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: Tanja M Raedle-Hurst, Karsten Koenigstein, Frank Gruenhage, Jochen Raedle, Eva Herrmann, Hashim Abdul-Khaliq
• Journal: American heart journal (Am Heart J) Vol. 160 Issue 6 Pg. 1105-12 (Dec 2010) ISSN: 1097-6744 [Electronic] United States
• PMID: 21146665 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2010 Mosby, Inc. All rights reserved.

Chemical References

• Biomarkers
• Growth Differentiation Factor 15

Topics

• 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, physiopathology, surgery)
• Heart Ventricles (abnormalities, diagnostic imaging, physiopathology)
• Hepatic Veins (physiopathology)
• Humans
• Male
• Postoperative Period
• Severity of Illness Index
• Systole
• Ventricular Dysfunction, Left (blood, diagnostic imaging, physiopathology)
• Ventricular Function, Left (physiology)
• Young Adult