Effects of Sacubitril/Valsartan on exercise capacity, natriuretic peptides and ventricular remodeling in a prospective cohort of patients with heart failure and reduce ejection fraction

Background: Sacubitril/valsartan, a novel therapy in the treatment of heart failure with reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise tolerance and cardiac performance. Aim of the study and methods: We prospectively enrolled a cohort of HFrEF outpatients eligible for sacubitril/valsartan and performed serial cardiopulmonary exercise tests (CPET), laboratory and echocardiographic assessments before and during the gradual titration of this treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. Results: We examined 38 patients treated with sacubitril/valsartan for at least 3 months. At a mean follow-up of 145±68 days, 95% of patients reached the maximum dose, without important safety concerns. Ejection fraction increased (Fig. 1a), while left ventricular end-diastolic and end-systolic volumes decreased (Fig. 1b). Peak oxygen consumption % of predicted (VO2%) improved (Figure 2), along with workload at maximal exercise (95.3±38.6 vs. 101.5±40.0 watt, p=0.0005). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) did not reach statistical significance in this sub-population. We also observed a significant reduction in NT-proBNP values (Figure 3) without significant worsening of renal function or hyperkaliemia. New York Heart Association functional class improved (Figure 4), together with a significant decrease of MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score from 4.4 (IQR 1.7-7.1) to 2.1 (1.1-4.9) %, with a positive impact on two-year HF prognosis (p=0.006). Conclusion: Medium-term treatment with sacubitril/valsartan demonstrated beneficial effects on exercise tolerance, left ventricular remodeling and functional status, confirming the results from previous clinical trials in real-life. A longer follow-up and larger population will further contribute to the assessment of its positive effects on HFrEF patients.