Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration

Abstract

Purpose Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. Methods We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. Results Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610–2757] to 780 [372–1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42–7.71] to 2.35% [1.24–4.96], p = 0.003. Conclusions A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

Effects of sacubitril/valsartan on the functional capacity of real-world patients in Italy: the REAL.IT study on heart failure with reduced ejection fraction

“…Several studies have shown improvements in the objective exercise capacity and tolerance measures of patients with symptomatic HF after the sacubitril/valsartan initiation (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Palau et al (23) and Vitale et al (24) showed improvements in the peak VO 2 and VE/VCO 2 slope in HFrEF patients after follow-up durations between 1 and 6 months after the sacubitril/ valsartan initiation (i.e., the peak VO 2 improved from 14.6 ± 3.3 to 17.2 ± 4.7 ml/kg/min; p < 0.0001, and the VE/VCO 2 slope decreased from 34.1 ± 6.3 to 31.7 ± 6.1; p = 0.006).…”