Dr Vivek Reddy Mt Sinai Hospital

Boston AF Symposium 2014

Renal Sympathetic Denervation (RSDN) for A-Fib?

Report by Steve S. Ryan, PhD Dr. Vivek Reddy of Mount Sinai School of Medicine, NY gave a presentation entitled “Renal Denervation for AF—Physiology, Mechanisms of Action and Rational in AF.”

RSDN Found Ineffective, Symplicity HTN-3 Trial

Background: (Before reading this report, it is recommended to first look at the our 2014 BAFS satellite presentation “Renal Denervation and Pulmonary Vein Isolation for PAF.)

Earlier in the Symposium, the results of the Medtronic Symplicity HTN-3 trial were announced and discussed. Medtronic’s renal denervation system was found to be basically no better than a sham procedure for reducing systolic blood pressure through six months.

Dr. Reddy described how previous surgical interventions (Thoracolumbar Surgical Sympathectomy—destroying some of the sympathetic nerve trunk) did reduce blood pressure by affecting the Sympathetic Nerves (Smithwick et al. JAMA 1953;152(16);1501-4). And the clinical trial Symplicity HTN-2 did work—84% of patients had a 10 mmHg or greater decrease in Systolic Blood Pressure (Esler et al. Lancet 2010;376(9756): 1903-9)

Then why was Symplicity HTN-3 a negative study? Was the catheter not properly employed? (Dr. Reddy described a new method of performing RSDN by using External Ultrasound Energy which has a minimal effect on the arterial wall.) Is refractory hypertension not primarily “sympathetically-driven?”

Does RSDN do anything?—Mechanistic Data

•  In a small study of patients with refractory high blood pressure (HBN) that couldn’t be lowered by drugs and other methods, RSDN did significantly lower high blood pressure (Brandt et al. JACC 59:901 [2012]).

•  In another study RSDN lowered blood pressure and Muscle Sympathetic Nerve Activity (MSNA) (Achlaich et al. NEJM 36:932-934 [2009])

•  In another study RSDN lowered renal hormones like Aldosterone, Metanephrine and Normetanephrine (Ahmed H/Neuzil P/Reddy VY: JACC-CV Interv 5:758-65 [2012])

•  RSDN improved heart rate variability (F. Himmel et al. J.Clin.HTN 14:654 [2012]}

Supporting Evidence for RSDN Helping A-Fib

•  Experimental studies of sheep show that high blood pressure (hypertension) produces fibrosis (interstitial collagen) and remodeling of the atria. (Heart Rhythm 2010;7:1282-1290)

•  In the ARIC study of nearly 15,000 people followed for 17 years, high blood pressure accounted for 20%-25% of all A-Fib cases (other factors were Obesity, Diabetes, Smoking and Prior Cardiac Disease). (Huxley et al Circulation 123:1501-1508 [2011])

•  Hypertension was the most significant predictor of recurrence after A-Fib ablation (Takigawa et al. JRAS, DOI: 10.1177/1470320312446212 [2012])

•  Sympathetic Nervous System overactivity predicted A-Fib recurrence (Arimoto et al. JCE [2011])

•  In Dr. Pokushalov’s work described under 2014 BAFS Satellite Presentations-Siberia, PVI with RSDN had much less recurrence than just a PVI (Pokushalov et al. JACC [2012])

But What About A-Fib Patients without High Blood Pressure—Would RSDN Help Them?

•  In a small experimental study using dogs, RSDN kept the dogs from going into A-Fib and reduced renal hormones (Q.Zhao et al. JICE [2012; DOI 10.1007/s10840-012-9717-y).

•  In another dog study, RSDN ameliorated pacing-induced changes in hormones and tissue structure (X.Wang et al. PloS ONE 8(5): e64611 [2013])

•  In a study of Obstructive Sleep Apnea in pigs, RSDN helped blood pressure and reduced A-Fib when the pigs had induced sleep apnea.(Linz et al. Hypertension 62:767 [2103])

Renal Sympathetic Denervation as Upstream Therapy in A-Fib?

Dr. Reddy described a multi-center randomized study of A-Fib and Hypertension. Patients with A-Fib and hypertension will have a catheter ablation procedure (PVI). Then some will be in the placebo group and others will have a RSDN procedure. Follow-up will measure A-Fib recurrence. (H Ahmed/MA Miller/VY Reddy, JCE 25:503-9 [2013]). The rational for this study is that Renal Denervation can dramatically affect sympathetic tone, is technically simple to do, and has minimal safety issues. In an earlier study, Renal Denervation significantly reduced blood pressure after three months (Ahmed H / Neuzil P / Reddy VY: JACC-CV Interv 5:758-65 [2012])

Dr. Reddy’s Final Thoughts

•  RSDN is a novel approach to modulate the sympathetic nervous system (one of several)

•  Many animal studies demonstrate the electrophysiological effects of RSDN

•  Potential Role for RSDN in A-Fib—Reduce A-Fib recurrence

Editor’s Comments:

In spite of the preliminary results of Symplicity HTN-3, Renal Denervation is not dead in the water. The full results of Symplicity HTN-3 haven’t been released and examined yet. And the new multi-center randomized study Dr. Reddy described may yet prove the effectiveness of RSDN.

Renal Denervation, in addition to helping people with high blood pressure and A-Fib, may benefit anybody with A-Fib. Because Renal Denervation is easy to do and relatively safe, RSDN may become another treatment option for A-Fib.

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Last updated: Wednesday, September 2, 2015