Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study.

Giuseppe Armentaro,Giorgio Sesti,Marcello Magurno,Franco Arturi,Giovanni Tripepi,Alfredo F Toscani,Raffaele Maio,Velia Cassano,Angela Sciacqua,Graziella D’Arrigo,Sofia Miceli,Valentino Condoleo

doi:10.3389/fphar.2021.733475

Abstract

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.

Highlights

Heart failure (HF) represents a widespread health problem with an estimated prevalence in European countries of 1–2% in the adult population and over 10% in elderly (Ponikowski, et al, 2016; Mosterd A, Hoes AW, 2007)
The Italian Network Heart Failure (IN-HF) registry showed that 1-year mortality rate was higher than 27% in patients who experienced worse clinical conditions and needed hospital admission (Tavazzi L, et al, 2013)
The Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme inhibitors (ACEs)-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial demonstrated that sac/val was able to reduce the composite endpoint of CV death or first hospitalization for HF by 20% and the relative risk of all-cause mortality by 16% in comparison with enalapril, during a 27 months median of follow-up, in HRrEF outpatients

Summary

Introduction

Heart failure (HF) represents a widespread health problem with an estimated prevalence in European countries of 1–2% in the adult population and over 10% in elderly (Ponikowski, et al, 2016; Mosterd A, Hoes AW, 2007). The Italian Network Heart Failure (IN-HF) registry showed that 1-year mortality rate was higher than 27% in patients who experienced worse clinical conditions and needed hospital admission (Tavazzi L, et al, 2013). In this context, HF with reduced ejection fraction (HFrEF) represents about a 50% of the whole affected population, and this is a fluctuating clinical condition characterized by phases of apparent clinical stability and clinical worsening which frequently require hospitalization (Iorio A, et al, 2019; Dharmarajan K, et al, 2013). Sac/val is more effective than enalapril among patients hospitalized for acute decompensated heart failure (ADHF) in reducing both N-terminal pro-brain natriuretic peptide (NT pro-BNP) and, in an exploratory analysis, the composite endpoint of rehospitalization and CV death (Velazquez EJ, et al, 2019; Morrow DA, et al, 2019)

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