title: Growth differentiation factor 15--an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts.
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.
authors.affiliation: Department of Pediatric Cardiology, Saarland University Hospital, Homburg/Saar, Germany. tanja.raedle-hurst@uks.eu
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Raedle-Hurst
authors.forename: Karsten
authors.initials: K
authors.lastname: Koenigstein
authors.forename: Frank
authors.initials: F
authors.lastname: Gruenhage
authors.forename: Jochen
authors.initials: J
authors.lastname: Raedle
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Hashim
authors.initials: H
authors.lastname: Abdul-Khaliq
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018618:Echocardiography, Doppler, Color; D005260:Female; D005500:Follow-Up Studies; D018729:Fontan Procedure; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006330:Heart Defects, Congenital / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D006352:Heart Ventricles / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D006503:Hepatic Veins / Q000503:physiopathology; D006801:Humans; D008297:Male; D011184:Postoperative Period; D012720:Severity of Illness Index; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15