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

• Published in: The Journal of heart and lung transplantation Vol. 37; no. 9; pp. 1075 - 1082
• Main Authors: Watanabe, Kae, Karimpour-Fard, Anis, Michael, Alix, Miyamoto, Shelley D., Nakano, Stephanie J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2018
• Subjects: Adolescent; biomarker; Biomarkers - blood; cardiac allograft vasculopathy; Child; Child, Preschool; Coronary Artery Disease - blood; Coronary Artery Disease - diagnosis; Female; heart transplant; Heart Transplantation; Humans; Infant; Male; pediatric; Retrospective Studies; Risk Factors; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; cardiac allograft vasculopathy; heart transplant; biomarker; vascular endothelial growth factor; pediatric
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2018.04.015

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.
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.
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.
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.