Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

Kae Watanabe, Anis Karimpour-Fard, Alix Michael, Shelley D. Miyamoto, Stephanie J. Nakano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population. Methods: In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate. Results: Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV. Conclusions: The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population.

Original languageEnglish (US)
Pages (from-to)1075-1082
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume37
Issue number9
DOIs
StatePublished - Sep 2018

Funding

The authors have no conflicts of interest to disclose. S.D.M. is a founder and scientific advisor for CoramiR Biomedical, LLC. The contents of this article are the authors’ sole responsibility and do not necessarily represent official views of the National Institutes for Health (NIH). This work was supported by the Addison Scott Memorial Fund, a Boedecker Foundation Award, the Jack Cooper Millisor Chair in Pediatric Heart Disease, a gift from the Nair Family, and grants from the NIH/National Heart, Lung and Blood Institute (K08 HL130592 to S.J.N.). The project was also supported by the NIH/National Center for Research Resources Colorado CTSI (UL1 RR025780).

Keywords

  • biomarker
  • cardiac allograft vasculopathy
  • heart transplant
  • pediatric
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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