Impact of Sacubitril/Valsartan in Cardiac Reverse Remodeling in Ischemic vs. Nonischemic Cardiomyopathy

Abstract

Guideline directed medical therapy with beta blockers, ACEi/ARBs, and aldosterone antagonists with the goal of affecting cardiac reverse remodeling (CRR) has previously been the cornerstone of management of patients with heart failure with reduced ejection fraction (HFrEF). More recently, PARADIGM-HF demonstrated the superiority of sacubitril-valsartan to enalapril in reducing HF hospitalizations as well as cardiac and all-cause mortality. Other studies demonstrated that ARNI therapy may enhance CRR to a greater degree than ACEI or ARB therapy alone. To date, the degree of CRR in nonischemic vs ischemic cardiomyopathy treated with ARNI has not been studied. A single-center retrospective chart review was performed assessing the effect of ARNI on echocardiographic parameters of CRR. Patients initiated on any dose sacubitril-valsartan from January 1, 2016 to October 1, 2019 were included. Baseline demographic and clinical information was collected. Serial echocardiograms performed at 3 month intervals following initiation of therapy were reviewed for markers of cardiac remodeling including ejection fraction (LVEF), left ventricular internal diameter end diastole and end systole (LVESD, LVEDD), and left ventricular mass index (LVMI). Of the 76 patients included in the analysis, 29 (38%) had ICM and 47 (72%) had NICM with a median age of 61.5. Both groups were treated with maximally tolerated doses of guideline directed medical therapy. There was no difference in the percentage of patients in each cohort treated with low, intermediate, or high doses of ARNI. Patients with ICM and NICM were treated with ARNI for an average of 1.7 years and 1.6 years respectively. In the ICM cohort, there was a statistically significant improvement in LVEF (P=0.004), but not in any other parameters of ventricular remodeling. In the NICM cohort, there was a statistically significant improvement in LVEF (P=0.007), LVESD (P=0.004), and LVMI (P=0.007). Our data suggest that less LV remodeling occurs in ICM vs NICM following treatment with ARNI. A subgroup analysis of PARADIGM-HF demonstrated similar clinical outcomes in these two patient populations. Taken together, these findings raise the possibility that the benefit of ARNI therapy occurs through mechanisms in addition to reverse remodeling.