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Pediatr Res. 2015 Feb;77(2):363-9. doi: 10.1038/pr.2014.183. Epub 2014 Nov 19.

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

Author information

1
Department of Pediatrics, Stanford University, Stanford, California.
2
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
3
Departments of Pediatrics and Medicine, Columbia University, New York, New York.
4
Department of Pediatrics, Children's Hospital Boston, Harvard University, Boston, Massachusetts.
5
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

BACKGROUND:

Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-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: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-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 β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-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 β-blocker therapy before progression to decompensated HF.

PMID:
25406899
PMCID:
PMC4298011
DOI:
10.1038/pr.2014.183
[Indexed for MEDLINE]
Free PMC Article

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