title: Vascular endothelial growth factor A is associated with the subsequent development of moderate or severe cardiac allograft vasculopathy in pediatric heart transplant recipients.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) is the leading cause of chronic allograft loss after pediatric heart transplantation. We hypothesized that biomarkers of endothelial injury and repair would predict CAV development in pediatric heart transplant recipients.
  
  
  METHODS
  Blood was collected from pediatric heart transplant recipients at the time of routine annual coronary angiography, and the concentrations of 13 angiogenesis-related molecules were determined. The primary end point was the presence of moderate or severe CAV by angiography during a 5-year follow-up period.
  
  
  RESULTS
  The study enrolled 48 recipients (57% male) with a median age of 15.5 years (range, 2-22 years) and median time post-transplant of 5.8 years (range, 2-15 years). Eight recipients developed moderate/severe CAV at a median follow-up of 4.7 years, of whom 3 died, 3 underwent retransplantation, 1 had a myocardial infarction, and 1 was listed for retransplantation. Clinical characteristics associated with the development of moderate/severe CAV included prednisone use at enrollment (p = 0.03) and positive recipient cytomegalovirus immunoglobulin G at the time of transplant (p = < 0.01). Multivariable Cox proportional hazards regression identified plasma vascular endothelial growth factor (VEGF)-A concentration greater than 90 pg/ml at the time of blood draw as a significant predictor of time to moderate or severe CAV (hazard ratio, 14.3; 95% confidence interval, 1.3-163). Receiver operating characteristic curve analysis demonstrated that VEGF-A shows moderate performance for association with the subsequent development of CAV (area under the curve, 0.77; 95% confidence interval, 0.61-0.92).
  
  
  CONCLUSIONS
  VEGF-A levels in pediatric heart transplant recipients are associated with clinically important CAV progression within the subsequent 5 years.
authors.affiliation: Transplant Research Program, Department of Medicine, Boston, Massachusetts; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Daly
authors.affiliation: Transplant Research Program, Department of Medicine, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Nephrology, Department of Medicine, Boston, Massachusetts.
authors.forename: Maria
authors.initials: M
authors.lastname: Stack
authors.affiliation: Transplant Research Program, Department of Medicine, Boston, Massachusetts; Division of Nephrology, Department of Medicine, Boston, Massachusetts.
authors.forename: Michele F
authors.initials: MF
authors.lastname: Eisenga
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
authors.forename: John F
authors.initials: JF
authors.lastname: Keane
authors.affiliation: Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Anesthesia, Boston Children's Hospital, Boston, Massachusetts; Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Blume
authors.affiliation: Transplant Research Program, Department of Medicine, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Division of Nephrology, Department of Medicine, Boston, Massachusetts. Electronic address: david.briscoe@childrens.harvard.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Briscoe
mesh_terms: D000293:Adolescent; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; allograft vasculopathy; biomarkers; coronary artery disease; heart transplantation