Renal Denervation Prevents Heart Failure Progression Via Inhibition of the Renin-Angiotensin System

J Am Coll Cardiol. 2018 Nov 27;72(21):2609-2621. doi: 10.1016/j.jacc.2018.08.2186.

Abstract

Background: Previously, we have shown that radiofrequency (RF) renal denervation (RDN) reduces myocardial infarct size in a rat model of acute myocardial infarction (MI) and improves left ventricular (LV) function and vascular reactivity in the setting of heart failure following MI.

Objectives: The authors investigated the therapeutic efficacy of RF-RDN in a clinically relevant normotensive swine model of heart failure with reduced ejection fraction (HFrEF).

Methods: Yucatan miniswine underwent 75 min of left anterior descending coronary artery balloon occlusion to induce MI followed by reperfusion (R) for 18 weeks. Cardiac function was assessed pre- and post-MI/R by transthoracic echocardiography and every 3 weeks for 18 weeks. HFrEF was classified by an LV ejection fraction <40%. Animals who met inclusion criteria were randomized to receive bilateral RF-RDN (n = 10) treatment or sham-RDN (n = 11) at 6 weeks post-MI/R using an RF-RDN catheter.

Results: RF-RDN therapy resulted in significant reductions in renal norepinephrine content and circulating angiotensin I and II. RF-RDN significantly increased circulating B-type natriuretic peptide levels. Following RF-RDN, LV end-systolic volume was significantly reduced when compared with sham-treated animals, leading to a marked and sustained improvement in LV ejection fraction. Furthermore, RF-RDN improved LV longitudinal strain. Simultaneously, RF-RDN reduced LV fibrosis and improved coronary artery responses to vasodilators.

Conclusions: RF-RDN provides a novel therapeutic strategy to reduce renal sympathetic activity, inhibit the renin-angiotensin system, increase circulating B-type natriuretic peptide levels, attenuate LV fibrosis, and improve left ventricular performance and coronary vascular function. These cardioprotective mechanisms synergize to halt the progression of HFrEF following MI/R in a clinically relevant model system.

Keywords: acute myocardial infarction; brain type natriuretic peptide; coronary vascular reactivity; neprilysin; renin-angiotensin system; sympathetic nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autonomic Denervation / methods*
  • Disease Progression*
  • Dose-Response Relationship, Drug
  • Echocardiography / methods
  • Female
  • Heart Failure / diagnostic imaging*
  • Heart Failure / metabolism
  • Heart Failure / prevention & control*
  • Kidney / diagnostic imaging
  • Kidney / innervation*
  • Kidney / metabolism
  • Kidney / surgery
  • Renal Artery / diagnostic imaging
  • Renal Artery / innervation
  • Renal Artery / metabolism
  • Renal Artery / surgery
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*
  • Swine
  • Swine, Miniature
  • Vasodilator Agents / pharmacology
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / physiology

Substances

  • Vasodilator Agents