Abstract 12111: Adrenergic Receptor Genotype is Associated with Ventricular Dysfunction and β-Blocker Response in Children with Dilated Cardiomyopathy
Adrenergic receptor (ADR) genotype predicts response to β-blocker (BB) therapy in adult heart failure (HF). We investigated if ADR genotypes are associated with ventricular function and BB response in children with dilated cardiomyopathy (DCM).
Methods: In a multicenter prospective study, pediatric patients with DCM were genotyped for 3 ADR variants previously associated with adult HF - α2cdel322-325, β1Arg389, and β2Arg16 as part of an NHLBI Pediatric Heart Network study. We analyzed association between genotypes, change in LV function and interaction with BB.
Results: In 131 genotyped patients, median age at diagnosis was 1.6 yrs, median follow-up, 7.6 yrs (51% male; 68% White; 78% idiopathic DCM). In the subset with serial echocardiograms (n=35), age at enrollment echo was 5.6 yrs and follow-up echo was 1.7±0.6 years. Baseline: LV end-diastolic volume z was 5.4±4.6, LV end-systolic volume (ESVz), 4.9±2.4 ml, and LV ejection fraction (EF), 40±11%; 66% were on BB at the time of echocardiography. Risk allele frequency was α2c, 11%, β1, 28% and β2, 38%. Genotype-associations: α2c risk genotype was associated with an increase in ESVz and decrease in EFz from baseline to last follow-up. This progression was not seen in patients on BB (see Table 1). β1 risk genotype was also associated with a decline in EFz which was not seen in patients on BB. Overall, a greater number of risk alleles in all 3 genes was associated with a decline in EFz of 1.36 for every additional risk allele; this was prevented with BB.
Conclusions: High-risk ADR genotypes are associated with worsening ventricular function in pediatric DCM. Pharmacogenetic analysis revealed that BB use was associated with ventricular function preservation in patients with the α2c or β1 risk genotypes. Knowledge of ADR genotype may identify patients at greatest risk of disease progression that may benefit from BB therapy.
- © 2011 by American Heart Association, Inc.