Effect of Sacubitril–Valsartan on Secondary Mitral Regurgitation and Left Ventricular Reverse Remodeling in Patients With Heart Failure With Reduced Ejection Fraction: A 2D and 3D Echocardiographic Study

BACKGROUND: Heart failure (HF) with reduced ejection fraction (HFrEF) is characterized by progressive left ventricular (LV) remodeling and is often complicated by secondary (functional) mitral regurgitation (MR). Sacubitril-valsartan (S/V), an angiotensin receptor-neprilysin inhibitor (ARNI), has demonstrated superiority over enalapril in reducing morbidity and mortality in HFrEF. Its mechanism of action includes promoting LV reverse remodeling (LVRR), but the comprehensive effect on both LVRR and secondary MR, particularly using advanced three-dimensional (3D) echocardiography, requires further elucidation. OBJECTIVES: To evaluate the effect of 1-year S/V therapy on LVRR and the severity of secondary MR in patients with HFrEF, utilizing both two-dimensional (2D) and 3D echocardiographic parameters. METHODS: This prospective, single-center study included 80 patients with HFrEF (LVEF ≤ 40%) initiated on S/V. Comprehensive 2D and 3D transthoracic echocardiography was performed at baseline 6 months, and 1 year of treatment. LVRR was assessed by changes in LV volumes (EDVI, ESVI), LVEF, and LV mass index (LVMI). MR severity was quantified using the effective regurgitant orifice area (EROA). Paired statistical tests (t-test or Wilcoxon signed-rank test) were used for pre- and posttreatment comparisons. Correlation and multivariable linear regression analyses were performed to identify predictors of LVRR. RESULTS: (-34.6%, p < 0.001), accompanied by reductions in regurgitant volume (RV) (-32.6%, p < 0.001) and regurgitant fraction (-30.8%, p < 0.001). LVRR was evidenced by significant increases in LVEF (3D: +42.1%, p < 0.001, Cohen's d = 2.63) and reductions in LVEDV (-18.0%, p < 0.001) and LVESV (-31.8%, p < 0.001), as well as a 14.7% decrease in LVMI (p < 0.001). Correlation analysis revealed that MR improvement closely paralleled LV remodeling, with ΔEROA strongly associated with reductions in LVESVI (r = 0.774, p < 0.001), LVEDVI (r = 0.558, p < 0.001), and LVEF improvement (r = -0.781, p < 0.001). Multivariable regression identified lower baseline LVEF (3D) as the strongest independent predictor of LVRR (β = -2.304, p < 0.001) CONCLUSIONS: S/V therapy induces significant and comprehensive LVRR and a marked reduction in secondary MR severity in HFrEF patients. The strong correlation between these two effects suggests that MR improvement is primarily driven by LVRR. Lower baseline LVEF is a powerful predictor of the magnitude of LVRR.