Sacubitril/valsartan Improves Exercise Performance in Patients with Heart Failure: a Dose-Dependent Effect

Background Sacubitril/Valsartan therapy has become a cornerstone of heart failure with reduced ejection fraction (HFrEF) pharmacological therapy due to its positive prognostic impact. However, conflicting results have emerged on the effects of sacubitril/valsartan on exercise performance assessed by cardiopulmonary exercise test (CPET). Aim of the study: The aim of this study was to prospectively evaluate the effects of sacubitril/valsartan on prognostically significant CPET parameters in a larger population of HFrEF patients at different drug doses. Methods We prospectively enrolled HFrEF outpatients eligible to start sacubitril/valsartan according to 2016 ESC Guidelines in 3 Heart Failure Units. Patients underwent CPET at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26 – 49/51 – 97/103mg doses), and 6 months after the maximum tolerated dose was reached (end–study). The subjective impression of disease–related limitation was assessed using the 12–item Kansas City Cardiomyopathy Questionnaire (KCCQ). Results 113 patients were enrolled (age 64.5±9.7, 81% males). Peak oxygen intake (peakVO2) improved at each step from 15.0±4.5 mL/min/kg at baseline to 16.5±4.9 mL/min/kg at end study visit, corresponding to 61.5±16.0 and 67.9±17.4 % of predicted, respectively (p<0.05). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) reduced from 39.6±5.5 to 35.9±7.1 (p = 0.005) in the 39 patients (42%) with pathological VE/VCO2≥34 at baseline. KCCQ improved significantly since the first visit with an overall summary score increase from 47.9±11.1 to 52.6±9.8 (p<0.001). Conclusions These findings suggest that sacubitril/valsartan benefits on exercise capacity are immediately evident at the lowest dose and progressively improve as the dose increases.