Abstract 18177: High Risk Angiogenic Genes Are Associated With Abnormal Cardiac Mechanics In Children With Hypertrophic Cardiomyopathy
Introduction: We previously reported diastolic dysfunction in children with hypertrophic cardiomyopathy (HCM) associated with high risk (HR) alleles in angiogenic genes (VEGF, HIF1α, TP53). This study aimed at investigating myocardial deformation and relaxation in patients with HR and low risk (LR) genotypes.
Methods: Subjects with HCM (<21yrs) were prospectively enrolled (2007–2010) and genotyped for VEGF (2578A/C); (1154A/G), (634C/G), HIF1α (145C/T); (1326C/T), TP53 (97–29 C/A); (Arg72ProC/G) polymorphisms. Presence of an allele associated with downregulation of angiogenic genes was defined as HR genotype. Systolic longitudinal, circumferential, and radial strain and systolic and diastolic strain rate at each myocardial segment were measured by 2D speckle tracking (EchoPac, GE). HR and LR genotypes were compared by Student's t-test.
Results: Fourteen HCM subjects (mean age 6yrs (range 1–15), 79% male, 79% Caucasian) were enrolled. Frequency of HR alleles A, A, T in VEGF were 64%, 50%, 36%, HIF1α (T, C; 71%, 79%) and TP53 (G, C; 64%, 64%) respectively. Septal and posterior wall thickness was similar between LR and HR except for thicker septum in HR VEGF (1154A/G) (p=0.03) and posterior wall in HR HIF1α (1326C/T) (p=0.08). In HR genotypes, both systolic circumferential strain and systolic (s) and diastolic (d) circumferential strain rate were significantly decreased in multiple segments, predominantly at the basal and apical levels : anteroseptal (VEGF1154A/G: 2.5±0.9 1/s vs. 1.5±0.6 1/s, p=0.04; TP53 Arg72ProC/G: 27±4% vs. 17±6%, p<0.001) anterior (VEGF1154A/G: 24±6% vs. 15±5%, p=0.02; (s) 1.9±0.71 1/s vs. 1±0.4 1/s, p=0.04; VEGF634C/G: (d) −2±0.8 1/s vs. −0.8±0.4 1/s, p<0.001) segments. HR genotypes had decreased longitudinal diastolic strain rate at the basal septum (VEGF634C/G: −1.4±0.5 1/s vs. −0.5±0.3 1/s, p<0.001), midseptum (VEGF634C/G: −1.3±0.7 1/s vs. −0.3±0.2 1/s, p<0.001) and basolateral (HIF1α145C/T −1.7±0.5 1/s vs. −1±0.4 1/s, p=0.03) segments, and decreased MV global radial peak systolic strain (VEGF1154A/G: 46±10% vs. 30±11%, p=0.02; HIF1α145C/T: 50±10% vs. 33±11%, p=0.04).
Conclusions: HR alleles that downregulate angiogenic genes are associated with adverse cardiac mechanics in children with HCM.
- © 2010 by American Heart Association, Inc.