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. Cardiopulmonary exercise test (CPET) provides functional prognostic parameters for patient with HFrEF (i.e. peakVO2 and ventilation/CO2 production [VE/VCO2] slope) and it is a well-recognized, valuable, accurate tool for risk stratification. Aim of the study and methods: The aim of the study is to prospectively enroll a cohort of 100 HFrEF outpatients eligible for sacubitril/valsartan and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. The procedures will be repeated along the follow-up at 1, 2 and 3 months after the enrollment (titration period) and at 6 months after the reach of the maximum tolerated dose. Inclusion criteria: age 18-80 years both males and females, New York Heart Association Class (NYHA) II-III in stable clinical conditions, reduced ejection fraction (< 35%), capability to perform a cardiopulmonary exercise test (CPET). Exclusion criteria: moderate-severe chronic obstructive pulmonary disease; chronic oxygen therapy; contraindication to CPET; planned procedures (i.e. cardiac surgery, revascularization procedures, CRT implantation) that could per se impact on CPET, echocardiography and laboratory values. Timing: the predicted duration of the protocol is 2 years. Statistical analyses: Differences between time-points of the study will be tested for significance using the paired t-tests or repeated measures analysis as appropriate. Analyses will be done using IBM SPSS Statistics software, version 25.0. A p value <0.05 will be considered for significance. Results: The study is currently ongoing, with 38 patients actually enrolled and treated with sacubitril/valsartan for at least 3 months. On this sub-population we performed an ad-interim analysis. 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.

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 / M. Mapelli, E. Salvioni, I. Mattavelli, S. Paolillo, P. Agostoni. ((Intervento presentato al convegno ARCA Liguria - Premio Young tenutosi a Genova nel 2019.

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

M. Mapelli
Primo
;
P. Agostoni
2019

Abstract

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. Cardiopulmonary exercise test (CPET) provides functional prognostic parameters for patient with HFrEF (i.e. peakVO2 and ventilation/CO2 production [VE/VCO2] slope) and it is a well-recognized, valuable, accurate tool for risk stratification. Aim of the study and methods: The aim of the study is to prospectively enroll a cohort of 100 HFrEF outpatients eligible for sacubitril/valsartan and perform serial CPET, laboratory and echocardiographic assessments before and during the gradual titration of the treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. The procedures will be repeated along the follow-up at 1, 2 and 3 months after the enrollment (titration period) and at 6 months after the reach of the maximum tolerated dose. Inclusion criteria: age 18-80 years both males and females, New York Heart Association Class (NYHA) II-III in stable clinical conditions, reduced ejection fraction (< 35%), capability to perform a cardiopulmonary exercise test (CPET). Exclusion criteria: moderate-severe chronic obstructive pulmonary disease; chronic oxygen therapy; contraindication to CPET; planned procedures (i.e. cardiac surgery, revascularization procedures, CRT implantation) that could per se impact on CPET, echocardiography and laboratory values. Timing: the predicted duration of the protocol is 2 years. Statistical analyses: Differences between time-points of the study will be tested for significance using the paired t-tests or repeated measures analysis as appropriate. Analyses will be done using IBM SPSS Statistics software, version 25.0. A p value <0.05 will be considered for significance. Results: The study is currently ongoing, with 38 patients actually enrolled and treated with sacubitril/valsartan for at least 3 months. On this sub-population we performed an ad-interim analysis. 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.
nov-2019
Sacubitril/valsartan; Heart failure treatment; Cardiopulmonary exercise test; echocardiography
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
Associazione Regionale dei Cardiologi Ambulatoriali
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 / M. Mapelli, E. Salvioni, I. Mattavelli, S. Paolillo, P. Agostoni. ((Intervento presentato al convegno ARCA Liguria - Premio Young tenutosi a Genova nel 2019.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/712560
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