title: Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy.
abstract: OBJECTIVE
  We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta1-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC).
  
  
  BACKGROUND
  Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta1-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder.
  
  
  METHODS
  Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta1-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis.
  
  
  RESULTS
  Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <30% (p = 0.001).
  
  
  CONCLUSIONS
  Autoantibodies directed against the second extracellular loop of beta1-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC.
authors.affiliation: Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: A
authors.initials: A
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Anzai
authors.forename: H
authors.initials: H
authors.lastname: Mitamura
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology / Q000276:immunology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005109:Extracellular Matrix / Q000276:immunology; D005260:Female; D006352:Heart Ventricles / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D017180:Tachycardia, Ventricular / Q000276:immunology* / Q000401:mortality
chemical_list: D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1