Abstract 2005: VEGF Genotype is Associated With Adverse Outcomes in Children With Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) causes an imbalance between myocardial oxygen demand and supply resulting in myocardial ischemia, dysfunction and progressive cardiac hypertrophy. Vascular endothelial growth factor (VEGF) is necessary for cardiac angiogenesis to prevent myocardial ischemia. We investigated the association between VEGF polymorphisms and the severity and outcomes of HCM.
Methods: Subjects with HCM (<21 yrs) were prospectively enrolled in two institutions (2004 – 09) and were genotyped for VEGF polymorphisms in 3 VEGF genes. Presence of an allele associated with VEGF downregulation i.e. 2578A, 1154A, or 634G, was used to define a risk genotype. Subjects were divided into high risk (HR, ≥2 risk genotypes) and low risk (LR; <2 risk genotypes) groups. Linear and logistic univariable regression models were used to test for association between risk groups and echocardiographic (M-mode, 2-D) measures and clinical outcomes.
Results: In 81 HCM subjects, frequency of risk alleles, A, A, G was 39%, 45% and 50% respectively; 53 subjects were HR and 28 were LR. Race, gender, and percent of subjects with sarcomeric mutations were not different between risk groups. A major cardiac event (arrhythmia, ICD, myectomy, transplant, death) occurred in 30% subjects. Left ventricular (LV) mass z score was not different between groups. However, subjects in the HR group tended to be younger at diagnosis, had more septal hypertrophy, higher LV outflow tract gradient, higher incidence of left bundle branch block (LBBB) and ST changes during exercise, and higher incidence of septal myectomy (Table⇓).
Conclusions: VEGF genotype can aid in risk stratifying patients with HCM and identify those at risk for myocardial ischemia and asymmetric septal hypertrophy requiring surgical intervention. Further studies are needed to assess if patients with a high risk VEGF genotype may benefit from therapies that promote angiogenesis.