Adrenergic receptor genotype influences heart failure severity and ?-blocker response in children with dilated cardiomyopathy.

ABSTRACT: Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and ?-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: ?2cdel322-325, ?1Arg389, and ?2Arg16. Data were analyzed by genotype and ?-blocker use. Mean age at enrollment was 8.5 y.One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While ?-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving ?-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving ?-blockers (interaction P < 0.05).Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of ?-blocker therapy before progression to decompensated HF.

SUBMITTER: Reddy S 

PROVIDER: S-EPMC4298011 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature