Abstract 16148: Serum Gdf-15 Identifies Patients at Risk for Acute Heart Failure but Not Ventricular Arrhythmias and Sudden Death

Introduction: GDF-15 (Growth Differentiation Factor 15), a member of the transforming growth factor beta superfamily, has been shown to be a biomarker of mitochondrial diseases. Additionally, increased levels of GDF-15 have also been associated with all-cause death and heart failure (HF) in patients with coronary artery disease. Conflicting data exists regarding GDF-15 levels and risk of ventricular arrhythmic events. Hypothesis: In a cohort of patients with reduced left ventricular systolic function, GDF-15 identifies patients at high risk of (1) worsening HF and (2) sudden arrhythmic death. Methods: PROSe-ICD is a multicenter prospective cohort study of 1,189 patients with ischemic and non-ischemic cardiomyopathy who underwent ICD implantation for primary prevention of sudden death, designed to compare patients who sustain an appropriate ICD firing for rapid VT or VF (surrogate for sudden death) to those who do not. Worsening HF was defined as any admission for acute decompensated HF during an average follow up period of 8 years. Blood samples were obtained on average every 6 months and GDF-15 was measured with an ELISA based assay from a subset of PROSe-ICD patients with appropriate ICD shocks (n=58; 228 samples), worsening HF (n=42; 157 samples), both HF and VT/VF (n=12; 46 samples) and 237 samples from 46 controls without ICD shocks and HF, matched for age and ejection fraction. Results: GDF-15 levels were elevated in patients who had acute decompensated heart failure, but not in patients who experienced ICD shocks in the absence of worsening HF (see Figure). Differences in GDF-15 levels were relatively stable over time within individual patients, and did not predict HF events. Conclusions: Future studies need to examine whether patients with the highest GDF-15 levels have underlying mitochondrial or nuclear DNA mutations leading to mitochondrial dysfunction and worsening HF.