Growth Differentiation Factor-15 Predicts Mortality and Heart Failure Exacerbation But Not Ventricular Arrhythmias in Patients With Cardiomyopathy

Abstract

Background Heart failure (HF) has been increasing in prevalence, and a need exists for biomarkers with improved predictive and prognostic ability. GDF-15 (growth differentiation factor-15) is a novel biomarker associated with HF mortality, but no serial studies of GDF-15 have been conducted. This study aimed to investigate the association between GDF-15 levels over time and the occurrence of ventricular arrhythmias, HF hospitalizations, and all-cause mortality. Methods and Results We used a retrospective case-control design to analyze 148 patients with ischemic and nonischemic cardiomyopathies and primary prevention implantable cardioverter-defibrillator (ICD) from the PROSe-ICD (Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention) cohort. Patients had blood drawn every 6 months and after each appropriate ICD therapy and were followed for a median follow-up of 4.6 years, between 2005 to 2019. We compared serum GDF-15 levels within ±90 days of an event among those with a ventricular tachycardia/fibrillation event requiring ICD therapies and those hospitalized for decompensated HF. A comparator/control group comprised patients with GDF-15 levels available during 2-year follow-up periods without events. Median follow-up was 4.6 years in the 148 patients studied (mean age 58±12, 27% women). The HF cohort had greater median GDF-15 values within 90 days (1797 pg/mL) and 30 days (2039 pg/mL) compared with the control group (1062 pg/mL, both P<0.0001). No difference was found between the ventricular tachycardia/fibrillation subgroup within 90 days (1173 pg/mL, P=0.60) or 30 days (1173 pg/mL, P=0.78) and the control group. GDF-15 was also significantly predictive of mortality (hazard ratio, 3.17 [95% CI, 2.33-4.30]). Conclusions GDF-15 levels are associated with HF hospitalization and mortality but not ventricular arrhythmic events.

Keywords: arrhythmias; biomarkers; heart failure; mortality.

Figures

Figure 1. GDF‐15 (growth differentiation factor‐15) values (pg/mL) with respect to time to decompensated heart failure admission (blue dots) or ventricular tachycardia/fibrillation (red crosses) event.

Negative numbers indicate days preceding heart failure admission date or ventricular tachycardia/fibrillation event, whereas positive numbers indicate days after the heart failure admission date or ventricular tachycardia/fibrillation event. CHF indicates congestive heart failure; GDF‐15, growth differentiation factor‐15; and VT/VF, ventricular tachycardia/fibrillation.

Figure 2. GDF‐15 (growth differentiation factor‐15) values (pg/mL) for heart failure and ventricular tachycardia/fibrillation subgroups at 90 days and 30 days before and after an event, as well as for the control group.

Median GDF‐15 values are shown, with the positive interquartile range shown in the gray box and negative interquartile range in orange. Maximum and minimum values for each group are represented by the whiskers. *P<0.01 from adjusted mixed model. GDF‐15 indicates growth differentiation factor‐15; HF, heart failure; and VT/VF, ventricular tachycardia/fibrillation.

Figure 3. Kaplan–Meier curve for patient mortality stratified by GDF‐15 level.

Values P<0.0001). GDF‐15 indicates growth differentiation factor‐15.