The Effect of Sacubitril/Valsartan on Functional Capacity of Patients Diagnosed With Heart Failure with Reduced Ejection Fraction Assessed by Six Minute Walk Test

Abstract

Heart failure (HF) constitutes a leading cause of morbidity and mortality worldwide and is associated with severe impairment in functional capacity. In patients with chronic HF and reduced ejection fraction (HFrEF), the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan reduced the risk of the composite of cardiovascular (CV) death or first hospitalization for heart failure (HF) by 20% compared to enalapril during a median follow-up of 27 months. Remarkably, the trial showed also an early beneficial effect of sacubitril/valsartan by reducing the risk of 30-day readmission for any cause and HF by 26% and 38%, respectively. However, there is limited data on the short-term effect of sacubitril/valsartan on patient's functional performance. In this study, we evaluated the short-term effects of sacubitril/ valsartan on submaximal exercise capacity evaluated by a 6-minute walk test (6-MWT) in stable patients with symptomatic HFrEF. From November 1, 2018 to June 1, 2019, we prospectively studied a cohort of patients with chronic HF, visited outpatients clinics in Ain Shams University Hospital and 6th October University Hospital. The inclusion criteria were: a) left ventricular systolic dysfunction ≤ 40%, b) stable New York Heart Association (NYHA) functional class ≥II, and c) prior treatment with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). In eligible patients, according to current guidelines, treatment with ACEI or ARB was replaced by sacubitril/valsartan. All patients provided informed consent and the protocol was approved by the research ethics committee in Ain Shams University. 6-MWTwas performed at two time points (baseline assessment and after 30-dayof initiation sacubitril/valsartan. Patients were instructed to cover the maximum distance possible in 6 minutes, pausing to rest when needed in a 30 meter flat corridor. In each visit we registered demographic information, medical history, vital signs, 12 lead electrocardiogram, 6-MWT, standard laboratory data and pharmacological treatments. Doses of sacubitril/valsartan were prescribed according to established recommendations. The recommended starting dose was 49/51 mg twice-daily. By protocol, no treatment changes occurred between the two visits other than titration of ARNI when feasible.