Impact of Angiotensin Receptor-Neprilysin Inhibitor Therapy on Cardiac Remodeling in Patients with Heart Failure and Reduced Ejection Fraction.

Abstract

Background: Cardiac remodeling in response to hemodynamic and neurohormonal factors is the primary driver of heart failure progression. Angiotensin receptor-neprilysin inhibitor (ARNI) has superior beneficial effects on mortality and quality of life compared to angiotensin-converting enzyme inhibitor (ACEI). Speckle-tracking echocardiography can detect early subtle changes in cardiac structure in numerous cardiac diseases. The study was conducted to evaluate the possible impact of ARNI therapy compared to ACEI on cardiac remodeling using echocardiographic parameters, including global longitudinal strain (GLS) in heart failure with reduced left ventricular ejection fraction (HFrEF) patients.

Methods: This prospective observational study included eighty recently diagnosed HFrEF patients with left ventricular ejection fraction (LVEF) ≤35%, prescribed the four pillars of guideline-directed medical therapy, and uptitrated to the maximally tolerated doses. The study included two groups: the ARNI group included forty patients prescribed ARNI, and the ACEI group included forty patients prescribed ACEI. All patients underwent two- and three-dimensional (2D and 3D) echocardiography to assess baseline parameters, including indexed left ventricular (LV) volumes and 2D and 3D GLS, at baseline and after a 6-month follow-up period.

Results: Both groups had no significant differences regarding demographic data and echocardiographic findings at baseline. After a 6-month follow-up period, there was a significant reduction in LV-indexed volumes in the ARNI group (P < 0.001) and indexed left atrial volumes (P = 0.013) compared to the ACEI group. There was a significant improvement in the ARNI group regarding LVEF (P = 0.011), 2D GLS (P < 0.001), and 3D GLS compared to the ACEI group, but no significant change in the LV mass index. Multivariate regression analysis showed that the use of ARNI, absence of diabetes mellitus, and a higher baseline GLS (above-9.1%) are independent predictors for the occurrence of reverse remodeling (defined as an increase in LVEF ≥5%).

Conclusion: The inclusion of ARNI in the pharmacotherapy of HFrEF patients is an independent predictor of LV reverse remodeling, as observed in a significant improvement in both 2D and 3D volumetric echocardiographic parameters, improved LVEF and longitudinal LV systolic function, represented in 2D and 3D GLS. Baseline 3D GLS and not LVEF or 2D GLS can help predict the occurrence of reverse remodeling in HFrEF patients.