Growth/differentiation factor-15 (GDF-15) as a predictor of serious arrhythmic events in patients with nonischemic dilated cardiomyopathy

Abstract Introduction Cardiac biomarkers have been proposed as a new tool to improve risk stratification of serious arrhythmic events in patients with heart failure (HF) beyond estimates of left ventricular ejection fraction. Growth differentiation factor (GDF)-15, a stress-induced cytokine, has been found to correlate with markers of myocardial fibrosis and adverse clinical outcomes, but its role as a predictor of arrhythmic events in patients with nonischemic HF is uncertain. Methods and results A prospective observational study was conducted in 148 nonischemic patients with HF who underwent comprehensive clinical and laboratory evaluation, including measurement of serum GDF-15. The study endpoints were serious arrhythmic events (which included appropriate implantable cardioverter-defibrillator therapy and sudden cardiac death) and all-cause mortality. Mean age of the cohort was 54.8 ± 12.7 years, and mean left ventricular ejection fraction (LVEF) was 27.4% ± 7.5%. During a mean follow-up time of 42 months, arrhythmic events occurred in 28 patients (19%), and 40 patients (27%) died. An increase in serum GDF-15 (log-transformed) correlated linearly with a higher risk of serious arrhythmic events (HR 1.14, 95% CI 1.01–1.28, p = 0.03) even after adjustment for other potential clinical predictors (HR 1.16, 95% CI 1.02–1.32, p = 0.02). GDF-15 was also strongly and independently associated with all-cause mortality (HR 1.17, 1.05–1.31, p = 0.004). Conclusion In this cohort of nonischemic HF patients on optimized medical treatment, serum GDF-15 levels were independently associated with major arrhythmic events and overall mortality. This biomarker may add prognostic information to better stratify the risk of sudden death in this particular population.