Abstract 17289: Hypoxia-Inducible Factor Gene Polymorphisms and Right Ventricular Adaptation in Children After Tetralogy of Fallot Repair
Chronic pulmonary insufficiency (PI) after tetralogy of Fallot (TOF) repair results in right ventricular (RV) dilation, RV dysfunction and arrhythmias. Hypoxia and mechanical stress increase hypoxia-inducible factor (HIF1α) which can promote fibrosis. We investigated the influence of single nucleotide polymorphisms (SNPs) associated with HIF1α downregulation on RV adaptation after TOF repair.
Methods:180 subjects with TOF <18 years of age were prospectively enrolled, and genotyped for 3 SNPs in HIF1α - 145C/T, 1326C/T, 1744C/T. Echocardiographic data were analyzed in a subset of 115 patients that were at least 5 years post TOF repair and included the severity of tricuspid (TR) and pulmonary insufficiency (PI), right ventricular size i.e RV outflow tract (RVOT) z-score, tricuspid valve (TV) z-score, and RV fractional area change (FAC). Linear and logistic regression models were used to test for associations between genotypes, RV size and function and freedom from interventions for RV dilation including pulmonary valve replacement (PVR). Analysis was adjusted for age, time since repair, and race.
Results: Mean age at repair was 1.02±0.8 years, mean age at echo was 9.01±3.5 yrs. 82% had moderate-severe PI, and 57% had moderate TR. Mean RVOT z-score was 3.0±1.6, TV z-score was −0.57±1.5, and FAC was 0.38±0.08%. Freedom from any RV dilation re-intervention at 5, 10 and 15 years was 92%, 84% and 67% respectively. 81% patients had at least 1 homozygous HIF1α genotype. All homozygous HIF1α genotypes were associated with a lower RVOT z-score (p≤0.01) with a significant correlation of a higher number of HIF1αgenotypeswith smaller RVOT z-scores (EST: −0.30z, p=0.001) and milder degree of PI (Odds ratio: 0.91, p=0.07). A higher number of HIF1α genotypes were also associated with a lower hazard of re-interventions for RV dilation (HR: 0.78, p=0.03).
Conclusion: The protective effect of HIF1α SNPs on RV dilation and need for re-intervention supports the beneficial effects of HIF1α downregulation on the volume-overloaded RV post TOF repair. The knowledge of the HIF1α genotype may help in early risk stratification and identifying patients at higher risk for progressive RV dilation that may benefit from early re-intervention.
- © 2010 by American Heart Association, Inc.