Abstract 11837: A Vascular Endothelial Growth Factor a (VEGFA) Genetic Variant is Associated With Improved Ventricular Function and Transplant-Free Survival After Surgery for Non-Syndromic Congenital Heart Defects

Introduction: We have shown the minor allele of VEGFA single nucleotide polymorphism (SNP) rs833069 is associated with improved transplant-free survival after surgery for CHD in infants. The biological mechanisms underlying the improved survival have not been delineated. The minor allele is associated with higher VEGF production. We hypothesized that the VEGFA SNP is associated with better systemic ventricular function after surgery for CHD, resulting in improved survival. Methods: This is an analysis of a cohort of 422 non-syndromic CHD patients who underwent cardiac surgery with cardiopulmonary bypass before 6 months of age, of which 105 (24.9%) were single ventricle. Echocardiography reports were reviewed. Systemic ventricular function was subjectively assessed and categorized as normal, or mildly, moderately or severely depressed. The change in ventricular function was calculated as the change from the preoperative study to last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion (AIC). Only variables that improved model prediction of change in systemic ventricular function were retained in the final model. Results: Genetic and echocardiographic data were available for 335/422 subjects (79%). Of these, 40 (11.9%) developed worse systemic ventricular function and none demonstrated an improvement in ventricular function during the study period. (mean followup 13.5 years). After covariate adjustment, presence of the VEGFA SNP rs833069 minor allele was associated with preserved ventricular function, (p=0.011). A decrease in systemic ventricular function was significantly associated with heart transplantation or death (p Conclusions: These data are consistent with the hypothesis that the mechanism by which the VEGFA SNP rs833069 minor allele improves survival may be preservation of ventricular function. Further studies are needed to validate this genotype-phenotype association and determine if the mechanism underlying preservation of ventricular function and improved transplant-free survival is related to increased VEGF production.