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 exercise capacity: a prognostic improvement that starts during uptitration / Mapelli, M., Mattavelli, I., Paolillo, S., Salvioni, E., Magri, D., Galotta, A., De Martino, F., Mantegazza, V., Vignati, C., Esposito, I., Dell'Aversana, S., Paolillo, R., Capovilla, T., Tamborini, G., Nepitella, A.A., Filardi, P.P., Agostoni, P.. - In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. - ISSN 0031-6970. - 79:9(2023), pp. 1173-1184. [10.1007/s00228-023-03527-y]
Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration
Paolillo S.;De Martino F.;Paolillo R.;Filardi P. P.;
2023
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
