Effects of sacubitril/valsartan on cardiac remodeling in heart failure with reduced ejection fraction: An integrated study of molecular biomarkers and imaging techniques

Abstract

Treatment of heart failure and reduced ejection fraction (HFrEF) using angiotensin receptor-neprilysin inhibitor demonstrates beneficial effects on cardiac remodeling (CR). We assessed the impact of sacubitril/valsartan on the concentrations of HF biomarkers in relation to parameters of CR using imaging techniques in patients with HFrEF. In a prospective single-center open-label study, 68 patients with symptomatic HFrEF were treated with sacubitril/valsartan and followed-up every three months for 12 months. Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured in blood samples. Additionally, echocardiography and cardiac magnetic resonance imaging (cMRI) were performed to assess heart structural and functional changes. Following treatment initiation, follow-up visits revealed an improved NYHA functional class in these patients, alongside significant decreases in all circulating biomarkers, increases in left ventricular ejection fraction (LVEF), and reductions in volume- and diameter-related LV parameters. Sustained gradual decreases in sST2 concentrations over time correlated with NT-proBNP concentrations (rho=+0.26, P < 0.001). Both biomarkers were inversely correlated with LVEF, and positively correlated with volume- and diameter-related LV parameters from echocardiography and cMRI. However, NT-proBNP concentrations exhibited stronger correlations with these LV parameters and were associated with the number of LV segments showing fibrosis, unlike sST2. Sacubitril/valsartan treatment in HFrEF leads to reduced sST2 and NT-proBNP concentrations with distinct decreasing curves, which are linked to reverse CR through LV-related parameters. In contrast to sST2, NT-proBNP is also associated with fibrosis, suggesting that both biomarkers unveil distinct mechanisms during CR in patients treated with sacubitril/valsartan.

Keywords: Biomarkers; Cardiac magnetic resonance imaging; Cardiac remodeling; Echocardiography; Fibrosis; Heart failure; NT-proBNP; SST2; Sacubitril/valsartan.