Big Endothelin-1 as a Predictor of Reverse Remodeling and Prognosis in Dilated Cardiomyopathy

This study aimed to investigate the predictive value of Big endothelin-1(ET-1) for left ventricular reverse remodeling (LVRR) and prognosis in patients with dilated cardiomyopathy (DCM). Patients with DCM and a left ventricular ejection fraction (LVEF) ≤ 50% from 2008 to 2017 were included. LVRR was defined as the LVEF increased by at least 10% or follow-up LVEF increased to at least 50% with a minimum improvement of 5%; meanwhile, the index of left ventricular end-diastolic diameter (LVEDDi) decreased by at least 10% or LVEDDi decreased to ≤33 mm/m². The composite outcome for prognostic analysis consisted of death and heart transplantations. Of the 375 patients included (median age 47 years, 21.1% female), 135 patients (36%) had LVRR after a median of 14 months of treatment. An independent association was found between Big ET-1 at baseline and LVRR in the multivariate model (OR 0.70, 95% CI 0.55-0.89, p = 0.003, per log increase). Big ET-1, body mass index, systolic blood pressure, diagnosis of type 2 diabetes mellitus (T2DM) and treatment with ACEI/ARB were significant predictors for LVRR after stepwise selection. Adding Big ET-1 to the model improved the discrimination (∆AUC = 0.037, p = 0.042 and reclassification (IDI, 3.29%; p = 0.002; NRI, 35%; p = 0.002) for identifying patients with LVRR. During a median follow-up of 39 (27-68) months, Big ET-1 was also independently associated with the composite outcome of death and heart transplantations (HR 1.45, 95% CI 1.13-1.85, p = 0.003, per log increase). In conclusion, Big ET-1 was an independent predictor for LVRR and had prognostic implications, which might help to improve the risk stratification of patients with DCM.