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.
Why were you initially drawn to interventional radiology?
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.
Today, what is it you enjoy most about interventional radiology?
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.
Have you had important mentors throughout your career? What have they taught you?
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.
Having worked in both Greece and the UK, what are the similarities and differences between these two healthcare systems for interventional radiologists?
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.
Late last year, you published a paper in the Journal of the American Heart Association (JAHA) that reported an increased mortality with paclitaxel devices in the femoropopliteal arteries. How do you see these findings changing practice in the future?
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.
How has your life changed as a result of publishing research that is not positive, and how have your coped with the reaction from the medical community to the JAHA paper specifically?
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.
How do you feel the regulatory bodies across the world have responded to the mortality signal reported in your publication?
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.
You hosted the first ever EndoVascular Access (EVA) meeting this year with Panagiotis Kitrou and Dimitrios Karnabatidis. What are your ambitions for this meeting, and how do you hope to see this field develop?
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.
In your opinion, what are the most exciting new developments in interventional radiology that we can expect in the next five to 10 years?
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.
What are your hobbies and interests outside of medicine?
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.