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

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...

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Detalles Bibliográficos
Autores principales: Reddy, Sushma, Fung, Alan, Manlhiot, Cedric, Selamet Tierney, Elif Seda, Chung, Wendy K., Blume, Elizabeth, Kaufman, Beth D., Goldmuntz, Elizabeth, Colan, Steven, Mital, Seema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298011/
https://www.ncbi.nlm.nih.gov/pubmed/25406899
http://dx.doi.org/10.1038/pr.2014.183
Descripción
Sumario: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.