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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / metabolism*
  • Base Sequence
  • Cardiomyopathy, Dilated / complications*
  • Child
  • DNA Primers / genetics
  • Echocardiography
  • Gene Frequency
  • Genotype
  • Heart Failure / etiology
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Heart Failure / pathology*
  • Hemodynamics / genetics
  • Hemodynamics / physiology*
  • Humans
  • Kaplan-Meier Estimate
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Adrenergic / genetics*
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-2 / genetics
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics
  • Stroke Volume
  • Survival Rate
  • Vascular Resistance
  • Ventricular Pressure

Substances

  • ADRA2C protein, human
  • ADRB1 protein, human
  • ADRB2 protein, human
  • Adrenergic beta-Antagonists
  • DNA Primers
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha-2
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2