Early Effects of Sacubitril/Valsartan on Exercise Tolerance in Patients with Heart Failure with Reduced Ejection Fraction.

Giuseppe Vitale,Cinzia Nugara,Salvo Storniolo,Giuseppe Romano,Antonino Di Franco,Silvia Sarullo,Giuseppina Novo,Filippo Sarullo,Francesco Clemenza,Valentina Agnese,Giuseppa Caccamo,Francesco Giallauria,Laura Ajello

doi:10.3390/jcm8020262

Abstract

Background. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. Methods. We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy. Results. At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3–14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg (p < 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% (p < 0.0001), peak oxygen consumption (VO2) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) (p < 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO2 Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min (p = 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min (p < 0.0001), and ∆VO2/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt (p = 0.0002). Conclusion. Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.

Highlights

Combining renin-angiotensin-aldosterone system blockade with natriuretic peptide system enhancement may deliver functional benefits to patients with heart failure (HF) with reduced ejection fraction (HFrEF)
Patients were included in the study in accordance with the Italian reimbursement criteria for sacubitril/valsartan: 1. symptomatic HF defined as New York Heart Association (NYHA) class II–IV, 2. left ventricular ejection fraction below 35%, as measured using echocardiography, 3. previous treatment with an individual optimal dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 6 months, 4. systolic arterial blood pressure ≥100 mmHg, 5. serum K+ level 30 mL/min/1.73 m2, 7. absence of severe liver insufficiency (Child-Pugh C), and 8. no history of angioedema
A statistically significant reduction in terms of VE/VCO2 slope was observed at follow-up in the subgroup of patients on the highest dose of sacubitril/valsartan (p = 0.01; Table 4, Figure 2A)

Summary

Introduction

Combining renin-angiotensin-aldosterone system blockade with natriuretic peptide system enhancement may deliver functional benefits to patients with heart failure (HF) with reduced ejection fraction (HFrEF). Recent studies showed an improvement in exercise tolerance at 6-min walk test (6-MWT) after initiation of sacubitril/valsartan in patients with HFrEF [2,3,4]. Cardiopulmonary exercise test (CPET) is a valuable tool in HFrEF, allowing accurate assessment of patients’ functional capacity and providing prognostically relevant parameters (e.g., peak VO2 and minute ventilation/carbon dioxide production relationship [VE/VCO2 slope]) [6,7,8,9,10]. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Further studies are necessary to better clarify underlying mechanisms of this functional improvement

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Discussion

Conclusion