Big Endothelin-1 And Long-term Clinical Outcomes In Heart Failure Patients Receiving Cardiac Resynchronization Therapy

Objective The goal of this study was to determine the role of big endothelin-1 (big ET-1) as a prognostic marker in heart failure (HF) patients receiving CRT.Methods In this single-center retrospective cohort study, a total of 249 patients which had CRT implantation between January 2010 and 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 a cut-off value of big endothelin-1 (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 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 of was 23 months.25 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(pmol/L)= 0.565 by ROC curve, patients with big ET-1≥0.565 had higher level of serum creatinine, uric acid, high sensitive CRP (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). Kaplan-Meier analyses demonstrated that the big ET-1> 0.565 pmol/L group had lower survival (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 2.054,95% CI 1.172-3.600, P= 0.012).Conclusion Big ET-1 was associated with clinical condition in CRT treated patients. Patients with big ET-1≥ 0.565 pmol/L had increased risk of all-cause mortality and HF hospitalization.