title: Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Sushma
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Fung
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Elif Seda Selamet
authors.initials: ES
authors.lastname: Tierney
authors.affiliation: Departments of Pediatrics and Medicine, Columbia University, New York, New York.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Children's Hospital Boston, Harvard University, Boston, Massachusetts.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blume
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kaufman
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
authors.affiliation: Department of Pediatrics, Children's Hospital Boston, Harvard University, Boston, Massachusetts.
authors.forename: Steven
authors.initials: S
authors.lastname: Colan
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D002648:Child; D017931:DNA Primers / Q000235:genetics; D004452:Echocardiography; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006439:Hemodynamics / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011941:Receptors, Adrenergic / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D013318:Stroke Volume; D015996:Survival Rate; D014655:Vascular Resistance; D017725:Ventricular Pressure
chemical_list: C547774:ADRA2C protein, human; C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D000319:Adrenergic beta-Antagonists; D017931:DNA Primers; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2