The first SYMPLICITY HTN trials generated enthusiasm for catheter-based treatment of hypertension resistant to pharmacotherapy. However, when the treatment arm of SYMPLICITY HTN-3 failed to show significantly lower systolic blood pressure than the control group, some industry observers concluded that the door had been closed on renal denervation. Despite this surprisingly negative result, most industry participants (manufacturers, physicians, etc.) remain optimistic about the future of renal denervation. The sponsor of SYMPLICITY has redesigned its product and refined its trial protocol, while other major medical device manufacturers continue with their own product development in the area. Key physician opinion leaders continue to view renal denervation as a potential hypertension treatment, not least as all clinical trials to date have shown the procedure to be safe. There are several factors driving this enthusiasm:
Insights from SYMPLICITY
Both the SYMPLICITY HTN-1 and HTN-2 studies demonstrated sustained reduction in blood pressure after renal denervation in patients taking three or more antihypertensive medications.7, 8 Surprisingly, in the randomized SYMPLICITY HTN-3 trial, patients in the renal denervation arm did not have significantly greater reduction in blood pressure compared to the control group. Both cohorts did show significant blood pressure improvement from baseline9, leading some to conclude that renal denervation was no better than a sham procedure in lowering blood pressure. There are several variables that may have affected the HTN-3 results:
Several second-generation renal denervation catheters are in various stages of development and clinical trials. The majority of these second-generation devices use multiple electrodes and unipolar radiofrequency to ablate tissue in the renal arteries.3 The use of multi-electrode catheters is expected to increase efficacy and decrease procedure time.
Will second-generation catheters make renal denervation “mainstream”?
Most stakeholders are optimistic that renal denervation will ultimately become an accepted treatment for uncontrolled hypertension. However, it’s unlikely that the second-generation catheters currently being studied will have the multiple positive characteristics that are needed to drive widespread adoption. Looking at other break-through medical devices areas such as transcatheter aortic valve implantation/replacement or left ventricular assist devices, it has been the third generation of device iterations that has initiated broader acceptance of these treatments. Third-generation devices generally incorporate designs that allow for greater efficacy, safety, and patient tolerability for the procedure, as well as improved ease of use and reduced procedure times.
Third-generation catheters for a turnkey procedure
It’s likely that this medical device “cycle” will hold true in the renal denervation market. Third-generation renal denervation catheters are expected to enable a turnkey ablation procedure. Renal Dynamics’ ReDy Renal Denervation System is one such third-generation product in development. The ReDy Renal Denervation System incorporates sensors and algorithms in a low-profile, multi-electrode catheter to create complete lesion formation from a single position in the renal artery. Predictable lesion formation can be achieved in 60 seconds or less at each denervation site in preclinical studies. With nine electrodes, the ReDy catheter can perform unipolar and bipolar ablation and uses low power RF energy, which may lead to less pain, damage to collateral tissues, and spasms when applied to humans.13
The door for renal denervation for uncontrolled hypertension remains open, with learnings from the SYMPLICITY trials already being effected in new catheter designs and trial protocols. Assuming second-generation systems demonstrate efficacy compared to control groups, it’s the third-generation of renal denervation catheters that are likely to provide a turnkey procedure that can be broadly adopted to treat the millions of patients with uncontrolled hypertension.
 Torres YC, Katholi RE. Renal denervation for treating resistant hypertension: Current evidence and future insights from a global perspective. Int J Hypertens. 2013:2013:513214.
 Bertog SC, Sobotka PA, Sievert H. Renal denervation for hypertension. J Am Coll Cardiol Intv. 2012;5:249-58.
 W. Wojakosdki, A. Januszewicz, A. Witkowski, M. Tendera. Catheter-based renal denervation. E-journal of the ESC Council for Cardiology Practice. March 2010 Vol.10, No.22.
 World Health Organization. A global brief on hypertension: Silent killer, global public health crisis. World Health Day 2013.
 Go AS, Bauman MA, King SMC, Fonarow GC, et al. AHA/ACC/CDC science advisory; An effective approach to high blood pressure control. A science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63:878-885.
 Heidenreich PA, Trogdon JG, Khavjou O, Butler J, et al. Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation. 2011;123:933-944.
 Krum H, Schlaich M, Whitbourn R, Sobotka PA, et al. Catheter-based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275-81.
 Esler MD, Krum H, Schlaich M, Schmeider RE, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: One-year results from the Symplicity HTN2-randomized, controlled trial. Circulation. 2012;126:2976-2982.
 Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393-401.
 Kandzari DE, Bhatt DL, Brar S, Devireddy CM, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J. 2015;36:219-227.
 Jung O, Gechtner JL, Wunder C, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31:766-74.
 Weber MA, Kirtane A, Mauri L, Townsend RR, et al. Renal denervation for the treatment of hypertension: Making a new start, getting it right. Clin Cardiol. 2015;38:447-54.
 Tzafriri AR, Bailey L, Keating JH, Markham PM, et al. Preclinical safety and efficacy of a novel multielectrode bipolar/unipolar over-the-wire renal denervation RF catheter. 2014.
Shawn Moaddeb is an entrepreneur with over 25 years’ experience in the medical device industry. Former VP of RF Technology at Vessix Vascular, Shawn is a named inventor on over 100 issued and pending patents in the areas of RF catheter-based renal denervation, percutaneous mitral valve catheter-based therapy, electrophysiology and cardiac ablation systems, medical laser systems, GI, and implantable pacemaker and defibrillator devices. Mr. Moaddeb is Chief Executive Officer at Renal Dynamics.