Division of Cardiology, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, USA.
J Heart Lung Transplant. 2018 Sep;37(9):1075-1082. doi: 10.1016/j.healun.2018.04.015. Epub 2018 Apr 30.
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.
心脏同种异体移植血管病（CAV）是儿科心脏移植受者再次移植和死亡的主要原因。我们的目的是评估血清血管内皮生长因子-A（VEGF）与儿科心脏移植人群 CAV 发展之间的关系。
在一所大学医院进行的这项回顾性研究中，通过酶联免疫吸附试验检测接受常规心导管检查的儿科心脏移植受者储存的血清中 VEGF 浓度。在 CAV 患者（n=29）中，在 2 个时间点采集样本：在 CAV 诊断之前（pre-CAV）和首次 CAV 诊断时（CAV）。在没有 CAV 的患者（no-CAV，n=16）中，仅使用 1 个时间点。共检测 74 份血清 VEGF 浓度（n=74），重复检测 2 次。
儿科心脏移植受者在基于导管的 CAV 诊断之前，血清 VEGF 升高（no-CAV 平均值：144.0±89.05pg/ml；pre-CAV 平均值：316.2±118.3pg/ml；p=0.0002）。pre-CAV VEGF 水平的受试者工作特征曲线分析显示曲线下面积为 87.7%（p=0.0002），226.3pg/ml 的 VEGF 水平预测 CAV 发展的敏感性为 77.8%，特异性为 91.7%。血管造影诊断为 CAV 的患者和血管造影正常但血管内超声（IVUS）显示 CAV 的患者的 VEGF 水平均升高。
在可检测到的 CAV 发生之前，血清 VEGF 的增加是其作为预测生物标志物的基础，这表明在儿科心脏移植人群中进一步研究 VEGF 在 CAV 发病机制中的作用是合理的。
