Association of baseline big endothelin-1 level with long-term prognosis among cardiac resynchronization therapy recipients

Background: Serum concentration of big endothelin-1 (ET-1) has prognostic significance in heart failure. However, its prognostic value in cardiac resynchronization therapy (CRT) recipients has not been well-characterized. Methods: A cohort of 367 consecutive patients who received CRT between January 2010 and December 2015 were enrolled, and categorized into three groups according to baseline big ET-1 tertiles: big ET-1 <= 0.34 pmol/L (N=119), big ET-1 between 0.34-0.56 pmol/L (N=127) and big ET-1 > 0.56 pmol/L (N=121). The primary endpoints included mortality rate (all-cause) and heart transplantation. Results: Over a median follow-up of 21 months, 48 (13.08%) patients died, 6 (1.63%) underwent heart transplantation and 100 (27.25%) had heart failure hospitalization (HFH). We found a significant difference in event free survival between the three groups, with high levels of big ET-1 correlating with worse survival (Log-rank test, P < .001). After adjusting for multiple factors in the multivariate model, big ET-1 > 0.56 pmol/L was an independent predictor for primary endpoint event [hazard ratio (HR): 2.005, 95% confidence interval(CI) 1.045-6.2621, P=.040] and HFH (HR=2.126, 95% CI 1.182-3.827, P=.012). Conclusion: Baseline big ET-1 > 0.56 pmol/L was independently associated with higher all-cause mortality and HFH among CRT recipients, and therefore can be added to the marker panel used for stratifying high risk CRT patients for priority treatment.