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

Background In 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. Methods Plasma 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. Results Mean 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 gamma GT 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%. Conclusions Growth 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. (Am Heart J 2010;160:1105-12.)