Effects of Sacubitril/Valsartan on Myocardial Tissue in Heart Failure With Left Ventricular Ejection Fraction Below 50%

Background: The effects of sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) on myocardial tissue in heart failure (HF) with left ventricular ejection fraction (LVEF) <50% remain unclear. Methods and Results: Sixty-four HF outpatients with LVEF <50% were randomized to ARNI (switching from an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker [ACEi/ARB] to ARNI) or control (continuing with ACEi/ARB). Left ventricular (LV) structure and myocardial tissue, including changes in LV extracellular volume fraction (ECV), were evaluated before and after the 9-month program using cardiac magnetic resonance imaging. The primary endpoint was changes in ECV. Secondary endpoints were changes in LVEF, LV volume and mass, and extra- and intracellular mass. Fifty-nine patients completed the 9-month intervention. ARNI decreased systolic blood pressure from the first month. The ARNI group showed significant reductions in LV volume, LV mass, and extra- and intracellular mass from baseline to 9 months, but there was no change in LVEF, or in ECV (31.6 +/- 5.0% vs. 31.9 +/- 5.0%, respectively; P=0.795). In the control group, there was no change in systolic blood pressure, LV volume, LV mass, ECV, or extra- and intracellular mass. There was no significant difference in the change in ECV between the ARNI and control groups (0.3 +/- 5.1% vs. 1.2 +/- 4.1%, respectively; P=0.461), whereas the change in extracellular mass was greater in the ARNI group (P=0.025). Conclusions: ARNI reduced LV volume and mass, resulting from decreases in both extra- and intracellular mass, without changing ECV. This suggests ARNI has potential to improve LV tissue characteristics in HF patients with LVEF <50%.