Elevated vascular endothelial growth factor levels are associated with aortopulmonary collateral vessels in patients before and after the Fontan procedure

Background Aortopulmonary collaterals (APCs) are frequently observed before and after the Fontan procedure. However, the mechanism of the development of APCs is unknown. We hypothesized that one or several antiangiogenic and/or angiogenic growth factors might play a role in the development of APCs. Methods Eighty-five patients were enrolled and divided into 3 groups (Fontan group: 30 patients after the Fontan procedure, cyanotic group: 29 patients with cyanotic heart disease, and control group: 26 patients with cyanotic heart disease after biventricular repair). We measured basic fibroblast growth factor, vascular endothelial growth factor (VEGF), hepatocyte growth factor, and endostatin at catheterization. Angiographic evaluation for the presence of APCs using a 4-point scale (grade 1: absent APCs, ≥grade 2: significantly present APCs) was performed, and the relation of the serum levels of these factors to the presence of APCs was assessed. Results The grade of APCs significantly increased in the Fontan group, but it decreased in the control group. The serum VEGF levels were higher in the Fontan group (280 ± 174 pg/mL) and the cyanotic group (302 ± 245 pg/mL) than in the control group (111 ± 91 pg/mL) (P = .0004), and they were higher in patients with APCs (383 ± 204 pg/mL) than in those without APCs (115 ± 65 pg/mL) (P < .0001). There was no significant difference in the serum basic fibroblast growth factor, hepatocyte growth factor, and endostatin levels between the 3 groups. Conclusions Aortopulmonary collaterals increase after the Fontan procedure. Serum VEGF levels are associated with the presence of APCs. Vascular endothelial growth factor may play a role in the development of APCs in patients with cyanotic heart disease and after the Fontan procedure.