At the ISET conference in January in Miami, USA, Horst Sievert, CardioVascular Center Frankfurt, Frankfurt, Germany, told delegates why he believes that renal denervation could become as important as percutaneous coronary intervention or percutaneous transluminal angioplasty. “I believe that renal denervation represents a great opportunity for interventionalists to make a difference,” he said.
Sievert clarified that for any procedure to be classified as a “great opportunity”, the disease that needed to be treated had to be frequent and important, and interventionalists needed to have direct access to the patients. “Any such new procedure should be do-able without huge infrastructure outlays and it should be effective, safe, durable and easy to learn,” he said.
Renal denervation, which is catheter-based interruption of renal nerves, reduces central sympathetic drive and this then results in blood pressure reduction. It may have other beneficial effects and is infrastructure-light as all you need is a cath lab, generator and catheter, noted Sievert.
Impact of hypertension
“With renal denervation, we can treat hypertension, which affects 30–40% of the adult population in the US/Europe. The prevalence is expected to increase with the ageing population and 65% of hypertensive patients are either untreated or have a blood pressure below the recommended goal,” he noted. “Please look around in this room! How many candidates to you see for renal denervation compared to TAVI, TEVAR or flow diverters?” Sievert asked in a lighter vein.
More seriously, Sievert noted that hypertension was associated with an increased risk of stroke, myocardial infarction, renal insufficiency, congestive heart failure, peripheral arterial disease and death. “A 20mmHg increase in blood pressure doubles cardiovascular mortality, and according to the WHO, hypertension is the most frequent cause of death worldwide,” he said.
Sievert also spoke about the limitations of best medical therapy. “Sixty to eighty per cent of hypertensive patients are either untreated or have suboptimal blood pressure control despite optimal medical therapy and many patients are troubled by medication side-effects,” he said referring to literature from Calhoun et al, Hypertension 2008; 51(6): 1403–19.
He noted that in addition to the Medtronic/Ardian Symplicity system, other techniques on the horizon for renal denervation include other radiofrequency-based approaches, heat, cryo, radiation, ultrasound and drugs.
Michael Jaff, Massachusetts General Hospital, Boston, USA, also speaking at the ISET meeting, highlighted how important it is to find a way of tackling hypertension. “Resistant hypertension is common, and becoming more common despite a huge armamentarium of pharmacologic agents. Renal denervation is based in physiology and the early literature is very impressive. There could also be additional benefits from the procedure such as control of congestive heart failure, treatment for obstructive sleep apnoea treatment/prevention of diabetes mellitus/metabolic syndrome,” he said.
Jaff also noted that there were more benefits for patients undergoing renal denervation than lowered blood pressure.
He presented the new research that demonstrated for the first time that selective denervation of the renal sympathetic nerves has the potential to improve glucose metabolism and blood pressure control concurrently in patients with resistant hypertension in the absence of significant changes in body weight and alterations in lifestyle or antihypertensive medication. In the study (Circulation 2011;123:1940–6) of 50 patients with drug-resistant hypertension, 37 underwent bilateral renal denervation and 13 were control patients.
The small pilot study has shown that renal denervation could potentially prevent the development of diabetes, or impaired glucose tolerance. Other conditions such as flares from congestive heart failure can also be stabilised and the procedure could have a positive impact on sleep apnea, he said.
Techniques and pitfalls
Sievert also spoke on the techniques and pitfalls of the procedure and said that patients who could undergo renal denervation had to be taking three or more antihypertensive medications, or be drug intolerant, have blood pressure greater than 160mmHg (or 150 in the case of diabetic patients). Patients who have renal insufficiency, type I diabetes or prior renal artery intervention need to be excluded.
The technique involves at least four to eight energy applications for each renal artery with two minutes per energy application. A maximum energy of eight 8W is recommended and with the Medtronic/Ardian system, the generator automatically switches off if temperature increases too fast or too slowly, if the temperature is higher than 75°C, or if the impedance does not decrease sufficiently.
He noted that pre-procedure, 10–20mg morphine plus sedatives had to be administered. Other details 5,000 units of heparin were required. Intra-arterial administration of nitroglycerine was needed and in terms of equipment, a 6F femoral sheath and a 6F renal guiding catheter.
“Selective angiography of all renal arteries needs to be performed and interventionalists should ablate if the vessel diameter is ≥4mm. Avoid diseased and stented vessel segments. Four to eight ablations are required and ablations of less than two minutes do not count,” said Sievert.
Sievert also referred to the potential complications with the procedure. “Dissection is a potential complication, but extremely rare and so far, only due to the guiding catheter. Have a stent ready, so that you are prepared, in case there is a dissection,” he said. He also noted that “spasm”, thrombus formation, perforation, severe hypotension during follow-up and contrast induced nephropathy are other potential complications.
“Little mistakes you should avoid”
Sievert told the delegates at ISET that they should be mindful of the following points. “Clearly the catheter tip has to be placed against the vessel wall for effective ablation to take place; otherwise the generator will switch off. You should not perform angiography or flushing during ablation, or else the generator will switch off. It is also important that the ‘Y-connector’ is not closed during ablation as this can cause a clot in the guiding catheter. Too much contrast should not be administered,” he said.
Jaff particularly highlighted that if the interventionist forgot to tell the patient that the effect of renal denervation is not immediate and that hypertension can rarely be cured, it could spell the end of their renal denervation programme. Similarly, he pointed out that forgetting to give morphine to patients would also have negative consequences.
Message from the CIRSE president
“Renal denervation is an exciting new technology that holds promise for the treatment of drug resistant hypertension which is an increasing problem worldwide. The technique seamlessly fits into the work practice of interventional radiologists who have pioneered the techniques of angioplasty/stenting of the renal arteries in hypertensive patients with renal artery stenosis.
Renal denervation trials to date, including the Symplicity 2 trial, have provided proof of concept but there are still many unanswered questions with regard to patient selection, achievement of target systolic blood pressure levels below 140mmHg and long-term efficacy. More randomised, controlled trials are needed to answer these questions before it finds its place in hypertension treatment. I am sure that interventional radiologists will be at the forefront of this research.”
Michael Lee, Dublin, Ireland
Message from the SIR president
“Interventional radiologists are very excited about the potential to significantly improve blood pressure control in those with resistant hypertension using this new procedure, as well as a way to treat a number of other important diseases like heart failure, diabetes, and sleep apnoea. SIR is encouraging members to learn more about the trials and to get involved.”
Timothy Murphy, Providence, USA