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

https://doi.org/10.1016/j.jacc.2018.08.2186Get rights and content
Under an Elsevier user license
open archive

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.

Key Words

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

Abbreviations and Acronyms

BNP
B-type natriuretic peptide
HF
heart failure
LV
left ventricle/ventricular
MI/R
myocardial ischemia/reperfusion
NE
norepinephrine
NP
natriuretic peptide
RAS
renin-angiotensin system
RF
radiofrequency
RDN
renal denervation
SNS
sympathetic nervous system

Cited by (0)

These studies were funded in part by a grant to Dr. Jenkins from the Ochsner Translational Medicine Research Initiative (OTMRI); and by National Institutes of General Medical Sciences (NIGMS) COBRE grant no. P30GM106392 to Dr. Kapusta. Drs. Polhemus and Lefer have a pending patent on the use of RDN therapy to treat cardiovascular diseases. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.