The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

Abstract

Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied. We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients with a class I indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF] < 35%, optimal dose with Renin-Angiotensin-System-Blocker [RAS-blocker]). Doses of sacubitril/valsartan were optimized to individual tolerance. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. One-hundred-twenty-five HFrEF patients (66±10years) were prospectively included. The amount of RAS-blocker before and after switch to sacubitril/valsartan was similar(P=.290), indicating individual optimal dosing of sacubitril/valsartan. Over a median(IQR) follow-up of 118(77-160)days after initiation of sacubitril/valsartan, LVEF improved (29.6±6% vs 34.8±6%; P<.001) and Left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) decreased (LVESV; 147±57mL vs 129±55mL; P<.001 and LVEDV; 206±71mL vs197±72mL; P=.027). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (1.59±1.0 vs 1.11±0.8; P<.001; [scale from 0-4]). Metrics of diastolic function improved; including a drop in the E/A-wave ratio (1.75±1.13 vs 1.38±0.88; P=.002) and diastolic filling time (% of cycle length) prolonged (48±9% vs 52±1%; P=.005). The percent of patients with a restrictive mitral filling pattern dropped from 47% to 23% (P=.004). A dose-dependent effect was noted for changes in LVEF (P<.001) and LVESV (P=.031), with higher doses of sacubitril/valsartan leading to more reverse remodeling. Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function.