Reduction of extracellular volume and reverse cardiac remodeling during sacubitril/valsartan therapy assessed by cardiac magnetic resonance in patients with heart failure (REMODELING CMR-HF)

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf REMODELING HF Background/Introduction: Extracellular volume (ECV) expansion is a major determinant of cardiac remodeling in heart failure. Cardiac magnetic resonance (CMR) T1 mapping has been developed as a noninvasive technique to estimate ECV. Purpose The objective of this study is to assess the response to Sacubitril/Valsartan by measuring changes in myocardial ECV and their association with reverse cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Methods Prospective, single-center, open-label study of two hundred-four HFrEF patients underwent CMR T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence for ECV calculation, and initiated with sacubitril-valsartan treatment according to Guideline-Directed Medical Therapy. Absolute change in myocardial ECV, serum levels of procollagen type I amino-terminal peptide (PINP) and procollagen type III amino-terminal peptide (PIIINP), left ventricular end-diastolic volume index, left ventricular end-systolic volume index and left ventricle ejection fraction (LVEF) were analyzed from baseline to 12-month follow-up. Results Baseline MOLLI-ECV was 48.2% ± 2.4 in 106 patients with ischemic cardiomyopathy (ICM) and 38.7% ± 2.7 in 98 with idiopathic dilated cardiomyopathy (DCM), decreasing to 34% ± 2.4 for ICM and 29.5% ± 2.7 for DCM (P < 0.001), at 12 months with sacubitril-valsartan therapy. These changes were correlated with a reduction of -36 μg/L for PINP (CI 95% 78-93, P < 0.001), and -3.0 μg/L for PIIINP (CI 95% 73-91, P < 0.001), -20 ml/m² in left ventricle end-diastolic and -18 ml/m² in end-systolic volumes, and an improvement in LVEF from 29% to 36% in both groups (P < 0.001). Conclusions For the first time, we observe that changes in extracellular volume induced by sacubitril-valsartan therapy are related to reverse cardiac remodeling in patients with in HFrEF. These findings suggest that there may be an opportunity to decrease adverse remodeling with the use of a CMR-guided therapeutic approach aimed at decreasing fibrogenic activity and modulate the remodeling process.