Sacubitril/Valsartan Improves Functional Capacity and Reverses LV Remodeling in Obese Patients with Hypertrophic HFpEF: A Randomized Open-Label Study.

Background: Heart failure with preserved ejection fraction (HFpEF) has multiple phenotypic manifestations with heterogeneous treatment responses. Objective: To evaluate the effect of sacubitril/valsartan (Sac/Val) on functional capacity and cardiac remodeling in overweight/obese HFpEF patients with concentric left ventricular hypertrophy (LVH). Methods: Sixty-one overweight/obese HFpEF patients (body mass index ≥ 25 kg/m2) with hypertensive LVH (LV mass index ≥ 115 g/m2 for men or ≥94 g/m2 for women) were randomized to Sac/Val (100-400 mg a day; n = 30) versus the usual care group (n = 31) for 6 months. Changes in six-minute walk test distance (6MWTD) were the primary outcomes. Secondary outcomes included changes in echocardiographic parameters of cardiac structure and function, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: After 6 months of Sac/Val therapy, 6MWTD increased, and E/e' ratio, LV mass index, LA volume index, and NT-proBNP levels decreased compared with the usual care group (p < 0.05 for all). Conclusions: In overweight/obese patients with HFpEF and LVH, Sac/Val significantly improved functional capacity and reduced LV mass and filling pressure compared with standard medical therapy.