Growth differentiation factor 15—an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts

BackgroundIn patients after the Fontan procedure, assessment of ventricular function is difficult and amino-terminal pro-B-type natriuretic peptide levels failed to be directly related to echocardiographic measures of systolic ventricular function.The aim of the study was to evaluate growth differentiation factor 15 (GDF-15), a marker of various stress pathways in the heart and extracardiac tissues.MethodsPlasma GDF-15 levels were measured in 38 consecutive patients after the Fontan procedure and compared to clinical, echocardiographic, and laboratory data; liver tissue stiffness; and venous hepatic flow velocities.ResultsMean GDF-15 levels were 987.2 ± 440.5 pg/mL in patients with an ejection fraction (EF) <50% as compared to 520.2 ± 143.1 pg/mL in those with an EF ≥50% (P < .001). Growth differentiation factor 15 levels were significantly related to the EF of the single ventricle (r = −0.66, P < .001), New York Heart Association functional class (r = 0.43, P = .008), and γGT levels (r = 0.50, P = .002) but weakly to liver tissue stiffness. According to receiver operating characteristic curve analysis, an EF <50% was best predicted by GDF-15 levels (area under the curve [AUC] 0.90, P < .001), peak venous hepatic flow at deep inspiration (AUC 0.89, P = .002), and age at Fontan operation (AUC 0.86, P = .001). Growth differentiation factor 15 and age at Fontan operation proved to be independent predictors in the multivariate analysis. The optimal cutoff of GDF-15 for the prediction of an EF <50% was calculated to be 613 pg/mL with a sensitivity of 90.0% and specificity of 85.7%.ConclusionsGrowth differentiation factor 15 might be helpful in detecting early abnormal function of the Fontan circuit in patients with univentricular hearts. In patients with GDF-15 levels exceeding 613 pg/mL, further cardiac evaluation should be considered because impaired systolic function of the single ventricle may be present.