Sacubitril/valsartan improves exercise performance in patients with heart failure: a dose-dependent effect

Abstract Funding Acknowledgements Type of funding sources: None. 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). Purpose 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) (Table 1). 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.