Sacubitril/valsartan reduces levels of procollagen types I and III and correlates with reverse cardiac remodeling

Abstract

Introduction and objectivesExtracellular matrix turnover is a major determinant of cardiac remodeling in heart failure. Sacubitril/valsartan decreases serum levels of procollagen type I amino-terminal peptide (PINP) and procollagen type III amino-terminal peptide (PIIINP), but its correlation with reverse remodeling is unknown. The purpose of this study is to determine the effect of sacubitril/valsartan on the profibrotic PINP and PIIINP biomarkers and their association with reverse cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). MethodsProspective, single-center, open-label study of 401 outpatients with HFrEF initiated with sacubitril/valsartan treatment according to Guideline-Directed Medical Therapy. Change in serum levels of PINP, PIIINP, left ventricle end-diastolic volume index, left ventricle end-systolic volume index and left ventricle ejection fraction were analyzed from baseline to 12-month follow-up. ResultsBaseline levels of PINP and PIIINP were highest (above-median) in 63 patients with ischemic cardiomyopathy and 19 with idiopathic dilated cardiomyopathy, decreasing −36μg/L for PINP (95%CI, 78–93; P<0.001), and −3.0μg/L for PIIINP (95%CI, 73–91; P<.001), at 12 months with sacubitril/valsartan therapy. These changes were correlated with an improvement in left ventricle ejection fraction from 29% to 36%, and a reduction in left ventricle end-diastolic (−20mL/m2) and end-systolic (−18mL/m2) volumes in this subgroup (P<.001). Advanced age, diabetes, hypertension, and greater dilation of left ventricle were more frequent in this subgroup (P<.001). ConclusionsThese findings suggest that changes in fibrosis markers induced by sacubitril-valsartan therapy in HFrEF are related to reverse cardiac remodeling in patients with higher PINP and PIIINP levels.