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Background We investigated serial serum levels of GDF‐15 (growth differentiation factor 15) in Fontan patients and their relation to outcome. Methods and Results In this single‐center prospective study of consecutive Fontan patients, serial serumGDF ‐15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association betweenGDF ‐15 and the combined end point of all‐cause mortality, heart transplant listing, and Fontan‐related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15–28 years). MedianGDF ‐15 serum levels at baseline were 552 pg/mL (interquartile range: 453–729 pg/mL).GDF ‐15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels ofNT ‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and ɣGT (γ‐glutamyltransferase) and negatively with exercise capacity. During a median follow‐up of 4.8 years (interquartile range: 3.3–5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baselineGDF ‐15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95%CI , 1.27–6.00;P =0.011). After 2 years of follow‐up, patients in whom serum level ofGDF ‐15 increased to &gt;70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95%CI , 1.03–6.99;P =0.043).Conclusions In Fontan patients, elevated serum levels ofGDF ‐15 are associated with worse functional status and predict Fontan‐related events. Furthermore, serial measurements showed that an increase inGDF ‐15 serum level was associated with increased risk for adverse outcome.

GDF‐15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation