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

Am Heart J. 2010 Dec;160(6):1105-12. doi: 10.1016/j.ahj.2010.08.033.

Abstract

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 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%.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Blood Flow Velocity
  • Child
  • Child, Preschool
  • Disease Progression
  • Echocardiography, Doppler, Color
  • Female
  • Follow-Up Studies
  • Fontan Procedure*
  • Growth Differentiation Factor 15 / blood*
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / physiopathology
  • Heart Defects, Congenital / surgery
  • Heart Ventricles / abnormalities*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology
  • Hepatic Veins / physiopathology
  • Humans
  • Male
  • Postoperative Period
  • Severity of Illness Index
  • Systole
  • Ventricular Dysfunction, Left / blood*
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / physiology
  • Young Adult

Substances

  • Biomarkers
  • Growth Differentiation Factor 15