Big endothelin-1 and long-term clinical outcomes in heart failure patients receiving cardiac resynchronization therapy

Abstract

Objective The goal of this study was to evaluate the role of big endothelin-1 (big ET-1) as a prognostic marker in heart failure (HF) patients receiving cardiac resynchronization therapy(CRT). Methods In this single-center retrospective cohort study, a total of 249 patients which had CRT implantation from January 2010 to December 2014 with chronic heart failure (CHF) were enrolled.Clinical outcomes were defined as all-cause mortality (including heart transplantation) and new hospitalization due to worsening HF.Receiver operating characteristic (ROC) curve was performed to determine the cut-off value of big ET-1 in predicting one-year all-cause mortality.All patients were divided into two groups according to the cut-off value.Pearson's bivariate correlation tests were performed to evaluate the relations between big ET-1 and other clinical variables.Kaplan-Meier survival analyses for each outcome were analyzed.Finally, Cox proportional-hazards regression model was used to determine whether big ET-1 was an independent prognostic factor in CRT treated patients. Results The median follow-up time was 23 months.Twenty-five patients (10.0%) died, 6 patients (2.4%) underwent heart transplantation and 65 patients (26.1%) experienced at least one HF readmission.Taking the cut-off value of big ET-1(0.565 pmol/L)by ROC curve, patients with big ET-1≥0.565 pmol/L had higher level of serum creatinine, uric acid, high sensitive C reactive protein (hsCRP), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction and New York Heart Association (NYHA) functional class with higher incidence of atrial fibrillation.The correlation analyses indicated that big ET-1 was positively associated with LgNT-proBNP, hsCRP, LAD and LVEDD (r=0.207, P=0.001; r=0.337, P<0.0001; r=0.275, P<0.0001; r=0.131, P=0.038, respectively). Kaplan-Meier analyses demonstrated that the big ET-1≥0.565 pmol/L group had lower survival rate (P=0.002) and increased new HF hospitalization (P<0.0001). Univariate and multivariate analyses indicated that big ET-1≥0.565 pmol/L was an independent risk factor for all-cause mortality (HR 2.331, 95% CI 1.060-5.125, P=0.035) and HF hospitalization (HR 2.662, 95% CI 1.599-4.432, P<0.0001). Conclusion Big ET-1 was associated with the clinical states in CRT treated patients.Patients with big ET-1≥0.565 pmol/L had increased risk of all-cause mortality and HF hospitalization. Key words: Big endothelin-1; Heart failure; Cardiac resynchronization therapy; Risk factor; Prognosis