, Germany) about a novel sirolimus-eluting self-expanding nitinol stent that Kahlberg claims “has the ability to improve the long-term results” of superficial femoral artery (SFA) endovascular treatment.
Kahlberg outlines some of the main features and unique properties of the stent. He notes that one of the “unmet needs” of SFA stenting is durability over time, explaining that the Sirolimus is combined with fatty acids helps to improve the dispersion of the drug inside the arterial wall which helps improve durability.
He finally goes on to discuss the first in-human trial with the device, which enrolled 100 patients across Europe, and notes that the two year results were “very satisfactory” compared to other major trials that involved drug-eluting stents.
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This article is sponsored by Terumo.
The first prospective study on the combination of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and Holmium-166 (166Ho) radioembolization has shown that significant tumour reduction can be achieved in patients with bulky liver disease, a significant advancement considering the liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Just published in Lancet Oncology, Arthur Braat (University Medical Center Utrecht, The Netherlands) et al conclude that the additional radiation boost provided by 166Ho-radioembolization following PRRT leads to a high objective response rate with acceptable side effects and only temporary changes in quality of life.
The HEPAR PLuS study (Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-DOTATATE in Salvage NET [neuroendocrine tumour] patients) was a phase 2, single centre, non-randomised, noncomparative, open label study. Patients received additional 166Ho-radioembolization within 20 weeks after the fourth cycle of 177Lu-DOTATATE. Senior author Marnix Lam speaks about the study’s implications, highlighting the investigators’ use of Quiremspheres (Quirem/ Terumo Europe), and how these particles are helping to usher in a new era of more individualised treatment planning when it comes to selective internal radiation therapy (SIRT):
In my opinion, the phase 3 NETTER-1 trial in patients with grade 1 and 2 gastrointestinal neuroendocrine neoplasms was a landmark study, showing that PRRT has a huge benefit for patients in terms of progression-free survival [PFS] and overall survival [OS]. However, objective response rate after PRRT was limited to only 18%. In addition, a subanalysis showed that 68% of patients in the NETTER-1 study had bulky disease, and of those patients, 70% had bulky disease in the liver. The outcomes in terms of progression-free survival are much worse: most patients with bulky disease did not reach the median PFS of >40 weeks of the NETTER-1 trial. In other words, for patients with bulky liver disease, there is definitely room for improvement.
I was discussing this with Dik Kwekkeboom (Rotterdam, The Netherlands), one of the founders of PRRT, and a friend and colleague of mine who sadly passed away in 2017. He told me he had a fantastic new treatment for neuroendocrine tumours, but that improvements were needed for patients with bulky liver disease. At the time, we were developing 166Ho-radioembolization for liver disease, so we joined forces and came up with the design of the HEPAR PLuS study, which combines the treatments: four cycles of PRRT followed by additional 166Ho-radioembolization, which provides a radiation boost. While PRRT is a systemic treatment, 166Ho-radioembolization is a local treatment, targeting the liver metastases.
With this method, we were able to improve that 18% response rate. Total hepatic objective response rate at six months was 47% in HEPAR PLuS—a huge increase. Of course, we always have to keep in mind that response rates do not necessarily translate into improved PFS or OS, and that is definitely the next step that we want to take: conduct a randomised controlled trial to evaluate whether the increased response rate translates into a better outcome for patients with bulky liver disease.
The timing of this publication is significant. PRRT is now the standard of care, as a lot of hospitals around the world have been performing this therapy for six to 12 months. They have gained experience with PRRT, which is great, but have also found that the response rate for patients with bulky liver disease is limited.
I think the future of SIRT is individualised treatment planning. The HEPAR PLuS study shows that it is safe to combine PRRT and 166Ho-radioembolization. However, when combining two treatment modalities that involve radiation doses, dosimetry is essential. You have to calculate the absorbed dose coming from PRRT and from radioembolization, so combining these modalities is a call for improved treatment planning.
This is where the benefit of the 166Ho-microspheres comes in: we can use the exact same particles (QuieremScout) in the test procedure as in the treatment (QuieremSpheres). During the test, we only administer a small fraction of the microspheres to the patients for diagnostic purposes—a scout dose. We evaluate the biodistribution of the microspheres, and then draw an individualised treatment plan. This is possible because, even at low activities, 166Ho-microspheres are fit for imaging, unlike Yttrium-90 (90Y)-microspheres, which can only be properly imaged at high activities. Therefore, when using 90Y-microspheres, you have to use a surrogate for the pre-treatment testing, and this is not always predictive enough for the final outcome.
Having an individual treatment plan in place is crucial when combining treatments. This is not only true for PRRT, but also if we start combining immunotherapy or chemotherapy with radioembolization. This is really where the benefit of 166Ho-microspheres lies in comparison to the 90Y-microspheres.
As with all innovation, study results need to be translated into clinical guidelines for reimbursement. In Germany and Belgium, 166Ho-radioembolization is already reimbursed specifically in the treatment of neuroendocrine tumours and liver metastases.
In the most recent US guidelines for neuroendocrine neoplasm patients with liver disease, PRRT is the standard of care. Radioembolization is listed as an option following the failure of systemic treatment such as PRRT, but is also considered investigational. We want to change that. This is the first step: we have shown that the combination is safe and effective in a prospective study; now we have to conduct a randomised controlled trial. If the outcomes of this concord with those of our present study, then I am convinced we will be able to change the guidelines and offer this combined treatment approach to patients with bulky liver disease.
Irene Bargellini (University of Pisa, Pisa, Italy) shares her early experience using 166Ho-microspheres (Quirem/ Terumo): “The initial cases we have performed have confirmed that there is something really interesting going on here that deserves more attention.
Several interesting features attracted us to 166Ho-microspheres. Our physicists and nuclear medicine physicians in particular were very interested in the dosimetry—the idea of the scout dose (QuiremScout) was intriguing to them. The concept of being able to evaluate the distribution of the microspheres with MRI was also interesting to us.
Initially, we had to set up a specific acquisition protocol for MRI and SPECT [Single photon emission computed tomography].
We have treated 15 patients so far. In our limited experience, we have seen the majority of our patients responding much quicker than what we are used to seeing with 90Y microspheres. The lesions were already shrinking just 45 days post-procedure. In fact, two of our patients originally deemed to be non-surgical candidates had a resection and a transplant, respectively, after radioembolization with QuiremSpheres. The response might be so quick because 166Ho has a shorter half-life than 90Y, so the dose is deposited much quicker. This is the reason why we are currently using 166Ho-microspheres for patients that could be resected or transplanted after an adequate and fast tumour downstaging. In five patients, the Holmium scout dose (QuiremScout) was performed after an initial 99mTc-MAA diagnostic work-up, whose findings would have excluded the patients from treatment, due to high lung shunting in one patient and to heterogeneous 99mTc-MAA distribution within the tumours in the remaining four cases. In all 99mTccases, the scout dose provided different information that allowed us to safely and effectively perform Holmium radioembolization. We also try to use 166Ho-microspheres in patients with colorectal metastases, because so far we have not had very good results with 90Y in this cohort.
“Current evidence shows uterine artery embolization (UAE) is a safe and effective option to treat giant fibroids,” Oliver Llewellyn (Royal Infirmary of Edinburgh, Edinburgh, UK), Neeral Patel, and Mohamad Hamady (Imperial College NHS Trust, London, UK) et al conclude in Cardiovascular and Interventional Radiology (CVIR). They recommend that “patients should be selected, counselled, and managed accordingly” in order to benefit from this minimally invasive therapy and limit the “relatively higher risk of complications and reinterventions when compared with non-giant fibroids.”
Evidence supporting UAE for giant fibroids—defined as having a diameter of at least 10cm, and/ or with a uterine volume equal to or greater than 700cc—is sparse, according to Llewellyn and co-authors. They therefore performed a systemic review and meta-analysis of UAE outcomes for symptomatic giant versus non-giant fibroids to try and consolidate existing knowledge.
“This systematic review and meta-analysis of the current available data on the treatment of giant fibroids with UAE indicates there are several key factors required for the successful management of this unique cohort of patients,” Llewellyn tells Interventional News. “This includes close collaboration between gynaecology and interventional radiology colleagues, as well as careful follow-up in the post-procedure period.”
Primary outcome measures of the study were fibroid size, uterine volume reduction, procedure time, length of hospital stay, patent symptom improvement, reintervention rate, and complication rate. Following a systematic literature review, the authors extracted data from four relevant retrospective cohort studies, including a sum of 843 patients in their analysis. Of these, 163 (19.34%) had giant fibroids, and 676 (80.19%) had non-giant fibroids.
The main findings were:
Commenting on the reported major complication rate following embolization of giant fibroids, Llewellyn et al write: “Broadly, of the seven major complications within the giant fibroid group, three related to fibroid expulsion requiring reintervention/ endocavitatory transformation, three related to uterine infection, and one patient suffered sexual dysfunction post-UAE.” Complications can be minimised with meticulous post-procedure follow-up for women undergoing UAE for giant fibroids and dedicated management pathways for patients who present with uterine infection may expedite treatment in this patient group, subsequently reducing the requirement for emergency surgery.
Elaborating on the clinical implications of this research, Llewellyn says to this newspaper: “The results from this meta-analysis will allow interventional radiology clinicians to fully discuss the risk profile with patients in the clinic setting, allowing a fully informed decision to be made. Further work in this patient population includes a comparison with current surgical techniques such as myomectomy and hysterectomy, as well as standardising patient outcome measures for UAE, which will allow patient centred data to be pooled and compared, as has been achieved with the International Prostate Symptom Score (IPSS) for prostate artery embolization.”
While the study investigators conclude that UAE is safe and effective in the treatment of uterine fibroids of various sizes, they highlight “the heterogeneous methods used by included studies in assessing symptom severity and quality of life pre- and post-UAE”. None of the included papers used a validated measure such as the uterine fibroid symptom and health-related quality of life (UFS-QoL) questionnaire. Instead, each publication utilised their own local questionnaires, which Llewellyn and co-authors say “prevented direct comparison between studies”, missing a valuable opportunity to pool patient related outcome measures for UAE.
Cerus Endovascular receives FDA approval for its first microcatheter. The 021 microcatheter will be offered with three different distal configurations, and commercial sales are expected to begin during the second quarter of 2020.
According to a press release, the company will be developing additional microcatheters of various dimensions to offer a comprehensive selection of instrumentation for the needs of interventional neuroradiologists.
Moreover, the company announced it has successfully completed its Series B financing that has raised a total of US$19 million from current and new institutional investors since the commencement of the round in July 2018.
Completion of the Series B financing will allow the company to execute on its go-to-market strategy and to complete the planned expansion of its product portfolio, including a smaller delivery platform for its recently CE marked Contour Neurovascular System, for the treatment of intracranial aneurysms.
The company’s second implant device, the Neqstent aneurysm bridging device, is advancing through the regulatory process, with a clinical trial currently enrolling, aimed at providing additional safety and efficacy data. The Neqstent is designed to be used in conjunction with conventional embolic coils for endovascular embolisation of bifurcated saccular intracranial aneurysms.
February 2020 brings another paclitaxel device meta-analysis of randomised controlled trials in chronic limb-threatening ischaemia (CLTI) patients. Krystal Dinh (Westmead Hospital, Sydney, Australia) et al report online ahead of print the risk of all-cause mortality after treatment with paclitaxel-coated devices vs. uncoated controls in patients with CLTI in the Journal of Vascular and Endovascular Therapy (JEVT) very differently than did Katsanos and colleagues earlier this year.
Dinh and colleagues, including Ramon Varcoe (Prince of Wales Hospital, Sydney, Australia), Andrew Holden (Auckland Hospita, Auckland, New Zealand) and Peter Schneider (University of California San Francisco, San Francisco, USA) performed a systematic review on 5 November 2019 to identify randomised controlled trials using intention-to-treat analysis to compare a paclitaxel-coated device to an uncoated device in peripheral arterial disease patients having clinical follow-up of at least six months. Half of the study population had to have CLTI, or extractable data on the CLTI subgroup, if this constituted less than 50%, write the authors.
The search revealed 11 trials with 1,450 patients who were randomised to treatment with a paclitaxel-coated device (n=866) or an uncoated control (n=584). The group included 94.3% (1,367) patients with CLTI. The single endpoint was all-cause mortality, which was analysed by pooling the mortality data in a random effects model. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI).
Importantly, Varcoe clarified that this meta-analysis included the five-year IN.PACT DEEP results that were overlooked by Katsanos and colleagues. Further, they included only studies that were published, or those that authors were able to confirm had been accepted for publication and were in press.
As described in JEVT, the mean follow-up was 25.6 months (range 6–60) and 10 of 11 studies reported a minimum 12-month follow-up. There were 18.6% (161) deaths in the 866 patients in the paclitaxel device group and 19.9% (116) deaths in 584 patients who received treatment with a non-coated devices (RR 0.93, 95% CI 0.78 to 1.12, p=0.45).
This led the investigators to conclude that “there was no observed difference in short- to mid-term mortality among a pooled patient population of predominately CLTI patients treated with paclitaxel-coated balloons or stents compared with uncoated controls”.
Ablative Solutions has announced that positive six-month results from the Peregrine post-market study demonstrating the safety and efficacy of the company’s CE-marked Peregrine System infusion catheter were published in the Journal of the American College of Cardiology: Cardiovascular Interventions.
The Peregrine post-market Study is a European multicentre open-label trial that evaluated additional safety and performance of the Peregrine System infusion catheter using a neurolytic agent (dehydrated alcohol) delivered into the space outside of the renal (kidney) arteries in 45 patients with systemic hypertension. Patients included in the study were taking at least three anti-hypertensive medications.
At six months, mean 24-hour ambulatory SBP was reduced by 11mm Hg, and diastolic blood pressure was reduced by 7mm Hg. Medication adherence was monitored and remained stable throughout the study. The primary safety endpoint, defined as absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within one month, was met in 96% of patients (95% CI: 85–99%).
“Publication of the Peregrine post-market study results in a respected peer-reviewed journal is a significant milestone for Ablative Solutions and shows the potential of the Peregrine System to become an important adjunctive therapy for managing uncontrolled blood pressure in this large patient population,” said Kate Rumrill, president and chief executive officer at Ablative Solutions. “We are committed to robust clinical research through our ongoing Target BP clinical trials program to further substantiate the procedural, clinical, and health-economic benefits of the Peregrine catheter for the treatment of hypertension.”
In an accompanying editorial, Deepak L Bhatt and Arjun Majithia (Harvard Medical School, Boston, USA) noted that “although the Peregrine system will clearly need to be tested in a randomised, blinded, sham-controlled clinical trial environment, the study investigators should be complimented for using rigorous, contemporary methods including objective adherence measurements (urine toxicology analysis) and appropriate, clinically relevant endpoints (ambulatory blood pressure).”
Twelve-month results from the study presented last fall at the 2019 European Society of Cardiology (ESC) Congress (31 August–4 September, Paris, France) showed that the statistically significant reduction of 24-hour mean systolic ambulatory blood pressure measurement (ABPM) at six months was sustained at 12 months, providing evidence of consistent blood pressure-lowering effect. Twelve-month results also showed a reduction of mean systolic 24-hour ambulatory blood pressure of 10mmHg (±17mmHg, p=0.001) and a reduction in systolic office blood pressure of 20mmHg (±23 mmHg, p=0.001). No patients had major adverse events.
“Results from this trial show that the renal denervation procedure using the Peregrine Catheter and alcohol as a neurolytic agent may be safe and effective for lowering blood pressure in patients with poorly controlled hypertension on medications,” said Prof. Felix Mahfoud, Saarland University Hospital, Homburg, Germany. “The publication of these data further proves the potential value of the system for both physicians and patients. We look forward to further studying the investigational product in the randomised, sham-controlled TARGET BP clinical programme.”
Worldwide, hypertension affects more than one billion people. Management of hypertension often requires multiple medications. More than half of those treated with antihypertensive medications do not achieve their target blood pressure. High blood pressure can eventually lead to serious health problems such as heart attack, stroke and loss of vision. Approximately half of people with uncontrolled hypertension die of heart disease related to poor blood flow, and another third die of stroke.
The investigational Peregrine Kit, which includes the Peregrine System Infusion Catheter (Peregrine Catheter) and Ablative Solutions dehydrated alcohol, is currently being investigated in the TARGET BP clinical program which comprises two clinical trials. Data from the TARGET BP I and TARGET BP OFF-MED trials will be used to continue to advance the understanding of renal denervation.
At CRT 2019, (2–5 March (Washington, DC, USA) Horst Sievert (Sankt Katharinen Hospital, Frankfurt, Germany) shared early results of alcohol-mediated renal denervation, which were presented as a late-breaking abstract at the conference. Watch the video here.
Peter Schneider (San Francisco, USA) talks to BLearning Peripheral at LINC 2020 (Leipzig Interventional Course; 28–31 January 2020, Leipzig, Germany) about the relevance of dose relationship and geographical data when discussing the controversy surrounding the use of paclitaxel devices in peripheral arterial disease patients.
Schneider says that the key thing is to understand whether the relationship between paclitaxel and mortality is just an association” or “an actual causal relationship”. He notes that “if we have a dangerous agent on our hands”, it should be consistent in terms of being equally dangerous no matter where it is employed. However, Schneider highlights that looking at the data of paclitaxel-coated balloons in various countries has shown that there is “no signal” in Japan, “little or no signal” identified in the EU” and that the only signal seems to be related to the US, which Schneider describes as a “geographical inconsistency”.
Schneider believes that the importance of understanding these issues is of paramount importance and that as a physician he takes any signal on mortality “extremely seriously” but also does not want to leave “our most efficacious tool on the shelf gathering dust” if the risk is not significant.
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The UK Royal College of Radiologists (RCR) has unveiled its new curricula for clinical radiology and interventional radiology. These are “based around a small number of high-level learning outcomes that describe the holistic capabilities needed for day-one consultant practice”, according to a press release.
The reshaped curricula reflect the General Medical Council’s Excellence by Design standards for postgraduate curricula. They replace the old extensive and granular lists of knowledge, skills and behaviours with concise outcomes and tables showing the presentations, conditions, and procedures that clinical and interventional radiologists in the UK need to be proficient in.
The curricula include a requirement to maintain general radiology skills alongside special interest or subspecialty practice, ensuring that all radiologists can meet changing patient and service needs. They also include a requirement for trainees to embrace and evaluate emerging techniques and technologies, such as AI and hybrid imaging.
All trainees will transfer to the new curricula by August 2020, except those due to achieve their Certificate of Completion of Training before September 2021.
Stephen Harden, Medical Director for Education and Training in Clinical Radiology at the RCR, says: “Under the new curricula, training activities on the hospital ‘shop floor’ will not be affected—what is changing is how trainee progress is monitored and how and when training requirements are deemed to be met fully.
“The expectation is that trainees will be able to deliver a broad range of care, as part of maintaining a generalist skill set.”
Under the current 2016 curricula, trainees are assessed against long lists of competencies. Under the new 2020 curricula, they will instead be judged against 12 high level capabilities in practice. Six of these describe generic capabilities that apply to all doctors, including areas such as ongoing professional and reflective practice, commitment to quality improvement, leadership and teaching and supervision abilities.
There are six radiology-specific capabilities in practice that describe the unique role of a radiologist, plus two additional capabilities for interventional radiology subspecialty trainees, which focus on the ability to provide high-standard interventional care to emergency and elective patients, and the ability to clinically manage all stages of a patient’s admission and treatment.
Assessment of the capabilities is based on intuitive entrustment scales that will support professional judgement and, along with progression grids, provides clear expectations for trainee progress.
Harden continues: “The idea behind the collated capabilities is that these rounded skills are what are expected of a new clinical or interventional radiologist on day-one of consultant practice.
“The new curriculum states much more clearly what is expected of—and to be demonstrated by—trainees, and makes clear to the public and the medical community just how broad the role of hospital radiologist is, around and beyond our core function of image interpretation.
“The inclusion of emerging technology and techniques future-proofs the curriculum and ensures that trainees are able to embrace new advances.”
The curricula and a package of key documents, implementation tools and supporting information are hosted on a dedicated section of the RCR website.
Robert Shahverdyan, head of the Vascular Access Center at Asklepios Klinik Barmbek, Hamburg, Germany, has recently published a retrospective analysis of his first 32 consecutive radiocephalic (forearm) VasQ External Support procedures in the Journal of Vascular Access. The paper demonstrated that using VasQ as standard of care for radiocephalic fistulas resulted in a significant improvement in his centre’s primary fistula failure and longer-term secondary patency rates with less repeat interventions when compared to historical controls.
Radiocephalic fistulas are the preferred vascular access to facilitate dialysis treatment as compared to other modalities despite the reported high rates of primary failure and need for frequent interventions. Historically, the primary fistula failure rate for radiocephalic fistulas at Shahverdyan’s centre before the use of VasQ was 29%, which compares well to the typically higher rates reported in the clinical literature for this type of fistula. That primary failure rate has dropped to 6% since he began using VasQ as the standard of care for his radiocephalic patients.
Additionally, his rate of repeat procedures required to make the fistulas usable dropped from 0.62 per pt-yr to 0.26 per pt-yr with VasQ. For context, typically reported rates for repeat procedure are between one and two interventions per pt-yr in Europe with rates in the USA reported at over three per pt-yr. His data aligns well with previously reported clinical studies for VasQ for upper arm fistulas and shows that the adoption of VasQ as the standard of care improved patient outcomes of an already high performing centre.
Shahverdyan commented: “Haemodialysis patients are a particularly challenging patient population with historically poor outcomes related to vascular procedures. As surgeons we must be skeptically optimistic about any new technology that promises better outcomes for our patients until we see it perform in a real-world setting. After careful review of my results over the last few years, I was excited to learn of the beneficial impact VasQ has had on my haemodialysis patient outcomes and am happy that I can offer them a better option with VasQ as my new standard of care for their vascular access.”
“The results from Shahverdyan’s practice is a significant step forward for Laminate to meet our goal of providing surgeons tools to create more usable fistulas,” said Laminate CEO Tammy Gilon. “We are excited to continue to partner with physicians like Shahverdyan as they work to create functioning fistulas for each of their patients.”
The Society of Interventional Oncology (SIO) hosted its first artificial intelligence (AI) hackathon at this year’s annual meeting (31 January–3 February, New Orleans, USA). Out of 11 international contestants, Leigh Casadaban (Brigham and Women’s Hospital, Boston, USA) won the competition for her project entitled “Feasibility study of deep learning convolutional neural networks to predict clinical benefit of transarterial radioembolization using pretreatment CT and SPECT imaging”.
“Our study plans to look for imaging or patient/treatment factors that predict outcome after transarterial radioembolization (TARE) with Yttrium-90 (Y-90) microspheres,” Casadaban explains. “Our hypothesis is that the deep learning system using 3D treatment planning data will outperform standard dosimetry estimates in predicting progression-free survival.”
Julius Chapiro (Yale School of Medicine, New Haven, USA) from the SIO Research Committee hosted and moderated the AI hackathon, which was funded with unrestricted grants from Guerbet and Visage Imaging. This novel type of session gave the opportunity to 11 international teams to pitch their pre-selected proposals to a jury panel, composed of international interventional oncology (IO) experts and industry representatives. The jury evaluated the proposals on the criteria of healthcare impact, innovation, translatability to product, and presentation. Each five-minute pitch presented “AI-driven research project proposals with high translational value”. The proposed projects all offered AI-based solutions to a specific clinical problem in IO, and presentations were followed by one minute of questioning from the judging panel.
Speaking to Interventional News about her win, Casadaban says: “I am happy to have won the hackathon because it validates our project idea. The prize money also helps us to afford software and hardware for data processing, and for our data scientists and software engineer collaborators.”
Some of the US$7,000 prize money will go towards a new computer with imaging software to process images, Casadaban shares, as well as statistical software for data crunching. The rest will go towards the Brigham and Women’s Hospital and Massachusetts General Hospital Center for Clinical Data Sciences, which hosts data scientists, software engineers, and clinicians working to solve healthcare problems.
“The hackathon was a fun format,” Casadaban says, as it is “different from other formal talks, in that presenters stood directly in front of the judges, not behind a podium”. She continues: “We had five minutes to ‘pitch’ our idea before the buzzer went off. I think the format made the session fun and exciting.
“AI already influences many things around us, and is incredibly powerful. The field is evolving quickly, and an event like this raises awareness of new developments and tools, encourages brain storming, and also enables IO projects to get their feet off the ground. We have just started to scratch the surface of how AI can improve our clinical practice. The opportunities are boundless.”
“We did not expect to collect so many excellent proposals as the AI hackathon was announced on very short notice”, says Chapiro. “The number of excellent and mature proposals and the great variety of different scientific questions raised during our session clearly illustrates the untapped potential of our community and the need for funding of structured machine learning-driven research. With this format, we can mobilise the IO community to enter the era of data science”. The SIO confirmed plans to make the AI hackathon a recurring session for upcoming meetings, including during the next SIO annual meeting, which will take place in San Francisco, USA, in January 2021.
Sirtex Medical has announced a collaboration with MIM Software. Under the terms of the agreement, Sirtex’s sales teams in the USA, Europe, and other key global markets will offer MIM SurePlan LiverY90 software alongside the company’s SIR-Spheres Y-90 resin microspheres to improve treatment precision for patients with hepatic tumours.
According to a company press release, MIM SurePlan LiverY90 provides timesaving tools and post-treatment dosimetry for interventional radiologists and nuclear medicine physicians treating hepatic tumours with SIR-Spheres. The software allows physicians to calculate the dose delivered by the microspheres to improve treatment decisions and patient care. The technology also incorporates CT, PET, SPECT and MRI scans simultaneously to deliver results on spheres deposition, coverage, and absorbed dose.
“Given the overlap of their technology and our SIR-Spheres product, Sirtex and MIM have a long history of working alongside clinical care teams,” comments Kevin Smith, Chief Executive Officer of Sirtex. “Now as partners, we will be able to combine our expertise and resources to provide an even higher level of support to treat liver tumours. We are excited to see how this collaboration will benefit physicians and ultimately improve treatment outcomes for patients.”
“We are proud and excited to partner with Sirtex, mainly because it will provide access to personalised dosimetry for a large number of patients across the globe,” says Andrew Nelson, Chief Executive Officer of MIM Software. “The treatment of liver tumours requires a multi-disciplinary approach, so it is a natural evolution for companies like ours to partner to provide an even faster, higher level of support and resources to treatment teams.”
In the USA, SIR-Spheres Y-90 resin microspheres received Premarket Approval (PMA) from the US Food and Drug Administration (FDA) and are indicated for the treatment of non-resectable metastatic liver tumours from primary colorectal cancer in combination with intrahepatic artery chemotherapy using floxuridine. SIR-Spheres Y-90 resin microspheres are approved for the treatment of inoperable liver tumours in Australia, the European Union, Argentina, Brazil, Canada, and several countries in Asia, such as India and Singapore.
Sean Lyden (Cleveland, USA) talks to VEITHtv at the VEITHsymposium 2019 (19–23 November, New York, USA) about the “tumultuous” year for the industry following the publication of the 2018 Katsanos meta-analysis which showed an increased mortality risk with the use of paclitaxel-coated balloons at five-years in intermittent claudication patients.
Despite FDA analysis which indicated that there “was something to this signal”, Lyden explains that that the Katsanos meta-analysis “did not have patient-level data” and says VIVA Physicians’ findings saw the FDA’s 58% mortality signal fall to 27% through five-years. Lyden goes on to discusses his views on the inconsistent data and how it might affect practitioners, outlining the need for “informed consent” from patients.
“We have seen a huge downturn in the use of paclitaxel” says Lyden, adding however that there is now “a light at the end of the tunnel” with the FDA, regulators, physicians and industry all partnering to decide on the next steps including looking at “improving trial design”.
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Dierk Scheinert (Leipzig, Germany) moderates a panel with Eva Freisinger (Münster, Germany) and Thomas Zeller (Bad Krozingen, Germany) to discuss the developments over the past 12 months surrounding the safety of paclitaxel.
Zeller notes that further analyses of the randomised controlled data of drug-coated device use in claudicants has indicated a lower risk of mortality. Importantly, he states that the addition of patient-specific data information, as requested by the US FDA, has highlighted a “significant reduction” in the overall risk. Zeller adds that with the inclusion of large real-world data analysis with appropriate sample size, the mortality risk totally disappears. He goes on to highlight his own centre’s findings of more than 1,500 patients suffering claudication or rest pain, split between a control group and those treated with a drug-coated balloon (DCB). The “major finding” of this comparison was a mortality benefit favouring the DCB approach, which Zeller notes contradicts the Katsanos et al findings in a real-world setting.
Freisinger discusses her team’s analysis of a real-world dataset which included insurants from German company BARMER Health Insurance. The findings showed “no evidence of a long-term mortality signal” at 7.6 years and a “slight beneficial signal” favouring DCB use. She outlines some of the study’s strengths, but cautions that there is “no study without limitations”.
Zeller maintains that it is important to complete the long-term follow-up of current trials, which he believes “will tell us that there is no real mortality issue”. He finally addresses Katsanos et al’s most recent meta-analysis (January 2020, Journal of Vascular and Interventional Radiology) – which he claims has “many limitations” – of DCB versus plain balloon angioplasty in below-the-knee lesions, which suggests a higher mortality in the short-term. This, according to Zeller, goes against the grain of the original findings which only showed a signal in the long-term.
Both Zeller and Freisinger conclude by agreeing that they will continue to use paclitaxel-coated devices, and Scheinert, for his part, says this new real-world safety data is “reassuring”.
This video is sponsored by Medtronic.
Bluegrass Vascular Technologies (Bluegrass Vascular) announced today that the US Food and Drug Administration (FDA) has granted a de novo classification order for its Surfacer Inside-Out access catheter system. The Surfacer system is intended to obtain central venous access to facilitate catheter insertion into the central venous system for patients with upper body venous occlusions or other conditions that preclude central venous access by conventional methods. The Surfacer system employs a novel Inside-Out approach.
“The Surfacer system offers a safe and effective approach to reliably preserve and restore critical upper body vascular access sites,” stated Mahmood Razavi, interventional radiologist at St. Joseph Hospital in Orange, USA and lead principal investigator of the SAVE-US (Surfacer system to facilitate access in venous Occlusions—United States) IDE study. “This is an unmet clinical need for patients who require life-saving therapies, such as dialysis, and who have limited options due to venous obstructions.”
The Surfacer system is the first FDA cleared medical device to facilitate upper body central venous access in patients with venous obstructions or other conditions that preclude access by conventional methods. Approval is based on the results of the SAVE-US trial. Of the thirty enrolled patients, 90% met both the primary and secondary efficacy endpoints despite a complex patient population comprised largely of Type 3 and 4 obstructions (3 or more obstructed vessels). No device related adverse events were reported, confirming the safety and performance of the Surfacer system.
“Thoracic central venous obstruction (TCVO) is a costly problem associated with increased patient morbidity and reduced quality of life,” stated Bart Dolmatch, interventional radiologist at The Palo Alto Medical Foundation (Palo Alto, USA). “We have recently published reporting standards that create a common language for understanding and describing signs, symptoms, functional impairment, and anatomy of TCVO. BVT incorporated elements of these reporting standards into the SAVE-US trial, demonstrating the clinical impact of the Surfacer system. Now that it has been FDA cleared, the Surfacer will be part of the treatment algorithm for my patients with TCVO.”
Thoracic central venous obstruction occurs in roughly 40% of patients where haemodialysis is performed via a central venous catheter. While permanent arteriovenous fistulas are the preferred form of vascular access for haemodialysis patients, central venous catheters continue to serve as an important bridge to securing long-term access for life-saving haemodialysis treatment. The current approach for most patients with central venous obstructions is to use an alternative vein, which reduces the ability to place and mature a functioning fistula, resulting in increased catheter days and costs.
The Caterpillar and Caterpillar Micro arterial embolization devices (BD) have received US Food and Drug Administration (FDA) clearance.
The Caterpillar devices utilise a novel dual action design that includes both nitinol fibre segments and an occlusive membrane, according to BD.
This is the eighth approval from the FDA for BD this year.
Rist Neurovascular recently announced that it has received US Food and Drug Administration (FDA) 510(k) clearance to market the Rist Cath Radial Access Long Sheath (Rist Cath) for the introduction of interventional devices into the peripheral, coronary, and neurovascular system.
Rist Cath is the first device specifically designed for the unique demands of accessing the neurovasculature through the radial artery in the wrist, enabling the full gamut of neurovascular procedures to be performed transradially.
“Although transradial techniques have become the standard of care in the cardiac interventional communities, neurointerventionalists have not previously had the appropriate tools to allow these advantages for patients undergoing neurovascular procedures,” said Pascal M Jabbour, professor of neurological surgery and chief of the Division of Neurovascular and Endovascular Neurosurgery in the Department of Neurological Surgery at the Sidney Kimmel Medical College at Thomas Jefferson University (Philadelphia, USA).
He continued: “Clearance of the Rist Cath provides neuroendovascular specialists a safe and durable tool to perform neuroendovascular interventions via a transradial approach, and allows us to offer improved care for patients while pushing the envelope of what our field has to offer.”
“The Rist Cath was developed to meet a well-documented need expressed among physicians conducting neurovascular surgeries,” said Martin Dieck, director, Rist Neurovascular. “This FDA clearance will allow us to make the Rist Cath broadly available to these surgeons, improving care for the millions of patients undergoing procedures to treat conditions such as stroke, brain aneurysms and other neurovascular conditions.”
While the American Heart Association has recommended a radial-first strategy for acute coronary syndrome since 2018, there has never before been a FDA cleared device that enabled the use of this strategy specifically for neurointerventional procedures.
Cardiology studies have demonstrated a significant reduction in access site complications as well as mortality with radial access. Furthermore, radial access procedures offer several additional advantages, including strong patient preference, immediate ambulation, and reduced costs.
At the International Stroke Conference 2020 (18–21 February), being held in Los Angeles, USA, there will be several presentations exploring the benefits of radial access for neurointerventional Surgery.
XableCath has announced that its XableCath Crossing catheters have received CE mark for peripheral use. Its crossing devices will be available for sale in Europe in two versions, a blunt tip and an abrasion tip, in a variety of diameters and lengths. XableCath received US Food and Drug Administration (FDA) clearance for its crossing devices last year.
Physicians in the USA have had remarkable success using the XableCath Crossing devices to cross challenging lesions in the peripheral vasculature. The product has been used to successfully cross recalcitrant chronic venous obstructions, including what is considered by many clinicians to be the most challenging venous procedures—crossing in-stent restenosis.
“I am pleased XableCath intravascular products continue to demonstrate a high degree of safety and effectiveness crossing a variety of challenging lesions successfully in both venous and arterial disease. Our devices have helped many patients and physicians in the U.S. Now that we have achieved CE mark, we will be able to offer our crossing solution to help patients and healthcare providers in Europe.
In a time where the vast majority of new products are more costly and complex than the technologies they propose to displace, it is especially fulfilling to our team to bring a new product to market that is easy to use, effectively crosses occlusions, and more favorably priced than the existing crossing devices. Economic pressures on our global healthcare system are tremendous and XableCath Crossing devices were conceived to improve patient care at a lower overall procedural cost, which I believe we have achieved,” said XableCath president and chief executive officer, Lisa Dunlea.
“With a CE mark, we look forward to bringing this wonderful, easy to use, and highly applicable interventional device into our Neu-Bethlehemcath-lab in Germany. Our centre conducted the first-in-man studies using the device to recanalise very challenging lesions in patients with no other interventional options and critical limb ischaemia. I am excited to bring it back more fully into my lab to help me and my patients,” said Johannes Dahm, professor of Medicine-Cardiology-Angiology in Göttingen, Germany.
Laminate Medical Technologies has announced the completion of enrolment into the VasQ external support US pivotal study. The study was conducted at 17 sites across the USA and prospectively enrolled 144 male and female patients in need of an arteriovenous fistula (AVF) for haemodialysis. Both brachiocephalic and radiocephalic AVF patients were included in the study. The patients will be followed for two years with the primary endpoint of primary patency analysed at six months.
AVFs are the preferred vascular access to deliver haemodialysis treatment due to the low rates of infection and mortality relative to alternative options for patients. However, the natural biologic responses to the changes in haemodynamics and mechanical stress at the vein wall from the arterial flow tends to induce in inward tissue growth and ultimately AVF failure. Reported failure rates for AVFs are as high as 60% and require costly additional procedures to correct or a new AVF creation altogether.
VasQ is designed to address both the haemodynamic and mechanical factors associated with AVF failure. The device is a nitinol external support placed around the artery and vein at the creation site that optimises the transition of arterial flow to the vein while reinforcing the vessel wall against the increase in mechanical stress. VasQ patients in Europe have demonstrated increased rates of receiving a usable AVF with fewer early failures and additional procedures in multiple prospective and retrospective studies. The clinical benefits of VasQ experienced in Europe are expected to be validated in the US dialysis patient population within this fully enrolled pivotal study.
Ellen Dillavou of Duke University (Durham, USA) stated: “VasQ promises to be a new standard of care for fistula creation to give my haemodialysis patients the greatest probability of success. The device has performed as expected in my study patients so far, and I look forward to continue to utilise it once commercially available in the USA.”
“We are grateful to our principle investigators for their commitment to this study,” said Laminate CEO Tammy Gilon. “The results will be an important addition to the mounting evidence supporting the benefits of VasQ to promote the usability of both forearm and upper arm fistulas.”
The first head-to-head randomised controlled trial to directly compare two different drug-coated balloons—the lower-dose density (2μg/mm2) Ranger and higher-dose density (3.5μg/mm2) IN.PACT—showed similar results with regard to effectiveness and safety through 12 months for femoropopliteal interventions, Dierk Scheinert (Leipzig, Germany) tells BLearning at LINC 2020.
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A proof-of-concept study has demonstrated the feasibility of using computed tomography (CT) with a novel composition of radiopaque microspheres in Yttrium-90 (Y-90) radioembolization to determine tumour radiation dose exposure. Presenting these early results at Spectrum (18–21 January, Miami, USA), Robert Abraham (Dalhousie University QEII Health Sciences, Halifax, Canada), told delegates that this technique “may provide increased confidence in the true spatial distribution of the microspheres, and hence the distribution of Y-90 activity in tumour”.
Outlining his hopes for Y-90 based CT radiopacity, Abraham said he thinks it “may improve characterisation of the absorbed dose heterogeneity in radioembolization”, and “may improve our understanding of the relationship between absorbed dose and tumour response, which could ultimately translate into improved patient outcomes.”
Using a proprietary blend of non-irradiated radiopaque Y-89 glass microspheres (30µm in diameter), Abraham described how the investigators injected 480mg through a 0.021” Cook Cantata microcatheter into the segmental arteries in the left kidney of a hybrid farm pig. Following sacrifice, the kidney was explanted and imaged by conventional CT scan. Three-dimensional convolution of the activity distribution with a validated Y-90 dose point kernel was implemented to produce a high-resolution dose distribution.
“The dose distribution images in the axial plane using MATLAB software simulates the effect of increasing microsphere deposition,” Abraham stated, showing the Spectrum audience five axial CT images of the left kidney with increasing amounts of deposited microspheres. “As you can see, from left to right, as you increase the quantity of microspheres that are deposited in the tissue, the radiopacity increases accordingly”, he shared. Indeed, there is a linear relationship between CT Hounsfield Units (HU) and microsphere concentration per CT voxel, according to previously published work by ABK Biomedical.
Explaining the implications of this relationship between increased deposition and increased radiopacity, he continued: “Using the specific activity at the time of administration, we could potentially convert radiopacity threshold maps to dose threshold maps.” As increased deposition of microspheres correlates with an increased dose, Abraham described how it is possible to build a colour map depicting specific thresholds. “For example, here we used a threshold of 210Gy which some studies have suggested is a minimum target threshold in order to obtain tumour kill with glass Y-90. Based on radiopacity mapping and conversion to dose we may be able to confirm a minimum of 210Gy in the target tissue” he said, again showing a CT scan of the left kidney coloured according to dose.
Turning to future work, Abraham said: “We are doing ongoing studies on different compositions that have been developed. We will evaluate the potential of CT dosimetry with both cone beam CT, to allow intraprocedural dosimetry, as well as post-procedural conventional CT. We will also be commencing a hypervascular tumour model trial with activated Y-90 product. This will compare CT radiopacity-based dosimetry with time of flight PET [positron emission tomography] dosimetry.”
ABK Biomedical products are not approved for clinical use; the radiopaque microspheres are strictly investigational.
Abraham is a co-founder and shareholder of ABK Biomedical Inc., co-inventor of ABK’s proprietary investigational products, and serves as ABK’s Chief Medical Officer.
Kenneth Ouriel (New York, USA) talks to BLearning Peripheral at LINC 2020 (Leipzig Interventional Course; 28–31 January 2020, Leipzig, Germany) about a recent independent analysis to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical programme—and further studies looking at data with the IN.PACT DCB and Stellarex DCB.
This particular independent analysis, explains Ouriel, included an oncologist on the review committee to re-examine the adverse events and deaths in order to determine if these were related to paclitaxel. The findings of this review committee found that the deaths “appeared not to be related to the paclitaxel” but rather other patient issues like heart disease or lung cancer caused by smoking for example.
Ouriel concludes that he believes it was the trial design and a “failure to follow patients through five years” rather than a problem with the drug which led to the mortality signal described by Katsanos et al in the 2018 meta-analysis. He adds that he is “95% sure that what we see is not related to a few milligrams of a drug that the oncologists have been using for a long time”.
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Medtronic has announced that it will begin enrolment in a pilot study evaluating the safety and efficacy of the Symplicity Spyral renal denervation (RDN) system using a targeted procedural approach with a reduced number of radio frequency (RF) ablations. Set to enroll 50 patients at up to 15 sites in the USA and Europe, the single-arm study is designed to focus on ablating the distal main renal artery and primary branches to lower blood pressure utilising a simplified procedural approach.
“In depth anatomical study indicates the renal nerves are closer to the renal artery in the distal renal artery and branches. Focusing the procedure on these targeted locations may help us understand if we can achieve meaningful blood pressure reductions more efficiently,” said Andrew Sharp, interventional cardiologist at the University Hospital of Wales, in Cardiff, UK, and co-principal investigator of the SPYRAL DYSTAL study. “Early evidence using this modified approach has been encouraging and we intend to build on that data with the DYSTAL study.”
Renal denervation is a minimally invasive procedure intended to regulate overactivity of nerves that lead to and from the kidney, which play an important role in controlling blood pressure.
“As we strive to build upon the rigorous renal denervation studies within the SPYRAL HTN clinical programme, the DYSTAL study will help inform how we can fine-tune the procedure and continue to address the unmet need in hypertension management,” said Dave Moeller, vice president and general manager of the Coronary and Renal Denervation business, which is part of the Cardiac and Vascular Group at Medtronic.
Spyral HTN-OFF MED pivotal trial data at ACC.20
Results from the SPYRAL HTN OFF MED pivotal trial will be presented as a late-breaking clinical trial at the American College of Cardiology 69th Annual Scientific Sessions on 29 March, 2020, in Chicago, USA. The prospective, international, randomised, sham-controlled study is investigating the blood pressure lowering effect and safety of renal denervation with the Symplicity Spyral system in the absence of medication.
“Medtronic is committed to realising the full potential of renal denervation, and we look forward to the highly anticipated results of the SPYRAL HTN-OFF MED Pivotal Trial to be unveiled at ACC in March,” said Moeller.
In addition to the SPYRAL DYSTAL Study, the Medtronic SPYRAL HTN Global Clinical Program includes the SPYRAL HTN-OFF MED Pivotal and SPYRAL HTN-ON MED trials, both prospectively powered, randomised, sham-controlled studies evaluating patients with uncontrolled blood pressure in the absence and presence of prescribed anti-hypertensive medications, respectively. The program also includes the real-world GLOBAL SYMPLICITY REGISTRY that has enrolled over 2,700 patients with the Medtronic Symplicity RDN system, including 600 patients with the Symplicity Spyral catheter.
Approved for commercial use in more than 50 countries around the world, the Symplicity Spyral system is limited to investigational use in the USA, Japan, and Canada.
In the wake of overwhelming support from the British Society of Interventional Radiology (BSIR) membership, Raman Uberoi argues that interventional radiology (IR) should become a specialty in the UK. He enumerates the advantages of gaining specialty status, and outlines the necessary steps to achieving this goal.
IR practice has changed significantly from diagnostic radiology, and interventional radiologists are in practical terms image-guided surgeons. Within the Royal College of Radiologists (RCR), IR is almost identical to Clinical Oncology in terms of its pattern of practice: it is a predominantly procedural specialty, the main purpose of which is to offer treatment. Although imaging remains at the heart of IR, images are primarily for guidance rather than diagnosis. Interventional radiologists must have the confidence and ability to see patients before treatment in order to consent them appropriately and discuss all options with them; in order to do that well, they need to have sufficient clinical knowledge, including a good understanding of what other specialties have to offer for the same condition.
Interventional radiologists need to have the confidence and ability to take primary responsibility for the patient during the treatment episodes, and interventional radiologists need to follow up their own patients; if they do not things will go wrong. In order to do this, interventional radiologists require better training in clinical practice and procedures than is possible under the current system. As with surgery, interventional radiologists need training in clinical and interventional techniques. Currently, however, the training of interventional radiologists is patchy, and results in huge knowledge gaps that potentially compromise patient safety. We of course have stringent requirements about knowledge in imaging, but no formally defined comprehensive requirements for IR procedures. The focus of training and examinations for future interventional radiologists therefore still involves having to know the detailed characteristics of imaging for cases they will likely never see once they leave FRCR [Fellow of the Royal College of Radiologists], such as certain rare bone tumours, but does not necessitate having an intimate knowledge of clinical management, techniques, procedures, and equipment, such as microwave or radiofrequency equipment that the interventionalist may use several times per week.
Many trainees who might be considering a career in IR are put off applying as they still see radiology as predominantly an imaging specialty, particularly those with a surgical interest. Trainees spend much of their time in the first three years doing few or, in many cases, no IR cases at all.
An IR specialty would result in a better-defined training, assessment, and career path for interventional radiologists, and the College would be in a better position to define the numbers of interventional radiologists required in hospitals and regions. The benefit and success of an IR specialty has been shown in the USA, where it is the country’s most sought after specialty.
Specialty of course would not only improve individual training; it would also help workforce planning, and ultimately allow provision of a national 24/7 service. There are currently no defined IR numbers, so it is impossible to undertake workforce planning, with huge implications for providing 24/7 IR care. Approximately, only one in seven units is currently able to provide a comprehensive lifesaving out-of-hours service in the UK. Without a specialty, workforce planning is not possible, because there is no generally accepted definition of who is and who is not an interventional radiologist. This does not mean that radiologists who do not belong to the IR specialty would be precluded from performing certain procedures, in the same way that radiologists can do endoscopy without being gastroenterologists. Nobody would be disenfranchised, as long as they have the required skills. In fact, it is vital that interventional radiologists are available in all hospitals and settings. Drainages and biopsies will remain a core radiology procedure, with interventional radiologists also having additional training to undertake more complex and varied interventions.
The RCR is the natural home of IR, with key shared competencies and interests in patient care. With the overwhelming vote endorsing the proposal to set up an IR specialty at the annual scientific meeting of the British Society of Interventional Radiology (BSIR) in November 2019 (see above), we now have a mandate from members to approach the RCR in taking the next steps in the creation of a new specialty. The process for the creation of a new specialty is not going to be quick, easy, or straightforward. It will be necessary not only to get the full backing of the RCR, but to obtain four-nation support from various relevant bodies—for example: NHS Improvement, NHS Employers, Scottish Association of Medical Directors, Health Education England, NHS Education for Scotland, Health Education and Improvement Wales, Northern Ireland Medical and Dental Training Agency. With this support, we should then be able to get endorsement from the UK Medical Education Reference Group (UKMERG), and then submit an application with UKMERG endorsement to the Department of Health. The decision of course will ultimately be made by the privy council. There have already been some informal discussions with the General Medical Council (GMC) last summer, and more formal discussions are planned for early in 2020. To achieve specialty status, we will need strong support from many quarters, but ultimately a lot of time and hard work will be essential from many colleagues to succeed in completing this process and achieve specialty status.
Raman Uberoi is a consultant interventional radiologist and Honorary Senior Lecturer at the John Radcliffe Hospital, Oxford, UK. He is a past president of the British Society of Interventional Radiology, and is running for vice president of the Royal College of Radiologists in the UK.
With an increasing number of interventional radiologists turning their technical and clinical expertise to musculoskeletal embolization, Sandeep Bagla and Abin Sajan believe it is important to have a thorough understanding of the anatomy specific to these procedures. Here, they detail the genicular artery anatomy, in the hope that increased physician familiarity translates into an increased ability to treat patients with challenging vasculature.
In an era of cutting-edge interventional procedures, genicular artery embolization (GAE) is a minimally invasive solution for patients with mild to moderate osteoarthritic (OA) knee pain. The primary goal of GAE is to disrupt the inflammatory process by embolizing the hypervascular synovium causing the pain and disability. Successful preliminary results in pilot clinical studies have fostered a randomised control trial (RCT) at the Vascular Institute of Virginia and UNC Chapel Hill, which has finished recruitment and we hope to present our findings at the annual meeting of the Society of Interventional Radiology (SIR) next year (28 March–2 April, Seattle, USA).
As the popularity of GAE increases, it is important to have a thorough understanding of the genicular arterial anatomy. The success of GAE, as well as the prevention of non-target embolization, is associated with recognising patterns on the initial angiogram and anticipating potential obstacles during the procedure. Possible anatomic challenges include variable presence of vessels, small sized vessels, acutely angled vessel origin, presence of atherosclerosis, and collateral supply. Familiarity with typical patterns and an understanding of angiographic relationships provide a dynamic foundation when presented with challenging anatomy.
We reviewed the angiographic patterns from our first two clinical trials to identify the basic arterial anatomy and review technical pearls for the procedure. We identified six main arteries: descending genicular artery (DGA), medial superior genicular artery (MSGA), medial inferior genicular artery (MIGA), lateral superior genicular artery (LSGA), lateral inferior genicular artery (LIGA), and anterior tibial recurrent artery (ATR). Since osteoarthritic knee pain can be lateralised to either the medial or lateral aspect of the knee, we present the anatomy using the same approach (Figure 1). Of note, other vessels, including the median genicular artery, contribute to the knee joint but were not included in our study.
The medial compartment of the knee is mainly perfused by the DGA, MSGA, and MIGA. The DGA originates from the distal superficial femoral artery and has a classic inverted “Y” appearance. It divides into a straight medial saphenous branch which courses superficially, and a more torturous lateral musculoarticular branch which courses deeper in the knee.
The MSGA arises from the proximal-mid popliteal artery just above the medial femoral condyle and classically courses superiorly before travelling down to the medial knee joint. Although the MSGA is often difficult to visualise given its smaller calibre, we have noted that the luminal size of the MSGA is inversely related to the size of the DGA. The MIGA originates from the popliteal artery near the joint space and descends along the upper margin of the popliteus, before coursing anteriorly and superiorly, creating an angiographic “V” around the medial tibial condyle. The MIGA arises adjacent to the sural arteries, which are distinguished by their steeper trajectory towards the gastrocnemius musculature.
The lateral compartment of the knee is mainly perfused by the LSGA, LIGA, and ATR. The LSGA arises from the mid-popliteal artery at the level of the lateral femoral condyle. Like the MSGA, it initially courses superolateral before travelling down to the lateral knee joint. The LIGA originates around the joint space and courses laterally above the fibular head before wrapping around the lateral tibial condyle, creating a “J” appearance. In addition, this reversecurved vessel may share a common trunk with the SMGA, making catheterisation more challenging. The ATR is the most inferior branch supplying the knee and originates from the very anterior tibial artery just beyond its origin.
Although the six arteries are typically present in all patients, absence of one or more arteries might suggest that another artery is more dominant in the affected compartment. Additionally, collateral supply can cross the joint space and embolizing in such cases can lead to non-target embolization of the asymptomatic side. Cutaneous branches often appear perpendicular to the main genicular artery and terminate at the skin surface. Skin purpura from embolizing these vessels is the most common side effect of GAE, and an attempt should be made to deliver particles distal to cutaneous branches, however this may be challenging given their ubiquitous presence. Ice-packs placed on the skin may minimise the risk of non-target related cutaneous changes.
The most technically challenging aspect of GAE is catheterising the acutely angled vessel origins (Figure 2). Wire placement can be challenging in the first 3cm, and wires with a floppy tip may not allow ample support during catheterisation. In our experience, a 2.4F microcatheter was adequate in catheterising these arteries. However, there is a role for pre-shaped microcatheters, especially in acutely angled vessel origins, most notably the SMGA and the SLGA.
GAE is an exciting procedure that is leading the way for musculoskeletal embolization. We believe that a thorough understanding of the angiographic anatomy and knowledge of commonly encountered challenges will increase interest in GAE and promote future cutting-edge interventional procedures.
Sandeep Bagla is the chair of Interventional Radiology at the Vascular Institute at Virginia, Woodbridge, USA. For his GAE clinical studies, Rachel Piechowiak and Ari Isaacson are coinvestigators.
Abin Sajan is a medical student at the State University of New York (SUNY) Downstate College of Medicine, New York, USA. He was awarded the SIR Dr and Mrs WC Culp Student Research Grant for his work on the “Cadaveric Classification of the Geniculate Artery Anatomy”. He is working with Maziar Sighary on the cadaveric studies.
For some patients, kidney cancer can be effectively treated without surgery, according to the Society of Interventional Radiology’s first-ever position statement on the role of percutaneous ablation in the treatment of renal cell carcinoma (RCC). The position statement was published with an accompanying quality improvement document, which establishes performance thresholds for patient safety for interventional radiology (IR) groups who wish to develop a renal ablation practice.
The position statement and quality improvement document, published in the February issue of SIR’s flagship Journal of Vascular and Interventional Radiology (JVIR), were written by a multidisciplinary group of experts, including interventional radiologists and urologists. They were endorsed by the Canadian Association for Interventional Radiology (CAIR) and the Society of Interventional Oncology (SIO).
The authors recommend thermal percutaneous ablation for kidney cancer patients with small renal tumors, calling it “a safe and effective treatment with less [sic] complications than nephrectomy [surgery] and acceptable long-term oncological and survival outcomes.” Unlike current existing guidelines, the position statement offers recommendations on the consideration of treatment over active surveillance and discusses the incorporation of ablation for appropriate patients with T1b disease.
“Interventional radiologists are critical members of the multidisciplinary team caring for patients with kidney cancer. They have an important role, not only in the diagnosis of cancer but in its definitive treatment,” says SIR president Laura Findeiss, (Grady Hospital and Emory University School of Medicine, Atlanta, USA). “An image-guided biopsy by an interventional radiologist can confirm a diagnosis of cancer, and the interventional radiologist can be a game-changer as a partner physician on the cancer care team, expanding access to the complete range of therapeutic options, tailored to the individual patient.”
Lead author of the quality improvement document Andrew Gunn (University of Alabama, Birmingham, USA) elaborates: “These documents should expand the interventional radiologist’s approach in recommending image-guided ablation for renal cancer. First, there is sufficient evidence to suggest that image-guided ablation has nearly equivalent oncologic outcomes to traditional surgery for tumours up to 4cm in size. Additionally, ablation has fewer complications and is less detrimental to renal function than surgery. Second, there is increasing evidence that ablation can be performed for curative intent in tumours up to 7cm. While surgery is still the preferred approach for tumours this size, many patients cannot or will not undergo traditional surgery. Therefore, interventional radiologists can now recommend ablation in this patient population with more confidence.”
The position statement’s authors deemed radiofrequency ablation, cryoablation, and microwave ablation “appropriate modalities”, noting that the “method of ablation should be left to the discretion of the operating physician.”
According to the statement, thermal percutaneous ablation may have a potential beneficial role to play in the treatment of high-risk patients with more advanced disease who are not candidates for surgery, but further research is necessary. Read the full position statement and quality improvement guidelines here.
Speaking to Interventional News, Gunn comments on the timeliness of these publications: “Image-guided renal ablation is a safe and efficacious procedure for many patients with renal cancer. Despite this, there is heterogeneity among medical organisations about who might be eligible for this procedure. For example, some organisations only recommend ablation for tumours <3cm in size, while others allow ablation as a viable option for tumors up to 4cm. Furthermore, there are increasing reports of safe and effective image-guided ablations for tumours up to 7cm, but this has yet to be addressed from a societal standpoint. Thus, it was an opportune time for the SIR to release an updated position statement and quality improvement guidelines.”
RCC is the most common type of kidney cancer and an estimated 73,820 new cases of kidney cancer will be diagnosed in the USA in 2019, resulting in 14,770 new deaths.
Merit Medical announces that both its EmboCube (syringe-loaded embolization gelatin foam) and Torpedo (uniform, pre-shaped gelatin foam loaded into a cartridge with optional blunt stylet) devices are now US Food and Drug Administration (FDA)-indicated for the embolization of blood vessels to occlude blood flow, which helps control bleeding and haemorrhaging in the peripheral vasculature.
EmboCube is the only gelatin foam that is delivered pre-cut and pre-loaded into a syringe for efficiency and ease of use. Torpedo provides physicians a uniformly pre-shaped gelatin foam loaded into a cartridge with an optional blunt stylet, removing the need for manual foam shaping, providing fast and easy attachment to the catheter for delivery, a Merit press release states. EmboCube and Torpedo are made of porcine gelatin and have no ferrous composition, making it safe for use in patients undergoing magnetic resonance imaging (MRI).
Frank Arko (Charlotte, USA) talks to VEITHtv at the VEITHsymposium 2019 (19–23 November, New York, USA), about the benefits of using Shockwave Intravascular Lithotripsy (IVL) when performing EVAR and TEVAR through calcified iliac arteries.
Arko, who shares some of the downsides of traditional procedures to deliver endografts in the presence of heavy calcification, underlines that Shockwave IVL technology has been a “game-changer”. The use of IVL, he points out, can help to avoid other costly, complicated or risky adjunctive procedures, keeping EVAR and TEVAR minimally invasive just as if a patient had non-calcified anatomy—and it enjoys “fantastic” results, he notes.
This video is sponsored by Shockwave Medical.
MedAlliance has announced the award of its first CE mark approval: for SELUTION SLR, a novel sirolimus drug-eluting balloon (DEB), for the treatment of peripheral arterial disease. This approval applies to sizes from 2x20mm to 7x150mm.
This award was supported by two-year results from the SELUTION SLR first-in-human study, involving 50 patients enrolled across four German centres. SELUTION SLR is the first and only sirolimus drug-eluting balloon to have six months’ clinical follow-up demonstrating a 2.3% target lesion revascularisation (TLR) and a 0.19 late lumen loss (LLL). Two-year clinical results confirmed no deaths or amputations. Patients demonstrated clinical improvement as measured by Rutherford classification, ABI and walking distance at six months and one year, which was maintained out to two years. This evidence demonstrates that a sustained limus release drug-eluting balloon is both safe and effective for the treatment of femoropopliteal lesions over a prolonged period.
The study involved 50 patients enrolled across four German centres and achieved excellent freedom from TLR through to two years in 87.5% of subjects, with no primary TLR event observed after month 11. These figures are low compared to reported historical first-in-human studies. There were no incidences of death or the need for minor and/or major amputations over this period. These Patients demonstrated clinical improvement as measured by Rutherford classification, ABI and walking distance at six months and one year, which was maintained out to two years.
“We are very excited to have been awarded our first CE mark, which is testament to the documented efficacy and safety of our novel sustained limus release eluting balloon”, said MedAlliance Chairman and CEO Jeffrey B Jump. “We now anticipate that patients in all markets where the CE mark is recognised will be able to benefit from this breakthrough in drug-eluting technology.”
MedAlliance has recently announced completion of its below-the-knee (BTK) first-in-human study in Singapore. Studies in arterial venous fistula (AVF) and pedal arch are to start enrolling soon. A 500 patient post marketing clinical study will follow shortly.
Philips today announced four-year results from the randomised controlled ILLUMENATE pivotal trial in the USA. The data show similar mortality rates through four years for patients treated with Stellarex compared to those treated with percutaneous transluminal angioplasty (PTA). The results were presented at the Leipzig Interventional Course (LINC; 28–31 January, Leipzig, Germany) by Sean Lyden (Cleveland Clinic Ohio, USA), the co-primary investigator for the ILLUMENATE trial.
The four-year ILLUMENATE pivotal trial data are the latest data from a series of trials evaluating the safety and efficacy of the Philips Stellarex 0.035″ low-dose drug-coated balloon (DCB) in restoring and maintaining blood flow in the superficial femoral artery and popliteal arteries of patients with peripheral arterial disease (PAD). The results were evaluated compared to PTA treatment with uncoated balloons, the current standard of care.
“The four-year data from the ILLUMENATE pivotal trial further substantiates the three-year results that were presented at LINC 2019 and published in Circulation in 2019,” said Sean Lyden. “The high compliance follow-up rate further affirms the findings of these data in a complex patient population.”
The study’s patient population is complex with a high proportion suffering from severely calcified lesions. The mortality rate at four years was virtually identical between the two patient groups, at 15.6% for the Stellarex patient group and 15.2% for the control group. Secondary safety outcomes were also similar across the two groups. The four-year data also show a clinically relevant lower rate of clinically-driven target lesion revascularisation (CD-TLR) in the Stellarex DCB patient group of 28.2%, vs. 34.1% in the control group. CD-TLR is a commonly used indicator of treatment efficacy durability.
“The ILLUMENATE pivotal four-year data builds on the robust, consistent long-term data of the Stellarex clinical evaluation program,” said Chris Landon, general manager, Image Guided Therapy Devices at Philips. “We continue to make relevant data available to healthcare providers in order to help them make an informed decision on the optimal treatment for often complex disease patients with peripheral arterial disease.”
Today at the 2020 Leipzig Interventional Course (LINC; 28–31 January, Leipzig, Germany), BD announced that interim findings from the Lutonix below-the-knee (BTK) investigational device exemption (IDE) trial show positive safety results at three years for freedom from mortality, freedom from major amputation and amputation-free survival.
The clinical study is a prospective, global, multicentre, single-blind, randomised (2:1 randomisation), controlled trial comparing the Lutonix 014 drug-coated balloon (DCB) to percutaneous transluminal angioplasty (PTA) for the treatment of narrowed or obstructed arteries below the knee. The safety endpoints were assessed using a Kaplan-Meier analysis through 36 months for the intent-to-treat population, with 70% of patients having completed three-year follow up at the time of analysis. At 1,095 days, there is no significant difference in freedom from mortality (DCB: 81% and PTA: 81%, p=0.946), freedom from major amputation (DCB: 95.5% and PTA: 93.8%, p=0.268) or amputation-free survival (DCB: 77.8% and PTA: 77.8%, p=0.495).
The Lutonix 014 DCB demonstrated statistically improved primary efficacy at six months when compared to PTA (K-M analysis), with K-M curves merging at one year. There were no statistical differences in safety or efficacy beyond six months in this interim analysis. These results show that the Lutonix 014 DCB versus PTA provided statistically significant efficacy outcomes at six months with no observed safety issues out to three years.
“Critical limb ischemia (CLI) is an aggressive disease affecting approximately 3.4 million patients in the USA,” said JD Meler, vice president, Medical and Clinical Affairs at BD. “The interim long-term Lutonix BTK IDE safety and efficacy data presented at LINC is a step toward advancing CLI research and finding new treatment options for this difficult-to-treat disease.”
The Lutonix 014 DCB has been commercially available in Europe, Canada and Australia for treatment of the below-the-knee arteries in patients with CLI since 2013. The product is an investigational device in the USA.
At the 2020 Leipzig Interventional Course (28–31 January, Leipzig, Germany), Sabine Steiner (University of Leipzig, Leipzig, Germany) presented one-year results of the COMPARE-RTC of low-dose versus high-dose paclitaxel balloons. Both types of balloons exhibited comparable results with excellent effectiveness and safety through 12 months for femoropopliteal interventions including a wide range of lesion lengths. The results were also published online ahead of print in the European Heart Journal.
The authors of the study, Steiner and colleagues, note that drug-coated balloons (DCBs) for femoropopliteal interventions have not been tested against each other. They aimed, therefore, to directly compare the efficacy and safety of a high-dose (IN.PACT) versus a low-dose (Ranger) DCB, with nominal paclitaxel densities of 3.5 vs. 2μg/mm2, respectively.
This prospective, multicentre, non-inferiority clinical trial included 414 patients with symptomatic femoropopliteal lesions (Rutherford classification 2–4). Patients were randomised 1:1 to endovascular treatment with either high- or low-dose DCB after stratification for lesion length. Primary efficacy and safety endpoints comprised primary patency and freedom from major adverse events. The investigators set a non-inferiority margin of -10% at 12 months.
Total occlusions were observed frequently (>40%) and provisional stenting was performed in every fourth intervention, and non-inferiority was determined for both primary efficacy and safety endpoints at 12 months.
Primary patency was 81.5% in the high-dose and 83% in the low-dose DCB group. Freedom from major adverse events was determined in 92.6% in the high-dose and in 91% in the low-dose DCB group. The overall death rate was low (2%) and no major amputation occurred.
Profusa has announced research findings that suggest the company’s Lumee oxygen platform may help improve the clinical management of patients with critical limb ischemia (CLI) who are undergoing endovascular revascularisation treatment (EVT). The data, from a recent post-market clinical study called OMNIA (Oxygen monitoring near ischaemic areas), were detailed in a series of presentations at the 2020 Leipzig Interventional Course (LINC; 28–31 January, Leipzig, Germany).
The Lumee oxygen platform is a tiny, injectable tissue-integrated biosensor with an intelligent data platform intended for continuous, real-time monitoring of tissue oxygen levels.
“Performing revascularisation in patients with critical limb ischemia is standard practice, but the tools surgeons and interventionalists typically use to gauge effectiveness of the procedure are not ideal,” said Marianne Brodmann, interim head of the Clinical Division of Angiology, Department of Internal Medicine, at Medical University in Graz, Austria. “These research findings from OMNIA suggest that continuously measuring tissue oxygen may result in better outcomes for these patients.”
OMNIA, a multicentre trial of the Lumee oxygen platform, monitored tissue oxygen levels in the affected limbs of 35 CLI patients who underwent EVT procedures, which are designed to clear obstructed arteries. Study participants were injected with four Lumee biosensors, three in the foot and one as a reference sensor in the arm. OMNIA collected measurements of oxygen throughout the revascularisation process (with measurements performed before, during, and one, three, six, and twelve months post-procedure). OMNIA also recorded traditional haemodynamic metrics, including ankle-brachial index and toe-brachial index, and clinical assessments of wound healing at each follow-up visit.
The OMNIA data presented by Brodmann showed that increases in tissue oxygen during EVT were significantly higher in patients who experienced wound healing than in those who did not (p<0.01). In addition, tissue oxygen levels during revascularisation were a better predictor of wound healing than traditional clinical measures, such as ankle-brachial index or toe-brachial index (p=0.59 and p=0.14, respectively).
“These findings show the importance of further investigating how continuous tissue oxygen measurements may satisfy an unmet clinical need to objectively evaluate how the increases in blood flow offered by EVT actually translate into nutritive oxygen delivery to the injured tissue,” added Brodmann.
Martin Werner, an angiologist at Hanusch Hospital in Vienna, noted that traditional angiography during EVT does not sufficiently measure microvascular blood flow, a special concern for people with diabetes who may have microvascular impairment. He presented results of a retrospective classification analysis from OMNIA in which continuous oxygen traces measured by the Lumee oxygen platform were analysed throughout EVT. Findings showed that oxygen changes between discrete time points, specifically start and end of EVT, may not be predictive of wound healing, but dynamic changes continually assessed throughout the procedure were.
“These results indicate that continuous measurements of blood flow in the foot during EVT may reveal factors that provide clues to treatment outcome that would have been missed if only measured at the start and end of the procedure,” said Werner.
Stephen Kanick, data science lead for Profusa, presented data from OMNIA that evaluated how Lumee biosensors assess long-term tissue viability following EVT treatments in patients with CLI. Results showed that patients who improved showed larger oxygen increases after EVT and maintained larger oxygen values at a three-month follow-up compared to patients who did not improve.
Miguel Montero-Baker, vascular surgeon and associate professor in the Division of Vascular Surgery and Endovascular Therapy at Baylor College of Medicine in Houston, USA, discussed how tissue oxygen measured before, during and after EVT can be combined to provide a more accurate predictor of patient healing. According to Montero-Baker, “The Lumee oxygen platform gives us insights we have not had before about how CLI patients are responding to treatment.”
“These findings from OMNIA affirm the emerging role of injectable biosensors in informing the treatment of patients with limb-threatening ischemia,” said Ben Hwang, chairman and CEO of Profusa. “Being able to monitor biochemical data such as tissue oxygen on a real-time basis may mean the difference between effective interventions and a catastrophic worsening of the condition.”
New arteriovenous (AV) access results were presented at the 2020 Leipzig Interventional Course (LINC; 28–31 January, Leipzig, Germany), including data on percutaneous AV fistula creation and also the use of drug-coated balloons (DCBs) in AV access interventions. While Robert Jones (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK) opened the session by revealing a high functional patency for endoAVF at six months, Andrew Holden (Auckland University School of Medicine, Auckland, New Zealand) revealed a sustained patency advantage for a DCB compared to percutaneous transluminal angioplasty (PTA).
EndoAVF shows high functional patency at six months
Jones opened the session by presenting initial multicentre experience results of the WavelinQ catheter. Concluding that “AV is now endovascular,” results of and EU and Canada post-market study showed 95% functional patency at six months as well as a limited need for secondary procedures.
“This is the first time that this additional data on the multicentre WavelinQ study has been seen,” Jones began. Endovascular AV fistula (endoAVF) devices—created with the intention of improving fistula outcomes—have performed well in clinical studies. “There are high rates of technical success in terms of creation, higher rates of maturation and patency and low rates of complications. But we have got to bear in mind that these closely monitored clinical trials are not the real world,” Jones commented.
At the University Hospitals Birmingham NHS Foundation Trust Jones and colleagues carried out a matched comparison of WavelinQ fistulas with surgical fistulas. They had 30 in the WavelinQ arm and 40 in the surgical arm. Patency results showed that WavelinQ fistulas outperformed those created surgically.
In terms of the post-market study, this was intended to collect data on WavelinQ cathether performance and outcomes in a prospective, multicentre, international study, which recruited 100 patients across 13 sites in the EU and Canada. Jones remarked: “The post-market study forms part of a wider programme of clinical trials looking at the WavelinQ device, most of which have already either completed or been published”.
Looking to the future, Jones informed the LINC audience that there are two other studies that are being lined up—a prospective, multicentre study in the USA, which aims to recruit 250 patients and a global study looking at another 100 patients. “Hopefully both of these will be rolled out in 2020,” Jones added.
Jones concluded: “In summary, this is the first time that this post-market data is being seen. We have got 95% functional patency at six months with a limited need for secondary reinterventions.”
DCB shows sustained patency advantage over PTA
Subsequently, Holden presented 12-month outcomes of the IN.PACT AV access study, showing a 63.8% target lesion primary patency in the DCB arm compared to 43.6% in the PTA arm, with no difference in mortality.
The AV access investigational device exemption (IDE) trial was designed to evaluate safety and effectiveness of the IN.PACT AV DCB compared to PTA for de novo or restenotic obstructive lesions of native AV fistulae in the upper limbs. This was performed in the USA, in Japan and in New Zealand.
A total of 330 patients were randomised 1:1. The primary safety endpoint was serious adverse event rate within 30 days and primary effectiveness endpoint was target lesion primary patency through six months, which is defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or access circuit thrombosis measured to six months post-procedure.
It was revealed last year that IN.PACT AV access was the first DCB versus angioplasty trial to meet its primary effectiveness endpoint—a “highly impressive” primary patency of 82.2% at six months compared to 59.5% with PTA with high statistical significance and also a significant advantage in terms of freedom from CD-TLR.
“I am delighted to share for the first time the 12-month primary effectiveness endpoint. Again, a highly significant difference in target lesion primary patency—63.8% in the DCB arm compared to 43.6% for the PTA arm,” Holden revealed, adding that “there was also a highly significant difference in CD-TLR, at 35% for the DCB arm and 54.3% in the PTA arm”.
Holden added that there was less than half the rate of access circuit thrombosis in the DCB arm. “This is such a severe and catastrophic complication that, even though it did not reach clinical significance, I think is worth mentioning”.
In terms of safety at 12 months, the serious adverse event rate for the DCB arm was 46.9% compared to 69.2% for the PTA group. In the DCB arm, 40.1% had lesion revascularisations compared to 62.4% in PTA arm. Holden added that there is “absolutely no mortality signal between the two groups at 12 months,” detailing that freedom from all-cause mortality in DCB arm was 90.6% and in PTA arm was 90.4%.
Holden summarised: “For the first time we have seen sustained patency advantage for a DCB over PTA using a combination of vessel preparation with a high-pressure balloon and DCB angioplasty with a target lesion primary patency of 63.8% for the DCB compared to 43.6% for PTA arm. Fewer interventions were required to maintain target lesion primary patency in the DCB arm compared to the PTA arm, and we also saw the incidence of access circuit thrombosis more than half—something I think is very important given the severity of that complication—and no difference in mortality out to 12 months.”
The US Food and Drug Administration (FDA) have granted Intact Vascular pre-market approval application for an additional size of its Tack Endovascular System, a dissection repair device used to treat peripheral arterial dissections after balloon angioplasties.
A larger version of the device has now been cleared for superficial femoral and proximal popliteal arteries ranging from 4–8mm in diameter.
The device features adaptive sizing, which allows the implant to adapt to tapering vessels while maintaining a relatively steady radial force.
The Flex vessel preparation system (VentureMed group) is safe and effective, and appears to limit the potential risks of dissection and perforation of chronic total occlusions. This is the conclusion given by Constantino Peña (Miami Cardiac and Vascular Institute, Miami, USA) at the 2020 International Symposium on Endovascular Therapy (ISET; 22–25 January, Hollywood, USA) in his featured abstract presentation. Peña is a member of the scientific advisory board for Venture Medical.
“The Flex vessel preparation system effectively modified real-world plaque, including chronic total occlusions in the superficial femoral and popliteal arteries,” he said. “Furthermore, post-Flex subnominal inflation pressures demonstrate improved vessel compliance.” However, he added that “Further studies are warranted to confirm reduction in long-term re-intervention rates.”
In an initial, multicentre, retrospective review, investigators used the Flex vessel preparation system in 185 real-world cases: all lesions were long (over 20cm in length), and 69% had moderate to severe calcification. In 100% of lesions, there was some type of chronic total occlusion. Lesions were prepped just with the Flex system prior to either plain balloon angioplasty or treatment with drug-coated balloons (DCBs). The researchers collected angiograms at baseline, post-Flex, and post-procedurally.
Crucially, Peña said, there was a 34% mean luminal gain prior to treatment after the Flex vessel preparation system was used. Peña also reported sub-nominal inflation pressures averaged 4atm, and that there was a low rate (4%0 and grade (A or B) of dissections. He added that there were no flow-limiting dissections, perforations, or embolizations, and that provisional stenting “only occurred” in 28% of cases.
Illustrating these findings with some case examples, he talked the audience through the use of the Flex vessel preparation system in a 71-year-old man with Rutherford class 5 peripheral arterial disease (PAD). The pre-procedural stenosis rate of the target lesion was 100%. Following treatment with the Flex vessel preparation system, this dropped to 30%. There was also a 70% luminal gain post-Flex. After angioplasty, stenosis was 0%.
In the second case Peña recounted, vessel preparation with the Flex system prior to angioplasty reduced the stenosis rate from 100% to 50% in a 72-year-old woman with Rutherford class 3 PAD. There was a 50% luminal gain following use of the Flex system. Following angioplasty, the stenosis rate was 10%. These results are reported for a 41cm long lesion.
Vessel preparation aims to improve outcomes
Before discussing its importance, Peña first defined vessel preparation for the ISET attendees: “Its goal is the safe dilation of vessels to improve outcomes. This can be achieved through the modulation of a vessel in order to allow dilatation to its final diameter for definitive therapy or by modifying plaque to improve vessel compliance and reduce dissections. Vessel preparation can potentially improve diffusion of drug-coated balloon [DCB] therapy.”
Specifically referring to the Flex vessel preparation system, Peña described how it is able to “optimise the revascularisation of long, complex lesions with micro-incisions.” He highlighted multiple characteristics of the system that facilitate this.
“Firstly it is safe,” he said. “The Flex vessel preparation system creates predictable, depth-controlled micro-incisions that minimise the risk of dissection, perforation, and other complications.” Next, Peña informed delegates that the system is easy to use: “It has a simple design for treating long, complex lesions. It has a retrograde pull-back with minimal user variation, and no vessel sizing is needed.”
The Flex vessel preparation system is also cost-efficient, according to Peña. No capital equipment is required, as only one or two catheters are necessary to use Flex, which has a “quick, over-the-wire set-up”. The system has two working lengths–40cm and 120cm (in US and outside US markets, respectively). It has a reinforced braided shaft “for enhanced deliverability and torque performance”, and an atraumatic tip for “improved trackability and crossing profile”.
The Flex vessel preparation system is for use in the femoral and popliteal arteries, as well as for arteriovenous fistulas and grafts.
Stratus Medical, a new company created to focus on advancing radiofrequency (RF) ablation treatment for chronic pain, has announced that it completed a private placement to acquire the assets of NimbusRF from Biomerics and provide growth capital funding to support the continued global expansion of the Nimbus RF Multitined Expandable Electrode for chronic pain. The investment was led by Med Venture Holdings.
Nimbus was developed to address the unmet need for an easy to use, efficient, cost-effective RF device that provides a large volume and optimally shaped lesion, which interventional pain specialists, orthopaedic surgeons and neurosurgeons can use to treat pain. Nimbus has been shown to reduce procedural time and increase efficiency for hospitals and surgery centres where Nimbus is utilised. The Nimbus device is US Food and Drug Administration (FDA) cleared and CE marked. Nimbus has been utilised in over 100,000 patient treatments in Australia, Brazil, Canada, USA, UK and other countries.
Bret Boudousquie, Stratus Medical CEO offered, “The rapidly growing global radiofrequency (RF) ablation for chronic pain market has been asking for innovation and Nimbus is well positioned to become the market leader in this space to treat chronic pain. Nimbus offers a highly differentiated and patented technology to meet the needs of patients and physicians alike. With the financial support and expertise from our lead investor, Med Venture Holdings, we will accelerate the global sales and marketing efforts of Nimbus and fund development of our new product pipeline.”
Travis Sessions, Med Venture Holdings Managing Partner commented, “We see great value in the interventional pain medicine space as so much emphasis is being placed on reducing the use of narcotics and improving interventional therapies to address chronic pain and improve quality of life. We have been involved with the Nimbus product line for some time and have seen an excellent response from physician users, hospitals and ASC customers. Under Bret’s proven leadership, we expect Nimbus to increase its global presence and Stratus Medical to bring innovation to the interventional pain space.”
NOTE: This video is ONLY available to watch in selected countries and geographies
The one-year IN.PACT AV trial results, first presented at LINC 2020 (28–31 January, Leipzig, Germany), reveal that the target lesion primary patency in the patient group treated with the IN.PACT drug-coated balloon (DCB; Medtronic) was 63.8% compared to 43.6% in the group treated with plain balloon angioplasty (p<0.001) for the treatment of arteriovenous (AV) access site lesions. The trial also showed a 35% reduction in reintervention rates when a drug-coated balloon was used instead of a plain balloon and “nearly identical” safety data in the two groups with respect to mortality.
Tobias Steinke (Düsseldorf, Germany; pictured in the centre) discusses this trial’s distinctive results with principal investigators Andrew Holden (Auckland, New Zealand; pictured on the right) and Robert Lookstein (New York, USA) and establishes the importance of considered vessel preparation using a high-pressure balloon. The panel also reflects on the data from a budget impact, economic model based on the German and US healthcare systems that shows substantial cost savings when the IN.PACT DCB is used. The physicians also emphasise the enthusiasm displayed by the audience to use DCBs in this patient population, when these striking results were presented.
The IN.PACT AV access trial was the first trial to meet its primary endpoint.
This video was sponsored by Medtronic.
A ground-breaking tumour-highlighting technology—OTL38—enhances the visualisation of lung cancer tissue, providing surgeons with a significantly better chance of finding and removing more cancer than previously possible, according to a scientific presentation at the 56th Annual Meeting of the Society of Thoracic Surgeons (STS 2020; 26–29 January, New Orleans, USA).
“Lung cancer is the most common and lethal cancer worldwide,” comments Inderpal (Netu) S Sarkaria, of the University of Pittsburgh Medical Center, Pittsburgh, USA. “Technologies to improve the care of these patients are needed. Near-infrared imaging with OTL38 during surgery for lung cancer is one such promising technology with the potential to significantly improve the completeness and quality of the operation, therefore improving patient outcomes.”
Sarkaria and colleagues at six institutions (University of Pittsburgh, University of Pennsylvania, Harvard University, Cleveland Clinic, Leiden University, and MD Anderson) participated in a phase 2 clinical trial, identifying 92 patients who had lung lesions and were to undergo pulmonary resection for non-small cell lung cancer (NSCLC). Before their operations, each patient received a measured intravenous dose of OTL38, composed of near-infrared dye and a targeting molecule. The molecule attaches to folic-acid-based receptors on cancer cells and can be illuminated during surgery using a special surgical endoscope. This helps identify small, hard-to-detect cancer lesions that might otherwise have been missed and should be surgically removed.
The researchers made assessments in three phases: “lung inspection,” “tumour resection,” and “specimen check.” During the inspection phase, the molecular imaging identified 10 additional cancers—all missed when using visual examination and manual touch—in seven patients (8%). In the resection phase, researchers determined that OTL38 enabled localisation of lesions that were not found in 11 patients (12%). After surgeons found that all margins were visually adequate or clear in the specimen check, the resected specimens were further assessed using the molecular imaging. Inadequate margins (microscopic residual tumour left at the edges) were uncovered in eight patients (9%). Overall, researchers determined that the OTL38 molecular imaging helped improve outcomes for one in four patients (26%).
“OTL38 is the first technique that is specific to imaging adenocarcinomas of the lung, which is one of the most common types of invasive lung cancer, making it unique and clinically useful in this respect,” says Sarkaria. “Localisation of tumours, identification of occult tumours, and immediate tumour margin assessment during surgery for adenocarcinomas of the lung were significantly improved with the use of this technology.”
Surgery remains the best potentially curative treatment for early stage NSCLC. However, research has shown that 30–55% of patients with NSCLC develop recurrence, which often is caused by microscopic clusters of cancer cells that were undetected by standard staging methods. This suggests that complete removal needs to be ensured both macroscopically and microscopically during surgery.
“Near-infrared imaging with OTL38 may be a powerful tool to help surgeons significantly improve the quality of lung cancer surgery by more clearly identifying tumours and allowing the surgeon to better see and completely remove them—one of the most vital components in the overall care of patients with this disease,” Sarkaria posits.
Surgeons traditionally use X-rays, magnetic resonance imaging, computed tomography (CT) scans, positron emission tomography, and/or ultrasound to determine the size and location of tumours before surgery. However, these imaging modalities are rarely, if ever, used during surgery.
OTL38 is believed to be the first targeted fluorescent marker to provide this type of benefit for lung cancer. The OTL38 technology is different in its ability to detect cancerous tissue not previously identified on preoperative scans and do so in real-time, while the surgeon is operating. This is crucial in ensuring that surgeons adequately detect and remove cancer cells that may not be visible to the naked eye or located through touch. The complete removal of diseased tissue during surgery helps to avoid additional surgeries and cancer relapse, as well as increase patients’ overall chances of survival.
“Use of advanced near-infrared imaging techniques such as OTL38 may provide surgeons with powerful tools to improve the quality of lung cancer operations by better identifying small, hard-to-find tumours, finding previously undetected cancers at the time of surgery, and better assessing if the entire tumour has been removed,” says Sarkaria.
In addition, with the implementation of lung screening and the increased use of CT scans in general, cardiothoracic surgeons are seeing more patients with small or undefined nodules, so the timing of the availability of technology such as OTL38 is just right, according to Linda W Martin, of the University of Virginia in Charlottesville, USA, who was not directly involved with this research.
“In many circumstances, a preoperative biopsy is not practical or feasible, and we are faced with the need for intraoperative identification of these nodules,” she says. “This research describes an exciting new approach to localise nodules that are difficult to find without a separate procedure. More importantly, the study showed that because of this technology, additional nodules that were in fact separate cancers were found, and useful information about margin status also resulted.”
Martin describes another significant advantage that the OTL38 technology offers—the ability to better identify small nodules. This may allow surgeons to more often utilise minimally invasive operative approaches in some patients who otherwise would have been required to undergo a thoracotomy in order to find these nodules. The completion of the OTL38 Phase 2 trial in lung cancer is a major milestone, advancing the technology closer to US Food and Drug Administration (FDA) approval and commercialisation. Phase 3 trials are currently under way.
Merit Medical has announced the official market launch of its Arcadia steerable and straight balloons for vertebral augmentation. These balloons are designed to help physicians achieve controlled, precise cavity creation during unipedicular or bipedicular vertebral augmentation procedures, the company state.
The Arcadia steerable balloon provides a bipedicular footprint through a unipedicular approach for increased control of balloon placement and cement delivery when treating vertebral compression fractures. The Arcadia steerable balloon’s design has the potential to reduce procedural and fluoroscopy times and lower costs associated with additional incisions, according to a Merit press release. The Arcadia straight balloon is designed for simplified cavity creation when treating vertebral compression fractures via a standard bipedicular approach.
“The Arcadia steerable balloon offers highly accurate balloon placement through a unilateral approach, as well as a balloon with enough size and durability to reduce prominent fractures and optimise cement fill,” explains Douglas P Beall, (Clinical Radiology of Oklahoma, USA). “This system has the capability to offer bilateral results with a unilateral approach.” Beall consulted with Merit Medical as part of its development and early evaluation teams for the Arcadia steerable balloon.
Pitching the positive design features of the device, Merit Medical claim that the pre-inflation length of both product offerings—five sizes ranging from 10mm to 30mm—accommodates diverse anatomies while providing reduced compliancy and increased balloon volumes. The company also state that the size range combined with steerability enables the ability to straddle the centre midline of the vertebral body, providing a balanced inflation footprint between endplates. A high-pressure rating of 700psi helps to form even cavity creation in varying vertebral body anatomies.
Imricor Medical received CE mark certification for its Vision-MR ablation catheter, a device guided by real-time magnetic resonance imaging (MRI).
The device, which is constructed to feel like a traditional ablation catheter, uses a fibre optic tip to provide temperature sensing and comes with active MR tracking features.
The ablation catheter is designed “with the intent of enabling higher success rates along with a faster and safer treatment compared to conventional procedures using X-ray guided catheters,” the company said.
Introduced as “a pioneer in the vascular arena”, Michael Dake, senior vice president of the University of Arizona Health Sciences, Tucson, USA, addressed the audience at the 2019 meeting of Vascular and Interventional Advances (VIVA; 2–5 November, Las Vegas, USA) in a keynote lecture entitled “The future of medicine and medical education: How do we prepare the next generation?” Responsible for the integration of undergraduate and graduate education at his institution, Dake enumerated the lessons he had learned from personal experience concerning physician training.
“Big biology and big medicine is meeting big data,” he began, elaborating: “Some have called it the fourth industrial revolution, where we have an accelerated, exponential convergence of data science, physical science, and life sciences. These are creating enormous opportunities, but also challenges, for all of us. Our main task as educators is to figure out how to integrate large scale, multidisciplinary datasets into our education.”
He is enthusiastic about the prospect, fervently anticipative of the future he is advocating: “We are in a period of great innovation. There are tremendous opportunities, and these will continue to grow with technological advances that promise to impact clinical practice and transform medicine and medical education. The pace of change is rapid; thinking outside the box is essential. The potential impact on medical education and medical care is enormous.”
The convergence of precision medicine and digital medicine
“How do we drive precision medicine and data-driven healthcare into routine clinical practice?” Dake asked. He believes the answer lies with artificial intelligence (AI). “Where AI can really help in the future of healthcare,” he said, “is with merging these two dominant trends: precision medicine and digital medicine.”
Dake detailed how new technology platforms that use profiling, automation, and computing to provide deep phenotyping and risk profiling will interact with the “expanded care space”—wearables, sensors, telemedicine, social media and lifestyle metrics, data on consumer patient engagement—to enable remote monitoring of patient health status. This interaction will be mediated by machine learning algorithms. The “potential power” of AI in this context, Dake explained, is to provide analytics for improved decisions and clinical outcomes at lower cost.
Indeed, the cost of big data has decreased dramatically over the last decade. Showing a graph plotting the cost of data relative to speed versus data consumption, Dake demonstrated that the cost of data per second has dropped from nearly $3 per Mbps in 2004 to less than $0.1 per Mbps by 2013, while data consumption per subscriber per month rose from less than 10MB a month in 2006 to 225MB a month in 2013. “We can feel confident that at least computation comes cheaply. All this big data certainly is not as expensive to process as it was years ago,” he said. “That is good for us.”
Exemplifying the uses of big data, he continued: “Everyone in any healthcare centre or academic community is aware of the buzzwords around precision medicine. There is a lot of emphasis on deep phenotyping: taking large-scale datasets, predicting complex traits and disease risk, whether it is by a variety of ‘omics’ that take large cohorts of individuals and stringently control for clinically phenotyped outcomes, or by mapping genetic overlap between different diseases involving shared pathogenic elements and co-morbidity risks.”
Illustrating the idea of genetic phenotype mapping with an example, he cited a study published in Nature Genetics in 2018 by Rainer Malik (Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany) et al that identified a genetic overlap between stroke and related vascular traits at 32 genome loci in 521,612 people. Twenty-two of these loci were new to the designation “stroke risk”. This is one example of the “tremendous opportunities” afforded to researchers with access to large datasets, Dake opined.
However, he did enumerate several challenges presented by the emergence of big data. “The problem with real world data,” he said, “is that it is, indeed, real world.” Elaborating, he explained how people analytics and large scale databanks had blurred the boundaries between medical research, clinical care, and daily life, rendering every monitored event as a potential data point, every individual as a data node and research asset. Social spaces are also becoming quantifiable, and with sufficient data, investigators could reveal increasingly predictable behaviour and individual risk patterns. “This blurring of private and public spaces could lead to complex ethical and legal issues,” Dake commented, noting that consent, privacy, security and surveillance were factors society was “only beginning to address”, and that they would be “increasingly important as areas of focus”.
One of the key benefits of AI, though, is the fact that it can overcome the “bandwidth” limits of humans, Dake enthused. “There is currently a data deluge,” he said. “Our cognitive bandwidth is certainly challenged and overwhelmed, but I think there is great promise in decision support, and ways that we really can impact the future of medical education for the better.”
He informed the VIVA audience that society was at the cusp of the “era of cognitive computing and decision-support systems”. Using AI algorithms can help draw patterns and sense from such large datasets. “Clearly we have limits to individual expertise,” Dake said. “We have limits to our individual abilities to multi-dimensionally evaluate data, we have limits to our sensory systems, cognitive experiences and perceptions, and limits to our objective decision-making. This is where AI, deep learning, and machine learning can come to help us.”
Envisioning the future of medicine as made possible by AI and big data, Dake predicted: “As we evolve from qualitative, descriptive information of variable quality and provenance to quantitative data of known provenance and validated quality, [we will] change from a complex ecosystem of largely unconnected data sources to an evolving, interconnected network of data sources for robust decisions and improved care.”
Digital Darwinism: A looming data divide in medical education
“If you are teaching today what you were five years ago, either the field is dead, or you are,” Noam Chomsky (University of Arizona, Tucson, USA) said. Sharing this quote, Dake added: “Noam Chomsky is 95 years of age, and he is aware of this—so should we be”.
Dake highlighted a shift in medical education, from being science-centric in the 20th century, to becoming more data-centric between 2000 and the present day. Extrapolating this trend, he said that education will next become network-centric, stressing the importance of students gaining mastery of escalating complexity and massive data.
“There is a digital Darwinism looming,” Dake warned. “Understanding data structure and application to improve decisions and outcomes will become a critical institutional competency. With major skill gaps and predicted personnel shortages, we are going to have to train a new cadre of data scientists, both medical and non-medical, and institutions that lack adequate computation infrastructure and are not committed to this training are going to suffer ‘cognitive starvation’ and relegation to competitive irrelevance.”
So how will medical education adapt to this demand? Dake outlined his thoughts on curricular emphasis in the 21st century, believing that knowledge capture and creation, not information retention, should be the priority, and that students should be taught to distinguish between information and knowledge. He said that he would like to see future physicians have a deep understanding of probabilistic reasoning, as well as collaboration with and management of AI applications. Lastly, he underlined the importance of cultivating empathy and compassion in the next generation of doctors, emphasising the “very real” issue of physician burnout, and advocating for a more holistic curriculum prioritising students’ mental health.
The University of Arizona has implemented a programme to “future-proof” its graduates, Dake recounted, taking all of these factors into account. The institution is following a health sciences strategic plan, comprised of 26 initiatives, which cover a range of topics, from reducing student debt, to increasing the number of nurses and primary care physicians, to creating more flexible learning pathways. While every institution will need to explore ways of tackling its own specific challenges, Dake said, his keynote lecture serves as a blueprint for building a comprehensive medical curriculum capable of reimagining the physicians of the future.
“Institutions should make every effort to take advantage of the strategic synergies that can arise by creating a virtuous cycle connecting education with research and patient care in a continuous feedback loop,” he concluded. “The ultimate goal is the creation of a real-time learning health system, in which the practice and teaching environments learn from each other and are informed by research.”
Stereotactic body radiation therapy (SBRT) in previously irradiated patients “appears clinically feasible”, and provides good disease control out to five years for men with locally recurrent prostate cancer. This is the conclusion of a recent prospective study from Donald Fuller (Genesis Health Care Partners, San Diego, USA), published in the International Journal of Radiation Oncology Biology Physics.
The investigators set out to evaluate the use of SBRT retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. For this patient cohort, the authors explain how a number of local salvage methods have been described, but say that none have been widely used, “primarily owing to elevated toxicity concerns”.
Analysing outcomes in the 50 patients enrolled in the study from February 2009 to March 2018 from two community-based radiation oncology centres, Fuller et al assessed toxicities before and after SBRT salvage using CTCAE v.3 criteria and International Prostate Symptom Score (I-IPSS). SBRT was performed with the CyberKnife system from Accuray.
The authors report that 69% of the patients required no androgen deprivation therapy (ADT) treatment within the first five years following CyberKnife prostate SBRT. There were also low overall rates of toxicity among the patients, all of whom had undergone radiation therapy treatment prior to SBRT.
“Most men, if treated, receive only ADT, which has the potential for long-lasting whole-body side effects while rarely eradicating the tumour completely,” Fuller comments. “Without effective local retreatment, it is likely that most, if not all of them [the patients treated in this study], would have needed ADT treatment at a far earlier point in their history. Because ADT has many long-lasting detrimental ‘whole body’ symptoms, effective SBRT local salvage thus preserves better quality of life, greatly delaying or avoiding ADT systemic effects for most patients.”
Furthermore, at five years, the disease-free survival rate was 60%, indicating patients experienced no signs or symptoms of their cancer during that time. The authors write: “In spite of the relatively high-risk patient population described herein, the five-year biochemical relapse-free survival rate of 60% confirms extended disease-free survival in the majority of SBRT salvage cases.”
Comparing SBRT favourably to radical prostatectomy, Fuller and colleagues say: “We also report a biochemical relapse-free efficacy rate that appears at least comparable to that reported with salvage radical prostatectomy; 60% five-year biochemical relapse-free survival in the present series versus 57% three-year biochemical relapse-free survival in a contemporary salvage radical prostatectomy series of similar size and similar median follow-up. This suggests a definite role for salvage SBRT, particularly well-suited for those who either do not desire to or are not physically able to withstand the rigors and potential complications of a salvage radical prostatectomy procedure.”
The median prostate-specific antigen decreased to 0.16ng/mL at five years, similar to initial treatment with brachytherapy and lower than typical conventional fractionation, based on results from other studies.
No grade two or higher gastrointestinal events were reported. Genitourinary toxicity also was lower than reported rates for salvage radical prostatectomy and seems less frequent after prior standard external radiation treatment.
“Our results suggest that efficacious salvage of locally recurrent prostate cancer with SBRT is possible, with an acceptable toxicity risk, in appropriately selected patients,” Fuller et al conclude.
David Hayes, former physician administrator at Mayo Clinic, Rochester, USA, has been appointed chief medical officer of Biotronik, a company press release reports.
“Our focus has always been on the patient. To help patients live their best lives, we remain in constant collaboration with physicians so we can intimately understand the challenges they face every day. Hayes’ clinical, teaching, and publishing accomplishments bring a new level of experience and expertise to the company,” comments Ryan Walters, Biotronik president. “His commitment to understanding the dynamics of patient care, the challenges health systems face, and the impact of technology aligns perfectly with our focus on expanding partnerships with physicians and institutions throughout the USA. With Hayes on our team, we are positioned to set a new standard in delivering cardiovascular care.”
Hayes joins Biotronik following a more than 40-year career with Mayo Clinic in Rochester, USA, where he held various roles including professor of Cardiovascular Medicine and physician administrator. He most recently served as medical director, Mayo Clinic Care Network. His career has been dedicated to treating patients and helping advance electrophysiology and cardiology through teaching.
“This is an opportunity for me to drive change and create positive patient impact from a very different perspective,” states Hayes. “As the chief medical officer of Biotronik, I have assumed a role rooted in collaboration, understanding, and action. We are ready to challenge norms and shake things up. Cardiology is an area of healthcare that should always be evolving and advancing. We are making sure that happens. I am personally committed to ensuring physicians know they have a trusted partner in Biotronik.”
Juan Granada (New York, USA) chats to Sahil Parikh (New York, USA) for VEITHtv about below-the-knee (BTK) intervention and innovation and how the paclitaxel controversy has influenced the treatment of BTK disease.
Parikh says: “Frankly there is a lot of dampened enthusiasm” about the use of paclitaxel for drug delivery below the knee and that “if there is any good that came from this controversy is that it has stimulated innovation”. Granada agrees, noting that the field is “wide open” for the development of alternative therapeutic solutions.
The duo also discuss the benefits of stents/scaffolds compared with balloons with Granada noting that recent data suggests stents/scaffolds may have the edge. Scaffolds are “intrinsically and intuitively attractive” says Parikh, adding however that many physicians, including himself, are reluctant are to stent below the mid-level of the calf.
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Argon Medical Devices has announced the commercial launch of its Single-loop and Triple-loop retrieval kits for sale in the USA. The Single-loop and Triple-loop Retrieval Kits are intended for percutaneous removal of retrievable inferior vena cava (IVC) filters that are no longer medically required, via a jugular approach.
“We are excited to improve the IVC filter retrieval options available to our customers with the introduction of these new products,” said George A Leondis, president and CEO of Argon Medical.
According to a statement, Argon Medical’s Single-loop and Triple-loop retrieval kits were designed with the rigour of IVC filter retrieval in mind, offering the following key features:
“IVC filters are a safe and effective treatment for the prevention of pulmonary embolism, however they should be removed when the need for the filter subsides,” said David Trost (Weill Cornell Medical Center, New York, USA). “I like that Argon’s new retrieval kits can be used on all retrievable IVC filters, regardless of brand, from the jugular vein, providing unique versatility,” he added.
Terumo has announced the launch of a new randomised clinical trial: the DIStal vs. COnventional RADIAL access trial (DISCO RADIAL). The trial compares the novel distal radial access with conventional radial access approach, in terms of radial occlusion rates at discharge. The first patient has been enrolled.
Transradial approach is the preferred vascular access for coronary angiography and interventions, a Terumo press release asserts. Recently, the distal radial artery from the anatomical snuffbox on the dorsal side of the hand (“distal TRA” or “snuffbox access”) has emerged as an alternative access to the conventional forearm radial artery for coronary angiography and interventions.
DISCO RADIAL is the first large international randomised study designed to investigate the benefits of distal radial access over conventional radial access approach. The study plans to enrol 1,300 patients, in approximately 13 centres in Europe and Japan. The patients will be randomly assigned to one of the two access groups.
DISCO RADIAL aims to generate clinical evidence on the potential benefits of this novel distal access approach over the conventional radial approach, and to support the use of the distal radial approach as an alternative to the conventional radial approach.
Principal investigator Shigeru Saito, interventional cardiologist from Shonan Kamakura General Hospital, Kamakura, Japan, comments: “The radial approach is a small world and just one of the access methods. However, its impact on the clinical field has been proven potent and significant. Everybody was thinking we will never have anything novel in this small world. However, unexpectedly it was not true. The distal radial approach is truly novel, and nobody has evidence yet proving its advantage over the conventional radial approach. As the group of physicians working in this field, we have the responsibility to show its efficacy. That is the reason to initiate the trial.”
Principal investigator Adel Aminian, an interventional cardiologist from the Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium, says: “This novel access has raised great enthusiasm among the radial community, despite the paucity of clinical evidence supporting its use. Beyond potential advantages related to improved operator/patient comfort, easier and shorter haemostasis, an important feature of this technique is a puncture distal to the superficial palmar arch. Distal transradial access has the potential to maintain antegrade flow in the forearm radial artery during haemostatic compression, reducing thereby the risk of retrograde thrombus formation in the forearm radial artery and therefore the risk of radial occlusion. The current available data on distal transradial access is limited to relatively small prospective and retrospective case series looking primarily at the feasibility and success rates with this approach. By assessing the potential benefit and limitations of this alternative access, DISCO RADIAL will have an important clinical impact for radial operators.”
Christophe Giot, chief medical officer, Terumo Europe, says that this study will generate clinical evidence for this novel distal access approach, and reflects Terumo’s commitment to evidence based clinical practice and to the improvement of patients’ healthcare.
Enrolment is expected to be completed within one year, and results are expected to be available in 2021. Terumo is sponsoring this new study.
Speaking at the 32nd Annual International Symposium on Endovascular Therapy (ISET; 22–25 January, Hollywood, USA), Lindsay Machan (University of British Columbia, Vancouver, Canada) said that there had been “significant advancements” in the development of radiation protection options, though added that it was “important to remember that all devices are tested in optimised, non-real world conditions”.
“We are all aware of some very inconvenient truths about radiation,” he began, highlighting how, in 2017, “It was pointed out that in all these procedures we are performing, not only do they cause evidence of radiation-induced DNA damage, but we are individually predisposed, and actually the less radiation we get exposed [to], the less DNA damage we get from doing those procedures.”
Of the multitude of new procedures for radiation protection that have emerged in the last few years, Machan said he believes they could be categorised into three general brackets. These are: protective shielding, reducing the radiation output, and reducing the biological effect.
“I think most of us are used to the idea of using shielding,” Machan said. “If you use the new three metal shielding [triple layer non-lead skirts], it actually works profoundly well.” He showed the ISET audience a video of physicians performing an endovascular aneurysm repair (EVAR), commenting that his own data show that if, in addition to the “typical shielding and the bedside shielding”, a triple layer non-lead skirt was added to the theatre set-up, “you can actually reduce radiation to the operator by 91% compared to what we call ‘commando’, or just wearing a lead [apron]”.
Adding more additional shielding resulted in a further 80% reduction in radiation exposure to the operator and staff, Machan shared. He showed the ISET audience “some pretty innovative lead gowns”, again with the tripe metal layering. The gowns are made from tungsten, antimony, and bismuth, the “secret sauce”, in Machan’s words. Speaking of this metal triplet, he said he “highly encouraged” his listeners to look into acquiring such a combination gown for their own practice.
“It is actually very light,” he said of the gown. “Compared to standard non-lead, so called ‘light’ lead, this is profoundly better in terms of radiation protection,” he emphasised. For a 0.25mm thick gown, the wearer would get 3.7% transmission from a 70kV beam, Machan said. In contrast, this drops to 1.7% transmission with a 0.35mm thick gown, and reduces further to 0.6% transmission with the triple metal gown, which is 0.5mm thick.
However, he also offered a word of caution. When investigating the radiation protection conferred by lead glasses, Machan reported that they were not particularly effective. Describing their experimentation, Machan said: “The magic innovation was eyelash glue that allowed us to put dosimeters on the face—the eyelids and the cheeks. We then put lead glasses over the top, and it was a little bit disturbing to find that in real-world circulations, lead glasses only reduce the radiation dose to the eye by 9.5%. If you look at the right eye, it is 14.2%, so in other words, our nose actually provides 15% of radiation protection. These things are tested in non-real-world circumstances; this needs our attention.”
In terms of reducing the radiation output, Machan said he was “conflicted”.
“There are many different ways of doing this, he stated. One way utilises artificial intelligence (AI) to limit the radiation exposure when using fluoroscopy to navigate intraprocedurally. “When we are doing procedures,” Machan explained, “we are usually focusing on a relatively small area of the image [generated by fluoroscopy]. We have used AI, and we have taught it to recognise catheters, guidewires, and contrast, and then we use that to guide sub-second coning to our areas of interest. Once per second, we open up the full field, so you get context.
“You step on the fluoro-pedal, and where the white box is [a white box is visible over a subsection of the fluoroscopy image], that is the AI actually changing the cones actively. It just looks like normal fluoroscopy.”
The first application of AI-enabled fluoroscopy demonstrated that it facilitated a median 61.8% radiation dose reduction to the patient, and a 59.4% reduction to everybody else in the operating theatre.
“This is interesting work reducing the biological effect of radiation,” Machan said, introducing work by Kieran Murphy (University Health Network Toronto Western Hospital, Toronto, Canada).
Explaining this research, Machan recounted: “All of us sitting here, we have this balance of excess free radicals and anti-oxidants to prevent DNA damage and oxidative stress. Radiation creates free radicals, which damage DNA, and results in all those noxious things that we talk about: stroke, heart attack, cancer, cataracts, and accelerated aging. Kieran [Murphy]’s thought is that if you take an anti-oxidant mixture dissolved in any drink, even ones we do not think of as being healthy, and if you do this every day before you go in and do a procedure, then actually the idea is that you prevent those free radicals from damaging your DNA.”
In a clinical study of 10 patients published in the Journal of Vascular and interventional Radiology (JVIR) in 2017 by Murphy et al, the investigators found that premedication with an oral antioxidant cocktail before medical imaging exams could significantly reduce DNA injury from the ionising radiation dose. Murphy claimed at ISET that this was “pretty impressive early phase work”, and teased that Murphy’s group were preparing to do the same kind of study on people before they do endovascular procedures.
However, whilst Machan is enthusiastic about these various options for radiation protection, eh concludes by saying that “There is no safe dose”.
Addressing the audience at the Spectrum meeting (18–21 January, Miami, USA), Theresa Caridi (MedStar Georgetown University Hospital, Washington, DC, USA) expands on the pros and cons of uterine artery embolization (UAE), and shares what factors she believes are necessary to discuss with the patient prior to the procedure.
Firstly, Caridi discussed the issue of fertility. In a 2008 study published in the Journal of Cardiovascular and Interventional Radiology (CVIR) by Michal Mara (General Faculty Hospital and First Medical Faculty of Charles University, Prague, Czech Republic) and colleagues, the authors concluded that, while UAE is less invasive and as symptomatically effective and safe as myomectomy, but has inferior reproductive outcomes in the first two years after treatment. One-hundred-and-twenty-one women with reproductive plans who presented with an intramural fibroid(s) larger than 4cm were randomly selected for either UAE or myomectomy; 58 embolizations and 63 myomectomies (42 laparoscopic, 21 open) were performed. Mara et al reported significantly more pregnancies and labours (33 and 19, respectively) and fewer abortions (six) following surgery than after embolization (17 pregnancies, five labours, nine abortions; p<0.05).
Listing her first positive for UAE, Caridi told the Spectrum audience how the procedure is uterine-sparing. Citing a study by Shannon Laughlin-Tommaso (Mayo Clinic, Rochester, USA) published in Menopause in 2018, Caridi demonstrated that ovarian-sparing hysterectomy, which had been touted as a potential way of avoiding some of the detrimental effects of hysterectomy, did not fully eliminate the risks. The Menopause study looked at approximately 2,000 women who had an ovarian-sparing hysterectomy and compared them to age-matched controls. Laughlin-Tommaso and colleagues found that even with ovarian conservation, there is an elevated long-term risk of cardiovascular disease and metabolic conditions, especially in women who undergo hysterectomy when 35 or younger. The authors concluded: “If these associations are causal, alternatives to hysterectomy should be considered to treat benign gynaecologic conditions.”
“Women are talking about this on social media,” Caridi commented. “They are asking ‘What are the risks if I have a hysterectomy, even if I leave the ovaries behind?’ I think it is important to know about this.”
However, while UAE offers a uterine-sparing alternative to hysterectomy, Caridi said that the presence of the uterus “means that we can get fibroid recurrence”. Sharing the five-year results of the prospective, randomised controlled REST trial, which directly compared UAE to surgical treatments—both myomectomy and hysterectomy—in patients with symptomatic uterine fibroids, Caridi reported how the authors, Jon Moss (Gartnavel General Hospital, Glasgow, UK) et al, found that adverse event rates were no different between the UAE and surgical arms, but that the reintervention rate was much higher with UAE. Moss and colleagues’ conclusion in 2011 was that “UAE is a satisfactory alternative to surgery for fibroids”, but that “the less invasive nature of UAE needs to be balanced against the need for re-intervention in almost a third of patients”. They recommended that the choice should lie with the informed patient.
In defence of UAE, Caridi added: “That being said, some of those people who got surgery actually got a hysterectomy, so of course they are not going to need a reintervention more than likely, whereas people who get a myomectomy may, so there is a little bit of bias. But several studies, some out to ten years, do show that the reintervention rate with UAE is about 30%.”
Moving on to her next pro of UAE, Caridi said: “UAE is very efficacious. In fact, it is one of the most efficacious procedures we do in interventional radiology (IR).” The clinical practice guidelines from the Society of Interventional Radiology (SIR) summarise the data in the literature, and show that, on average, “rates of success are really good”: leiomyoma size reduction, 50–60%; uterine size reduction, 40–50%; reduction of bulk symptoms, 88–92%; elimination of abnormal uterine bleeding, >90%; successful elimination of symptoms, 75%; patient satisfaction (would recommend UAE to a friend), 80–90%.
However, another con of UAE is the possibility of fibroid passage. “We treat fibroids really well, but sometimes they detach and pass,” Caridi explained. “We have to worry about that, particularly in submucosal fibroids.”
A meta-analysis from Sundeep Toor (The Ottawa Hospital and University of Ottawa, Ottawa, Canada) et al published in the American Journal of Roentgenology in 2012 reported an incidence of leiomyoma tissue passage of 4.7% (with a range of 3.9–5.7% in 8,159 patients). “That is much higher in a risky site like the submucosal location,” Caridi commented. “It is something we have to worry about. What is the consequence of this [fibroid passage]? Patients can get endometritis and infection and require a secondary intervention. Maybe it is a myomectomy, maybe it is a hysterectomy, if you cannot get the infection under control. Or, they can just get a chronic vaginal discharge that lasts upwards of six months or even a year, and some would like to have a hysterectomy for that reason.”
Returning to her pros of UAE list, Caridi said that “probably one of the key reasons why women seek” UAE is that the recovery time is shorter than for surgical intervention. In the CVIR study by Mara and colleagues that demonstrated the inferior reproductive outcomes of UAE when compared with myomectomy, the authors also reported that the minimally-invasive option fared much better than myomectomy, with significance, for average length of hospital stay, recovery period, and disability greater than two weeks. “It is a quicker recovery, no doubt,” Caridi stated.
She continued, “Though there is a lot of pain associated with UAE”. She elaborated: “Despite our best efforts to look into this in many ways, and all the research that has been done—we have this arsenal of anti-inflammatory and PCA [patient-controlled analgesia] medications, [but] more than 90% of women still report post-procedural pain, and about 35% of women experience pain that is equal to or greater than [that experienced in] labour. So this is a real issue.
“In terms of how to mitigate this, we have some adjunctive techniques, but some of them require a second procedure or have their own risks. We could use superior hypogastric nerve block, intra-arterial lidocaine after embolization—this is pretty widely used as its low-risk profile has been shown in a prospective randomised controlled trial—and then you could go as far as to perform an epidural if you cannot get the pain under control.”
Informed consent is key
Concluding, Caridi commented: “All that being said, I think the summary of this lecture is that there are a lot of pros and a lot of cons to doing a UAE, but the most important factor is to discuss these in a clinic visit.”
Caridi showed the Spectrum audience a consent form that she uses in her own institution, Georgetown University Hospital, that she said she would be happy to share with any interested parties. “We go over all these things with the patient,” she explained. “It helps me stay on track. I sign it, they sign it, I give them a copy.”
The form covers a description of the procedure and the anticipated outcomes: “I tell them [the patient] this is a global treatment, it is uterine-sparing, it is about 90% efficacious, the recovery time is limited. I tell them to take a week off work, although they oftentimes do not need it, but at least they have planned ahead.
“We talk about the alternatives. We talk about the risks, some of which—but this is not an inclusive list—are fibroid recurrence, passage, and pain. Then we talk about future fertility, this actually has its own category. There is no guarantee for future fertility, and if someone desires that, we certainly talk about whether they are a myomectomy candidate.”
The “Standard versus ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism” (SUNSET sPE) trial, a randomised, single-blinded clinical trial comparing ultrasound-assisted thrombolysis (USAT) to standard catheter-directed thrombolysis (SCDT), has completed enrolment, as announced on Friday 17 January by principal investigators Efthymios Avgerinos and Rabih Chaer (University of Pittsburgh Medical Center, Pittsburgh, USA).
The SUNSET sPE trial was designed to address the controversy of the role of ultrasound in improving clot reduction during catheter-directed thrombolysis for acute submassive pulmonary embolism. The study was launched as an institutional trial at the University of Pittsburgh Medical Center in 2016, and more recently two more institutions joined as collaborators; the Department of Cardiology, Emory University, and the Piedmont Heart Institute, both in Atlanta.
As reported in Venous News, participants were randomised 1:1 to a USAT catheter (EKOS System) or a SCDT catheter (Unifuse, Cragg-McNamara). Technical details of the procedure were left to the discretion of the treating physician, with a general guidance for short periods (less than 12 hours) of thrombolysis to match the favourable outcomes demonstrated by the “Optimum duration of acoustic pulse thrombolysis procedure in acute pulmonary embolism” (OPTALYSE) study.
In order to simulate real-life practice, termination was recommended when there was an objective improvement of vital or echocardiographic signs (pragmatic trial). The primary outcome was clearance of pulmonary thrombus burden, assessed by post-procedure computed tomography angiography using a modified Miller score.
According to the investigators, this was partly chosen due to thrombus clearance being the distinct assumed advantage of ultrasound-assisted catheter-directed thrombolysis, but most importantly because it is the only outcome that could power this randomised clinical trial, since the use of clinical outcomes would require a prohibitive sample size.
The study was powered for 80 patients to detect a 50% improvement in pulmonary artery thrombus clearance. Secondary outcomes include resolution of right ventricular strain by echocardiography; improvement in pulmonary artery pressures; and a three- and 12-month improvement in echocardiographic, functional capacity, and quality of life measures.
Efthymios Avgerinos (University of Pittsburgh Medical Center, Pittsburgh, USA) presented interim results of the overall outcomes at the Society for Vascular Surgery (SVS) Vascular Annual Meeting (VAM; 12–15 June, National Harbor, USA).
It was shown that catheter thrombolytic techniques can achieve a significant and quick thrombus and RV/LV ratio reduction, and are safe and effective. With enrolment complete, follow-up data and analyses are pending, and comparative results will be announced within the forthcoming months.
George Adams (Raleigh, USA) talks to VEITHtv at the VEITHsymposium 2019 (19–23 November, New York, USA) about the benefits of using easy-to-use Shockwave IVL (Intravascular Lithotripsy) in calcified below-the-knee vessels, which he says, results in “great outcomes”.
Adams explains that calcific plaque, particularly medial calcification in smaller below-the-knee vessels can contribute to adverse events and poor acute outcomes, such as vessel recoil and dissections. However, Adams explains that the use of Shockwave IVL, in which pulsatile sonic pressure waves fracture intimal and medial calcium, can help avoid these events and maximize luminal gain in order to get much-needed blood supply to non-healing wounds in critical limb ischaemia patients.
This video is sponsored by Shockwave Medical.
Investigators report a 100% technical success rate in creating their planned ablation volume and no major device-related complications in the first-in-human clinical cases using histotripsy, a novel ablation modality. Presented at Spectrum (18–22 January, Miami, USA) by Emily Knott, a research intern at the Department of Radiology, University of Wisconsin, Madison, USA, and currently applying to medical school, these early positive results offer “real potential” for the future of this therapy.
Histotripsy is a non-invasive, non-thermal ablation modality that uses focused ultrasound to create a cavitation bubble cloud which destroys the target tissue. This cavitation bubble cloud is precise at the histologic level: the resultant ablation zones are within millimetres of the prescribed location. “Coupled with a robotic arm, you can virtually prescribe any size and shape of ablation zone,” Knott described. The tissue within the ablation zone is completely necrotic.
“An interesting characteristic,” Knott observed, “is that because of these mechanical tissue destruction effects, there is architecture preservation within the ablation zone, including bile ducts and large vessels.
“The most interesting part of this technology, though,” she continued, “is the potential for an immune response.” Sharing early histotripsy studies conducted in mice at the University of Michigan, she described how investigators witnessed an abscopal response that is greater than radiation therapy and thermal ablation, as well as finding decreased metastases in the pulmonary area.
Describing the first ever human clinical cases, Knott told the Spectrum audience of the 100% technical success rate in creating the planned ablation volume, and of the lack of device-related complications.
Two patients demonstrated a potential abscopal response to therapy. Showing the MRI scans of one of these patients on her slides, Knott said: “The really exciting thing with this patient is that when we treated one tumour, a small percentage of this patient’s disease, the AFP [alpha-fetoprotein, a tumour marker] dropped disproportionately over eight weeks.”
In a second patient, with metastatic colorectal cancer, Knott recounts how the team treated a single tumour in the left lobe of the liver. One day post-treatment, imaging showed the tumour swelling slightly “with some inflammation”, but over time, it decreased in size to smaller than before ablation. “CEA [carcinoembryonic antigen, used as a diagnostic and prognostic tumour marker] also dropped disproportionately to the one tumour that we treated in the liver,” Knott said.
She concluded: “Histotripsy is a non-thermal and non-invasive ablation modality. It can safely create a planned ablation volume, and there is a potential immune stimulation in early pre-clinical results in mouse models, and in two of eight patients in an early clinical trial. This clinical trial will be more finalised and [eventually] published, and will also be presented at SIO [the annual meeting of the Society of Interventional Oncology; 31 January–3 February, New Orleans, USA].”
Shimadzu Medical Systems USA, a subsidiary of Shimadzu, along with NZ Technologies of Vancouver, Canada, and developers of TIPSO technology, have announced that they have signed a one-year renewable agreement that allows Shimadzu to market and sell the innovative TIPSO AirPad in the US healthcare market.
TIPSO is a specialised medical technology that has evolved from the technical expertise and industrial experience of its engineering team through contributions from physicians as co-inventors who practice in the field of interventional radiology.
Proprietary technology enables various modes of image navigation over the TIPSO AirPad surface (functioning as mouse and keyboard at bedside) while a real-time representation of the hand and menu is shown on the system monitor display. A simple USB dongle connects the AirPad to any workstation wirelessly without having a connection to the hospital network or any type of transfer/storage of patient data to keep within HIPAA (Health Insurance Portability and Accountability Act) compliance.
AngioDynamics has announced the launch of the PATHFINDER I: Post-Market Registry (PATHFINDER I-Registry, EX-PAD-05), a pilot study to evaluate the safety and efficacy of the company’s AURYON atherectomy system in the treatment of de novo, re-stenotic, and in-stent restenosis (ISR) lesions in infrainguinal arteries of patients with peripheral arterial diseases (PAD).
The AURYON atherectomy system, previously known as the Eximo B-Laser, is a proprietary 355nm wavelength laser-technology platform that was acquired by AngioDynamics in October 2019.
“The PATHFINDER I study will provide valuable, scientifically-backed data to further differentiate the AURYON system from competitive products in this space and build upon the excellent long-term results that patients experienced during the IDE,” says Juan Carlos Serna, AngioDynamics Vice president for Clinical Affairs and Healthcare Economics.
AngioDynamics’ PATHFINDER I registry is a prospective, non-randomised, single arm, multicentre observational study that will evaluate the performance of the AURYON atherectomy system during procedures and measure clinical outcomes, both intermediate and long-term. A total of 100 eligible PAD patients treated with the AURYON atherectomy system in a post-market setting will be enrolled and tracked for a 36-month period after the initial procedure.
Initial findings from the pilot registry study will contribute to a subsequent large pivotal phase registry that is expected to include approximately 1,000 patients.
The commercial release of the AURYON atherectomy system in the USA will occur in the second half of the fiscal year.
The TriForce peripheral crossing set, from Cook Medical, is now commercially available in the USA. As of January 2020, these products are available to physicians in the USA to support procedures to treat patients with vascular obstructions.
According to the company, the TriForce peripheral crossing set is designed to be percutaneously introduced into blood vessels and support a guidewire while performing a peripheral intervention. The device is also intended for injection of radiopaque contrast media for angiography.
It is offered in two lengths and four configurations, providing several product options to treat blocked or restricted vessels in a variety of locations in the body, Cook Medical state.
With provision of interventional radiology (IR) services varying across the UK, the Getting It Right First Time (GIRFT) programme aims to identify and reduce unwarranted variation in English trusts to help bring about improvements. GIRFT is publishing a report later this year outlining the issues that have led to this discrepancy, and providing recommendations for solutions at the local and national level. Katharine Halliday anticipates this report here, elaborating on her keynote lecture at the British Society of Interventional Radiology annual meeting (13–15 November, Manchester, UK).
Introduction to GIRFT
GIRFT is a national programme aimed at reducing unwarranted variation in the National Health Service (NHS). It began as a pilot in orthopaedic surgery, led by Professor Tim Briggs, who visited orthopaedic units across the country and led peer-to-peer discussions about the local service. The pilot was very successful, improving the standard of care for orthopaedic patients and reducing costs. The model has subsequently been rolled out to 40-plus clinical specialties, including radiology.
For each trust, a pack of comparative data is produced from national sources—this forms the basis of a discussion with clinical staff and mangers, facilitated by the clinical lead. The visit provides an opportunity for departments to showcase their good work to their executive team and for the senior managers to fully understand the vital role played by radiology in most patient pathways. The clinical lead identifies areas of good practice which can then be shared with other departments. Areas the department would like to work on are also discussed and documented.
The GIRFT radiology team has now visited almost every trust in England. The process has been a hugely educational one and we have been very impressed by the enthusiasm with which the radiology community has embraced the opportunity to review services, identify possible areas for improvement, and learn from others
Regarding interventional radiology, some strong themes have emerged:
Workforce
In 2018, the Royal College of Radiologists (RCR) identified that only one in five trusts had six interventional radiologists, considered to be the minimum number necessary to cover a comprehensive on-call service. There is no evidence that this situation is improving.
In many trusts the shortfall in the elective interventional service is mitigated by extending the role of radiographers and nurses, who now undertake many and varied interventional procedures. But radiographers and nurses are also in short supply, and some trusts are not capitalising on their training investment because staff cannot be released from image acquisition or other duties. Innovative departments have maximised the contribution of healthcare assistants to release higher banded staff for advanced practice, but over recruitment is essential for role extension to be effective.
The stimulating and varied nature of radiology nursing is not always recognised, and, on the background of a national nursing shortage, recruitment issues are keenly felt. In some cases, working with theatres has enabled a more sustainable workforce. Close liaison with other nurses from across the hospital, including students, is helpful when attracting staff. Several interventional radiology (IR) nurses have mentioned that there are few nationally-run training courses. There is an opportunity here to strengthen the nursing division of the British Society of Interventional Radiology (BSIR).
Some departments are more successful than others at recruiting and retaining their staff. A focus on training and continuing professional development proves very popular with all grades. Ideally more staff would be able to progress from the lower bands to Bands 5 and 6, but this is still challenging. GIRFT is working with national bodies to identify and reduce barriers.
Environment
We have seen wide variation in the environments for patients and staff. Those departments that operate most efficiently can admit and discharge patients from radiology, ideally with a small day case unit dedicated to imaging, overseen by nursing staff. These units are often shared with cardiology and provide a safe environment for patients and avoid expensive and frustrating delays waiting for inpatient beds. We have seen excellent radiology day case units in hospitals where there are no vascular beds which allow patients to be treated much closer to home.
Paediatrics
Paediatric intervention is particularly challenging. Although facilities and expertise in children’s hospitals are excellent, most children are seen and treated in general hospitals. Even in very small departments where most patients are adults, liaison with play therapists and the identification of a lead radiographer for paediatrics can vastly improve the experience for paediatric patients and their families. Volumes of paediatric intervention are too low to have a dedicated paediatric IR team in any but the largest specialist centres, and it is necessary for adult IR teams to develop and maintain some skills in this area.
Data
Although large quantities of radiology data are collected, the quality is often poor because there is huge local variation in the way individual procedures are coded and counted. There is also no unifying code for interventional procedures so collecting outcome data for appraisal and audit is difficult locally and impossible at a national level. GIRFT is working with a team of data experts to address these issues.
Networking
The challenges identified above result in very variable access to interventional procedures, particularly for patients presenting out of hours. The vascular surgical networks supported by the vascular surgery GIRFT work stream are maturing and continue to improve pathways for vascular patients, while many radiology departments are working together to form IR networks. The model varies depending on local circumstances and expertise but in the best departments individual pathways are identified for specific conditions and these are clearly conveyed to clinical teams. The document recently published by NHSI/E—Transforming Imaging services in England: A national Strategy for imaging networks—sets out a vision for networking in radiology which will be helpful for developing robust IR services. Strong leadership from interventional radiologists and close liaison with clinical colleagues is essential if these are to be successful.
Next steps
At the end of each GIRFT presentation the local team are asked to identify issues they would like to work on, together with good practice. These are summarised in a short report which is sent back to each trust within a couple of weeks. Local support is offered to the trust by the GIRFT implementation team who help to develop the themes and put together an action plan. Many trusts have also appointed their own GIRFT lead who will assist with local improvements. It is often possible to put departments in contact with other people who have overcome similar challenges and for good practice to be shared between institutions.
Each GIRFT work stream publishes a national report and in many of those, the essential role of radiology has been highlighted. The radiology GIRFT national report will be published in 2020. In several areas the team are already working with national bodies, but the report will highlight the issues identified across imaging departments and will make national recommendations.
Katharine Halliday is the clinical lead radiologist for the GIRFT programme and is a consultant paediatric radiologist at Nottingham University Hospitals NHS Trust, Nottingham, UK. She is past chair of the British Society of Paediatric Radiology from 2010 to 2016.
A new meta-analysis, just published in the Journal of Vascular and Interventional Radiology (JVIR), suggests significantly worse amputation-free survival at one year with the use of paclitaxel-coated balloons in arteries below the knee in the treatment of chronic limb-threatening ischaemia (CLTI). However, some experts advise cautious interpretation of results and question whether these data will impact practice. The new systematic review and study-level meta-analysis of eight randomised controlled trials was conducted by Konstantinos Katsanos (School of Medicine, University of Patras, Patras, Greece) and colleagues.
Several physician thought-leaders believe that the conclusions are not yet definitive, with multiple vascular interventionalists and surgeons cautioning how these data should be interpreted. Most emphasised the challenge of teasing out scientifically meaningful information from a patient cohort that suffered from CLTI, which is associated with “mortality, amputation, and impaired quality of life”. They also point to the inclusion of unpublished data (which has therefore not gone through the peer-reviewed process); the inclusion of summary-level data; the inclusion of the IN.PACT DEEP data (which used a device that has long since been withdrawn from the market); and the study’s short-term follow-up period.
As reported in JVIR, the eight randomised controlled trials included in this most recent summary-level analysis included 1,420 patients, of which 1,380 (97.1%) had CLTI. The primary safety and efficacy endpoint was amputation-free survival, defined as freedom from all-cause death and major amputation (above the ankle). At one year, there was a 13.7% crude risk of death or limb loss among the 835 patients who had received treatment with paclitaxel-coated balloon—74 deaths and 40 major amputations. In comparison, the crude risk of death or limb loss in the cohort treated with an uncoated balloon was 9.4%—39 deaths and 17 major amputations. For the primary amputation-free survival endpoint, the number needed to harm was estimated to be 22 patients (95% confidence interval [CI] 11–94). The authors claim there was consistent evidence from the randomised studies that freedom from major amputation or death was significantly lower in cases with paclitaxel-coated balloons with a pooled hazard ratio (HR) of 1.52 (95% CI 1.12–2.07; p=0.008).
However, Katsanos et al also report consistent evidence that paclitaxel reduces the need for target lesion revascularisation in below-the-knee arteries by approximately 40%. Target lesion revascularisation constituted the secondary efficacy endpoint. The crude risk of target lesion revascularisation was 11.8% (103 revascularisation events among 875 cases) versus 25.6% (159 events among 620 control patients) for patients treated with a paclitaxel-coated balloon and an uncoated balloon, respectively. The calculated pooled risk ratio was 0.53 (95% CI 0.35–0.81; p=0.004), with a corresponding number needed to treat of eight patients (95% CI 4–25).
The study authors claim there is a dose–response relationship between paclitaxel and amputation-free survival. They compared outcomes with low and high doses of paclitaxel, and found significantly more deaths or amputations (lower amputation-free survival) in cases with high-dose devices, defined as 3–3.5µg/mm2 (HR 1.62; 95% CI 1.16–2.27; p=0.005). In comparison, amputation-free survival was higher (fewer deaths or fewer major amputations) when a low-dose device (2µg/mm2) was used (HR 1.06; 95% CI 0.48–2.34). This low-dose was found to be safe and effective, the authors report.
The authors of the present study say they performed a “comprehensive literature review” due to the “major concerns about systemic safety of paclitaxel” prolific in the endovascular community today as a result of their earlier meta-analysis published in the Journal of the American Heart Association (JAHA) in 2018. This concluded that there was an increased association of mortality beyond two years through five years of follow-up when paclitaxel-coated balloons and paclitaxel-eluting stents were used in the femoropopliteal arteries.
“The paper published today by Konstantinos Katsanos and colleagues raises important questions about the treatment of patients with CLTI, and is an important contribution to the medical literature. As with any meta-analysis, validation of the findings will require further dedicated investigation. In particular, the lack of patient-level data and the inclusion of unpublished data sets in this analysis may weaken the strength of the conclusions.
“Patients with CLTI are vulnerable and have few care options. It is important to know what treatments will best enhance their life expectancy and quality of life. The Society of Interventional Radiology will continue to work with the [US] Food and Drug Administration to support its work in developing practice guidance on the use of paclitaxel-coated balloons in the infrapopliteal arteries for CLTI treatment as we look to build rigorous scientific evidence for available treatments.”
“It is an interesting publication that unfortunately adds little to the overall lack of conclusive evidence supporting the use of paclitaxel-coated devices in the infrapopliteal circulation in patients with CLTI.
“I am concerned that flaws in systematic reviews highlighted in universal comments on the authors’ previous meta-analysis in JAHA may also have contributed to the negative results for paclitaxel-coated balloons in this systematic review. No doubt this paper will excite many comments and publications on this topic in the next 12 months.
“The topic is a very important one considering the ongoing controversy of paclitaxel-coated devices in the femoropopliteal circulation. The subject is muddied by the potential adverse effects of different excipients and the lack of individual patient safety data. I do not think that this contributes significantly to the ongoing controversy regarding any potential link between paclitaxel-coated balloons and mortality. However, the authors’ conclusion that distal embolization of paclitaxel and/or excipient may adversely affect amputation-free survival is reasonable. Finally, the inclusion of the IN.PACT DEEP data (using a withdrawn device) involving almost a third of the patients in this review, with its known negative influence on mortality and amputation-free survival, is likely to have adversely contributed to the overall negative results on amputation-free survival in this publication.
“In common with most vascular practitioners in the UK, I do not use paclitaxel-eluting devices below the knee in patients with CLTI. This is partly due to the Medicines and Healthcare products Regulatory Agency (MHRA) statement on paclitaxel devices in 2019, and partly due to a perception of lack of efficacy of these devices in CLTI. In view of the above, these data will not impact my current vascular practice.”
“Aside from The Godfather Part II, sequels are rarely as compelling as the original version, often with an impact that is a mere ripple of the force produced by the initial statement. Predictably, I suspect this will be the case for the current report, although its contribution to the medical literature will be of interest to many stakeholders in the field of vascular disease.
“The results of this meta-analysis of randomised controlled trials focused on patients with CLTI are more difficult to interpret than the earlier femoropopliteal publication. The medical complexity of the underlying disease and the vulnerability of CLTI patients contribute to a greater heterogeneity in the population studied. Consequently, added caution must be exercised when attempting to make conclusions from this meta-analysis.
“In terms of the methodology used, the current study shares some of the frequently noted limitations of the original femoropopliteal meta-analysis. The lack of patient-level data available to the authors from the randomised studies included in the meta-analysis restricts evaluation of the total dose of paclitaxel used in individual patients and any correlation with mortality. In addition, the relatively small number of patients analysed and [the] short follow-up (46% of the patients had only six-month follow-up) make any conclusions problematic. Unlike the first meta-analysis, however, an additional limitation is noted. The current report of pooled trials includes unpublished data. Results from three of the eight trials used in the analysis have not been published. This represents one-quarter of the patients included.
“Nevertheless, the paper raises interesting points about the effect of drug-coated balloon treatment for patients with CLTI, and questions the possible association of downstream drug embolization and amputation in patients with compromised distal arterial circulation. In addition, it echoes the call after the earlier femoropopliteal publication for more data and an urgent need for adequately-powered multicentre studies with longer follow-up. Its effect on clinical practice for management of CLTI patients with limited treatment options is questionable. Most likely, future substantiation using larger, well-controlled trials will be required before changing strategies for the application of drug-coated balloons in treating CLTI.”
“Concerns about drug-eluting balloons in the tibial arteries have been around since the DEBATE-BTK and IN.PACT DEEP trials, so while not as disruptive as the prior study from this group, this new meta-analysis certainly adds more grist to the paclitaxel mill. Some of the same limitations of the previous study apply here: the absence of patient-level data, and differences in the technologies between trials. Most patients in this meta-analysis had CLTI, a more challenging population than the patients with claudication due to the femoropopliteal artery that dominated the previous study. Other differences are that only balloon-based devices were studied, there are a paucity of data on inflow and target lesion revascularisation procedures, and the number of patients analysed is smaller. Of note, data from several of the included trials are only available as conference presentations online, rather than peer-reviewed publications. However, most important is that the follow-up is far shorter than in the previous meta-analysis—between six months and 12 months. Is it possible that over time we will see these amputation and mortality rates stabilise or even equalise? Will extended follow-up of patients treated with new devices bend the curves in the right direction? With this new analysis we are left in the same place as before; paclitaxel devices have better lesion-based outcomes, but there may be trade-offs. We need to be really thoughtful as we learn how and when to best use them, especially in the tibial arteries.”
“Reading the methodologically-excellent paper by Katsanos et al, their conclusions do not come as a surprise. The so called “low flow” phenomenon after drug-coated balloon use was recognised in coronary arteries four years ago. Also, the observation of “slow flow” directly after peripheral drug-coated balloon [use] has been discussed by others in the corridors of several meetings. In our department, drug-coated balloons are used very scarcely (four a year for recurrent early superficial femoral artery restenosis only), but we have already seen two patients with instant reduction of foot perfusion after drug-coated balloon use in the superficial femoral arteries. This acute reduction in flow was documented with perfusion angiography. These were both patients with intermittent claudication where no clinical consequences were seen, probably due to the sufficient reserve capacity of the microcirculation perfusion. However, in serious CLTI, this embolization could have devastating consequences for the outcome. This also proves that, at least partly, micro-particles loaded with paclitaxel are trapped in the microcirculation. A simple prospective trial using perfusion angiography after drug-coated balloon implantation would be enough to prove this micro-particle embolization as cause for a reduction in amputation-free survival.
“In Katsanos et al’s paper, the hazard ratios are calculated for amputation-free survival as a primary clinical endpoint, and target lesions revascularisation is a secondary non-clinical endpoint. A secondary endpoint can sometimes be used for clinical decision-making if the primary endpoint of a study is borderline statistically not significant or equivalent. Mostly, a secondary endpoint is used to calculate the cost-efficacy of a treatment. The fact that the target lesion revascularisation is 50% better after drug-coated balloon use is, however, irrelevant if the primary clinical endpoint (amputation-free survival) shows that the hazard ratio for a lower amputation-free survival is 1.52 after the use of a drug-coated balloon. This strong primary clinical endpoint makes any drug-coated balloon treatment questionable.
“Combining the previously-documented data of a mortality increase with paclitaxel-coated devices after two and five years with this new findings of a lower amputation-free survival after drug-coated balloon use in CLTI patients should make us seriously re-think the concept of drug-coated balloons in CLTI as a (failed) treatment concept.”
“I have two immediate remarks:
“Nevertheless, there are several major limitations of the recent publication:
“In summary: Katsanos et al unfortunately increase the uncertainty in the safety of drug-eluting technology. What does it end with? Fewer patients will get drug-coated balloons and more target lesion revascularisations and [consequently] more amputations may occur. Does it affect my clinical practice? No, for two reasons:
“While this analysis of the efficacy and mortality of paclitaxel use in the infrapopliteal CLTI population has similar methodological limitations to the first Katsanos publication of paclitaxel used to treat claudication, it also reaches the similar concerning conclusion that paclitaxel use in peripheral vascular disease is associated with increased mortality. But this time the authors use the most relevant of clinical endpoints for this population, amputation-free-survival, to evaluate for the ultimate goal of an intact living patient. While it took use of this composite endpoint to achieve statistical significance, it is alarming that both mortality and amputation came very close to independently reaching statistical significance (p=0.1; p=0.09, respectively), and I suspect that with a larger sample size one or both may have. If further evidence confirms either that paclitaxel does not decrease the rate of amputation but does increase the mortality, then the prospects for its continued use appear bleak. The possible ray of sunshine in this cloud is the observation that the lowest dose paclitaxel device analysed (Lutonix, BD) appeared to be free of increased mortality yet still effective, perhaps indicating that the dosing sweet-spot has yet to be found while acknowledging that we have no accurate way of measuring actual paclitaxel tissue delivery or systemic release. The complicated nature of paclitaxel delivery and its pharmacology, however, portend that this will remain a complicated mystery to unravel.
“There has been a significant shift towards the use of paclitaxel delivering devices in treating peripheral vascular disease since their introduction several years back. Given this and the ever-growing population of peripheral vascular disease patients being treated, it is critical that physicians know the full risk:benefit profile of the therapies they employ and always put the patient’s outcome first. The methodological limitations of this pooled analysis are divulged by Katsanos et al and are similar to those of the group’s previous publication on the use of paclitaxel in the claudication population. Nonetheless, his prior report called attention to a signal that was, in fact, subsequently confirmed, though still not understood, so the findings of this analysis are highly relevant and need further analysis.
“When considering a risk like mortality, erring on the side of caution only makes sense, especially considering the multitude of other revascularisation options available to most patients, the irreversibility of death, and the risk of litigation. This is especially true when the effectiveness of the therapy itself is in question, as this analysis has suggested. Until we have greater clarity on the safety and efficacy of paclitaxel devices, I believe that most will opt to use them very selectively in the small subset of patients at high risk for restenosis and no other reasonable revascularisation options.”
“My first reaction was that it was good to see a group looking to define the risks of paclitaxel devices in the CLTI population. The CLTI group is very different to the claudicants evaluated in the previous meta-analysis and warrants specific attention.
“My reaction to the results was mixed. The authors showed no difference in all-cause mortality or major amputation rates but when they combined the two as the endpoint amputation-free survival, they appeared to find a difference between drug-coated balloons and percutaneous transluminal angioplasty, with better amputation-free survival in the control group. The other positive finding was that they showed a 47% reduction in reinterventions, underlining the well-established effectiveness of these devices.
“It must be said from the outset that—with limited numbers and such short-term follow-up—care must be taken not to overreach in our conclusions. Moreover, taking a deeper dive into the meta-analysis revealed several methodological questions and important validity concerns.
“For example, why were only drug-coated balloons evaluated and not drug-eluting stents? This differed from the methodology of the previous meta-analysis and meant excluding the PADI trial, which has published five-year follow-up. This is the very group identified in the previous meta-analysis as having the most pronounced safety signal. Second, why was amputation-free survival determined to be the primary endpoint, when all-cause mortality was used in the previous meta-analysis? Why was no protocol published on the PROSPERO database to assure the reader that the endpoint was determined a priori, not after the analysis? Third, why were only below-the-knee studies included when the authors speculate it is the particulate embolisation of the drug that provides an explanation for the safety signal? Particulate embolisation is known to occur when CLTI patients are treated for above- and below-the-knee disease. However, ultimately these are questions for the authors, which may have a reasonable explanation.
“My major concern is the inclusion of unpublished data. This was the case in three of the eight studies pooled. We must take great care in including data that has not been peer reviewed. It is common that event rates change between presentation and final publication, which may alter the findings of a meta-analysis and its conclusions. This is particularly true for low-frequency endpoints such as amputation-free survival at six to 12 months. It is also very difficult for the reviewers to grade the quality of evidence from a short congress presentation, as opposed to a peer-reviewed manuscript. However, including unpublished data is not unheard of, particularly when there are few published studies in the literature. What concerns me most is the glaring omission of the most significant study of drug-coated balloon use in below-the-knee arteries of CLTI patients. The five-year results of the IN.PACT DEEP study were presented by Thomas Zeller at the AMP symposium last year (14–17 August, Chicago, USA). Like the other three studies, it was unpublished in September 2019 when the systematic review was conducted. However, if you include some unpublished data you must include all.
“IN.PACT DEEP was a rigorously conducted trial which fulfilled all of the inclusion criteria for the meta-analysis, as evidenced by inclusion of its earlier 12-month results. In that study, amputation-free survival was numerically better in the drug-coated balloon group (drug-coated balloon 135/239 [56.5%] vs percutaneous transluminal angioplasty 65/119 [54.6%]). The inclusion of such a study is important for two reasons. It provides long-term follow-up, which was linked to mortality in the original meta-analysis in claudicants and it had a high number of events (death and amputation). Statistically, meta-analysis gives additional weight to large studies with high event rates because observed differences are less likely to be due to chance. It is my view that if those contemporary results had been included in this meta-analysis, the conclusions regarding amputation-free survival and safety would have been very different. Given the reintervention reducing benefit of drug-coated balloons, the authors have demonstrated we must get this right. A serious omission such as this must be corrected if we are to determine the truth—our very patients’ lives depend on it.
“These results are under a cloud due to methodological questions and the omission of the most important study. This should not impact anyone’s practice until those issues have been addressed.”
“I do not think this is really a big surprise, as the results from IN.PACT DEEP regarding a higher observed rate of major amputation in the paclitaxel-coated balloon arm have been known, and the only other reasonably large study (Lutonix-BTK) has yet to report one-year data. The other six trials are modest in size and the number of events is small. So the pooled data is dominated by the two larger trials, only one of which has reported one-year data with these effects known. There are and have been concerns about the adverse effects of paclitaxel embolisation in CLTI patients and this publication keeps the issue on the front-burner but does not resolve it much further.
“CLTI is a major global health problem and current treatments have significant limitations, contributing to high morbidity and mortality rates in these patients. Interventions for infrapopliteal arteries, in particular, have high rates of failure and thus there is considerable unmet need for more effective approaches. Thus the interest in various methods to improve the results of angioplasty, such as drug-elution, remains high.
“The limitations of this study relate to both the analysis itself and, more importantly, the state of the field it reflects. The meta-analysis involves pooled data and is not patient-level. Thus it is not possible to evaluate confounders (e.g. unbalanced comorbidities or clinical severity) that may be driving the outcomes. The actual event rates in these trials are lower than expected across the board, e.g. overall major amputation rate of 4% suggesting that the degree of limb threat at presentation may have been modest. The two larger trials employed a 2:1 randomisation ratio, leading to a significantly larger population with PCB exposure than controls. As stated above, the results are dominated by the two larger studies, and these studies have only reported short to mid-term outcomes. This is particularly relevant for the death outcome. CLTI itself has a broad clinical spectrum and the need for improved staging systems (for example, the Society for Vascular Surgery Wifi classification system) is evident to allow for better trial designs and balanced randomisation by limb severity. Finally, one has to ask—where are the five-year data from IN.PACT DEEP and where are the one-year data from Lutonix BTK? The vascular community deserves timely, complete, and honest reporting from the trials.
“The conclusions are cautiously stated by the authors and reflect the current data available. But the quality and quantity of data available in this space remains seriously lacking.
“No [I do not think the paper will change practice] because in the USA there are no currently approved paclitaxel-coated balloons for the infrapopliteal arteries at this time. It will be interesting to see if the final results of Lutonix BTK are reported and whether they allow for regulatory approval by the FDA. Until then I believe it is reasonable to continue to conduct appropriately monitored, well-designed RCTs to evaluate the safety and efficacy of drug-eluting devices for CLTI given the significant unmet need.”
“In my view, this manuscript may very well misinform the medical community and the patients we serve. It is important to note that the scientific community has been utilising higher level scientific analyses (i.e. patient-level data) to evaluate the role of paclitaxel in peripheral vascular procedures. The original question of whether paclitaxel has adverse outcomes in these procedures was a good one. However, there is a need to react scientifically to any potential investigator bias and ascertainment bias in the original data sets as well as the patient level data from the randomised trials and very large real-world data.
“First, patient care including safety and outcomes are foremost in my thoughts. However, this manuscript included data from non-peer reviewed studies presented at medical symposia as well as single-centre datasets and data published in lower-tiered journals. Both of these types of data, especially with the low total number of patients may be interesting, but do not have the level of accuracy to apply to a meta-analysis trying to make definitive patient safety claims. One of the cardinal sins for meta-analyses is to try and prove a point or to go in with an agenda.
“It is interesting that the authors chose to utilise certain data sets from the public sector, while at the same time leaving out others such as the many presentations of the longer-term follow-up of the INPACT DEEP study where the risk of amputation and survival actually reverse with uncoated balloon angioplasty demonstrating more risk. There have also been numerous presentations in the femoropopliteal bed with DCB (with an actual patient-level data meta-analysis) demonstrating a continuously decreasing relative risk as more complete follow-up data is obtained. These data have been submitted for publication and are under evaluation.
“The relevance of CLTI is important as typically there has been a “mantra” from the current authors that much larger public data sets that have been published without any safety signal has been due to the dilution by the increased risk of the critical limb population. The authors do not even address the fact that their first data sets evaluating the potential mortality signal appeared at a delayed time point of over a year, and here they seemingly find it at 6–12 months? This publication serves no useful purpose, in my opinion.”
“I was surprised about the inclusion of short-term outcomes in this study—the follow-up period ranges from six to 12 months. In a previous meta-analysis of the same study group regarding safety of paclitaxel-coated balloon use in femoropopliteal artery disease, absolutely no safety concern was evident at one-year follow-up. Now, in the present study, the authors raise a safety concern already within a couple of months after paclitaxel exposure that does not fit together with their assumption of an increased mortality risk as the consequence of a chronic paclitaxel toxicity due to disseminated multi-organ embolisation.
“The study data must be interpreted with caution due to several reasons. The limitations of the present meta-analysis are even more relevant as compared to the previous one related to femoropopliteal disease treatment. The overall study size of 1,420 patients is meaningful but still underpowered regarding the primary endpoint amputation-free survival considering the wide variation of the numbers found in the literature for the both individual endpoints: all-cause death and major amputation rate. In five of the eight studies, data from congress reports are included in the meta-analysis. The primary endpoint of the study is amputation-free survival. Secondary endpoints are all-cause death, major amputation, and target lesion revascularisation rates. Amputation-free survival was significantly worse for the drug-coated balloon group (HR 1.52, 95% CI 1.12–2.07, p=0.008), whereas all-cause mortality and amputation rates were not statistically significant different. The target lesion revascularisation rate was significantly lower after drug-coated balloon treatment (HR 0.53, 95% CI 0.35–0.81, p=0.004). Again, same as for drug-coated balloon application in femoropopliteal arteries, the authors postulate a dose-dependent increase of risk of mortality and amputation rate with “high-dose” drug-coated balloon devices.
“Katsanos et al conclude: “There appears to be an increased risk of death or major limb loss during the first year when paclitaxel-coated balloons are applied in the infrapopliteal arteries for CLTI treatment. Actual causes for this detrimental clinical outcome remain largely unknown, but downstream and systemic paclitaxel embolization is a plausible mechanism.
“First of all, the conclusion is wrong. The study does not show an increased risk of “death or major limb loss”: all-cause death rate does not significantly differ between the study groups (HR 1.39, 95% CI 0.94–2.07) nor does major amputation rate (HR 1.63, 95% CI 0.92–2.90). It is the combination of both endpoints—amputation-free survival—that is favouring the percutaneous transluminal angioplasty strategy.
“Are the findings real? The review includes study data derived from study-level data published or presented on recent congresses. Three out of eight studies are single-centre studies without independent clinical events committee adjudication of the safety events, three out of eight studies analysed are not yet published congress reports and the data may be subject of change during the publication process.
“The “trend to an increased all-cause mortality risk” following drug-coated balloon exposure in this study is not in line with the finding of the same study group for the treatment of femoropopliteal disease with drug-coated balloon. In the former study, the all-cause mortality rate was identical at one-year follow-up, whereas in the present study mortality rate was already higher after a short-time follow-up of six to 12 months only. If paclitaxel exposure during drug-coated balloon treatment should result in a chronic systemic toxic effect, as claimed by Katsanos et al, it should result in a uniform time to harm from exposure in particular considering that the paclitaxel doses applied during treatment of femoropopliteal disease is much higher as compared to below-the-knee disease. In addition, assuming a toxic drug effect, a dose–dependency of the mortality endpoint is crucial. The study found a lower mortality rate for “low-dose” drug-coated balloon, defined as 2μg/mm2, compared to “high-dose” drug-coated balloon (3–3.5μg/mm2). However, only one out of eight studies used a “low-dose” device and for this particular study only six-month follow-up data are published.
“The trend towards a non-significant higher major amputation rate following drug-coated balloon treatment in short-time follow-up must be interpreted with caution. Only one study (SINGA-PACLI) reported a significantly increased one-year amputation rate at one year. Major amputation rate is a study endpoint with high potential for bias due to the lack of uniform post-procedure wound care guidelines. In addition, study cohorts included in the meta-analysis are hard to be comparable regarding disease severity, in particular regarding the presence of wounds or ulcers ranging from 56.1% in Lutonix BTK—the only “low-dose” drug-coated balloon study—to 96.5% in DEBATE-BTK and SINGA-PACLI. In addition, patients included DEBATE-BTK were in 100% diabetics. The combination of diabetes and wounds characterises a high-risk patient population for amputation. Nevertheless, DEBATE-BTK resulted in the lowest odds ratio for major amputation despite the use of a “high-dose” DCB (3.5μg/mm2) that disproves the suggestion of the authors of dose-dependent local tissue toxicity.
“In summary, the current meta-analysis raises concerns regarding the short-term safety of paclitaxel-coated balloon treatment of below-the-knee disease in a CLTI study population resulting in a significantly reduced amputation-free survival rate after a follow-up of six to 12 months. Not going into statistical details, the study is characterised by major limitations but the safety signal deserves a higher quality data work-up including patient level data analysis and a longer-term follow-up of at least three years considering the high general mortality rate of a CLTI study population.
“These data will not impact practice because, as a result of the JAHA publication in 2018, drug-coated balloons are, in general, already used with caution. In addition, until the recent congress presentations of ACOART II (Guo et al, LINC 2019, Leipzig, Germany) and ACOART BTK (Liistro, VEITH 2019, New York, USA) no clear evidence existed regarding the technical efficacy of drug-coated balloons in below-the-knee lesions. Both afore mentioned studies for the first time demonstrated a patency benefit of a drug-coated balloon over percutaneous transluminal angioplasty. Therefore, so far the use of drug-coated balloon in below-the-knee disease in daily practice was experimental and limited to “drug-coated balloon believers” that will not be changed by the present publication. In my daily practice I will still use the drug-coated balloon brand investigated in the two ACOART studies in long below-the-knee total occlusions. Interestingly, in IN.PACT DEEP, the to date only study with a published five-year follow-up using a “high-dose” drug-coated balloon, the composite endpoint consisting of all-cause death, major amputation, and clinically-driven target lesion revascularisation was identical for both study cohorts (drug-coated balloon 59.8% vs. percutaneous transluminal angioplasty 57.5%, p=0.309) as well as the all-cause mortality rate (drug-coated balloon 39.4% vs. percutaneous transluminal angioplasty 44.9%, p=0.727).”
A range of interventional radiologists experts including Michael Dake (Tucson, USA), John Kaufman (Portland, USA), Jim Reekers (Amsterdam, The Netherlands) and Gunnar Tepe (Rosenheim, Germany) give their thoughts on the recently released meta-analysis in JVIR, which has suggested an increased risk of death or amputation at 12 months when paclitaxel-coated balloons are used in the infrapopliteal arteries for the treatment of critical-limb threatening ischaemia (CLTI).
Vascular and interventional cardiology experts including Kim Hodgson (Springfield, USA), Ramon Varcoe (Sydney, Australia) and Gary Ansel (Columbus, USA) give their thoughts on the recently released meta-analysis in JVIR, which has suggested an increased risk of death or amputation at 12 months when paclitaxel-coated balloons are used in the infrapopliteal arteries for the treatment of critical-limb threatening ischaemia (CLTI).
MedAlliance, the first drug-eluting balloon (DEB) company in the world to receive US Food and Drug Administration (FDA) breakthrough device designation status for a sirolimus DEB, has now been awarded breakthrough status for SELUTION SLR, its sustained limus release DEB catheter, in the treatment of AV fistula indications. This is the third breakthrough designation awarded to MedAlliance for its sirolimus DEB, following coronary in-stent restenosis and peripheral below-the-knee indications.
According to a press release, SELUTION’s technology involves unique micro-reservoirs made from biodegradable polymer intermixed with the antirestenotic drug sirolimus. These micro-reservoirs provide controlled and sustained release of the drug. Extended release of sirolimus from stents has been demonstrated highly efficacious in both coronary and peripheral vasculatures. MedAlliance’s proprietary CAT (cell adherent technology) enables the micro-reservoirs to be coated onto balloons and adhered to the vessel lumen when delivered via an angioplasty balloon.
“MedAlliance is honored to have our sirolimus DEB selected for the FDA’s breakthrough device programme for a third time. This may provide US patients faster access to a new technology with the potential to provide safer and more effective treatment,” said Jeffrey B Jump, chairman and CEO of MedAlliance.
The FDA breakthrough device programme is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide MedAlliance with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.
The goal of the breakthrough devices programme is to provide patients and healthcare providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and de novo marketing authorisation, consistent with the agency’s mission to protect and promote public health.
Two-year clinical follow-up data on the company’s SFA (superficial femoral artery) sirolimus DEB and six-months follow up data on the coronary de novo and in-stent restenosis DEB were presented at TCT and VIVA last year.
Reflow Medical has announced that its Temporary Spur stent system for treating below-the-knee peripheral arterial disease (PAD) won US Food and Drug Administration (FDA) breakthrough device designation.
The Temporary Spur stent system includes radially expandable spikes designed to create multiple pathways for delivering antiproliferative drugs for increased uptake into the vessel wall for facilitating acute luminal gain without leaving anything behind, a company press release explains.
Reflow Medical developed the device in response to unmet clinical needs that resulted in high rates of restenosis and treatment challenges for patients with below-the-knee PAD, according to a news release.
The San Clemente, US-based company said it plans to build on clinical evidence supporting the Temporary Spur stent system and continue development in other clinical areas based around the Spur platform.
“We are extremely grateful to the FDA for their expedited designation of the Temporary Spur stent system as a breakthrough device,” Reflow Medical CEO Isa Rizk says. “We plan to take full advantage of the programme’s benefits, accelerating our efforts towards meeting the requirements of the review process as we advance this novel technology, with the goal of improving the lives of patients.”
There is no sign of increased all-cause mortality following the use of paclitaxel-coated devices for the treatment of symptomatic peripheral arterial occlusive disease, a new study based on German claims data attests in the European Journal of Vascular and Endovascular Surgery.
The study investigators set out to determine the survival of patients after use of paclitaxel-coated devices using a propensity score matched retrospective analysis of German health insurance claims. BARMER is the second largest insurance fund in Germany, and lead author Christian-Alexander Behrendt (University Medical Centre Hamburg-Eppendorf, Hamburg, Germany) and colleagues used this dataset to identify index femoropopliteal arterial interventions between 1 January 2010 and 31 December 2018. To ensure first paclitaxel exposure, patients with prior deployment of paclitaxel were excluded.
The study cohort—37,914 patients; mean age 73.3 years; 48.8% female—was stratified into patients with chronic limb threatening ischaemia (CLTI) and intermittent claudication, then into balloon versus stent cohorts. Within each stratum, paclitaxel was compared with uncoated devices.
Contextualising this research by highlighting how multiple US and European guidelines have recommended drug-eluting devices as “first-line treatments in the femoropopliteal segment”, Behrendt et al cite a 2018 meta-analysis published in the Journal of the American Heart Association (JAHA) as the cause for heightened scrutiny on these devices in recent months. The JAHA meta-analysis, authored by Konstantinos Katsanos (School of Medicine, University of Patras, Patras, Greece) and colleagues, evaluated data from 28 randomised controlled trials, and reported a higher risk of death at two and five years following the use of paclitaxel-coated balloons and paclitaxel-eluting stents in the femoropopliteal arteries.
However, this finding was not repeated in analyses involving “real-world data”. As reported in this newspaper, Eva Freisinger (University Hospital Münster, Münster, Germany) also used the BARMER dataset to conduct a real-world safety analysis of paclitaxel-based devices in peripheral arteries, concluding in the European Heart Journal that the use of drug-eluting devices is “safe for endovascular therapy of the lower limbs”. Indeed, Freisinger et al explicitly stated: “Particularly with regard to long-term mortality, neither drug-coated balloons nor drug-eluting stents was associated with increased risk compared to non-drug-eluting devices”.
The present study is differentiated from that of Freisinger et al by restricting the included patients to ensure a more homogenous study population. Behrendt and his co-investigators write: “Aiming to add to the existing evidence, the current approach rested on a rigorous study design involving a more homogeneous study population (only femoropopliteal segment, no prior major amputation), with a lookback period of up to five years and follow-up periods (left and right censoring) of five years.”
In this most recent analysis of the BARMER insurance claims dataset, Behrendt and co-authors also have opposing conclusions to the Katsanos et al JAHA meta-analysis. They report that paclitaxel-coated balloons and stents were associated with improved overall survival (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.77–0.90), amputation-free survival (HR 0.85, 95% CI 0.78–0.91), and freedom from major cardiovascular events (HR 0.82, 95% CI 0.77–0.89) versus uncoated devices at five years for CLTI. In the intermittent claudication cohort, mortality was significantly lower after using drug-coated balloons (HR 0.87, 95% CI 0.76–0.99) or combined drug-coated balloons and drug-eluting stents (HR 0.88, 95% CI 0.80–0.98).
Additionally, Behrendt et al note that the annual proportion of paclitaxel use increased from 3% to 39% during the study period for CLTI, and from 4% to 48% for intermittent claudicants (both p<0.001).
“In this propensity score matched retrospective analysis of health insurance claims,” the authors summarise, “comprising a rapidly increasing proportion of paclitaxel-coated devices in the treatment of peripheral arterial occlusive disease, higher long-term survival, amputation-free survival, and adverse cardiovascular event-free survival after the treatment of CLTI with paclitaxel-coated devices (both balloon and stent) was found, when compared with the uncoated control group. In patients with intermittent claudication, paclitaxel-coated devices were associated with higher long-term survival only, visible in the group where balloons and stents were combined and for balloons but not for stents. Unlike any other prior analysis, a persistent, robust, and positive association of paclitaxel exposure and survival is documented for a wide range of subgroups.”
The US Food and Drug Administration (FDA) has released draft guidance detailing the information device-makers should include in 510(k) submissions of catheter-based devices intended to treat peripheral vasculature lesions.
The guidelines, which cover class II peripheral percutaneous transluminal angioplasty (PTA) balloons and specialty catheters—including infusion catheters, PTA balloon catheters for in-stent restenosis and scoring/cutting balloons—include suggestions on labelling, performance testing, biocompatibility, and other issues.
Labelling should include information on indications, contraindications, warnings, product information, directions for use and a summary of clinical trial data, if applicable, the agency said.
TriSalus Life Sciences (“TriSalus”, formerly Surefire Medical) today announced the launch of its TriNav infusion system (“TriNav”). Powered by its proprietary pressure-enabled drug delivery (PEDD) approach with SmartValve technology, TriNav is designed to help overcome the infusion barriers that limit therapeutic uptake in solid tumours, including hepatocellular carcinoma (HCC) and liver metastases.
The TriNav system can provide interventional radiologists intravascular tumour access with improved trackability, compatibility with standard angiographic catheters, and workflow comparable to standard interventions, a TriSalus press release states.
The tumour microenvironment creates pressure barriers that limit flow into solid tumors. PEDD with SmartValve creates a high-pressure gradient that improves delivery and penetration of therapy into tumours. The porous expandable SmartValve is designed to allow antegrade flow, and leverages blood flow to carry the dose deep into the solid tumour. SmartValve enables therapy delivery to the intended target while minimising non-target delivery that has been shown to damage healthy tissue.
In a clinical study, PEDD with SmartValve demonstrated the ability to overcome tumour infusion barriers and significantly improve response rates in HCC. Outcomes from a retrospective, single-centre study of patients with solitary HCC tumors who underwent treatment utilising either PEDD or standard end-hole microcatheters, showed 100% objective response (OR) with PEDD versus 76.5% with standard end-hole microcatheters (p=0.019). Additionally, after first treatment, Pathological response (PR) as shown by tumour necrosis percentage was significantly greater with PEDD (88.8%) versus standard end-hole microcatheters (33.8%; p=0.026). Improving response rates could potentially help more patients meet transplant criteria, lead to successful down-staging, bridging, and post-transplant survival.
“Tumour-directed delivery of therapeutics is an exciting opportunity to help improve outcomes across a wider range of procedures by overcoming intratumoral pressure that can prevent drugs from adequately penetrating the tumour,” says Mary Szela, president and CEO of TriSalus. “The new TriNav infusion system utilises SmartValve, a first-in-kind, proprietary technology that has been shown to modulate pressure and flow with the goal for improved therapeutic delivery and deeper penetration into the tumour while helping to protect healthy tissue.”
Acknowledging its technology for therapeutic delivery, the Centers for Medicare and Medicaid Services (CMS) granted TriNav transitional pass-through payment as part of the 2020 Medicare Hospital Outpatient Prospective Payment System and Ambulatory Surgical Center Payment System (CMS-1717-FC), effective 1 January, 2020.
This supplemental payment is intended to “facilitate access for [Medicare] beneficiaries to the advantages of new and innovative devices”. The TriNav infusion system met the required criteria to receive transitional pass-through status, including the demonstration of substantial clinical improvement, with the CMS saying it believes there is no existing pass-through payment category for this device because its SmartValve technology offers a unique mechanism for therapy delivery to selected sites in the peripheral vascular system, including solid tumours in the liver.
Patient enrolment in the PRESTIGE below-the-knee (BTK) clinical trial has been completed. The objective of this clinical investigation is to evaluate the six-month safety and performance outcomes of SELUTION SLR, MedAlliance’s novel sirolimus-eluting balloon, for the treatment of long tibial occlusive lesions (TASC C and D) in patients with critical limb ischaemia (CLI).
PRESTIGE is a prospective, single-centre, physician-initiated clinical study, being run at Singapore General Hospital, Singapore, by Chong Tze Tec and Tang Tjun Yip. Twenty-two patients have now been enrolled. Clinical follow-up will be at one, three, six and 12 months.
“The initial performance of SELUTION SLR has been very encouraging”, Tec says. “We have observed good blood flow in the amputation segment and some cases of fast wound healing. The device is also easy to track and deliver. We are eagerly awaiting the study’s follow-up data”.
Singapore has a high percentage of diabetics in its population, and CLI therefore constitutes a major challenge among patients seen with peripheral arterial disease (PAD). Singapore General Hospital (SGH) performs over 1,000 interventional procedures a year on patients suffering from CLI.
The PRESTIGE study, utilising a sirolimus-eluting balloon, is particularly significant in the wake of current controversy surrounding paclitaxel-coated balloons, a MedAlliance press release states.
Historically, paclitaxel has been the drug of choice for use in drug-coated balloons (DCBs). SELUTION SLR is the first sirolimus drug-eluting balloon specifically designed to treat PAD. This device combines the safety and efficacy of sirolimus with advanced MicroReservoir and cell adherent technology to offer a sustained therapeutic effect for over 60 days, achieving long-term clinical benefits.
The MicroReservoir combines sirolimus with a biodegradable polymer. Millions of these MicroReservoirs act as miniature drug delivery systems, achieving sustained sirolimus release.
The cell adherent technology achieves an unmatched drug bioavailability and minimal systemic loss, allowing for a lower drug dose concentration on the balloon surface (1μg/mm²). Proprietary amphipathic lipid technology binds micro-reservoirs to the balloon surface to protect during insertion and navigation of the balloon. Once the balloon is inflated, the cell adherent technology ensures transfer of micro-reservoirs to the tissue and cellular uptake of the sirolimus drug.
“We are excited at the prospect of demonstrating that our breakthrough technology is effective in below-the-knee lesions, so bringing much-needed relief to a substantial group of patients who might otherwise not be effectively treated”, adds MedAlliance chair and CEO Jeffrey B Jump.
MedAlliance was granted breakthrough designation by the FDA on 20 September 2019.
Positive, two-year data from the first-in-human study of SELUTION SLR was presented at the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA) by principal investigator Thomas Zeller (Universitaets-Herzzentrum, Bad Krozingen, Germany). The study involved 50 patients treated with the investigational device in lesions of the superficial femoral artery and popliteal artery.
Alucent Biomedical has received US Food and Drug Administration (FDA) approval to proceed with a phase 1 clinical trial to evaluate the safety and efficacy of its Natural Vascular Scaffolding (NVS) technology. The therapy is designed to treat peripheral arterial disease (PAD) of the lower extremities, a condition that affects over 200 million people worldwide.
According to a press release, the Alucent NVS vessel restoration system with photoactivated linking combines standard angioplasty with linking of the structural proteins in the wall of a blood vessel. The intervention is designed to deliver immediate restoration of the vessel’s lumen and sustained improvement of blood flow, without the introduction of a foreign implant, such as a metallic stent, into the patient’s body. Because there is no rigid foreign material, the arterial wall has the potential to retain its natural functionality and flexibility, and avoid the complications of permanent stents. Alucent NVS photoactivated linking is also designed to mitigate the adverse effects of angioplasty, such as vessel recoil. Sustained, improved blood flow is expected to result in pain relief, limb preservation, and an improved quality of life for patients.
“FDA approval to commence human clinical testing allows us to move this revolutionary therapy into PAD patients, many of whom are in acute need of a better and more durable alternative to currently available treatments,” comments Myles Greenberg, CEO of Alucent.
Preclinical testing of NVS in animal studies has shown acute and long-term safety and patency without the pro-inflammatory and mechanical risks of placing a rigid foreign implant into the blood vessel.
“Alucent NVS is a novel and disruptive medical therapy that may promote better clinical outcomes in patients with symptomatic femoropopliteal atherosclerosis without the use of a metallic implant. Moreover, given the novel nature of this therapy, which in animal models was able to restore vessel wall architecture, it has the potential to dramatically improve quality of life in patients with peripheral arterial disease”, says Krishna Rocha-Singh, chief scientific officer at HSHS St John’s Prairie Heart Institute in Springfield, USA, and chief medical advisor of Alucent Biomedical.
Enrollment for the phase 1 clinical trial is expected to begin in Q1 2020. Up to 15 patients will be enrolled across five research sites, including the Cardiovascular Institute of the South in Houma, USA, and the Wellmont Hollston Valley Medical Center in Kingsport, USA.
An artificial intelligence (AI) programme has been developed that is better at spotting breast cancer in mammograms than expert radiologists, an article published in Nature reports.
“Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful,” lead author Scott Mayer McKinney (Google Health, Palo Alto, USA) et al write. “Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives.”
To assess the performance of their AI system in the clinical setting, the investigators curated a large, representative dataset of mammograms for 25,856 patients in the UK, and a large, enriched dataset of 3,097 patients from the USA. These datasets were used to train the AI system, before it was used to identify the presence of breast cancer in mammograms of women who were known to have had either biopsy-proven breast cancer or normal follow-up imaging results at least one year later.
In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than that AUC-ROC for the average radiologist by an absolute margin of 11.5%. Mayer McKinney and colleagues further demonstrate an absolute reduction in false positives of 5.7% in the USA and 1.2% in the UK, and an absolute reduction in false negatives of 9.4% in the USA and 2.7% in the UK.
“This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening,” Mayer McKinney et al conclude.
If the programme proves its worth in clinical trials, the software, developed by Google Health, could make breast screening more effective and ease the burden on health services such as the UK’s National Health Service (NHS), where radiologists are in short supply.
Writing in an accompanying editorial in Nature, Etta Pisano (American College of Radiology, Philadelphia, USA, and Beth Israel Lahey Medical Center, Harvard Medical School, Boston, USA) says “Screening is used to detect breast cancer early in women who have no obvious signs of the disease. This image-analysis task is challenging because cancer is often hidden or masked in mammograms by overlapping ‘dense’ breast tissue. The problem has stimulated efforts to develop computer-based AI systems to improve diagnostic performance. […] Despite some limitations, McKinney and colleagues’ study is impressive. Its strengths include the large scale of the data sets used for training and subsequently validating the AI algorithm.
“McKinney and colleagues’ results suggest that AI might someday have a role in aiding the early detection of breast cancer, but the authors rightly note that clinical trials will be needed to further assess the utility of this tool in medical practice.”
Several reports emerged last year concerning issues with MRI safety.
In October 2019, officials at Sunderby Hospital in Luleå confirmed that a hospital staff member and two security guards were injured in an accident at a mobile MRI unit outside the hospital. According to the Swedish press at the time, a specialist nurse got stuck outside the gantry. When his screams and the appearance of a hand inside the scanner alerted the patient that something was wrong, the patient reportedly got out of the machine and tried to help the nurse. With the help of a security officer, the nurse was pulled out of the mobile unit, although he was unconscious at this stage.
At a press conference on 24 October, Aleris, the company that owns the equipment, the MR trailer, and employs the injured person) reported that the nurse had been moved from the intensive care unit to a regular ward. His condition has improved, and he said he was feeling OK under the circumstances, Emma Bergström Wuolo, press officer of the Norrbotten region, noted.
In early November 2019, reports appeared in the Swedish press about a second MRI accident that occurred in Varberg, Sweden, in April. A staff member at the Halland hospital in Varberg, who was accompanying an anxious patient into the MRI scanner room, was wearing a metallic ankle band with steel balls, and their leg got stuck to the scanner, according to a report in Aftonbladet, a Stockholm-based tabloid newspaper.
There were no injuries, but the machine had to be shut down for more than two weeks. The total cost to the hospital was around 1,000,000 Swedish krona (£82,800), Magnus Warfvinge, deputy head of X-ray operations in Halland, told Aftonbladet.
Meanwhile, a court case continues following the death of a man in India in January 2018 following an MRI accident. The man was accompanying his mother-in-law into an MRI suite, and was killed when he was sucked into the magnet bore while carrying an oxygen tank.
An analysis of data from the ATTRACT trial, published in the Journal of Vascular Surgery: Venous and Lymphatic Disorders (JVSVL), has revealed that quality of life (QoL) measures improve after pharmacomechanical catheter-directed thrombolysis (PCDT). According to the findings of the analysis, this is particularly true early on and for iliofemoral deep venous thrombosis (DVT).
It is said that, despite treatment with anticoagulation and compression stockings, up to 50% of patients with proximal DVT develop post-thrombotic syndrome (PTS), which causes patients to experience severe pain and swelling of the limb, as well as increasing the risk of pulmonary embolism (PE).
As Venous News has previously reported, the results of the ATTRACT trial showed that PCDT does not reduce the occurrence of PTS at two years but does lessen its severity, as well as treating acute symptoms faster.
In this analysis, lead investigator Susan Kahn (Jewish General Hospital, Montreal, Canada) and colleagues aimed to assess the effect of PCDT on both short-term and long-term QoL in all of the patients enrolled in the ATTRACT trial—as well as predefined subgroups with (iliofemoral DVT) or without (femoral-popliteal DVT) involvement of the iliac or common femoral vein—before examining whether this effect differed over time.
As part of the investigation, QoL was evaluated in a total of 692 patients between 2009 and 2014, with follow-up taking place at one, six, 12, 18 and 24 months. Randomisation resulted in 337 being allocated to PCDT, and 355 to no PCDT; upon analysis, it was found that VEINES-QOL change scores were greater (and therefore better) in the PCDT cohort vs. no PCDT from baseline to one month (difference, 5.7, p=0.0006), and from baseline to six months (5.1; p=0.0029). For all other intervals, there was no difference.
According to the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS), scores were greater in PCDT vs. no PCDT from baseline to one month (difference, 2.4; p=0.01), but not for other intervals.
However, among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs. no PCDT group, and this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; p<0.0001) and 6 months (8.8; p<0.0001). SF-36 PCS change scores were greater in PCDT vs. no PCDT from baseline to 1 month (difference, 3.2; p=0.0010), but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in both cohorts.
Commenting on these findings, Kahn said: “First, most of the improvement in QoL was in the first six months, and the trial did find that PCDT reduced clot burden and early leg pain and swelling over no PCDT, and was associated with a reduced point prevalence of PTS at six months, but not thereafter. Though PCDT did not prevent PTS, it did reduce its severity.”
Furthermore, a statement from the Society for Vascular Surgery (SVS) noted that the decision to proceed with lytic therapy for patients with iliofemoral DVT can be complicated. “This data supports offering this therapy to selected patients with severe symptoms, low bleeding risk and a willingness to undergo a catheter-based procedure,” it read.
The Society of Interventional Oncology (SIO) has announced that Jena Eberly Stack will assume the role of executive director effective 1 January, 2020. As a certified project management professional through the PMI Institute, Stack brings expertise in strategic development, change management, and association governance, a society press release states.
“I am thrilled to be joining SIO as the new executive director,” Stack comments. “This is such an exciting time for the society and for the field of interventional oncology. I have had the pleasure of getting to know SIO’s board of directors in recent weeks and I know we will continue to accomplish great things for SIO’s members and the industry.”
Stack has worked in association management for the past six years, previously having worked in other non-profit management and education settings. Her association management experience has been focused in healthcare organisations, having served a variety of clinical societies. She is excited to join SIO in this capacity and help further advance the field of interventional oncology.
Cameron Curtis, the current executive director, is leaving SIO to pursue another opportunity. “On behalf of the SIO board of directors, I would like to thank Cameron for her strong leadership,” said board president William Rilling. “We have accomplished a great deal with her energy and guidance and look forward to building on our momentum as Jena assumes executive leadership of SIO.”
“Cameron has served as an exceptional leader and partner of the board, playing an integral role in the evolution and success of the society,” continued Rilling. “Under her leadership, SIO has achieved tremendous success, and we cannot thank her enough for her commitment and service to SIO. Although she will be greatly missed, we wish her all the best in her future endeavours.”
PQ Bypass announced today that it has received approval for coverage from the Centers for Medicare and Medicaid Services (CMS) for the Investigational Device Exemption (IDE) study titled TORUS 2. This approval will affect coverage across all Medicare administrative regions.
TORUS 2 (The PQ Bypass pivotal IDE intra-arterial stent graft study for occlusive and restenotic fem-pop revascularisation) will evaluate the safety and effectiveness of the TORUS stent graft system in the treatment of obstructive atherosclerotic lesions of the superficial femoral and/or proximal popliteal arteries. Led by national coprincipal investigators Peter Schneider (Division of Vascular and Endovascular Surgery, University of California San Francisco, San Francisco, USA) and Ehrin Armstrong (Director of Interventional Cardiology, Rocky Mountain Regional VA Hospital; University of Colorado School of Medicine, Aurora, USA), this prospective, single arm study will enrol up to 188 patients at up to 40 sites.
“The TORUS Stent Graft System represents the first major stent graft advancement in more than a decade for patients with SFA lesions and is the vanguard for the next generation of medical devices,” says Heather Simonsen, General Manager of PQ Bypass. “Currently, patients and physicians have only one stent graft option, which gained approval for the SFA in 2005, on the market in the USA.”
Previously studied in the DETOUR 1 and TORUS 1 studies in Europe, and currently under investigation in the DETOUR 2 IDE trial, the TORUS stent graft was granted CE mark as a part of the DETOUR procedure in 2017.
The TORUS stent graft is limited by federal law to investigational use only and is not available for sale in the USA. For more information, please visit www.pqbypass.com
The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK, has become the first in the country to offer patients audio-visual goggles to distract and comfort them when undergoing an IR procedure without general anaesthesia or with only local anaesthetic. With a 100% patient satisfaction, the iTV FPView 3D HD goggles have been used in a variety of interventional radiology procedures where the patient lies supine for longer than 20 minutes, including prostate artery embolization, transarterial chemoembolization, superior rectal artery embolization, complex vascular recanalisation, and for GI bleeds. Here, project leader Clare Bent discusses the lessons learned from the patient experience, and how her Trust could serve as a model both nationally and internationally.
Audio-visual (AV) technology may be the next global initiative within interventional radiology (IR) to improve the patient experience during invasive medical care.
I have been leading the IR team at the Royal Bournemouth and Christchurch Hospitals (RBCH; Bournemouth, UK) in a quality improvement project to assess the benefits of AV goggles in the IR setting. These video goggles stream personal entertainment directly to the patient during IR procedures (HD and 3D videos, daytime television, box sets or real-time procedural imaging), aiming to distract and reduce anxiety and awareness. Published data suggests that AV distraction is a promising analgesic technique that is safe, reduces intravenous sedation and general anaesthetic requirements, and consequently allows for earlier ambulation and discharge following medical treatment.
Why were the goggles introduced?
With IR at the front-line of medical innovation, newer complex procedures frequently result in an increase in procedural duration. Further research into non-pharmacological methods to optimise patient experience and complement these technical advancements is warranted.
For longer procedures, a static position, lying on a relatively hard IR table, can be poorly tolerated by patients. With pain perception known to have a large psychological component, distraction techniques such as AV use a) allows time to pass expeditiously and b) deflects the patient’s attention from noxious stimuli with a consequential reduction in perceived pain.
Patient experience and pain measures—using visual analogue score (VAS), sedation requirements, length of postprocedural hospital stay, and a cost-benefit analysis—are examined. The RBCH IR team is hopeful that the AV goggles will benefit the patient and improve hospital throughput.
What was the patient experience like?
To date, 30 patients have trailed the AV goggles with 100% positive feedback.
Patients have commented that the focus of attention to streamed media has meant they have not noticed the invasive treatment being undertaken.
One patient undergoing resuscitation and embolization for a gastrointestinal bleed requested to watch Formula One during the procedure to distract him from the resuscitation team’s clinical management, and fed back positively that the distraction had improved his otherwise traumatic experience.
What are the key lessons from the quality improvement project?
How could this be rolled out nationally and internationally?
The quality improvement project will run initially for a six-month period to enable data collection. Following completion, the RBCH IR team aim to present and publish their findings to Trust management and to a wider audience within IR.
Internally, endoscopy, day theatres, and cardiac intervention have already requested a roll out of AV goggle use to facilitate improved patient experience in their own departments drawing on data and learning from this quality improvement project. Additionally, RBCH have received positive enquiries from national hospitals and industry, with the latter considering inclusion as part of IR suite specifications for future projects.
This quality improvement project hopes to recommend the use of AV goggles as a simple, non-invasive, low cost, and non-pharmacological method to improve patient experience and hospital throughput, which will in turn complement recent and future advances in IR.
Clare Bent is an interventional radiologist at the Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK.
The improvements in quality of life measurements and International Prostate Symptom Score (IPSS) in patients following prostatic artery embolization (PAE) are “far superior” to those due to the placebo effect, a new study just published in European Urology, the official journal of the European Association of Urology (EAU), concludes. Publishing a paper positively describing PAE in a urology journal has historically been difficult for interventional radiologists, and co-author Tiago Bilhim (Hôpital Saint-Louis, Lisbon, Portugal) tells Interventional News that this publication “might help our way into the urology guidelines with PAE”.
The most recent EAU guidelines for the diagnosis and treatment of men with lower urinary tract symptoms (LUTS)/ benign prostatic hyperplasia (BPH), published in 2017, are cautious when describing the potential clinical role of PAE, saying that the selection of LUTS patients who will benefit from the procedure still needs to be defined, and highlighting that PAE is technically demanding. The European guidelines state: “A multidisciplinary team approach of urologists and radiologists is mandatory as the basis for future RCTs [randomised controlled trials] of good quality with long-term follow-up in order to integrate this treatment option into the spectrum of efficient, minimally invasive treatment options.”
Bilhim says that the present study is the “kind of research” called for by the European urology community in order to accept PAE into their guidelines for the treatment of LUTS due to BPH. He therefore hopes that this research, which he says demonstrates that PAE is not a placebo procedure, “will be a fundamental study to raise the level of evidence of PAE to treat LUTS due to BPH, and to help get PAE in the [European] urology guidelines.”
In the USA, the American Urological Association (AUA) also mention PAE in their guidelines, published in The Journal of Urology—but only to explicitly not recommend the procedure outside the context of a clinical trial. Interventional radiologists have been advocating for the procedure’s acceptance by urologists, with several prominent figures in this community calling for more widespread awareness of the safety and efficacy of this minimally invasive treatment option for select LUTS/ BPH patients.
The authors of this recent publication therefore underline the importance of sharing their data with the urology community, writing: “PAE is considered experimental in the urology guidelines. For a novel technique such as PAE to be considered as a first-line option, sham-controlled trials are very helpful, and hence the present study.”
In light of the positive outcomes observed in the PAE group, they believe “The results of this clinical trial will be a reference for future research consensus panels and guidelines on the management of LUTS/BPH.”
Speaking to this newspaper in May 2019, Ari Isaacson (Department of Radiology, University of North Carolina, Chapel Hill, USA) highlighted the importance of interventional radiologists publishing their work in urology specific journals, as a way of communicating their views directly to this community. However, he reported that this is challenging: “We have attempted to [publish in a urology journal] several times; it is very difficult to get a PAE paper in a urology journal”. Riad Salem (Northwestern University, Chicago, USA), who is one of few US interventional radiologists that has published a PAE paper in a urology journal, supports this assertion, commenting earlier this year: “In my 20 years of publishing over 330 papers, getting accepted into a urology journal was the most difficult, challenging, controversial process I have ever been through. The reviews were replete with opinions that seemed to have been made before even reading the study. We tried several times, and finally got accepted into the fourth urology journal. This was a prospective, phase II, FDA [US Food and Drug Administration]-approved study, so it met all the high level criteria, but it was still dismissed by many urology journals.”
However, the European urology community has been more welcoming, as Bilhim describes. “The overall experience was very positive,” he says. “We received very constructive reviews from urology experts in the field of BPH that helped make the manuscript better. We wanted to target the urology community because the major goal of this manuscript was to prove to the urology community that PAE is not a sham procedure, and is in fact safe and effective for the treatment of LUTS, without compromising sexual function.
“The major goal of this study was to raise the level of evidence for PAE as a safe technique to treat LUTS due to BPH, so that PAE can be considered as [an] effective alternative in the urological guidelines for patient management. The submission process in the urology journal was similar to standard scientific journals and it took around four to six months from submission to final acceptance.”
Trial findings: PAE superior to sham procedure
Lead author João Pisco (Hôpital Saint-Louis, Lisbon, Portugal), who died in March 2019 after completion of the trial, and co-authors set out to assess the safety and efficacy of PAE “above and beyond the placebo effect” compared to with a sham procedure for the treatment of LUTS/BPH. They conducted a parallel-group, single-blind, sham-controlled superiority randomised clinical trial in 80 men, aged 45 or above, with severe LUTS/BPH non-responsive to medical treatment between 2 September 2014 and 3 March 2018 at Hôpital Saint-Louis, Lisbon, Portugal, with an efficacy assessment at six months after randomisation. This was followed by an open extension phase, where all 38 patients of the sham trial arm who completed the single-blind period crossed over to the PAE arm (underwent the procedure). A final evaluation was conducted at 12 months after randomisation. One patient in the PAE group and three in the sham group did not complete the study.
Patients were randomised 1:1 upon successful catheterisation of a prostatic artery to either PAE or a sham PAE procedure without embolisation. Pisco and colleagues describe the procedure: “In the PAE group, Bead Block (BTG plc, London, UK) 300–500mm was used; in the sham group, after catheterisation of one prostatic artery, the catheter was removed and no particles were injected, but there was a wait of some minutes before the removal of the catheter in order to avoid revealing the treatment arm to patients of the sham group.” All procedures were performed by five interventional radiologists with between three and 10 years of experience in PAE.
The investigators performed an intention-to-treat analysis of all randomised patients. The co-primary outcomes were the change from baseline to six months in the IPSS and the quality of life score at six months, analysed with analysis of covariance and t test, respectively.
At six months, patients in the PAE arm had a greater improvement in IPSS than patients in the sham arm. For those that underwent PAE, the decrease from baseline to month six in IPSS was 17.1±7.25. In comparison, the decrease in IPSS from baseline to six months for patients who underwent the sham procedure was only 5.03±8.13 (difference between groups in changes from baseline: 13.2, 95% confidence interval [CI]: 10.2–16.2, p<0.0001). After six months, the mean IPSS in the PAE group was 8.75±5.73, and 21.9±7.34 in the sham arm.
This pattern was also true of improvements in quality of life: for patients treated with PAE, mean quality of life score at six months was 3.48±1.38, while for patients treated with the sham procedure, mean quality of life score at six months was 1.35±1.12 (difference in the means of quality of life scores between groups at month six: 2.13, 95% CI: 1.57–2.68, p<0.0001).
The occurrence of adverse events was similar between the two groups: 16 events in 14 patients (35%) after PAE, and 17 events in 13 patients (32.5%) following the sham procedure. One serious adverse event took place in the sham group during the open period.
“The results of this randomised clinical trial provide clear evidence that the improvement experienced by patients after PAE is due to a real treatment effect that is much larger than the placebo effect associated with the procedure,” Pisco et al summarise. “The marked and sustained amelioration in all primary and secondary outcomes, with no negative influence on erectile function, offers strong evidence that PAE, through the reduction it imposes on prostate size and possibly because of several other mechanisms, actually modifies the course of LUTS/BPH, and this explains the high clinical success rates reported so far with this treatment.”
PAE “still in the investigational phase” but this study “fills the gap in the evidence base”
Setting out the case for PAE, Pisco et al write: “PAE is a minimally invasive treatment that has been shown in many observational studies and meta-analyses to be safe and effective, reducing LUTS/BPH. In addition, many phase II trials without controls already exist, showing the safety and efficacy of PAE for BPH.
“However,” they add, “LUTS/BPH is known to be very susceptible to placebo treatments, and conclusive demonstration of efficacy will require randomised controlled trials, but until now only three randomised clinical trials of PAE have been published, all comparative to TURP [transurethral resection of the prostate], and none has conclusively demonstrated the efficacy of PAE in LUTS/BPH.” They therefore conclude that, prior to their present study, PAE was “still in the investigational phase”, as “as evidence of efficacy compared with standard treatment has not yet been clearly demonstrated and randomised placebo-controlled clinical trials have not previously been conducted.”
The authors conclude that “The single-blind period of this randomised clinical trial fills the gap in the evidence base on the treatment effect of PAE by demonstrating both clinically and statistically significant differences in patients treated with PAE as compared with patients submitted to a sham procedure. In addition, the trial open extension period offers evidence of sustainability of effects up to 12 months.”
Nonetheless, they concede that “major questions still remain”, especially regarding the durability of the treatment effect. Pisco et al call for non-inferiority clinical trials providing data on long-term outcomes after PAE in large patient cohorts, and say that future research should focus on providing comparative studies of PAE with surgery or medical care with appropriate cohort sizes and long-term follow-up.
Thrombolex has announced that the company has received US Food and Drug Administration (FDA) clearance for the Bashir Endovascular Catheter – Short Basket (BEC S-B). The indication for use of the BEC S-B is for the controlled and selective infusion of physicianspecified fluids, including thrombolytics, into the peripheral vasculature.
Thrombolex provides an innovative line of endovascular catheters, which feature a unique combination of mechanical-pharmaco, expandable infusion basket for effective treatment of venous thromboembolic (VTE) conditions.
According to Thrombolex, the BEC S-B represents the third FDA 510k premarket pathway clearance achieved this year by the Company. This new medical device is part of the Company’s platform technology.
The Bashir line of interventional catheters are the first interventional catheters to rapidly create multiple cross-sectional channels to allow the patient’s own endogenous lytics to immediately begin to flow into the culprit thrombus. The treatment is then enhanced by infusing small amounts of exogenous thrombolytics directly into the culprit thrombus, the combination of which accelerates the dissolution of the clot burden.
The Bashir Endovascular Catheter (BEC) and the Bashir N-X Endovascular Catheter (BEC N-X) previously received FDA 510k premarket pathway clearance earlier this year. The BEC is cleared for the controlled and selective infusion of physicianspecified fluids, including thrombolytics, into the peripheral vasculature. The BEC N-X is a device intended for the localised infusion of physician specified fluids, into the peripheral vasculature, including the pulmonary arteries.
The company has advised that the BEC S-B will be introduced into the USA through a controlled roll-out at hospitals with established VTE treatment protocols.
Cardiovascular Systems announced today that the first patient in Europe has been treated with its Stealth 360 peripheral orbital atherectomy system (OAS) 1.25mm Micro Crown with GlideAssist (1.25 Micro Crown).
According to a press release, the 1.25 Micro Crown is designed with flexibility for tortuous vessels and tight bends below the knee. The GlideAssist feature enables the crown to spin at a slow speed of 5K rpm, facilitating tracking and smoother movement to access diffuse, calcified lesions below the knee.
Michael Lichtenberg, chief physician, Clinic for Angiology, Hochsauerland Hospital, Arnsberg, Germany, successfully treated the first peripheral patient with the 1.25 Micro Crown.
Lichtenberg said, “CSI’s new Stealth OAS 1.25 Micro Crown with GlideAssist is a welcome addition to my toolbox for treating challenging critical limb ischemia, or CLI, cases. In particular, the device’s dual mechanism of action of differential sanding and pulsatile forces will be instrumental in the treatment of the challenging calcified lesions I often see in lesions below the knee.”
Scott Ward, chairman, president and chief executive officer of CSI, said, “With our distribution partner, OrbusNeich, we are excited to introduce the 1.25 Micro Crown in Germany. One million German patients suffer from CLI, a severe condition that can result in severe pain, tissue damage and loss of limbs. The 1.25 Micro Crown provides physicians with a minimally invasive therapy to access and effectively treat this condition by modifying calcified lesions below the knee and restoring blood flow to the foot.”
Merit Medical Systems has announced the commercial launch of the PreludeSYNC EVO radial compression device in European, Middle Eastern and African markets.
The product has clearance from the US Food and Drug Administration (FDA) and has CE mark in the EU for use in diagnostic cardiac catheterisation procedures and percutaneous coronary interventions (PCIs).
Merit’s PreludeSYNC EVO is a sterile, single-use, disposable device used to assist in gaining haemostasis of the arterial percutaneous access site following catheterisation procedures.
“PreludeSYNC EVO adds to our extensive line of radial compression devices that support PCI from start to finish. It was developed to meet the evolving clinical and health economic needs of physicians, administrators and catheter lab teams around the globe. Our intent with PreludeSYNC EVO, the latest innovation in our premium cardiology product portfolio, is to provide physicians with even more procedural clarity and uniformity and their patients with safety and comfort,” says Fred P Lampropoulos, Merit Medical’s founder, chair, and Chief Executive Officer.
The device has a large, clear window area, which provides unobstructed site visibility. It is also optimised for diffuse and uniform balloon pressure. The safety features include a specialised connection and Slip-n-Lock cap that secures the syringe during inflation and deflation. A soft, comfortable band, which is easy to secure, adjust and clean, is available in 24 and 29cm sizes.
The PreludeSYNC EVO is immediately available in the EU, with registration coming in Middle East and Africa.
Imperative Care has completed the initial closing of a Series C financing of US$85 million to support the commercial launch of the company’s portfolio, which is composed of the latest advances in neurovascular devices treating ischaemic and haemorrhagic strokes.
The round was co-led by new investors Ally Bridge Group and Bain Capital Life Sciences. Existing Imperative Care investors Ascension Ventures, Delos Capital, Rock Springs Capital, 3H Health Investment, and Incept LLC also strongly participated in the round. Frank Yu, Ally Bridge’s founder, and Andrew Hack, managing director of Bain Capital, will join Imperative Care’s board of directors.
“We are thrilled to have Ally Bridge and Bain Capital leading this round of financing at this important stage in our company’s growth. We look forward to Frank and Andrew’s support and guidance as we continue to propel forward Imperative Care’s unique mission,” said Fred Khosravi, Chairman and CEO of Imperative Care. “This is an exciting time for our company. We are poised to launch the industry’s first Large Distal Platform (LDP) access technology and our unparalleled ZOOM Aspiration System. In addition, we continue to develop a pipeline of innovations in the continuum of stroke-care, with significant investment and emphasis on clinical evidence.”
Imperative Care has received 510(k) clearance from the US Food and Drug Administration (FDA) for its family of access catheters designed to facilitate smooth, consistent navigation into blood vessels of the brain. The company has also received FDA clearance for its ZOOM Aspiration System, a family of products designed to facilitate clot removal during ischaemic stroke.
Canon Medical has concluded a contract to acquire all shares of Skope Magnetic Resonance Technologies AG. Skope specialises in the development and sales of magnetic field monitoring systems and image reconstruction software for MRI. The acquisition was completed according to the required approval procedures.
A press release details how Skope is equipping leading MRI research sites with its high-precision magnetic field monitoring systems and sophisticated image reconstruction software to facilitate next-generation MR imaging and diagnostics.
Canon Medical Systems developed and introduced the first Japanese MRI in 1983, and today is dedicated to the research and development of innovative MRI technologies, such as Pianissimo, the company’s unique acoustic noise reduction technology.
Narayan Karunanithy outlines the benefits of intravascular ultrasound (IVUS) during haemodialysis access intervention.
Thoracic central veins include intra-thoracic segments of the internal jugular, subclavian, brachiocephalic veins and superior vena cava. These veins are located central to the superior thoracic aperture (C7–T1 intervertebral disc level), central to the lateral margin of the first rib and superior to the diaphragmatic caval opening.1 Patients with haemodialysis access are prone to developing Thoracic Central Vein Obstruction (TCVO) due to their underlying renal failure, altered haemodynamics of the arteriovenous circuit and previous central vein catheter, pacemaker or defibrillator placement. The incidence of TCVO in this patient cohort is thought to be rising and currently estimated to be 20–40%.2 TCVO may be partial (i.e. stenosis) or complete (i.e. occlusion).
Patients with TCVO can present with arm/neck/face/breast swelling, pain, access dysfunction and respiratory distress. Visible chest wall collaterals may also be unsightly for the patient.
Most of the haemodialysis circuit can be imaged readily with standard ultrasound, as the circuit is very superficial. However, TCVO can be virtually impossible to image with ultrasound. CT or MR venography can provide excellent depiction of central venous anatomy. However, CTV carries an additional radiation burden and MRV usually requires administration of gadolinium, which may be complex in this cohort of patients with end stage renal failure or approaching it. Hence the mainstay of CVS assessment currently is digital subtraction angiography (DSA).
IVUS is an invasive modality that provides cross-sectional imaging of the veins but without the need for ionizing radiation or contrast administration. In addition to being a diagnostic tool that is easy and repeatable, it aids treatment decision-making.
The VIDIO trial has demonstrated that DSA can underestimate the degree and morphology of iliofemoral vein stenosis when compared to IVUS. There is paucity of published literature evaluating IVUS for TCVO assessment in haemodialysis patients.3 de Graaf et al performed DSA and IVUS on 12 patients with suspected TCVO. IVUS showed significant stenosis in 12/12 versus 8/12 with DSA. After angioplasty, significant residual stenosis was demonstrated in 10/12 versus 3/12 with DSA. The authors concluded that IVUS was more sensitive in diagnosing significant TCVO and aided the decision-making process in deciding treatment strategy.4 This is in line with what we have learned from the iliofemoral venous treatment literature that IVUS aids precise device dimension selection (diameter and length of stenosis), appropriate landing zones and adequacy of treatment (for e.g. wall apposition of stent). These are fundamentally important steps that contribute to optimised outcomes.5 Clearly high quality large data studies are required to demonstrate the benefit of IVUS in haemodialysis access.
Currently no consensus exists on the optimum treatment of TCVO. The mainstay of treatment is high-pressure balloon angioplasty but the outcomes are generally poor with reported patency at six and 12 months 29–60% and 25% respectively. The use of bare metal stents has similarly poor outcomes with one-year patency 33–56%. The reported outcomes even with stent grafts are as low as 40% patency at 12 months. The patency rates with drug coated balloon angioplasty are better.6 Reliance on DSA alone to determine adequate treatment may have contributed to these relatively poor outcomes.
In conclusion, reliance on DSA alone for TCVO can under-estimate the extent and severity of these lesions. This can be overcome with use of IVUS. IVUS use during treatment aids appropriate device selection and adequacy of treatment.
References
Narayan Karunanithy is a consultant interventional radiologist at Guy’s and St Thomas’s Hospital (London, UK) and honorary senior lecturer at the School of Biomedical Engineering and Imaging Sciences at King’s College London (London, UK).
Merit Medical has announced the commercial launch of the Resolve mini locking drainage catheter, the most recent addition to the company’s line of innovative Resolve locking drainage catheters. The Resolve mini is intended for the percutaneous drainage of fluid from body cavities, and its mini pigtail design—which is up to 42% smaller than the standard Resolve locking drainage catheter pigtail—allows the catheter to be placed into small fluid pockets.
The Resolve mini features a tapered tip and hydrophilic coating for smooth introduction, designed to reduce patient discomfort, a Merit Medical press release reports. Depth markers located on the catheter shaft aid accurate placement and act as a reference for correct positioning, and a radiopaque marker band denotes where the pigtail is to ensure all the holes are in the fluid pocket. The device features multiple large holes to help maximise drainage.
Additionally, the Resolve mini includes a secure locking mechanism that makes it difficult for patients to unlock the catheter, a pigtail straightener to help insert the cannulas into the catheter easier, and a catheter tip positioned within the pigtail curve, designed to reduce tissue irritation. Flexible polyurethane material prevents kinking and ensures catheter rebound, and an included repositioning tool helps unlock and reposition the catheter at any time.
“For years, Merit has been deeply committed to the drainage space, developing novel and innovative catheters and drainage devices that improve the standard of care,” comments Fred Lampropoulos, chair and CEO of Merit Medical. “The commercial launch of the Resolve mini furthers that legacy by offering customers a device designed to provide safety, usability, and patient comfort.”
Last month (November), the FDA approved Medtronic’s paclitaxel-coated balloon IN.PACT AV for the management of failing arteriovenous fistulae (AVF). Approval for the device was based on data from the IN.PACT AV Access trial, which showed the device to significantly increase primary patency compared with standard percutaneous transluminal angioplasty. Andrew Holden (Department of Interventional Radiology, Auckland, New Zealand), the principal investigator of IN.PACT AV Access, says having a treatment that improves access circuit patency is a “huge gain”.
According to Holden, ensuring the patency of arteriovenous fistulae is an ongoing concern. He notes that while haemodialysis is the most common method of renal replacement therapy, “dialysis access circuits are prone to high rates of dysfunction” and this is primarily because of access circuit stenotic lesions. Furthermore, he says, these lesions are “often refractory” to standard percutaneous transluminal angioplasty and “require high pressure or specialty balloons to adequately dilate”. “Of more concern is the extremely high rate of restenosis, with many studies reporting a primary patency rate below 50% at six months,” Holden observes.
Therefore, given outcomes seen with drug-coated balloons for treating femoropopliteal lesions, interest in the use of these devices to treat failing arteriovenous fistulae has been considerable. However, until recently, the efficacy of drug-coated balloons in this context had not been definitively demonstrated. Holden explains: “Although many studies reported a trend towards better patency with drug-coated balloons compared with plain balloon angioplasty, the confidence intervals were wide and some studies failed to showed a benefit. Not surprisingly, there was considerable heterogeneity in technique in the papers, particularly the requirement and quality of vessel preparation prior to drug-coated balloon deployment.” He adds these studies reinforced the need for larger, multicentre, randomised trials.
Efficacy data
IN.PACt AV
The Lutonix AV Access investigational device exemption (IDE) trial was the first such randomised trial, and it evaluated the drug-coated balloon Lutonix 035 (BD). Scott Trerotola (Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA) and others recently reported the two-year results of this study (285 patients with dysfunctional arteriovenous fistulae) in the Journal of Vascular and Interventional Radiology. They note that the study did not meet its primary endpoint—superior target lesion primary patency (TLPP) at six months compared with control therapy (standard percutaneous transluminal angioplasty)—but did show statistically significant TLPP at nine months (58%±4 vs. 46%±4 for control therapy; p=0.02). Lutonix AV was not associated with better TLPP at any other time point (12 months, 18 months, and 24 months). Trerotola et al conclude that the data represent “an important step forward in the development of novel therapies that improve the quality of life of patients undergoing haemodialysis”. “We hope the further introduction of other such therapies, as well as the analysis of more patients treated with drug-coated balloons, will result in a future precision-based approach to arteriovenous fistulae stenosis,” they add.
Unlike the Lutonix AV Access IDE trial, Holden reports, IN.PACT AV Access trial (330 patients) “well and truly met its primary efficacy endpoint”. At 210 days, per Kaplan-Meier estimates, the primary patency of the target lesion was 81.4% in the IN.PACT AV arm vs. 59% in the control arm (p<0.01). Additionally, patients in the IN.PACT AV arm required 56% fewer reinterventions to maintain target lesion patency through 210 days compared with those in the control arm. Holden observes: “It is highly likely that this reduced reintervention rate will make a primary drug-coated balloon angioplasty approach to arteriovenous access circuit stenoses a very cost-effective treatment.” He adds that a detailed cost-effectiveness analysis of the IN.PACT AV Access Study will be presented early 2020.
The six-month data were reported at the 2019 Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain) and subsequent data were presented at the recent VIVA meeting (2–7 November, Las Vegas, USA). Holden comments that these data show “a significant patency advantage for the drug-coated balloon in de novo and restenotic lesions and all anatomic locations, particularly for the arteriovenous anastomosis and cephalic arch”.
Safety data
As Holden puts it, the possible relationship between paclitaxel exposure and all-cause mortality in claudicants (for the management of femoropopliteal lesions) “is a hotly debated issue” at present. However, he says that there “should be great caution” about extrapolating these data to the use of paclitaxel devices for “other arterial devices and for different clinical indications.” “The life-expectancy of haemodialysis patients may be very different to a claudicant population and the benefits of a patent vessel even more profound. In the USA, it is estimated the two-year mortality for haemodialysis patients is 33.2%, more than twice that of a claudicant population,” Holden observes.
Additionally, none of the studies evaluating drug-coated balloons for haemodialysis patients have identified any safety concerns (so far). For example, there were no significant differences in mortality between the IN.PACT AV group and the control group at 12 months—90.6% vs. 90.4%, respectively—in the IN.PACT AV Access trial. Also, Holden notes: “A recently published meta-analysis of mortality after paclitaxel-coated devices in arteriovenous access showed no difference in short to mid-term mortality for drug-coated balloon compared to plain balloon angioplasty”.
Future devices
Merit Medical is hoping to following Medtronic in having a FDA-approved device for the management of failing arteriovenous fistulae. On the same day that Medtronic announced that it had received FDA approval for the IN.PACT AV (21 November 2019), Merit announced that it had received FDA Breakthrough Device Designation for its Wrapsody endovascular graft system. According to a press release, the system is a flexible, self-expanding endoprothesis for use in haemodialysis patients for the treatment of stenosis within the central veins of the outflow circuit of arteriovenous fistula (up to the superior vena cava).
Concept Medical also has FDA Breakthrough Device Designation (as of August 2019) for a device for treating dysfunctional arteriovenous fistulae—the MagicTouch AVF sirolimus-coated catheter. A press release reports that the proposed indications for the catheter are “for use in percutaneous transluminal angioplasty, after appropriate vessel preparation, for the treatment of stenosis lesions of dysfunctional native arteriovenous dialysis fistula or graft”.
Whether or not Merit Medical and Concept Medical get a device onto the US market, Holden believes, just having IN.PACT on the market is good news for all concerned. He says: “It is well recognised by clinicians, funders and—most importantly—patients that a technology that significantly improves access circuit patency and reduces reinterventions is a huge gain. Haemodialysis patients have a challenging quality of life and will be delighted at a more effective treatment with reduced reintervention.”
Of note, in Europe, the MagicTouch AVF received CE mark approval in November this year and the IN.PACT Admiral was CE-marked approved for treating arteriovenous fistulae in 2016. Furthermore, the Lutonix 035 received FDA approval for this indication in 2017.
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Internal BIBA MedTech data show that perceptions on paclitaxel devices have shifted considerably in the twelve months that have elapsed since Konstantinos Katsanos (Patras, Greece) et al published their meta-analysis in the Journal of the American Heart Association (JAHA) alleging an increased death rate in patients treated with paclitaxel-coated balloons or paclitaxel-eluting stents in the femoropopliteal arteries. A recent survey reports that for 43% of physicians, the leading cause for this increased concern is due to published statements from regulatory bodies and international societies. Exactly one year on from the initial JAHA publication, Interventional News collates these position statements.
Society for Cardiovascular Angiography and Interventions (SCAI):
After reviewing the Katsanos et al meta-analysis, experts from the Society for Cardiovascular Angiography and Interventions (SCAI) concluded in a statement published on 25 January 2019 that the methods used by Katsanos et al were appropriate and within constraints of trial-level meta-analysis. However, the society statement said: “It is important to note that SCAI believes the associations are hypothesis-generating and require further investigation with patient-level data.”
Cardiovascular and Interventional Radiological Society of Europe (CIRSE):
On 29 March 2019, CIRSE made the following recommendations:
Medicines and Healthcare products Regulatory Agency (MHRA):
The MHRA issued a medical device alert (MDA) on 4 June 2019 warning physicians not to use paclitaxel-coated balloons or paclitaxel-eluting stents in the routine treatment of patients with intermittent claudication until further notice, “as the potential mortality risk generally outweighs the benefits”. However, the agency accedes that use of these devices may still be considered in patients with critical limb ischaemia, taking National Institute of Care Excellence (NICE) guidance into consideration, in view of their increased risk of stenosis and reduced life expectancy. This MDA was published one day after an independent expert advisory group (EAG), consisting of leading UK clinicians from multiple specialties (including interventional radiology, vascular surgery, toxicology and statistics) advised the MHRA to limit the use of paclitaxel devices to patients with CLI. The EAG was established following the publication of the Katsanos et al meta-analysis.
Society for Vascular Surgery (SVS):
The SVS Vascular Quality Initiative (VQI) used large, multicentre registries as datasets for the analysis of vascular patient care in the USA. At the SVS annual meeting (12–15 June, National Harbour, USA), Daniel Bertges (Burlington, USA) demonstrated how the VQI could potentially be used for surveillance of the safety of new peripheral arterial devices. “In this large, real-world sample,” he shared, “there is no difference in mortality at a mean of 12.4 months. The results are similar for patients treated with paclitaxel-coated balloons or paclitaxel-eluting stents. Certainly, a longer registry follow-up is required and ongoing, and we hope that the VQI Peripheral Vascular Interventions Registry will be part of that cumulative body of evidence on this important topic.”
In Spring 2019, the SVS formed a Paclitaxel Safety Task Force, with the mission of facilitating the performance and interpretation of an Individual Patient Data meta-analysis using patient-level randomised controlled trial data from industry partners.
US Food and Drug Administration (FDA):
The FDA admitted in an update from 7 August 2019 that treatment of peripheral arterial disease (PAD) with paclitaxel-coated balloons and paclitaxel-eluting stents is potentially associated with increased mortality. While the regulatory body reported the presence of the mortality signal in its own analysis, it said that the magnitude of the signal should be interpreted with caution due to several limitations in the available data. The FDA advises diligent patient monitoring, that the Katsanos et al meta-analysis be included in the patient consent process, that the device risks and benefits are discussed prior to treatment, and that physicians report any adverse events experienced with the use of paclitaxel-coated balloons and/or paclitaxel-eluting stents. These recommendations are based on the agency’s analysis of long-term follow-up data from premarket trials. The FDA is working with manufacturers and investigators to update device labels and to garner additional clinical evidence for assessment of the long-term safety of these devices.
Women of reproductive age with symptomatic fibroids experience significantly improved quality of life and significantly reduced symptoms following treatment with uterine fibroid embolization (UFE), a recent study reports. Published in Cardiovascular and Interventional Radiology (CVIR) Endovascular, the authors also conclude that functional uterine contractility seems to have a positive impact on quality of life and sexual function in this population.
While changes in uterine contractility pattern after UFE have already been assigned by cine magnetic resonance imaging (MRI), the impact of these changes had not been evaluated previous to this study. Lead author Vinicius Adami Vayego Fornazari (Universidade Federal de São Paulo, São Paulo, Brazil) and colleagues therefore set out to investigate the impact of uterine contractility on the quality of life of women undergoing UFE, measured by the Uterine Fibroid Symptom and Quality of Life questionnaire. The questionnaire, they say, is “a validated tool for measuring patient-reported symptoms and documenting clinical outcomes from surgical and interventional procedures.”
Whilst UFE is recognised as a Level A treatment option for managing leiomyomas in carefully selected patients, Fornazari et al claim that the procedure’s use for women of reproductive age “is still controversial”, and that the impact of fibroids on infertility is “not yet clear”. The majority of patients who wish to become pregnant therefore opt for a myomectomy, though there have been some studies that demonstrate successful pregnancies post-UFE. “One of the hypotheses for the association between fibroids and infertility,” the study authors write, “is alteration of uterine contractility.”
Uterine contractions act to eliminate peeling endometrium during the menstrual period, and also have various functionalities relating to pregnancy maintenance and fertility. However, these contractions are also implicated in dysmenorrhea (menstrual cramps). It has been hypothesised that fibroids could alter uterine contractility and functionality, Fornazari and colleagues write.
The present study supports this theory: half of the 26 patients prospectively included in the study experienced positive changes in their uterine contractility pattern following UFE. These patients were classified as group A during analysis. However, in a significant minority (38%) of patients, the uterine contractility pattern was unchanged after the procedure. These patients made up group B. Three patients (11%) lost uterine contractility after the procedure, and were categorised as group C.
The study investigators gave each of the 26 patients a questionnaire at their first MRI scan, which varied from 30 to seven days prior to undergoing UFE. All patients were then given the questionnaire again at their one-year follow-up consultation. Fornazari et al then analysed the survey results according to change in contractility from baseline after UFE (whether the patients were group A, B, or C).
All UFE patients presented a statistically significant reduction in mean symptom score, as well as a statistically significant increase in mean quality of life scores. Quality of life scores included worry, activity, energy, self-control, self-confidence, and sexual function.
Breaking this down by group: in those patients with an unchanged uterine contractility pattern (group A), the authors report a statistically significant reduction in mean symptom score, and an increase in the mean score of all quality of life scores, with the exception of the sexual function subscale (p=0.3232). For the 50% of patients with a favourably modified uterine contractility pattern (group B), there was a statistically significant reduction in mean symptom score, and an increase in mean quality of life score. As there were only three patients with loss of uterine contractility after UFE (in group C), no analysis could be performed.
Form these results, Fornazari et al surmise that “The significant improvement of uterine contractility and simultaneous improvement of quality of life these patients experienced after UFE suggests that uterine contractility may have a positive impact on quality of life.”
A comparative analysis between groups A and B found that, before UFE, group A had a higher sexual function score. As sexual function is a quality of life metric, the higher the score, the better. In patients with no change in uterine contractility pattern after UFE, there was also no significant change in sexual function. For patients who did experience a beneficial change in uterine contractility pattern (group B), however, there was a statistically significant increase in sexual function score. Fornazari and colleagues say that, in their previously published work, they “did not identify statistically significant variables that could be correlated to this data. In this study, the only potentially relevant variable that could be associated with a low interference in sexual function, both before and after UFE, is the fact that this group experienced no change in uterine peristalsis.”
However, Fornazari et al do note that their sample size was small, and say that additional studies are required to confirm or denounce their finding that functional uterine contractility has a positive impact on fertility and quality of life.
The first UK clinical trial site for the treatment of diabetic patients with chronic limb-threatening ischemia (CLI) using a novel patient-specific regenerative therapy has opened for patient recruitment at the University Hospital of Wales in Cardiff, UK. The site will be evaluating Rexgenero’s REX-001 in two Phase III trials, codenamed the SALAMANDER trials. The trials are being led by Ian Williams, a consultant vascular surgeon and the principal investigator at the site. recruiting
The University Hospital of Wales is participating in the trials through a consortium, the Midlands-Wales Advanced Therapy Treatment Centre (MW-ATTC), part of the Advanced Therapy Treatment Centre Network (ATTC) which aims to bring pioneering advanced therapy medicinal products (ATMPs) to patients. THE MW-ATTC has been working in collaboration with the Cardiff and Vale University Health Board to progress the initiation of the two SALAMANDER trials and is planning to activate new clinical trial sites in the Midlands in England shortly.
REX-001 represents a new class of regenerative medicines. It is an autologous cell therapy manufactured using the patient’s own bone marrow and consists of immune cells (lymphocytes, monocytes, and granulocytes) and progenitor cells involved in immune modulation and tissue regeneration. It is administered as a single dose within four days after collection of bone marrow cells.
Williams comments: “Chronic limb-threatening ischaemia is a serious disease with severe consequences and limited treatment options. There is a high unmet need for novel and innovative therapies—such as REX-001—that have the potential to be a highly effective treatment and to reduce amputation and mortality rates amongst the patient population.”
Rexgenero, the company pioneering the development of REX-001, says that the experimental product has already demonstrated efficacy in Phase I/II studies. In the Phase II clinical trial, 82% of patients with non-healing ischaemic ulcers were healed within the first 12 months after a single administration dose of REX-001.
Joe Dupere, CEO of Rexgenero, adds: “Treating our first patient with REX-001 in the UK represents an important milestone for our Phase III programme in diabetic patients with chronic-limb threatening ischaemia, a severe condition with high unmet need. With clinical trial sites and manufacturing bases now open across multiple countries in Europe, we are one step closer to completion of the Phase III studies and potential regulatory and market approval for an innovative and much-needed product.”
Rexgenero is planning to treat a total of 60 patients with CLI and rest pain and 78 patients with CLI and non-healing ischaemic ulcers in two independent Phase III SALAMANDER trials in approximately 25 hospitals across Europe. In addition to the trial sites in the UK, Rexgenero is also recruiting patients for both trials at sites in Spain, Austria, Portugal, Poland, Hungary, The Netherlands and the Czech Republic.
Akhilesh Sista (New York, USA) talks to Interventional News at VIVA 2019 (Vascular InterVentional Advances; 4–7 November, Las Vegas, USA) about the results of the EXTRACT-PE study, that were presented in a late-breaking clinical trial session at the meeting.
EXTRACT-PE successfully met the primary endpoints, demonstrating the safety and efficacy of the Indigo Aspiration System (Penumbra) for aspiration mechanical thrombectomy in patients with acute pulmonary embolism (PE).
Sista says that “up to this point, there had been no prospectively collected data on this new but promising device”. Catheter-directed thrombolysis and systemic thrombolysis both carry the risk of bleeding and the inconvenience of having to drip the patient with tissue plasminogen activator (tPA) over the course of time. That is why, Sista says, the purpose of the EXTRACT-PE study, was to evaluate the efficacy and safety of aspiration thrombectomy with the Indigo Aspiration System.
While Sista says that the data indicates “this is another tool in our toolbox to remove thrombus quickly in patients who need thrombus removal”, he also believes that the “scientific pulmonary embolism (PE) community” has to go beyond the RV to LV ratio and needs to look at clinical outcomes and randomise patients, both for this device and in general, to try to evaluate whether clot removal in submassive PE “is the right thing to do, and if so, in whom”.
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A real-world study investigating the luminor drug-coated balloon (DCB; iVascular) in Brazil has started, following approval for commercialisation of the device by ANVISA, the Brazilian regulatory authority. LUMBRA (LUMinor balloon in a BRAzilian registry for real world lesions) aims to corroborate the efficacy and safety results of luminor in Europe demonstrated by the EFFPAC and TINTIN trials.
The LUMBRA trial has the objective of evaluating the long-term outcomes of treatment with the luminor DCB, followed by potential bail-out stenting with the iVolution stent (iVascular) in symptomatic femoropopliteal arterial stenotic or occlusive lesions in 200 patients from Brazil. The first patient to be enrolled was included on 30 November 2019.
The primary endpoint of the registry is primary patency at 12 months. The secondary endpoints include: technical success, procedural success, primary patency rate freedom from target lesion revascularisation, changes in ankle-brachial index measurements, and serious adverse events, as defined per ISO 14155:2011.
Pierre Galvagni (Federal University of Santa Catarina, Florianopolis, Brazil), principal investigator of the trial states: “We were expecting to have luminor in Brazil; this trial will allow us to corroborate in [a] real-world Brazilian population the great outcomes of luminor DCB”.
During the November SIR and SIR Foundation Nominating Committee meetings, the Society of Interventional Radiology (SIR) elected a new Executive Council for 2019–2020. Following the Annual Members’ Business Meeting in spring this year (28 March–2 April, Seattle, USA), Katharine Krol (Lafayette, USA) will become chair of the SIR Foundation Board of Directors.
Theresa Caridi (Washington, DC, USA), currently serving as development division chair, has been elected vice chair of the society. She will hold this position for a two-year term, before succeeding to chair in 2022.
Parag Patel (Milwaukee, USA) has been elected SIR secretary, and will succeed to president-elect in 2021 following his one-year term as secretary.
Akhilesh Sista (New York, USA) has been elected as councillor-at-large, for a four-year term.
Alda Tam (Houston, USA) has been reappointed standards division councillor, and will serve a three-year term.
Clifford Weiss (Baltimore, USA) has been appointed grants and education division chair, a position he will hold for a three-year term.
Philips has announced a major clinical trial to assess the impact of a direct-to-angiosuite workflow on stroke patient outcomes. The study will assess whether with Philips’ advanced image-guided therapy platform it is possible to diagnose, plan and treat stroke patients in the interventional suite without requiring an initial CT or MRI exam. The multicentre, prospective, randomised, controlled, open-label, blinded-endpoint trial will be run across eight sites and over 460 patients globally. It will begin in the first half of next year and is expected to be completed in 2022.
Outcomes for stroke patients are closely tied to how quickly they receive treatment: every 30 minutes’ delay before treatment reduces the chance of a good outcome by 14%1, and every hour of delay ages the brain by 3.6 years compared to a normally aging brain2.
Currently, when a possible stroke patient arrives at the emergency department, they typically first undergo a CT or MRI exam and, in the case of an ischaemic stroke, are then treated in an interventional suite. Several studies have indicated that a direct-to-angiosuite workflow can reduce the time to treatment and improve patient outcomes. Philips is developing new technology to further improve the CT-like images of the brain created with the X-ray system in the suite. The WE-TRUST (Workflow optimisation to reduce time to endovascular reperfusion in stroke treatment) trial will provide the most comprehensive assessment to-date of the impact of this technology and workflow innovation on time to treatment and patients’ neurological outcomes.
“Significant advances in technology mean that we are now able to identify, plan and treat ischaemic stroke patients in the angiography suite, without the need for a separate CT or MR scan” said Raul G Nogueira, director, Neuroendovascular Service Marcus Stroke & Neuroscience Center at Grady Memorial Hospital in Atlanta, USA, and principal investigator for the WE-TRUST trial. “Now is the right moment to perform a randomized controlled trial to objectively assess the benefits of a streamlined Direct to Angio Suite workflow on patient outcomes.”
“With extensive clinical research demonstrating the benefit of a treatment approach that combines thrombectomy and clot-busting drugs, stroke patient triage and treatment has changed dramatically in recent years,” said Ronald Tabaksblat, General Manager Image Guided Therapy Systems at Philips. “For stroke patients, ‘time is brain’. The WE-TRUST trial will assess the impact of a streamlined direct-to-angiosuite workflow on patient outcomes and has the potential to make a significant impact in this rapidly advancing field.”
The trial will primarily be carried out on Philips Azurion, the company’s platform for interventional procedures, at eight leading stroke sites in Europe and the USA. The primary endpoint of the WE-TRUST trial is patients’ cognitive function at three months after the procedure.
Additional ultrasound-accelerated catheter-directed thrombolysis does not lower the risk of post-thrombotic syndrome in patients with acute iliofemoral deep-vein thrombosis (DVT), according to findings of the CAVA trial presented at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland). Preliminary results of a post-hoc subgroup analysis suggest that if recanalisation is successful, post-thrombotic syndrome is less severe and quality of life scores are higher one year after an acute DVT.
Examined in presentations by both Pascale Notten (Maastricht, the Netherlands) and Cees Wittens (Maastricht, the Netherlands)—winners of the best abstract session at UIP— and published in The Lancet Haematology, results of the CAVA trial also showed a high rate of thrombotic events, mostly due to in-stent thrombosis.
Post-thrombotic syndrome is a common long-term complication of deep-vein thrombosis , particularly in cases where the localisation of the thrombus is iliofemoral or more cranial. The ‘open vein hypothesis’ suggests early removal of the thrombus as a means of preserving venous function and restoring venous outflow, thereby preventing the development of post-thrombotic syndrome; ultrasound-accelerated catheter-directed thrombolysis was considered a promising option for this removal.
As part of the multicentre, randomised controlled CAVA trial, which aimed to determine whether additional ultrasound-accelerated catheter-directed thrombolysis can decrease the risk of post-thrombotic syndrome, 184 patients with a first-time acute iliofemoral deep-vein thrombosis were randomly assigned to one of two treatment groups; either standard post-thrombotic treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment (including early anticoagulant therapy, compression therapy, and mobilisation) alone.
Results of the trial showed that post-thrombotic syndrome occurred in 22 of the 77 patients (29%) randomised to the additional thrombolysis group, compared to 26 out of 75 patients (35%) in the standard treatment cohort (odds ratio 0.75, 95%CI, 0.38-1.50, p=0.42). Major bleeding occurred in four patients (5%) from the intervention group, compared to none in the control group, (p=0.06). Furthermore, a total of 24 thrombotic events occurred in 20 patients: 14 patients (18%) from the intervention group developed 17 events versus seven events in six patients (8%) from the control group (P=0.06). Of the 17 thrombotic events in the intervention group, more than 70% (12 out of 17) were due to in-stent thrombosis.
Speaking to Venous News about the results, presenter Notten said: “When comparing our results to the two previous large trials (CaVenT and ATTRACT), our outcomes regarding the development of post-thrombotic syndrome are similar to those found in the ATTRACT trial and show no statistically significant difference between treatment groups as opposed to the CaVenT trial.
“With the CAVA trial being inconclusive, the discussion regarding the role of additional catheter-directed thrombolysis in the treatment of acute iliofemoral deep-vein thrombosis persists. Further research including optimising patient selection, interventional techniques, and peri-interventional treatment regimens is essential.”
Can successful thrombolysis prevent post-thrombotic syndrome?
Presented by Wittens at UIP, a sub-group analysis of the results aimed to assess the success rate of additional ultrasound-accelerated catheter-directed thrombolysis in restoring patency (to 90% or more) and its relation to development of post-thrombotic syndrome at one year. As the degree of residual vein occlusion correlates with the risk of post-thrombotic syndrome, it has been said that the preventative impact of ultrasound-accelerated catheter-directed thrombolysis might depend on its ability to achieve successful recanalisation.
According to the preliminary analysis, recanalisation was considered successful in 41 out of the 77 patients (53%) who received additional ultrasound-accelerated catheter-directed thrombolysis, while a total of 75 patients in the CAVA trial received standard treatment only. Overall, post-thrombotic syndrome developed in nine patients (22%) from the successful thrombolysis subgroup and 26 (35%) of the control patients (P=0.15).
Comparing the successful thrombolysis sub-group to those who underwent unsuccessful thrombolysis—post-thrombotic syndrome developed in 13 out of 36 patients (37%) —no significant difference in proportion of post-thrombotic syndrome was seen (p=0.17). However, the severity was significantly lower in those successfully treated. Generic and disease-specific quality of life questionnaires also differed significantly between groups, once again favouring those who had been successfully treated.
Based on the findings of the sub-group analysis, successful thrombolysis does result in benefits such as less severe symptoms and improved quality of life when considering multiple aspects. Commenting on these results, Cees Wittens said to Venous News: “The subgroup analysis shows that proper quality control of an intervention is essential to evaluate an intended treatment. Unfortunately, this trial shows that only 53% of the patients who received the intervention had a successful intervention.
“Since the preliminary subgroup analysis showed a significant improvement in clinical scores and quality of life in those successfully recanalised, the overall conclusion of the various trials should not be that early thrombus removal is not effective in achieving better clinical outcomes and that this treatment should be abandoned; it tells us that early thrombus removal actually has the capacity to limit long-term post-thrombotic morbidity, if only we are able to improve the process of patient selection and develop better interventional treatments.”
Ultrasound-only guidance is technically feasible for a substantial proportion of cryoablation procedures, Alex Barnacle (Great Ormond Street Hospital, London, UK) reported at the 2019 annual meeting of the British Society of Interventional Radiology (BSIR; 13–15 November, Manchester, UK). Using ultrasound instead of computed tomography (CT) for intraprocedural imaging eliminates the radiation burden, which Barnacle said “is of primary importance”, especially when treating children.
“Wherever possible, ultrasound is the preferred imaging modality in paediatric interventional radiology, to avoid or minimise radiation dose in childhood,” she stated. Therefore, Barnacle and colleagues set out to investigate if ultrasound-only guidance was viable for intraprocedural navigation, and an assessment of their initial experience proves that it is.
The team reviewed all cryoablation procedures performed at their institution, and selected those for which only ultrasound was used. They collected their data prospectively, and had institutional review board approval for the study.
Over 29 months, interventionalists at Great Ormond Street Hospital performed 25 cryoablation procedures using only ultrasound as image guidance. Twenty-one lesions were treated in 20 children; most of these were soft tissue lesions in the extremities. “The age range and therefore the weight range was really diverse in this paediatric group”, Barnacle said. The median age was 11.4 years (ranging from five months to 16.5 years), and the median weight was 37.9kg (ranging from 7.5kg to 94.2kg). Whilst cone beam CT was available as back up for all cases, no procedure required the investigators to convert to CT guidance.
Since starting a new ablation service, interventional radiologists at the London-based paediatric hospital have been referred increasingly complex cases. “As often happens when you start a new service, you get sent quite a hodgepodge of cases,” Barnacle explained. “We were often sent patients as a last resort, where people had tried every other therapy first, so our initial experience was with a whole bunch of different conditions, from venous malformations to fibro-adipose vascular anomaly (FAVA), which is one of the primary diseases that we use cryoablation for in our centre.” Incidentally, this latter pathology was the first condition in children for which treatment with cryoablation was fully described. “Increasingly,” Barnacle continued, “we are being referred more aggressive diseases, and some oncological diseases as well.”
Detailing some examples of these more complex cases, Barnacle went on to describe a patient with a fast flow vascular anomaly in their forearm. Surgical debulking had been attempted twice previously, but had been followed by rapid regrowth. There was a large vessel in the centre of the lesion, and the arm was “very hot”, Barnacle recounted. “We wanted to cryoablate this,” she said, “but we were not sure what to do about the temperature.” The interventionalists performed an angiogram and embolized the central vessels, before going on to cryoablation. This had “really good results”, according to Barnacle, who enthused: “We are trying to push the boundaries with what we are doing in these patients.”
This involves being more aggressive in their treatment. Whilst Barnacle and colleagues used a range of one to five probes per procedure for the 20 patients in this study, they now sometimes use significantly more than five in some circumstances. The team use a standard freeze-thaw cycle twice, and lots of hydrodissection. Commenting on this, Barnacle opined: “I think this just reflects the fact that many of these lesions are very superficial, especially in children, who by their very nature do not have much subcutaneous fat.”
Speaking from the floor, Society of Interventional Oncology (SIO) president-elect Matthew Callstrom (Mayo Clinic, Rochester, USA) asked about the natural history of these vascular malformations in children, and how aggressive Barnacle felt the interventionalists need to be to have an impact on tumour growth over time. “Do you treat the entire mass, or do you try and treat 80%—what is your goal?”, he asked.
“We are getting more aggressive now,” Barnacle replied. “The nice thing is you are not having to get margins, so you have some leeway. […] Increasingly, we are trying to get the whole thing in one go.” However, she cautioned against using very aggressive cryoablation with large ice balls in very small children, describing a one-and-a-half-year-old patient who did not respond well to this type of intervention. “She was pretty unwell for a few days [after cryoablation]”, Barnacle reported. “She clearly had some kind of immune response and a cytokine storm afterwards. She tolerated the second procedure much better, when we used a decreasing dose of steroids over a week and gave her antibiotics and other support, but that initial experience made us wary.”
Many regulatory jurisdictions are establishing different approaches for medical devices, Misti Malone, assistant director in the Office of Cardiovascular Devices at the US Food and Drug Administration (FDA) said recently at the 2019 Vascular and InterVentional Advances meeting (VIVA; 4–7 November, Las Vegas, USA). She talked the audience through recent regulatory changes across the world, and outlined her vision for a global regulatory consensus.
Speaking in the “Most controversial clinical challenges of 2019” session at VIVA, Malone joked, “I hope you do not consider the FDA the most challenging and controversial aspect of clinical care” as she took to the podium to deliver her talk “Shifting worldwide regulatory priorities: How will changes in the 510(k) and CE mark process affect device availability for patients?”
“We [the FDA] are here to interact and collaborate with you,” she told the physicians, “and we appreciate the hard work you are doing. […] Regulatory pathways are evolving across the world. While I was asked to comment on whether this may affect device availability, our primary mission is to promote and protect public health, and our goal is to bring safe and effect devices to patients. We try to do this as quickly as possible, so we hope that our pathways are not changing how devices are available, other than potentially making devices available more quickly, and as needed by some of our new pathways.”
While she detailed how many regulatory jurisdictions are establishing different regulatory approaches for medical devices, exploring the changes to the FDA pathways in the US, she urged the VIVA audience to consider global strategies when appropriate. “We [the FDA] highly recommend discussing these proposals with multiple regulatory agencies early in the process,” she counselled, “so they can be efficient and predictable”.
The FDA 510(k) pathway
The FDA’s 510(k) pathway is required for most medium-risk devices, classified as Class II by the agency. These include guidewires, introducers, balloon catheters, and peripheral atherectomy devices. Approval via this pathway requires the demonstration of “substantial equivalence to a legally marketed, predicate device”, meaning that the new device design, performance, and intended use must be similar enough to an existing device.
On 20 September 2019, the FDA released a guidance document outlining a new “safety and performance-based pathway”, representing an alternative to the 510(k) process. According to Malone, the clearance was based on the intended use being equivalent to the predicate, and performance testing following FDA-specified methods and criteria, which may be based on recognised standards and the historical performance of comparable products, rather than testing intended to demonstrate substantially equivalent performance to a specific marketed device via methods selected by the manufacturer.
However, Malone acknowledged that this new 510(k) pathway may not be suitable for all devices: “Due to the lack of comprehensive standards and guidances available, particularly for cardiovascular devices […], identifying performance criteria and placing devices in a box may be challenging. Our goal is not to reduce innovation—it is to support innovation by allowing the process to move as efficiently as possible.”
One of the goals of this new pathway, Malone shared, is to make the approval process in the USA “more similar to regulatory paradigms in other countries”, such as the third party certification in Japan, which relies on performance criteria set by the Japanese government. As this only includes a limited number of cardiovascular devices, Malone anticipated that “This [system in Japan] may be pathway that will be valuable for some of our simpler devices for which we can set our performance criteria, but not for all devices.” She was enthusiastic, though, about the potential for global regulatory synergy, commenting: “It may facilitate convergence for global regulatory decision-making.”
EU MDR changes will take effect from May 2020
The European Union is moving to replace its Medical Device Directive (MDD) with the Medical Devices Regulation (MDR), a more extensive regulatory document, introducing significant revisions to quality and safety standards, and the range of regulated devices. The MDR was initiated in May 2017, and a three-year transition period applies. The changes outlined in the MDR legislation are currently due to take effect from May 2020, though, as Malone pointed out, “There is continual discussion on the topic at these forums [referring to meetings like VIVA] and from the EU”.
The goals are to reinforce provisions for clinical evidence. Clinical evaluation will be required pre-market for some devices and modifications, and it will continue into post-market with regular updates, surveillance, and analyses. Another goal is to encourage transparency, using unique device identification (UDI) traceability and data availability for both clinicians and patients. “We hope that this will provide more information, or at least that the EU will provide more information to support clinical decision-making and patient decision-making,” Malone stated.
One worry she shared with the VIVA audience was that clinical data may be required, and that this may affect device availability. Devices that are most likely to require clinical investigation are those that are implants and high-risk devices, those assigned to Class II, low-risk devices where the technology has little or no experience, or devices that extend the intended purpose of an existing technology, Malone informed delegates. For devices classified as Class III and implantable devices, a post-market clinical follow-up report may be required to update a summary of safety report, and clinical performance needs to be updated at least annually with these data.
“How this will affect device availability I think is more of a question for industry,” Malone opined. “I think it may be based on their cost-analysis. However, we look to clinicians to help us understand the ramifications of some of the regulatory decisions, and also to develop a global consensus, so the process can be efficient.”
Harmonising global regulatory requirements
“We have global groups, such as the International Medical Device Regulators Forum, in which we cooperate with numerous countries across the globe,” Malone said. This is a voluntary effort among medical device regulators to, in Malone’s words, “harmonise various regulatory requirements across their jurisdictions. The goal”, she elaborates, is “to be transparent and predictable, and create a reliable pathway, that is efficient for industry, clinicians, and regulators. It is currently high-level, but it is driving cooperation at the device level.”
The FDA and the Center for Devices and Radiological Health (CDRH)—the branch of the FDA responsible for the premarket approval of all medical devices—consider it a strategic priority to use opportunities and collaborations like IMDRF to put in place building blocks for creating a medical device single review programme with the potential goal that, once established, market authorisation and decision in one place may be supported in another country.
The clause in the 2018–2020 CDRH strategic priorities document, published January 2018, outlining how this may work reads: “We also will explore international convergence of some of these pathways—but not change our regulatory standard for market authorisation nor our reliance on valid scientific evidence—as we continue to work under the auspices of the International Medical Device Regulators Forum to put in place the building blocks for creating a Medical Device Single Review Program. Under such a programme, should it be established, the market authorisation decision made by or on behalf of one participating jurisdiction would be relied on wholly or in part to support marketing authorisation by other participating jurisdictions.”
Malone drew the audience’s attention to Japan as a case study of international collaboration. She described a successful harmonisation between the USA and Japan: “The USA collaborates closely with Japan due to the similar regulatory environments and patients. They [Japan] have made some recent policy developments, including [the] Sakigake (pioneer) device scheme, shifts in pre- and post-market balance, similar to the FDA, the use of non-domestic data, establishment of registries and use of real-world evidence, and pathways for early feasibility studies. We have continuing US and Japanese collaboration via HBD [harmonisation by doing].”
HBD facilitates the cooperation of industry, government, and academia in Japan and the USA to align medical device regulations in both countries through clinical trials and the approval review process.
Endovascular arteriovenous fistulas (endoAVF) platforms add additional fistula options for patients and physicians, argues Dheeraj Rajan (University Health Network, University of Toronto, Toronto, Canada, and a paid consultant for BD) at the 2019 Vascular and InterVentional Advances meeting (VIVA; 4–7 November, Las Vegas, USA). He argues that, due to higher patient satisfaction, good technical success, and low complication rates, as well as the attendant cost savings, endovascular AVF creation will soon be “essential” for any dialysis programme.
The first AV fistula, described in 1966 by Michael Brescia, James Cimino, Kenneth Appel, and Baruch Hurwich (all Veterans Administration Hospital, New York, USA), involved the side to side surgical anastomosis of the patient’s cephalic vein and radial artery near the wrist.
“It is important to note,” Rajan said to the VIVA audience, “that over 50 years [since the first AV fistula], we are still talking about the surgical creation of AV fistulas; not a lot has changed in that time. If you think about what kind of innovation has happened in different areas of medicine over those 50 years, and compare it to that in dialysis access, then you can see that we have not really had a lot of innovation in this space.”
He thinks this is changing, however, predicting the mainstream adoption of endovascular AVF creation.
Rajan highlighted the 20–60% failure rate of surgical AVFs to mature, as reported in “meta-analyses and multiple, large studies”—though he did also note that, anecdotally, AVFs may have a higher maturation rate, with several conference attendees reporting a 90% success rate in their own experience. In addition, he told delegates that 80% of patients start dialysis with a central venous catheter (CVC) in place, which he said “is not good for the patient”. Added to these downsides of surgical AVF creation, he commented, “In the world of patient-centred care, it is important to note that 30% of patients do not want to get surgery. It is something we rarely talk about.”
There are two devices currently commercially available for endovascular AVF creation: the 4Fr or 6Fr WavelinQ endoAVF platform, from BD, and the 6Fr Ellipsys vascular access system, from Avenu Medical. These were both approved by the US Food and Drug Administration (FDA) in 2018, following CE mark approval for Ellipsys in 2016, and WavelinQ in 2017. The WavelinQ system is a dual catheter system, which uses radiofrequency (RF) energy to vaporise tissue between the artery and the vein, thereby creating an anastomosis between the two vessels.
Describing the commonalities between surgical and endovascular AVF creation, Rajan says screening is “relatively similar”, with both requiring ≥2mm vessels and a perforator. The interventionalist arterialises the deep venous system to the superficial system.
However, he then went on to detail the differences in outcomes between the two methods. The prospective, multicentre NEAT (novel endovascular access) trial, published in the American Journal of Kidney Diseases in 2017 by Charmaine Lok (University Health Network, University of Toronto, Toronto, Canada) et al, concluded than “An endoAVF can be reliably created using a radiofrequency magnetic catheter-based system, without open surgery and with minimal complications. The endoAVF can be successfully used for haemodialysis and demonstrated high 12-month cumulative patencies. It may be a viable alternative option for achieving AVFs for haemodialysis patients in need of vascular access.”
Indeed, primary and secondary patency were better for endovascular AVF creation than outcomes from surgical creation. Primary patency was time from successful AVF creation to the first intervention designed to address thrombosis or stenosis, assist in maturation, or cannulation of AVF abandonment. Secondary patency was time from creation to the abandonment of AVF.
“Maturation rate, with both devices [WavelinQ and Ellipsys], was better than what we see typically with surgery,” Rajan said. Presenting data on WavelinQ from Lok et al’s NEAT trial, he said that the maturation rate in this study for endovascular AVF creation was 91%. In comparison, Rajan showed data from Michelle Robbin (University of Alabama, Birmingham, USA) et al, published in Radiology, that reported a maturation rate of 76% in the upper-arm and 53% in the forearm when using surgical AVF creation.
Patient satisfaction is also superior with endovascular haemodialysis AVF creation, Rajan reported. Indeed, Lok et al found that 96% of patients said they were “satisfied” with endovascular AVF creation. Illustrating this statistic with an anecdote, Rajan recounted: “I will never forget a conversation I had with a vascular surgeon where he grabbed me, physically grabbed me by my lapel, and said ‘I want in’. I asked him what he meant, and he said ‘You are working on this endovascular fistula thing, I want to invest’. I said ‘We do not know if it really works or not yet or how good our numbers are going to be’, and he said ‘It does not matter, every patient is going to want this first before they want surgery’.”
Another advantage of the endovascular approach listed by Rajan is the reintervention rate. He continued: “In terms of post-creation procedures,” Rajan continued, “the total number of interventions with endovascular access, using WavelinQ specifically, is 0.6 per patient year, compared to surgical, where it is 3.4 per patient year. So looking at our intervention rate, that is six times’ lower than with the surgical approach.” In addition, time to first intervention is longer when the endovascular approach is used.
Rajan also outlined how these factors translate into cost savings: a study by Shuo Yang (Quorum Consulting, San Francisco, USA) and colleagues, published in Journal of Vascular Access in 2017, found that US$11,240 was saved per patient-year following endovascular haemodialysis AVF creation compared with surgically created AVFs, due to the reduced number of reinterventions. “We have follow-up data that shows the cost-savings are even better than that,” Rajan added.
“One of the things to note is, with both devices [WavelinQ and Ellipsys], you are actually not getting rid of traditional surgical options. This actually adds more options for the patient, so you are not eradicating surgical choices. Working distal to proximal, you are adding more sites to create accesses, and these are autogenous fistulas: you are not leaving prosthetic material behind, you are not leaving a stent graft, you are not leaving a stent, there is no suture material here, and that all translates into better outcomes.”
To demonstrate this, Rajan collated the outcomes of major studies published recently, where the technical success rate with endovascular access was consistently above 80%. These studies included the Flex study (2015), the NEAT study (2017), and the EASE study (2019), which all used WavelinQ, as well as the two Hull studies (2017 and 2018), and the Mallios study (2018), which utilised the Ellipsys device. Mean maturation time ranged from 42 days to 118 days, and functional patency was “very high” for both devices, ranging from 87% to 100%.
Adverse events are also rare in endovascular AVF creation, Rajan commented. The number of serious adverse events recorded in these major studies ranged from 0% to 8%, though Rajan noted that events may not always be due to AVF creation. “Depending on the study and how you record adverse events,” he said, “keeping in mind that in studies, when you talk about serious adverse events, this includes strokes, cardiac attacks, car accidents and so on, so there are different adverse events that can be attributed to devices.”
He summarised: “I think this will accelerate and improve patient care. We are talking about not needing pre-operation visits. You could potentially screen patients with ultrasound the day they get a dialysis catheter; you do not need anaesthesia, these are outpatient procedures that can be done with conscious sedation, and this all potentially gets you to getting a fistula on a patient sooner, but also potentially cannulating sooner as well.
“This is coming. I think this adds a different platform for patients, the data suggests technical success and the complication rates are acceptable, there is high cannulation success, high patency with low interventions, and, most importantly, high patient satisfaction. I do think this will be a key part of any dialysis programme going forward, and there have probably been around 2,000 cases performed between both devices globally. I think patients will demand this, and they will actually drive a large part of the adoption.”
Writing to members of the American Venous Forum (AVF), president Brajesh K Lal (Baltimore, USA), has revealed that the AVF has established a partnership with the C-TRACT study, a randomised controlled trial funded by the National Institutes of Health. As part of the collaboration, AVF will contribute its expertise, perspective, and work effort to advance the trial’s success.
In his letter, Lal described the C-TRACT trial as a large study of endovascular therapy for post-thrombotic syndrome (PTS). Furthermore, the aim of the study is to understand whether image-guided procedures reduce the severity of PTS and improve patients’ quality of life. While long-term safety and costs of endovascular procedures are also being evaluated, the findings of the trial will provide new information on optimal ways to care for patients with PTS. Twenty-three clinical centres are currently participating in C-TRACT, with availability for more to join.
The partnership expands AVF’s tradition of leadership in promoting evidence-based practice in venous and lymphatic disease. As part of agreement with C-TRACT, which is led by Suresh Vedantham (St Louis, USA), AVF will leverage its knowledge and resources to increase awareness of the study, as well as helping to identify investigators and sites to participate in the study, encourage enrolment in the trial, and promote best practices for study conduct.
Discussions of C-TRACT will be presented at AVF meetings, including the 32nd annual meeting of AVF (March 3–6 2020, Amelia Island, Florida) and the Fall and Spring AVF Fellows’ courses. It will also be discussed during AVF sessions at other society meetings and in AVF’s scientific journal, Journal of Vascular Surgery: Venous and Lymphatic Disorders.
Speaking to Interventional News, chief investigator of the C-TRACT trial Vedantham said: “We are grateful to the AVF for its strong support of the C-TRACT Trial. The AVF has a distinguished history of advancing venous research, so this is a perfect fit. This partnership will promote the study’s success and provide insights into a new community partnership model that can be applied to benefit future studies.
“The investment of $12 million in this study by the NIH demonstrates its awareness of the potential for endovascular stent therapy to reduce disability in patients with post-thrombotic syndrome. As such, the C-TRACT Investigators and the AVF have a golden opportunity to develop high-quality evidence that secures access to innovative therapy for patients suffering with this condition.”
The Society of Interventional Radiology (SIR) Foundation is already partnering with C-TRACT investigators. Since January 2019, SIR Foundation has worked with Vedantham to raise awareness of the trial within the IR community, support site and patient enrolment, and encourage patient follow-up activities.
“Studies such as C-TRACT exemplify SIR Foundation’s mission to further interventional radiology through high-quality research that impacts our patients,” comments SIR Foundation chair Jeremy C Durack (Memorial Sloan Kettering Cancer Center, New York, USA). “We are proud to support this effort and continue to raise awareness among SIR members and the IR community about the value of this ground-breaking trial.”
Medtronic today announced US Food and Drug Administration (FDA) approval of the IN.PACT AV drug-coated balloon (DCB), a paclitaxel-coated balloon indicated for the treatment of failing arteriovenous (AV) access in patients with end-stage renal disease (ESRD) undergoing dialysis.
AV fistulae are created and used to enable haemodialysis for patients with ESRD. Over time, vessel restenosis limits the ability to use AV fistulae effectively. In order to restore function, patients often undergo one to three maintenance procedures per year,1 which can result in significant disruptions to critical haemodialysis care and increased costs to the healthcare system. Pivotal randomised trial results from the IN.PACT AV Access trial have shown IN.PACT AV DCB can extend the time between reinterventions by maintaining AV access site patency, therefore maximising a patient’s uninterrupted access to lifesaving dialysis care.
“In many cases, AV fistula are considered lifelines for patients with ESRD as they are the primary access point for life-saving dialysis treatment. When these access sites fail, patients experience delays in their dialysis treatment and require multiple reinterventions to keep the site functioning,” said Vincent Gallo, interventional radiologist at Holy Name Medical Center in Teaneck, USA, and an investigator for the IN.PACT AV Access trial. “With this approval physicians now have access to a safe and extremely effective therapy to slow the progression of restenosis, which results in fewer reinterventions and disruptions in care for these patients.”
The FDA approval is based on data from a prospective, global, multicentre, blinded, randomised (1:1), investigational device exemption (IDE) study, which enrolled 330 subjects, and evaluated the safety and effectiveness of the IN.PACT AV DCB at 29 sites in the USA, Japan, and New Zealand. Early data presented at the Cardiovascular Interventional Radiological Society of Europe (CIRSE) met the primary endpoints in demonstrating the comparable safety and the superior effectiveness of IN.PACT AV DCB compared to percutaneous transluminal angioplasty (PTA). Patients treated with IN.PACT AV DCB maintained patency longer and required 56% fewer reinterventions compared to those treated with standard PTA through six months. Through 12 months the data also showed no difference in mortality rates between the IN.PACT AV DCB group and the PTA control group. Finally, data presented at VIVA 2019 demonstrated superior patency was achieved with IN.PACT AV DCB versus PTA in both de novo and restenotic lesions, and all studied types of AV access.
“Until now, there were virtually no therapies available to treat AV fistulae lesions that had demonstrated an ability to maintain primary patency and reduce reinterventions over time,” said Robert Lookstein, national principal investigator in the USA and professor of radiology and surgery, vice-chair of interventional services, and medical director of clinical supply chain at Mt. Sinai Healthcare System in New York, USA. “In the largest AV DCB pivotal study to-date, IN.PACT AV DCB demonstrated the highest primary patency rate through six months and significantly lowered the rate of reinterventions required to maintain patency. With this evidence and approval in hand, we now have a technology that provides a significant clinical benefit of a 56% reduction in repeat interventions, which I believe is a huge win for the haemodialysis community and the patients we treat.”
IN.PACT AV DCB, leveraging technology from Medtronic’s IN.PACTTM AdmiralTM platform, increases blood flow and reduces thickening of the vessel wall by delivering the proven anti-proliferative drug paclitaxel. This drug penetrates deep into the vessel wall to prevent restenosis and has the potential to extend time between reinterventions. In 2016, the CE Mark indication for IN.PACT Admiral DCB was expanded for the treatment of failing arteriovenous (AV) access in patients with end-stage renal disease undergoing dialysis.
“The FDA approval of IN.PACT AV DCB marks a significant step forward for paclitaxel-coated devices. Importantly, it allows us to expand our proven IN.PACT DCB platform beyond the superficial femoral artery,” said Mark Pacyna, vice president and general manager of the Peripheral Vascular business in the Medtronic Cardiac & Vascular Group. “We are excited to bring this technology to physicians in the U.S. and to help improve the lives of patients living with ESRD.”
In collaboration with leading clinicians, researchers, and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular and end-stage renal disease. The company strives to offer products and services that deliver clinical and economic value to healthcare consumers and providers around the world.
References
Merit Medical Systems has announced that it has been granted breakthrough device designation by the US Food and Drug Administration (FDA) for the Merit Wrapsody endovascular stent graft system. The Wrapsody system is a flexible, self-expanding endoprosthesis for which Merit intends to seek indication for use in haemodialysis patients for the treatment of stenosis within the central veins of the outflow circuit of an arteriovenous fistula (AVF) up to the superior vena cava.
The FDA breakthrough devices programme is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA provides priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions. The Wrapsody system is nearing completion of its “first-in-man” studies, and is not currently available for sale.
“We are pleased with the recognition by the FDA of this worthwhile technology as well as the efforts of many members of our research and development team to bring the project to this point,” says Fred P Lampropoulos, Merit Medical’s chair and CEO. “Most importantly, we believe this system will provide substantial benefits to patients who may be treated with it in the future.”
Siemens Healthineers presents its new Somatom X.cite single-source CT scanner, together with the new myExam companion user guiding system, based on artificial intelligence (AI).
The intelligent user guidance system guides the user through the workflow using specific questions. The user interface works with the latest scanner hardware “to open up new possibilities,” a company press release states. myExam companion makes use of available patient data, such as sex, height, and age, and combines these with additional patient-specific information gathered by asking the user specific questions; for example, about the presence of metal implants, or the ability of patient to hold their breath. The scanner then optimises the scan parameters accordingly to ensure the best possible result. Siemens say that, in combination, these innovations help structure workflow more efficiently, smooth out differences in experience between the users, and achieve extremely high-quality results even in difficult diagnostic situations.
The first CT scanner with myExam companion is the new Somatom X.cite, featuring the Vectron X-ray tube that has previously only been used in the Somatom Force dual-source CT scanner.
“We have been testing Somatom X.cite with the new software platform for the past two months with successful results. We were impressed by both the excellent images and the way the new user guidance system made the workflows faster. The large gantry [82cm] facilitates the examination of seriously ill patients”, comments Christoph Stippich, chair and director, University Hospital Zurich, Zurich, Switzerland.
“We are driving the digital transformation of radiology through constant innovation of our devices. At the same time, we offer—for example, through remote solutions—more and more ways for our partners to create high-quality diagnostics. Somatom X.cite and myExam companion are a big step for our imaging portfolio along this plan into the world of intelligent user support and for Siemens Healthineers on our way to becoming a leader in clinical decision support “, says André Hartung, president Diagnostic Imaging at Siemens Healthineers.
myExam companion
The new intelligent user guidance system lets users utilise the full potential of the new Somatom X.cite, as well as the Somatom go scanner platform, which is already used on the market. It is now also possible to share established examination protocols between scanners quickly and without complications. Using AI, Siemens Healthineers has analysed thousands of scanning processes and identified key questions about the general conditions for achieving optimized scanning results. This led to the development of decision trees that ask the users relevant questions at each stage, thus guiding them through the scan preparations without complications. Workflows and their results are also more standardised, since this makes it possible to reduce deviations at a patient and user level.
“The decision trees found in almost every hospital, which have often previously been sketched on paper at an individual department level and define particular scanning parameters for different cases, are now directly integrated in the scanner software—in other words, exactly where they are needed,” comments Hatem Alkadhi, consultant radiologist at University Hospital Zurich (Zurich, Switzerland).
TriSalus Life Sciences (formerly Surefire Medical) has announced that the Centers for Medicare and Medicaid Services (CMS) granted approval for transitional pass-through (TPT) payment for its Surefire Spark Infusion System. Effective 1 January 2020, Surefire Spark Infusion System (to be known as TriNav) was granted transitional pass-through payment status as part of the 2020 Medicare Hospital Outpatient Prospective Payment System and Ambulatory Surgical Center Payment System (CMS-1717-FC) final rule posted on 1 November 1 2019.
TriNav is designed to improve therapeutic distribution and penetration into solid tumors. This system, using pressure-enabled drug delivery technology, has demonstrated the ability to overcome intratumoral pressure in solid tumors and potentially improve distribution and penetration of therapy during transcatheter arterial chemoembolization (TACE) and transcatheter arterial radioembolization (TARE) procedures.
This additional payment is intended to “facilitate access for [Medicare] beneficiaries to the advantages of new and truly innovative devices”. The Surefire Spark Infusion System met the required criteria to receive transitional pass-through status, with the CMS saying it believes there is no existing pass-through payment category for this device because of its pressure-enabled drug delivery (PEDD) valve, which offers a unique mechanism for therapy delivery to selected sites in the peripheral vascular system, including solid tumors in the liver and pancreas.
“We thank CMS for its efforts to expand access to devices such as our Surefire Spark Infusion System that provide improved benefits to patients,” says Mary Szela, president and CEO of TriSalus. “As we transform TriSalus into an oncology therapeutics focused company dedicated to improving outcomes in solid tumors, this highly favourable reimbursement status validates our innovative delivery system and confirms its role in our unique, multi-pronged approach to treat liver metastases and pancreatic cancer.”
With widespread urological acceptance of prostate artery embolization (PAE) impending, Tiago Bilhim (Saint Louis Hospital, Lisbon, Portugal) calls for caution when selecting patients for the minimally invasive treatment of benign prostatic hyperplasia (BPH). In a recent commentary published in the Journal of Vascular and Interventional Radiology (JVIR; doi: 10.1016/j.jvir.2019.08.003), Bilhim says “It is important to better select patients before PAE to avoid clinical failures”, emphatically concluding: “Avoid pedunculated intravesical prostatic protrusions!”
The commentary was written following another article published in JVIR (doi: 10.1016/j.jvir.2019.07.035) in November 2019 by Simon Yu (Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China) and collaborators, who reported that the thickness-to-height ratio of intravesical prostatic protrusions (IPPs) predicts the clinical outcome and morbidity of PAE for BPH.
Both the prospective, single centre study conducted by Yu et al and the subsequent commentary from Bilhim were carried out within the context of a dearth of information regarding the implications of the median lobe for patients with BPH. Defining the median lobe, Bilhim writes: “There are many different types of IPPs (intravesical prostatic protrusions) that may be due to median lobe overgrowth, but also from the central or transitional zone of the prostate, or even the anterior fibromuscular stroma. Usually, the terminology of ‘median lobe’ refers to the continued growth of the periurethral glands, leading to a well-demarcated expanding midline retrourethral tissue; thus, IPP connotes a broader reach, encompassing both the median lobes, as well as all IPP from other glandular zones of the prostate.”
According to Bilhim, a frequent question posed by physicians and patients alike is whether the median lobe is a contraindication for PAE. In praise of the study from Yu and colleagues in Hong Kong, Bilhim writes that “the present study sheds some light on this specific topic”. Indeed, the answer provided by Yu and his team is that not all median lobes are the same.
Yu and collaborators found that pedunculated IPPs, which are taller than they are wide, are indicative of poor outcomes after PAE. They postulate that this is due to a bladder outlet obstruction that “becomes more prominent after embolization, as the prostatic tissue gets softer and more mobile with ischaemia”. In their study, they evaluated 82 patients with an International Prostate Symptom Score (IPSS) ≥15 and a quality of life score ≥3, treated between June 2015 and December 2018 at their institution. IPPs were present in 57 of 82 patients (69.5%). They reported the presence of IPPs correlated with the occurrence of post-procedure complications (p=0.009), but not with suboptimal IPSS at 12 months (p=0.758). However, IPPs with a thickness-to-height ratio ≤1.3 did correlate with suboptimal IPSS at 12 months (p=0.025) and suboptimal quality of life at six months (p=0.025) and 12 months (p=0.008), as well as with the occurrence of post-procedure complications (p=0.009). They therefore concluded that while IPPs with a thickness-to-height ratio ≤1.3 predicted the occurrence of post-procedure complications with urinary obstruction up to 12 months after PAE, merely the presence of IPPs alone did not predict the clinical outcome.
This raises several questions about the median lobe, Bilhim argues: “What type of imaging classification can we use to assess it? What is the impact of the median lobe on the natural progression of disease in patients with BPH? Does the median lobe also limit the efficacy of other minimally invasive surgical techniques such as prostatic urethral lift (PUL) or water vapour thermal therapy? What do we know already about the effect of PAE for the median lobe? Can we target the median lobe during PAE? Is PAE effective when treating patients with BPH and a median lobe?”
Whilst seeking answers to these questions, Bilhim acknowledges that what Yu et al’s study does elucidate is that PAE can target the IPP, but it highlights that there are different clinical outcomes depending on the subtypes of IPP present. “Clearly,” Bilhim writes, “pedunculated IPPs with taller than wide protrusions into the bladder neck are poor candidates for PAE, with 34% of patients presenting worsening of bladder outlet obstruction symptoms, acute urinary retention, or failure to remove the bladder catheter, and 11% requiring bailout surgery after embolization. One would not want to end up as Stealers Wheel: ‘Here I am stuck in the middle with you’.”
However, he ends on a positive: “The good news is that these types of pedunculated IPPs have an overall reported prevalence of 10%, even though they were documented in 43% of patients from the study of Yu et al, which may be due to selection bias. The vast majority of IPPs are broad-based and respond well to PAE.”
Members of the British Society of Interventional Radiology (BSIR) have voted overwhelmingly in favour of interventional radiology (IR) becoming a specialty in the UK. Of 350 votes cast, 80% (279) were in favour, and 20% (71) were against.
BSIR members had 24 hours to vote on the motion “Should interventional radiology become a specialty?” during the society’s 2019 annual scientific meeting (13–15 November, Manchester, UK). The society’s annual general meeting (AGM) took place during this voting window, and allowed participants to discuss the ramifications of voting for or against granting IR specialty status.
Whether or not interventional radiology will become a specialty is still under the auspices of the Royal College of Radiologists (RCR), explained BSIR vice president Philip Haslam (Freeman Hospital, Newcastle-Upon-Tyne, UK), but he said that the results of this vote “give us [BSIR] a mandate now, from our members, to take this forward with the college of radiologists, with the General Medical Council (GMC), and hopefully achieve our aims”.
IR became a specialty in the USA in 2014 and, by 2018, was the most sought after specialty amongst medical students. While the healthcare system differs between the USA and UK, proponents of IR becoming a specialty in the UK argued that “there is much to learn” from this US success. The Royal Australian and New Zealand College of Radiologists (RANZCR) have recently published a white paper looking to develop an IR specialty in Australasia. In continental Europe, the German Society of Interventional Radiology and Minimally Invasive Treatment (DeGIR) have their own exam, which implements a modular system for training. France and The Netherlands are currently exploring options for IR to become a specialty.
What happens next?
“This is the start of a long and slightly painful process,” Raman Uberoi (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) told BSIR delegates, “because it is tricky to become a specialty”.
BSIR will begin talks with the RCR, and then jointly with national training bodies, including the GMC, the clinical oversight group (COG), and the UK Medical Education Reference Group (UKMERG), to make the case for IR becoming a specialty. This decision will ultimately come from the Privy Council, but Uberoi emphasised that “the message needs to come from the bodies to say that it is vitally important that IR becomes a specialty”.
The Privy Council is a formal body of advisers to the Sovereign of the UK, and is responsible for some of the affairs of the GMC. Following an initial, positive reaction from the GMC, Uberoi reported that the Privy Council were not supportive of IR becoming a specialty (“Their knee-jerk response is ‘no’ to any new specialty,” he said). However, he added that the case had never been made directly to the Privy Council, and that BSIR needed to work with the RCR and GMC “to make the arguments cogent” before making the final submission to the body.
This process may take “many years”, he said. Specifically addressing the BSIR members, he urged: “A lot of us will need to go into the college, a lot of us will need to be involved in the creation of the specialty and actually delivering for the future.
“Ultimately, this is about quality and patient safety, and improving outcomes,” he continued. “That means, we have to have better training, we need better access to clinics, and to occupy those clinics, and then to get better workforce planning for the future. But this needs buy in from all interventional radiologists, because this is not something that Council or a small group of people can take forward. We all need to push for this and we all need to believe in this project, because it will take some time. It will not impact on any consultants working today. This is the future; this is next generation of interventional radiologists that we are looking to. So we are looking at something that is going to take eight or nine years before we see the full benefits. We need to be doing other things besides, but I think this is vital for the future survival of IR, and more importantly, it is going to give us high-quality, focused care.”
Graham Plant Lecture advocates for IR to become a specialty
In his Graham Plant Lecture at the annual meeting, entitled “Interventional Radiology: A 21st century specialty”, Uberoi took the opportunity ahead of the vote to make the case in favour of IR gaining specialty status. “We have become integral to the management of not all, but a large number of patients in virtually every specialty in the hospital setting,” he said. “We play a key role in their treatment in nearly every sense that I can think of.”
However, he continued: “I think there is a problem. […] This issue that Charles Dotter [founder of interventional radiology] himself identified, and others after him identified, is the role of clinician versus technician. It is really about who is clinically responsible for the patient? Who is clinically responsible for the patient has huge connotations: the hospital management team, NHS England, the Trust, really focus on those individuals, supporting them with infrastructure and resources. They are seen as the primary clinician managing that patient. I argue that many of us are still behaving very much as technicians; the responsibility lies with surgeons or physicians. They are seen as the specialist clinician and, not unreasonably, a lot of organisations will focus their attention and their resources on those areas.”
Speaking in advance of the BSIR membership vote on the matter, Uberoi said, “I think it is vitally important that we consider becoming a specialty. I am not one for doing things just for the sake of it; I really believe this is crucial for our future development and survival. We can carry on sculling, keep doing the same things that we have been doing for the last 20 years, but I can tell you that, yes, it has given us some benefit, but I do not think that we can do much more.” Listing what he saw as the potential benefits, he enumerated:
Uberoi did mention concerns his IR colleagues had raised with him over the last few months about becoming a specialty, though, which he hoped to alleviate in his Graham Plant Lecture. Firstly, he said, some people worried that becoming a specialty may adversely impact the number of doctors joining IR. Addressing this concern, he said: “I think we are in a poor place [with recruitment]; I think we can only get better.”
Furthermore, he said there is “a lot of confusion” about what happens with diagnostic radiologists who currently do IR. “This does not stop anybody from doing IR. On the contrary, it gives greater guidance and support for their practice in their roles from the specialty, which will ensure the quality standards that we need to adhere to,” he explained. “Similarly, those who do diagnostic radiology (DR) and IR will be able to continue doing so. DR is key to what we do, it is what distinguishes us from other surgeons. We need imaging, and we can and should continue to do DR, as long as we adhere to the RCR quality standards and look to our patient’s needs. We will continue to be trained in imaging, and we will continue to do imaging.”
This concern was discussed further by BSIR members after the Graham Plant Lecture, before voting closed. In particular, congress attendees asked about the RCR’s attitude towards IR becoming its own specialty, with one audience member flagging that the college may view this as taking numbers away from DR. “I do not think they are overjoyed,” Uberoi conceded, “because I think this is an unnecessary, from their perspective, headache, and it is a real problem for them.” However, he went on to counter: “Yes, we will be taking numbers from DR initially, but of course, these would reflect for trainees who are currently going into IR. Over time, I think we will increase IR numbers not at the expense of DR.”
Uberoi described the RCR’s stance towards designating IR specialty status as “lukewarm”, in his opinion, and announced his intention to run for vice president of the college once nominations open, as he believes it is important for the IR voice to be represented. “My intention is to do this from within the college. I think we can only do this with full college support. I think we need to make people understand why we want to do this: it is not a backlash against DR, it is about our future, the future survival of our specialty.”
Following dialogue with RCR, BSIR president Ian McCafferty (Queen Elizabeth Hospital Birmingham, Birmingham, UK) was positive about the college’s response: “They [RCR] also understand that we cannot stay where we are. They know we have to evolve in some shape, way, or form.”
The BSIR women and diversity committee formally launched the Professor Anna Maria Belli Travelling Grant on 14 November, at the 2019 annual scientific meeting of the British Society of Interventional Radiology (BSIR; 13–15 November, Manchester, UK). The launch took place during the first ever women and diversity networking luncheon to be hosted at the annual congress.
Speaking to Interventional News at the launch, the grant’s namesake, Anna Maria Belli (recently retired from St George’s University Hospitals NHS Foundation Trust, London, UK), commented: “More than half of medical graduates are female, yet we still do not have them entering interventional radiology (IR), because they perceive it as a very male-dominated specialty. Women make fantastic interventional radiologists. They bring a different perspective and have a healthy team approach, and we really need to attract them for our specialty to thrive.”
BSIR women and diversity committee co-chair Fiona Miller (King’s College Hospital NHS Foundation Trust, London, UK) shared Belli’s enthusiasm, saying: “I am delighted that the BSIR committee decided to support this grant to promote interventional radiology, while carrying the message that everyone is welcome to join our team.”
Tze Wah (The Leeds Teaching Hospitals NHS Trust, Leeds, UK), also BSIR women and diversity committee co-chair, added: “It has been a real privilege to celebrate this amazing milestone with professor Anna Maria Belli. We would like to spread this magical ripple forward, and I believe we can change the landscape for women in interventional radiology, and increase the colour in our IR community. All good standing BSIR members can apply for it [the grant], so they can go out and promote diversity in IR.”
Funds from the Professor Anna Maria Belli Travelling Grant will be used to cover second class travel expenses for individual lecturers to deliver talks to medical students, junior doctors, and consultants regarding women in IR, diversity and recruitment. One night’s accommodation, if necessary and at “reasonable costs”, may also be included.
According to BSIR, the purpose of the travelling grant “is to showcase IR, facilitate access to female and other role models, allowing trainees the opportunity to discuss as well as ask sensitive questions relating to a career in IR. The hope would be that these visits would in addition result in informal/ formal point of contact that would blend with our vision to commence a mentoring programme.”
Applicants must be UK-based IR consultants, a current member of BSIR, have a track record of teaching and education, and submit a statement explaining what the lecture would be based on. The women and diversity committee will then review applications and select the grant recipients.
Raman Uberoi (Oxford University Hospitals NHS Foundation Trust, Oxford, UK), another member of the BSIR women and diversity committee, explained the importance of the grant to this newspaper: “What we need are role models; we need mentors who are going to inspire people, give them the opportunity to see interventional radiologists as being an embracing community of like-minded doctors who are using image-guiding treatments. Having this diversity group [the women and diversity committee] means we are inclusive, we are trying to bring everybody into IR who is interested in treating patients using minimally invasive techniques, regardless of their gender, ethnicity, or orientation—that should not be the issue. The only issue is that they are keen on patient care, on improving outcomes, on quality and safety, and really, getting the best results for our patients. Having people who are going out from the BSIR demonstrating that we are very open and receptive to any ethnicity, any gender, is important. We want them to become skilled in interventional radiology, ultimately to provide the best possible care for our patients.”
During the official launch of the travelling grant, incoming BSIR women and diversity committee chair Rosemina Ahmad (University Hospitals of Leicester NHS Trust, Leicester, UK) spoke on unconscious bias in interventional radiology. In her presentation, she highlighted how innate human unconscious bias was seeping into machine learning algorithms, warning: “Early evidence shows that unconscious bias is magnified by artificial intelligence. We need to be aware of this, because this is shaping the future.”
The BSIR women and diversity committee, and the new Professor Anna Maria Belli Travelling Grant, hope to address both unconscious and conscious biases facing women and marginalised groups interested in a career in interventional radiology. The ultimate goal, Elika Kashef (Imperial College Healthcare NHS Trust, London, UK) explained, is to further the conversation around diversity so that it goes beyond “simply celebrating being a woman, for example, and an interventional radiologist”, but matures to the point when the discipline is so inclusive for its diversity to be unremarkable.
This advertorial is sponsored by Boston Scientific.
Boston Scientific leads the largest clinical programme investigating drug-eluting therapy for the treatment of peripheral arterial disease (PAD), in an effort to capture safety and efficacy data, and to help physicians make informed decisions. PAD affects an estimated 27 million adults in Europe and North America, and is associated with significant morbidity and mortality, as well as impaired quality of life and lower-extremity functioning over time. Boston Scientific’s ELUVIA® drug-eluting stent is a safe, effective option for these patients, writes Yann Gouëffic, MD, PhD (Paris, France).
Endovascular intervention for the treatment of femoropopliteal lesions is established as a first-line strategy. In the 2000s, self-expandable stents showed superiority over percutaneous transluminal angioplasty (PTA), but in-stent restenosis rates were still high (19–37%). Paclitaxel-coated balloons have been shown to successfully prevent intimal hyperplasia, but the use of scaffolding appears to be a more effective option to reduce restenosis.
In 2011, Michael Dake (Tucson, USA) et al evaluated a polymer-free, paclitaxel-eluting stent (ZILVER® PTX®, Cook Medical), and showed that it was superior to balloon angioplasty in terms of patency and reintervention, with provisional stenting. However, there was still room for improvement, notably in terms of controlled drug release: ZILVER® PTX® does not utilise a polymer to release paclitaxel, and delivers approximately 95% of the total drug load within 24 hours of deployment. Paclitaxel levels are sustained in the artery wall for 56 days. However, in-stent restenosis predominantly occurs a year after nitinol stenting in the femoropopliteal segment, so the kinetics of paclitaxel release by ZILVER® PTX® do not match the kinetics of restenosis at the femoropopliteal level.
ELUVIA® is characterised by its nitinol platform (INNOVA®), low paclitaxel loading (0.167μg/mm2 dose density), and use of polymer to control drugelution. The amount of paclitaxel is much lower for ELUVIA® compared with other drug-eluting devices. The polymer is similar to the polymer used in coronary paclitaxel-eluting stents, and, as a result, its safety and biocompatibility have been well studied.
The polymer is composed of a dual layer. The primer layer (poly n-butyl methacrylate) promotes adhesion of the active layer (poly[vinylidiene fluoridehexafluoropropylene]) to the stent, while the active layer controls the release of paclitaxel.
After promising preclinical studies, ELUVIA® was first evaluated in humans in the MAJESTIC registry. In MAJESTIC, 57 patients were treated for femoropopliteal lesions with an average length of 70.8mm±28.1. The primary patency at one year reached 96.4% (Kaplan-Meier [KM] estimate). Subsequently, a randomised (2:1) controlled trial was launched comparing ELUVIA® to ZILVER® PTX® for femoropopliteal lesions: IMPERIAL.
The IMPERIAL trial was designed as a non-inferiority study, including patients with Rutherford category 2–4, with lesions that range from 30–140mm in length. Sixty-five centres were included to enrol 465 patients. The primary efficacy endpoint was primary vessel patency at 12 months, defined as a binary endpoint based on a duplex ultrasound peak systolic velocity ratio of 2.4 or lower at the 12-month follow-up visit in the absence of clinically-driven target lesion revascularisation or bypass of the target lesion.
The primary safety endpoint was the occurrence of major adverse events, defined as all causes of death through one month, major amputation of the target limb through 12 months, or target lesion revascularisation (TLR) through 12 months. Additionally, a prespecified post-hoc superiority analysis for the primary efficacy endpoint was included within the statistical analysis plan. A duplex ultrasound core laboratory and a clinical events committee were involved to assess the primary endpoints.
Between December 2015 and February 2017, 309 patients were included in the ELUVIA® group and 156 in the ZILVER® PTX® group. The mean age of participants was 68.5 and 67.8 years old, respectively, and 42–44% of the patients were diabetic. The mean length of the treated lesions ranged from 81.8–86.5mm. Non-inferiority was shown for both efficacy and safety endpoints at 12 months. Primary patency was observed for 231 (87%) of 266 patients in the ELUVIA® group, and for 106 (82%) of 130 patients in the ZILVER® PTX® stent group (difference 5.3% [one-sided lower bound of 95% CI –0.66]; p<0·0001).
Moreover, statistical superiority was met in the post-hoc analysis of 12-month primary patency in the full cohort analysis. Among the secondary endpoints, the rates of thrombosis in the ELUVIA® and ZILVER® PTX® groups were 1.7% and 4%, respectively (p=0.20). One year TLR rates were 4.6% for ELUVIA® and 8.1% for ZILVER® PTX® (p=0.0142). This statistically significant difference is maintained out to two years, with TLR rates of 12.9% and 20.5% for ELUVIA® and ZILVER® PTX®, respectively (p=0.0472).
Prespecified subgroups at high risk of restenosis and reintervention, namely chronic total occlusion (CTO), high calcium lesion, diabetes, and long lesions, were analysed in the IMPERIAL dataset. Lesions at high risk of restenosis demonstrated a consistent two year TLR rate (Figure 1).
In the ELUVIA® group, non-CTO lesions had a higher average one-year primary patency (90.6% vs. 83.9%). Of the 193 lesions considered to have moderate or severe calcifications, a primary patency rate of 89.2% was recorded at one-year compared to lesions with no or mild calcification, which had a patency of 87%. In diabetic patients, ELUVIA® showed primary patency results of 87.4%, consistent with the overall cohort, and in comparison to 80.2% with ZILVER® PTX® at one-year.
Lastly, the 50 long femoropopliteal lesions in IMPERIAL (mean length 162.8mm) had an 87.9% primary patency rate at one year (KM estimate). These data are in line with a previous long femoropopliteal lesion ELUVIA® registry. At one-year, the primary patency rate was 87% (KM estimate). There is remarkable consistency in efficacy across all lesions at high risk of restenosis for this device.
In December 2018, a meta-analysis showed a late mortality signal with certain paclitaxel-coated devices compared to non-coated devices. Notably, the ELUVIA® stent was not included in this. Recently, a new meta-analysis was presented at the FDA Panel in June 2019, though, again, ELUVIA® was not part of these contributing datasets.
However, during this June meeting, additional data were released regarding the comparison between ELUVIA® and coronary drug-eluting stent designs. Interestingly, the polymer release design principles are similar between both, but paclitaxel concentration is higher in coronary paclitaxel-eluting stents. Over 4,000 patients have been included in randomised clinical trials comparing paclitaxel-eluting coronary stents versus bare metal stents, and no all-cause mortality signal has been observed in a meta-analysis, negating the hypothesis of a systemic effect of paclitaxel delivered by this method. The FDA highlighted “that for individual patients judged to be at particularly high risk for restenosis and repeat femoropopliteal interventions, clinicians may determine that the benefits of using a paclitaxel-coated device outweigh the risk of late mortality”.
Boston Scientific has developed the largest clinical programme regarding drug-eluting therapy for PAD. The EMINENT RCT is recruiting 750 patients to compare ELUVIA® to bare-metal stents. To ensure long-term data capture both IMPERIAL and EMINENT, follow-up has been extended to five years. SPORTS, an investigator-sponsored study, is an RCT with three arms (total 222 patients) to compare a bare metal stent, a paclitaxel-eluting stent, and a paclitaxel-coated balloon (SeQuent Please®, from B Braun) for long femoropopliteal lesions.
Data from this clinical programme, as well as from other ongoing drug-eluting device trials and analyses, should provide further information to help physicians with patient-centric decision-making in the endovascular treatment of femoropopliteal disease, and in particular the treatment of lesions at high risk of restenosis.
Yann Gouëffic, MD, PhD, is affiliated with the department of vascular and endovascular surgery, Hôpital Paris St Joseph, Paris, France.
Establishing the first Interventional Radiology department in Argentina, Ricardo García-Mónaco is a pioneer of minimally invasive, image-guided therapies in South America. Looking back on a career that spans more than three decades, he discusses how establishing interventional radiology (IR) as a clinical discipline rather than a technical one is crucial for the field’s survival and success, and recalls a particularly memorable case where IR intervention in a two-day-old baby saved the patient from amputation and enabled her to go on to become the healthy, active teenager she is today.
When I was in my second year of residency in radiology, in 1985, my hospital incorporated digital subtraction angiography equipment, the first of its kind in my country. Before that the Radiology departments in Argentina did not have vascular suites. I was selected by the chair of Radiology to join the new Angiography Unit (at the time the unit only performed diagnostic examinations), in addition to the regular residency curricula. I was very happy with the patient commitment I could get in radiology through this subspecialty, and started reading about the subject in the radiology journals that we had at the time in Argentina: American Journal of Roentgenology (AJR) and Radiology. I was rapidly fascinated by the possibilities of therapeutic angiography, as it was then called. I foresaw the tremendous future of the endovascular approach as a proper tool to treat different diseases, especially through embolization procedures that were not recognised or regularly performed at that time in my country. Except for cardiologists performing angioplasty procedures, there were not many physicians interested in vascular procedures, and I realised it was a great opportunity to develop my career in what was a rather “unknown” area in Argentina at the time.
I was very lucky to have important mentors in my career, who positively marked my professional and personal pathways. First of all, during my residency, Eduardo De Santibanes, an outstanding young liver surgeon at the time, introduced me to the importance of clinical commitment and patient follow-up—not very common amongst radiologists. He always encouraged me to be in the operating room while surgery was being conducted on any of my angiography patients, and then to go to the pathology department to observe the specimen resected. He was very keen to explain every detail of the surgery to me, and to elucidate the correlation with the imaging studies I had performed preoperatively. Years later, when I went to France to train in vascular and interventional radiology, I was lucky enough to meet two outstanding mentors: Pierre Lasjaunias and Alain Roche. Knowing them and incorporating their ways of practicing IR was a breakthrough in my career. They were top IR physicians ahead of their time, and they developed the foundations of many of the clinical and technical interventions still performed to this day worldwide. Indeed, both of them were mentors for a whole generation of interventional radiologists, and many that trained with them are now successful professionals at different international facilities.
As I have been in IR for 30 years, I have seen many innovations, including technical developments, material refinements, new devices, new interventions, new indications of IR treatments, and improvements in equipment and software. But what has most influenced my career has been the conceptual shift from IR being a technical speciality to becoming a clinical, patient-centred one. Indeed, this “innovation” is increasing IR recognition among other clinical and surgical specialties, allowing interdisciplinary interactions to offer IR as a solution to the patient as it occurs with medical or surgical therapies. A nice example of innovation in this setting is the recent development of interventional oncology, now regarded as the forth pillar of cancer care, joining medical, surgical, and radiation oncology.
Argentina being a rather conservative country, one of the biggest challenges was overcoming the disbelief that a radiologist could have a therapeutic role and run an interventional department. As radiologists are commonly regarded as physicians who only work with images and who do not interact with patients, both patients and doctors were unaware of the possibilities of IR. I remember in my early days back from France, every indication and every procedure I performed were like tests, because my results were under constant scrutiny from other physicians. Demonstrating that IR training differs a lot from that of diagnostic radiology and that we are specifically trained to treat certain diseases, along with our positive results, minimised this reluctance. Another big challenge was to organise all the staff, including nurses and technicians, as the path to success is dependent on paramedical staff as well as IR. Doing so many procedures requiring specific materials for the very first time in my country (such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), transjugular intrahepatic portosystemic shunt (TIPS), and venous stenting), I had to explain the advantages of IR to the hospital administrators and payers, as these were initially regarded just as additional costs. Indeed, this challenge still continues today with procedures recently introduced to my country, such as radioembolization, cryoablation, and venous deprivation. On the other hand, establishing an Endovascular Therapy and Interventional Radiology department was very rewarding. Developing a single department performing all types of image-guided therapies regardless of the organ (except for the heart) prevented other specialties from developing these types of procedures in their own domain. This was different to other hospitals, where neurointerventions, peripheral angioplasty, aortic aneurysm grafts, vertebroplasty, and many other procedures were being performed by other specialities. A single, broad department allowed not only important clinical activity, but also enabled educational endeavours, evidenced by the number of young Latin American interventional radiologists trained at our facility. Being recognised as one of the best teaching centres in Latin America and the high quality standards advocated by the Joint Commission is one of the biggest rewards for me.
I was the first president of this recently created society. The main goals are to foster education in IR and to work with the national government to recognise IR as a true speciality. Additionally, it is a facilitator for physicians interested in the subject and wanting to pursue an IR career. It is also a professional and juridical way to interact with other medical specialities and the minister of health from an official position.
The expenditure on research in South America is very low compared to other regions. However, some exciting research has originated from South America, such as the introduction of stent grafts to treat aortic aneurysms (albeit developed by a vascular surgeon), or the first prostate arterial embolization (together with Portugal). The latter, developed by Francisco Carnevale in Brazil, is probably the most relevant research to come out of South America in recent years. The same group is still performing additional work on the matter, and we have studied the macro- and microvascular anatomy of the prostate and its implications for embolization. The field of interventional oncology is very exciting, and we are part of some international randomised controlled trials, including RETNET, the first study to compare bland embolization versus conventional TACE versus DEBTACE in neuroendocrine liver tumours.
I have many memorable cases—some due to amazing, positive results, and others that have saved patients’ lives or much improved their quality of life. Among these, maybe the most memorable was a newborn with a life-threatening condition due to multi-organ haemorrhages and congestive heart failure, secondary to a giant right lower limb tumour (Kaposiform Hemangioendothelioma). The patient was so critically ill, despite medication, that amputation of her right leg was considered to stop the irreversible coagulopathy caused by the tumour. Instead, we intervened to embolize the tumour early on the second day of life—a challenging intervention in this 3kg, decompensated newborn—which lead to a dramatic and total recovery. Most memorably, I met the patient recently, now a teenager with a normal life, practicing several sports, including volleyball and dancing. This made me very happy, especially considering she risked amputation as a newborn, and this was not done thanks to our IR decision.
IR has a bright future, because innovations and improvements in imaging capabilities are constant. However, IR needs to become a true clinical specialty, just like surgery or paediatrics. IR has not yet found the correct pathway to succeed and survive. Should it be a subspecialty of radiology, or should it run separate and by itself? Should the medical community or payers accept IR as a self-specialty, or as a therapeutic technique inside a broad specialty (as is the case with “interventional neurosurgery”, performed by neurosurgeons, and “endovascular surgery”, performed by vascular surgeons)? Of course I do not have the answer, but new generations of interventional radiologists should consider that clinical competence is as important as technical skill. IR procedures will continue to grow, because in my view the number of open surgeries being performed will continue to fall, and ultimately these will be replaced by minimally invasive or medical options, except for in a few indications.
Atomisation of the specialty by other disciplines could jeopardise the future of IR. The most notorious examples are neurointerventional procedures that in many countries are performed by neurosurgeons, or endovascular interventions performed by vascular surgeons. Interestingly, in some countries there is a trend for surgical departments to establish a “percutaneous surgery unit” that performs drainage of fluid collections, gastrostomy, bile duct interventions, and even tumour ablations. I think this is one of the biggest challenges in IR at the moment; strategies must be built accordingly. Fortunately, SIR, CIRSE, and many other IR societies are aware of this and are currently facing this problem.
I am a family man, so enjoy spending time with my family, watching soccer games with my son or daughter in stadiums, and seeing my son play in the Argentinian Rugby Union tournament. I love sports, and played rugby in the first division during my youth. More recently, I have been coaching young rugby teams for several years. I used to ski with the family every winter and like to fly cast in Patagonia lakes and rivers in the summer. I also like to cook a typical Argentine meal called “asado” on Sundays, a kind of firewood grilled beef, and to watch movies or TV series at night, or dine with friends and family.
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Konstantinos Donas (Münster, Germany) reported five-year data from a single-centre, retrospective study with 238 patients in the first CIRSE session. The long-term, real-world dataset showed no increased mortality for the matched patients who underwent paclitaxel-coated balloon treatment vs. those treated with plain balloon angioplasty.
“In addition, there was no correlation between mortality and the dose of paclitaxel used,” the researchers write in the study that was published in CVIR.
These data, which refute the findings from the Katsanos et al meta-analysis, are important as they shed light on whether the meta-analysis can be replicated in a real-world setting, says Donas. He also notes that the researchers designed this study to avoid the limitations of the randomised data included in the meta-analysis.
This investigator-initiated study set out to assess the long-term mortality of patients treated by the IN.PACT Admiral (Medtronic) compared with standard plain balloon angioplasty.
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Since founding the Ghana Society of Interventional Radiologists in November 2015, Benjamin Dabo Sarkodie has been working to establish the offering of minimally invasive, image-guided procedures in the west African nation. He describes his recent successes performing the first cerebral aneurysm coiling in West Africa, and discusses how, through collaboration with interventionalists from Hungary, he is setting his sights on hyper-acute stroke management as the next frontier in Ghanaian interventional radiology.
Ghana is a developing country located in West Africa, bordered by Ivory Coast, Togo, Burkina Faso, and the Atlantic Ocean, with a growing population of 30 million people. Although endovascular neurointerventional practices are well-established in many developed countries, they are non-existent in many low- and middle-income countries, due to a shortage of doctors with the required training, and to limited infrastructure. This is despite the huge demand. Until recently, there were minimal treatment options in Ghana for neurovascular conditions such as arteriovenous malformation (AVM) or cerebral aneurysms. Many patients travel thousands of miles to access treatment, an expensive venture that some patients are not fit for. Indeed, several developed complications like deep vein thrombosis during these long haul, transatlantic flights.
The infrastructure needed for this specialty is not readily available in Ghana. The establishment of a neurointerventional service is also hindered by the lack of good quality angiographic machines and trained angiographic laboratory personnel. However, adequate resources are emerging.
In March 2019, supported by interventional radiologist Istvan Lazar (Borsod County University Teaching Hospital, Miskolc, Hungary), we successfully completed the first case—to our knowledge—of cerebral aneurysm coiling in West Africa. This was after the acquisition of a digital subtraction angiogram (DSA) and road mapping software at the Euracare Advanced Diagnostics and Heart Center in the Ghanaian capital, Accra. We continue to collaborate with Lazar for assistance with difficult cases. Our team is comprised of doctors, nurses, and radiographers who have been adequately trained to assist with these endovascular neurointerventions.
Since this first case, we have successfully completed six cases of coiling and one case of flow diverter stent insertion. We have also undertaken 22 cases of diagnostic cerebral angiograms, two cases of tumour embolization, and three cases of AVM embolization.
With the good outcomes from these initial procedures, coupled with awareness creation, we are set to embark on even more endovascular neurointerventions.
It is an exciting time for healthcare in Ghana, as we are now equipped to cater for both ruptured and unruptured cerebral aneurysms, as well as other neurovascular conditions.
With the launch of a stroke centre at Euracare, hyper-acute stroke management is our next major focus. We have acquired various devices to aid us in offering mechanical thrombectomy to people with large vessel ischaemic infarcts.
As all patients are evaluated by a neurologist prior to intervention, a strong partnership with other specialties, such as neurology, neurosurgery, and anaesthesia, is needed as the basis for these procedures.
As we forge ahead with our endovascular offering, we hope that the surgical options for treating some of these conditions will also become more readily available. These will serve as an alternative modality, in addition to treating those conditions unsuitable for endovascular management.
We are also embarking on conferences and workshops, backed by the Ghana Society of Interventional Radiologists, to aid physicians in identifying common conditions like subarachnoid haemorrhage. There is a low level of awareness among general practitioners, who serve as the first point of call.
To provide an example of this: a client of mine had been on admission for a week in a small facility receiving treatment for malaria. She had been suffering from severe headaches and suddenly collapsed whilst singing at church. Fortunately for her, the pastor presiding over the assembly thought it prudent to request a transfer to a tertiary facility, as her condition was not improving. A head CT scan was requested on admission to the facility: the diagnosis, an acute subarachnoid haemorrhage.
Many patients are not able to afford these interventions, as treatment is on a “cash and carry” basis. Local insurance companies, as well as the National Health Insurance Scheme, do not offer cover for these procedures. However, an altruistic cerebral aneurysm survivor has founded the Ghana Brain Aneurysm Foundation, which aims to fund and make accessible treatments to those who are not as fortune as he was to receive management abroad.
Benjamin Dabo Sarkodie is a consultant endovascular and interventional radiologist in the department of Radiology at the School of Medicine and Dentistry, University of Ghana, Legon, Accra, Ghana.
XACT Robotics has announced the successful completion of its latest financing round, totalling US$36 million.
The company intends to use the proceeds to support the commercialisation and continued development activities in support of the recently US market cleared XACT Robotic System, which also has CE mark. The XACT Robotic System is the first hands-free robotic system combining image-based planning and navigation with insertion and steering of various instruments to a desired target across an array of clinical applications and indications.
“As we continue to build momentum for our robotic system, we will use the recent funding to launch the system to select US radiology Centers of Excellence partners,” says Chen Levin, CEO, XACT Robotics. “In addition, we will invest to continue expanding the utilisation of the system and support our future launch cycle, including compatibility of the XACT Robotic System with additional imaging modalities and clinical applications to address a broad range of patient care needs.”
The current financing round included leading investors in the surgical robotics space, such as Chasing Value Asset Management who previously held positions in MAKO Surgical (acquired by Stryker in 2013), Mazor Robotics (acquired by Medtronic in 2018), and most recently Corindus Vascular Robotics (acquired by Siemens in 2019). They join the current shareholders of the company, including Shizim Group and MEDX Ventures Group.
XACT Robotics was founded by entrepreneur Harel Gadot. The technology is based on research originally conducted at the Technion—Israel Institute of Technology, by Moshe Shoham, founder of Mazor Robotics (acquired by Medtronic in 2018).
Nick Hopkins (Buffalo, USA) talks to BLearning Neuro at VEITH Symposium 2018 (13–17 November 2018, New York, USA) about the DAWN trial, which showed that in carefully selected acute ischaemic stroke patients that “intervention out to 24 hours is viable”.
“Stroke intervention is the next horizon in medicine,” says Hopkins, who also discusses the shortage of trained neurointerventionists who can perform stroke thrombectomy. “The only way we are going to solve this problem”, adds Hopkins, “is by training interventional cardiologists, interventional radiologists and vascular surgeons interventionists in outlying areas who can perform endovascular treatment for stroke ‘on the spot.’”
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The SELUTION SFA trial met its primary endpoint and demonstrated an late lumen loss of 0.19mm. Furthermore, excellent freedom from clinically driven TLR was achieved through 24 months in 87.5%, with no primary TLR event observed after month 11. Thomas Zeller (Bad Krozingen, Germany) presented these results at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas, USA (4–7 November).
SELUTION SFA is a prospective, controlled, multicentre, open-label, single-arm clinical trial treating superficial femoral artery (SFA) lesions (lesion length, 51.3±40.3 mm; 34% moderate to severe calcification). The trial enrolled 50 patients in four German centres between November 2016 and May 2017. Patients enrolled were symptomatic with de novo or restenotic lesions with ≥70% diameter stenosis or occlusion.
Clinical improvements were seen in Rutherford classification, ABI, and walking impairment at six months and were further improved to 12 months and maintained to 24 months. This initial first-in-human trial demonstrates that SELUTION SLR is a viable option to treat lesions in the SFA. It is the first demonstration of a sirolimus safety and efficacy in peripheral intervention.
The SELUTION SLR (MedAlliance) is based on microreservoir balloon coating technology, which provides controlled and sustained sirolimus release with a therapeutic effect for over 60 days. The cell adherent technology is a proprietary amphiphatic lipid technology that binds microreservoirs to the balloon surface, and it contains and protects microreservoirs during insertion and inflation. Also, it facilitates higher drug transfer efficiency, allowing for low drug dose (1 µg/mm2) on the balloon surface, and maximises the drug bioavailability.
Medtronic today announced four-year data from the IN.PACT Global study, which reinforce the long-term durability and safety of the IN.PACT Admiral drug-coated balloon (DCB) in patients with peripheral artery disease (PAD) in the superficial femoral (SFA) and popliteal arteries. The data were presented this morning in the late-breaking clinical trial session at the Vascular Interventional Advances (VIVA) 2019 conference in Las Vegas, USA (4–7 November).
Thomas Zeller, director of the Department of Angiology at Universitaets-Herzzentrum, Freiburg-Bad Krozingen, Germany, presented the new, four-year results from the full clinical cohort of the IN.PACT Global Study. The results are the first four-year, real-world, fully adjudicated DCB data to be presented in a scientific congress. IN.PACT Admiral DCB demonstrated durable effectiveness and a strong safety profile in a real-world population.
“The IN.PACT Global study is the largest independently adjudicated real-world evaluation of any peripheral intervention undertaken and includes patients with the most complex lesions observed in any existing DCB clinical study, many of whom have commonly known risk factors for progressive PAD,” said Zeller. “Even in this real-world patient population, including those with critical limb ischemia, we continue to see durable treatment effect through four years. These data further demonstrate the clinical benefit of IN.PACT Admiral DCB and its ability to be a first-line therapy for patients with challenging lesions.”
Kaplan-Meier estimates demonstrated a freedom from clinically-driven target lesion revascularization (CD-TLR) rate of 73.4% (n=1,406) in a large, real-world patient population through 4-years. Of the subjects enrolled, the mean lesion length was 12.09 ± 9.54 cm, 18.0% had in-stent restenosis, 35.5% had occluded lesions, 39.9% had diabetes, and 68.7% had calcified lesions. Overall, the average time to first CD-TLRs in this complex patient population was approximately 570 days.
Based on Kaplan-Meier estimate, IN.PACT Admiral demonstrated a solid safety profile through four years with a low major target limb amputation cumulative incidence of 1.1% through four years. The freedom from all-cause death through four years was 83.5%, which is comparable to what would be expected in this patient population.1 This rate is based on data from all subjects enrolled in the IN.PACT Global study, among which 98% had known vital status.
Furthermore, an additional analysis was conducted to evaluate the performance of IN.PACT Admiral through four years in patients with intermittent claudication and critical limb ischemia (CLI) based on Rutherford Classification (RCC). The Kaplan-Meier estimated freedom from CD-TLR was 74.5% (n=1,246) in the intermittent claudication (RCC 2/3) patient cohort and 64.8% (n=156) in the CLI (RCC 4/5) patient cohort respectively.
“The body of evidence on paclitaxel-coated devices continues to mature with recent significant publications and presentations, including the IN.PACT Global four year data, adding to the totality of evidence generated,” said Mark Pacyna, vice president and general manager of the Peripheral Vascular business, which is part of the Cardiac and Vascular Group at Medtronic. “Outcomes from the IN.PACT Global study specifically show that IN.PACT Admiral DCB, which has now been used to treat approximately 500,000 patients worldwide, can prolong the time between reinterventions in a very challenging patient population by over a year and a half. Long-term and real-world data continue to demonstrate both the safety of these devices and the overall treatment benefit to the patient.”
In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services that deliver clinical and economic value to healthcare consumers and providers around the world.
Boston Scientific today announced positive data for two devices within the peripheral drug-eluting product portfolio during separate late-breaking clinical trial presentations at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas, USA (4–7 November).
Data presented included a 12-month interim analysis from the RANGER II SFA trial of the Ranger drug-coated balloon (DCB) as well as 24-month results from the IMPERIAL trial of the Eluvia drug-eluting vascular stent (DES), which exhibited the highest 24-month primary patency reported to date for the treatment of femoropopliteal disease in a US pivotal trial with a DCB or DES.1
The RANGER II SFA study evaluated the safety and effectiveness of the Ranger DCB, which has a low drug dose density of paclitaxel, versus standard percutaneous transluminal angioplasty (PTA) for the treatment of patients with peripheral artery disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal artery (PPA).
In the trial, the Ranger DCB exhibited a primary patency rate—a measure of the target vessel remaining unobstructed at 12 months—of 89.2% compared to 72.9% percent in patients treated with standard PTA (p=0.0022), by Kaplan Meier estimate. Additional key findings from the trial include:
“These excellent clinical data coupled with the ease of deliverability of the Ranger DCB are reassuring for physicians as we evaluate the most appropriate therapies based on individual patient needs,” said Ravish Sachar, University of North Carolina Rex Hospital physician-in-chief for Heart and Vascular services and principal investigator of the RANGER II SFA trial. “The high primary patency rate as well as the significantly lower TLR rate, which reduces the need for repeat procedures, are very encouraging.”
Also presented at the meeting was a 24-month analysis of data from the IMPERIAL trial, which evaluated the Eluvia stent versus the Zilver PTX drug-eluting peripheral stent for the treatment of patients with symptomatic PAD that had SFA and PPA lesions up to 140mm in length. The Eluvia stent utilises a drug-polymer combination and offers controlled delivery and sustained release of the lowest dose of paclitaxel of any peripheral drug-eluting device. In the study, the Eluvia stent exhibited a primary patency rate of 83.0% versus 77.1% with Zilver PTX, by Kaplan Meier estimate, the highest 24-month primary patency reported to date for the treatment of femoropopliteal disease in a US pivotal trial with a DCB or DES.1 The analysis also confirmed:
“We are very pleased with the safety and efficacy demonstrated by the Ranger DCB and the Eluvia stent, both of which showed exceptional durability while preventing repeat TLRs in 66% and 40% of treated patients, respectively,” said Ian Meredith, executive vice president and global chief medical officer, Boston Scientific. “The excellent outcomes presented today underscore our commitment to physicians and their patients with PAD. We continue to drive innovation in the drug-eluting vascular space and these results add to the growing body of evidence supporting our therapy options for the treatment of this challenging disease.”
The RANGER DCB gained CE Mark in 2014 and the company submitted for US Food and Drug Administration approval of the device earlier this year. The combination of the RANGER DCB as well as the Eluvia stent positions Boston Scientific as the only company to have both a DES and a DCB for the treatment of PAD in their portfolio.
In the USA, the Ranger DCB is an investigational device and is not available for sale.
References
Findings from the REVEAL study confirm a favourable safety and effectiveness profile through six months for the Revolution peripheral atherectomy system from Rex Medical. The results were presented today at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas (4–7 November).
The Revolution rotational atherectomy system incorporates continuous aspiration and has a dual indication for atherectomy and thrombectomy. The device is intended for atherectomy of the peripheral vasculature in patients with obstructive atherosclerotic disease both above and below the knee. No capital equipment is required. The spheroid-shaped burr rotates at 140,000 rpm to ablate plaque, which is aspirated into the catheter.
The primary objective of the REVEAL trial was to evaluate the safety and effectiveness of the Revolution peripheral atherectomy system in patients with symptomatic infrainguinal lower extremity arterial obstructive disease. One hundred twenty-one patients were enrolled at 17 US sites. Patients with Rutherford category 2 to 5 disease and lesions with ≥70% stenosis were eligible.
The primary safety endpoint was a composite of 30-day major adverse events, including all-cause mortality, clinically driven target lesion revascularisation, amputation, vessel perforation, and embolisation. The primary effectiveness endpoint was technical success, defined by core laboratory–assessed ≤ 50% diameter stenosis after treatment prior to adjunctive therapy.
The 30-day primary safety and effectiveness endpoints were met, with freedom from 30-day major adverse events in 110 of 113 (97.3%) intention-to-treat patients at 30 days (both distal embolisations were clinical events committee–adjudicated as nondevice-related) and technical success in 111 of 123 (90.2%) target lesions.
Excluding lesions that were treated with a burr not appropriately sized for the vessel diameter from the data set in which the postatherectomy stenosis was > 50%, the technical success rate was 95.7% (111 of 116 patients) (nonimputed). The procedural success rate was 93.7% (119 of 127 patients). The 6-month outcomes were also favourable.
One-year results of the MIMICS-3D study were announced today at the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA). Freedom from clinically-driven target lesion revascularisation (CD-TLR) was 89%, which aligns with results from the MIMICS RCT and MIMICS-2 studies, despite treatment of more complex disease.
In addition, the percentage of patients with improvement of ≥1 Rutherford category at one year compared to baseline was 87% (322/370), and for patients treated with or without a drug-coated balloon and BioMimics 3D, there was no difference in CD-TLR (89.5% and 88.5%, respectively; P>0.88).
BioMimics 3D (Veryan Medical) is a nitinol stent designed to provide optimal radial support, flexibility, durability, visualisation, and delivery accuracy for femoropopliteal intervention. The addition of a unique three-dimensional (3D) helical centreline provides the advantages of biomechanical stability and swirling blood flow.
BioMimics 3D was evaluated in the MIMICS randomised controlled trial (RCT) in which patients received either a BioMimics 3D helical stent or a straight stent control. The Kaplan-Meier estimate of freedom from clinically driven target lesion revascularisation (CD-TLR) at 1 year for those treated with BioMimics 3D was 91%. A second study, MIMICS-2, conducted in the USA, Japan, and Europe, met 30-day safety and 12-month primary patency endpoints, and the 1-year Kaplan-Meier estimate of freedom from CD-TLR was 88%.
The MIMICS-3D European registry is now investigating outcomes in patients with longer, more complex lesions; complementary use with drug-coated balloons occurred in 50% of procedures. MIMICS-3D enrolled 507 patients at 23 sites. The primary safety endpoint is a composite of major adverse events (MAEs) or CD-TLR through 30 days. The primary outcome measure for effectiveness is freedom from CD-TLR through 12 months. An independent clinical events committee adjudicated MAEs.
Today at the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA), Thomas Zeller (Bad Krozingen, Germany) gave an update on the DEEPER OUS trial. He concluded that the Temporary Spur stent system (Reflow Medical) appears to be a feasible and safe method for the treatment of disease in the infrapopliteal arteries.
This trial is a prospective, multicentere nonrandomised, single-arm study. Trial enrolment began in July 2019 and is presently ongoing, with anticipated completion in 2020. The study will consist of 100 patients in New Zealand, Germany, and Switzerland.
The purpose of the DEEPER OUS study is to evaluate the safety and efficacy of a novel device, the Temporary Spur stent system in conjunction with a commercially available drug-coated balloon. An angiographic substudy examining recoil will be conducted on the first 10 patients from each site.
Examination of patency rates and long-term safety data is ongoing in the DEEPER OUS trial.
It was announced today at the 2019 Vascular Interventional Advances conference (VIVA) (4–7 November, Las Vegas, USA) that, through six months, TOBA II BTK met all endpoints in a 100% dissected vessel population.
This prospective, multicentre, single-arm global pivotal study was designed to investigate the safety and effectiveness of the Tack endovascular system (Intact Vascular) to repair dissections in below-the-knee (BTK) arteries. Primary safety and efficacy endpoints were analysed at six months and compared with performance goals derived from the critical limb ischemia (CLI) literature.
It was concluded that high rates of dissection resolution, wound improvement, and freedom from clinically-driven target lesion revascularisation (CD-TLR) support the Tack system as an ideal adjunct to PTA and potentially as the first permanent vascular implant to improve results of infrapopliteal angioplasty.
In more detail, TOBA II BTK met both primary endpoints (p<0.0001) of safety (30-day major adverse limb event or perioperative death) and efficacy (six-month major adverse limb event or 30-day perioperative death). All (100%) dissections were resolved following Tack implantation, with 92.0% 6-month Kaplan-Meier freedom from CD-TLR, 87.3% 6-month Kaplan-Meier target lesion patency, and 95.7% 6-month Kaplan-Meier amputation-free survival. Wounds were healed or improved in 73.8% and Rutherford category was ≤3 at six months in 74% of CLI patients.
TOBA II BTK is the first investigational device exemption clinical trial approved to investigate safety and effectiveness of a permanent implant to repair dissections in BTK arteries. The study evaluated the Tack system 233 patients who had ≥1 dissection requiring repair after PTA in the mid/distal popliteal, tibial, and/peroneal arteries. There were 918 Tacks implanted from the mid popliteal to 1 cm above the tibiotalar joint, with 122 placed in the distal third of the vessels.
The Tack system has four preloaded self-expanding nitinol implants on a single catheter. Each implant is 6mm long and self sizes to vessels ranging from 1.5 to 4.5mm in diameter, using sufficient radial force to appose dissected tissue against the vessel wall.
Ramon Varcoe today announced positive five-year results of the ABSORB BTK trial at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas, USA (4–7 November). Primary patency of the Absorb bioresorbable vascular scaffold (BVS) from Abbott achieved a 72.9% primary patency rate and 90.7% freedom from clinically-driven target lesion revascularisation (CD-TLR).
The ABSORB BTK trial is a prospective, nonrandomised, single-centre study designed to evaluate the novel bioresorbable, drug-eluting Absorb scaffold used for the treatment of peripheral artery disease below the knee. There were 71 scaffolds utilised in 55 limbs of 48 patients who fulfilled the inclusion criteria (72.7% with critical limb ischemia). Most scaffolds were implanted in arteries of the proximal half of the calf, and the mean lesion length was 20.1 mm (range, 5–50 mm). There was 100% procedural and technical success.
Over the 5-year follow-up period, 38% of patients had died, all from causes unrelated to the procedure or study device; 95% of patients had sustained clinical improvement. Complete wound healing occurred in 90% of those treated for tissue loss, with no major amputations and a limb salvage rate of 100%. No late or very late scaffold thromboses were observed.
This novel bioresorbable, drug-eluting scaffold has several inherent advantages over stents, related to its biological resorption. These results represent best-in-class durability for a stent-like device in this challenging vascular territory.
LimFlow SA today announced the presentation of positive six-month data from the full patient cohort in its PROMISE I early feasibility study of the LimFlow percutaneous deep vein arterialisation system. Results were presented on the podium at the 2019 Vascular InterVentional Advances conference (VIVA; 4–7 November, Las Vegas, USA) by Daniel Clair, PROMISE II principal investigator and chair of the department of surgery at the University of South Carolina (USC) and Palmetto Health-USC Medical Group.
“Findings from this early feasibility trial are very promising,” said Clair. “They show that the LimFlow system is a novel, safe and reproducible approach for improving wound healing and reducing amputation rates in a patient population for whom amputation would otherwise be considered inevitable. It is very encouraging to be able to offer hope to patients that cannot be treated with any current technology today.”
PROMISE I is a multicentre, prospective, single-arm study conducted at seven US centres encompassing 32 end-stage—or “no option”—CLTI patients, 100% of whom had non-healing wounds on the target foot, 69% of whom had diabetes, and 34% of whom had renal insufficiency.
At six months, the LimFlow system achieved an amputation-free survival rate of 74%. A strong trend of successful wound healing was also demonstrated, with 67% of wounds classified as healed or healing at six months and 100 percent healed or healing at nine months. Technical success was 97%.
When all other therapeutic options have been exhausted and a CLTI patient is facing major amputation, the minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated blood back into the foot via the veins. For many patients, restoring perfusion in the lower limbs resolves chronic pain, improves quality of life, enables wound healing and prevents major amputation.
“We are enthusiastic about the exceptional results for the LimFlow System,” said LimFlow CEO Dan Rose. “Our goal with the technology is to fully heal previously non-healing wounds and save more patients from amputation, improving their quality of life and preventing the downward spiral that comes from losing a limb. With the recent FDA approval of our pivotal trial, we look forward to shortly commencing enrolment in the USA and continuing to build evidence for the therapy.”
CLTI is the most severe form of PAD and often occurs in patients suffering from coronary artery disease, diabetes, obesity, high cholesterol and high blood pressure. Patients with CLTI often experience profound, chronic pain and develop festering wounds or infections that lead to major limb amputation, an event closely associated with increased mortality and reduced quality of life. To relieve the symptoms of CLTI, patients today are treated primarily with angioplasty or open bypass surgery. In many late-stage patients, however, neither option is feasible due to extensive disease in the target arteries or other anatomical constraints.
It was announced today that results of the TANGO low-dose cohort compared to controls are positive, both for primary and secondary endpoints. These latest findings were presented by Ehrin Armstrong at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas, USA (4–7 November). According to Armstrong, perivascular temsirolimus is being developed as a “viable alternative” to prevent restenosis after below-the-knee (BTK) peripheral artery interventions, and TANGO high-dose data is “forthcoming”.
The TANGO trial is a phase II, dose escalation, double-blinded trial comparing the delivery of temsirolimus to saline control in patients with severe claudication or critical limb ischaemia. This is the first US trial to investigate a sirolimus analogue to improve the durability of peripheral revascularisation procedures. Armstrong commented that the present results warrant a move to Phase III trials.
The purpose of the trial is to limit neointimal hyperplastic tissue growth into the artery after endovascular BTK revascularisation procedures, where paclitaxel-coated balloons have had limited success.
Results are now available comparing Bullfrog micro-infusion device (Mercator MedSystems) delivery of either low-dose temsirolimus treatment (0.1mg/mL; n=20) or saline control (n=20) into the perivascular tissue around lesions subsequent to revascularisation. Patients (Rutherford category 3–5) with up to 30cm-long BTK lesions were enrolled in the study.
The primary safety endpoint was 30-day freedom from major adverse limb event or postoperative death, and no events were observed. The primary efficacy endpoint was improvement in 6-month transverse view vessel area loss, an angiographic measure that uses the opacified area of the lesion to approximate the neointimal volume.
At six months, excluding subjects with unstented severe dissections in their target lesion, transverse view vessel area loss improved to 19% in treatment subjects compared to 38% in controls. With respect to secondary endpoints, six-month freedom from target lesion failure was reported in 58% (11/19) of treatment subjects compared to 42% (8/19) of controls, favouring treatment by a relative 38%. In patients with total occlusions at baseline, 78% (7/9) of treatment subjects and 25% (2/8) of control subjects were free from reocclusion at 6 months.
In treatment subjects with wounds upon enrolment or who developed wounds on their target limb during the study, 71% (5/7) of treatment subjects had full healing of wounds by 12 months without the need for clinically driven target lesion revascularisation, whereas 44% (4/9) of control subjects had wound healing without prior clinically driven target lesion revascularisation.
Low-frequency, high-intensity ultrasound energy delivery followed by percutaneous transluminal angioplasty (PTA) may improve clinical outcomes in below-the-knee (BTK) lesions without the need for a drug-eluting device, but a larger randomised study is needed to confirm these results. This was the main conclusion presented by Costantino Del Giudice during the ULYSSE registry late-breaking trial presentation at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas (4–7 November).
The ULYSSE registry is a retrospective, nonrandomised, single-centre study evaluating the safety and the efficacy of ultrasoundplasty before angioplasty to treat below-the-knee (BTK) lesions in 22 critical limb ischemia (CLI) patients (35 BTK lesions). All patients were Rutherford category 4 to 6 and had moderate-severe calcification. Ultrasoundplasty was performed using the Kapani catheter (Apani Corporation), which delivers a local, low-frequency, high-intensity ultrasound energy to the lesion.
The objective of the study was to demonstrate that locally delivered ultrasound energy may modify plaque structure using microcavitational effects and change plaque compliance without risk of vessel dissection and rupture. Modifications of plaque structure may potentially improve the outcome of a simple balloon angioplasty.
The primary safety outcomes were the major adverse events at 30 days, recurrence of CLI, and surgical or endovascular revascularization at 6 months. The primary efficacy endpoint was angiographic restenosis and target lesion revascularisation at six months. Immediate outcomes showed good results, with 100% technical success and no major adverse events. At six-month angiographic control, primary patency was 97.1%, with 100% ulcer healing and no target lesion revascularisation and no CLI recurrence. At 24 months, freedom from restenosis was 91.4% as evaluated by Doppler ultrasound control, with no target lesion revascularisation and no CLI recurrence. No major adverse events were reported.
Penumbra today announced that the EXTRACT-PE trial successfully met the primary endpoints, demonstrating the safety and efficacy of the Indigo Aspiration system for aspiration mechanical thrombectomy in patients with acute pulmonary embolism (PE). The data were presented in a late-breaking clinical trial session today at the 2019 Vascular Interventional Advances conference (VIVA) in Las Vegas, USA (4–7 November).
“The positive results of the EXTRACT-PE trial, the first prospective safety and efficacy study of the Indigo Aspiration System, are a step forward in building needed clinical evidence around catheter-based embolectomy in patients with acute pulmonary embolism,” said Akhilesh Sista, EXTRACT-PE national principal investigator, chief of Vascular and Interventional Radiology at NYU-Langone School of Medicine, and vice chair of the recently published Interventional Therapies for Acute Pulmonary Embolism guidelines from the American Heart Association. “New AHA guidelines state that catheter-based embolectomy may have an important role in severe PE, but that more study is needed. EXTRACT-PE is an important first step in determining how and when we should employ promising and innovative catheter-based technologies such as the Indigo aspiration device.”
EXTRACT-PE was a prospective, single-arm, multicentre trial conducted under an Investigational Device Exemption (IDE) from the US Food and Drug Administration (FDA) that evaluated the safety and efficacy of the Indigo Aspiration System in the treatment of acute pulmonary embolism (ClinicalTrials.gov Identifier NCT03218566). The study enrolled 119 participants across 22 US study centres. The primary efficacy endpoint was met with a significant mean reduction in right ventricular (RV)/left ventricular (LV) ratio of 0.43, corresponding to a 27.3% reduction, at 48 hours after intervention. The primary safety endpoint was reached with a low major adverse event composite rate of 1.7% within 48 hours. The major adverse event composite included device-related death, major bleeding, and device-related serious adverse events as measured by the clinical events committee. Additional data reported included median time of Indigo System usage (37 minutes) and median ICU stay (one day). No thrombolytic drugs were used in 98.3% of patients.
“From a pulmonologist’s perspective, the results of the EXTRACT-PE trial are another important dataset that help broaden the mechanical treatment options for patients with pulmonary embolism,” said Victor F Tapson, pulmonary critical care specialist at Cedars-Sinai Medical Center in Los Angeles and EXTRACT-PE steering committee member. “The safety profile of the Indigo System and the low rate of bleeding events, combined with the significant reduction in RV/LV ratio seen in the EXTRACT-PE trial, can positively impact the emerging field of acute pulmonary embolism intervention.”
“The Indigo Aspiration System has demonstrated tremendous potential to address patients with clot in other parts of the body, and today’s data show its specific potential in the pulmonary arteries,” said Adam Elsesser, chairman and chief executive officer of Penumbra. “Pulmonary embolism is a deadly disease where we see an unmet clinical need and patient opportunity, and we commend the dedication of physicians who are focused on addressing this area. We are excited about the excellent results of this trial and look forward to working together with physicians in the field to bring better treatment options to patients.”
At this year’s Vascular Interventional Advances (VIVA) conference (4–7 November, Las Vegas, USA), Michael D Dake presented data on Zilver PTX that supports the device’s benefits across different patient groups.
Dake presented the latest data regarding Zilver PTX, Cook Medical’s paclitaxel-coated stent that is used to treat peripheral arterial disease (PAD). His presentation focused on findings that Zilver PTX shows benefits for a variety of patients.
“Our ultimate goal is to help patients suffering from PAD. That is why these data are so important—behind each one of these data points is a real person. As we continue this discussion on paclitaxel-coated devices, we will keep providing as much information on Zilver PTX as we can so that patients and physicians can make the best decisions,” said Mark Breedlove, vice president of Cook Medical’s Vascular division.
In Cook Medical’s ongoing review of data relating to the Zilver PTX peripheral arterial stent, patient-level data for Zilver PTX were evaluated to determine if there was an increased mortality risk due to paclitaxel and the impact of risk factors on outcomes. Data presented at VIVA was collected from a five-year randomised controlled trial. In the trial, patients with PAD were initially randomised to be treated with either Zilver PTX or angioplasty. When the data were analysed, it was discovered that patients assigned to the Zilver PTX group had more risk factors than the control group, despite the trial’s randomisation of patient assignment.
The trial had a study design that allowed for patient crossover to treatment with Zilver PTX within the first year. Taking actual treatment into account, analyses of the complete 5-year data for Zilver PTX show no increase in long-term mortality for the paclitaxel-eluting stent. When evaluating potential risk factors for freedom from target lesion revascularisation (TLR), data continue to support the benefit of Zilver PTX across a variety of patient risk factor groups.
When considering treatment options for PAD, the FDA recommends that physicians discuss both risk and benefit possibilities with their patients.
The first patient has been enrolled in the TORUS 2 multicentre, clinical trial, evaluating the use of the self-expanding Torus stent graft system (PQ Bypass), a novel technology designed for the treatment of peripheral arterial disease (PAD) in the superficial femoral artery. This inaugural enrollment comes less than a month after the study received unconditional approval from the US Food and Drug Administration (FDA) for the TORUS 2 original investigative device exemption (IDE).
The TORUS 2 study (The PQ Bypass pivOtal IDE intra-aRterial stent graft study for occlUsive and re-Stenotic fem-pop revascularization) is a prospective, single-arm trial of 188 patients at up to 40 sites. The study is led by national co-principal investigators Peter Schneider (Division of Vascular and Endovascular Surgery, University of California San Francisco, USA) and Ehrin Armstrong (director of Interventional Cardiology, Rocky Mountain Regional VA Hospital; University of Colorado School of Medicine, Aurora, USA).
The objective of the trial is to evaluate the safety and effectiveness of the Torus stent graft system in the treatment of obstructive atherosclerotic lesions of the superficial femoral and/or proximal popliteal arteries. The Torus stent graft system received CE mark in 2017 for use in the DETOUR percutaneous femoropopliteal bypass procedure, based on the DETOUR 1 global study. The technology has also been evaluated in the TORUS 1 study in Europe and is currently under evaluation in the DETOUR 2 IDE for percutaneous femoropopliteal bypass in the USA and Europe.
“There is an unmet need in our care of PAD patients for an updated, optimised, and specifically designed stent graft for SFA-popliteal use,” Schneider says. “I believe this technology could become an important part of our endovascular armamentarium.”
Armstrong adds, “This study is intended to further the growing body of evidence for the TORUS stent graft. I am pleased to be involved in such an important step forward in the percutaneous treatment of PAD.”
Vaqar Ali, vice president and catheter lab director at First Coast Cardiovascular Institute in Jacksonville, USA, enrolled and treated the trial’s first patient.
“Our patient had a challenging SFA lesion that was treated thanks to the radial strength and flexibility afforded by the robust design of the TORUS stent graft,” Ali says. “We are thrilled to be the first site to enrol in this important trial and to be part of bringing this technology forward as a potential option for our patients.”
PQ Bypass general manager Heather Simonsen called the enrollment of the first patient “a significant milestone for PQ Bypass as we initiate our second pivotal IDE evaluating our unique technology in two different applications for patients with PAD. We are thrilled to commence TORUS 2, continue enrollment in DETOUR 2, and look forward to working with our investigators to execute two efficient and rigorous pivotal trials.”
The first preclinical study of a novel embolization agent, GPX, reports its successful performance in a rabbit aneurysm model. High rates of complete angiographic occlusion were achieved and maintained, said Ruben Mühl-Benninghaus (Saarland University Hospital, Homburg, Germany), presenting these “promising” results at the 2019 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (7–11 September, Barcelona, Spain).
In recent years, liquid embolic agents have emerged for endovascular treatment of cerebral aneurysm. “There are multiple liquid embolics available right now”, Mühl-Benninghaus said, before describing the properties of the ideal embolic agent: “It should have good control and precision during embolic injection, it should not adhere to any adhesion or clumping within the catheter, and the penetration of the liquid embolic agent should always target the distal vessel, which is the aim of the occlusion. Ease of use is also very important, [to] minimise the preparation steps and minimise complications during preparation. Of course, no fragmentation and no reflux should be achieved in the optimal liquid agent.”
Introducing the CIRSE audience to GPX, he described it as a polymer in a hypersaline solution, which solidifies upon injection into the blood vessel in response to a decreased sodium chloride concentration. The agent is prepackaged in a single, standard syringe and comes with an empty syringe. The interventionalist connects the two syringes and needs to mix them 25 times before the agent is ready to use. “Due to its waterborne composition, no specialised catheters are needed and no DMSO [dimethyl sulfoxide] and no vortexing prior to the procedure is required”, Mühl-Benninghaus explained.
In the present, pre-clinical study, the investigators set out to assess the in vivo performance of the GPX in a rabbit model.
To this end, elastase-induced aneurysms were created in 10 New Zealand white rabbits. Each aneurysm was embolized with low viscosity GPX using an Echelon 10 microcatheter (Medtronic) with balloon assistance. The mean aneurysm neck diameter, width, and height were 3.6±1mm, 3±0.8mm, and 7.4±1.4mm, respectively. The mean dome-to-neck ratio was 0.9±0.2.
Ninety per cent of aneurysms (nine of 10) showed complete stagnation of intra-aneurysmal flow within 30 minutes of device deployment. One aneurysm showed moderately diminished intra-aneurysmal flow within 30 minutes due to distal migration of GPX that still was connected to intra-aneurysmal embolic. This was assessed via digital subtraction angiography (DSA), performed predeployment, as well as five, 10, and 30 minutes post-deployment.
DSA was also performed one month after the procedure in the eight surviving rabbits (two of the study animals did not survive to one-month post-procedure). All eight aneurysms were completely occluded.
“We did not see microscopically any fragmentation of GPX, and we did not see any adhesion to the catheter or the balloon”, Mühl-Benninghaus noted. “We did observe some resistance during injection from the new embolic agent through the Echelon 10 microcatheter. Our impression was that there was a little varying visibility of GPX.”
“Upon gross examination at 28-days, tissue appeared normal”, he reported. Histological examination of the vessel wall, however, did reveal “evidence of some inflammation reaction”, but Mühl-Benninghaus said that he did “not have the final results”.
Compared to stent-assisted coil embolization in the same model, Mühl-Benninghaus said that the occlusion rates achieved with GPX were similar. “We have also performed previously in the same model the same thing with onyx, and we did see less fragmentation with GPX. We did not use any remodelling balloon due to the cost of balloons. The remodelling balloons could provide better stability of the microcatheter. For further investigations, this might be an option.”
When concluding, he outlined some limitations of the present study. Namely, the small study population, and the outstanding final histological results. He summarised that while GPX was easy to use and did not require DMSO, the agent’s viscosity needs improving, and although it has the potential to achieve durable occlusion of cerebral aneurysms, its clinical relevance will have to be assessed in larger and longer-term studies.
“It looks to us to be a promising embolic agent for neuro-intervention therapy,” he stated. embolization embolization
The first-in-human robotic-assisted neurovascular intervention has been performed at the Toronto Western Hospital (Toronto, Canada), by a team led by Vitor Mendes Pereira. A press release states that this “landmark” robotic-assisted stent-assisted aneurysm coiling case marks a “significant milestone” in interventional medicine as the first step in building a new treatment paradigm for patients suffering from neurovascular disease. The technology used for the procedure, the CorPath GRX system, has been developed by Corindus, which has recently been acquired by Siemens Healthineers.
Before the procedure commenced on 1 November this month, Pereira performed a rehearsal procedure on a Biomodex three-dimensional (3D)–printed flow model of the specific anatomy of the patient, a 64-year-old female Canadian resident. According to the press release, using the 3D model allowed Pereira to develop a plan for the novel robotic procedure and ensure an optimal treatment approach.
During the procedure itself, Timo Krings and Patrick Nicholson, neuroradiologists, provided bedside physician support while Nicole Cancelliere, medical radiation technologist, acted as the bedside robotic technician.
“Precision is a key element of neurovascular interventions, and it is evident to me that augmenting these delicate procedures with robotic assistance can positively impact how we treat patients,” Pereira commented in the company’s announcement. “I felt honoured to perform this procedure and look forward to continuing to support the development of robotic technology to help address access issues of stroke patients in the community.”
Mark Toland, CEO of Corindus, added: “The field of neurovascular intervention is changing rapidly, but there remains a significant need to expand access to care and reduce treatment times.” He further put forward that implementing robotic capability for neurovascular intervention is the first step toward the company’s vision of providing patients access to the world’s best specialists, regardless of their geographic location. “Building a body of clinical research on neurovascular robotics while training physicians to be robotics experts today will allow us to maximise physician impact and reach with remote telerobotics tomorrow,” said Toland.
Kyaw Zay Ya caught up with Interventional News at the 2019 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain) to discuss the opportunities and challenges Myanmar faces in developing its interventional radiology (IR) offering.
My country is still developing, so IR in Myanmar is in the very initial phase. For me, I wanted to become an interventional radiologist after my radiology residency. In 2002, I had the chance to apply for fellowship training in Singapore General Hospital (SGH) with Bien Tan Soo—he is my mentor. He helped me a lot, not only to get the training, but also to get continuing interventional activities in Myanmar.
We interventional radiologists need to use so many advanced technologies and equipment, especially consumables—catheters, wires—that were very difficult to get at that time [early 2000s]. Anyhow, I requested that my colleagues at SGH get me some of the instruments and materials, and I tried to develop the interventional procedures in my country. At the same time, I tried to get the younger generation to get similar training like me in Singapore. I try to go to every conference in Singapore and took some of the consumables from SGH. From 2008, I got a chance to get the younger generation, my junior colleagues, training at SGH. One or two radiologists get that chance at SGH each year. Today, I have around 15 to 20 junior colleagues who perform interventional procedures in Myanmar.
SGH is very suitable for us. The case load and the instruments available make it the perfect place to train. When I first went in 2002, there were five interventional suites; nowadays, there are about 10 interventional suites in the department, and each and every day, there are at least 15 to 30 cases—on some days, there are 40 cases. Over a training period of one year, therefore, my colleagues can gain a lot of experience.
Primarily, we assist the interventional radiologists at SGH with their procedures. Later, when we [the trainees from Myanmar] are reliable, they give us the chance to do the procedures ourselves, under supervision. If there is a complication, they would come in and help, so it is very good training.
At the same time, Tan Soo and some of the other consultants at SGH not only help us with training and materials, but they also give us the chance to attend international conferences like CIRSE.
Due to being a member country, we have gained more international exposure. Every year, in January, we have an IR workshop in our country. It is an APSCVIR outreach programme, in collaboration with the Myanmar Radiology Society, in which there is a vascular and interventional radiology section. I am president of this section.
Due to these workshops, the interests of our clinicians and radiologists in IR has become bigger and has spread across the country. Next year, CIRSE president Afshin Gangi and Society of Interventional Radiology (SIR) president Laura Findeiss will come and teach, and help us to improve the status of IR.
This collaboration has led to my attendance at CIRSE this year. This is a great opportunity for me to meet with industry and to discuss access to consumables in Myanmar. My aim at these conferences is to get international contacts, and for my junior colleagues to receive training.
Our country is now open—politically, socially, and economically. IR is very quickly developing and, to ensure quality of care for our patients, we need international support. Because of the population of our country [54 million people], there is a lot of potential to develop a great IR specialty, but we still need some human resources and consumables.
I would like to invite interventional radiologists across the world to come to my country and help us in any way, through training or instrument support. I hope I can improve the status of IR in Myanmar; within the next five years, it will become an international standard [of IR care]. We must dedicate our time and efforts to improving this valuable specialty.
Collaboration, academic support, and hands-on training provided by the Singapore General Hospital, Singapore, have driven the small interventional radiology (IR) community of Myanmar to the international stage. As one of the organising members of the Asia-Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR), the group of interventional radiologists in Myanmar have been working more closely with members of the Society of Interventional Radiology (SIR) and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) to promote the specialty locally. Despite huge strides over the last decade in the number and complexity of IR cases being undertaken in the country, Myanmar faces several challenges, which Kyaw Zay Ya (an interventional radiologist based in Nyaung, Myanmar; full interview from CIRSE 2019 here) summarised as the “three Ms: man, money, and materials”.
Due to a cancelled flight, Bien Soo Tan (Singapore General Hospital, Singapore) addressed delegates on behalf of Ya, speaking at the 2019 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).
Myanmar is a large country in South East Asia with a population of 54 million, and a land area of 676,575km2. In the late 1970s and early 1980s, a conventional angiography system with serial changer was installed for diagnostic purposes in Yangon General Hospital (Yangon, Myanmar). By the end of the 1980s, digital subtraction angiography (DSA) was possible in the country, and some vascular and non-vascular interventional radiology (IR) procedures were performed in the early 1990s, though there was no proper training for interventionalists.
“At that time,” Tan said, “there were several very senior radiologists in Myanmar who were trained in Europe, in particular the UK, and when they went back [to Myanmar], they did introduce some of these procedures, […] primarily angiography and even chemoembolization.”
Following this informal introduction of IR to the country, Tan’s own institution, the Singapore General Hospital, provided IR training to radiologists in Myanmar. This paved the way for the first two Myanmarese interventional radiologists to gradually start working in their home country in the early 2000s, with “very limited consumables available to them”.
Since then, IR has grown steadily in Myanmar. From 2008, interventional radiologists at Singapore General Hospital have trained one or two candidates, and have provided some of the required consumables. These are often consumables in Singapore which are close to expiry, as Tan explained: “They are not freely available; the distributors are not really bringing in these consumables, because there is not much volume in Myanmar itself.”
Today, Myanmar is one of the organising members of APSCVIR, and Tan told delegates that, increasingly, Myanmar is in contact with SIR, based in the USA, and CIRSE, in Europe. Indeed, earlier in the session, APSCVIR president Andrew Holden (Auckland, New Zealand) had praised the “very active outreach programme” in Myanmar; when CIRSE president, Robert Morgan (London, UK) visited the country in January 2019 to take part in said programme. Of this experience, he said: “I was struck firstly by how large Myanmar is as a country, and secondly by how beautiful it is as a country. The people are all very friendly, so I would certainly recommend anyone who wishes to go and visit to do so. I was impressed by the set-up in the hospitals there. I may have had pre-conceived ideas that things would be relatively primitive, but they were not, in fact; there were pretty good facilities in each of the hospitals I went to in Yangon and Mandalay. […] I think it was a very good venture for CIRSE to be involved in, and I am pleased that Afshin Gangi [CIRSE president since September 2019] will continue this in January next year.”
Speaking about convincing hospitals and governments to support the establishment and progression of IR, Tan commented: “For us [in Singapore], I think some of these arguments have been ongoing within our own institutions and national systems, but you can imagine that in Myanmar, the conversations are [at a] much earlier [stage], [as they] try to argue why IR should be supported.” On his presentation slide, Ya had outlined shorter hospital stays, money saving, reduction in transfusion requirements, better quality of life for patients, faster recovery times, and high intensity local treatments as convincing arguments supporting the development of an IR department.
“These advantages are all very clear to us”, Tan acknowledged to the CIRSE audience, while in Myanmar, he explained how the country’s interventional radiologists “have to start the conversation and lobby the hospital administrators, the ministry, to get more training, more equipment.”
Regaling the CIRSE audience with a personal anecdote, Tan shared: “I think one very telling story I have—I have visited Myanmar quite regularly for ten years now—when I went in 2009, they had an angiography unit installed in Yangon General Hospital that was quite new, I think it was two to three years old, but the tube had blown. So in 2009, there was no angiography available in Yangon General Hospital, which is the largest public hospital in the whole of Myanmar. When I went back over the next three to four years, they still had not got the money to buy the tube. Only about six or seven years later did they decide to junk the machine, and they got a new machine in. So these are the challenges that they are facing.”
Despite the difficulties with procurement, a “whole spectrum” of IR procedures are currently being conducted in Myanmar, tailored to the disease distribution seen in the country. There are six public centres and six private centres offering IR services. Between 2015 and 2019, in public centres across Myanmar, there have been, each year, on average: 612 transarterial chemoembolization (TACE) procedures (“one of the main treatments for inoperable HCC”, Tan told the audience, “they do not have the other modalities available, like Y90”), 721 guided biopsies, 67 percutaneous transhepatic biliary drainages (PTBD), 44 angioplasties, 21 intracranial arteriovenous malformations (AVM) treated, and three abdominal aortic aneurysms (AAA) stented. In the private sector, there is on average 352 TACE procedures, 35 guided biopsies, 23 PTBDs, and 18 angioplasties performed each year.
Remarking on the 21 intracranial AVMs treated in the public centre, Tan observed: “Very little neurointervention for such a huge population”.
These procedures have all been conducted by the small group of interventional radiologists working in the country. Modern-day Myanmar has 15 practicing interventional radiologists, trained at several institutions across Asia, including Singapore, Thailand, the Republic of Korea, Japan, and India. There are two senior radiologists in the country with interventional training who have retired from public practice, but still work in the private sector. Twenty Myanmarese trainees have received local training, and are preparing to move abroad to “gain more intense exposure”, in Tan’s words, to the discipline.
In addition to procurement difficulties and the low number of interventional radiologists, Myanmar faces other challenges in being able to offer IR services to its 54 million inhabitants. Access to adequate training stymies the discipline’s development. Furthermore, awareness of IR among interventionalists’ clinical colleagues is low, according to Tan, “and therefore the referral system is not robust.”
However, he then said that the healthcare system is starting to invest in IR. “They [the Myanmarese healthcare system] are now starting to be vendors and distributors, gaining interest, but unfortunately, a lot of the interest is focused on cardiology, because that is where the money comes in, and less on IR.”
Enumerating Ya’s aspirations for the development of IR in Myanmar, Tan listed the following:
XACT Robotics has just received clearance from the US Food and Drug Administration (FDA) to sell its first robotic system in the USA for use during computed tomography (CT)-guided percutaneous interventional procedures. XACT’s technology is the first hands-free robotic system combining image-based planning and navigation with insertion and steering of various instruments to a desired target across an array of clinical applications and indications.
“We are committed to redefining the way the entire medical community utilises robotics, beginning with interventional radiologists,” says Harel Gadot, founder, executive chair, and president of XACT Robotics. “Being the first to introduce a hands-free robotic system, we have the potential to provide significant clinical, technical and economic value while democratising interventional procedures. Our system’s small footprint and high mobility design will enable care providers to treat a broad range of patient care needs in various clinical sites of service.”
“The XACT Robotic system provides a unique platform to the interventional radiology community which can help improve the delivery and quality of care for the patients we serve,” comments Nahum S Goldberg, the principal investigator in a multi-site study using the system, which is still an investigational device in Israel, where XACT Robotics is based. Goldberg is the head of the Interventional Oncology Unit and director of the Applied Radiology Research Lab at Hadassah Hebrew University Medical Center, Jerusalem, Israel. “Based on our experience with this unique robotic technology, we can reach very small targets with unprecedented accuracy. Furthermore, this system holds much promise for enabling more efficient use of time and hospital resources.”
The XACT Robotic system is based on research originally conducted at the Technion—Israel Institute of Technology, by Moshe Shoham, founder of Mazor Robotics (acquired by Medtronic in 2018). The company plans to launch the system to select US radiology centres of excellence partners, and will debut its technology at the 2019 Radiological Society of North America conference (RSNA; 1–6 December, Chicago, USA).
A Philadelphia jury has awarded more than US$33 million to a woman who was injured as a result of a defectively designed inferior vena cava (IVC) filter. The trial was overseen by Philadelphia Judge Michael Erdos.
The litigation focused on allegations that the defendant, the company Rex Medical, failed to properly warn about the dangers of the filter devices, which were designed to prevent blood clots, but can allegedly migrate or fracture in patients’ bodies, causing perforations. The injuries, according to the accusers, put patients at risk for a host of medical problems, including gastrointestinal difficulties, kidney failure and death.
The trial result prompted Cook Medical to release a statement defending their IVC filter devices. Penned by Cynthia Kretz, vice president and general counsel for the company, this reads in full:
“Earlier today, a decision was made in Philadelphia against Rex Argon, an IVC filter device manufacturer.
“Cook Medical’s IVC filters are quality products that have saved thousands of lives and are critical to patient well-being. Our design and materials are different from the Rex Argon Option filter.
“To date, Cook Medical has had over 1,000 cases dismissed by the courts and we will continue to defend all of our IVC filters.
“IVC filters are an important option for physicians working to prevent the estimated 100,000 deaths associated with pulmonary embolism each year in the United States. Physicians and companies like Cook worked together to develop IVC filters to help patients and reduce the risk of these deadly pulmonary embolisms.
“Physicians choose to use IVC filters based on each patient’s medical needs. Every patient’s situation is different, and individual patient factors and risks must be considered when evaluating treatment options.
“We are dedicated to providing life-saving treatment options for patients.”
As of 16 September 2019, federal records showed more than 7,000 cases were pending against Cook Medical in Indiana federal court, and more than 8,600 were pending against Bard in Arizona federal court.
Cook won the first IVC filter trial in 2017, but it lost a US$1.2 million verdict in Texas state court in May 2018. Cook was also lost a US$3 million verdict in February. In March 2018, plaintiffs won a US$3.6 million verdict against Bard. That verdict included a US$2 million punitive damages award against Bard. The company, however, followed up in June 2018 with a defence win.
The first patient in the United Arab Emirates has been treated with the Stealth 360 peripheral orbital atherectomy system (Cardiovascular Systems), intended for the treatment of patients with peripheral and coronary artery disease.
The first peripheral patient in the Middle East was treated by Faisal Hasan at the Cleveland Clinic Abu Dhabi, UAE.
Hasan comments: “Cardiovascular System’s orbital atherectomy simultaneously removes calcified plaque within the vessel and modifies medial calcium. This dual mode of action helped restore blood flow and vessel motility in a very challenging peripheral patient. The ability of orbital atherectomy to safely treat calcified peripheral lesions, both above and below the knee, will allow me to serve an unmet need in the United Arab Emirates.”
Scott Ward, chair, president and chief executive officer of Cardiovascular Systems, says, “In the last year, we have successfully introduced our orbital atherectomy system technology in Asia, Europe and the Middle East. As our distribution partner, OrbusNeich, identifies new markets, we are providing best-in-class training to physicians committed to improving patient outcomes within this underserved patient population.”
Omega Medical Imaging, manufactures of Artificial Intelligence Fluoroscopy/Cine (AIF/C) Imaging systems, has announced US Food and Drug Administration (FDA) 510(k) clearance of FluoroShield with their 2020 cardiac flat panel detector.
The FluoroShield system allows for auto-collimation during interventional fluoroscopy or cine cases, while maintaining a perspective of the surrounding anatomy. The blended image incorporates a lower frequency refresh of the peripheral image area, a press release explains. This combined image (live fluoroscopy or cine and background refreshed at a rate of once or twice per second) increases the quality of information presented during interventional procedures.
Brian Fleming, president of Omega Medical Imaging, states, “Until now, products on the market have only been able to manage radiation to patients and staff. FluoroShield is the only system in the world that provides an actual reduction in dose. The impact of this ground-breaking solution for patients and healthcare providers is substantial. I am very grateful to be a part of a team that pushes the envelope in the development of safer healthcare solutions.”
A recent study comparing holmium-166 (QuiremSpheres, from Terumo) to technetium-99m-macroaggregated albumin (99mTc-MAA) as a work up for selective internal radiation therapy (SIRT) has found QuieremSpheres to be superior in terms of predicting which patients with liver cancer will benefit from SIRT treatment. The results were published in the European Journal of Nuclear Medicine Molecular Imaging.
The aim of the study was to analyse whether the intrahepatic distribution of QuiremScout has a better agreement with the QuiremSpheres distribution when compared with 99mTc-MAA. Several scientific papers have indicated that the widely used 99mTc-MAA has limited predictive value, a Terumo press release claims.
The present study included 53 patients that had been included in either phase 1 or phase 2 Holmium Embolization Particles for Arterial Radiotherapy (HEPAR) studies, and showed QuiremScout has superior predictive value for intrahepatic distribution in comparison to 99mTc-MAA.
“Previous studies already demonstrated that QuiremScout is safe in this population, and, moreover, a better predictor for lung shunting than 99mTc-MAA,” first author Maarten Smits comments. “As a result, QuiremScout allows for more accurate SIRT patient selection. Now, our study shows the potential of QuiremScout to also improve the efficacy of SIRT, by allowing a more accurate and truly personalised pre-treatment activity planning.”
“This is an important next step towards unlocking the full potential of Quirem Scout,” says Rijk de Jong, medical director of Quirem Medical. “Smits et al publication further strengthens the evidence base of QuiremScout, demonstrating superiority over 99mTc-MAA in the evaluation of the subsequent treatment. We believe this will translate into enhanced efficacy and safety for the benefit of patients undergoing SIRT procedures.”
“This is a very exciting milestone for QuiremScout and the next step in building the future for SIRT,” adds Peter Coenen, president of Interventional systems, Terumo. “This publication further validates the advantages of QuiremScout over 99mTc-MAA during the SIRT work up, which we at Terumo believe is a vital step in advancing patient selection and optimising dosimetry for better patient outcomes.”
QuiremScout is the first SIRT work up product that utilises the same technology as the therapeutic microspheres, which aims to optimise patient selection and advance treatment planning when compared to using 99mTc-MAA.
Interventional News speaks with Atul Gupta about the future of interventional radiology (IR). As a chief medical officer for Image-Guided Therapy, Philips, he enthuses about the possibilities of radiation-free interventional procedures, and a medical world advanced by augmented reality and artificial intelligence solutions.
I have been practicing for about 20 years, so when I first started my career, it was simple: just X-ray and a device. Procedures are becoming increasingly complex. When I do an intervention today, it is no longer just X-ray and device—I have to analyse data from a whole bunch of sources: haemodynamic data, electronic health records, 2D and 3D live imaging, intravascular ultrasound (IVUS) and ablation data.
I have also seen a change in the types of procedure that we do. My entryway to the human body used to be the femoral artery, but now, as we do things like uterine fibroid embolization (UFE), prostate artery embolization (PAE), transarterial chemoembolization (TACE), peripheral vascular disease (PVD) work, and even biliary procedures, we have several different access points: radial, pedal, femoral, jugular, transabdominal. I want to be able to rapidly image wrist to wrist, from head to toe, and I need to be able to do it very quickly and with great image quality. That is the biggest change I have seen in the last 20 years, the increased complexity of these procedures. Fortunately, technology now exists to help us make these procedures a lot more efficient.
At CIRSE 2019 [the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe; 7–11 September, Barcelona, Spain], we heard a lot about how we as a specialty have an identity crisis. Not just with patients, but also with other physicians. It is well understood that cardiologists treat the heart, neurologists treat the brain—but what do interventional radiologists treat? Put simply, everything, everywhere. What other field can treat a liver blockage, a stroke patient, a trauma patient, a prostate patient, kill a kidney tumour, and drain from the lungs, all in one day? We do it all, and that is a challenge. But there are three ways I think you can overcome this identity issue.
Firstly, education in the impressionable years. Any individual specialist knows us for our procedures specific to them: gynaecologists know us as the UFE expert, trauma doctors know us for doing splenic embolization, and geriatricians know us as the people who perform kyphoplasties. They are amazed to hear of all the things that we do outside of their specialty. At CIRSE, the European Trainee Forum bought 300 medical students to the congress. Not all of those 300 are going to go into IR, but they will be IR ambassadors for us, as they learn about all the things that we do.
Secondly, interdisciplinary congresses such as VIVA, ISET, CX and CIRSE, where all these specialists from across disciplines gather, are important.
Finally, social media, which gives us interventional radiologists the opportunity to get the word out is increasingly playing a role.
Lots of things! That is the cool part of the job, I get a glimpse of the future and help define what the next five to ten years of innovation are going to be, and the world that I and my colleagues are going to work in. Philips is an innovation company, so we are very much about creating technology, but it is very important to remember that it is not just about the technology. We are not here to push technology for technology’s sake—technology is the enabler to help physicians do a procedure better.
I think we are going to be working increasingly in a radiation-less, or maybe even radiation-free, world. We are going to be using ultrasound instead of X-ray. We [at Philips] have technology called TrueView, where I can photo-realistically render 3D ultrasound on the fly, so I can guide a device using ultrasound and see it in 3D, maybe even see it in a hologram in the world of augmented reality (AR). In addition to sound, we are going to be using light to navigate our devices instead of X-ray. Philips is developing devices using technology called Fibre-Optic RealShape (FORS), which lets me visualise wires and catheters in 3D using light, instead of X-ray; this was presented to the world through first-in-human cases shown at the 2019 Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), the International Symposium on Endovascular Therapy (ISET; 27–30 January, Hollywood, USA), and the Charing Cross Symposium (CX; 15–18 April, London, UK). Philips acquired EPD Solutions last year, and we now have a new technology called dielectric imaging, which lets you visualise not just the device, but the anatomy, in high definition and 3D, without X-ray. If we can do all this imaging without X-ray, and support it with artificial intelligence (AI), this is, I think, going to be massively disruptive, not just for IR, but for all interventionalists.
I think that collaboration is the most important thing that interventional radiologists bring to the table. We know that no two patients are the same, and so we are often asked by other specialities to solve very unique problems, and that lets me as an interventional radiologist be creative. Interventional radiologists are the innovators; we are always inventing new ways of treating patients. That is a hot topic every year, from the annual meeting of the Society of Interventional Radiology (SIR) to CIRSE. By collaborating with industry and with other physicians, the procedures that we develop disseminate into other fields. I think that other medical disciplines love interventional radiologists’ passion for innovation and creativity, but most importantly for collaboration. If I fast forward 10 or 15 years, I would not be surprised to see a blurring of lines between specialties, because a lot of the procedures that we do are increasingly overlapping. What specialist today is the expert in critical limb ischaemia (CLI), or AAA, or venous disease? Many people: cardiologists, surgeons, and interventional radiologists. I think that we are starting to see physicians meet across specialties. I saw vascular surgeons, cardiologists, and radiologists joining CIRSE. At conferences like ISET and Vascular InterVentional Advances (VIVA), we also see multiple specialties coming together. None of us work in a vacuum, and so crossing over to approach patient care is extraordinarily important, not just for physicians, but also for industry. Collaboration leads to the very best in innovation.
This is the part of my job that I like the best, the innovation piece. The process of how we innovate and co-create with physicians is both extraordinary and fascinating, because you never want to just push technology out, everything has to start with the end-user and patient. Recently, we brought teenagers into our innovation centre, and allowed them to sit in an interventional suite and start playing with it. These adolescents were born after the iPhone was introduced in 2007, and they are going to be the physicians of the future. Their insights are tremendous. So the process starts early on, but we also work with the world’s leading interventionalists to help us improve our devices, imaging, and software.
Atul Gupta is chief medical officer for Image-Guided Therapy, Philips. He is also a practicing interventional radiologist in Philadelphia, USA.
The 11th Symposium on Clinical Interventional Oncology (CIO; 11–13 October, Miami, USA) hosted a virtual reality (VR) case presentation, where delegates placed their smartphones into a provided cardboard headset and watched Auh Whan Park (UVA Health, Charlottesville, USA) perform a pre-recorded thyroid ablation as though they were in the operating room. This case presentation followed a series of talks discussing state of the art thyroid intervention, versing the audience in the current mainstay of thyroid cancer treatment.
Speaking in his capacity of panel moderator, Ziv Haskal (UVA Health, Charlottesville, USA) introduced the live case: “I have had the great fortune and pleasure of being involved in this meeting for ten years, and they have tolerated a lot of the things I have done. There is a certain atmosphere here—maybe it is the Miami meeting or the southern Florida meeting that just makes it a cool and hip way to learn things—and I think, at least for me, things just stick better when you can meet faculty and talk to them and see things that might be defining. I will never forget the first time I saw a live EVAR [endovascular aortic repair] case at ISET [International Symposium on Endovascular Therapy] a few decades ago. No matter how many papers you had read beforehand, seeing that live was transforming. It was several years before I did my first case, so there is sort of an inertia, but [witnessing that live case is nevertheless] a marked event.
“What we are going to do here is try to give you a little bit of that cool by putting you in that intimate, close-up seat, in the room, where you can watch Dr Park do a thyroid ablation. The purpose is to take something that probably none of you have done, and show you that […] you can actually do this: this is something you can learn and put into your practices. The opportunity is enormous. This will happen in the USA; whether it is going to be interventional radiologists (we all have experience with ablation, after all), or endocrine surgeons [is to be decided]—it is going to be performed by whoever is going to bring it [to institutions], and whoever is going to do it well.”
Prior to the session, attendees downloaded a free application to their smartphones, and then used this to stream the case. By placing a smartphone into the cardboard headsets provided, attendees were transported to Park’s operating room, where they watched a 15-minute thyroid ablation case. Haskal provided commentary throughout, describing operator decisions and drawing the audience’s attention to certain technical aspects of the case. Turning around whilst wearing the VR headset, session participants could see a presentation slide outlining the procedural steps.
The case
The patient was a woman with two benign nodules in the right thyroid lobe, which had been growing for two years prior to the procedure. Her pre-procedural thyroid function tests were normal. The patient had opted for radiofrequency ablation (RFA) over a thyroidectomy to preserve her singing voice.
The procedure was a success, with Park reporting: “She [the patient] is now really happy. She sent me a thank you letter to say that she had an invitation to perform at a concert, she is a jazz singer, so she is really happy and grateful.”
Prostate artery embolization (PAE) may become the standard of care procedure for the management of symptomatic benign prostatic hyperplasia (BPH), proposed Tiago Bilhim (CHULC, Saint Louis Hospital, Lisbon, Portugal), due to “good clinical results” presented at the 2019 annual meeting of the Cardiovascular and Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).
The investigators set out to evaluate the outcome of PAE for symptomatic BPH patients with moderate to severe lower urinary tract symptoms (LUTS). The single-centre, retrospective study examined data on 1,550 patients, prospectively-collected between March 2009 and February 2019.
“Subjective and objective parameters were assessed”, Bilhim said. The International Prostate Symptom Score (IPSS), quality of life (QoL) score, and international index of erectile function (IIEF-5) were categorised as subjective measures, whilst the investigators also calculated changes in prostate volume (PV) using trans-rectal ultrasound, peak urinary flowrate (Qmax), post-void urinary residual (PVR), and prostate specific antigen (PSA) concentration. All of these were assessed before PAE, and one, six, and 12 months after PAE, then yearly for up to 10 years.
Clinical outcomes
There was a statistically significant change from baseline in the evaluated parameters (p<0.001) across all time scales. In the short-term, defined as one to 12 months after PAE, the mean cumulative clinical success rate was 88.1% (range: 77.6–92.4%). In the medium-term, two to five years after the procedure, this was 85.1% (range: 71.3–93.1%), and over the long-term, from six to ten years post-PAE, the mean cumulative clinical success rate was 76.8% (range: 69.1–84.6%). Bilhim described the change in cumulative clinical success rate from short- to longterm—88.1% to 76.8%—as “not that much of a drop” over ten years.
Mean IPSS reduction was 13.5±6.9 in the short-term, 14.1±7.3 in the medium-term, and 13.9±8.7 in the long-term. Mean quality of life improvement was also consistent out to ten years: 1.8±1.2 in the short-term, 2.1±1.3 in the medium-term, and 1.7±1.5 in the long-term. Prostate volume reduction was also observed out to ten years, with the mean long-term reduction being 16.9±26.6cm3, and a short-term reduction of 18.3±27.9cm3.
From the 156 patients in acute urinary retention (AUR), 140 (89.7%) had the bladder catheter removed between two days and three months; 10 had repeated successful PAEs, and six had surgery. For the 312 patients with prostates larger than 100mL, there was a high rate of clinical success: in 80.7% of patients (252 individuals) over the short-term; 77.6% of patients (242 individuals) over the medium-term; 75.3% of patients (235 individuals) in the long term. Bilhim reported three major complications: a bladder wall ischaemia, a perineal pain for three months without sequela, and a patient had expelled prostate fragments and AUR treated by trans-urethral resection of the prostate (TURP) without sequela.
Describing the technical outcomes, Bilhim reported that in 90% of patients (1,324 people), the interventionalist gained access to the vasculature through the femoral artery. Since 2016, interventional radiologists at Saint Louis Hospital in Lisbon, Portugal, have been using left radial access, so 10% of the cohort (148 patients) experienced this. “This is our first-line approach”, he said of the technique, adding that now they are using it “more and more”.
Patient characteristics
Enrolled patients were 40 or older (with no upper limit on age; mean age was 65.1 years), and “severely symptomatic”, with an IPSS greater than 18 (mean IPSS: 21.8), a prostate volume greater than 30mL, and a peak urinary flowrate less than 15mL per second. The prostate was larger than 100cm3 in 312 patients, and 156 patients were in acute urinary retention (AUR). In the initial phase of the trial, only patients failing medical therapy were accepted, meaning that 65% of the cohort were given medical therapy prior to PAE. However, Bilhim said that “a significant proportion” (35%) of patients had no medical therapy pre-PAE, as “they do not want the adverse events” attributed with the alpha-blockers and 5-alpha-reductae inhibitors, such as retrograde ejaculation.
Concept Medical received CE certification for their MagicTouch group of products on 16 October 2019.
The CE certified products/brands are as listed below:
MagicTouch—PTA is the only commercially available and CE certified sirolimus-coated balloon catheter for peripheral arterial diseases.
Several studies have demonstrated that erectile dysfunction is increasingly prevalent with age. Approximately 40% of men are affected by the age of 40, and nearly 70% of men are affected by the age of 70. MagicTouch ED is the only CE certified, commercially available sirolimus-coated balloon catheter in the world for the therapeutic management of erectile dysfunction.
Concept Medical state in a press release that the company will now intensify its efforts to market and promote its products in all of Europe and other relevant markets that accept the CE certification for marketing authorisation.
Scientists of Jena University Hospital, Germany, conducted a meta-analysis sought to evaluate benefit and risk of paclitaxel-coated balloon angioplasty compared to plain old balloon angioplasty as therapy of intermittent claudication. The study confirms an increased all-cause mortality, which has formerly been stated, and found a broad heterogeneity in the effectivity of the procedure depending on pre-dilation strategy, lesion complexity, and the paclitaxel density. The authors raise doubts about a class effect of drug-coated balloons and suggest a highly individualised therapeutic decision. This meta-analysis has recently been published by The Lancet in EClinicalMedicine.
For intermittent claudication, drug-coated balloon angioplasty is the therapy of choice to reduce the risk of target lesion restenosis, and consequently, the necessity of reintervention. However, numerous types of those balloons are distinguished by drug density and coating. Clinical efficacy is not proven for all that types. Moreover, conflicting evidence exists about the risk of mortality that arose from the meta-analysis of Katsanos et al. one year ago. Scientists of Jena University Hospital, Germany, now conducted a meta-analysis sought to evaluate benefit and risk of drug-coated balloon angioplasty compared to non-coated balloon angioplasty assessing the main outcomes of freedom from target lesion revascularisation and all-cause mortality. Their results are published by The Lancet in EClinicalMedicine.
The authors working in the department of radiology and the centre for clinical studies took a closer look on 14 randomised trials comparing both procedures for the treatment of femoropopliteal artery disease. Including a total of 2504 patients, the trials were conducted between 2005 and 2019. Actually, the risk of all-cause mortality at two years was indeed increased significantly with a trend to a paclitaxel dose-response relationship, but without evidence of causation. Drug-coated balloon angioplasty significantly increased the risk of target lesion restenosis.
However, results showed substantial heterogeneity due to substantial inter-study design differences, inter-study lesion complexity differences and inter-study device differences. There is a risk of overestimation of the benefit due to high risk of bias within studies, mainly driven by missing blinding of study personal. Head-to-head comparisons of different coated balloons under the same conditions will be needed to evaluate different product efficacy. Additional pharmacological studies are needed to generate robust and meaningful evidence on safety or risk of intra-vessel paclitaxel application. Professor Ulf Teichgräber, the corresponding author of this meta-analysis, states: “There are first trials that are already beginning to examine if sirolimus-coated balloons could be an alternative to paclitaxel-coated ones. Also newer coating technologies of paclitaxel-balloons seem to have less drug loss during the procedure and better drug release to the target lesion. Innovation in this field clearly is leading towards better efficacy and safety.”
The National Institute for Health and Care Excellence (NICE) has published the final appraisal determination (FAD) recommending the use of Xarelto (rivaroxaban) by the National Health Service (NHS) in England at a dose of 2.5mg twice daily combined with aspirin (75–100mg) once daily as an option for preventing atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) who are at high risk of ischaemic events.1
Publication of the NICE FAD for Xarelto (rivaroxaban) is based on evidence from the COMPASS study, the largest Phase III study with rivaroxaban (27,395 patients). This study showed that rivaroxaban vascular dose—2.5mg twice daily combined with aspirin 100mg once daily—statistically significantly reduced the risk of the composite of cardiovascular (CV) death, stroke or myocardial infarction (MI) (major adverse cardiovascular events; MACE) by 24% (relative risk reduction, ARR: 1.3%) compared with aspirin 100mg once daily alone amongst patients with stable atherosclerotic vascular disease (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001).2
In the COMPASS trial, for patients with stable CAD, addition of rivaroxaban 2.5mg twice daily with aspirin 100mg once daily lowered major adverse cardiovascular events compared with aspirin once daily (347 [4%] of 8,313 vs. 460 [6%] of 8,261; HR 0.74, 95% CI 0.65–0.86, p<0.0001)3. Moreover, patients with PAD who received rivaroxaban 2.5mg twice daily combined with aspirin 100mg once daily also had fewer major cardiovascular events compared with the aspirin 100mg once daily alone group (126 [5%] of 2,492 vs. 174 [7%] of 2,504; HR 0.72, 95% CI 0.57–0.90, p=0.0047).4
Rivaroxaban is an anticoagulant that targets Factor Xa, an enzyme which acts at a key point in the blood clotting process, inhibiting its ability to generate thrombin.5 NICE is recommending use of rivaroxaban as part of a dual pathway approach (in combination with aspirin) to prevent atherothrombotic events in patients who are at high risk of such events. CAD patients who are at high risk of ischaemic events are defined by NICE as those aged 65 or over, patients with atherosclerosis in at least two vascular territories, or those presenting risk factors such as smoking, diabetes, kidney dysfunction, heart failure or a history of stroke.1
Derek Connolly, COMPASS trialist, consultant interventional cardiologist and honorary senior clinical lecturer at Birmingham city hospital, Birmingham, UK, said: “Cardiovascular disease remains the biggest cause of years of life lost in the UK. There have been few recent major new advances in the medical management of patients with CAD and PAD to protect them against strokes or heart attacks.”
“The COMPASS trial showed that adding rivaroxaban vascular dose (2.5mg) to low-dose aspirin significantly reduced vascular events. The large reduction in events [such as strokes], outweighed the increase in major bleeding events seen. Conducted in more than 30 countries, including the UK, COMPASS was one of the largest ever trials of oral anti-thrombotic therapy providing robust results, overall, and particularly for key patient subgroups at high-risk of recurrent events such as those with renal dysfunction or stable ‘mild’ heart failure.
“Rivaroxaban vascular dose in combination with aspirin is the first treatment of its kind for this patient population and this recommendation from NICE provides clinicians with an important additional option for treating patients at risk of major adverse cardiac events such as CV death, stroke or MI.”
Matthew Fay, General Practioner (GP) in Queensbury, Bradford, UK, with a special interest in cardiology and Trustee of AF Association and Thrombosis UK said: “We are only too aware that cardiovascular diseases carry an unacceptable burden, accounting for a quarter of all deaths in the UK. As GPs, we are always looking for new options for protecting our patients living with cardiovascular diseases, especially as the risk of atherothrombotic events remains high despite current treatment options.
“The COMPASS study showed that the rivaroxaban vascular dose (2.5mg) is an effective option for patients with coronary and peripheral artery disease and holds promise for helping patients with these conditions. I am sure that GPs across England will join me in welcoming this decision by NICE.”
Speaking on 17 October, when NICE made the recommendation, Jo Jerrome, CEO of Thrombosis UK, said: “Cardiovascular disease is one of the leading causes of deaths across the UK, accounting for more than 460 deaths per day. Today’s recommendation from NICE is great news for thousands of patients at risk across the nation.”
More than seven million people are living with cardiovascular disease in the UK. It is estimated that CVD, including CAD and PAD, is responsible for 170,000 deaths in the UK each year, representing a quarter of all annual deaths.6
Lars Bruening, CEO Bayer UK and Ireland, said: “Bayer has a long and successful heritage in cardiology. The NICE recommendation provides those with high risk CAD and symptomatic PAD with an effective treatment option that will provide additional tailored protection from atherothrombosis. Ten years on from the introduction of rivaroxaban into the UK we are continuing to see the enduring impact that it has on patients treated across its licensed indications—and now this new patient population with previous unmet needs can be considered.”
Publication of the NICE FAD for Xarelto (rivaroxaban) follows approval by the European Commission (EC) in August 20187 for the regimen of rivaroxaban 2.5mg twice daily plus aspirin 75–100mg once daily for the prevention of atherothrombotic events in adult patients with CAD or symptomatic PAD at high risk of ischaemic events. Rivaroxaban is the most broadly indicated NOAC worldwide. It is approved in the UK for:8,9,10
It is recommended that physicians assess a person’s risk of bleeding before considering rivaroxaban. Treatment to be commenced once an informed discussion has taken place, weighing up the risk of atherothrombotic events against the risk of bleeding.1
References
1 NICE. Rivaroxaban for preventing atherothrombotic events in people with coronary or peripheral artery disease. Available at: https://www.nice.org.uk/guidance/ta607 [Last accessed October 2019]
2 Eikelboom, JW., et al. N Engl J Med 2017; 377:1319–30.
3 Connolly S. J., et al. Rivaroxaban with or without aspirin in stable coronary artery disease an international, randomised, double blind, placebo-controlled trial. The Lancet 2017: DOI 10.1016/s0140-6736(17)32458-3
4 Anand, SS et al. The Lancet 2018,391:219-229.
5 Turpie AG. Arterioscler Thromb Vasc Biol. 2007; 27(6):1238-1247
6 BHF factsheet UK: bhf-cvd-statistics-uk-factsheet. Available at: https://www.bhf.org.uk/-/media/files/…statistics/bhf-cvd-statistics—uk-factsheet.pdf [Last accessed July 2019]
7 eMC. 2018. Xarelto. Available at: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/xarelto [Last accessed July 2019]
8 eMC. 2018. Xarelto SPC 2.5 mg. Available at: https://www.medicines.org.uk/emc/product/3410/smpc [Last accessed July 2019]
9 eMC. 2018. Xarelto SPC 10 mg Available at: https://www.medicines.org.uk/emc/product/6402/smpc [Last accessed July 2019]
10 eMC. 2018. Xarelto SPC 20 mg. Available at: https://www.medicines.org.uk/emc/product/2793/smpc [Last accessed July 2019]
11 Lloyd-Jones, D., et al. Lifetime risk of developing coronary artery heart disease. The Lancet. 1999;353(9147):89–92.
12 Bosch J, et al. Can J Cardiol. 2017;33(8):1027-1035
13] emc. 2019. Xarelto. Available at: https://www.medicines.org.uk/emc/product/3410/rmms [Last accessed July 2019]
Boston Scientific recently announced that vascular medicine specialist Michael R Jaff (Newton-Wellesley Hospital, Newton, USA) will be joining the company as vice president, clinical affairs, innovation and technology, peripheral interventions. His role will involve, according to Boston Scientific, leading clinical and medical affairs strategies to support the development and commercialisation of the company’s peripheral vascular medical device portfolio. In this interview with Interventional News, Jaff discusses his new position and says that “collaboration and innovation” is at its core.
Why did you decide to make the switch from medical practice to industry?
I have had an amazing career and I have been able to have a positive effect on the lives of many incredible patients. Also, I have had the privilege of participating in some of the most impactful clinical trials that have shaped and evolved our field. Most recently, I had the honour of leading a remarkable group of healthcare professionals at Newton-Wellesley Hospital. This opportunity to join an extraordinary medical technology company [Boston Scientific] is the crown jewel in my career.
Why Boston Scientific?
I have had multiple opportunities to collaborate on clinical trials with Boston Scientific, and I have been impressed with their innovative spirit, integrity and ethical standards. Their business approach has always been of interest to me and I feel honoured to have the opportunity to partner with them to improve the health of patients around the world.
How do you think your experience as a physician will help you in your new role?
Being a physician is key to this role—there is nothing more important that I can bring to the table than the perspective of what matters most to patients. My hope and my goal is that these insights will lead Boston Scientific to innovations and discoveries that will change the outcomes for patients and increase longevity.
What will your new role involve?
At the core of this new role is collaboration and innovation; we want to develop medical solutions that will transform lives. I will collaborate with colleagues at Boston Scientific to develop novel clinical trials, source new technologies and advance innovation.
In your new role, you will be looking at innovation. What do you think will be the biggest innovation in peripheral technologies over the next few years?
I am enthusiastic about advancing revascularisation strategies in peripheral artery disease, particularly given the recent confusion surrounding paclitaxel. I want to help solve the management conundrums of venous thromboembolic disease, advance interventional treatment of various malignancies, and progress artificial intelligence associated with implantable devices.
Are you able to say what Boston Scientific has in the pipeline in terms of peripheral technologies?
This is an exciting time to be joining the Boston Scientific Peripheral Interventions business, especially with the recent merger with BTG. The new portfolio of products will advance care for patients in ways that could not be realised by either company alone. My focus will be on driving innovation and clinical evidence of minimally-invasive treatments. I am excited about the totality of products in the Boston Scientific peripheral portfolio and what they offer physicians and patients.
Michael R Jaff is to be vice president, clinical affairs, innovation and technology, peripheral interventions of Boston Scientific by January 2020. In this role, a press release reports, Jaff will lead clinical and medical affairs strategies to support the development and commercialisation of the company’s peripheral vascular medical device portfolio, and drive engagement with external stakeholders to advance technologies that deliver strong clinical value and enable patient care.
The press release adds that Jaff is currently president of Newton-Wellesley Hospital (part of the Partners Healthcare system in Massachusetts), “where he has been instrumental in the hospital’s growth since 2016”. Previously, he was responsible for process improvement efforts to redesign healthcare delivery at Massachusetts General Hospital and led its Fireman Vascular Center.
With more than 25 years of experience as a vascular clinician, his research has been published in more than 300 peer reviewed medical journals. Jaff is also the founder of VasCore, which is the world’s largest core laboratory for non-invasive vascular imaging and clinical trials. Furthermore, he is currently professor of medicine at Harvard Medical School and has served on multiple professional society and hospital boards of directors.
Jaff says: “I have had the privilege of collaborating with Boston Scientific over the course of my career and have participated in numerous clinical trials investigating the company’s devices. The Boston Scientific culture of innovation, dedication to the highest ethical approach to interventional therapies and commitment to bringing forward solutions that improve the care of patients made this the best decision for the next phase of my career.”
Jeff Mirviss, senior vice president and president, peripheral interventions, Boston Scientific, comments: “Michael’s experience as a clinician, researcher and hospital administrator will bring a unique perspective in our efforts to help solve complex healthcare challenges and support our customers in advancing the care of patients suffering from debilitating vascular diseases and conditions. We are looking forward to Michael joining our Boston Scientific team.”
Philips has received US Food and Drug Administration (FDA) approval for two Stellarex 0.035” low-dose (200mm and 150mm) drug-coated balloons for the treatment of de novo and restenotic lesions in native superficial femoral or popliteal arteries.
According to a press release, the new balloons broaden physicians’ treatment options for peripheral artery disease (PAD) patients with a high risk of restenosis and expand the Stellarex portfolio, which has a proven significant treatment effect and high safety profile. The 200mm and 150mm Stellarex 0.035” low-dose DCBs are now available in the USA and will be rolled out to other markets in due course.
“With its unique coating, Stellarex is unlike any other DCB in the industry for the treatment of PAD,” said Chris Landon, general manager, Image Guided Therapy Devices at Philips. “Stellarex is the only low-dose drug-coated balloon with a proven treatment effect at three years compared to the existing standard of care in the USA and Europe. By expanding our range of Stellarex balloons, we are adding to the treatment options that physicians can use to provide optimal care for each patient with peripheral arterial disease.”
All Philips’ Stellarex DCBs feature EnduraCoat technology, a coating consisting of a polyethylene glycol excipient with amorphous and crystalline paclitaxel particles dispersed in it. The coating provides drug transfer and effective drug residency coupled with high coating durability and minimal particulate loss, thereby enabling a low therapeutic drug dose. The Stellarex balloon is now available in 40, 60, 80, 100, 120, 150, and 200mm lengths for the treatment of lesions in the superficial femoral and popliteal arteries with vessel diameters of 4–6mm.
The results of third-party analyses of patient-level data from worldwide clinical trials of the Philips Stellarex 0.035″ low-dose DCB in lengths under 150mm were recently published in Circulation. Primary safety analysis of Philips Stellarex DCB three-year data, comprising a large published, pooled set of randomised controlled trial (RCT) data for a single paclitaxel-based device, showed no difference in mortality between patients treated with the Philips Stellarex DCB and those treated with percutaneous angioplasty, the current standard of care. The analyses represent one of industry’s most extensive and rigorous safety assessments of a paclitaxel-based device.
During a session on radiation protection technologies at the 2019 Transcatheter Cardiovascular Therapeutics (TCT) meeting (25–29 September, San Francisco, USA), Lloyd W Klein (Rush Medical College, Chicago, USA) said that Henry V led the heavily outnumbered English army to victory at the Battle of Agincourt (1415) because he “figured out how to use an old weapon in a new way”. He added that physicians needed to take a similar innovative approach to developing technologies for reducing radiation exposure.
He explained that, at the Battle of Agincourt: “The French had the best weapons, the best armour; they had the best everything. They [the English] were outnumbered seven to one. And yet, 7,000 French troops died during the battle vs. a few hundred English. How did Henry V do this?” According to Klein, the answer is not the “great motivational speech” that Shakespeare gave him (“probably the best speech ever written in the English language”) but Henry V’s innovative military tactics. “Henry figured out that the French’s armour could be used against them. So, he made them charge through a muddy field. And then to take further advantage, he figured out how to use an old weapon in a new way—the longbow [more than 80% of the English army had longbows]. The longbow made the heavy armour obsolete,” Klein said. He added that physicians were “now looking for our longbow” in terms of innovation to reduce radiation exposure.
Klein made clear that there is a need to reduce radiation exposure, outlining the damaging side effects of exposure to patients, operators and staff. He stated that the side effects could be related to the radiation itself (deterministic injuries and stochastic injuries) and/or to having to wear lead-lined aprons to protect against exposure (musculoskeletal injuries). Therefore, Klein said, it was “time for a safer environment”.
Lloiyd W Klein
While he did acknowledge that technologies for reducing radiation exposure were already available, he said that they had limitations. The Zero-Gravity radiation protection system (Biotronik), for example, was “cumbersome” and the CorPath robotic angioplasty system (Corindus Vascular Robotics) gave “less procedural control than we would like”. Concluding, Klein said: “If the same level of commitment to innovation that has been applied to other fields of interventional medicine was transferred to workplace safety, then the career of the interventionalist and their staff would undoubtedly be more comfortable”.
Jennifer A Tremmel’s (Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, USA), who was speaking at the same radiation protection technologies session as Klein, agreed that there was a need to reduce radiation exposure and that current technologies have limitations. “The downside to many radiation reduction techniques is that they take effort. You have to push a button, move yourself or a device, or learn a new technique. Ideally, a system would reduce radiation for us and our patients automatically without interrupting our workflow.” She then proposed that ControlRad was such a system.
Tremmel explained that ControlRad worked on the principle that peripheral vision was not as important as central vision. “Peripheral vision has value but there is no need to have the same image quality, [and thus] the same amount of radiation, over the entire field of view. Instead, it would be better to limit the radiation only to the area we are focusing on (which is 5% of our visual field), but keeping the periphery visible.”
According to Tremmel, ControlRad focuses on the operator’s area of interest while maintaining the peripheral view. It attenuates radiation (and image quality) for the peripheral view by using dynamic semi-transparent filters. The system can be integrated into existing fixed and mobile C-arm units, and the operator identifies the area of interest via a tablet (ControlRad Trace) or via eye-tracking (ControlRad View). Tremmel reported, based on the results of a 2016 study, that this leads to a “75% or greater radiation reduction from whatever dose you would have been getting”.
“Radiation risk is a real concern for operators, staff, and patients. It is our responsibility to minimise that risk. This includes getting our administrators to pay for equipment that keeps everyone safe. Technology is increasingly offering us solutions—those that require minimal learning and do not affect our workflow will be easier to adopt,” she concluded.
Following Tremmel, Jean-Michel Paradis (Quebec Heart and Lung Institute, Québec, Canada) spoke about the Newton system. He explained that it was a “double suspension system” that was designed to support the weight of the leaded aprons of two operators, adding that the system could be used “with your personal radiation protection apron, with virtually no motion restriction”. Furthermore, Paradis commented, the Newton system could potentially allow you to choose “a thicker/heavier garment” to improve your radiation protection because you did not have to support the weight of your apron.
In contrast to Paradis, both James A Goldstein (Department of Cardiovascular Medicine, Beaumont Health System, Royal Oak, USA) and Amir Belson (Neoguide Systems) spoke about technologies that were designed to eliminate the need for radiation protection. Goldstein reviewed the Protego system, describing it as a shield that provided “comprehensive total body exposure protection” but one that did not “interfere with procedural performance”. In his talk about a “innovative robotic shield device” (Radiaction), Belson commented: “It is deployed to encapsulate the imaging beam. The system blocks scattered radiation at its source—the patient and the table, and it provides 360-degree, full-body protection”.
During the discussion following the talks on the new technologies, Klein called for action to better protect operators against the dangers of radiation exposure. He said: “Our [interventional] societies should come together to demand technologies that reduce radiation exposure. We need to be clear that this [the current situation] is something we are no longer OK with; change is something we should insist on. It is time for us to say that this is no longer acceptable. We do not want to have to live our lives like this.”
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Gerard Goh (Melbourne, Australia) talks to BLearning IR at CIRSE 2019 (Cardiovascular and Interventional Radiological Society of Europe; 7–11 September; Barcelona, Spain) about Australian public Medicare data which has shown a “huge disparity” between the number of hysterectomies performed each year compared with the number of uterine artery embolisations procedures performed.
The data showed that of the 22,500 hysterectomies each year, of which you would expect to see four to five thousand performed for fibroids, fewer than 150 uterine artery embolisations were actually performed.
Goh says that it is “interesting” that a procedure which has been proven to be efficacious has such a poor take-up globally. A major reason for this, Goh states, comes down to a lack of “patient awareness and referrer awareness”. To tackle this issue, he believes interventional radiologists from across the world need to “come together” and work with societies to help educate women and referrers because currently “a lot of women are really missing out on uterus-sparing surgery for fibroids”.
VEITHsymposium and BLearning, the digital education division of BIBA Medical, are pleased to announce a collaboration on the creation and dissemination of digital education video content, which will be filmed at the 46th Annual VEITHsymposium in New York, USA (19–23 November 2019, New York City).
VEITHsymposium is a leading global conference covering all aspects of vascular medicine, vascular surgery and endovascular intervention. BIBA Medical’s mission is to provide education, news, and insights to connect the global community of physicians, healthcare providers, and medical manufacturing industry. BLearning is the company’s video production capability that seeks to develop and deliver high-quality digital education content.
As part of this specific co-operation project, the VEITHsymposium leadership will work closely with BLearning to create and realise the filming, production and release of digital education videos that will be filmed in a dedicated studio during this year’s conference. The videos will be released on the VEITHsymposium website and its social media as well as BIBA Medical’s flagship newspaper sites, Vascular News and Interventional News, and their associated social media channels.
“VEITHTV is a new initiative from VEITHsymposium that is designed to extend the meeting’s global digital presence and impact throughout the year, after the five days of symposium in New York. Interesting video highlights and late-breaking information will be filmed by our expert faculty during the meeting, edited professionally and released in a timely fashion to provide vital educational material to keep the vascular community clinically up-to-date. This material may also include exciting new developments from our industry partners,” said Frank J Veith, chairman of VEITHsymposium.
“It is a privilege for BLearning to collaborate with VEITHsymposium. The creation of a dedicated studio will ensure that many of the key highlights of the outstanding education presented at VEITHsymposium can be shared with the global vascular community in a new, watchable format,” said Stephen Greenhalgh, business development director, BIBA Medical.
Jos van den Berg (Lugano, Switzerland) tells Interventional News at CIRSE 2019 that the results of the APERTO AVF China trial provide strong evidence of the benefits of using the APERTO drug-coated balloon (DCB; Cardionovum) in haemodialysis patients who had stenosis of, mainly, de novo arteriovenous fistulas. The APERTO paclitaxel-releasing haemodialysis shunt balloon was tested against high-pressure balloons in a randomised fashion. Significantly more patients treated with APERTO were free of restenosis at six months and from clinically driven target lesion revascularisation at 12 months, compared to those treated with the high pressure balloon, says van den Berg, who also pointed to the fact that there was no cause for concern in terms of safety of the paclitaxel-coated device at one year.
There is now an “increase in the body of evidence” that supports a primary treatment strategy using DCB for arteriovenous fistula stenosis—and the landscape of treatment for vascular access stenosis “is going to change”, van den Berg, says.
This video is sponsored by Cardionovum.
A real-world safety analysis of paclitaxel-based devices in peripheral arteries, recently published in the European Heart Journal, showed no evidence for increased mortality over a period of 11 years. “In summary,” the authors remark, “our analysis found the use of drug-eluting devices to be safe for endovascular therapy of the lower limbs”.
Elaborating on the findings, they comment that “Particularly with regard to long-term mortality, neither drug-coated balloons nor drug-eluting stents was associated with increased risk compared to non-drug-eluting devices”. Furthermore, they say the analysis “exemplarily demonstrates the significance of health claims data for assessing urgent safety concerns without undue delay”.
In 9.2 million insurants of the German BARMER Health Insurance, Eva Freisinger (University Hospital Münster, Germany) and colleagues retrieved data on the application of paclitaxel-based drug-eluting stents (DES) and drug-coated balloons (DCB) from their introduction on the market in 2007 until the present.
They then indexed all patients with first endovascular revascularisation between 2007 and 2015 and followed them until 31 December 2017. Freisinger and colleagues included each subsequently applied DES, DCB, bare-metal stent, and uncoated balloon in further analysis.
Multivariable Cox regression analysis considered potential non-linear time-dependent hazard ratios of DES and DCB over 11 years. The authors identified 64,771 patients who underwent 107,112 endovascular revascularisation procedures using 23,137 drug-eluting devices (DED).
The investigators report that this analysis showed paclitaxel-based DES not to be associated with increased long-term mortality for over 11 years past application (all p>0.057). DCB was associated with decreased long-term mortality for the first year past application (HR 0.92; p<0.001), and indifferent correlation in the years thereafter (all p>0.202).
Addressing the significance of the study, the authors remark: “Our study debilitates current safety concerns resulting from previous findings,” referring to recent data which has indicated a two-fold increase in long-term mortality among patients treated with paclitaxel-based DED.
While DED represent a well-established therapy being widely used for endovascular revascularisation for peripheral vessels, the authors note, these safety concerns affected international regulatory authorities to call for several alerts for further application of DED.
“Compared to the meta-analysis by Katsanos et al that resulted from small-sized selected cohorts of the underlying RCTs,” Freisinger and colleagues continue, “our data reflect the unselected real-world patient collective to which the devices actually apply to.”
Commenting on the patient cohort, they say it is “representative compared to other large epidemiological studies in terms of age, sex, cardiovascular risk burden, and LEAD [lower extremity artery disease] severity,” referring directly to studies by Olinic et al and Fowkes et al.
While the authors stress that the present analysis covers a “large and comprehensive” database of unselected real-world patients, they admit that it is limited by the “general constraints” in the use of secondary healthcare data. Specifically, they note, real-world administrative data do not provide information on the underlying reason for DED treatment, representing a potential selection bias.
Medtronic today announced it has received breakthrough device designation from the US Food and Drug Administration (FDA) for its Valiant TAAA stent graft system for minimally invasive repair of thoracoabdominal aortic aneurysm (TAAA).
The FDA breakthrough device programme is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide Medtronic with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.
The Valiant TAAA is currently being evaluated in the USA within five physician-sponsored investigational device exemption (PS-IDE) trials for treatment of TAAA. The system under evaluation in these trials was developed in collaboration with Patrick Kelly, a vascular surgeon and inventor specialising in complex vascular disease who leads Sanford Health Commercialization. The Valiant TAAA is intended to offer an off-the-shelf endovascular solution with a size matrix to enable broad patient applicability for one of vascular surgery’s most difficult pathologies.
“Breakthrough designation from the FDA means that we will be able to deliver this much needed treatment to patients sooner than expected. With an open surgery mortality rate of 25%, it is critical that we deliver for this unmet patient need,” said Murray Shames, professor and chief division of Vascular Surgery at the University of South Florida Morsani School of Medicine (Tampa, USA) and an investigator for the Valiant TAAA. “Physicians and industry must continue to innovate and provide hope for those with challenging disease states.”
“In addition to a high mortality rate for open surgical repair, physicians do not have good options when it comes to treatment for failed endografts,” said John Farquhar, vice president and general manager of the Aortic business, which is part of the Cardiac and Vascular Group at Medtronic. “The FDA’s breakthrough designation for Valiant TAAA and our collaboration with leading physicians is an example of our willingness to take a courageous approach and challenge the limitations of current treatment options. This is about going further, together to improve patient outcomes.”
Continuing expansion into breakthrough technologies with Valiant Navion LSA
The Valiant Navion LSA branch thoracic stent graft system received breakthrough designation from the FDA in May 2019 to allow for more timely delivery of treatment options for patients in need of left subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR).
Valiant Navion LSA is based on Valiant Mona LSA investigational device and the FDA-approved Medtronic Valiant Navion stent graft system. Like Valiant Navion, the off-the-shelf, single branch device leverages a low-profile design, which may further enable patient applicability and access. The branch cuff is intended to replicate the natural anatomy of the LSA to maximise seal and patency.
“About 40% of thoracic aortic aneurysms in branch vessels involve coverage of the LSA. With no currently available off-the-shelf solutions, surgical bypass remains the standard of care for these patients,” added Farquhar. “By leveraging our low-profile, Valiant Navion platform, we hope Valiant Navion LSA will expand endovascular treatment options to those in need. It is a matter of putting patients first and delivering innovation where it matters most.”
Luminor 18 and Luminor 35 drug-coated balloons (DCB; iVascular) are now listed on the French LPPR list for de novo lesions of the femoropopliteal arteries.
Luminor is a paclitaxel-coated balloon specifically designed for dilatation of stenosis located in the iliac, femoral, iliofemoral, popliteal, infrapopliteal and renal arteries, as well as for the treatment of obstructive lesions of arteriovenous fistulas, whether original or artificial.
Eric Ducasse (CHU Bordeaux, Vascular Surgery Unit, France) has been one of the first Luminor users in France. He comments: “Luminor is the first paclitaxel DCB reimbursed in France since the Katsanos et al publication. It underlines that French authorities do trust its last generation coating technology, which is unique and has demonstrated efficacy, and, above all, safety. I am confident that French use and data analysis will confirm it shortly.”
The latest EFFPAC trial two-year outcomes with Luminor have shown positive results in terms of primary patency (90.2%) and freedom from target lesion revascularisation (97.2%) in the superficial femoral artery and popliteal artery for TASC A and B lesions. The trial also demonstrated no increased risk of death detected at two-years (one death in the DCB group versus two deaths in the percutaneous transluminal angioplasty group), evidencing a relative risk of 0.48.
The Luminor DCB has a proprietary nanotechnology coating, TransferTech. This uses paclitaxel in a microcrystalline molecular structure that is spread on the balloon, together with the excipient, by ultrasound spray pulse. The balloon surface is covered with multiple and independent nanodrop layers, providing a flexible coating that adapts to the balloon movement and ensures paclitaxel is released in the target lesion without particle loss in the blood flow.
The Society of Interventional Radiology (SIR) Women in IR section has launched the Women in IR Champion Award to recognise an individual who has consistently made a significant contribution to the advancement of women in interventional radiology (IR). The award will be presented each year at the society’s annual meeting, with the first honouree receiving the award at the 2020 Annual Scientific Meeting (28 March–2 April, Seattle, USA).
According to the SIR website, the significant contribution towards women in IR can be in “sponsorship, mentorship, teaching, promotion, advocacy, and recruitment”. The nominee must be a member of SIR for at least 10 years after completing their training, and must be an actively practicing interventional radiologist.
Calls for nominees opened on 9 September 2019, and will be conducted through to 31 October 2019. Individuals can self-nominate or be nominated by a peer. The SIR website details that all nominations must be accompanied by two letters of support (three if it is a self-nomination) outlining how the nominee has contributed to the advancement of women in IR and a copy of the nominee’s CV.
Aneesa Majid, an interventional radiologist based in Chicago, USA, and founder and president of No Limits Radiology, expands on why she believes this award is so important: “Currently, approximately 8% of interventional radiologists are women. While we have had amazing women interventional radiologists achieve great things and lead the society, we are still a minority. Advancement requires advocacy, and recognising those who promote women in IR is important in helping to grow the community of IR to be more inclusive of women interventionalists.”
Majid also tells this newspaper why this award is timely: “Gender equality in the workplace is the topic now, and the focus of gender equality in medicine is front and centre in the discussion. There is not a day that goes by on social media and #medtwitter where this topic is not discussed. It is important for us to join that conversation and highlight those who are active in working to achieve that equality within our field.”
The future of interventional radiology will be more gender inclusive, Majid enthuses. “We are already seeing female medical students and residents learning about IR early in their training, showing interest and pursuing it as their field of choice”, she says. “Data has shown that being gender inclusive results in better performance than single gender teams, provides a wider talent pool, offers different perspectives, which sparks greater creativity and innovation, enhances collaboration, improves staff retention, is a better reflection of the patient population we serve, improves recruitment and reputation, and [leads to] greater profitability. Thus, I look forward to seeing many more amazing innovations from female interventional radiologists, particularly in the areas of women health and women health services that are also consistently ignored. I also look forward to seeing strong interventional departments that break the myth that IR is not a profitable field.”
You can make a nomination here.
Andrew Holden (Auckland, New Zealand) provides perspective on the first results from the Disrupt PAD III observational registry that were presented at the Charing Cross International Symposium 2019. This large registry is designed to evaluate the use of Intravascular Lithotripsy (IVL; Shockwave) in the treatment of calcified arteries beyond the femoropopliteal segment, in anatomies such as below the knee and the iliac arteries.
As the clinical experience and evidence base for this technology grows, Holden, one of the earliest users in the world of IVL, shares his views on the broadening applications for IVL in larger vessel beds, such as the common femoral artery and facilitating transfemoral access for large bore devices.
This video is sponsored by Shockwave Medical.
BD has announced the publication of a company-initiated, independent analysis of the Lutonix 035 drug-coated balloon (DCB) femoropopliteal clinical programme in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions. These data were simultaneously presented in a late-breaking session at Transcatheter Cardiovascular Therapeutics (TCT; 24–29 September, San Francisco, USA), the annual scientific symposium of the Cardiovascular Research Foundation.
This independent analysis evaluated Lutonix 035 DCB (n=1,093) and standard percutaneous transluminal angioplasty (PTA; n=250) safety outcomes using patient-level data and propensity-matching from three Lutonix DCB randomised controlled trials: LEVANT 1, LEVANT 2, and LEVANT Japan, as well as the Continued Access cohort of the LEVANT 2 trial, and confirmed that there was no statistically significant increase in mortality with the use of LUTONIX 035 DCB.
“While the FDA and Advisory Committee of Circulatory System Devices Panel in June identified a late mortality signal after treatment with paclitaxel-coated devices using a meta-analysis of randomised controlled trials at five years from multiple companies, they recognised the benefits of these devices, including fewer reinterventions. They agreed that the magnitude of the signal should be interpreted with caution due to multiple limitations in the available data,” said Kenneth Ouriel, president and CEO, Syntactx, the clinical research firm that conducted the independent analysis, and former chairman of Surgery at the Cleveland Clinic.
He continued: “This large patient-level analysis found no statistically significant increase in mortality associated with LUTONIX DCB treatment. LUTONIX DCB remains a viable medical therapy for patients with peripheral arterial disease who demonstrate a high risk for restenosis and repeat femoropopliteal interventions.”
Further, a medical advisory committee comprised of an interventionalist and oncologist re-evaluated the cause of death in the LEVANT 1 and LEVANT 2 trials, including the LEVANT 2 Continued Access cohort. This independent review confirmed through adjudication that zero deaths were determined to be related to paclitaxel. Moreover, no clustering or pattern of death in any cardiovascular or non-cardiovascular categories was observed, which would have indicated a causal relationship between paclitaxel and death.
“The published patient-level analysis from Syntactx provides important information that health care providers can use to make an informed decision on the use of paclitaxel devices until additional long-term data are available,” said JD Meler, vice president of Medical and Clinical Affairs for BD’s Peripheral Intervention business. “Patient safety is our top priority, and BD remains committed to improving the quality of life of patients with PAD.”
Lorenzo Patrone (London, UK) shares with Blearning at CIRSE 2019 (7–11 September, Barcelona, Spain) the benefits of using the OUTBACK™ Elite Re-entry Catheter (Cordis, a Cardinal Health Company) in chronic total occlusions—in any arterial segment from the iliacs to the toes.
Patrone speaks about the use of the re-entry device used via the standard antegrade access or via a distal superficial femoral artery/below-the-knee retrograde approach to be able to re-enter in the proximal superficial or common femoral artery in patients with history of previous bypass, where the need and the difficulty in achieving an accurate re-entry are maximum.
He emphasises the importance of operator expertise and recommends for the device to be used earlier, rather than later in the treatment plan [to avoid dissection of the subintimal space], in order to achieve effective outcomes. Regarding costs, his opinion is that the cost of the device itself is nothing in compared to [savings] in “time, contrast, and radiation to the patient”.
“In my experience, to cross the lesion is the most challenging part [of the procedure],” says Patrone, “once you cross the lesion, you can angioplasty, you can stent, and the patient will have a new vessel, new vessel means new blood to the limb, and new blood to the limb means new life to the patient”.
This video is sponsored by Cordis, a Cardinal Health Company.
Intact Vascular has announced the positive one-year results of its Tack Optimised Balloon Angioplasty (TOBA) III clinical trial, successfully achieving both primary and secondary endpoints. Marianne Brodmann, head of the Clinical Division of Angiology, Medical University of Graz, Austria and principal investigator of the TOBA III trial, presented the data during the high impact clinical research session of the 31st Transcatheter Cardiovascular Therapeutics (TCT) meeting (25–29 September, San Francisco, USA), the annual scientific symposium of the Cardiovascular Research Foundation.
This multi-centre, single-arm, prospective study was conducted in Europe and investigated the combination of the Tack endovascular system with Medtronic’s IN.PACT Admiral drug-coated balloon as a treatment in the superficial femoral (SFA) and/or proximal popliteal (PPA) arteries. The study enrolled 201 patients, including 169 patients with arterial lesions ≤150mm in length and a subset of 32 patients with long arterial lesions (>150 and ≤250mm). All patients suffered from peripheral arterial disease (PAD) and underwent balloon angioplasty, consequently experiencing at least one dissection requiring repair.
Results from the 169 patient standard lesion cohort (≤150mm) impressively demonstrated 97.7% complete dissection resolution, 95% K-M vessel patency and 97.5% K-M freedom from clinically-driven reintervention at 12-months. This was accomplished with a 0.6% bailout stent rate. These results add to the body of clinical evidence supporting the use of the Tack system for post-PTA dissection repair and further demonstrate the long-term effectiveness of the technology, an Intact Vascular press release states.
“I am extremely pleased with the clinically compelling results of the TOBA III study,” comments Marianne Brodmann. “The Tack system provides a safe and effective solution for treating post-angioplasty dissections. I believe this new therapeutic paradigm will change the standard of care for above-the-knee interventions.”
The observational data from the long lesion subset (>150 and ≤250mm) was analysed separately. Results from these 32 patients notably demonstrated 98.8% complete dissection resolution and 89.3% K-M vessel patency, with 96.8% K-M freedom from clinically-driven reintervention at 12-months and a 0% bailout stent rate.
“The data presented at TCT further validates the use of Tack implants to improve balloon angioplasty results,” says Peter Schneider, co-founder and chief medical officer of Intact Vascular. “The data suggest that we have been implanting too much metal for far too long with traditional stents. We are thrilled to offer a minimal metal therapeutic solution that enhances patient outcomes and preserves future treatment options.”
“We would like to thank the excellent team of physicians and coordinators who contributed to the success of the TOBA III study,” states Bruce Shook, Intact Vascular’s president and CEO. “The results presented are the most impressive reported to date for balloon angioplasty in above-the-knee arterial disease. We look forward to offering this technology to more patients as we continue the rapid expansion of our commercial efforts.”
Terumo Medical have announced that it has introduced the Radial to Peripheral (R2P) MISAGO RX self-expanding peripheral stent at the 31st Transcatheter Cardiovascular Therapeutics (TCT) conference (25–29 September, San Francisco, USA). The introduction of R2P MISAGO helps physicians bring the benefits associated with a radial access approach to patients with peripheral arterial disease (PAD).
According to the US Centers for Disease Control and Prevention (CDC), PAD affects approximately 8.5 million people in the USA, and is characterised by a narrowing or blockage of arteries limiting blood flow to the lower extremities; an endovascular approach is often used for treatment.
R2P MISAGO is a device within the R2P portfolio, the first and only portfolio of longer-length radial devices specifically designed for peripheral procedures. R2P MISAGO is the longest stent platform specifically designed for above-the-knee PAD interventions via radial access, incorporating Rapid Exchange (RX) technology and innovative bare metal stent design.
The launch of R2P MISAGO is complemented by the introduction of R2P CROSSTELLA RX PTA balloon dilatation catheter, the longest 0.018″ balloon designed for use in radial to peripheral procedures. Both R2P MISAGO and R2P CROSSTELLA have a 200 cm working length, enabling physicians to perform more peripheral procedures for more patients.
“As the industry leader in radial access, Terumo is very proud of the work we have done in partnership with the medical community to drive utilisation of radial procedures,” says Chris Pearson, Executive Vice President, Commercial Operations, Terumo Interventional Systems. “The launch of these additional devices enhances our existing R2P portfolio, and underscores Terumo’s commitment to developing new, innovative technology to advance peripheral vascular care.”
“Using radial artery access is associated with quicker ambulation, improved patient comfort, and satisfaction. Terumo’s introduction of R2P MISAGO and R2P CROSSTELLA as part of the R2P portfolio provides physicians with additional options to treat PAD patients from the wrist,” comments John Coppola (NYU Langone Medical Center, New York, USA).
R2P MISAGO is currently in a limited market release within the USA, and will have full commercial availability in October 2019. R2P CROSSTELLA is currently commercially available as part of the R2P portfolio of radial length devices.
Bart Dolmatch gives an overview of the history of haemodialysis access in the USA, and balances the pros and cons of current access options. He outlines his hopes for the increasing role he believes interventional radiologists should play in the management of end-stage renal disease patients, and how innovation is helping physicians achieve better clinical results.
While the incidence of end-stage renal disease (ESRD) in the USA has reached a plateau over the past few years, prevalence continues to climb due to lower mortality rates.1 ESRD is treated with renal replacement, but it is costly and places a growing financial burden upon Medicare participants. Medicare-paid claims for ESRD, including renal replacement, represented over 7% of all Medicare payments and exceeded US$35 billion in 2015–2016.2
Renal replacement can be performed with a kidney transplantation, peritoneal dialysis, or haemodialysis. For many people, transplantation may be the best option, but due to the ongoing shortage of donor organs, fewer than 3% of people with ESRD received a pre-emptive transplant. Peritoneal dialysis, conveniently performed at home by most people, accounted for only 9.7% of all renal replacement. Haemodialysis accounted for renal replacement for nearly 90% of the ESRD population in the USA.1
Haemodialysis is simply the process of cycling a person’s blood through a filtration system, removing toxins while balancing fluids and electrolytes, and returning the blood back to the patient’s circulatory system. Efficient cycling of blood requires a way to both remove and replace blood, typically through one of three methods: a dual lumen catheter; an arteriovenous graft (AVG); or an arteriovenous fistula (AVF). An AVG is a surgically inter-posed conduit between an artery and vein that is accessed for haemodialysis. An AVF is the direct connection of an artery to vein, where the venous side of the circuit serves as the access site. Both an AVG and AVF are accessed for haemodialysis using two-needle cannulation—one for cycling blood to the dialyser, the other to return blood to the patient.
All three types of vascular access have pros and cons. Catheters are convenient but have the highest morbidity rates compared to AVGs and AVFs.3,4 AVGs had a high rate of usability, but up to 75% failed in their first year.5 Once an AVF is ready for repeated successful haemodialysis, it is often an excellent long-term vascular access solution with better durability than an AVG. However up to 60% of AVFs were not ready for use within four to five months after surgery, and many were abandoned before any attempt to salvage.6
While there are problems with all forms of haemodialysis access, the AVF remains the preferred modality and accounts for about two-thirds of haemodialysis access in the USA.5 For more than 50 years, creation of an AVF was the purview of surgeons. However, in 2018, two catheter-based systems were cleared for percutaneous AVF creation by the US Food and Drug Administration (FDA)—BD’s WavelinQ and Avenu Medical’s Ellipsys. The hope is that percutaneous AVFs, created without pre-operative delay, will have high rates of early unassisted usability and remain functional. So far, data are encouraging.6,7
AVGs and AVFs often develop stenoses that reduce dialysis efficiency and can lead to thrombosis. Percutaneous transluminal angioplasty (PTA) has been used for decades, though with varying durability. We have learned that bare metal stents do not improve durability over successful PTA.8,9,10 However, covered stents from BD such as the Flair, Fluency and Covera, as well as Gore and Associate’s Viabahn, reduce restenosis rates. These covered stents have demonstrated superior outcomes in prospective clinical trials when compared to PTA.11,12,13,14,15 In addition, BD’s Lutonix drug-coated balloon also confers improved outcomes compared to PTA.16
The past few years have seen great strides in creating and maintaining haemodialysis access. We now have new ways to achieve better results, with the hope that through ongoing innovation and comparative prospective clinical research, we can improve the lives of patients with ESRD.
Bart Dolmatch is an interventional radiologist at The Palo Alto Medical Foundation and El Camino Hospital, Palo Alto, USA.
References
The late mortality risk associated with paclitaxel-coated balloons and stents when used in the femoropopliteal arteries for the treatment of peripheral arterial disease (PAD) is lower than initially reported, as investigators incorporate more patient-level data into the analysis, but the signal persists nonetheless. This is the finding of a new meta-analysis presented by independent researchers from VIVA/NAMSA at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting (25–29 September, San Francisco, USA).
The latest data from the independent, patient-level analysis showed a mortality risk (HR 1.27, 95% CI 1.03–1.58) “incrementally” lower than the last update from the US Food and Drug Administration (FDA) device panel convened in June this year (HR 1.38, 95% CI 1.06–1.80), Krishna Rocha-Singh (Prairie Heart Institute, HSHS St John’s Hospital, Springfield, USA) told the TCT audience.
“This updated meta-analysis, which represents the most comprehensive analysis of available individual patient data to date, demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify any explanation,” he said.
On 6 December 2018, Konstantinos Katsanos (Patras, Greece) and colleagues published a meta-analysis in the Journal of the American Heart Association (JAHA) reporting an increased association of mortality when paclitaxel devices were used in the leg to treat PAD patients. The mortality signal they found was HR 1.93. Amongst the ongoing international conversation spawned by the publication of these data were criticisms of the lack of patient-level data in the original JAHA meta-analysis. Industry stakeholders and the FDA started working to gather individual-level data.
Today, the paclitaxel device issue is “by no means a done deal” and has “taken over the majority of our work load,” Eleni Whatley, of the FDA, reportedly said at TCT. She informed the audience that any new application for a device containing paclitaxel has to apply at least five years of data and have minimal loss to follow-up.
In June this year, the FDA panel concluded that devices already on the market should remain available given their risk-benefit ratio, but agency advisors also called for a change in labelling. Whatley said at TCT that this was imminent, to be expected in the next few weeks.
No mechanism for increased mortality has been shown.
Rocha-Singh summed up: “The updated met-analyses [sic], which represents the
most comprehensive analysis of available IP [individual patient] data to date, demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel, however, it did not identify an explanation. Consideration of ‘real world evidence’, although hindered by issues of reliability, lack of follow-up, selection bias and internal controls, may offer insights [into] paclitaxel device use and mortality.”
The prospective, randomised SINGA-PACLI trial sought to compare the results of drug-coated balloon (DCB) treatment to plain balloon angioplasty (POBA) for the treatment of infragenicular lesions in patients with critical limb ischaemia.
Tan Bien Soo (Singapore), principal investigator of the trial, reported 12-month results at CIRSE 2019 (Cardiovascular and Interventional Radiological Society of Europe; 7–11 September; Barcelona, Spain). He tells Interventional News that while six-month patency rates (around 42% for DCB group vs. 38% for POBA group) and limb salvage rates (75% for DCB group vs. 85% for the POBA group) were similar between patients treated in both arms of the trial, the results of amputation-free survival was significantly different in both groups. Patients in the group treated with DCB experienced significantly worse amputation-free survival (62% vs. 77% for the POBA group) leading the investigators to comment that there was “no strong evidence to recommend the routine use” of drug-coated balloons in critical limb ischaemia patients below the knee, unless there were “compelling” reasons to do so.
The six-month results of TINTIN (Treatment with the lumINor DCB and The IVolutioN self-expanding stent) trial have been revealed at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain) by Koen Deloose.
TINTIN is a physician-initiated trial investigating the safety and efficacy of the treatment with the Luminor DCB and iVolution self-expanding stent (both iVascular), in TASC C and D femoropopliteal lesions.
Both iVolution and Luminor present excellent outcomes in TASC A & B lesions, but it is clear, out of the literature, that neither BMS nor DCB alone are winners in long, complex lesions and on the longer run. The combination of both is the key to success in these situations.
TINTIN trial outcomes:
At the end of the presentation Deloose concluded that “The Belgian TINTIN trial shows impressive 6 months results in lesions of 24 cm”.
Zoom in on a tête-à-tete between Marianne Brodmann (Graz, Austria) and Giovanni Torsello (Munster, Germany) who talk through the latest clinical evidence that directly compares drug-eluting stents in a head-to-head fashion.
Brodmann and Torsello talk through thorny issues such as which patients qualify as “high-risk” patients who would benefit most from the use of paclitaxel-coated devices in light of the most recent US FDA guidance on the topic. They also outline the poor outcomes obtained before the era of drug-elution with bare metal technologies.
Torsello highlights the latest results from drug-eluting stent trials, particularly the IMPERIAL trial that compares the Eluvia drug-eluting stent platform (Boston Scientific) with the Zilver PTX drug-eluting stent platform (Cook Medical), emphasising the importance of polymer-mediated, low dose, sustained local drug release over time.
Both look to the near future and the upcoming EMINENT trial that will compare Eluvia with best practice US FDA approved bare metal stents, and comment on the importance of long-term data from the Muenster Eluvia registry which is testing this drug-eluting stent system in a complex patient cohort with lesions at high risk of restenosis to provide evidence of its clinical benefits in this patient population.
This video is sponsored by Boston Scientific.
NOTE: ONLY intended for healthcare professionals outside of the USA.
Ulf Teichgräber (Jena, Germany) and Koen Deloose (Dendermonde, Belgium) discuss the 24-month results of the EFFPAC trial and the six-month outcomes of the TINTIN trial. Both trials used the luminor drug-coated balloon (DCB; iVascular) with TINTIN testing it in combination with the iVolution self-expanding stent (also iVascular). The latest trial results were presented at CIRSE 2019 (Cardiovascular and Interventional Radiological Society of Europe; 7–11 September; Barcelona, Spain).
Teichgräber, analysing the latest EFFPAC data, points out that luminor is a third-generation DCB with a “very innovative nanotechnology” that is designed to release paclitaxel just at the target lesion.
EFFPAC has shown “outstanding” results in terms of patency (90.2%) and freedom from TLR (97.2%) in the superficial femoral artery and popliteal artery for TASC A and B lesions, and at 24 months, no risk of increased death in the paclitaxel group, says Teichgräber.
The TINTIN trial is a physician-initiated trial evaluating the use of combined treatment with two products that have already “proven their efficacy”, says Deloose—the luminor DCB and the iVolution self-expanding stent—in complex and long lesions (mean lesion length of 24cm), such as those seen in real-world practice. At six months, TINTIN data “showed a clear and good signal” with a 96% primary patency and 98% freedom from target lesion revascularisation in patients with difficult disease, says Deloose.
This video is sponsored by iVascular.
LimFlow has announced that the US Food and Drug Administration (FDA) has approved its investigational device exemption (IDE) for the PROMISE II pivotal study of the LimFlow Percutaneous Deep Vein Arterialisation (pDVA) System.
PROMISE II is a multicentre, prospective, single-arm study to be conducted in the USA and Japan. Using an adaptive statistical design, the study plans to enrol 60 to 120 “no option” chronic limb-threatening ischaemia (CLTI) patients. Endpoints include amputation-free survival at six months, limb salvage and wound healing, and subjects will be followed out to three years. The “no option” patients who are candidates for the PROMISE II study are no longer eligible for conventional endovascular or surgical therapy for CLTI, as determined by an independent physician committee.
The approval to initiate the pivotal trial follows completion of six-month follow-up of the US early feasibility study—PROMISE I—that successfully enrolled 32 patients at seven centres. Interim outcomes from the first 10 patients treated in the PROMISE I study showed nine patients surviving and amputation-free at one year, with seven of these patients experiencing complete wound healing. These results were presented in May at the New Cardiovascular Horizons Conference by Steve Henao, of the New Mexico Heart Institute. The complete results of PROMISE I will be presented during the Late Breaking Trials Session at the VIVA conference in Las Vegas in November.
“For these late-stage CLTI patients, success can be defined in two ways: wound healing and amputation-free survival. This exciting new therapy has the potential to restore blood flow to the ischaemic foot, which may help patients heal their wounds and keep their feet. I am very encouraged by the early experiences in the USA, and outcomes from this pivotal trial may offer hope to the many Americans who might otherwise face major amputations,” said Daniel Clair, PROMISE II principal investigator and chair of the department of surgery at the University of South Carolina (USC) and Palmetto Health-USC Medical Group.
“Major amputations have a devastating effect on the lives of patients and their families, and each one is a personal tragedy. Chronic Limb-Threatening Ischemia is a public health crisis and far too many limb amputations are performed in the world today, costing the healthcare system many billions of dollars,” said LimFlow CEO Dan Rose. “As part of the FDA Breakthrough Devices program, LimFlow is excited to commence its US pivotal trial on the heels of the successful experience from the US feasibility study. This is a tremendous milestone that furthers our mission of empowering vascular specialists to offer new hope to their CLTI patients who may be only days away from losing a limb.”
CLTI is the most severe form of PAD and often occurs in patients suffering from coronary artery disease, diabetes, obesity, high cholesterol and high blood pressure, many of which are growing health problems. Patients with CLTI often experience profound, chronic pain and develop festering wounds or infections that lead to major limb amputation, an event closely associated with increased mortality and reduced quality of life. To relieve the symptoms of CLTI, patients today are treated primarily with angioplasty or open bypass surgery. In many late-stage patients, however, neither option is feasible due to extensive disease in the target arteries or other anatomical constraints.
The results of AVeNEW, the first level one clinical study dedicated solely to the use of a covered stent designed to treat stenosis in the arteriovenous (AV) fistula access circuit, show that the Covera vascular covered stent (Bard) demonstrates “significantly better” target lesion primary patency compared to percutaneous transluminal angioplasty (PTA) at six months, with the difference sustained in the 12-month data, and better access circuit patency was maintained at 12 months.
Lead investigator Bart Dolmatch, (The Palo Alto Medical Foundation, Mountain View, USA) recently presented this “first look” at the 12-month results of the AVeNEW study at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).
Dolmatch and colleagues describe AVeNEW as a prospective, international, multicentre randomised controlled clinical trial, designed to assess the Covera vascular covered stent compared to angioplasty for the treatment of stenotic lesions in the venous outflow of upper extremity AV access circuits in patients dialysing with an autogenous fistula.
The Covera stent, which received US Food and Drug Administration (FDA) approval in July 2018, is described on the FDA website as “an expandable, flexible, metal [nitinol] tube covered with a material called expanded polytetrafluoroethylene [ePTFE].”
Dolmatch and colleagues comment that AVeNEW is “the first level-one clinical trial dedicated solely to the use of a covered stent graft designed to treat stenosis in the AV fistula access circuit,” and they conclude that the covered stent group demonstrated “significantly better” target lesion primary patency compared to the PTA group at six months, with the difference sustained at the 12-month data. Access circuit primary patency was numerically different at six months, and “statistically better” for the stent graft group at 12 months.
The investigators enrolled 280 patients with stenosis ≥50 per cent in the venous outflow of the AV access circuit, and with clinical or haemodynamic evidence of fistula dysfunction, at 20 centres across the USA, Europe, Australia, and New Zealand.
They detail that patients received either PTA alone or PTA followed by covered stent placement. The primary endpoints were six-month target lesion primary patency and 30-day safety. Secondary outcomes included target lesion primary patency at 12 months, and access circuit primary patency at six and 12 months.
The majority of patients included in the study were Caucasian (68.6%) with a mean age of 63±12.4 years, and most patients were male (61.8%). Patients included in the study had multiple risk factors for renal dysfunction, including diabetes mellitus (69.6%) and hypertension (97.1%). Lesions were restenotic in 73.2% of cases, were on average 29.3±17.2mm long (diameter stenosis: 72.5±12.5%), and 53% were in the cephalic vein arch.
The proportion of patients free from a primary safety event with the covered stent (95%) was non-inferior to PTA (96.4%) at 30 days (p=0.002, significant for non-inferiority). Target lesion primary patency was significantly better for the covered stent group (78.7%) versus the PTA group (47.9%) at six months (Kaplan-Meier analysis) and remained statistically significant at 12 months (57.5% vs. 21.2%, respectively; p<0.001). Access circuit primary patency at six months numerically favoured the covered stent (50.7%) group compared to the PTA group (43.8%) while at 12 months the difference was statistically significant (28.9% vs. 17.7%, respectively; p=0.016).
The investigators summarise that the results of the AVeNEW study have shown that the covered stent conferred more than a 30% improvement in patency at the target lesion compared to PTA at both six and 12 months. Furthermore, the covered stent group had statistically superior access circuit patency at 12 months. “Clinical follow-up is ongoing,” they comment, “and will continue out to three years”.
Orchestra BioMed, in partnership with Terumo Corporation, today announced that the company has secured breakthrough device designation by the US Food and Drug Administration (FDA) for its Virtue sirolimus-eluting balloon (SEB) in the treatment of below-the-knee (BTK) peripheral arterial disease.
According to a press release, Virtue SEB is a novel, first-in-class drug/device combination product that delivers a sustained-release sirolimus formulation directly to the artery during balloon angioplasty without the need for a coating.
“Virtue SEB’s unique design enables delivery of sustained-release sirolimus during angioplasty without the need for coating or permanent implant. This highly differentiated design makes this product the ideal candidate for Breakthrough Device Designation in BTK peripheral artery disease,” says James P Zidar, clinical professor of medicine, UNC Health Systems, physician-in-chief, Heart & Vascular Corporate.
He continues: “Currently, there is a significant unmet need in the BTK stenosis treatment landscape. The presence of underlying comorbidities renders many patients unsuitable for bypass surgery. Angioplasty with plain balloons, which has been the default endovascular therapy for years, has a low success rate. Adding a proven anti-restenotic agent like sirolimus has the potential to enhance this treatment approach and drive better patient outcomes.”
“Our team is grateful that the FDA has recognised the potential value Virtue SEB can provide patients and physicians by granting this second Breakthrough Device Designation for an important arterial therapeutic indication,” said Darren R Sherman, president, chief operating officer and co-founder of Orchestra BioMed. “This designation will be critical as we continue to work with Terumo to accelerate Virtue SEB’s global clinical and regulatory program in both coronary and peripheral indications. In BTK disease, treatment with Virtue SEB has the potential to improve long-term outcomes and reduce periprocedural complications which can extend hospital stay and increase cost of treatment.”
The US Food and Drug Administration (FDA) has cleared the Artis icono, a family of angiography systems from Siemens Healthineers that permit a range of minimally invasive procedures to be performed in a single interventional suite.
The Artis icono biplane system is engineered for optimal utilisation in neuroradiology and abdominal imaging, while the Artis icono floor is a floor-mounted, single-plane system for vascular, interventional cardiology, surgical, and oncology procedures. Both systems in the Artis icono family expand the reach of precision medicine.
At its core, the Artis icono platform delivers the new OPTIQ image chain, which fundamentally redesigns image processing for 2D imaging. OPTIQ increases image quality across a wide range of C-arm angles and patient weights, regulating acquisition parameters to automatically achieve optimal image contrast at patient radiation doses that conform to the As Low As Reasonably Achievable (ALARA) guiding principal for radiation safety. The platform also improves the Siemens Healthineers roadmap function, which creates subtracted angiography images for easier navigation of the patient’s vascular system during subsequent fluoroscopy, allowing dose reduction during the fluoro mode.
Additionally, the Artis icono platform significantly enhances ease of use through Case Flows, which provide personalised workflow plans to optimise imaging parameters and system positions, in addition to displaying layouts for the entire procedure. Case Flows adapt to user needs, providing flexibility when executing certain sequences. Users can therefore standardise procedures across multiple Artis icono labs for improved outcomes and more consistent documentation.
Hammed Ninalowo (Lagos, Nigeria) and Scott McLafferty (Columbus Radiology Corporation, Cincinnati, USA) performed the first prostate artery embolization (PAE) in Nigeria on 29 August 2019.
The patient was a 77-year-old man with a long history of benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS), according to Ninalowo and McLafferty, and was initially seen for a consultation in July 2019. Describing the patient’s condition prior to treatment, the interventionalists tell Interventional News that, “A few months prior, he had developed acute urinary retention, necessitating placement of a suprapubic catheter. Since that time, he had a significant worsening in his quality of life due to catheter dependence. The presence of the catheter caused him both significant physical and emotional distress, with the patient regressing into a state of depression, and refusing to have guests around his home. Due to a complex medical history including a prior coronary artery bypass surgery, prostate surgery was not an option.”
Ninalowo and McLafferty say they are “proud” to have performed the first PAE in Nigeria, and to help this patient. “At the time he was seen in clinic”, they recount, “it was clear he was desperate for a solution and prepared to leave Nigeria to find one. However, with [the] continued awareness of local physicians and the possibilities of interventional radiology, he was sent to us for consideration of minimally invasive PAE.”
PAE is a minimally invasive treatment for LUTS secondary to BPH, and is frequently used to treat men who have failed traditional medical management. Ninalowo and McLafferty explain that this is the story for a large number of older men in Nigeria, saying “many are desperate for a solution to improve their symptoms or be free of their catheter dependence”. However, they also state that local options have been limited, especially in high-risk non-surgical candidates.
“Myriad Nigerian men suffered and did not have the means to seek PAE as a therapy locally”, they comment. “This is no longer the case. By offering this in Lagos, we create the first step towards improving access to care for these men.”
Nigeria is a country with a long history of its citizens traveling internationally for medical care. Five practising interventional radiologists today serve a country with a population of 200 million people. Ninalowo is helping to lead the effort to establish greater access to interventional radiology for all Nigerians. Following his own medical training in the USA, he founded the organisation IRDOCNIGERIA, which aims to train an additional 100 interventional radiologists in his home country over the next decade. The first interventional radiology training programme in Nigeria also launches this month, with Ninalowo at its helm.
McLafferty expands on the importance of this work: “I think this model of a local physician trained in America repatriating his skills to his own people is the key to achieving a sustainable interventional radiology practice in a virgin country. His [Ninalowo’s] practice, IRDOCNIGERIA, currently offers high-level interventional radiology procedures in Lagos, Nigeria.
“In addition, Ninalowo and I are managers with RAD-AID International’s IR4Nigeria effort to establish a sustainable IR training programme in Nigeria. With this, we have established a primary collaboration with the Nigerian Society of Interventional Radiology (NiSir), and also established a primary training site at the University College Hospital in Ibadan, Nigeria. The enthusiasm of local radiologists to learn interventional radiology has been tremendous and we plan to continue to provide immediate access to simple and complex interventional radiology procedures and help build long-term sustainability.”
According to a press release, Proximo Medical has been announced as the commercial partner for Biotronik’s peripheral vascular intervention (PVI) platform in select US markets.
Proximo Medical is a fractional commercial organisation for start-up medical device technologies and established medical device companies looking to expand adoption on select products in the US market.
Biotronik’s PVI portfolio is designed for the treatment of peripheral artery disease and includes the Pulsar stent, which is the only 4-French (4F) self-expanding stent approved in the USA. Additional products include the Astron stent system, Passeo PTA balloon catheters and Fortress introducer sheaths.
“By partnering Biotronik’s solutions and innovations with Proximo, we accelerate our ability to help physicians deliver improved outcomes to patients,” states Ryan Walters, president, Biotronik. “At Biotronik, our focus is always on innovation that improves patient lives. We know millions of American’s suffer from peripheral artery disease and this partnership will help ensure this patient population has access to safe and effective treatment options.”
“I was an investigator in the trial of the Biotronik Pulsar stent,” states Craig Walker, president and medical director, Cardiovascular Institute of the South; clinical professor of Medicine, Tulane University and Louisiana State University Medical Schools; and chairman, New Cardiovascular Horizons. “I was impressed that this stent, which has a 4F delivery system, was easy to deploy accurately and had good clinical patency. I think this will be very helpful particularly in cases where standard 5F or 6F sheaths may be occlusive.”
The American Urological Association (AUA) have published guideline amendments in the September issue of The Journal of Urology, but have not changed their stance on prostate artery embolization (PAE). The AUA does not recommend PAE for the treatment of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) outside the context of a clinical trial, a recommendation attributed to the expert opinion of a panel of urologists. This news is unwelcome to the interventional radiology (IR) community, which has been advocating for the procedure’s acceptance by the wider medical world. US interventional radiologists were awaiting these guideline amendments hopeful that new recommendations would better reflect the conclusion of multiple IR societies that PAE is a safe, effective, minimally invasive treatment option in select BPH patients.
The guidelines, authored by Harris Foster (American Urological Association Education and Research, Linthicum, USA) and colleagues, cite the following as their rationale:
SIR urges AUA to reconsider their “unnecessarily restrictive” recommendation, and to expand access to available treatment options for men
This has sparked a response from US interventional radiologists. In May this year, the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Société Française de Radiologie (SFR), and the British Society of Interventional Radiology (BSIR) published a position statement in the Journal of Vascular and Interventional Radiology (JVIR) concluding that current evidence supports the use of PAE for the treatment of LUTS for the symptoms of BPH in appropriately selected patients. The AUA has not accommodated this viewpoint in their latest guidelines amendments.
Speaking in her capacity as president of the SIR, Laura Findeiss (Emory University School of Medicine, Atlanta, USA) provides this newspaper with the following statement:
“The AUA’s recent guideline amendment to explicitly not recommend the use of PAE for the treatment of BPH outside of the context of a clinical trial fails to acknowledge the medical evidence supporting the safety and efficacy of this minimally invasive treatment option. It also fails to recognise the US Food and Drug Administration (FDA) approval of embolization devices for this use.
“SIR’s 2019 multi-society position statement on the application of PAE cites multiple randomised controlled trials and comparative studies of PAE versus the gold standard urologic treatment of lower urinary tract symptoms (LUTS) caused by BPH—TURP, or transurethral resection of the prostate. These studies show that symptomatic improvement following PAE approaches are seen after TURP, while maintaining a superior safety profile. The multisociety statement’s authors cite dozens of other prospective and retrospective cohort studies and meta-analyses that also support the safety and efficacy of PAE as a treatment option for LUTS caused by BPH.
“Due to the strong nature of the evidence supporting PAE, the societies endorsed PAE as ‘a definitive treatment option for multiple underserved patient groups, who may not have satisfactory urologic treatment options’. These patient groups include older patients with multiple medical conditions, patients with very large prostates, patients with bleeding from the prostate, patients with long-term bladder catheters, patients who cannot stop anticoagulation therapies and patients who desire to preserve sexual function.
“Furthermore, the National Health Service (NHS) in the United Kingdom has also acknowledged the strength of the evidence and supports the use of PAE to treat BPH symptoms in appropriately selected patients.
“AUA, however, has ignored the peer-reviewed data supporting PAE as appropriate for the sizeable population of men who are poor candidates for surgery and those who seek a nonsurgical, prostate-sparing option to treat their BPH symptoms. While AUA reasonably calls for increasing the level of evidence for the standard patient, the abundance of positive data moves PAE significantly beyond experimental. What is yet to be determined is where this therapy fits in the treatment algorithm. It is our hope that the urology community will partner with IR on behalf of patients in completing such recommended studies. Despite the AUA position, PAE is supportable as an evidence-based treatment modality that will remain available to men with LUTS secondary to BPH who seek this therapy.
“We urge the AUA to reconsider this recommendation, which is unnecessarily restrictive and is not founded in evidence. The SIR and the IR community stand ready to partner with urologists to ensure provision of the treatment that is most appropriate for each patient based on his clinical situation, risk tolerance and priorities.”
While AUA calls for more Level 1 evidence, some interventional radiologists claim this is “an impossibility”
In April this year, an SIR Foundation-sponsored research consensus panel for PAE was convened with urologists from the AUA with the aim of positively establishing the procedure in the urology society’s guidelines. The meeting was chaired by Clifford Davis (University of South Florida, Tampa, USA) and Jafar Golzarian (University of Minnesota, Minneapolis, USA). Davis informs Interventional News that since their conversation in the spring, where the AUA made it clear that it wanted additional Level 1 evidence, nothing has changed. He is therefore “unsurprised” by the consistent recommendation of the AUA to not recommend PAE outside of the context of clinical trials, and is planning funding applications for a randomised controlled trial aimed at producing Level 1 data.
There are multiple barriers to an RCT involving PAE, however. Firstly, the research consensus panellists need to decide on a study design: PAE versus a sham, or PAE versus surgery. There are concerns with conducting a trial of PAE against a sham due to crossover issues. Current guidelines from the AUA are based on RCTs with at least 12 months of data, and many had up to five years of follow-up. Patients randomised to a sham procedure or to PAE may move across to the opposite cohort before the 24-month mark, and could therefore cofound the data, but this would be still be considered as low Level 1 evidence.
Furthermore, as RCTs are so expensive, Davis explains that “industry or our national associations [in the USA] cannot afford to fund them”. Instead, interventional radiologists are looking to the National Institutes of Health (NIH) for funding. Four years ago, following an earlier SIR-sponsored research consensus panel meeting, a decision was made to apply for NIH funding for a PAE versus sham study, but this was rejected. With this precedent in mind, Davis favours “building a large, multicentre RCT comparing PAE to a surgical procedure”. A follow-up meeting to the April research consensus panel is to take place later this year to decide on which surgical procedure this may be.
“This sounds very simple”, Davis says, “but it is complicated because the patients that do best with PAE may have comorbidities for surgery. We feel that the patients who do best with PAE have bigger prostates in general, over 80g, which is not the typical patient seeking surgery. We have to compare PAE to a surgical technique that is generally accepted for a similar population. In my opinion, I think we should do an RCT [on either PAE] versus simple prostatectomy, or versus Holmium laser.” This latter option is a transurethral procedure that enucleates the prostate through the urethra, and is usually performed on men with larger prostates.
“I also think”, Davis elaborates, “an RCT trial with PAE should focus on patient satisfaction, including symptoms, quality of life, pain, and morbidity, and should not solely focus on flow rates and post-void residual (PVR) urine volumes, which are considered to be quantitative measures of surgical success. If PAE is found to be durable but less efficacious (regarding flow rates and PVR) but with fewer complications, lowers costs and reduced hospital time compared to surgical options, then I would hope the AUA would reconsider it in its guidelines for certain populations.
“In all other RCTs of surgery versus a control group, there was noted a significant drop in International Prostate Symptom Score (IPSS) even without therapy. This is a major argument of the urology community against our current data with small samples sizes and lack of long term follow-up.” In terms of data regarding the safety of radiation dose during PAE, Davis says that he and his team are currently working on publishing data from their centre in response to this concern raised by the PAE Research Consensus Panel.
Commenting on the status of the development of an RCT involving PAE, Ari Isaacson (Department of Radiology, University of North Carolina, Chapel Hill, USA), a co-author of the multisociety consensus document published in May, says: “The initial design and protocol and attempt to get funding [from the NIH] is underway, but it is a slow process. In the meantime,” he explains, “I think that a lot of urologists are going to feel handcuffed, because they do not feel that they can go against their society’s guidelines, and therefore there are going to be a lot of patients who either are not told about PAE or who are going to be dissuaded from pursuing it due to these guidelines.”
Even with funding, an RCT may not be feasible due to patient-driven issues with enrolment. Riad Salem (Northwestern University, Chicago, USA), another co-author of the multisociety position statement and an outspoken advocate of PAE, explains to this newspaper why this is the case: “An RCT has been tried, and it has been rejected, not by the medical community, but by the patients that would enroll. The BEST trial, while initiated as an RCT, was subsequently revised to a prospective comparison to TURP, because patients are not willing to be randomised to TURP. Patients are looking for minimally invasive treatments—so an RCT randomising TURP versus PAE is effectively an impossibility. It is not feasible and not constructive to wait for this clinical trial that will never happen.”
Nabeel Hamoui, one of three physicians dual-trained in urology and interventional radiology in the USA (Brooksville, USA) agrees with Salem. Hamoui expands, “I have seen this in my own experience at Northwestern. If you sit a patient down and say ‘we can do this therapy called PAE, which has fewer side effects, where you most likely do not need a catheter for more than a day, if that, and your recovery time is essentially zero, and if it fails, you can always have the other treatment option’, it is going to be very difficult to enroll enough patients into the TURP or surgery arm of an RCT. How do you accumulate Level 1 data if the patient becomes the rate-limiting factor?”
However, Isaacson tells Interventional News that the AUA was unmoved by discussions with interventional radiologists concerning past attempts to get US RCT data on PAE. “We tried to suggest alternatives as far as what types of data we could get”, he explains, “but despite our, I think solid, arguments, the reply was that unless there is RCT data, the AUA will not consider PAE as part of their guidelines. I think this methodology is flawed—their unwillingness to look at studies of other types excludes most of the evidence available that shows PAE is safe, so I think their evaluation of the procedure is limited, and they cannot gain a full, accurate picture of the safety and effectiveness of PAE. In my view, this is narrow-minded.” He adds that he is “disappointed” by the lack of change to the AUA guidelines for the surgical management of BPH.
This difficulty with accumulating Level 1 data on PAE, and the insistence of the AUA that interventional radiologists provide evidence from a US RCT investigating the procedure, has led to a “stalemate”, in Salem’s words.
Multidisciplinary cooperation called for to break the stalemate
As the US healthcare system operates on a fee-for-service model, one criticism levelled against either side in a dispute about procedural choice is that, instead of fighting for the best patient outcomes, individuals are fighting to protect their pay checks. Hamoui explains, “This is the reality of the US healthcare system. Unlike the NHS [in the UK], our system is based on the intensivity of care, not outcomes per se. As a urologist, if my practice is largely BPH-based, and I get paid to do surgery and treat them, then I am not going to want to give that up because that will affect my bottom-line. The opposite is also true: if an interventional radiologist aggressively markets PAE as the ultimate procedure, and recommend it over TURP and prostatectomy in a vast majority of cases, then they are doing so because they want money.”
However, Timothy McClure (Department of Urology, Weill Cornell Medicine, Lefrak Center for Robotic Surgery, New York, USA), a second dual-trained urologist/interventional radiologist in the USA and another co-author of the multisociety consensus position statement, says that urologists are acting solely on behalf of the patient: “I think the AUA is just being overly cautious, in part because of a lack of understanding of PAE. PAE is technically challenging, and they do not want problems arising in their patients. The guidelines are established to protect patients, so the bottom line is that they are trying to protect patients from having a procedure done that either will not make a difference or will potentially harm people. In fact, most urologists I have spoken with think PAE is a good option for certain patient populations. I think their concerns stem from a lack of understanding of what PAE is and what interventional radiologists can do. They view this as a technically challenging procedure that requires a certain level of skill which may not be applicable to the entire IR community. PAE is a complex case but skilled interventional radiologists do complex cases on a daily basis. Their concerns over radiation, complications, and side effects suggests a lack of understanding of PAE. These concerns could have been addressed by having an interventional radiologist participate with the guidelines. It is unfortunate that the AUA did not include a representative from IR.”
Davis likewise sympathises with the AUA guidelines committee, saying: “Some have negative feelings against the AUA; I feel differently. They hold their standards for their recommendations based on Level 1 data. They have held every other surgical procedure to that same level. It is just more difficult to compare a procedure across specialties. There is distrust in the USA, because in an RCT design by definition one specialty will lose patients to the other, which could introduce subspecialty bias during patient selection into the trial.”
The AUA guidelines are not all based on Level 1 evidence, though. For example, they state that “Water vapour thermal therapy may be offered to eligible patients who desire preservation of erectile and ejaculatory function”. This is a conditional recommendation, based on Grade C evidence. Grade C means “Low quality evidence: observational studies that provide conflicting information or design problems (such as very small sample size).” However, Davis notes that, although the evidence is marked as Grace C for this recommendation, it is based on an RCT of a sham versus therapy with three months crossover, and that this trial now has follow-up to two years.
“PAE is not alone in having heterogeneous outcomes”, Salem says. “If you look at a lot of data in urology, that too is heterogeneous. Heterogeneity is unfortunately a reality in medicine. Per the AUA guidelines, urologists should only offer robotic prostatectomy if they possess the necessary skillset. Why could that recommendation also not be made for PAE?”
Hamoui points to the urology procedure transurethral nuclear ablation, TUNA, highlighting its obsolescence. “We ourselves have done procedures that are now in the dustbin of urology”, he comments. “Many of those procedures that people thought were cure-all, and that were advocated for by some of the more prominent names in urology and pushed by industry, were largely financially driven, had poor evidence, and in five to seven years completely failed. The nuclear ablation machine in the practice where I work is now collecting dust in the corner. We no longer use it due to bad outcomes, but when it was recommended, I do not think that was based on Level 1 evidence.”
Salem urges urologists to understand that PAE is not in competition with TURP or prostatectomy. “All interventional radiologists are saying”, he says, “is that PAE should be part of the discussion, and one of the treatment options. Nobody is saying that anything should be replaced. Let the patient participate in the decision-making process. By urologist’s own admission, many of their treatments do not really work in glands over 80g. Most of their trials exclude glands larger than that volume. Glands this size or larger are the ideal candidate for PAE. So we are filling a niche, a treatment gap, that exists. To me, it is short-sighted to acknowledge there is a difficulty in treating larger glands, exclude them from urology studies, and then dismiss PAE.”
That interventional radiologists wish PAE to exist within the current treatment algorithm as one option for patients is something many are eager to highlight. “The key thing that I want to get across is that PAE provides a great addition to the BPH treatment algorithm”, Isaacson articulates. It does not replace the current surgical therapies, but it does provide a nice alternative to certain patients: those with very large prostates, those on anticoagulation medication, or patients with surgical comorbidities.”
“PAE is radically different from any of the urologic treatment modalities”, Hamoui says. However, he explains that this can be a hindrance as well as a positive. “In vascular surgery and IR, there is a huge overlap, so if vascular surgeons were to come up with new guidelines, they would have a lot of legitimacy because they understand IR procedures. For me, having the dual perspective [of urology and IR], I can understand that the treatment options sit alongside each other. I do not think that urologists fully understand the benefits of the procedure.”
Hamoui believes urologist education about PAE is critical. He, alongside McClure, advocates for the involvement of interventional radiologists on the AUA guidelines committee when discussing treatment options for BPH. Speaking at urology conferences is another method used by interventional radiologists to reach out across specialty borders. Salem gave a talk at a recent meeting of the Chicago Urologic Society, which reportedly helped diminish their scepticism of PAE, and aided the attending urologists’ understanding of which patients would and would not benefit from the procedure.
Publishing in urology specific journals would also be an effective communication tool for interventional radiologists to communicate to urologists, suggests Isaacson. However, he reports that this is challenging: “We have attempted to [publish in a urology journal] several times; it is very difficult to get a PAE paper in a urology journal”. Salem, who is one of few US interventional radiologists that has published a PAE paper in a urology journal, supports this assertion, commenting, “In my 20 years of publishing over 330 papers, getting published in a urology journal was the most difficult, challenging, controversial process I have ever been through. The captious reviews were rude, insulting, and, worst of all, replete with emotional bias. We tried several times, and finally got accepted into the fourth urology journal. This was a prospective, phase two, FDA-approved study, so it met all the high level criteria, but it was still dismissed by many urology journals.”
As well as operating on the community level, many interventional radiologists have also expressed the need to start locally. “Where I work”, McClure says, “we have great collaboration with the BPH experts, and we have a good, collaborative, multidisciplinary approach to [treating] men with LUTS. Not every patient is a good candidate for PAE, and not every patient is a good candidate for TURP, so ultimately patients benefit when you have this cross-over between disciplines.”
McClure believes that urologists need to understand that interventional radiologists are clinicians and not just technicians, and that for this there needs to be a “friendly, collegial” relationship between these two specialist groups. Hamoui, who mainly works as a urologist, thinks this is easier for him due to his dual training: “I am able to appreciate what interventional radiologists bring to the table”, he says, “so I can foster that by being friendly and receptive from the get-go, rather than being hostile and looking at them as competition. I think it is unfortunate to have PAE under such hostile attack. My own father, himself also a urologist, declined a TURP and opted for PAE, [performed] by Dr Salem, and was happy with the results.”
Salem is unequivocal in how he believes the debate should move forward: “The only way to break this stalemate is to engage individuals from both sides that can take a reasonable, tempered, non-emotional approach to this therapy. Get patients and get neutral physicians involved. Create a guideline that is tempered, recognises the limitations of the data we have, and incorporates PAE as one of the many treatment options for BPH. Until the loudest, most cynical voices are excluded from the discussion, this sensationalised and vitriolic debate will never end.”
Merit Medical has announced the commercial launch of Torpedo, a proprietary gelatin foam indicated for use in the embolization of hypervascular tumours. The Torpedo provides physicians a pre-shaped gelatin foam loaded into a cartridge with an optional blunt stylet, removing the need for manual foam shaping and providing fast and easy attachment to the catheter for delivery, a press release describes.
The Merit Torpedo is easy to prepare and use, requiring only hydration with a 50:50 saline-to-contrast mixture. The product is available in two diameters (2.5mm and 5mm) and two lengths (10mm and 20mm), and is designed for use with a catheter with an inner diameter large enough to allow delivery of the Torpedo to the target vasculature via syringe injection. The gelatin foam in the Torpedo is biocompatible, hydrophilic, and resorbable.
“In the operating room, time and consistency are crucial,” comments Fred Lampropoulos, chair and CEO of Merit Medical. “The Torpedo device, which includes embolizing gelatin compressed into a cylindrical shape and pre-loaded into a cartridge, will save physicians valuable time and improve material delivery with precision and predictability by eliminating manual cutting and shaping. The Torpedo’s launch exemplifies Merit’s commitment to ongoing innovation in the field of embolotherapy, and we look forward to bringing physicians even more ground-breaking technologies soon.”
The Torpedo’s commercial launch follows the recent 510(k) clearance of Merit’s EmboCube. The EmboCube offers uniformly cut cubes of gelatin foam preloaded into a syringe, specifically designed to save time and avoid inconsistent particle sizes associated with manual preparation of gelatin foam sheets. Torpedo and EmboCube, the newest additions to Merit’s suite of microcatheters and embolic products, together address an important market need: reducing surgical time without compromising quality of care.
Theresa Caridi is an interventional radiology advocate, and believes passionately in spreading awareness of minimally invasive, image-guided procedures to both potential patients and referrers. In July 2019, Caridi appeared on ABC 7 News WJLA, an ABC affiliate covering national and local news in Washington, DC, USA, where she talked about uterine fibroid embolization for Fibroid Awareness Month. Here, she describes why it is important for interventional radiologists to market themselves, and how individuals, as well as organisations like the Society of Interventional Radiology (SIR), can best spread their message about what interventional radiology has to offer. outreach
Understanding interventional radiology (IR) as a specialty and descriptor has been a topic of much discussion over the last two decades, if not for even longer.1–5 The name itself has been questioned for its reductive nature, in that the term “interventional radiology” fails to explain the complexity and value of what we do.1 We interventional radiologists cannot always describe the type of doctor we are, so it is easy to see how our patients and referrers have a gap in understanding in what IR is and how we can help. It has even been speculated that IR cannot be easily understood because both the specialty and term are in the forefront of true interdisciplinary medicine—specifically the blending of image, body, and physician.1 Public outreach in the form of speaking/lectures, radio, media, or print marketing may help to provide clarity to both patients and referring physicians on treatment options provided by IR.
Additional factors play an important role in the lack of awareness of IR. As interventional radiologists, we may become involved in a patient’s treatment plan later than a primary specialty. Once the traditional specialties have offered what they can and failed, or are ruled out as an option due to a patient’s advanced disease, a referrer may think to involve an interventional radiologist, or a patient may ask for other options. Due to the diverse nature of our specialty, we lack the longstanding relationship that begins early in a patient’s life, such as that seen with a primary care physician or obstetrician/gynaecologist. Furthermore, interventional radiologists have knowledge of and treatments for the entire body, and are sometimes lost in the treatment algorithm because we are not the first specialty that comes to mind for a specific organ system. Lastly, there are many different types of IR practices, and the patient or referring physician may only be familiar with one—and this practice model may not be the one they are looking for.
A good marketing tool is one that derives traction from both patients and colleagues. One of the most effective ways that I have found to reach patients and referrers is through educational videos that demonstrate a physician’s knowledge, but perhaps more importantly also their character and disposition. When a patient comes in for consultation after having watched one of my educational videos, I get a sense that it has accelerated their comfort level and also their ability to speak about sensitive issues—this tends to be pretty valuable in a women’s health focused practice where a woman has spent her lifetime building a relationship with her gynaecologist, but has never met her interventional radiologist. This is one of the many challenges that we face.
Podcasts, particularly with video, can have a similar beneficial effect. Any type of video allows viewers to see the physician’s human side and allows for nuances that cannot be demonstrated in a social media snippet. It also seems a bit more credible than the average social media post. This is not to diminish the effect of social media, which has been shown to improve the transparency and accessibility of medicine.6 Social media can be very useful in promoting speaking engagements, radio, traditional media, or print marketing. But social medial must be used appropriately. Information that could identify a patient must be removed, including age and specifics about disease. Further, one must be careful not to give medical advice outside of suggesting a person get evaluated by a physician.7
I think most would agree that promoting IR in this manner is necessary, but it is time consuming. It takes institutional infrastructure and often an eager physician to get follow through. Fortunately, the Society of Interventional Radiology (SIR) is launching a national awareness and education campaign this fall—the Vision to Heal, Together—which takes a multipronged approach, with aspects that promote IR to patients and elements that market the discipline to referrers. Stay tuned and, in the meantime, do not be afraid to ask for help from your institution’s marketing team or to learn from an IR colleague who already has a successful marketing plan in place.
Theresa Caridi is an interventional radiologist at MedStar Georgetown University Hospital, Washington, DC, USA.
References:
Two-year results of EffPac—a randomised controlled trial to assess the safety and efficacy of a novel drug-coated balloon (DCB) with a nanotechnology coating—have been announced. The investigators, Ulf Teichgräber (University Hospital Jena, Germany) and colleagues, report that use of the DCB in question, iVascular’s Luminor, resulted in a significantly lower incidence of binary restenosis compared to plain old balloon angioplasty (POBA).
The new data, presented for the first time at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain), also showed a significant clinical and haemodynamic improvement from baseline, similar to the level of improvement achieved with POBA, but with considerably fewer repeat revascularisations. The investigators found no difference to POBA regarding safety.
The EffPac (Effectiveness of paclitaxel-coated Luminor balloon catheter versus uncoated balloon catheter in the arteria femoralis superficialis) trial was designed to assess the safety and efficacy of the Luminor paclitaxel drug-eluting balloon in inhibiting restenosis and in ensuring long-term patency. The investigators compared the DCB catheter to non-coated POBA in stenotic or occlusive lesions of the femoropopoliteal artery.
Between September 2015 and December 2016, the investigators enrolled 171 subjects across 11 German study centres. Eighty-five of these patients were randomised to DCB angioplasty, with the remaining 86 being assigned to the POBA group. They note that before the 24-month mark, analysis was discontinued for 25 patients in the DCB group and 30 patients in the POBA cohort.
The primary endpoint of the study was defined as late lumen loss at six months. The secondary endpoints at six, 12, and 24 months included primary patency, target lesion (TLR) and vessel (TVR) revascularisation, quality of life—assessed by the EQ-5D—change of Rutherford-Becker classification (RBC), ankle-brachial index (ABI), and major and minor amputation rates, among others.
The authors comment that 12 months in to the study, the investigational DCB catheter proved “highly effective and safe in inhibiting restenosis,” and demonstrated a walking improvement in change of RBC compared to POBA.
Twelve-month results of the safety and efficacy of the Luminor device had been released prior to the CIRSE 2019 presentation. The authors detail that at six months, the late lumen loss was on average 0.92mm lower in the DCB group than in the POBA group (95% confidence interval [CI]: -1.36mm; -0.49mm, p<0.001). Significantly more patients showed a walking improvement after DCB treatment at six months (p=0.021).
Looking now at the 24-month results, Teichgräber and colleagues reveal that primary patency (the rate of freedom from restenosis) was 90.2% (80.4–95.2) in the DCB arm, compared to 94.7% (86.4–98) at 12 months. The corresponding figures for the POBA cohort were 62.7% (50–73) and 71.3% (59.4–80.3).
Freedom from TLR in the DCB group was 97.2% (89.1–99.3) at 24 months, compared to 98.7% (91.1–99.8) at 12 months. In the POBA group, the figures were 78% (66.5–86) and 81.6% (71–88.7), respectively.
The investigators detail that in both groups patients were of similar age. While the DCB cohort was 68±7.5 years old, on average, the POBA group was 68.1±8.8 (p=0.979). There were slightly fewer male patients in the DCB group (60%) than in the POBA group (69.8%; p=0.239), and also slightly fewer diabetic patients in the DCB group (36.5%), compared to 40.4% in the POBA group (p=0.681). There were fewer current smokers in the POBA group than among DCB patients (40.5% vs. 43%; p=0.856). There were just over double the number of patients with critical limb ischaemia in the DCB group (3.6%) than there were in the POBA group (1.2%; p=0.929).
Following the publication of a meta-analysis in the Journal of the American Heart Association late last year that reported an increased association of mortality with paclitaxel devices used in the leg, Konstantinos Katsanos found himself at the centre of a maelstrom of debate and division within the international endovascular community. Here, he discusses that spotlight on his science, as well as enthuses about the future of vascular access and interventional radiology as a whole, which he imagines will ultimately become needleless.
I was just about to finish my undergraduate studies at the Patras School of Medicine in 2001 when I was exposed to a peripheral Angiojet thrombectomy case that was the first one to be performed in Europe, by professor Dimitris Siablis. I still remember my fascination with the specific medical device fragmenting and aspirating the thrombus through remote pinhole access in the groin—being a medical student at the time, the sheer potential of catheter-based technologies was mind boggling to say the least. Over the next couple of years, I slowly became addicted to the field of interventional radiology (IR) and image-guided therapies in general through attending national and international symposia (including CIRSE [the annual meeting of the Cardiovascular and Interventional Radiology Society of Europe]) that confirmed in my eyes the transformational and cutting-edge character of IR.
Nowadays, I most enjoy combining general clinical skills with image interpretation and image guidance to deliver highly accurate therapies with the use of sophisticated catheters and dedicated miniaturised medical instruments. Transcatheter atherectomy for plaque excision/removal, the use of drug-coated balloons and stents for the inhibition of vascular restenosis, utilising radioactive beads for targeted internal organ radiation therapy, balloon kyphoplasty and new-generation vertebral augmentation techniques are some of my favourite procedures—all of which demonstrate the unique, minimally invasive, and highly effective nature of IR treatments.
Professor Dimitris Siablis has been my IR teacher and mentor from the very beginning. He had the courage to believe in me whilst I was still an undergraduate student, invested his time in teaching me most catheter and guidewire skills, and had the kindness to mentor me through my early academic endeavours. He has actually been more of a coach and mentor then a professor of medicine. His ‘inheritor’ and my current director, professor Dimitris Karnabatidis, has continued the tradition by delivering unlimited, unselfish and considerate education and guidance not only to myself, but to a whole team of more than a handful aspiring junior IR fellows. Finally, Professor Andreas (Andy) Adam, who was my director for nearly five years at St Thomas’ Hospital in London, UK, has been a unique role model by exhibiting exemplary leadership and sharing unparalleled insights into the future of the IR profession.
I have been very fortunate to work in two completely different healthcare systems both as a trainee/fellow and as a consultant/professor. Greece has been the stepping stone in my early training days in IR and the UK has been the landing site for my junior consultant job. I was lucky to enjoy the benefits of the more liberal, more forgiving Greek healthcare system early on followed by the more mature and conservative UK National Health Service later as I was transitioning to a consultant level job with different priorities and responsibilities. I think that in a combined way they both contributed to my education by amalgamating current standards of clinical practice, academic research and medical ethics.
By employing good research and statistical practice, we showed that there is increased risk of all-cause patient death with the use of paclitaxel-coated balloons and stents in the femoropopliteal artery in the lower limbs for treatment of intermittent claudication. Interestingly, since our contentious publication in JAHA, two companies have produced errata of mortality counts in industry-sponsored studies. Meanwhile, new evidence has also come to light, mostly in the form of so-called individual patient data (IPD). Both the IPD analysis performed by the US Food and Drug Administration (FDA) and the one performed by the non-profit VIVA consortium have confirmed a significant mortality risk with the use of paclitaxel (when analysing the data from the pivotal randomised controlled clinical trials). I personally maintain the view that the future of endovascular peripheral arterial disease (PAD) treatments is going to be drug-coated or drug-eluting, but in a different way. As I have stated before, endovascular treatment is not going back to the Stone Age of plain balloons and metal any time soon. I personally think that had there been an alternative means (other than paclitaxel) to treat restenosis, we would not have had the kind of intense reaction we experienced.
Our findings have initially been received with anger and denial—often regrettably so by our own peers. However, we are scientists and we need to read the numbers, apply good statistical practice and acknowledge and act on the results regardless of personal, commercial, emotional or other conflicts of interest. The fact that paclitaxel is the only difference in the treatment between active and control arms across all randomised controlled studies makes it very likely that paclitaxel is also the cause of the problem—in a direct or indirect way. This is not to say that we definitively know that paclitaxel causes the problem. Ultimately, we have the responsibility to report both positive and negative findings to be able to advance science for the sake of patient safety and public health. To quote Sir Bradford Hill in his 1965’s presidential address: “All scientific work is incomplete—whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.” Being in the spotlight should not disrupt or affect in any way solid, credible scientific research.
I think that regulatory bodies across the world (the FDA, the Medicines and Healthcare products Regulatory Agency [MHRA], etc.) have responded swiftly, responsibly and above all professionally in validating our findings and interacting with the industry to guide next steps. On their mandate, industry stakeholders have quickly collected and delivered a wealth of new data in order to better understand this alarming situation. Unfortunately, however, in my personal opinion it is a real shame that the average researcher or scientist is not allowed access to all that individual patient data for more in-depth analyses and explorations of alternative hypotheses.
Our aim has been to create a meeting fully dedicated to the emerging role of endovascular management of dialysis access. EVA encompasses topics from access creation (surgical or endovascular) to percutaneous maintenance and declotting by treatment of stenoses and thromboses. EVA will strive to disseminate the highest quality of relevant medical research and increase awareness among healthcare professionals on the important service they can provide to their dialysis patients by increase access longevity and improving quality of life. This is extremely important as we strongly believe that the future of dialysis access is endovascular. We envision that EVA will soon become the go-to meeting of reference in the field of endovascular access interventions.
I am currently predicting/dreaming of augmented reality in the IR suite for improved perception and manual skills, routine use of perfusion monitors for diagnosis and aftercare of critical limb ischaemia, multi-drug-coated balloons for angioplasty and multichemo-laden microparticles for cancer embolization, integration of optics and photonics for the design of next-generation needles and catheters, and most likely the gradual emergence of completely needleless procedures, for example high-intensity focused ultrasound ablation of a tumour or magnetically guided microparticles to concentrate into particular tissue sites or intravascular micro-robots harnessing energy from the host to propel themselves and clear the arteries and/or deliver medications on demand.
My hobbies outside of medicine are: movies, computers and tech, occasionally running and cycling. Personal interests beyond academia include European and global geopolitics, space exploration and an ongoing fascination with numbers and maths.
Philips and B Braun have announced the launch of Onvision, a breakthrough ultrasound guidance solution for real-time needle tip tracking in regional anaesthesia. Available on the latest version of the B Braun and Philips Xperius ultrasound system, Onvision gives anaesthesiologists the confidence to accurately position the needle tip inside the body. The introduction is part of a multi-year strategic alliance between Philips and B Braun to innovate in ultrasound-guided regional anaesthesia, a rapidly growing alternative to general anaesthesia. Onvision is being launched at the 38th Annual Conference of the European Society of Regional Anaesthesia and Pain Therapy (ESRA) in Bilbao, Spain (11–14 September).
Accurate needle placement is critical to the success of regional anaesthesia procedures, such as peripheral nerve blocks, both in terms of effective pain relief and the avoidance of unintended nerve and vessel punctures or collateral damage to surrounding tissue. While real-time ultrasound imaging has proved to be a valuable tool for needle guidance, failure to optimally visualise the needle tip remains a challenge for both novice and experienced anaesthetists. Currently, 10–20% of all peripheral nerve blocks are ineffective on the first attempt. By simplifying alignment between the needle and ultrasound probe, Onvision reduces the effort needed to interpret the ultrasound image. This allows the anaesthesiologist to more confidently guide the tip of the needle to its target.
“Regional anaesthesia is a rapidly growing alternative to general anaesthesia and has the potential to improve patient outcomes as well as increase workflow efficiency in the hospital,” says Bert van Meurs, chief business leader, Image Guided Therapy at Philips. “By combining B Braun’s expertise in needle design with Philips’ capabilities in real-time image guidance, we have created a solution to one of the biggest challenges in regional anaesthesia—accurate positioning of the needle tip in the body. Our alliance with B Braun is a strong example of our commitment to partner with industry leaders to grow our footprint in the therapy market.”
“Our customers want intuitive solutions that allow them to focus on the patient rather than the technology, so they can achieve the best outcomes. As demand for regional anaesthesia grows, improved efficiency can also help reduce the pressure of an increasing workload,” comments Meinrad Lugan, member of the board for the Hospital Care Division at B Braun. “Onvision is a perfect example of what can be achieved through shared expertise to meet the evolving needs of our customers, bringing regional anaesthesia to more patients in more hospitals worldwide.”
Together, B Braun’s Stimuplex Onvision needles and Philips’ Onvision needle tip tracking technology indicate the position of the needle tip in relation to the ultrasound viewing plane to an accuracy of better than 3mm, a press release reports. A sensitive micro-sensor placed on the needle, combined with advanced signal processing and visualisation techniques on the Xperius system, indicate the real-time location of the needle tip in relation to the 2D ultrasound viewing plane. The solution provides greater flexibility in needle trajectory and can reduce procedure times. The increased confidence and predictability offered by Xperius and Onvision will empower more anaesthesiologists to embrace regional anaesthesia as a viable and effective alternative to general anaesthesia.
Regional anaesthesia or analgesia involves the injection of an aesthetic in the proximity of a nerve, targeting areas of a patient’s body that are subject to surgical intervention. Regional anaesthesia can have significant advantages over general anaesthesia for both patients and hospitals. Patients undergoing regional anaesthesia typically benefit from reduced opioid consumption and fewer side-effects, such as nausea. Moreover, regional anaesthesia may lead to faster post-surgical recovery, allowing patients to ambulate or leave the hospital sooner, which benefits both patients and hospitals.
Together, Xperius and Onvision form an integrated point-of-care solution for supporting current and future needs in regional anaesthesia. They are co-branded and sold via B Braun’s global sales network, with Philips providing installation and service. Xperius is part of Philips’ complete portfolio of point-of-care ultrasound solutions, which offers clinicians the ability to confidently diagnose and care for their patients in any work environment.
CIRSE 2019 Gold Medal awardee, Thierry de Baère (Villejuif, France), tells Interventional News at the society’s annual meeting (7-11 September, Barcelona, Spain) that this award is a reflection of CIRSE’s interest and engagement with interventional oncology (IO).
On the IO education front, the natural next step after the creation of the curriculum, which acts as a foundation for interventional radiologists, will be to have teaching materials as well, he states.
He also addresses the current thinking on drug delivery to tumour, which “does not always need [to be achieved alongside] embolization”, he says, emphasising that interventional radiologists are well placed to deliver drugs directly to the tumour with the view to eliciting an immuno-oncologic response. Such intratumoural delivery enables high local dosage to destroy the tumour, without the toxicity of systemic delivery.
Twelve-month results of the BIOFLEX COF trial have demonstrated that the implantation of stents with low chronic outward force (COF) was associated with less neointimal hyperplasia, consequently resulting in less restenosis. Patients treated with Biotronik’s low COF Pulsar stent showed significantly lower restenosis rates than patients treated with the high COF LifeStent implant. Martin Funovics, Medical University of Vienna, Austria, presented the full cohort primary endpoint data at the annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).
BIOFLEX-COF is the first randomised controlled trial (RCT) to investigate differences in clinical outcomes of nitinol stents with high versus low COF in de novo superficial femoral artery occlusive arterial lesions. The low-COF Pulsar stent had a mean restenosis rate of 26%, while the high-COF LifeStent implant showed 35%, as measured on CT angiography at one year (p<0.001, t-test and Mann-Whitney U test).
“We initiated the BIOFLEX COF trial to close the gap on how COF impacts the human neointima,” explains principal investigator Funovics. “These RCT data support our hypothesis that high COF leads to increased neointimal hyperplasia, which causes restenosis and increases the risk of repeat interventions for the patient. Our results suggest that COF impacts clinical outcomes and should therefore be an important factor in the choice of the stent.”
Self-expanding nitinol stents must be oversized by at least a minimal amount to ensure contact with the vessel wall and prevent migration. Once the stent is deployed, it exerts a continuous force upon the vascular wall, termed COF. While an animal study has found increased neointimal hyperplasia, inflammation and injury scores in vessels treated with high COF stents, human data were not available until now.
The investigator-initiated BIOFLEX-COF RCT enrolled 83 patients with symptomatic peripheral arterial lesions eligible for endovascular stent implantation. The patients were randomised 1:1 to either a high COF group or a low COF group. The trial’s primary endpoint is the amount of in-stent restenosis at one and two years as assessed by contrast-enhanced CTA.
“At BIOTRONIK, we develop our technologies to continuously improve patient outcomes,” comments Alexander Uhl, senior vice president of Corporate Marketing at BIOTRONIK. “With its unique design, Pulsar stent offers the benefits of a low COF stent and thin struts while resisting crush force: the optimal balance of radial forces keeps the vessel open, increase blood flow and reduce stress to the vessel wall. This helps to decrease patients’ risk of restenosis and need for re-interventions.” chronic
Cook Regentec has announced enrolment of the first patient in an international clinical trial evaluating the HemaTrate Blood Filtration System to treat patients with critical limb ischemia (CLI) due to peripheral arterial disease (PAD). To treat CLI, the HemaTrate system produces an autologous, peripheral blood-derived total nucleated cell (TNC) concentrate for intramuscular injection into the ischemic limb.
“Critical limb ischemia is the final stage of peripheral arterial disease and is associated with major morbidity and mortality despite current medical and surgical treatment,” noted Bijan Modarai, the study’s principal investigator, who treated the first enrolled patient at Guy’s and St. Thomas’ Hospital in London, UK. “Circulating nucleated cells are thought to stimulate vascular repair and regeneration and are of growing interest as a potential therapeutic option for these patients.”
The HemaTrate CLI (HT-CLI) trial is an international, multicentre, randomised controlled study that will enrol up to 350 patients. Subjects with Rutherford class 4 or 5 CLI will be randomised to receive a series of three intramuscular injection treatments of TNCs or saline, six weeks apart. The primary endpoint is clinical benefit through 12-month follow-up, defined as freedom from reintervention, major amputation or death. Following the 12-month study period, all patients will be offered TNC treatment for both study and non-study limbs. Patients will be followed for a total of 24 months.
“Patients with PAD-associated CLI who are poor candidates for surgical or endovascular procedures require alternative treatment options that deliver improved long-term outcomes,” said Brad Shirley, business leader at Cook Regentec. “We are excited that patients enrolled in our global CLI trial will begin to receive HemaTrate as treatment for this often-devastating condition.”
Bijan Modarai is a principal investigator of the HemaTrate CLI trial and is a paid consultant of Cook Regentec.
New data on the use of Zilver PTX, Cook Medical’s paclitaxel-coated stent for peripheral arterial disease (PAD), confirms the safety of the device. These data were presented at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).
Michael Dake, senior vice president of health sciences at the University of Arizona, Tucson, president-elect of the Society of Interventional Radiology Executive Council, and global principal investigator, presented new 5-year data on Zilver PTX that Cook Medical gathered from the randomised controlled trial (RCT) performed to obtain US Food and Drug Administration (FDA) approval.
Cook Medical is the only organisation that has publicly provided long-term, patient-level data on the use of paclitaxel-coated devices for PAD. In addition to previously released information, the presentation included new data that had not been previously published.
These new data include information from patients who had not previously completed the study, such as those who had been lost to follow up, giving a more complete view of how paclitaxel-coated devices affect patients.
The data confirm no significant difference in all-cause mortality for the Zilver PTX drug-eluting stent compared to traditional angioplasty or a bare metal stent (BMS). The findings further show that treatment with Zilver PTX and paclitaxel dose were not predictors of mortality. However, age and other serious conditions common in PAD patients were associated with mortality.
The findings that Dake presented have been published online in CardioVascular and Interventional Radiology (CVIR), a peer-reviewed journal, which can be found here.
“Our clinical program evaluates the Zilver PTX technology across a broad, real-world patient population—including patients at high risk for restenosis and reintervention. Zilver PTX offers proven long-term benefits that help patients get back to living,” said Mark Breedlove, vice president of Cook Medical’s Vascular division.
The patient-level data used for the RCT analysis, as well as Dr Dake’s presentation and other Zilver PTX information, is available at https://www.cookmedical.com/peripheral-intervention/paclitaxel/.
Dr Michael Dake is a paid consultant for Cook Medical.
NOTE: This video is ONLY available to watch in selected countries and geographies
Geniculate artery embolization (GAE) is responsible for statistically significant improvements in pain scores from baseline out to three months, the preliminary results of the first European prospective study on the procedure show. Mark Little (University of Reading and Royal Berkshire NHS Foundation Trust, Reading, UK) presented these early results of the GENESIS study (Geniculate artEry embolisatioN in patiEnts with oSteoarthritis of the knee) today at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).
While cautious about overinterpreting what he stresses are early data, Little is nonetheless optimistic about these positive results, telling delegates at CIRSE: “Musculoskeletal (MSK) embolisation is the next frontier in embolotherapy”.
The GENESIS investigators report “excellent recruitment”, with 34 patients enrolled since the trial started recruiting. Little believes this reflects the fact that GAE is serving an unmet clinical need. Osteoarthritis is a common condition with a growing prevalence due to an increasingly obese and elderly European population. For those patients older than 45 years of age who have mild to moderate osteoarthritis that is resistant to conservative treatment, yet is not severe enough to warrant joint replacement, GAE is being hailed as a potential solution.
Detailing the scientific rationale for GAE, Little explained to the CIRSE audience that inflammation of the knee joint drives synovial angiogenesis through macrophage activation. “It is hypothesised that angiogenesis contributes to structural damage and pain in osteoarthritis”, he explained, “and GAE can be used to treat this pain”.
The single centre, prospective GENESIS study (funded by Merit Medical and the National Institute for Health Research, NIHR) uses changes in pain measurements from baseline to post-procedural follow-up to assess the efficacy of GAE. Consultant interventional radiologists performed the procedure using 100–300micron Embosphere particles (Merit Medical) diluted in 20ml contrast.
Pain is a complex multifactorial process and the GENESIS study protocol is using a number of novel tools to assess patient’s pain. Little’s research group at University of Reading, UK, is using neuropsychological assessments employing functional magnetic resonance imaging (fMRI) of the brain to map pain, in addition to measuring Visual Analog Scores (VAS) pain scores, and using the Knee Injury Osteoarthritis Outcome Score (KOOS), a validated questionnaire used throughout the orthopaedic literature on knee osteoarthritis.
Overall Visual Analogue Scale (VAS) decreased from baseline at both six weeks and three months follow-up: mean VAS was almost 70 pre-GAE, and just below 30 six weeks post-procedure. VAS score was 33 at three months (p<0.005). Meanwhile, Knee Injury and Osteoarthritis Outcome Score (KOOS) increased from baseline to one-year follow-up, representing a reduction in pain and symptoms. Mean KOOS was 39 at baseline, 62 (p<0.005) and 85 one-year post-procedure.
There were two minor complications, observed in the 22 patients treated with GAE for this interim analysis—two cases of transient skin discoloration early on.
Explaining the significance of these results, Little tells Interventional News, “I really want to stress how important it is to precisely measure patient’s pain. We need to up our game in terms of accurate outcome measures in MSK embolization. We are very fortunate to have the Center for Integrative Neuroscience and Neurodynamics (CINN) at the University of Reading to carry out the pain assessments as part of the GENESIS study.”
Little reported that preliminary neuropsychology data reveal signals that may predict treatment failure. “We are continuing to model the neuropsychological pain experiments with the ultimate aim of aiding patient selection”, he said. The triallists are instituting neuromodulation prior to the procedure to improve clinical outcomes.
Omar Ishrak, Medtronic’s chairman and CEO is to retire on 26 April 2020, following the end of the company’s current fiscal year. Also, the Medtronic Board of Directors has announced key leadership appointments as part of its multi-year, leadership succession planning process. A press release reports that these announcements will ensure a smooth and successful transition in leadership across the company.
The Board of Directors has unanimously appointed Geoff Martha, currently executive vice president (EVP) of the company’s Restorative Therapies Group (RTG), to assume the newly created role of Medtronic president and become a member of the Medtronic Board of Directors, effective 1 November 2019. He will also succeed Ishrak as Medtronic CEO, effective 27 April 2020. As president, according to the press release, Martha will lead Medtronic’s operating groups and regions. Brett Wall, president of Medtronic’s Brain Therapies division, was appointed EVP and group president of RTG, succeeding Martha, effective 1 November 2019.
At the start of Medtronic’s next fiscal year, on 27 April 2020, Ishrak will assume a new position of executive chairman. He will provide counsel and guidance to Medtronic’s leadership, oversee CEO succession, and drive the ongoing successful execution of Medtronic’s long-term strategic plan. These changes are designed to ensure a smooth transition, continuity of leadership and a continued focus on delivering Medtronic’s innovation strategy and financial performance.
Ishrak comments: “We have announced leadership changes that meet both the Board’s objective of executing a thoughtful leadership transition as well as my personal desire to begin transitioning my duties as CEO to a new leader coinciding with the start of our next fiscal year. This plan and its timing enable Geoff and I to partner on achieving Medtronic’s key financial performance goals as well as delivering on our critical pipeline milestones, including several important product launches. Leading Medtronic as CEO is an honour and a privilege, and I know that Geoff is the right leader to take Medtronic to the next level of its growth and evolution. Geoff is a results-oriented, dynamic, and innovative business leader who is passionately committed to our mission, the advancement of our growth strategy and the development and diversity of our people. I am confident he has the right track record, commitment, vision and judgment to lead our company.”
Scott Donnelly, Medtronic’s lead director, and chairman, president and CEO of Textron, says: “As Omar approaches the company’s mandatory executive officer retirement of 65 years of age next year, we have ensured Medtronic has the right leadership at the right time to advance its mission and deliver shareholder return through a seamless transition. The Board is extremely grateful to Omar for his outstanding leadership—as the company’s annual revenues have doubled and its market capitalisation has increased by more than US$100 billion during his tenure. We are confident Omar’s contributions to Medtronic will continue as executive chairman. The Board’s succession planning process prioritises developing leaders from within the company, and we are pleased that we could advance Geoff and Brett for these roles. During his time at Medtronic, Geoff has demonstrated his unique ability to lead, innovate and drive results, and the Board has full confidence in him and his ability to take Medtronic into its next chapter of growth.”
Michael Dake (Tucson, Arizona) presented the two-year data from the VERNACULAR trial at CIRSE 2019 on 8 September in Barcelona, Spain.
Dake said: “The 24-month results from the VERNACULAR trial using the BD Venovo stent show absolutely sustained benefit in terms of patency [and] quality of life from one year to two years. We saw a very high follow-up of 83% of patients coming back for a follow-up at two years. We had an overall 83% primary patency of two groups, the non-thrombotic iliac vein lesions and the post-thrombotic syndrome lesions. And again, we can see that the target lesion revascularisation and target vessel revascularisation was less than 11%. These are fantastic results and we coupled that with the fact that radiographic evaluation, a very high percentage of patients, showed zero fractures not only at one year, but at two years.”
This video was filmed by BD and is being sponsored for distribution in association with Venous News, Vascular News and Interventional News.
Speaking at the 2019 annual meeting of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE; 7–10 September, Barcelona, Spain), Vincent Vidal (Marseille, France) describes the Fair-Embo technique, detailing how to obtain the inexpensive embolic agents, the technical efficacy of the procedure, and his ambitions for the project’s future.
An initial preclinical study in a porcine model tested the feasibility and safety of arterial embolization with absorbable and nonabsorbable suture fragments. The investigators reported a technical success, demonstrating the proof of concept of the feasibility and safety of the so-called “FAIREmbo” procedure. Demonstrating the in vivo feasibility of the procedure led Vidal and colleagues to propose what they termed the “FAIR-Embo technique”. Writing in Cardiovascular and Interventional Radiology (CVIR) earlier this year, they concluded: “Embolization by absorbable and non-absorbable suture is a feasible and effective treatment, which opens up the possibility of global use of this inexpensive and widely available embolization agent”.
At present, Vidal is working with the French Society of Radiology (FSR) to send out a survey to countries with emerging economies—“potential Fair-Embo recipients”, in his words—to map interventional radiology services around the world. The survey will be sent to more than 3,000 email addresses across Africa, South America, Asia, the Middle East and eastern Europe. The survey asks basic questions about access to interventional radiology services, such as:
Although the survey results are yet to be received, Vidal speaks to Interventional News about his expectations. He tells this paper that he anticipates the results “mapping the places where interventional radiology is possible”, as the answers will delineate where in the world trained physicians are working, the availability of imaging hardware such as X-ray machines, and where access to implantable medical devices is an issue. “The final goal”, he says, “is to target the places where FAIR-Embo will be helpful, and also where the existence of an educational programme will be useful as a first point of action”.
With this in mind, the future steps of the Fair-Embo project that Vidal envisions centre around creating a global community of interventional radiologists. Initially, he plans to create a foundation with the capacity to fund a FAIR-Embo clinical programme in developing nations. Outlining this idea to Interventional News, Vidal enumerates the features of this potential future foundation: “We will get help from a proctor if necessary to set it up. I foresee the foundation as one which can offer tips and tricks to interventional radiologists working in low resource settings, which will help provide any necessary materials, and which can help elaborate an existing clinical research programme.”
Further to the development of a FAIR-Embo foundation, Vidal would like to link this with “all the interventional radiology organisations around the world”. Ambitious in his aims for the project, Vidal says that he would like to collect data from the FAIR-Embo community (such as the number and outcomes of embolizations performed) “in order to give feedback to international healthcare organisations such as the International Atomic Energy Agency (IAEA) and the World Health Organisation (WHO)”.
By taking these steps, Vidal hopes to create “a virtuous cycle”. He imagines it working thus: FAIR-Embo will help to develop embolization practices in low resource settings; data collected from these procedures will help to obtain funding from international organisations; this funding will help interventional radiology research in the form of the development of clinical programmes in emerging countries.
At CIRSE, Vidal presented a new study demonstrating how to obtain non-spherical particles with suture material. Using scissors, he advises interventional radiologists to cut sutures into small fragments between 700 and 1,100 microns long. So called “FAIR particles” (Figure 1) are then injected via a catheter to the target site, and their technical success is demonstrated through post-embolization imaging (Figure 2).
Afshin Gangi (Strasbourg, France), CIRSE vice-president, is enthusiastic about FAIR-Embo, commenting: “Even if this concept is not adapted for all cases, if this material becomes clinically available [as an embolic agent], it will be a game changer for developing and even for industrial countries.”
Detailing why he thinks this, Gangi says to Interventional News: “Traumatic, post-partum or post-surgical bleeding is a major cause of mortality. Until the late 1970s, operative management was considered the only legitimate course for blunt and penetrating abdominal and extremity vascular injuries. Interventional techniques first popularised in the early 1970s now offer a wide range of solutions, principally using transcatheter arterial embolization. Various embolic agents (for example, coils or gelfoam) and particles may be used to stop or control bleeding. All these agents used individually or in combination can save lives by stopping life-threatening bleeding.
“An embolization performed by a well-trained interventional radiologist is essential in all centres dealing with bleeding—trauma centres, maternity wards, surgical units where high blood loss is common, to name a few. In developing countries, training interventional radiologists to safely perform embolization is key. However, regardless of IR training or the presence of an angiosuite with high resolution C-arm fluoroscopy capabilities, availability of the embolic agent is an issue. The idea of having an efficient embolic agent which is available anywhere and is cost-effective is very attractive.
“The idea underpinning ‘the FAIR-Embo concept’, which demonstrates the feasibility and efficacy of using non-absorbable and absorbable sutures, is about making a cheap embolic agent available everywhere. In addition to this availability, the benefits of this material are that it is inexpensive, can be temporary or permanent, that it leads to mechanical obstruction, and that suture fragments are easy to work with.”
Medtronic has announced the first-ever results from the IN.PACT AV access clinical study comparing the investigational IN.PACT AV drug-coated balloon (DCB) to percutaneous transluminal angioplasty (PTA) in patients with de novo or non-stented restenotic arteriovenous (AV) fistulae lesions. The study met primary safety and effectiveness endpoints and data were presented today at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting (7–11 September, Barcelona, Spain).
“Maintaining patency and limiting the frequency of reinterventions needed to keep AV access sites functioning properly remain significant treatment challenges for physicians treating AV fistulae lesions,” says Andrew Holden, director of interventional radiology at Auckland Hospital and associate professor of radiology at Auckland University (Auckland, New Zealand). “These results demonstrate the promise of IN.PACT AV DCB to not only address these critical issues, but to potentially improve the quality of life of patients undergoing dialysis.”
AV fistulae, otherwise known as AV access sites, are created and used to deliver haemodialysis to patients with end-stage renal disease (ESRD). Over time, vessel restenosis limits the ability to use AV fistulae effectively. In order to restore function, patients often undergo one to three AV fistula maintenance procedures per year. The need for frequent reinterventions can result in significant disruptions to critical haemodialysis care and increased costs to the healthcare system. Drug-coated balloons have the potential to extend the time between reinterventions by maintaining AV access site patency, therefore maximising a patient’s uninterrupted access to lifesaving dialysis care.
The IN.PACT AV Access study is a randomised controlled trial (RCT), which has enrolled 330 subjects at 29 sites in the USA, Japan, and New Zealand. The primary effectiveness endpoint was defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or access circuit thrombosis measured through six months post-procedure and the primary safety endpoint was defined as the serious adverse event rate involving the AV access circuit through 30 days post-procedure. Additional endpoints include but are not limited to: access circuit primary patency, cumulative target lesion revascularisations, and number of interventions required to maintain target lesion patency.
The study enrolled a challenging patient population who had been undergoing dialysis for an average of 4.3 years. Overall, the IN.PACT AV DCB group demonstrated clinical benefit compared to the PTA control group. Key data highlights include:
Additionally, the Kaplan-Meier estimated freedom from all-cause death through 360 days was 90.6% in the IN.PACT AV DCB study group and 90.4% in the PTA control group. This data adds to the initial safety data presented at US Food and Drug Administration’s Advisory Committee meeting of the Circulatory System Devices Panel in June, showing no difference in mortality rates in this patient population.
“The data presented today at CIRSE demonstrate the potential of IN.PACT AV DCB to address restenosis in high-risk patients who currently have few long-term treatment options available to them,” comments Mark Pacyna, vice president and general manager of the Peripheral Vascular business, which is part of the Aortic, Peripheral, and Venous division at Medtronic. “As part of our commitment to improving outcomes, we look forward to generating further clinical evidence in support of this therapy.”
In the USA, IN.PACT AV DCB is an investigational device and not yet approved for commercial use. In January 2016, the CE (Conformité Européene) indication for the IN.PACT Admiral DCB was expanded for the treatment of failing arteriovenous access in patients with end-stage renal disease undergoing dialysis.
In collaboration with leading clinicians, researchers, and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services that deliver clinical and economic value to healthcare consumers and providers around the world.
A meta-analysis, recently published in Osteoporosis International, has found that the application of percutaneous vertebroplasty (PVP) is safe and effective only in patients with acute osteoporotic vertebral compression fractures (OVCFs) having persistent and severe pain. The investigators recorded no benefits among patients with older fractures or those bearing non-severe symptoms.
According to the authors, S Lou (The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China) and colleagues, OVCFs are common in the elderly population and are often treated using PVP. However, the effectiveness of PVP reported by various randomised controlled trials (RCTs) is inconclusive. This study therefore aimed to analyse, from published literature, the efficacy and safety of PVP for OCVFs.
Lou and colleagues conducted searches in Medline, EMBASE, and Cochrane Libraries since their respective inceptions on 1 January 2019 for RCTs of OVCFs treated with PVP compared with non-operative treatment. The primary outcomes were pain relief at one to two weeks, one to three months, and six to 12 months. The secondary outcome was the rate of occurrence of new vertebral fractures, and the meta-analysis was performed using a random effect model.
The investigators included a total of 12 RCTs, comprising 1,624 patients, in the analysis. For the blinded studies, they found statistical differences between PVP and the sham injection group for the three primary outcomes in the subgroup of the Vertebroplasty for acute painful osteoporotic fractures (VAPOUR) trial. Although pain scores were similar between the PVP group and the sham injection group for the VAPOUR trial at each period, the effect size of PVP increased over time.
They found that in the open label studies, PVP significantly reduced pain at all the time points, and that the risk of the new vertebral fractures was similar between the PVP groups and control groups.
Due to certain limitations of the meta-analysis, Lou and colleagues warn that the results should be “interpreted cautiously”. They note, for example, methodological limitations in the quality of the original studies, such as the unclear random method, the unclear concealment of the treatment allocation, and the inadequate blinding.
In addition, the possibility of publication bias might exist because of the ongoing and unpublished trials, although no statistical evidence for this was detected.
They also note that while the baseline of pain scores and duration of fracture might be key factors affecting the PVP, there might be other clinically relevant but unreported confounding factors, such as the types of patients, the degree of bone mineral density, and the types of PVP techniques. Moreover, owing to the limited studies, whether the baseline of pain scores and duration of fracture truly affect the PVP “still needs to be determined by further trials”.
Considering the direction of future research, the investigators suggest that it should “focus more on [patients with acute OVCFs and experiencing severe pain] and use more consistent inclusion criteria”. They suggest, for example, that each study should add the confirmation of OVCFs with magnetic resonance imaging (MRI) to the inclusion criteria and use the same threshold of the baseline scores for patient eligibility.
Lou and colleagues also suggest that, since they determined that the baseline information could affect the effect of PVP, further studies “should clearly report the baseline information, such as the duration of back pain, the baseline pain scores, the methods of non-operative therapy, the PMAA volume, and the baseline T-scores, and other clinically relevant factors, to find the association between these factors and PVP.”
Finally, they indicate that a longer follow-up—more than 12 months—with a large enough sample size is “necessary for further studies to determine the long-term therapeutic effects of PVP”.
Thousands of eligible patients are not receiving endovascular thrombectomies after suffering a stroke due to a shortage of neurointerventionalists worldwide. In an effort to combat this, the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), and the Interventional Radiology Society of Australasia (IRSA) believe interventional radiologists must treat acute ischaemic stroke patients. SIR has today published an update of its stroke guidelines, outlining the pathways to ensure adequate training for those performing the procedure. David Sacks, lead author of these guidelines and a physician who has been involved in stroke intervention since the original publication of the PROACT trial in 1999, here describes why involving interventional radiologists in stroke care is critical.
How many patients with acute ischaemic strokes could be treated with emergency endovascular thrombectomy (EVT) but are not? Why is this happening? What can be done to help?
In the USA in 2015–2016, only 2.6% of stroke patients received EVT.1 A European survey on stroke care authored by Aguiar de Sousa et al on behalf of the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN), and the Stroke Alliance for Europe (SAFE) found that EVT was offered in 40 of 44 European countries. On average across the continent, the procedure was offered for 1.9% of all strokes.2 The highest country rate was 5.6% of all strokes. Assuming that 5% is a reasonable goal, this means that 67,000 patients were clinically eligible for EVT but not treated.
Notably, the European survey considered 5% to be a conservative estimate. There is strong evidence from the DAWN and DEFUSE 3 trials3 to treat selected patients up to 24 hours after stroke onset. Furthermore, patients over 80 years of age have a similar odds ratio of benefit compared to younger patients.4 Randomised trials are underway to evaluate the benefit of EVT for mild strokes, large core infarcts, and patients with moderate baseline disability. In one published national registry of current practice, 11% of treated patients had mild strokes, not currently included in treatment guidelines.5 Patients with large core infarcts are also likely to benefit.6 In the UK, it is estimated that about 10% of stroke admissions would be eligible for EVT, an estimate which does not include patients with mild strokes, large cores, baseline disability, or time from stroke onset >12 hours.7 It is estimated that 30–46% of acute ischaemic strokes involve large vessel occlusions,8–11 and a recent commentary suggests that every stroke patient with an acute large vessel occlusion “should undergo thrombectomy unless the weight of evidence is strongly against treatment”.12
Why are more eligible patients not being treated? In the European survey, the most common reasons were lack of specifically trained personnel, lack of facilities, and costs. Multiple studies have demonstrated that EVT is a highly cost-effective intervention, but stroke interventions involve complex care, from ambulance staff to emergency department and radiology evaluation, patient transport, endovascular treatment, critical care management, stroke unit care, and rehabilitation. The resources to provide this care have not yet caught up with the recent proof of effectiveness of EVT.
One way to provide additional personnel is to train vascular interventional physicians to provide EVT. In theory, this would allow EVT to be provided in locations where neurointerventional physicians are not able to provide 24/7 care, or not available at all. Hospitals that may not have sufficient volumes of cerebral aneurysms or vascular malformations to support multiple neurointerventional physicians may be able to provide EVT by sharing the EVT work with other endovascular colleagues. This raises a series of questions: can other interventional physicians be trained sufficiently to provide EVT such that outcomes meet international benchmarks? Might the learning curve for training be such that patients would be better off not being treated at all, or being transferred to another hospital with delayed treatment? If a hospital cannot provide 24/7 coverage by physicians specifically trained for neurointerventional procedures, might it also lack the infrastructure to provide all of the rest of the complex care that is necessary to achieve good outcomes? Might the treatment of stroke patients at many local hospitals lead to many low-volume centres with suboptimal outcomes compared to a few high-volume centres? Many of these questions will require trials for answers. In the meantime, patients with acute ischaemic strokes are being vastly undertreated with EVT.
Interventional radiology societies believe that appropriately trained interventional radiologists can help address the manpower needs. Interventional radiologists are currently active providers of EVT. The majority of the interventional physicians in The Netherlands who participated in the MR CLEAN trial and registry were interventional radiologists. The odds ratio for benefit in the MR CLEAN trial was the same as for the neurointerventional trial sites.13 The vast majority of the physicians providing EVT in the Czech Republic are interventional radiologists, and published results from the Czech registry are comparable to neurointerventional outcomes. In the USA, 60% of primary stroke centres perform EVT, and of these, 41% rely on interventional radiology physicians,14 and overall, 34% of EVT cases were performed by physicians who had not trained in dedicated neurointerventional fellowships.15 In a survey conducted by the Society of Interventional Radiology (SIR), approximately 25% of interventional physicians providing EVT at certified comprehensive or thrombectomy-capable stroke centres are interventional radiologists. SIR, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), and the Interventional Radiology Society of Australasia (IRSA) have published a joint statement on the role of interventional radiologists in acute stroke interventions.16 Working with neurologic and neurointerventional sister societies, SIR and CIRSE have published international benchmarks for EVT outcomes.17 A European pathway for training interventional radiologists in stroke interventions has been established.18 SIR has just published an update of its training guidelines written by multispecialty authors from Interventional radiology, neurointerventional, combined interventional radiology and neurointerventional, stroke neurology, and endovascular neurosurgery backgrounds. The SIR training guidelines require a background of endovascular expertise supplemented with stroke specific imaging, cognitive, and technical training.
EVT is a powerful tool to reduce disability from acute ischaemic stroke. There is strong evidence that eligible patients are not receiving EVT due to a shortage of EVT physicians. IR physicians are currently working with our neurointerventional colleagues to provide this care with acceptable outcomes.
David Sacks is an interventional radiologist in the Department of Interventional Radiology at The Reading Hospital and Medical Center, West Reading, USA.
References:
The Society of Interventional Radiology (SIR) has today published new training guidelines for endovascular stroke treatment in the Journal of Interventional Radiology (JVIR). This is the first update since 2009, when the society released training guidelines for intra-arterial catheter-directed treatment of acute ischaemic stroke.
“Obviously, the world of stroke intervention has changed tremendously since then”, lead author of the guidelines David Sacks (The Reading Hospital and Medical Center, West Reading, USA) tells Interventional News. At the time, catheter-directed thrombolysis was the only such therapy studied in randomised trials. In the intervening decade, mounting positive evidence for endovascular thrombectomy from randomised trials and meta-analyses, and the subsequent growth in the number of these procedures being performed each year, has led the SIR to believe that these new recommendations are timely and necessary.
The guidelines were authored by a diverse group of interventional radiologists, specifically-trained neurointerventionalists, endovascular specialists, and stroke neurologists, as well as academics and community hospital staff; they varied to being freshly out of training themselves, to having over 30 years’ experience of stroke interventions. Sacks explains to this newspaper: “We solicited people from a range of backgrounds so that we could have a diversity of opinion, experience and knowledge. We wanted to make sure that we were meeting the needs of people in many different environments, as well as meeting the needs of patients.”
However, no official representative of the Society of NeuroInterventional Surgery (SNIS) participated in the creation of these guidelines. Despite the SIR inviting various leaders and former leaders of SNIS to participate in the creation of these guidelines, “for various reasons those individuals declined”, Sacks reports. Several of the guidelines authors are members of SNIS, though. Sacks also adds, “We [SIR and the guidelines authors] have maintained lines of communication with the current leaders of SNIS, and we remain open to working with them in whatever ways would advance patient care for stroke interventions”.
“Interventional radiologists are seeking guidance as to how they should train”
Earlier this year, SIR, the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), and the Interventional Radiology Society of Australasia published a joint position statement in the Journal of Vascular and Interventional Radiology (JVIR) outlining the role of interventional radiologists in acute ischaemic stroke interventions. Sacks, who was also the lead author of this joint statement, describes this as “an acknowledgement that interventional radiologists have an important role to play in stroke care”, but adds that “it was also cautionary, stating that interventional radiologists must be adequately trained”. These latest guidelines provide the training pathway alluded to in the earlier joint statement.
Sacks says that the new guidelines “make clearer what training and experience interventional radiologists are expected to have to be performing these [endovascular stroke] procedures”. He continues: “I think there are an increasing number of interventional radiologists already who are involved in stroke interventions, and like any kind of medical care, there will be a range of experiences and capabilities. We are trying to bring more uniformity at a high level of what that training and experience should be. I think there are already many hospitals that are turning to their interventional radiologists to help provide this care, and those interventional radiologists are seeking guidance as to how they should train. They want to do a good job, and they need to know what the recommendations are for them to train to be able to do the good job they are committed to.”
Specific training requirements
The updated guidelines state: “The IR physician is expected to have baseline mastery in accordance with the Accreditation Council for Graduate Medical Education (ACGME) milestones of level 4 or higher of arterial access, selective vascular catheterisation, including microcatheters, and mechanical revascularisation, including thrombectomy and thrombolysis of extracranial vessels. The IR physician is also expected, as part of core training and certification in diagnostic radiology, to have experience with neuroimaging including CT, MRI, and perfusion imaging.”
There is no requirement for full-scope neuroendovascular training through either a formal neurointerventional fellowship or near equivalent. “However”, the authors note, “specific and rigorous training with demonstration of competence is required”. Adequate training, according to Sacks et al, involves the following:
In addition, the new SIR guidelines stipulate that “a minimum of six months of documented cognitive neuroscience training during or post-residency is necessary to become competent in the interventional care of patients with acute ischaemic stroke”.
Three training pathways are outlined in the document to highlight how this competency could be achieved. Firstly, the new ACGME accredited IR/diagnostic radiology residency programme in the USA will provide trainees with at least two years of dedicated clinical and procedural training, with “motivated residents” able to access up to six months of neuroscience training. Alternatively, practicing interventional radiologists could achieve competency to treat ischaemic stroke through a proctorship. The guidelines authors elaborate: “Ideally, supervised training would include robust, hands-on training, not limited to interventional techniques but also workup prior to and management after thrombectomy”. The final training pathway detailed in the guidelines is for physicians to enrol in an educational stroke course involving procedural simulations and potentially virtual reality to supplement stroke training.
The consensus of the guidelines’ authors is that a minimum of 10 procedures per year for each operator is recommended for maintenance of physician competence. The onus also falls on institutions to provide appropriate infrastructure and support, according to Sacks and colleagues. They conclude: “Institutions performing stroke intervention must establish quality assurance programmes to optimise processes and outcomes, and both technical and clinical outcomes must be entered into a database or registry”.
Endovascular thrombectomy procedures on the rise
“I think the number of stroke interventions will continue to increase”, Sacks predicts. The current number of stroke interventions are vastly fewer than the number of patients generally acknowledged to be eligible. A 2018 survey from the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN) and the Stroke Alliance for Europe (SAFE) investigated the access to and delivery rates of stroke care in 44 European countries—and found that over 65,000 stroke patients eligible for endovascular treatment were not provided with this intervention. On average, 1.9% (95% confidence interval [CI], 1.3–2.5) of all patients with an ischaemic stroke in Europe received endovascular treatment, while a recent UK study estimated that approximately 10% of stroke patients are good candidates.
The most common reason that stroke intervention was not performed on an eligible patient was the lack of adequately trained physicians, leading Sacks to argue that there is a need for well-trained interventional radiologists to perform these procedures. “Having more interventional radiologists who are adequately trained will allow more patients in total to be treated when it is appropriate to treat them”, he says.
In addition to the potential increase in stroke interventions caused by treating a greater majority of eligible patients, Sacks also believes the overall number of eligible patients will rise. “The estimates on which these articles are relying [for estimates of eligible patients] are based on the well-accepted indications: patients within six hours, patients with ICA-M1/M2 occlusions, and patients whose strokes are sufficiently severe but do not have large core [infarcts]”, he says. “There are multiple trials underway looking at whether patients with mild strokes or patients with large core [infarcts] will benefit.
“I think that in the future, we are going to be treating increasing numbers of patients with a broader set of indications. Stroke patients will be treated at an increasing number of centres [in the USA] rather than [just at] the current number of thrombectomy-capable stroke centres. I think there will be more uniformity in the way people are training, and more uniformity in the expectations for outcomes.”
Beacon Tip catheters (Cook Medical) are once again available to physicians in Europe. As of September 2019, the catheters are available in the UK, Ireland, Norway, Sweden, Finland, Denmark, Germany, Poland, the Netherlands, Luxembourg, Belgium, France, Switzerland, Austria, Hungary, Spain, and Italy. Cook is continuing to work on releasing the products to customers in the rest of Europe, the Middle East, and Africa in the near future.
“Patient safety is always a priority for us, and we are proud of the changes we have made. Improved packaging allows for physicians to once again have access to catheters, designed for torqueability, visibility and pushability, to improve procedural outcomes”, said Mike Williams, global director of Cook Medical’s Vascular programmes. Beacon Tip catheters are used for diagnostic angiographic procedures and feature a visible distal tip designed to improve visualisation when using fluoroscopic guidance.
In 2016, Cook Medical issued a voluntary global recall of all Beacon Tip catheters following concerns that the tips were fracturing due to environmental factors. As patient safety is always a priority, engineers at Cook began intensive testing to find a solution. The products now come with specialised foil packaging to help protect the catheters from the environmental effects that contributed to the recall.
Cook invested resources into innovating the product packaging and meeting regulatory standards from multiple governing bodies. The catheters were reintroduced in the USA and Canada in 2018 and are now approved for physician use in many countries in Europe.
Foundation trainees’ perception of interventional radiology (IR) is “generally poor due to a lack of adequate knowledge”, a recent survey from the Radiology department of the Pennine Acute Hospitals NHS Trust, Manchester, UK, reports.
Marawan El Farargy, Khalid Bashaeb, Linda Watkins, and Aws Alfahad, all from said institute, set out to assess perceptions of the specialty amongst foundation trainees, with the simultaneous aim of exploring the means by which these perceptions could be addressed, “with the overall outcome of encouraging junior doctors to consider a career in this advancing sub-speciality.”
El Farargy et al distributed a physical copy of an anonymised survey to a total of 79 students in the first and second year of their foundation course (FYs), all of whom responded. Forty-five per cent (34 of 79) were introduced to interventional radiology within their prescribed training posts, and 38% (29 of 79) were “interested enough to learn more through self-directed reading”, El Farargy and colleagues report. Approximately 28% (22 of 79) had heard of interventional radiology during medical school rotations and a few trainees (six of 79) were exposed to the specialty during elective placements.
“The findings of the present survey are indicative of the poor general knowledge of FYs regarding interventional radiology,” the authors surmise, “and highlights that interventional radiology is not introduced appropriately to undergraduates”. They continue: “The Royal College of Radiologists has already made recommendations regarding the embedding of clinical radiology as a whole in medical education. Interventional radiologists must take a leading role in the education of both undergraduate and junior doctors to address the apparent lack of interest in radiology of newly qualified doctors. In addition, universities and societies should ensure that a basic level of general radiology and IR knowledge is obtained by medical students prior to graduation.”
Three-quarters of foundation year students unwilling to consider a career in IR
“Despite reasonable awareness of the IR sub-speciality, 75% of FYs (59 of 79) stated that they were not willing to consider a career in interventional radiology, and around 11% were unsure about pursuing a career in interventional radiology,” the authors write. “Of those who did not wish to consider IR as an option, 53/59 lacked general interest in radiology and 13/59 felt they did not have enough information about this career option”.
While almost all respondents demonstrated awareness that interventional radiology is both an elective and an emergency specialty, over 45% did not know that attending clinic is part of the consultant role. Citing an American study by Julia Fielding (Department of Radiology, University of North Carolina, Chapel Hill, USA) et al that found that less patient contact discourages medical students from selecting radiology as a speciality, El Farargy and colleagues say, “it is understandable that inadequate knowledge of the typical interventional radiology consultant job plan may dissuade junior trainees from pursing interventional radiology as a future career”.
Survey respondents were asked to rate possible ways of raising awareness about interventional radiology on a scale of one to five, with lower scores being worse. “Surprisingly, 65% (50 of 79) rejected the notion of learning more about interventional radiology at all”, El Farargy et al describe, though the most popular method of awareness-raising was deemed to be elective placements and teaching throughout foundation years, followed by lectures in medical schools. Attending multidisciplinary team meetings was the least preferred option.
Discussing these methods, the authors suggest that “multiple strategies can be employed, including radiology placements, electives, and student-selected modules, encouraging attendance at interventional radiology procedures, provision of student access to interventional radiology conferences, and embedding appropriate multidisciplinary team meetings within the student timetable”. For foundation schools, they advise teaching sessions, adequate access to taster week programmes, and the inclusion of radiology rotations within their foundation posts.
“Again,” they write, “the interventional radiology community need to step up and ensure they are involved in both decision-making and face-to-face teaching levels to capitalise on available opportunities”.
They conclude with a call to action for current interventional radiologists: “It is essential that we, as a radiology community, take responsibility for this crucial issue and work to boost perceptions of interventional radiology amongst the consultants of tomorrow”.
Balloon-occlusion prostatic artery embolization (PAE) is as effective as conventional microcatheter PAE in the treatment of benign prostatic hyperplasia (BPH) with a potential to reduce nontarget embolization, Tiago Bilhim (Saint Louis Hospital, Lisbon, Portugal) and colleagues report in the Journal of Vascular and Interventional Radiology (JVIR). However, the authors were surprised to note that there was no clear advantage of balloon-occlusion PAE over the conventional technique.
The investigators set out to compare the safety and efficacy of these two types of PAE. In this single-centre, prospective, randomised, single-blind clinical trial, 89 patients with symptomatic BPH were assigned to conventional microcatheter PAE (43 patients) or balloon-occlusion PAE (46 patients), and were treated between November 2017 and November 2018. All patients were embolized with 300–500µm Embosphere microspheres (Merit Medical), and were evaluated one and six months post-procedure.
All efficacy variables improved in both groups with statistical significance, with the exception of International Index of Erectile Function, which remained constant in both groups, and prostate-specific antigen levels, which decreased significantly in the conventional microcatheter PAE group (0.9nb/mL±2.22; p=0.01).
Assessments at six months after PAE showed mean International Prostate Symptom Score (IPSS) reduction from baseline was 7.58±6.88 after conventional microcatheter PAE, and 8.30±8.12 after balloon-occlusion PAE (p=0.65).
Mean prostate volume reduction was 21.9cm3±51.6 (18.2%) after conventional microcatheter PAE and 6.15cm3±14.6 (7.3%) after balloon-occlusion PAE (p=0.05).
Additionally, Bilhim et al report no statistically significant difference in the average maximum pain reported within 24 hours after the procedure (0.74±1.31 and 0.93±1.70 in conventional microcatheter PAE and balloon-occlusion PAE groups, respectively; p=0.056).
Longer term data are needed to determine if the relapse rate is different between the two PAE procedural methods.
Comparing the two PAE procedures, Bilhim and colleagues are surprised by their results, writing: “Balloon-occlusion PAE relies on the potential to prevent reflux and to reverse blood flow in the anastomoses between the prostate and surrounding organs. Thus, it would be reasonable to expect fewer adverse events in balloon-occlusion PAE and less need for protective coil blockage of the prostatic anastomoses. These assumptions were not proven here, as the overall rate of adverse events was not significantly different between the two groups.”
Indeed, no major adverse events occurred in either group, whilst minor adverse events occurred in 23 patients (53.5%) in the conventional microcatheter PAE group, and in 26 patients (56.5%) in the balloon-occlusion PAE cohort. Penile skin lesions and rectal bleeding, which the study authors say can be due to nontarget embolization, only occurred in the conventional microcatheter PAE cohort: three patients (7.1%) had penile skin lesions and two (4.7%) had rectal bleeding.
Interpreting these findings, the investigators say that “these observations are probably clinically relevant, as they represent indirect measures of nontarget embolization”. They continue: “The lower rate of these adverse events [penile skin lesions and rectal bleeding] in the balloon-occlusion microcatheter PAE group (with no reported events) could be due to the protective features of balloon-occlusion. However, the wedged embolization technique used as opposed to a free-flow embolization and a low usage of protective coils (14%) could have led to a higher rate of nontarget embolization in the conventional microcatheter PAE group (n=5; 11.9%).”
Bilhim and colleagues recommend that future trials compare the two types of PAE procedures using radiopaque microspheres or macroaggregates, in an effort to clarify “any potential benefits related to reduced nontarget embolization in particular”.
When enumerating the potential benefits of balloon-occlusion PAE in comparison with conventional microcatheter PAE, Bilhim et al list reduced coil usage (as the placement of coils has been shown to increase procedural times and radiation exposure) and the establishment of an intraprostate negative pressure, which the authors claim “could likely allows the use of a larger amount of embolic volume”. If this latter benefit holds true, Bilhim and colleagues postulate that balloon-occlusion PAE “could lead to greater prostatic destruction, together with higher values of prostate-specific antigen in the 24 hours following embolization, and greater clinical relief”. However, this was not proven in the present study.
Furthermore, the authors note that their work corroborates earlier studies in showing that 5α-reductase inhibitors are not detrimental to the clinical outcomes after PAE. In fact, the present study “uncovered a potential positive interaction with PAE outcomes—that is, the use of 5α-reductase inhibitors before PAE may lead to better clinical outcomes”, according to Bilhim and colleagues.
Concept Medical has been granted breakthrough device designation from the US Food and Drug Administration (FDA) for MagicTouch AVF, its sirolimus drug-coated balloon (DCB) catheter, for the treatment of stenotic lesions of arteriovenous fistulae or arteriovenous graft in haemodialysis treatment of renal failure.
The FDA received a request from Concept Medical to designate MagicTouch AVF as a breakthrough device in July 2019. The proposed indications for the breakthrough device designation for the MagicTouch sirolimus-coated balloon catheter is indicated for use in percutaneous transluminal angioplasty (PTA), after appropriate vessel preparation for treatment of stenotic lesions of dysfunctional native arteriovenous dialysis fistula or graft with 4–12 mm diameter and up to 100mm in length.”
On 28 August, Concept Medical was informed by the FDA that “your combination product and proposed indication for use meet the criteria and have been granted designation as a breakthrough device.”
The world’s first pilot study to investigate the safety and efficacy of Magic Touch percutaneous transluminal angioplasty (PTA) sirolimus balloon in vascular access interventions was started in Singapore in 2018. Led by principal investigator, Tan Chieh Suai, a multi-disciplinary team of doctors consisting of interventional nephrologists, vascular surgeons and interventional radiologists, is conducting the study entitled “Sirolimus coated angioplasty balloon in the salvage of thrombosed arteriovenous graft” in Singapore General Hospital.
In response to the breakthrough designation for Magic Touch AVF, adjunct assistant professor Tan Chieh Suai, senior consultant and director for the Interventional Nephrology Program in the Department of Renal Medicine in Singapore General Hospital and Duke-NUS Medical School, said, “The award of the breakthrough device designation for the use of sirolimus-coated balloons in dialysis access is fantastic news for patients on haemodialysis, as there is an urgent need for effective and durable treatment for narrowing (stenosis) within the dialysis circuit.”
Tjun Yip Tang, associate professor and consultant vascular and endovascular surgeon, Singapore General Hospital, Singapore has highly appreciated the success of Concept Medical and said, “We are still in the early stage in the clinical study of drug-coated balloons for haemodialysis access patients. The paclitaxel-based technology study results have certainly been encouraging, but more research is required to determine if other devices may prove to be more effective or uniquely beneficial for specific anatomical or clinical subtype presentations.”
The breakthrough device designation granted to Magic Touch AVF offers Concept Medical an opportunity to interact with the FDA’s experts. Under the programme, the FDA will provide Concept Medical with priority review and interactive communication regarding device development and clinical trial protocols through to commercialisation decisions.
An updated guideline on the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer has been unveiled by the American Society of Clinical Oncology (ASCO) in its Journal of Clinical Oncology. An expert panel convened by ASCO reviewed evidence—including randomised controlled trials (RCTs) and meta-analyses of RCTs—from the period between 1 August 2014 and 4 December 2018, before providing a list of findings and recommendations.
Patients with cancer are at a higher risk of developing VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), than those without cancer, and have higher rates of VTE recurrence and bleeding during VTE treatment. Consequently, VTE is an “important cause of morbidity and mortality” among cancer patients.
According to the review, two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer patients confirmed the efficacy of edoxaban and rivaroxaban, but found that they could be associated with an increased risk of bleeding compared to low-molecular-weight heparin (LMWH). Furthermore, two additional RCTs underlined the potential benefits and side-effects of DOACs for thromboprophylaxis in ambulatory cancer patients at a higher risk of VTE.
Co-chaired by Nigel S Key (Chapel Hill, North Carolina, USA) and Anna Falanga (Bergamo, Italy), the panel’s systematic review included a total of 35 publications (26 meta-analyses and nine RCTs) on VTE prophylaxis and treatment, and 18 publications on VTE risk assessment (six included multiple types of cancer, while 12 focused on individual cancer types). In addition to Key and Falanga, 15 additional authors worked on the project.
Speaking to Interventional News about the importance of these guidelines, Key comments, “This iteration of the ASCO guidelines on VTE prevention and treatment reflects an evolving evidence-based set of recommendations on a common problem in a challenging patient population. Perhaps the greatest advances are the recommendations to consider certain oral direct factor Xa inhibitors for the treatment of VTE and for VTE prevention in higher risk cancer patients.”
Falanga is in accordance, adding, “The updated ASCO guidelines reflect the new evidence from clinical research showing the efficacy of new anticoagulant drugs for VTE management in oncology. The addition of some DOAC to our armamentarium to prevent and treat cancer-associated VTE expands our choice and allows the possibility to personalise treatment based on patient characteristics and type of cancer.”
The updated guideline addresses six clinical questions:
In response to the first clinical question, “Should hospitalized patients with cancer receive anticoagulation for VTE prophylaxis?”, ASCO’s guideline states that hospitalised patients who have active malignancy and acute medical illness, or reduced mobility, should be offered pharmacologic thromboprophylaxis in the absence of bleeding, while patients with active malignancy but no additional risk factors may be offered pharmacologic thromboprophylaxis. However, pharmacologic thromboprophylaxis should not be offered to patients admitted for minor procedures or chemotherapy infusion, nor patients undergoing stem-cell or bone marrow transplantation.
On the subject of whether ambulatory patients with cancer should receive anticoagulation for VTE prophylaxis during systemic chemotherapy, a new addition to the guideline is that high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH Patients with multiple myeloma receiving thalidomide or lenalidomide with chemotherapy should be offered pharmacologic thromboprophylaxis, according to the guideline.
For cancer patients undergoing surgery, it is recommended that all persons with malignant disease undergoing a major surgical intervention receive perioperative VTE prophylaxis with either unfractionated heparin (UFH) or LMWH, unless they present a high bleeding risk or other contraindications. Prophylaxis should be commenced preoperatively and continue after surgery for at least seven to 10 days, while extended prophylaxis with LMWH, for up to four weeks, is recommended for cancer patients undergoing major open, laparoscopic abdominal or pelvic surgery.
Regarding the best method of treating cancer patients in order to prevent VTE recurrence, a number of recommendations are included in the guideline. Initial anticoagulation may involve LMWH, UFH, fondaparinux, or rivaroxaban, though LMWH is preferred over UFH for the initial five to 10 days of anticoagulation for patients with newly diagnosed VTE. For long-term anticoagulation of six months, it is stated that LMWH, edoxaban, or rivaroxaban are more effective and therefore preferred. Patients with active cancer, including those with metastatic disease or persons receiving chemotherapy, should receive anticoagulation with LMWH, DOACs or vitamin K antagonists (VKAs) beyond six months.
Responding to expert opinion in the absence of randomised trial data, uncertainty towards short-term benefits, and evidence of long-term harm from filters, ASCO has recommended against the insertion of a vena cava filter for patients with established or chronic thrombosis. Additionally, the guideline asserts that filter insertion has no role for primary prevention or prophylaxis of PE or DVT, though a vena cava filter may be offered as an adjunct to anticoagulation in patients with progression of thrombosis. Incidental PE and deep vein thrombosis should be treated in the same manner as symptomatic VTE, according to ASCO.
Answering the question of whether patients with cancer should receive anticoagulants in the absence of established VTE to improve chances of survival, anticoagulant use is not recommended to improve survival in patients with cancer without VTE.
Finally, the guideline addresses what is known about risk prediction and awareness of VTE among patients with cancer, recommending that those persons should be assessed for VTE risk initially and periodically, particularly when starting systemic antineoplastic therapy or at the time of hospitalisation. At the same time, individual risk factors do not reliably identify patients with cancer at high risk of VTE. ASCO argues that oncologists should educate patients regarding VTE, particularly in settings that increase risk such as major surgery and hospitalisation.
Oleksandra Kutsenko, a radiology resident at Upstate Medical University, Syracuse, USA, and Society of Interventional Radiology-Resident Fellow Student (SIR-RFS) advocacy chair, has given a TED talk expressing the possibilities of minimally invasive, image-guided medicine.
Focusing on the “science-fiction” like capabilities of interventional radiology (IR), Kutsenko began her talk by describing three case studies where patients were not treated with IR procedures, but could have potentially received better treatment if they had been. In the first example, she detailed how a woman who had a hysterectomy could have been saved an invasive surgery, a long recovery time, and her fertility if she had been treated with a uterine fibroid embolization. In the next example, she detailed how a young veteran treated for back pain with opioids could have been spared his resultant painkiller addiction through original treatment with nerve ablation and vertebroplasty. Lastly, she spoke of a liver cancer patient who could undergo “potentially curative” microwave ablation or chemoembolization in order to avoid either liver transplant and a lifelong immunosuppression, or a long course of chemotherapy with its attendant side effects: infection, bleeding, hair loss, fatigue, and stomach pains.
Reaching an audience of millions, TED talks are an effective means of communicating with large swathes of the general public. This accords with one of SIR’s key mission statements, to reach “around the world and out to partners across corporate, public, and private sectors to ensure the story of interventional radiology is spread through a range of communication channels”. In addition to public outreach, SIR advocates on behalf of its members and interventional radiology as a whole before Congress, insurance carriers and other key decision-makers.
Improving the public awareness of interventional radiology procedures was central to Kutsenko’s talk. “It seems that interventional radiology has been the best kept secret of medicine”, she told the audience. “So let us change this”.
Speaking to Interventional News, Kutsenko comments, “Interventional Radiology covers a broad spectrum of minimally-invasive procedures that diagnose and treat almost every organ in the body; we work with physicians in nearly every specialty of medicine and provide some of the best healthcare value and outcomes, and yet our specialty is strikingly unknown among other physicians, legislative bodies, and most importantly patients.
“To change this, we need to reach out to large masses of people in the general population and spread the word about the treatment options we have to offer. TED is one of the greatest media platforms that is doing exactly that. Extremely popular TED educational videos can increase awareness about IR far beyond single hospitals, cities, or even countries. As a result, the information on value of minimally invasive image-guided procedures can be delivered to large populations, and through them further influence hospital and national policies. The voice of our patients will be heard, and we all should make sure that their health decisions are based on understanding new technically-advanced, IR-inclusive, better medicine.”
After sharing her TED talk on Twitter, Kutsenko was quickly the recipient of much praise from other interventional radiologists on the platform. Replying on the site, aspiring interventional radiologist Alex Sher (Mount Sinai, New York, USA) wrote: “Great talk and thanks for spreading the word about interventional radiology!”
Adept Medical has launches its Antegrade IR platform, which provides a work surface for antegrade femoral approach during interventional radiology vascular procedures. The device sits within the company’s existing range of access and patient positioning devices designed for interventional radiology, cardiology and vascular procedures.
Designed to provide a stable, radiolucent, height- and length-appropriate work surface for supporting light-weight equipment during the antegrade femoral approach, the Antegrade IR Platform offers clinical benefits to the current practice of laying procedural equipment on the mattress and patient, a press release states.
The narrow portion of the Antegrade IR Platform extends alongside the patient towards the femoral artery, offering a steady platform for the clinician to rest their wrists on during wire manipulation. It can be set up at two different lengths and at various heights according to the patient and procedure, providing flexibility.
“Having the Retrograde IR Platform in market now for a few years gave us deeper insights into the requirements surrounding femoral artery access and that product was the conversation starter for the Antegrade IR Platform”, Adept Medical’s product development manager Matt Lazenby comments. “It became a common request when promoting at congress meetings and we worked closely with director of Medical Imaging, Marcus Mykytowycz of Western Health (Melbourne, Australia), with iterations of prototypes before widening our trial sites. Lower leg interventions for ischaemia is going through a rapid upsurge due to the increase in diabetes cases and we felt that the timing was right to release a specific platform for facilitating antegrade femoral access with all the same benefits as our existing retrograde platform.”
Ideally used in conjunction with the Adept Medical Drape Support and ArmSure, these two products offer drape management, patient comfort and security during interventional radiology procedures.
Crafted from carbon fibre composite and high-performance engineering plastics, the platform is light-weight yet strong and has a high resistance to chemical attack from commonly used cleaning products.
According to a press release, Surmodics has completed enrolment in TRANSCEND, its pivotal clinical trial for the SurVeil drug-coated balloon (DCB).
“TRANSCEND is a rigorous level one, randomised controlled trial that comes at a very important time for the vascular and interventional community,” said Kenneth Rosenfield, a principal investigator of the TRANSCEND study. “By providing a head-to-head comparison with today’s market leading DCB, this trial will provide data regarding the relative performance of the SurVeil DCB, which represents a new generation of DCB. Beyond the device itself, the new trial design will ultimately provide insight into clinically important questions regarding long-term results. There is great promise that this third-generation DCB will further improve upon current outcomes for this technology and provide additional benefit for clinicians and the patients that they treat.”
The TRANSCEND trial enrolled 446 patients at 65 global sites. The randomised study will evaluate the safety and efficacy of the SurVeil DCB compared with a commercially available DCB in treating peripheral artery disease (PAD) in the upper leg. The results of the trial will also include long-term, patient-level data out to five years.
“I am excited about the potential of the SurVeil DCB to improve the treatment of PAD,” said Marianne Brodmann, a TRANSCEND principal investigator and the trial’s leading enroller with 44 randomisations. “Our focus now shifts to follow-up and monitoring of these patients and the collection of high-quality data.”
“Completing enrolment in the TRANSCEND trial marks an important milestone and brings us one step closer to bringing this next-generation treatment to PAD patients,” said Gary Maharaj, Surmodics’ president and chief executive officer. “I would like to thank our principal investigators—Kenneth Rosenfield, Marianne Brodmann, and William Gray—our trial advisor, Peter Schneider, and the entire steering committee for their leadership and guidance, all our investigators, support teams and, importantly, the patients we enrolled. Without their participation, we would not be here today.”
In February 2018, Surmodics entered into an agreement with Abbott that provided Abbott with exclusive worldwide commercialisation rights for the SurVeil DCB. Pursuant to the terms of the agreement, Surmodics received a US$25 million upfront payment and will receive a US$10 million milestone payment in connection with the completion of patient enrolment in the TRANSCEND trial. Approximately US$5 million from this milestone payment will be recognised as revenue in the company’s fiscal fourth quarter. Surmodics may earn an additional US$57 million for other various product development milestones.
Upon the regulatory approval of the device, Surmodics will be responsible for manufacturing clinical and commercial quantities of the product and will realise revenue from product sales to Abbott as well as a share of profits resulting from sales to third parties.
The Society of Interventional Radiology (SIR) invites practising physicians, early career professionals, research scientists, clinical associates, trainees and medical students to submit original research for possible presentation during the society’s Annual Scientific Meeting, 28 March–2 April, 2020, in Seattle, USA. Online abstract submission is open at sirmeeting.org until 5pm ET on 26 September, 2019.
“Interventional radiology is constantly redefining the landscape of minimally invasive, image-guided treatments. You can play a role in this evolution by sharing your ideas, innovations and state-of-the-art technology at the SIR 2020 Annual Scientific Meeting. SIR 2020 is the place to see what is at the forefront of the specialty that will enable us to continue to provide the best patient care,” says SIR 2020 scientific chair Baljendra S Kapoor, an interventional radiologist at the Cleveland Clinic, Cleveland, USA. “The SIR Annual Scientific Meeting highlights collaboration in interventional radiology and addresses bold strides in clinical practice. I invite you to join us in Seattle and share your research and expertise with attendees from around the world.”
SIR details how to get involved: “Submissions may be accepted for oral or poster presentation for scientific abstracts and traditional paper posters for educational exhibits. Please note, single-case reports will not be accepted. Original scientific research abstracts accepted for oral presentation, ePoster or traditional poster presentation will be published in the supplement to SIR’s flagship Journal of Vascular and Interventional Radiology (JVIR), and on jvir.org, and will be a citable reference.
“Selected abstracts will be designated as ‘Distinguished’, ‘Featured’ or ‘Abstract of the Year’. Additionally, national and international consumer and trade media will report on ground-breaking research presented at SIR 2020.”
SIR 2020 is expected to attract more than 5,000 attendees from around the globe to Seattle, a city known for germinating new technologies and bold scientific thinking. Researchers who are accepted will have the opportunity to grow the field of image-guided interventions by sharing their discoveries, device and procedure innovations, clinical outcomes, and breaking research in areas that address many of today’s most challenging medical problems, including cancer, vascular disease, and men’s and women’s health.
According to SIR, in 2020 the meeting will include lecture-based didactic sessions; centrepiece plenaries that will inspire and educate; Angio Clubs, a series of case-based workshops; SIRConnectLive, a unique town-halltype session that promotes interactive learning; self-assessment CME (SACME) sessions, which help fulfil maintenance of certification (MOC) requirements; hands-on workshops and much, much more.
High-level scientific abstract presentations are featured during the meeting’s scientific sessions, where attendees will learn about current clinical trials, technical innovations, and the basic science shaping the foundation of the specialty.
Abstracts presented during the scientific sessions span a wide breadth of categories, including arterial interventions; venous interventions; nonvascular interventions; dialysis interventions; education and training; practice management; health care policy; and quality improvement.
SIR Expo
The SIR 2020 exhibit hall at the Washington State Convention Center is open to all registered attendees and guests with a badge. Attendees should watch for special events and hands-on sessions at select booths. Throughout the meeting, attendees will be encouraged to attend “Compelling Conversations,” a series of informal, popular question and answer sessions on timely topics, held at SIR Central in SIR Expo.
About Seattle
Seattle is a world-class metropolis set within beautiful, natural surroundings, offering the best of an urban lifestyle while embracing the outdoors. Many of Seattle’s top visitor attractions are within a few blocks of the Washington State Convention Center, including the Pike Place Market, Seattle Art Museum, ferries, world-class restaurants, and a historic theatre district. Three national parks lie within a two-hour drive of Seattle and the city is a gateway to the San Juan Islands, Washington Wine Country, and British Columbia.
About the Society of Interventional Radiology
The Society of Interventional Radiology is a non-profit, professional medical society representing more than 8,000 practising interventional radiology physicians, trainees, students, scientists and clinical associates, dedicated to improving patient care through the limitless potential of image-guided therapies. SIR’s members work in a variety of settings and at different professional levels—from medical students and residents to university faculty and private practice physicians.
Data from the University of Pittsburgh Medical Center (Pittsburgh, USA) indicate that the open approach to managing thrombosed haemodialysis grafts with venous anastomotic lesions is not associated with superior primary patency when compared to the hybrid approach. These findings also show that an existing stent in an arteriovenous graft (AVG) is a strong predictor of loss of patency and graft abandonment.
Catherine Go (Division of Vascular Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA) presented the data at the 2019 Society for Vascular Surgery (SVS) Vascular Annual Meeting (VAM; 12–15 June, National Harbor, USA). She told delegates that AVG were “plagued by poor patency” and failure of an AVG leads to “increased cost and morbidity”, adding that thrombosis in an AVG most commonly occurred because of a venous anastomosis stenosis.
However, according to Go, the “jury is still out” about how to manage such thromboses. Two meta-analyses—published in 2002 and 2019—have reported the superiority of the open treatment over purely endovascular methods, but few studies have investigated the hybrid technique, which Go reported is commonly used at her centre (University of Pittsburgh Medical Center). She explained that this involves “open thrombectomy followed by endoluminal treatment (balloon angioplasty, cutting balloons, or stents/stent grafts)”.
“Based on historical data, we hypothesised that open revision for AVG venous anastomosis is associated with better patency when compared to hybrid therapies”, Go stated. Therefore, in the retrospective study, Go and colleagues compared patency outcomes for patients who underwent open repair for a first-time AVG thrombosis with those for patients who underwent the hybrid approach. The primary endpoints were primary patency (time from index thrombectomy to first reintervention or thrombosis) and secondary patency (time from index thrombectomy to graft abandonment). The investigators also reviewed technical success and primary-assisted patency (time from index thrombectomy to first rethrombosis).
Overall, 97 patients underwent intervention for occluded AVGs at the University of Pittsburgh Medical Center between 2014 and 2018. Of these, 34 underwent the open approach (73.5% patch angioplasty and 26.5% jump bypass) and 63 (22.2% stent graft, 7.9% cutting balloon, and 1.6% bare metal stent) underwent the hybrid approach. At 30 days, there were no significant differences in rate of the failure of the approach: 29.4% for open vs. 27% for hybrid (p=0.799). A multivariate analysis showed that a higher number of prior fistulograms and African-American race were both predictive of protection against failure. There were also no significant differences between groups in primary patency, primary-assisted patency, or secondary patency at either six months or 12 months.
Go reported that the number of prior fistulograms was again predictive of protection against primary patency failure (at six/12 months). Central occlusion and a hypercoagulable state were predictive of loss of primary-assisted patency. An existing venous anastomosis stent predicted both loss of primary patency and loss of secondary patency.
“AVG patency after thrombectomy is poor. Open versus hybrid treatment of AVG venous anastomosis stenosis are not associated with differences in patency. An existing stent at the venous anastomosis is a strong predictor of loss of patency and abandonment,” Go reported. She added that, given the association between an existing stent and graft abandonment, an operator should “start planning future access options” when using a stent to salvage a thrombosed AVG.
Nicholas (Nick) Inston calls for “more creative solutions” to vascular access challenges, commending interventional radiologists’ innovative reputation as instrumental to increasing the number of treatment approaches available to physicians. Outlining the complexities of end-stage vascular access in an ever-increasing patient population, Inston expresses the need for a multidisciplinary team approach, claiming that the “outlook is improving” due to the fruitful cross-pollination of ideas and skills.
The age of the dialysis population continues to increase, and whilst some of this may be attributed to older patients initiating dialysis, the main component is improved survival in prevalent dialysis patients. As a consequence, the vascular access needs of this population become more challenging. As primary access sites become depleted, more creative solutions must be employed.
In a small but increasing group of patients, standard, multiple, autologous, and synthetic options may have all failed, and these patients may be deemed to have exhausted all vascular access options except for the use of a central venous catheter (CVC). This situation may be termed end-stage vascular access (ESVA).1
If a patient with a limited lifespan expresses a wish to remain on a CVC, this may be a suitable option. However, this group of patients are likely to require multiple interventions to maintain their CVC patency and may require kinase infusions and even emergency CVC exchange to maintain an ability to dialyse.2
In those patients keen to pursue definitive access options, classifying the underlying issues is helpful. This can be done on an anatomical basis such as the radiological classification outlined by the Society of Interventional Radiology,3 or by using a simplified, more basic classification, such as that described by Julien Al-Shakarchi (University Hospital Birmingham, Birmingham, UK).1
A simple classification for endstage vascular access failure is proposed based on a sequential broad categorisation of: stage 1) no upper limb vascular access option; stage 2) no lower limb vascular access options; stage 3) no vascular access options at any site.
These can have the underlying anatomical problem added to allow more detailed definition (see Table 1).
An illustrative example may be a patient with tight superior vena cava (SVC) and brachiocephalic stenosis who has a right iliac vein occlusion and a left groin line. This would be classed as ESVA 2a, and possible solutions that could be considered are a left femoral vein transposition or loop thigh arteriovenous (AV) graft, attempts at recanalising the upper body central veins with recanalisation and stenting, or use of a Surfacer device (Bluegrass Vascular) and insertion of a HeRO (Merit Medical).4 Other options may be a non-standard graft configuration—here a right axillo-femoral graft may be possible. Peritoneal dialysis should not be forgotten.
When balancing each of these the risks and benefits should be carefully considered.
Lower leg access is not without complications. Femoral vein transposition, whilst having the advantage of use of the autologous vein and of reducing infection, is associated with lower limb congestion and venous insufficiency. Additionally, amputation has been reported with this method. Lower limb prosthetic grafts are associated with high rates of infection and low patency.5
Recanalisation of upper body central vessels may require expert interventional radiology skills and devices. The Surfacer device has potential, but robust data are not yet available to allow evaluation. Even with recanalised vessels the next step towards definitive access requires either extensive stenting or the use of a HeRO device. In patients with CVC infections (common in groin access), this is contraindicated. In such patients, a staged approach to recanalisation with initial upper body CVC, eradication of infection, and subsequent conversion to a HeRO graft may be a better approach.
Patients with arterial insufficiency can pose a problem and inadequate inflow may not only threaten the access, but also the limb. The resistance within longer grafts and HeRO grafts requires a suitable inflow including a reasonable blood pressure. Hypotension should be carefully evaluated when these options are being considered.
A further consideration is that of transplantation. Younger patients with ESVA may have had a long history of renal replacement and multiple CVCs. In the example above, a groin line in the only patent iliac vein poses a great threat to future kidney transplantation. It may be proposed that such patients are considered higher priority in organ allocation schemes as a working transplant is their optimal option. When considering such patients for lower limb access there is little to support avoidance of lower limb options and many transplants have been performed successfully above patent ipsilateral loop thigh grafts.
For patients where attempts to gain access are unsuccessful—stage 3 ESVA—there are still solutions that can be found.
This group traditionally were treated with a translumbar or transhepatic CVC. For many this was seen as a pre-terminal option, although data support reasonable short and mid-term survival.6 A relatively simple definitive option in these patients is the arterial arterial prosthetic loop (AAPL), which is an interposition graft in the subclavian/axillary artery.7
This unique configuration requires special consideration when cannulated and cannot be used for drug delivery but has been shown to have good patency with low complications.
Smaller series of axillary atrial grafts are published and advocated by some authors, however complications are greater and more significant.6
In deciding treatment options, an access life plan should be defined, as highlighted in the recent Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines from the National Kidney Foundation.8 Where multiple options exist, these should be considered and staged with the simplest and safest option first, whilst retaining the possibility of further interventions later down the line.
The best approach to managing these difficult cases is with a multidisciplinary team, using a treatment utilising their experience and expertise, and chosen based on its applicability to the patient. The availability of surgical and radiological expertise is required not only for the index procedure, but also for many of these patients’ subsequent interventions and salvage procedures, conducted to maintain patency. An identified pathway should be defined with access to suitable facilities to allow this.
ESVA provides a very challenging problem for the vascular access surgeon, and the bad news is the incidence is likely to increase. Fortunately, there are an increasing number of possibilities for treatment with innovative devices and techniques. Historically, the prognosis was bleak for patients with ESVA, but by combining surgery and interventional radiology skills, the outlook is improving. As always in access, the approach used should be the right access, for the right patient, at the right time. This applies especially to ESVA, where the whole team’s input and detailed discussion with the patient are essential.
Nicholas Inston is a consultant transplant and vascular access surgeon at the University Hospital Birmingham NHS Trust, Birmingham, UK.
References
Merit Medical have announced the commercial launch of the PreludeSYNC EVO radial compression device in the USA. The PreludeSYNC EVO is a sterile, single-use, disposable device used to assist in gaining haemostasis of the arterial percutaneous access site following catheterisation procedures.
Merit Medical’s launch of the PreludeSYNC EVO follows nearly two decades of innovation in haemostasis band products, the company asserts. The PreludeSYNC EVO was designed to provide operators improved clarity, safety, and patient comfort. According to a press release, the clear balloon and curved backer plate provide optimal visualisation of the puncture site, facilitating easy placement. The band, which is easily adjustable and fits securely around a patient’s wrist, comes in two sizes (24cm and 29cm). The device also features the new Slip-n-Lock Connection for safe and easy inflation and deflation.
“A core part of Merit Medical’s mission is to continually evolve and improve our product offerings, including in the area of access and hemostasis,” says Fred P Lampropoulos, Merit Medical’s founder, chair, and CEO. “Accordingly, the PreludeSYNC EVO is a needed solution that elevates the radial compression experience for operators and their patients. The Merit leadership team is excited to put the EVO in the hands of specialists across the USA.”
Ashutosh Rao (Atlanta, USA) talks to Interventional News at SIR 2019 about the OnControl device. Before switching to OnControl, Rao explains, “we did not realise how easy bone biopsies could be”.
Rao notes that sometimes bone lesions are not on the proximal side of the bone and that the OnControl device, with its outer cannula, allows those using it to drill through the front cortex and “get to difficult lesions we may not have otherwise been able to get to.”
He also talks about how it has transformed his practice for both bone biopsies and bone marrow biopsies and how the patients do not feel “all the pushing and pulling” you would normally get from manual pressure.
This video is sponsored by Teleflex.
“Interventional radiology is uniquely equipped to shape the next generation of nanotherapeutics,” Sarah White, associate professor of Radiation and Surgical Oncology at the Medical College of Wisconsin (Milwaukee, USA) and adjunct professor of Radiology at Northwestern University (Evanston, USA) informed delegates at the 2019 annual meeting of the Society of Interventional Oncology (SIO; 7–11 June, Boston, USA). She presented research detailing how the local delivery of nanoparticles directly to the tumour site enables enhanced care to cancer patients. nanotechnology
“I think nanotechnology really allows us to troubleshoot some of the problems in interventional oncology, and then to find applications and create solutions”, she said.
Globally, US$10 billion is spent on nanotechnology research, across many different disciplines. Explaining why she believes this technology has so much potential in the medical field specifically, White said, “Nanoparticles are the right size. One nanoparticle is a billionth of a metre. To visualise that: a marble to the size of the Earth. The diameter of a DNA double helix is 2nm, and the smallest bacteria is 200nm long. Nanotechnology is the size between cells and their organelles, such as mitochondria. They are right in that cellular realm, which is why it is so advantageous to use them in this field.”
In cancer research, nanoparticles are usually used in a theranostic setting, meaning that the nanoparticle can be used not only as a drug—as the treatment—but also as an imaging tool. Currently, systemic chemotherapy used to treat cancer patients is non-specific and, due to lymphatic drainage of the chemotherapy agent from the target tissue, needs to be administered in such high doses to be concentrated enough in the tumour to destroy the cancer that side effects are common and severe.
However, when the chemotherapy drugs are formulated into a nanoparticle, these do not leach out of the tumour cells as easily. This is because healthy cells are packed close together in an orderly structure, and have tight junctions with a lymphatic outflow system threaded throughout. In comparison, tumour cells have antigenic factors that mean they grow rapidly, proliferating in a disordered fashion without tight junctions. The larger gaps between tumour cells means the normal lymphatic outflow cannot form to drain the tissue correctly, altering what passes into and out of the cancerous cells. Smaller molecules, such as nanoparticles, can enter the tumour, and due to the lack of lymphatic drainage, remain there. This method of drug delivery is known as passive tumour targeting, and it increases the ability of the interventionist to get the drug into the tumorous tissue. Due to the proper lymphatic drainage of the non-tumour cells in the body, the nanoparticles are filtered out of these more effectively, meaning the concentration of these small molecules is greater in the cancer.
Active targeting of the tumour
Active targeting of the tumour by nanoparticles also improves clinical outcomes. White explained at SIO: “Tumours often overexpress receptors, so we can put things on the nanoparticles to actively target those surplus receptors.”
According to White, this active tumour targeting increases the efficacy of the treatment due to greater internalisation of the chemotherapy agent. Another drug delivery method explained by White at SIO is endothelial cell targeting, where, similarly to the overexpression of surface receptors on the tumour cells, investigators can formulate nanoparticles to specifically target overexpressed receptors on angiogenic endothelial cells. These line the newer blood vessels feeding the tumour, and using nanoparticles to target these cells helps eradicate the source of the blood flow to cancerous or benign growths.
“The last thing we can do [with drug delivery] is triggered drug release”, White described, “and this is one of the most interesting to me. We can stimulate the release of the cargo. The cargo is the imaging agent or the treatment.”
Clinical applications of nanotechnology in interventional oncology
Addressing the SIO audience, White described current and potential clinical applications of nanoparticles. The first example she used was in the delivery of hydrophobic drugs: “We want to deliver hydrophobic drugs. We think sorafenib can help us treat the surge in vascular endothelial growth factor receptor (VEGF) after transarterial chemoembolization (TACE) that we see at 24 hours.”
Sorafenib is currently the only first-line multi-kinase inhibitor approved for use in hepatocellular carcinoma (HCC). It inhibits the activity of several kinases, including VEGF, which are involved in tumour cell signalling, proliferation, angiogenesis and apoptosis. Thus, sorafenib inhibits tumour growth and neoangiogenesis. Several recent studies, including work by Baosheng Ren (The Second People’s Hospital of Changzhou, Changzhou, China), Wansheng Wang (The First Affiliated Hospital of Soochow University, Suzhou, China) et al in the Journal of Cancer, have reported that overall survival is improved in HCC patients when treated with a combination of sorafenib and TACE compared with TACE alone.
“But when sorafenib is administered systemically”, White explained, “which is done in order to get high enough levels of the drug into the tumour, it can cause extreme side effects.”
In an effort to eliminate these side effects, nanoparticles can be used to deliver sorafenib locally, rather than systemically. According to White, it is possible to make a nanoconstruct with sorafenib that will deliver and deposit the drug straight to the tumour. White and collaborators have fabricated poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumours during liver-directed embolotherapies. These constructs co-encapsulated iron oxide nanoparticles (IONP) so that the investigators could observe microsphere delivery via magnetic resonance imaging (MRI). Following intra-arterial microsphere infusions in a rabbit VX2 liver model, White demonstrated in 2015 that these sorafenib particles normalised VEGF activity and decreased microvessel density. Writing at the time in Biomaterials, she concluded “These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors”.
A second clinical application of nanoparticles in interventional oncology is to expand the ablation zone when treating patients with metastatic colon cancer who are not candidates for resection. The ablation zone is limited by size (4mm being approximately the largest possible size) and location (due to the risk of damage to adjacent structures). Using a rat model of colorectal liver metastases, White and colleagues compared the size of ablation zones in three groups—rats injected with hybrid magnetic gold nanoparticles tagged with monoclonal antibodies, rats injected with hybrid magnetic gold nanoparticles only, and a control group.
After undergoing photothermal ablation with a fibre-coupled near infrared diode laser, haematoxylin-eosin staining revealed a significant difference in tumour necrosis across the three groups. In the antibody and nanoparticles group, tumour necrosis was 38%±29. In contrast, tumour necrosis in the nanoparticles only group was 14%±17, demonstrating a lack of toxicity. The control group, which were only injected with the colorectal liver metastasis cell lines, had a tumour necrosis of 7%±8 (p=0.043). The addition of the monoclonal antibodies to the nanoparticles also resulted in statistically significant higher levels of delivery to the tumour compared to nanoparticles alone. Published in Radiology in 2017, the investigators concluded that targeted monoclonal antibody–conjugated hybrid magnetic gold nanoparticles can serve as a catalyst for photothermal ablation of colorectal liver metastases by increasing ablation zones. nanotechnology
Society of Interventional Oncology (SIO) president William (Bill) Rilling notes that you do not need to be a full time cancer specialist to describe yourself as an interventional oncologist, and that such a prescriptive definition is unhelpful. “Being an interventional oncologist is not about how many cases you do or what percent of your practice is IO, it is a mindset and a dedication to be a part of the cancer care team”, he says.
As interventional radiology (IR) continues to evolve and mature, it seems only natural that the development of subspecialties is a part of that evolution. Currently, IR physicians may focus on a variety of subspecialty practices including peripheral arterial disease (PAD), venous disease, musculoskeletal interventions, women’s health, oncology, and many other new and exciting facets of IR. Encouraging and enabling IR physicians to focus on subspecialties is important to drive innovation and research and subsequently advance practice. From a practical perspective, the diversity and richness of IR practice helps protect us as IR physicians from large losses in patient and procedure volumes as we can often compensate by expanding other areas of our practice. If a drug is developed tomorrow that cures atherosclerosis, many interventional radiologists would lose a significant and important part of their practice, but the vast majority would still have a job.
However, the diversity of IR can also be a weakness. Others who practice in the field of oncology, for example, focus exclusively on caring for cancer patients. Very few medical, surgical, and radiation oncologists spend a significant portion of their time on anything but oncology. This presents a challenge for interventional oncologists, as there are very few IR/ interventional oncology (IO) physicians who practice in IO exclusively. It makes it more difficult for us to be part of “the club.” For example, my practice is about 70% IO, but I also treat vascular malformations, hereditary haemorrhagic telangiectasia (HHT) patients, along with all the other things most of us take care of on a daily basis, and still have to be able to treat aortic catastrophes on call. Having a single-minded focus on oncology is a challenge for most interventional radiologists.
How do we overcome this challenge? In my view, there are several solutions. First and foremost, we must practice multidisciplinary patient care at its highest level with patients as the focus. Cancer care is the ultimate team sport and most cancer patients will have many different oncologic specialists caring for them at various times throughout their cancer journey. This requires the IR/IO physician to participate in multidisciplinary tumour boards, have a meaningful role in treatment decision making, see patients in clinic to discuss options, follow them in clinic to assess response, and understand the evidence basis for IO therapies and the complimentary medical and surgical options. If you are doing these things in your practice, even if IO is not the majority, you are an interventional oncologist. Thus, being an interventional oncologist is not about how many cases you do or what percentage of your practice is IO, it is a mindset and a dedication to be a part of the cancer care team, providing a unique perspective on image guided therapy and hopefully helping to move the field forward.
IR/IO physicians have a significant advantage being part of the cancer team: we have a role in cancer care from diagnosis, through treatment, and continuing to palliation. Therefore, the definition of what are “IO procedures” also warrants additional discussion. Targeted biopsies are becoming increasingly important as personalised cancer therapy expands at an exponential rate. We not only biopsy for initial diagnosis but also to identify new mutations and resistant clones to modify targeted therapy. This is a central and critical role in the cancer patient which will continue to expand. Image guided therapeutic procedures are clearly the realm of IO and we all need to work to expand access to these procedures for our patients. Central to this will be proving the effectiveness of IO treatments by expanding clinical trials and other data collection platforms. IO/IR physicians also play a unique role in palliation and improving quality of life for cancer patients with fluid management techniques, pain palliation, management of malignant bowel obstruction and many other interventions to improve quality of life and decrease narcotic usage in this patient population. This broad spectrum of involvement from diagnosis, to treatment and continuing to palliation is a unique advantage and perspective for IO.
Moving forward, I believe we should continue to encourage and enable subspecialty evolution in IR. This does not weaken IR as a whole but strengthens it. As interventional oncology matures as a subspecialty, we should embrace our inherent and significant advantages as cancer specialists. Currently, as patient reported outcomes, quality of life metrics, and cost effectiveness all become central to cancer therapy, we have a unique opportunity to expand the role of IO and expand patient access to IO therapies. We will need all IO/IR physicians functioning at a high level in their cancer centres to accomplish these goals. The door is open, we simply must walk through it.
William (Bill) Rilling is professor of Radiology and Surgery at the Medical College of Wisconsin, Milwaukee, USA.
Automatic characterisation of Lipiodol (Guerbet) deposition is feasible, workflow efficient, and improves consistency across patients, argued Sophie Stark (Yale School of Medicine, New Haven, USA) at the Society of Interventional Oncology’s annual meeting (SIO; 7–11 June, Boston, USA). Stark presented an automated quantitative and pattern-based method for the characterisation of Lipiodol deposits on CT scans taken 24 hours after cTACE (conventional transarterial chemoembolization).
“This work paves the way for the development of automated algorithms that predict tumour response from preprocedural MRI and 24 hour CT, and may allow earlier and more personalised therapy”, she enthused at the meeting.
“Lipiodol use in cTACE plays a unique multifunctional role”, Stark explained. “It has drug delivery capabilities with transient microembolic effects, and its radiopacity allows drug delivery visualisation on post-procedural CT scans. Previous studies already show that Lipiodol deposition is correlated with tumour response.”
The investigators within the Yale Interventional Oncology Research Lab, led by Julius Chapiro, set out to see if they could further establish Lipiodol as an early imaging biomarker for the therapeutic efficiency of cTACE using this automated system on 24 hour CT scans. Contextualising this research, Stark informed the SIO audience that liver cancer is the fourth leading cause of cancer-related deaths worldwide, and that cTACE is a guideline approved treatment option for patients with intermediate to advanced stage disease.
They conducted a retrospective study of 42 primary and secondary liver cancer patients, with a total of 65 tumours between them, who underwent cTACE between 2012 and 2018 at the Yale School of Medicine. All patients had a baseline contrast-enhanced MRI scan before undergoing cTACE, then a CT scan 24 hours after the procedure, followed by a second MRI scan 30 days post-procedure. Detailing this image analysis workflow, Stark explained how she and her colleagues volumetrically segmented all of the tumours at all imaging time points. This was followed by an automatic, enhancement-based quantification of viable and necrotic tumour tissue on MRI. Next, the investigators performed an enhanced-based volumetric response assessment using qEASL (Quantitative European Association for the Study of the Liver).
“On the 24 hour CT, which was our focus, we characterised Lipiodol deposition automatically”, Stark continued. The researchers looked at the tumour coverage with Lipiodol, as well as areas of different Lipiodol densities—categorised as low, medium and high—using intensity thresholds from the Hounsfield units scale. The cut-off values were: low density, 87–145 Hounsfield units (HU); mid density, 155–240 HU; high density, 241+ HU. The automated quantification method was developed by one of Stark’s co-workers, Clinton Wang, who is currently a graduate student at the MIT in Boston, USA, and was previously involved with research at Yale. Based on these density values, the developed algorithm creates a colour coded overlay for the CT image of the liver, where low density areas were shaded green, mid density areas shaded yellow, and high density areas shaded red (see Figure 1).
Stark continued: “Specifically, we looked at homogenous deposition of Lipiodol, sparsity, rim deposition of Lipiodol, and peripheral deposition. The homogenous and sparsity deposition of Lipiodol could be determined through volumetric analyses of the whole tumour, whereas for the rim and peripheral Lipiodol deposition, a more complex approach was required.” Expanding on these complexities, she said: “First, we calculated the volume of the tumour, and then created a sphere with exactly the same volume. Then we used operations such as morphological erosion and dilation to separate the core and the periphery of the tumour.”
Lipiodol coverage in viable areas was significantly higher than that of necrotic areas, the investigators found through comparing contrast-enhanced MRI scans. There was approximately 8.2% more Lipiodol coverage in viable areas than necrotic zones, averaged throughout all tumours. “We also looked at several subgroups, and the analysis was consistent throughout”, Stark said.
Looking at Lipiodol density distribution, the fraction of low density deposition was significantly higher in necrotic areas compared with viable areas, whereas the fraction of high density Lipiodol was significantly higher in viable compared to necrotic areas. There was no significant difference for mid density Lipiodol. Also, this analysis was consistent throughout several subgroups, according to Stark.
The investigators reported a stratification of tumour response by Lipiodol density. Areas that deposited Lipiodol became necrotic at a higher rate, as seen on follow up MRI, than areas without Lipiodol (p=0.0475). Higher concentrations of Lipiodol enhanced this effect with increasing Lipiodol densities, there was an increasing percentage of necrotic tissue.
When deposited peripherally, Lipiodol is associated with an improved tumour Homogenous, non-sparse, and rim deposition were all associated with accelerating the slowing of tumour volume growth. In Stark’s words: “Homogenous deposition, non-sparse deposition, and rim deposition within sparse tumours showed an increased decrease of enhancing tumour volume on follow up MRI”.
This led Stark and colleagues to conclude that the automated characterisation of Lipiodol “can be easily incorporated into a standardised framework for cTACE management”. Stark summarised: “Our approach improves the consistency for patients because it leverages the standardised Hounsfield units scale. We show that tumour enhancement on contrast-enhanced MRI can make predictions not only about the presence, but also about the density, of Lipiodol deposition, which is strongly correlated to tumour response to cTACE. Also patterns, including homogenous, non-sparse, rim and peripheral deposition of Lipiodol were positive predictors of tumour response. We think this work paves the way for the development of fully automated algorithms that can predict tumour response from pre-procedural MRI and 24 hour post-procedural CT, and may allow earlier and more personalised therapy to our liver cancer patients”.
The Society of Interventional Oncology (SIO) is working more closely within cooperative groups and taskforces, as well as amongst the guidelines commentariat, to provide a global voice to interventional radiologists working in cancer care. Within the various groups the society is active amongst, SIO president William (Bill) Rilling (USA) tells Interventional News they have the strongest presence on relevant National Cancer Center Network (NCCN) panels.
SIO is working on developing and submitting evidence-based recommendations to various NCCN panels. Commenting on this growing integration into the formal process of commenting on and reviewing guidelines, Rilling says: “We have been very welcomed into this process, especially by medical oncologists. Everyone can recognise that there is a benefit to the patient to have as broad a view as possible. The vast majority of people involved at the moment [with guideline review] are medical oncologists.”
NCCN kidney cancer guidelines
Earlier this year, updates to the NCCN renal guidelines were submitted by Ronald Arellano (Harvard University, Cambridge, USA), Thomas Atwell (Mayo Clinic, Rochester, USA), and S William Stavropoulos (University of Pennsylvania, Philadelphia, USA) on behalf of SIO. Their letter requests the NCCN kidney cancer guideline panel review six specific changes for inclusion in the management of T1a renal masses.
Speaking to Interventional News, Stavropoulos explains the society’s ambitions for how the guidelines will change: “We hope the NCCN guidelines are updated to accurately reflect the latest research showing the oncologic success and safety of percutaneous ablation for renal cell carcinoma (RCC) relative to surgery and active surveillance.
“It is critical that national guidelines reflect the latest developments in research and clinical practice. Updating the NCCN guidelines will help interventional oncologists at the local and national level. Locally, it could help interventional oncologists during discussions regarding treatment options at individual tumour boards. At the national level, updating the role of ablation in the NCCN guidelines could assist with issues such as funding of clinical trials, procedural reimbursement coverage and industry investment in research and development.”
These specific changes SIO are requesting are:
Atwell outlines his ambitions for the guidelines to Interventional News: “My hope is that we could bring the NCCN guidelines closer to those currently provided by the American Urological Association (AUA) and the American Society of Clinical Oncology (ASCO), both of whom include thermal ablation as a front-line treatment alternative for small renal masses. There are particular attributes of ablation that warrant consideration in the NCCN guidelines, including favourable perioperative outcomes.”
Enthusing about the society’s involvement in these requested guidelines changes, Stavropoulos says: “SIO has been critical in spearheading these type of efforts. For interventional oncology (IO) to take its place as the fourth pillar of cancer care, we need to engage with the major oncology organisations. In this instance, the SIO was instrumental in bringing our RCC working group together and helping us through the specifics of the NCCN submission process. Other areas of SIO advocacy include establishing the first IO Working group within ECOG-ACRIN [a cancer research group formed from a 2012 merger between the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network], spearheading multiple IO clinical trial concepts in gastrointestinal (GI), genitourinary (GU), and thoracic oncology within the National Cancer Institute (NCI) Cooperative Groups. Establishing a footprint within organised oncology increases the visibility of IO and recognition of what we offer patients among our medical, surgical and radiation oncology colleagues.”
NCCN breast cancer guidelines
SIO also submitted updates to the NCCN breast cancer guidelines this year. Submitted by Amy Deipolyi (Memorial Sloan Kettering Cancer Center, New York, USA), Maureen Kohi (University of California, San Francisco, USA), and Gloria Hwang (Stanford University, Stanford, USA).
Deipolyi explains to Interventional News: “The NCCN publishes guidelines that guide physicians and patients on ‘standards of practice’ for cancer treatment. These guidelines not only drive decision making in tumour boards and in clinic, but are also used by insurance companies to justify witholding reimbursement for procedures and diagnostic exams. The current NCCN guidelines for breast cancer do not mention minimally invasive procedures, despite good evidence that local therapies are effective for palliating pain and liver-directed therapies can confer progression free survival intervals. The NCCN committee for breast cancer does not include a single diagnostic or interventional radiologist. We have petitioned the committee to consider including radiologists, and to consider minimally invasive therapies in the treatment of metastatic breast cancer. Our hope is to improve patient outcomes and to help physicians offer these procedures while minimising the difficulty in obtaining insurance coverage. We appreciate the support and effort of SIO to advocate for interventional oncology physicians and their patients.”
To this end, their letter suggests including a section for locoregional therapies for stage IV metastatic breast cancer and illustrates three clinical examples.
These three clinical examples are: if the patient has painful bone metastases, for oligometastatic disease, and for liver-dominant hepatic metastasis refractory to systemic therapy.
Regarding the first example, the authors write: “Bone metastasis occurs in 65–75% of patients with metastatic breast cancer. Image-guided cryotherapy, heat-based thermal ablation, and cementoplasty have been demonstrated to be effective and fast-acting methods to improve bone pain due to metastasis from a wide range of tumours, including breast cancer.”
Similarly, for oligometastatic disease, Deipolyi, Kohi and Hwang justify their recommendation through this statement: “Local ablative therapies for five or fewer sites of metastasis have been shown to provide longer progression free survival and may prolong overall survival. Hepatic resection and/or thermal ablation of hepatic oligometastatic disease can confer disease free intervals lasting several years and perhaps, more importantly, allow long intervals of disease control without chemotherapy. This is particularly beneficial in patients not tolerating systemic therapy.”
For their final clinical example, they expand: “Liver metastasis commonly occurs in breast cancer patients and is associated with poorer oncologic outcomes. Liver tumours may cause abdominal pain or result in compression of the portal vein or obstruction of bile ducts. In selected patients who are not eligible for resection such as chemoembolization and radioembolization have demonstrated radiologic responses that translate to prolonged patient survival. Combining liver-directed treatments in the management of metastatic breast cancer with liver-only or liver-dominant disease can provide longer disease control while delaying the need to change to another line of systemic therapy. Also, in patients with hormonally responsive breast cancer and new-onset liver metastases, transarterial locoregional therapy can delay the initiation of systemic chemotherapy and benefit the patient’s quality of life.”
NCCN lung cancer guidelines
Additionally, SIO submitted updates to the NCCN non-small cell lung cancer guidelines. The letter was penned by Patrick Eiken (Mayo Clinic, Rochester, USA), Florian Fintelmann (Harvard Medical School, Cambridge, USA) and Robert Suh (David Geffen School of Medicine at UCLA, Los Angeles, USA), and requests updating the role of image-guided thermal ablation in the Clinical Practice Guidelines in Oncology for non-small cell lung cancer.
The letter authors describe image-guided thermal ablation as “inclusive of radiofrequency ablation, microwave ablation and cryoablation” and as “a form of ‘local therapy’ or ‘local ablative therapy’ and, generally, may be considered as a potential alternative to other local therapies, particularly for lung lesions <3cm”.
They argue for the inclusion of a section on the principles of image-guided thermal ablation in the NCCN non-small cell lung cancer guidelines, as well as the addition of a section titled “Image-guided thermal ablation” in the discussion of treatment approaches in the guidelines. Currently, the guidelines include a similar section on the principles of radiation therapy; Eiken, Fintelmann and Suh say that as image-guided thermal ablation is “increasingly being studies and used clinically in the treatment of lung cancer”, including a summary of what it is and of its appropriate applications “would be useful to include”.
The third specific change called for by these interventionists is to give greater attention to ablation for medically inoperable stage IA cancer under the “initial treatment” options. Currently, when deemed medically inoperable, the guidelines suggest stereotactic ablative radiotherapy (SABR), with two footnotes, m and n. SIO is calling for NCCN to delete footnote “n” (which reads “Interventional radiology ablation is an option for selected patients”) and to include image-guided thermal ablation in the algorithm proper, alongside SABR. They state their rationale for this: “A growing volume of literature shows the efficacy of image-guided thermal ablation for local control of primary and secondary malignancies of the lung. While the evidence for surgery or SABR may be more robust, use of image-guided thermal ablation may expand the pool of patients for whom local tumour control is possible. Image-guided thermal ablation may be of particular value in patients with limited pulmonary reserve or for those who have reached the limits of tissue toxicity from radiation therapy.”
“It is very important that we, as interventional oncologists, embrace the immuno-oncology field,” Thierry de Baère (Institut Gustave Roussy, Villejuif, France) said in his keynote address on the future of interventional oncology at the Society of Interventional Oncology annual meeting (SIO; 7–11 June, Boston, USA). Drawing from an SIO white paper published recently in Radiology detailing the challenges and opportunities of further integrating these two cancer disciplines and from the literature, de Baère outlines why “Immuno-oncology in cancer care is a fantastic opportunity for interventional oncology”.
In the Radiology white paper, lead author Joseph Erinjeri (Memorial Sloan Kettering Cancer Center, New York, USA) and 17 other leading interventional oncology and immuno-oncology experts define the two IOs, and their potential importance in a more synergistic approach to cancer care: “Interventional oncology is a subspecialty field of interventional radiology that addresses the diagnosis and treatment of cancer and cancer-related problems by using targeted minimally invasive procedures performed with image guidance. Immunooncology is an innovative area of cancer research and practice that seeks to help the patient’s own immune system fight cancer. Both interventional oncology and immuno-oncology can potentially play a pivotal role in cancer management plans when used alongside medical, surgical, and radiation oncology in the care of cancer patients.”
Erinjeri et al, as well as de Baère in his keynote lecture, urge the interventional radiology community that this is possible with an increasingly close collaboration with medical oncology colleagues. From an initial meeting on 23 January 2017 at the Memorial Sloan-Kettering Center in New York, USA, and through multiple subsequent teleconferences, the white paper authors evaluated key areas in immuno-oncology considered integral to the interventional oncologist’s practice.
“We are at the beginning of an exciting revolution in cancer care with the advent of immunotherapy,” Erinjeri et al summarise. “The role that interventional oncology will play in immunotherapy will depend on our collective efforts to address rational questions regarding the fundamental immune effects of local and regional image-guided interventions.”
The SIO white paper makes four recommendations for future work on combining immunotherapy and interventional oncology. These are:
Standardise the lexicon between the two disciplines
Personalise interventional oncology
Understand the tumour-stimulating effects of interventional oncology procedures
Develop imaging biomarkers for interventional oncology procedures combined with immunotherapy
Combining interventional oncology therapies with intratumoral immunotherapy
Speaking to Interventional News, de Baère underlines the importance of the coordination of human intratumoral immunotherapy (HIT-IT) and interventional oncology. This year, the American Association for Cancer Research (AACR) held a specific session on HIT-IT at their annual meeting (29 March–3 April, Atlanta, USA), as do the European Society for Medical Oncology (ESMO; 27 September–1 October, Barcelona, Spain). The 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) will also host a full day of discussion and presentations on the topic (6–10 November, Fort Washington, USA).
This increasing international discourse on HIT-IT can be traced to an ESMO-sponsored expert meeting held 8 March 2018 in Paris, France. This comprised 11 experts from academia, 11 from the pharmaceutical industry, and two clinician representatives of ESMO. They met to produce a document that would “help to structure the ongoing and future development of HIT-IT”.
The resultant paper, published in Annals of Oncology by lead author Aurélien Marabelle (Villejuif, France) and colleagues, including de Baère, made six recommendations. These are: 1) To carefully select the paptient population for clinical trials, 2) To conduct translational studies systematically to facilitate better understanding of the mechanism of action of HIT-IT, 3) To organise face-to-face meetings or surgeons and oncologists, 4) To use ultrasound guidance for the injection of superficial tumour lesions, ultrasound guidance or CT-scans to guide the injection of deeper tumour lesions, and to use doppler ultrasound to ensure no big vessels are injected in error, 5) To measure injected and noninjected lesions at each injection time point to better capture the kinetics of tumour growth, and 6) To generate diagrams or photographs at every visit or time point of injection, which should be recorded on specific body-map proformas.
Erinjeri and colleagues state in their white paper that interventional radiologists need to work out how to monitor the effects of immunotherapy. They explain that “because immunotherapy mostly facilitates or modulates the inflammatory response rather than causing tumour cell death through cytotoxic effects, to our knowledge no specific guidelines exist to evaluate changes in tumour imaging appearance after treatment.”
Several response criteria have been developed, but to date none have been validated with intratumoural delivery methods or approaches combining locoregional therapy with systemically delivered immune-reactive agents. The SIO white paper authors claim this will be “essential” before physicians can successfully evaluate treatment response.
The group of 18 leading experts are categorical in their conclusion, stating emphatically: “Regardless of the challenges we face in investigating and incorporating immuno-oncology into an interventional oncology practice, immunotherapy is destined to become an integral part of interventional oncology care, and the integration is therefore essential for the future of IO.”
In accordance with this sentiment, de Baère told the SIO audience: “Immuno-oncology will be a much bigger part of practice and research in the next five to 10 years. The reason for this is that we already know how great immuno-oncology is for cancer treatment.” Showing a graph depicting the number of trials investigating intratumoural immunotherapy opening every year, he demonstrated their exponential growth; from fewer than five opening each year between 1992 and 2004, to 40 opening in 2017. de Baère argues that intratumoural delivery allows for a high enough local dose to efficaciously destroy the tumour, without the toxicity of systemic delivery. “We can help medical oncologists specifically target the tumours,” he said.
“There is a lot of noise about this,” he enthused. Indeed, industry have started taking note, with some companies having their own dedicated compounds. One such example is Lytix Biopharma, which manufactures short, oncolytic peptides that cannot be delivered systemically. “Who can inject it locally?” de Baère asked the SIO delegates, “Interventional radiologists. This is the future of interventional oncology, and it is very important that we are part of it”.
“Arm yourself with the comprehensive but nuanced science behind hepatocellular carcinoma (HCC),” Riad Salem (Northwestern Memorial Hospital, Chicago, USA) instructed the audience at the Global Embolization Oncology Symposium Technologies (GEST; 9–12 May, New York, USA) during his Honorary Lecture, which concluded with the warning: “Do not let yourself be bullied by the tyranny of the randomised controlled trial”.
Arguing that “so-called evidence-based medicine is really not [that] 90% of the time”, Salem challenged the notion that randomised controlled trials with a primary endpoint of overall survival should be the gold standard in interventional radiology. However, he began by conceding that “the randomised design is ideal—it is the best. It directly compares [the control] to the treatment, it minimises the bias and gives you causality where you can say ‘this treatment led to this endpoint’. You can power a randomised control trial with a large enough sample size that you minimise type 1 and type 2 error, and of course it is the most influential data”. However, though he says this is all possible in theory, he goes on to recount how in practice, this is often far from the case.
Speaking generally, Salem opined: “In interventional radiology (IR) and other areas, these are very expensive and complicated studies to do, with sample sizes that are sometimes impractical, if not impossible. They take years to complete and, as a result, what is their relevance [when completed]?”.
There is a precedent for using lower level data to inform procedural decisions
Salem argued that there are precedents for not relying on randomised controlled data to guide procedural choice. In the late 1990s, Salem informed GEST delegates that he used to perform a lot of chemoembolization procedures. However, it was only in 2002 that Josep Llovet (University of Barcelona, Barcelona, Spain) and colleagues published in The Lancet findings from a randomised controlled trial that reported chemoembolization improved survival compared with conservative treatment. Writing at the time, Llovet et al said: “There is no standard treatment for unresectable HCC. Arterial embolization is widely used, but evidence of survival benefits is lacking.” In response to this, Salem continued, “Before 2002, we were all performing chemoembolization based on phase II data”. However, Salem emphasised its limitations: “You have a 112 patient clinical trial with three arms; notice each arm is about 35 to 40 patients, so it is very small. This study here, that we all quote [to support the use of chemoembolization as the standard of care in unresectable HCC patients], basically was a single-centre study. There is a low sample size, there is no active control, so there is relatively limited power—all the things that we currently need in a randomised controlled trial are not necessarily present in this clinical trial.” In fact, the trial was stopped when the ninth sequential inspection showed that chemoembolization had survival benefits compared with conservative treatment.
Examining the evidence presented in the various guidelines that help inform physician’s practice, Salem reported a distinct lack of level 1 data. Of the National Comprehensive Cancer Network (NCCN) guidelines, Salem said: “95% of the recommendations are based on non-level 1 evidence”. Continuing through other frameworks, he stated that in the American Association for the Study of Liver Diseases (AASLD) guidelines, two of the 21 recommendations are based on level 1 data. He stressed that “everything else is lower level evidence”. The European Association for the Study of the Liver (EASL) guidelines tell a similar story: three of their 36 recommendations hinge on level 1 evidence.
Salem summarised: “We have guidelines that tell us what we should and should not do, yet most of them are not based on the very data that we are supposed to be generating, so there is some confusion. […] As interventional radiologists, we have to recognise that many standards of care are not supported by randomised controlled trials, particularly with overall survival as the endpoint.”
He then goes on to enumerate the several procedures performed by interventional radiologists for which level 1 evidence does not exist: bland transarterial chemoembolization (TACE), drug-eluting bead (DEB) TACE, or Yttrium-90 (Y-90) TACE to treat HCCs or neuroendocrine tumours; ablation in colon cancers and HCCs; resection for colon cancer or HCC metastases. “Liver transplantation,” he added, “a goal that many of us seek to achieve for our patients, a gold standard, curative option—what is that based on? A phase II, single-arm study published in 1996 and based on 48 patients. It is the standard of care, I understand that, but we have to make sure that we compare our therapies and their respective levels of evidence with what other standards are based on.”
Not all randomised controlled trials change clinical practice
“What we want are randomised controlled trials that provide clinically meaningful results. I think that is what we believe in interventional radiology,” Salem stated. However, he went on to highlight how several randomised controlled trials were far from practice-changing.
Using the example of a phase III pancreatic cancer study published in the Journal of Clinical Oncology in 2007 by Malcolm Moore (Princess Margaret Hospital, Toronto, Canada) et al, Salem explained how, despite filling all the criteria for a randomised controlled trial, the results may still not be illuminating. Moore and colleagues set out to see if they could improve the chances of survival in patients with unresectable, locally advanced or metastatic liver cancer by adding erlotinib to gemcitabine. Comparing the erlotinib and gemcitabine group with the gemcitabine only cohort, the investigators found there was an overall survival benefit of 9.9 days in the combined group. “More than 500 patients, level 1 evidence—and a survival benefit of 9.9 days,” Salem reiterated. “Is erlotinib and gemcitabine the gold standard? I am not a medical oncologist, I do not know, but this trial satisfies everything the purists really want when it comes to generating level 1 evidence. I do not know if it actually changes standard of care though.” A recent publication in Oncology Reviews by Amrallah Mohammad (Zagazig University, Zagazig, Egypt) concluded that “only [a] small set of patients get small benefit” from the combined use of erlotinib and gemcitabine.
Randomised controlled trials “do not necessarily reflect real-world outcomes”
Randomised controlled trials are often designed by statisticians and physicians to fit what is logistically possible, and therefore do not necessarily reflect real-world outcomes, Salem said. He uses several examples to illustrate this point. Firstly, he explained how he suspects there is “a little bit of doctoring” going on when choosing the sample size for a randomised controlled trial: “Interestingly, if you look at many of these trials that we reported, sample size is 300, 400, 600—it is almost always an even number”. The sample size is the result of back and forth between the principal investigator and the statistician, and is, in theory, calculated from the initial hypothesis and the DELTA (difference elicitation in trials). Salem explains how, in practice, determining the sample size is often a case of calculating how many patients a physician believes they may realistically be able to enrol in a trial, and then “reverse engineering” a hypothesis and DELTA from that number (though he accedes he is “a little bit cynical”).
In addition to this alleged data engineering, Salem pointed to narrow inclusion criteria as slowing recruitment to trials. That so many are excluded slows recruitment, he said, and means that by the time enough patients are enrolled and have been followed-up, and the data have been analysed, the findings are no longer timely. According to Salem, there is “about a 90% non-enrolment rate”; he extrapolated from this that “the findings of a randomised study are [therefore] not applicable to 90% of the patients that you see, so it is a very strict patient population you are making conclusions about”.
Recruitment can also be an issue when enrolling for large, multicentre trials, Salem explained, due to the biases and beliefs individual institutions hold. In the mid-2000s, Salem and colleagues were designing a multicentre trial to compare Y-90 with RFA and TACE RFA. However, what was initially intended as a six-centre clinical trial devolved into a single-centre trial of 45 patients. The investigators could not enrol enough patients in each of the three arms—Y-90, TACE and TACE RFA—because of physician and institutional preference over certain procedures. Nevertheless, Salem used the data derived from the beginnings of this trial to redefine the institutional standard of care at Northwestern Memorial Hospital to Y-90.
Using another example from his own work in liver cancer, Salem explained that the STOP-HCC trial, of which he is the global principal investigator, further demonstrates the difficulties of recruitment in a randomised controlled trial. The initial vision was to have STOP-HCC as an open-label, prospective, multicentre, randomised, phase III trial evaluating Yttrium-90 (Y-90) transarterial chemoembolization (TACE) in the treatment of patients with unresectable HCC. “In 2010, when we started the trial, all we had was sorafenib, and we wanted to see if this would add to the standard of care”, Salem said at GEST. “This started as a 400 patient clinical trial; it is now eight years later, the technique has improved, there are seven other drugs approved, and our sample size is now 600. While I hope it will have an effect on standards of care, I am not sure what the impact of this trial will be, whether it is positive or negative.”
Overall survival “is not a good outcome for randomised trials with effective subsequent therapies”
Advising the listening interventional radiologists as to how he believes they should devise trials to further their field, Salem guards against using overall survival as a primary endpoint when the patient will receive multiple interventions. Quoting statisticians writing in the Journal of Clinical Oncology, Salem said that “survival is not a good outcome for randomised trials with effective subsequent therapies”. He elaborated: “We cannot attribute overall survival to the initial treatment, say TACE or radiofrequency ablation (RFA), if later on the patient had other interventions. After a patient progresses, they may be given regorafenib, lenvatinib, nivolumab, cabozantinib, ramucirumab. This gets very complicated.”
Indeed, the Barcelona Clinic Liver Cancer (BCLC) staging system (stages A/B) is predominantly predicated on level 2 data without data on overall survival. “It is too complicated to do overall survival studies, and there is a prohibitive statistical barrier”, Salem explained. “We must use imaging surrogates for BCLC A/B studies, such as time to progression and progression-free survival. Overall survival is possible in end-stage care, but really for everything else, we have to use imaging.”
He emphasised this point in his concluding remarks, reiterating: “I think in our quest to improve overall survival, we have let the statisticians rule a little too much, and we need to push back a little bit, and get a bit more clinical relevance in our clinical trials. For two therapies that might provide the same overall survival, we need to find surrogates that matter and reject the trope that overall survival is the supreme endpoint”.
Designing trials to push practice in interventional radiology
To combat these shortcomings, Salem made two proposals to the GEST audience for how interventional radiologists should go about designing trials in future.
Firstly, he suggested physicians conduct an initial, exploratory analysis. This would be an 80 patient study in a randomised, phase II trial design. “Forty versus 40, this bead versus that bead, this probe versus that probe”, Salem described. “Whatever it is you are investigating, you can compare it to a different option and make sure there is a difference you are identifying between the two.” If the investigators are aiming to change the standard of care, Salem suggested using this same model, but for 100 versus 100 patients: “If you cannot determine a difference in 100 patients versus 100 patients, there probably is not much there that is clinically relevant in the IR space”, he said. “Then you do not have to get a patient population of 1,000 and have a negative clinical trial.”
The second proposition Salem has for the GEST attendees is that investigators largely stop using overall survival as an endpoint, and use a clinically meaningful alternative. “I personally think response is a very important one”, he suggested. He explicated: “Imagine you have three treatments. One gives you stable disease, one gives you minor response, and one gives you major response. All three of those treatments have the same time to progression and the same progression free survival. But if you are a believer in the lethal tumour model in the liver, then the person with the best response rate is the person furthest away from the lethal tumour load line. So, everything else being the same, the best response becomes a relevant and important concept.”
He concluded: “I think we need to limit the amount of weight we give randomised controlled trials, and be careful not to prematurely and quickly discount other types of rigorously developed evidence. I think physicians rely on randomised controlled trials when supportive of their position, but interestingly ignore them when they do not; that is clear, we see that all the time.
“Do not accept in isolation the fact that we have limited level 1 randomised controlled trial data [in IR]. Take everything in totality—phase II, big data, randomised controlled trials—process, triangulate, and carry this knowledge to tumour board. You are certainly not alone in relying too heavily on phase II data, and please, whatever you are confronted with, do not let yourself be bullied by the tyranny of the randomised controlled trial.”
MRI Interventions said its ClearPoint Neuro navigation system has been used in 3,000 neurosurgical procedures.
The milestone procedure was completed at the University of California, San Francisco, USA, according to the vendor.
“This milestone is a testament to the value surgeons are placing on precision guided therapy, especially in neurosurgery where the stakes are the highest,” comments Joe Burnett, president and CEO of MRI Interventions. “Although the timing is coincidental, we were thrilled to share this success with the team at the University of California, San Francisco, who have partnered with us for the last decade in refining our platform and ensuring the voice of not only the doctor, but also that of the patient, is included in every improvement. It is also important to note that not only did UCSF perform the 3,000th case using ClearPoint, they also performed the 3,001st case that same day. UCSF is among the now ten centres scheduling two cases per day utilising the same MRI scanner, which has been a strategic push for us in the past year.”
Cook Medical recently released the second generation of the 2.6Fr CXI support catheter with platinum-iridium marker bands. The CXI catheter is used in small-vessel anatomy or super-selective anatomy for diagnostic and interventional procedures, including peripheral use.
“We strive to offer physicians the tools they need to provide the best possible outcomes for patients,” comments Mike Williams, director of global vascular programmes. “Physicians frequently asked for the 2.6Fr CXI support catheter to have the same visibility as smaller-sized CXI catheters. Platinum-iridium marker bands were added in response to these needs.”
This second-generation CXI catheter provides clinicians with better visualisation under fluoroscopy because of the platinum-iridium marker bands. The catheter comes with additional tip configurations and a new 135cm length. Its stainless steel braid provides responsive torque and pushability, and the 2.3Fr and 2.6Fr sizes can fit coaxially in the 4.0Fr size to increase the amount of support.
The new design of the 2.6Fr platform is now available in Europe, the USA and Canada.
Siemens Healthineers will acquire all issued and outstanding shares of common stock of Corindus Vascular Robotics, Corindus announced this month.
The cash transaction is US$4.28 per share, resulting in an aggregate purchase price of US$1.1 billion by Siemens Medical Solutions, a subsidiary of Siemens Healthineers, according to Corindus.
“We are pleased to have reached this agreement with Siemens Healthineers,” comments Mark J Toland, president and CEO of Corindus, in the news release. “We believe the transaction will deliver immediate, compelling and certain value to all Corindus stockholders, as well as substantial benefits to our customers. The combination of Siemens Healthineers’ advanced, high-quality imaging, digital and artificial intelligence tools with Corindus’ precision robotics platform has the potential to transform the way healthcare is delivered to those suffering from cardiovascular or peripheral disease. The tremendous technology synergies and shared vision between both companies should allow us to achieve a seamless integration between our businesses.”
“Corindus has established a leading position in vascular robotics with a compelling technology platform for robotic-assisted coronary, peripheral, and neurovascular procedures,” says Michel Therin, president of advanced therapies at Siemens Healthineers. “The acquisition of Corindus, combined with Siemens’ strong advanced therapies portfolio, will help further advance the growth of vascular robotics. The integration of our technologies could lead to reduced variability, improved efficiency, expanded access to care, and ultimately improved patient outcomes. We look forward to welcoming the Corindus team to Siemens Healthineers.”
Corindus Vascular Robotics’ CorPath is the first US Food and Drug Administration-cleared medical device to bring robotic technology to percutaneous coronary and vascular procedures. Siemens Healthineers is a multibillion-dollar health-care technology company.
The merger is expected to close in the fourth quarter of 2019, Corindus said.
According to a BIBA MedTech survey, 52% of neurointerventionalists believe that they are the only specialists who have the relevant skills and experience to perform interventional stroke procedures (e.g. mechanical thrombectomy). However, of those who believe other specialities—with the appropriate training—could potentially perform such procedures, 58% propose interventional radiologists. Previous discussions about other specialists performing interventional stroke procedures have focused on interventional cardiologists.
Mechanical thrombectomy is now an established treatment for patients with emergent large vessel occlusion, but who should perform this procedure is controversial. A 2016 multisociety consensus document—published in the Journal of NeuroInterventional Surgery—states that “physicians providing intra-arterial treatment for acute stroke are required to have appropriate training and experience for the performance of neuroangiography and interventional neuroradiology”. However, some believe that restricting interventional stroke procedures (specifically, mechanical thrombectomy) to neurointerventionalists may limit the number of patients who are able to access the therapy given the lack of relevant operators in some areas. For example, in the 2019 Vascular and Endovascular Challenges Update, cardiologist Jan Kovac writes “collaboration of various interventional specialists is desirable to deliver this therapy to a wider population”.
A previous poll on this issue, conducted at the 2019 Charing Cross Symposium (15–18 April, London, UK), indicated that 57% of respondents were against mechanical thrombectomy being restricted to neurointerventionalists. However, these respondents were predominantly vascular and endovascular surgeons. Therefore, BIBA MedTech sought to understand how practising neurointerventionalists felt about the issue.
Of 54 neurointerventionalists surveyed, 52% agreed that “only neurointerventionalists should perform interventional stroke therapy” vs. 48% who did not agree. Of those who did not agree (26), 58% said “interventional radiologists” in response to the question “who else (with appropriate training) do you feel might be able to perform interventional stroke procedures?”. Of note, only 15% said interventional cardiologists. See Figure 1.
In his chapter in the 2019 Vascular and Endovascular Challenges Update, Kovac proposes interventional cardiologists as suitable alternative specialists to perform interventional stroke procedures. He states that cardiologists are “no strangers to stroke care”, commenting that “cardiologists have traditionally played an important role in stroke prevention by providing both comprehensive medical and interventional management of cardiovascular risk factors [for stroke] including atrial fibrillation”. He adds: “It appears reasonable to complement the existing workforce of neurointerventional radiologists by interventional cardiologists being properly trained in mechanical thrombectomy, joining the interdisciplinary stroke teams led by neurologists”. However, Kovac does stress that there is “absolutely no doubt that a fully trained neurointerventionalist, with audited practice outcomes, and adequate skill maintenance, is the optimal provider of mechanical thrombectomy for stroke patients”.
The 2016 multisociety consensus statement observes: “The technical skills needed to safely deliver devices into the intracranial circulation are significantly more involved than simply placing a catheter for medical infusion. Catheter skills from other circulations do not replace the need for formal training in safe intracranial microcatheter navigation and device placement.”
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Irene Bargellini (Pisa, Italy) tells BLearning IR at the first Embolotherapy conference (ET; 26–29 June, Valencia, Spain) that non-target embolization is a frequently under-diagnosed, sometimes fatal, problem that interventional radiologists encounter every time they work with embolics.
Understanding the vascular anatomy, identifying the non-target vessels, positioning the catheter properly, choosing the right embolic, and checking injection under fluoroscopy are all part of reducing the risk of non-target embolization, Bargellini says.
She also draws attention to new devices, such as an innovative novel microcatheter with side-holes that received CE mark in April. This device is designed to reduce the risk of embolic material reflux and works on the principle that fluids, but not embolic material, exit from the side-holes and create a vortex that acts as a barrier to prevent reflux.
Guerbet sponsored this video and its distribution in association with Interventional News.
The statements by Guerbet’s key opinion leader described here are based on results that were achieved in their unique setting. Since there is no “typical” hospital and many variables exist (e.g. hospital equipment, case mix, patients’ conditions) there can be no guarantee that other physicians will achieve the same results. Availability of Guerbet products may vary by country.
Sanjay Misra (Rochester, USA) talks to Interventional News about his research into whether stem cell therapy can help AVFs (arteriovenous fistulas) mature and also prevent venous stenosis. The pilot study with a small group of haemodialysis AVF patients led to “promising results” according to Misra, who is planning a larger study to validate the findings. He also discusses the optimal point to deliver the therapy, its future direction and finally, addresses some of the safety concerns around stem cell therapy.
Boston Scientific has announced the completion of its acquisition of BTG, pursuant to the previously announced scheme of arrangement. BTG develops and commercialises products used in minimally-invasive procedures targeting cancer and vascular diseases, as well as specialty pharmaceuticals.
BTG has three key businesses, the largest of which is its highly-differentiated interventional medicine portfolio that encompasses interventional oncology therapeutic technologies for patients with liver and kidney cancers, as well as a vascular portfolio for treatment of deep vein thrombosis, pulmonary embolism, deep venous obstruction and superficial venous disease.
“The addition of the BTG interventional medicine portfolio reinforces our category leadership strategy and enables us to offer best-in-class technologies, unparalleled clinical evidence and a strengthened commercial infrastructure to support physicians treating some of the most challenging diseases impacting patient health around the world,” comments Mike Mahoney, chairman and chief executive officer, Boston Scientific. “Leveraging the employee talent and clinical and commercial expertise of these two high-performing organisations will generate continued innovation and access so that we may advance patient care in ways that neither company could do alone.”
In addition to the interventional medicine product lines, the BTG portfolio also includes a specialty pharmaceutical business comprised of acute care antidotes to treat overexposure to certain medications and toxins, and a licensing business that receives royalties related to BTG intellectual property and product license agreements.
Upon the effectiveness of the scheme of arrangement, BTG became a wholly-owned subsidiary of Boston Scientific, and BTG shares no longer trade on the London Stock Exchange. Under the terms of the previously announced transaction, holders of BTG common shares will receive 840 pence in cash per share.
Boston Scientific expects to complete the previously announced sale of its global embolic microspheres portfolio—comprised of Embozene, Embozene TANDEM and ONCOZENE brands—to Varian Medical Systems. in due course, a transaction entered into in connection with obtaining the antitrust clearances required to complete the BTG transaction.
In addition, the company is initiating a process to explore the divestiture of the royalty stream associated with BTG’s Zytiga licensing arrangements and anticipates closing this divestiture by the end of 2019.
The transaction is expected to be immaterial to adjusted earnings per share in 2019 as a result of the BTG transaction closing later than originally anticipated, the divestiture of the Boston Scientific embolic microspheres portfolio, and the treatment of the licensing business as an asset for accounting purposes and its intended divestiture. The transaction is expected to be four to five cents accretive in 2020 on an adjusted basis, and increasingly accretive thereafter. On a GAAP basis, the transaction is expected to be less accretive, or more dilutive as the case may be, due to amortization expense and acquisition-related net charges. acquisition
The BASIL-3 study, which was halted in response to findings reported in the Journal of the American Heart Association (JAHA) that paclitaxel-coated and –eluting devices were associated with an increased mortality signal when used in the femoropopliteal arteries, is on course to resume in September 2019.
Following the announcement that the trial is set to continue, the Vascular Society for Great Britain and Ireland have provided an update on the trial’s progress. In a news release, the society state: “Based on the aggregate data we have so far on the 411 patients who had been randomised at the time we paused recruitment in December 2018, our statistical colleagues tell us that, maintaining 90% power and a minimum of two-year follow-up (as per the original protocol), we will probably need just short of 500 patients to answer the original question.
“In addition, in concordance with advice from MHRA [Medicines and Healthcare products Regulatory Agency] (and FDA [the US Food and Drug Administration]), we are discussing with NIHR HTA [National Institute for Health Research Health Technology Assessment], and other stakeholders, the possibility of extending follow-up to a minimum of five years (to look at the late mortality).
The FDA has been in touch “very recently” with the British Society of Interventional Radiology (BSIR) regarding a data sharing agreement. The news release on the Vascular Society for Great Britain and Ireland’s website states, “We will be discussing their approach and proposals at our next TMG [trial management group] meeting in September”. BASIL
International Cardio Corporation (ICC) announced that it has achieved the first human use of its high-intensity focused ultrasound (HIFU) system to designed to treat peripheral vascular disease (PVD).
The Minneapolis-based company said its HIFU Synthesiser system is undergoing a 15-patient safety study in The Netherlands to investigate its feasibility and safety for the treatment of atherosclerotic plaques. The system uses high-intensity ultrasound to noninvasively treat vulnerable and occlusive plaques in peripheral arteries to reduce stroke mortality and improve the quality of life for those suffering from PVD.
“The potential for noninvasively ablating and stabilising vulnerable vascular plaques is a compelling opportunity to both reduce stroke risk and deliver better outcomes with higher patient safety than current treatment options for patients suffering from PVD,” says ICC chief operating officer David Lee in a news release.
The safety study is the first step toward achieving the CE mark and FDA approval HIFU Synthesiser.
On The Netherlands Trial Register website, the investigators summarise their study: “Current treatment of lower extremity peripheral arterial disease consists of risk factor modification, exercise therapy and pharmacological treatment initially, but intervention is frequently needed when patients are significantly disabled. Interventional treatment is invasive, either surgical or endovascular. This study investigates a new non-invasive technique that uses high intensity focused ultrasound to treat atherosclerotic arterial disease.”
The primary endpoint of the study is the 30-day major complication rate, which is a composite endpoint that includes 30-day major adverse limb event rate and 30-day mortality rate. Secondary outcomes assessed include a range of technical, MRI, echo-duplex, clinical, and quality of life parameters.
Concept Medical has been granted breakthrough device designation from the US Food and Drug Administration (FDA) for its MagicTouch percutaneous transluminal angioplasty (PTA) sirolimus drug-coated balloon (DCB) catheter, used in the treatment of peripheral arterial disease (PAD) in infra-popliteal lesions. The first breakthrough device designation received by Concept Medical was on 30 April 2019 for its MagicTouch sirolimus-coated balloon, for the treatment of coronary arterial disease (CAD) in patients with in-stent restenosis.
Concept Medical has pioneered the sirolimus drug delivery platform technology (Nanolute Technology) which has been used in more than 30,000 patients worldwide. The MagicTouch PTA sirolimus-coated balloon is developed using this Nanolute Technology for use in PAD.
In an ongoing clinical study (XTOSI), associate professor Edward Choke, principal investigator of the trial and chief of Vascular Surgery, Sengkang General Hospital, Singapore, said, “XTOSI study is the world’s first pilot study to investigate the safety and efficacy of novel MagicTouch PTA sirolimus drug-coated balloon in the treatment of below the knee arterial lesions in addition to femoropopliteal lesions. The majority of patients enrolled had major comorbidities (diabetes and end stage renal failure) and the indication for angioplasty was for severe critical limb ischaemia (more than 90% had the most severe Rutherford scores of 5 or 6). The extent of peripheral arterial disease treated were also severe, and about 80% of patients did not have any patent below the knee arteries before angioplasty.
“I am very encouraged by the excellent results so far in these challenging cohort of patients. Device and technical success were both 100%. Freedom from device and procedure related mortality was 100%. Limb salvage rate at 30 days was 97%. At six months, freedom from clinically driven target lesion revascularisation (TLR) was 91%; and primary patency, independently and blindly assessed by duplex ultrasound, was 82%. I did not encounter any distal embolization or ‘slow flow phenomenon’ after application of sirolimus-coated balloon in below the knee vessels.”
Sahil Parikh, an interventional cardiologist and associate professor of Medicine and director of Endovascular Services at the Columbia University College of Physicians and Surgeons (New York, USA) says, “The breakthrough designation demonstrates how important it is for us to have new technologies for below the knee intervention. Patients with critical limb ischemia (CLI) represent an enormous burden to our healthcare system and comprehensive care for these patients begins with effective revascularisation. The MagicTouch PTA will hopefully bring us closer to our goals of reducing amputations in the USA and the world.”
According to a press release, this breakthrough device offers Concept Medical an opportunity to interact with the FDA’s experts through several different programme options “to efficiently address topics as they arise during the premarket review phase, which can help manufacturers receive feedback from the FDA and identify areas of agreement in a timely way”. Manufacturers can also expect prioritised review of their submission. Under the programme, the FDA will provide Concept Medical with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.
A private equity firm, Palatine (Manchester, UK), has announced that it has made a “significant investment” into a UK centre—Veincentre—that provides endovenous laser ablation (EVLA) for the management of varicose veins. The investment, according to Palatine, is the fourth to be made from the firm’s £100m “Impact Fund” that “targets companies with a social and/or environmental impact, alongside industry-standard returns”.
A press release reports that, in the UK, the NHS withdrew funding for varicose veins treatment after determining it was “non-essential”. Last year, the NHS released a consultation document on stopping or reducing the routine commissioning of 17 interventions for which “less invasive, safer treatments are available and just as effective”. One of these interventions was surgery for varicose veins, with the document noting that patients with varicose veins should only be referred for treatment when they meet specific criteria (such as having a venous leg ulcer). It states: “For patients whose veins are purely cosmetic and are not associated with any symptoms, do not refer for NHS treatment.”
According to the press release announcing the investment from Palatine, EVLA reduces recovery times associated with traditional forms of treatment (i.e. conventional surgery) and significantly reduces scarring. David West, the clinical director of Veincentre, says: “With the help of the Palatine team, our aim to bring this specialist, yet affordable treatment to as many people as possible seems more achievable than ever. The work we do has become increasingly important following falling NHS funding in the sector, and now with the help of this investment, we will be able to offer a necessary social service where access might otherwise be scarce.”
Veincentre now plans to continue to build on its recent nationwide expansion, opening new clinics in Glasgow and Leeds later this year, before carrying out a plan to open two new centres across Britain annually. Beth Houghton (head of the Impact Fund, Palatine) comments: “We are very excited to work with Veincentre; with the lack of NHS funding for what can for some people be a debilitating condition, it is important that people are able to access treatment at affordable prices, in convenient locations. With the planned roll-out of clinics to Scotland and Yorkshire, Veincentre will be able to offer treatment in almost every major region in the nation, and the management team has ambitions to offer full coverage of the UK. Veincentre is exactly the type of business we want to support, and we look forward to working with the management team in order to help accelerate growth and consolidate the company’s position as a leader in the industry.”
West told BIBA Briefings: “I am delighted that we have teamed up with Palatine who recognise the impact varicose veins and other problems with venous insufficiency have on people’s lives and the lack of comprehensive provision of modern treatment by the NHS. Most of our patients are bothered by both the cosmetic appearance and troublesome symptoms and many tell us that treatment has changed their lives. Although in an ideal world, all UK patients would be able to access NHS treatment it is difficult to justify treating all cases at the inevitable expense of patients with other more pressing health issues. This investment ensures that we can achieve our short-term expansion plans in the UK and put us on a firm footing for international growth in the future. Veincentre also encompasses the specialist medical devices company EVLA Expert, which provides UK manufactured all in one kits for EVLA at a fraction of the price of the major laser manufacturers. We are always on the lookout for ‘hungry’ keen vascular specialists to join our friendly multidisciplinary team of nurses, surgeons and radiologists.”
This article is part of a series of BIBA Briefings columns published in Venous News International. For previous columns, see past issues.
In a new consensus statement, the Joint UK Societies (JUKS)—which includes the British Society of Interventional Radiology—say that the evidence for renal denervation is “insufficient” to recommend its routine use in clinical practice. However, they add that they support ongoing clinical trial programmes of renal denervation and “strongly encourage” clinicians to tell their hypertensive patients about ongoing renal denervation studies.
Melvin D Lobo (William Harvey Research Institute, Queen Mary University London, London, UK) and colleagues write in Heart that a previous JUKS consensus statement on renal denervation—published in 2014—“placed a moratorium” on the use of renal denervation in routine UK clinical practice until further “favourable evidence had emerged”. They explain that the 2014 statement was in response to the results of the SYMPLICITY HTN-3 trial, which found that renal denervation with the Symplicity system (Medtronic) did not significantly reduce blood pressure compared with a sham procedure.
According to Lobo et al, recommendations from this 2014 statement and those from the European Clinical Consensus Conferences “led to new and improved clinical trials of renal denervation utilising input from experts in the field to lead on both the design and execution of studies in collaboration with commercial sponsors”. Therefore, now that several of these studies have been published, JUKS have published a new consensus statement to “consider the new evidence that they provide”.
The authors review data both for Medtronic’s radiofrequency Symplicity Spyral system and for ReCor Medical’s ultrasound Paradise system, noting that both system have been associated with significant reductions in ambulatory blood pressure (albeit in different patient populations). “The SPYRAL and RADIANCE [Paradise] study programmes to date have provided encouraging data to suggest that renal denervation may have a role in the treatment of hypertension,” Lobo et al comment. They add that, together, the studies have shown the “value of collaboration” better different disciplines (including industry) and “rekindled enthusiasm for renal denervation in the clinical community”.
However, Lobo et al do outline the limitations of the studies—such as being of short duration—and that the studies have “reported considerable heterogeneity in the response to renal denervation”. Furthermore, they note: “At present, it is unclear which technology may be best for renal denervation, with radiofrequency and ultrasound systems appearing more or less similar in efficacy and ongoing trials of chemical ablation systems are not published yet.”
Thus, Lobo et al report that the JUKS are not changing their position that there is “insufficient evidence to recommend the routine use of renal denervation and that the use of renal denervation should remain restricted to clinical trials”. They do though provide an “agenda” for important areas for future research. These areas include further studies to determine the role of renal denervation in the treatment of hypertension, establishing the safety/durability of different renal denervation technologies, and identifying which patients will be the best responders.
Although they do not advocate the use of renal denervation in routine clinical practice, Lobo et alsay that the JUKS support ongoing clinical trials programmes from the different device manufacturers across the spectrum of renal denervation technologies. They add that they “strongly encourage clinicians who look after patients with hypertension to inform their patients about these studies which are recruiting participants who are on and off medications in order to inform future practice.”
Lobo told BIBA Briefings that he thinks there will be a definitive answer about the role of renal denervation for managing hypertension in “the next two to three years”.
Expanding the role of renal denervation
The need for further studies to better understand the role of renal denervation to manage hypertension has not, however, prevented studies exploring the use of the procedure to treat other cardiac conditions. Lobo said: “I think these studies make a lot of sense particularly where those conditions are characterised by high sympathetic drive. The design of these studies, however, will need to be very carefully thought out given how complex it has been to evaluate the efficacy of renal denervation for hypertension.”
Speaking at EuroPCR 2019 (21–24 May, Paris, France), Marshall Heradien (Department of Internal Medicine, Stellenbosch University, Tygerberg, South Africa) presented a study that evaluated the use of renal denervation for the management of atrial fibrillation. He said that several previous studies “support the idea that renal denervation may have an antiarrhythmic effect”, adding that he and his fellow investigators sought to test the hypothesis that “upstream renal denervation treatment can reduce atrial fibrillation in patients with hypertensive heart disease”.
In the study, 42 patients were randomised to receive treatment with renal denervation (10 with the first-generation Flex catheter and 32 with the second-generation Spyral catheter) and 38 underwent “sham” renal denervation. The primary endpoint was the first event of subclinical atrial fibrillation atrial fibrillation at least six minutes on an implantable loop recorder (which was scanned at six-month intervals).
After an average of three years of follow-up, 19% of the renal denervation group had an episode of atrial fibrillation compared with 47% of the sham procedure group (0.011). Furthermore, patients in the sham procedure experienced significantly more episodes of fast atrial fibrillation: 12% vs. 2% (p=0.002). Renal denervation was also associated with a significant reduction in cardiovascular death at two years: one patient vs. six patients for the sham procedure (p=0.04). However, there were no significant differences in office systolic blood pressure at six months between groups.
Heradien concluded: “In this single-centre randomised controlled trial of patients with hypertensive heart disease, upstream treatment of renal denervation reduced subclinical and fast atrial fibrillation and cardiovascular death.”
Renal denervation has also been explored for the management of heart failure secondary to Chagas’ disease. In Catheterization and Cardiovascular Interventions, André G Spadaro (Heart Institute, University of São Paulo Medical School, São Paulo, Brazil) and others report that renal denervation was “safe and feasible” for patients with Chagas cardiomyopathy. They add that after nine months of follow-up, the primary endpoint (all-cause mortality, myocardial infarction, stroke, need for renal artery invasive treatment or worsening renal function) occurred in 36.4% of 11 patients randomised to undergo renal denervation compared with 50% of six patients randomised to conservative treatment (p=0.06). Spadaro et al state that these findings warrant “future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.”
This article is part of a series of BIBA Briefings columns published in Interventional News. For previous columns, see past issues.
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Medtronic has issued the following statement regarding the US Food and Drug Administration’s (FDA) updated letter to healthcare providers for paclitaxel-devices in patients with peripheral artery disease (PAD) in the superficial femoropopliteal artery (SFA):
“Medtronic would like to thank FDA and the panel members for their thoughtful deliberations and dedication to providing physicians, patients, and administrators with updated recommendations following the Advisory Committee meeting of the Circulatory System Devices Panel in June [19–20 June, Washington, DC, USA). The next steps as outlined by [the] FDA are critical to ensuring that physicians and their patients with PAD retain the option to utilise paclitaxel-coated therapies. The IN.PACT Admiral drug-coated balloons (DCB) have demonstrated a clear positive benefit on clinical outcomes and quality of life across multiple randomised controlled clinical trials.
“Importantly, this guidance will allow:
“Medtronic is encouraged by this path forward, but our work to evaluate the root cause of this safety signal is not complete. It is important to remember that causality was not able to be established in the FDA or VIVA/NAMSA [Vascular InterVentional Advances/ North American Science Associates] analyses. Therefore, it is critical that Medtronic and our industry partners continue to work together to share safety and effectiveness data to further facilitate the benefit-risk conversation. This work is consistent with the Medtronic Mission, and we look forward to continued collaboration with physician societies, FDA, and our industry partners throughout the next phase of this effort.
“Medtronic remains confident in the safety and effectiveness of IN.PACT Admiral. In the IN.PACT SFA trial, three out of four DCB patients remained intervention-free through five years, and for DCB patients who required a repeat procedure, the time to reintervention was prolonged for more than two years. In line with FDA’s recommendations, we encourage physicians to talk to their patients about the benefits and risks of all available treatment options.”
Clinical studies of paclitaxel-coated balloons and paclitaxel-eluting stents “may continue and should collected long-term safety (including mortality) and effectiveness data”, says the US Food and Drug Administration (FDA) in a letter to healthcare providers on 7 August. This is due to “the demonstrated short-term benefits of the devices, the limitations of the available data, and uncertainty regarding the long-term benefit-risk profile of paclitaxel-coated devices”.
The letter provides an update on the agency’s stance on the use of paclitaxel devices to treat peripheral arterial disease (PAD) in the femoropopliteal arteries. The FDA say clinical studies investigating these devices in the lower leg “require appropriate informed consent and close safety monitoring to protect enrolled patients”, and confirm they are working with study investigators to modify informed consent documents to include information about the late mortality signal.
The FDA state: “Based on the conclusions of our analysis and recommendations of the advisory panel, the FDA is taking additional steps to address this signal, including working with manufacturers on updates to device labelling and clinical trial informed consent documents to incorporate information about the late mortality signal. The FDA is also continuing to actively work with the manufacturers and investigators on additional clinical evidence development for assessment of the long-term safety of paclitaxel-coated devices.”
The recommendations
In full, the FDA recommendations are:
FDA actions
In full, the FDA actions are:
Summary of earlier FDA statements
In June this year, the agency convened a Circulatory Systems Devices Panel meeting (19–20 June, Washington, DC, USA) on the late mortality safety signal associated with paclitaxel-coated balloons and paclitaxel-eluting stents used to treated PAD in the femoropopliteal arteries.
Following the two-day discussion, which included the presentation of the agency’s own analysis of long-term follow-up data from pivotal premarket randomised trials, an FDA Circulatory System Devices Panel Advisory Committee concluded that there is a “late mortality signal”, as first described in the Journal of the American Heart Association (JAHA) paper authored by Konstantinos Katsanos et al (Patras, Greece) in December 2018.
However, they also concluded that better data collection was necessary going forward, as some data were missing, a small sample size meant there were wide confidence intervals, and there was pooling of studies of different paclitaxel devices that were not intended to be combined. The panel determined that there were not enough data to confirm a class effect, and no consensus was reached on the cause(s) of death.
In their most recent letter to healthcare providers, dated 7 August 2019, the FDA summarise the deductions of the advisory committee back in June: “In the three randomised trials which enrolled a total of 1,090 patients, the crude mortality rate at five years was 19.8% (range 15.9–23.4%) in patients treated with paclitaxel-coated devices compared to 12.7% (range 11.2–14%) in subjects treated with uncoated devices. The relative risk for increased mortality at five years was 1.57 (95% confidence interval 1.16–2.13), which corresponds to a 57% relative increase in mortality in patients treated with paclitaxel-coated devices. A meta-analysis performed by VIVA (Vascular InterVentional Advances) physicians of patient-level data provided by manufacturers reported similar findings with a hazard ratio of 1.38 (95% confidence interval 1.06–1.80). […] The Panel determined, and the FDA concurs, that additional clinical study data are needed to fully evaluate the late mortality signal.”
In the largest cohort study to date, new research from Jefferson (Philadelphia University and Thomas Jefferson University, Philadelphia, USA) demonstrates that transradial surgery, done via the wrist, is safe and effective for a broad range of neuroendovascular procedures, and gives patients faster recovery with less procedural risk. Neurointerventionists most commonly use a transfemoral approach, threading instruments through arteries in the groin.
“Despite improved safety shown in large cardiology trials, transradial brain surgeries via the wrist are much less common”, says senior author of the study and neurosurgeon Pascal Jabbour (Jefferson, Philadelphia, USA). “Neurosurgeons tend to prefer the transfemoral approach on which many of us were trained. But our research demonstrates that all kinds of neurological procedures can be done effectively and even more safely via the wrist.”
Transradial access has been widely adopted by interventional radiologists across a range of procedures, with many advocating for its use due to its positive clinical outcomes and patient satisfaction measures.
Jabbour and his team, including first author Omaditya Khanna, retrospectively examined the medical records of 223 patients who underwent 233 consecutive neuroendovascular interventions via radial artery access at Jefferson. The procedures included diagnostic angiograms, mechanical thrombectomies, arteriovenous malformation (AVM)/ arteriovenous fistulae (AVF) embolizations, coiling, stent-assisted-coiling, Woven EndoBridge (WEB) intracranial aneurysm device placement and flow-diversion treatments of cerebral aneurysms, and carotid stent placement.
A subset of 66 patients who had undergone both transfemoral and transradial surgeries were selected to complete a satisfaction survey to assess their preference. As published in Stroke, the majority of patients—94%—said they preferred surgery through the transradial route.
In addition, patients overall reported shorter recovery times with transradial access. It is easier to ensure a blood vessel in the wrist has clotted, and so patients can go home shortly after surgery, rather than laying horizontally for four to six hours after transfemoral surgery. The mean procedure time was also shorter for diagnostic angiograms performed via transradial versus transfemoral access (18.8±15.8 versus 39.5±31.1 minutes; p=0.025).
“Lying flat after certain kinds of brain surgery should be avoided in cases with high intracranial pressure, and yet it is the best way to prevent groin and internal bleeds,” comments Jabbour. “For these cases surgery via the wrist is by far the safest option.”
One of the most compelling reasons to change practice, says Jabbour, is that it eliminates the risk of rare but potentially dangerous complications of post-surgical bleeds in the groin and retroperitoneal area, which can be difficult to detect. The overall incidence of perioperative and postprocedural complications was investigated, and was found to be low across all procedures performed via transradial access. Periprocedurally, only two patients had symptomatic radial artery spasm, and there were no instances of iatrogenic complications (such as vessel dissection, stroke, and haemorrhage).
In 10 cases (4.3%), the intended procedure could not be completed via a transradial approach, and, thus, femoral artery access had to be pursued instead. Ten patients complained of minor postprocedural complications, although none required therapeutic intervention.
Jabbour and colleagues conclude: “Radial artery catheterisation is a safe and durable alternative to perform a wide range of neuroendovascular procedures, with a low rate of complications. On the whole, patients prefer transradial compared with transfemoral access.”
Transradial access in acute ischaemic stroke intervention
Jabbour was one of the first neurosurgeons to perform brain surgery via the wrist and has continued to teach others this technique.
In 2016, Diogo Haussen (Emory University School of Medicine and Grady Memorial Hospital Marcus Stroke and Neuroscience Center, Atlanta, USA) and colleagues set out to describe the feasibility and safety of transradial access in the interventional management of acute ischaemic stroke. Publishing their findings in the British Medical Journal (BMJ), they concluded that failure of transfemoral access in the endovascular treatment of acute ischaemic stroke is uncommon, “but leads to unacceptable delays in reperfusion and poor outcomes. Standardisation of benchmarks for access switch could serve as a guide for neurointerventionalists. Transradial access is a valid approach for the endovascular treatment of acute ischaemic stroke.” neuroendovascular
The US Food and Drug Administration (FDA) have denied BD premarket approval (PMA) for the company’s Lutonix drug-coated balloon (DCB) in the treatment of peripheral arterial disease (PAD).
Speaking in the company’s third quarter conference call on 6 August, BD CEO Vincent Forlenza told analysts: “Regarding our FDA, PMA submission for Lutonix below the knee [BTK], as you are all aware, we have been working with the FDA in a collaborative review process. Subsequent to the FDA Advisory Committee meeting on paclitaxel, the statutory review time for our BTK PMA submission concluded, and the FDA notified us that our PMA was not approvable in its current form.
“While this determination was based on the clinical evidence provided to-date, we continue to review, collaborate and align with the FDA on the path forward regarding our submission, including the need to potentially provide additional clinical data.
“As a result, the approval process timeline has extended out from our previous expectations and we no longer expect approval this calendar year. We will keep you informed as we work with the FDA and make further progress.”
Paclitaxel devices have come under regulatory scrutiny in the last eight months, following the publication of a meta-analysis in the Journal of the American Heart Association (JAHA) by Konstantinos Katsanos (Patras, Greece) and colleagues reporting an increased association of death when paclitaxel devices are used in the lower leg. The FDA analysed all available clinical randomised controlled trials or single-arm registries conducted with agency-approved devices with at least two year follow-up. The investigation compared drug-eluting or coated devices with non-eluting or coated devices.
At two years, the observed mortality rates for the paclitaxel-coated device group were higher for the Zilver PTX (Cook Medical) trial, Levant 2 (evaluating BD’s Lutonix DCB), and IN.PACT SFA I and II trials (looking at Medtronic’s Admiral DCB) in the FDA’s own analysis.
On the same call, the company reaffirmed its full-year revenue and earnings forecasts, and reported quarterly revenues of US$4.35 billion for the third fiscal quarter (which ended 30 June this year). According to a BD press release, this represents an increase of 1.7% over the prior-year period. The company state that on a comparable, currency-neutral basis, revenues increased 5.7% over the prior-year period.
Clinical trials are a critical tool for getting new treatments to people who need them, but research shows that difficulty finding the right volunteer subjects can undermine the effectiveness of these studies. Researchers at Cincinnati Children’s Hospital Medical Center (Cincinnati, USA) designed and tested a new computerised solution that used artificial intelligence (AI) to effectively identify eligible subjects from Electronic Health Records (EHRs), allowing busy clinical staff to focus their limited time on evaluating the highest quality candidates.
The study is published online in JMIR Medical Informatics. It shows that compared to manually screening EHRs to identify study candidates, the system—called the Automated Clinical Trial Eligibility Screener (ACTES)—reduced patient screening time by 34% and improved patient enrollment by 11.1%. The system also improved the number of patients screened by 14.7% and those approached by 11.1%.
Busy emergency departments often serve as excellent locations for clinical trial coordinators to find people who may be good study candidates. According to the study’s lead investigator, Yizhao Ni, (Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA), ACTES is designed to streamline what often proves to be inefficient clinical trial recruiting process that does not always catch enough qualified candidates.
“Because of the large volume of data documented in EHRs, the recruiting processes used now to find relevant information are very labour intensive within the short time frame needed,” comments Ni. “By leveraging natural language processing and machine learning technologies, ACTES was able to quickly analyse different types of data and automatically determine patients’ suitability for clinical trials.”
How it works
The system has natural language processing, which allows computers to understand and interpret human language as the system analyses large amounts of linguistic data. Machine learning allows computerised systems to automatically learn and evolve from experience without specifically being programmed. This makes it possible for computer programs to process data, extract information, and generate knowledge independently.
The automated system extracts structured information such as patient demographics and clinical assessments from EHRs. It also identifies unstructured information from clinical notes, including the patients’ clinical conditions, symptoms, treatments and so forth. The extracted information is then matched with eligibility requirements to determine a subject’s suitability for a specific clinical trial.
The system’s machine learning component also allows it to learn from historical enrolments to improve its future recommendations, according to the researchers. Much of the analyses are handled by carefully designed AI algorithms, essentially procedures or formulas that computers use to solve problems by performing a set sequence of specified actions.
Advanced to live clinical setting
Previously the system was successfully pilot tested in a retrospective study published in 2015 by the Journal of the American Medical Informatics Association. The current study tested the solution prospectively and in real time in a busy emergency department environment, where clinical research coordinators recruited patients for six different paediatric clinical trials involving different diseases.
Using the technology in a live clinical environment involved significant collaboration between data scientists, application developers, information service technicians and the end users, clinical staff.
“Thanks to the institution’s collaborative environment, we successfully incorporated different groups of experts in designing the integration process of this AI solution.” Ni says.
The researchers listed as limitations the small number of clinical trials used in the study, all from a single clinical department. They also pointed to some lingering issues involving the system’s accuracy at interpreting data. These issues will be resolved in future studies through ongoing enhancements to the technologies and also by testing the system in a wider variety of clinical departments, according to the investigators.
Complications are an inevitable component of an interventional radiologist’s practice, says Eric Keller, especially as a newer specialty with a reputation for pushing medical frontiers. As such, he elaborates on the ethics of procedural complications, and describes how he believes physicians should conceptualise and learn from their mistakes. Keller calls for more research on the ethics of complications in interventional radiology (IR), detailing how the innovation that characterises the specialty could be directed towards reimagining approaches to answering hard-hitting questions.
Some people consider “errors” and “complications” distinct, in that an error implies a mistake was made, while complications occur even when everything is done correctly. This distinction is helpful from a systems perspective, but these events do not feel very different personally or ethically.1 When a procedure does not go as expected and hurts someone, it violates a basic assumption held by patients and clinicians: doctors heal people. It leaves us with questions and uncertainty that can undermine our relationships with patients and colleagues and leave clinicians asking, “What if I had…?”. Complications seem particularly personal for interventionalists. When a patient dies on a medical service, people tend to ask, “What happened?”, but when a patient dies on a surgical service, people ask “What did you do?”.2 Although successes define one’s career, it is often responses to shortcomings that defines one’s character. Complications challenge us to be better and to support those hurt in our efforts to improve. When they occur, we should question what we owe our patients, selves, and colleagues, and to some degree, the answers are similar: reflection, confession, and resolution.
First, we should try to understand why a complication occurred and how to best avoid it in the future. It can be tempting to consider a complication merely as something that happens or attribute the fault to someone or something else, but we should always reflect upon our role in the event. Likewise, it can also be tempting to feel like a failure and let complications paralyse us, but the only interventionists that do not have complications are those that do not perform procedures. Neither extreme is helpful.
One useful approach for reflection is Charles Bosk’s categorisation of operator errors,2 which is summarised in Table 1 (below) with examples for interventional radiology (IR). Errors of technique or clinical judgement happen to everyone and are easier to improve with more training and experience. However, errors of character (normative or quasi-normative errors) are more difficult. In the face of these errors, we should look for deeper causes. Was the interventionalist depressed, burnt out, or overwhelmed by other aspects of life? Is the current practice or career not the right fit? If this is the case, we owe it to our patients, selves, and colleagues to step away and get help.
Once one has reflected upon the cause of the complication, this understanding should be used to provide an explanation and support to patients, families, and colleagues. For patients and families, complications can undermine trust, which is central to the patient-clinician relationship.3 It is trust that allows people to let us render them unconscious and thread catheters and wires into their bodies. Without this trust, it can be difficult for people to get the care they need, so in the face of complications, we owe it to patients to help rebuild that trust, not just in one clinician, but healthcare in general. Rather than abandoning patients, we should advocate for them by providing information, support, and guidance.4 An apology can also go a long way. Some may worry that an apology will increase the risk of a law suit, but research tends to suggest otherwise. Patients that sue tend to be those who did not receive the information or support they felt they deserved.5
Similarly, we should not leave our colleagues to deal with our complications alone. Rather, we should take responsibility for what occurred and partner with them. In IR, referrals networks are important, and complications can weaken these relationships. Just as with patients, we owe our colleagues an explanation and support to rebuild their trust. Colleagues can also be invaluable for stopping a difficult situation from getting worse, and we should have the humility and insight to ask for help when things go awry.6 We can also provide an opportunity for our colleagues to learn from our complications via morbidity and mortality conferences. Ideally these should be constructive and supportive rather than whipping posts for subordinates. Again, everyone has complications, and we owe it to our patients, selves, and colleagues to learn from them together.
This approach of reflection, confession, and resolution is not specific to IR, so it is also worth considering some unique aspects of IR culture related to complications. As a newer specialty, there tends to be less data to guide clinical decision making. The specialty has a reputation of being the cowboys and cowgirls of medicine, always willing to try something. We even have an entire forum to celebrate “extreme” cases that could easily end up in morbidity and mortality conferences of other specialties. This creates a complex relationship with complications. IR has classification systems to measure and report complications but not a robust forum for discussing the cases that did not save the day and how this relates to our drive for innovation or willingness to push the envelope. Furthermore, discussions of complications tend to be limited to more tangible periprocedural events such as bleeding or infection. There is little work in IR exploring issues of consent, futility, conflicts of interest, or tribalism. Overall, there seems to be a need for a balance; forums to celebrate innovation and to discuss the difficult ethical questions that interventionalists face each day.
In summary, complications and errors are likely to feel similar to interventional radiologists, their patients, and their colleagues. These events contradict expectations and hopes and leave people with uncertainty that can undermine relationships with patients, families, and colleagues. In response, we should reflect upon our complications, try to understand what caused them, and give ourselves permission to be human and learn from them. We can then use this understanding to provide an explanation and support to our patients and colleagues to rebuild trust and rapport with them. On a larger scale, we should also consider developing more research on and forums to discuss ethics in IR. Perhaps IR can develop innovative approaches to the difficult ethical questions we all face as well as the clinical ones.
Eric Keller is an interventional radiology resident at Stanford Medical School, Stanford, USA, and has a Master of Arts in Medical Humanities and Bioethics from Northwestern University, Chicago, USA.
References:
Thrombolex has announced the enrolment of the first patient in their Early Feasibility and Safety Study, investigating the Bashir Endovascular Catheter for the treatment of submassive pulmonary embolism (PE). The device was designed to quickly and safely dissolve thrombus and restore blood flow in patients with thrombotic vascular occlusions.
The Bashir catheter includes an expandable infusion basket comprised of six mini-infusion catheters with 48 precision, laser-drilled infusion holes. When expanded, it can promptly restore blood flow to enable endogenous lytics in the blood to help accelerate clot lysis. In this investigational study the device is used to administer thrombolytics through multiple cross-sections of the culprit clot to enhance clot dissolution.
“We are pleased to have been the first site to enrol a patient in the Thrombolex Early Feasibility and Safety Study,” said Parth Rali, assistant professor, Thoracic Medicine and Surgery at Lewis Katz School of Medicine at Temple University in Philadelphia, USA. “The catheter removed a large volume of clot from the pulmonary arteries efficiently, and safely restored blood flow, that resulted in a very rapid improvement in the patient’s overall clinical status.”
In this patient with a critical, large submassive PE that severely compromised blood flow to both lungs, a total of 14mg of r-tPA was administered over eight hours. “There was a dramatic improvement in the patient’s haemodynamic state and oxygenation as well as evidence of a marked reduction in clot burden as compared to what has been seen in other catheter-directed thrombolysis studies using a similar dose of r-tPA,” said Riyaz Bashir, director of Vascular and Endovascular Medicine at Temple University Hospital. “We believe that the Bashir Endovascular Catheter may represent a quantum leap in the treatment of venous thromboembolism patients, not just acutely, but also in terms of their longer-term health status,” said Brian Firth, chief scientific officer at Thrombolex.
“Thrombolex is focused on developing more advanced therapies for treatment of patients suffering with venous thromboembolic (VTE) disorders,” said Mike Cerminaro, president & COO of Thrombolex. “We are passionate about our focus because PE is a common disease, which is the third highest cause of cardiovascular mortality and is responsible for up to 180,000 deaths annually in the USA alone.”
“Currently available infusion catheters used to treat PE and other large clots are not able to rapidly restore blood flow through the thrombus and allow for only limited radial diffusion of exogenously administered thrombolytics like r-tPA into a clot,” said Marv Woodall, chairman & CEO of Thrombolex. The Thrombolex investigational trial is designed to examine if lower doses of thrombolytic via the Bashir Endovascular Catheter can be administered much more effectively over less time and thereby minimise major bleeding complications. This investigational study is a 10-patient prospective, multicentre clinical study to evaluate feasibility and safety of the catheter to treat patients with intermediate-risk PE. It represents the first in a series of planned clinical trials to evaluate this new platform technology that has been developed by Thrombolex.
The interim results of a multicentre, European retrospective analysis investigating the use of drug-coated balloons (DCBs) in symptomatic central venous stenosis (CVS) suggest that these devices could be a valid option for treatment, slowing down the effect of neo-intimal hyperplasia (NIH) leading to restenosis. Though with data mining still underway, the investigators warn against drawing any premature conclusions. Panagiotis Kitrou (Patras University Hospital, Patras, Greece) presented these preliminary results at the annual EndoVascular Access Meeting (EVA; 21–22 June, Patras, Greece) earlier this year.
Against the backdrop of the current paclitaxel controversy (where Konstantinos Katsanos, along with Kitrou and other colleagues, reported in the Journal of the American Heart Association (JAHA) an increased risk of death at two and five years following the use of paclitaxel devices), Kitrou first provided insight into how the publication has affected his own clinical practice. He told delegates: “We [at Patras University Hospital] have not changed our practice with regard to DCB use in dialysis access management. We believe that paclitaxel is an independent predictor of death, but its effect is different in different populations. Thus, a claudicant suffering more comorbidities compared to a claudicant with fewer comorbidities will have a greater number of factors antagonistic for the same event, which is death. Hence the signal and the effect of paclitaxel becomes faint and diluted while the actual benefit from NIH inhibition becomes more apparent.”
For patients with CVS, the gold standard treatment is percutaneous transluminal angioplasty (PTA). “However, Kitrou explained, “the patency rates may be as low as 28.9% at six months. This rate doubles to 60% when you use a high pressure balloon. The main problem [when using balloons] remains elastic recoil. You may also use a stent or a covered stent, is the latter being a much more aggressive treatment”.
Going through today’s evidence on CVS treatment, Kitrou showed EVA attendees the results from a 2015 retrospective analysis by Alexander Massmann et al that compared standard balloon angioplasty with paclitaxel-coated balloon angioplasty for symptomatic central vein restenosis in patients with impaired native haemodialysis fistulas. The study investigators concluded that paclitaxel-coated balloon angioplasty yielded a statistically significant longer freedom from target lesion revascularisation compared to standard balloon angioplasty. Although, Kitrou noted, Massmann and colleagues did include axillary veins, so he thinks these results “are not strictly for central veins”.
He next talked the audience through his own randomised controlled trial from 2017, which included 40 patients with de novo, restenotic and occluded lesions. Twenty patients were treated with the Lutonix DCB (BD), and twenty were treated with a non-coated balloon. In this study, the primary end-point was a clinically-assessed intervention-free period. In this, Kitrou et al found a significant difference in favour of DCBs. Additionally, DCB angioplasty was numerically better in the longitudinal analysis compared to plain balloon angioplasty.
Despite the fact that these studies found a significant difference between treatment arms consistently in favour of paclitaxel-coated balloons, Kitrou highlighted that these results have been observed in fewer than 30 patients. The present, multicentre European retrospective analysis therefore will provide data detailing DCB use in a greater number of patients. The primary outcome measures are a clinically assessed intervention-free period of the treated segment at six months, a dialysis access circuit with no need for clinically driven target lesion repeat intervention for symptom recurrence (verified angiographically), and no procedure-related minor and major complications.
The study included 87 patients from 11 centres across Greece, Germany, France, Italy, Portugal, and the UK. Though still only early data, the interim analysis reveals that at six months, the target lesion primary patency was 52%, and the median target lesion primary patency was 280 days, meaning lesions remained open following intervention for an average of nine months. “The results are already much better compared with our randomised controlled trial”, Kitrou said, referring to his 2017 study.
The investigators also measured primary patency of the access circuit. This was 48% at six months, and the median time to reintervention was 257 days. The access circuit survival was approximately 70% at six months, Kitrou shared.
“There is a lot of work in progress, we are still mining data—we are looking at this huge Excel [document] with a lot of data in there, and we will soon have more to share with you”, Kitrou concluded. interim interim
Jos van den Berg (Lugano, Switzerland), Antonio Micari (Bergamo, Italy) and Marianne Brodmann (Graz, Austria) sit down after a specially convened US FDA panel reviewed paclitaxel device data, with recommendations still to come. The physicians discuss the safety of paclitaxel devices and examine what the evidence says.
Micari presented a patient-level analysis from the IN.PACT randomised controlled trials to state that they have collectively shown there is no drug-related mortality signal and suggests that study design and conduct might be responsible for the “transient” mortality signal. He also looks at the long-term effectiveness of paclitaxel devices to state that the IN.PACT DCB (Medtronic) provides a vast improvement over plain balloon angioplasty, and shows “durable treatment benefit”.
Brodmann, meanwhile, outlines evidence from real world data sources – such as Medicare, OPTUM and VQI – which has indicated that there is “no difference in mid-term or long-term survival between patients treated with drug-coated or non drug-coated devices”.
Summing up, van den Berg states that several methods of investigation have demonstrated the absence of a dose relationship to mortality. “What we need to do now,” he says, is to “perform well-conducted real world comparative studies that are followed up for a sufficient duration”.
This webinar was filmed by SparkBio. Medtronic sponsored its distribution in association with Vascular News and Interventional News.
Medical devices manufacturer Boston Scientific has partnered with Mayo Clinic, a non-profit academic medical centre, to launch an accelerator focused on medical solutions for diseases with unmet clinical needs.
Named Motion Medical, the new 1,800ft² venture will receive funds from partners over three years to develop new medical technology and minimally invasive therapies.
Motion Medical research facilities will be located in the Discovery Square research district’s bioscience centre called One Discovery Square in Rochester, USA.
Boston Scientific and Mayo Clinic have been working together for approximately ten years for the development of medical devices and technologies across interventional cardiology, neuromodulation and urology therapeutic areas, among others.
To date, the companies have submitted eight patent applications and partnered on two first-in-human clinical trials, according to Mayo Clinic.
Boston Scientific develops a variety of medical solutions for endoscopy, rhythm management, interventional cardiology, peripheral interventions, neuromodulation, urology and pelvic health.
In November last year, the company signed an agreement to buy BTG for £3.3bn. BTG has three main businesses and Interventional Medicine is said to be the largest.
The acquisition is expected to help boost Boston Scientific’s capabilities in cancer and pulmonary embolism.
The National Institute for Health and Care Excellence (NICE) in the UK has published a positive draft final appraisal determination recommending the use of rivaroxaban (brand name Xarelto, Bayer) by the National Health Service (NHS) in England. The NICE recommendation sets out a dose of 2.5mg twice daily, combined with 75–100mg aspirin once daily, as an option for preventing atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral arterial disease (PAD) who are at high risk of ischaemic events.
Publication of this NICE draft is based on evidence from the COMPASS study, the largest Phase III study with rivaroxaban (27,395 patients). This study showed that rivaroxaban vascular dose, 2.5mg twice daily combined with aspirin 100mg once daily, statistically significantly reduced the risk of the composite of cardiovascular (CV) death, stroke or myocardial infarction (major adverse cardiovascular events; MACE) by 24% (relative risk reduction, ARR: 1.3%) compared with aspirin 100mg once daily alone amongst patients with stable atherosclerotic vascular disease (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; p<0.001).
In the COMPASS trial, for patients with stable CAD, addition of rivaroxaban 2.5mg twice daily with aspirin 100mg once daily lowered major adverse cardiovascular events compared with aspirin once daily (347 [4%] of 8313 vs. 460 [6%] of 8261; HR 0·74, 95% CI 0·65–0·86, p<0·0001). Moreover, patients with PAD who received rivaroxaban 2.5mg twice daily combined with aspirin 100mg once daily, also had fewer major cardiovascular events compared with the aspirin 100mg once daily alone group (126 [5%] of 2492 vs. 174 [7%] of 2504; HR 0·72, 95% CI 0·57-0·90, p=0·0047).
Rivaroxaban is an anticoagulant that targets Factor Xa, an enzyme which acts at a key point in the blood clotting process, inhibiting its ability to generate thrombin. NICE are recommending use of rivaroxaban as part of a dual pathway approach (in combination with aspirin) to prevent atherothrombotic events in patients who are at high risk of such events. Coronary artery disease patients who are at high risk of ischaemic events are defined by NICE as those aged 65 or over, patients with atherosclerosis in at least two vascular territories, or those presenting risk factors such as smoking, diabetes, kidney dysfunction, heart failure or a history of stroke.
Derek Connolly, COMPASS trialist, consultant interventional cardiologist and honorary senior clinical lecturer at Birmingham City Hospital (Birmingham, UK) said: “Cardiovascular disease remains the biggest cause of years of life lost in the UK. There have been few recent major new advances in the medical management of patients with CAD and PAD to protect them against strokes or heart attacks.
“The COMPASS trial showed that adding rivaroxaban vascular dose to low-dose aspirin significantly reduced vascular events. The large reduction in events [such as strokes], outweighed the increase in major bleeding events seen. Conducted in more than 30 countries, including the UK, COMPASS was one of the largest ever trials of oral anti-thrombotic therapy providing robust results, overall, and particularly for key patient subgroups at high-risk of recurrent events such as those with renal dysfunction or stable ‘mild’ heart failure.”
“Rivaroxaban vascular dose in combination with aspirin is the first treatment of its kind for this patient population and this recommendation from NICE provides clinicians with an important additional option for treating patients at risk of major adverse cardiac events such as cardiovascular death, stroke or myocardial infarction.”
Lars Bruening, CEO Bayer UK & Ireland, said: “Bayer has a long and successful heritage in cardiology. The NICE recommendation provides those with high risk CAD and symptomatic PAD with an effective treatment option that will provide additional tailored protection from atherothrombosis. Ten years on from the introduction of rivaroxaban into the UK we are continuing to see the enduring impact that it has on patients treated across its licensed indications—and now this new patient population with previous unmet needs can be considered.”
Publication of the NICE draft for rivaroxaban follows approval by the European Commission (EC) in August 2018 for the regimen of rivaroxaban 2.5mg twice daily plus aspirin 75–100mg once daily for the prevention of atherothrombotic events in adult patients with CAD or symptomatic PAD at high risk of ischaemic events. Rivaroxaban is the most broadly indicated NOAC worldwide. It is approved in the UK for:
In a retrospective, single centre study, the vast majority of patients who underwent uterine artery embolization (UAE) were able to have a successful pregnancy after the procedure. This led Muthusubramanian Rajasekaran (Department of Interventional Radiology, HCG Cancer Centre, Bangalore, India) to conclude that UAE has “satisfactory and acceptable outcomes” concerning fertility and pregnancy amongst patients of reproductive age, as he informed the audience at GEST 2019 (Global Embolization Cancer Symposium Technologies; 9–12 May, New York, USA). pregnant
As a commonly performed interventional radiology procedure, UAE is used to treat a variety of pathologies, including leiomyomas (fibroids), arteriovenous malformations (AVMs) and post-partum haemorrhages. “However”, Rajasekaran told the GEST audience, “the beneficial effects of UAE over the surgical treatment are still up for debate in patients of reproductive age, as the adverse effects of the procedure on fertility and pregnancy are not known”. As such, Rajasekaran and colleagues felt further investigation into the effects of UAE on pregnancy and fertility was warranted.
They conducted a retrospective analysis of their hospital records between January 2012 and January 2018, where they found that 42 patients had undergone UAE for various uterine pathologies. Of these, nine were excluded for being over the age of 35, three were excluded as they did not wish to get pregnant in the future, and two were lost to follow-up. This left 28 patients, with an age range of 22 to 35 years, for the analysis. Fourteen per cent underwent UAE to treat AVMs, 43% had post-partum haemorrhage, and the remaining 43% had fibroids.
Twenty-four (86%) of these 28 patients had at least one successful pregnancy after UAE, and 21% of the patients (six of the 28) had two successful pregnancies following the procedure. The majority of these women—62%, or fifteen of the 28—had normal vaginal delivery, and 38% (nine of the 28) had a caesarean section.
The average time interval for the first pregnancy after UAE was 15 months; the shortest time to pregnancy was six months, and the longest gap between pregnancy and procedure was 30 months. No procedure-related complications were observed in any of these patients.
Of the four (14%) patients who did not get pregnant following UAE, one (4%) did not get pregnant at all, and three (11%) had miscarriages. When asked about whether there were any unifying characteristics of these three patients by moderator Robert Mitchell Ermentrout (Department of Radiology, Emory University School of Medicine, Atlanta, USA) at GEST, Rajasekaran said that when they were evaluating the patients during follow-up, they found nothing that specifically explained why these women in particular were having difficulty with pregnancy.
“The more data we have, the more likely that this will become more standard practice”
An American audience member asked Rajasekaran what the referral rate and process was like in India, and if it is standard practice for gynaecologists to transfer patients across to the interventional radiology department. “We are still finding it hard to convince gynaecologists to refer patients to us”, Rajasekaran said. “The practice in India is for these patients to first go to the gynaecologist, and then it is their role to refer back to us.”
The questioner said that this is similar to the case across most of the USA we well. He elaborated: “There are many patients who hear about UAE from advertisements, and that is actually how we built up a lot of our practice. A lot of gynaecologists have started referring many patients to us, and normally it is because the patient already knows about the procedure and asks about it in their consultation, from what I understand. But there is still a recommendation to have them evaluated for myomectomy if they do desire future fertility, at least in the USA. But I think anecdotally, at least in our experience—so this is unpublished—fertility is certainly a possibility for patients who have had this procedure [UAE], and I think the more data we have, the more likely that this will become more standard practice across the world.” Rajasekaran agreed.
Medtronic and Viz.ai have partnered to accelerate the adoption of Viz.ai’s new technology, which helps synchronise stroke care and decrease time to treatment, potentially improving outcomes for patients.
Viz.ai’s technology uses artificial intelligence (AI) to identify suspected large vessel occlusion (LVO) strokes and automatically notify specialists. The Viz.ai software connects to hospital computed tomography (CT) scanners and alerts stroke specialists within minutes that a suspected LVO stroke has been identified, sending the radiological images directly to their smart phones where they can be viewed. Viz.ai enables a physician to provide the patient with the treatment they need as quickly as possible.
“Medtronic is an innovative company focused on therapies that extend life and restore health,” said Chris Mansi, neurosurgeon, co-founder and CEO of Viz.ai. “As the largest medical device company in the world, Medtronic is an ideal partner to help physicians access Viz.ai’s cutting-edge technology to ensure as many patients get the care they need as quickly as possible.”
Stroke is a serious and time-sensitive medical condition that requires emergency care and can cause lasting brain damage, long-term disability and death. A stroke occurs if the flow of oxygen-rich blood to a portion of the brain is blocked. When this happens two million brain cells die every minute. It is the number-one cause of disability in the USA and the leading cause of death outside of the USA.
“Viz.ai allows clinicians to receive an alert for suspected LVO’s and the corresponding visual data” said Elad Levy, chairman in the Department of Neurosurgery with the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences and medical director of Neuroendovascular Services at Gates Vascular Institute. “The combination of AI powered alerts, mobile image viewing, and HIPAA compliant communication facilitates synchronisation of stroke care with great potential to impactfully reduce door-to-needle time and help an increased number of patients.”
Every two minutes someone in the USA has an LVO, but only an estimated 15% receive a potentially lifesaving mechanical thrombectomy, a minimally-invasive procedure that removes blood clots. A Viz.ai study in two centres showed that in 95.5% of true positive cases, its technology alerted the stroke specialist earlier than the standard of care, saving an average of 52 minutes.
“We are excited about this partnership because Viz.ai’s technology has the potential to significantly reduce the time it takes for patients suspected of LVO stroke to receive the care they need,” said Stacey Pugh, vice president and general manager of Medtronic’s Neurovascular business, which is part of the Restorative Therapies Group at Medtronic. “Viz.ai’s software coupled with our network is going to increase access to needed therapies.”
Through this agreement, Medtronic will distribute Viz.ai’s existing LVO detection and triage software services, which are currently permitted for marketing in the US. It was the first clinical decision support software designed to analyse CT results that may notify providers of a potential stroke in their patients cleared by the US Food and Drug Administration (FDA). The technology is available in over 200 hospitals, with the goal of making Viz.ai available to every stroke centre in the country.
Preliminary results of a first in man trial demonstrate that robotically-assisted sonic therapy (RAST) can create a planned ablation volume without significant device-related adverse events. Timothy Ziemlewicz (Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, USA) informed delegates at the 2019 annual meeting of the Society of Interventional Oncology (SIO; 7–11 June, Boston, USA) that short-term local tumour control with RAST may be similar to that of other ablation modalities.
The study investigators conducted a phase I trial with the aim of evaluating the safety and short-term efficacy of RAST for hepatic ablation in patients with primary or metastatic liver cancer. RAST is the automated treatment of a defined volume of tissue utilising histotripsy, the first non-thermal, non-ionizing, non-invasive ablation modality. Prior to this research, RAST had successfully been applied in pre-clinical porcine liver models.
The study patients were recruited from, and procedures were performed at, two hospitals near Barcelona, Spain: Mutua Terrassa, where the study’s principal investigator Joan Vidal-Jove is located, and Vall D’Hebron Hospital, where Xavier Serres is based. The underlying technology was developed by members of the Department of Biomedical Engineering at the University of Michigan.
When delineating the advantages of RAST, Ziemlewicz emphasised the precision, telling the SIO audience that the cavitation bubble cloud is precise at the histologic level (“so you can literally cut cells in half with it”), and that planned treatment volumes are within nanometres of the resultant ablation.
The phase I, open-label, non-randomised trial had a primary endpoint of technical success, defined as the ability to create an ablation zone per the planned volume, as assessed by MRI one-day post-procedure. There were multiple secondary endpoints, the most important of which, according to Ziemlewicz, was safety, measured as the number and severity of adverse events. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0), a descriptive scale from Grade 1 (mild) through to Grade 5 (death related to adverse event). The study investigators also evaluated local tumour progression, liver function, involution of the ablation zone, and analgesic requirements. Follow-up MRI, laboratory draws, and clinical visit were planned at one day, one week, one month, and two months.
Eight patients, five female, three male, have had a tumour treated under this protocol. Most patients (six) had a single tumour, one patient had two tumours, and one patient had three tumours. The mean tumour size was 1.3cm, and the range was 0.5cm to 2.3cm. “We were somewhat limited in size by having to fit treatments within livers with multifocal tumours”, Ziemlewicz said.
The triallists achieved 100% technical success in creating the planned ablation volume using RAST. In the axial plane, the ablation zone was within an average of 0.1cm of the plan, and in the coronal plan the ablation zone was an average of 0.5cm larger than the plan. “We did not control for respiration”, Ziemlewicz commented, “so we knew that these would be elongated in the coronal plane”. In terms of targeting tumours, the investigators report a 90.9% success rate—one of the eleven tumours treated was mistargeted immediately adjacent to the 0.5cm tumour. Ziemlewicz ascribed this mistargeting to poor ultrasound visualisation, and explained that the patient is set to undergo a second procedure for local control.
Concerning safety, there was one Grade 4 adverse event (classified as life-threatening, with urgent intervention indicated), which Ziemlewicz explained was not thought to be device-related. The patient was admitted to hospital and the complication was attributed by the independent treating physicians to their underlying Crohn’s disease. In addition, there was one Grade 2 (designated as a moderate complication) adverse event, which was also not attributed to the device. This patient was admitted to hospital for fever and given supportive treatment. One patient had a complication that was device-related; a Grade 1 (mild) adverse event, they presented with post-ablation syndrome one day after the procedure and had a fever of 39°C. This patient was the only one of the eight to have three ablative treatments; 64mL of total ablation. “They had a fever and some malaise for a couple of days after the procedure, which resolved and they are doing fine [now]”, Ziemlewicz assured the audience.
The deepest tumour treated by the study investigators did experience some local progression. Explaining this, Ziemlewicz said: “The prototype transducer we used is only capable of treating to about 10cm; we were pushing it to the edge of the envelope [with trying to treat this tumour].” Showing the audience some post-procedural images of the patient’s liver, he commented “You can see at one month the ablation zone is nicely absorbed, and then at the three-month follow-up scan you can see the progression. One of the benefits of this technology is that you can see this relatively early.”
In terms of analgesic requirements, another of the study’s secondary endpoints, there were no analgesic requests and no reported pain.
The involution data were of particular interest to the investigators as they were unsure how this would translate from previous laboratory studies. Ziemlewicz tells Interventional News: “We did note this in our original study published in Radiology last year. We survived half of those treated animals which is where we noted this involution. We honestly were not sure how this would hold up in human livers, which were either cirrhotic or patients were treated with chemotherapy previously.”
There was significant involution after two months: an average of 88.1% volume contraction and 51.1% diameter contraction. Ziemlewicz suggested that rapid involution may allow earlier identification of incomplete treatment.
All RAST procedures (VORTX RX system, Histosonics) were performed with the patient under general anaesthesia. Speaking from the floor, John Kachura (Toronto General Hospital, Toronto, Canada) asked about this decision: “No patients reported pain afterwards, and all procedures done under general anaesthetic. Has anyone tried doing it without general anaesthetic, and just with conscious sedation, or is there concern about that?”.
Ziemlewicz replied that initially, the investigators did not know how the patients were going to feel, and decided to use general anaesthetic to stay consistent with their institution’s policy of using it for all ablation patients. He did say, though, that “Anecdotally, none of the patients showed any vital sign changes to suggest they were having pain during the procedure. […] In the future, we will definitely consider doing this with conscious sedation”.
Yuji Okuno (Okuno Clinic, Tokyo, Japan) gave an update on the status of musculoskeletal embolization for pain management and sports related injuries at the GEST Symposium this year (Global Embolization Cancer Symposium Technologies; 9–12 May, New York, USA).
He began by detailing the first report on musculoskeletal embolization, published in the Journal of Vascular and Interventional Radiology (JVIR) in 2013 by himself and colleagues, which demonstrated the feasibility and efficacy of transcatheter arterial embolization (TAE) using imipenem and cilastatin sodium for tendinopathy and enthesopathy refractory to nonsurgical management. Imipenem and cilastatin sodium have been used as a temporary embolic agent in Japan since 1990, and the Japanese investigators selected the material for its established safety record. Local tenderness score, used as a proxy for pain, reduced rapidly following the procedure, and pain disappeared at three months.
Okuno and his colleagues were encouraged by the results of this pilot study, seeing potential in the procedure’s use to alleviate pain. Current understanding is that chronic inflammation leads to an increase in abnormal neovessels, and that embolizing these vessels and reduce pain and consequently the dependence on alternative pain management strategies, such as taking opioids. However, more data are needed to solidify TAE’s position as a pain management treatment, and Okuno said at GEST that comparative studies of TAE versus a placebo and TAE versus another treatment are needed.
Recently, there has been an upswell in interest around musculoskeletal embolization, with multiple studies investigating the technique’s use in the knee, shoulder and elbow. Sandeep Bagla (chair of Interventional Radiology at the Vascular Institute at Virginia, Woodbridge, USA) presented the positive results on an early preclinical study of GAE in 20 patients with mild to moderate knee osteoarthritis in spring this year at the Society of Interventional Radiology’s annual meeting (SIR; 23–28 March, Austin, USA). A randomised controlled trial focusing on GAE in a larger cohort is underway. Meanwhile, Mark Little (Royal Berkshire Hospital, Reading, UK) is the principle investigator for the first clinical trial examining GAE in knee osteoarthritis patients in Europe, the GENESIS trial. A placebo-controlled randomised controlled superiority trial embolization in the knee headed by Steve Landers (Barwon Medical Imaging, Barwon Health, Geelong, Australia) has also recently completed enrolment in Australia.
Musculoskeletal embolization for pain management in athletes
Specifically thinking about sports injuries, Okuno believes musculoskeletal embolization will have a much larger role to play in the future of pain management for athletes. He gives two case examples at GEST.
The first case report is of a 26-year-old male patient with patellar tendinopathy. The patient is a professional goal keeper for a football team in the Japanese top league, and does not wish to undergo surgery due to the slow post-operative recovery. The patient’s chief complaint is knee pain, which is exacerbated by running, jumping, flexing and kneeling, Okuno informed the audience, “all movement crucial to his profession”. The goalkeeper was resistant to conservative treatment, having had one corticosteroid injection and two hyaluronic acid injections prior to trying TAE.
Post-procedural imaging revealed that the abnormal vasculature was no longer visible, and the patient’s pain score as measured by the Numerical Rating Scale (NRS) dropped from eight to two within a month, and was zero three months post TAE. Two days after the procedure, the patient returned to light training, and was back to full training with the rest of the football team two weeks after the embolization was performed. Six weeks’ post-procedure, the patient had their first competitive game. “The patient had rapid progression and quick reduction in symptoms after the embolization”, Okuno described. He opined, “This is particularly advantageous for sportspeople, as they cannot rest for long. At two-years follow-up, this patient’s knee has a normal appearance”.
The second case Okuno presented to the GEST audience was a chronic hamstring injury in a long distance athlete, who competed at the Rio Olympics. The 34-year-old female athlete complained of hip pain, and was resistant to conservative treatment after one year. “It is very difficult to have surgery and then go back to training”, Okuno explained, “so she was reluctant to have that treatment, even though this was recommended surgery by the orthopaedic surgeon”. Instead, Okuno performed embolization twice in two months. She was back training again after three to four months.
Okuno used these success stories to promote the potential of embolization to allow athletes and active patients to continue engaging in their chosen sport pain free. Marc Sapoval, who was chairing the session “Vanguard in embolization” at GEST, said in response to Okuno’s presentation: “I am very optimistic about this being a new area of embolization for the future”.
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) signposts the IASIOS process:
