Release of growth-differentiation factor 15 and associations with cardiac function in adult patients with congenital heart disease

Abstract

BackgroundGrowth-differentiation factor-15 (GDF-15), a cytokine with broad cardiac and non-cardiac activity, has diagnostic and prognostic value in various diseases, including heart failure. We aimed to investigate the release of GDF-15 in adults with congenital heart disease (ConHD), and assess the association with cardiac function and functional capacity. MethodsA total of 587 consecutive adults with ConHD (median age 33 [IQR 25–41] years, 59% men, and 90% NYHA I) underwent electrocardiography, echocardiography, venepuncture and were seen by a cardiologist. A subset of 143 patients underwent bicycle ergometry on the same day. ResultsMedian plasma GDF-15 was 618 [IQR 487–867] ng/L. In 87 patients (15%), GDF-15 was above the reference value of normal (1109 ng/L). GDF-15 levels were higher in older patients (r=0.367, p<0.001). GDF-15 was higher in patients with elevated pulmonary pressure (median 1114 [IQR 796–2320 ng/L) than in patients with normal pulmonary pressure (median 606 [IQR 481–826] ng/L, p<0.001). GDF-15 correlated positively with NT-proBNP (r=0.445, p<0.001). In multivariate analysis adjusting for age, sex, and NT-proBNP, hs-TnT and hs-CRP, GDF-15 above the reference value was associated with NYHA class (odds ratio for NYHA≥II: 3.5 [95% CI 1.8–6.8], p<0.001), and decreased exercise capacity (odds ratio for workload >85%:0.2 [95% CI 0.06–0.8], p=0.018), but not with systolic ventricular function or ECG rhythm. ConclusionsGDF-15 is elevated in a substantial number of patients and higher in those with elevated pulmonary pressures, regardless of underlying congenital diagnosis. GDF-15 is associated with NYHA class, NT-proBNP and exercise capacity, suggesting the marker has diagnostic and potential prognostic value in adults with ConHD.