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

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

Author information

1
Cardiovascular Research Center, School of Medicine, Louisiana State University Health Science Center, New Orleans, Louisiana.
2
Cardiovascular Research Center, School of Medicine, Louisiana State University Health Science Center, New Orleans, Louisiana; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Science Center, New Orleans, Louisiana.
3
Department of Cardiology, Heart and Vascular Institute, Ochsner Medical Center, New Orleans, Louisiana.
4
Cardiovascular Research Center, School of Medicine, Louisiana State University Health Science Center, New Orleans, Louisiana; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Science Center, New Orleans, Louisiana. Electronic address: dlefe1@lsuhsc.edu.

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

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