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

作者：Reddy Sushma; Fung Alan; Manlhiot Cedric; Tierney Elif Seda Selamet; Chung Wendy K; Blume Elizabeth; Kaufman Beth D; Goldmuntz Elizabeth; Colan Steven; Mital Seema^*

来源：Pediatric Research, 2015, 77(2): 363-369.

DOI：10.1038/pr.2014.183

BACKGROUND: Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and beta-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).
METHODS: Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: a2cdel322-325, beta 1Arg389, and beta 2Arg16. Data were analyzed by genotype and beta-blocker use. Mean age at enrollment was 8.5 y.
RESULTS: 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 beta-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving beta-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving beta-blockers (interaction P < 0.05).
CONCLUSION: 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 beta-blocker therapy before progression to decompensated HF.

• 出版日期2015-2