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

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. (J Am Coll Cardiol 2018; 72: 2609-21) (c) 2018 by the American College of Cardiology Foundation.