title: Presence of autoantibody directed against β1-adrenergic receptors is associated with amelioration of cardiac function in response to carvedilol: Japanese Chronic Heart Failure (J-CHF) Study.
abstract: BACKGROUND
  Autoantibody against β1-adrenergic receptors (β1-AAb) exerts agonist-like action inducing receptor uncoupling and myocardial damage. We attempted to determine the significance of β1-AAb in chronic heart failure (CHF) patients who received carvedilol in a substudy of the Japanese Chronic Heart Failure study.
  
  
  RESULTS
  In this prospective, randomized, multicenter trial, 117 patients were assigned to 2.5 mg, 5 mg, and 20 mg (n = 38, 36, and 43) carvedilol groups according to the target dose. β1-AAb was positive in 51 patients (44%, P) and negative in 66 (56%, N). The percentage increase of left ventricular ejection fraction over 56 weeks (ΔLVEF) was larger in P than in N (P = .050) and in the high-titer group (H) than in the low-titer group (L; P = .04). Left ventricular (LV) volume decreased to a greater extent in H than in L over 56 weeks. β1-AAb titer was significantly correlated with ΔLVEF and the percentage change of LV volume and was an independent predictor of them. No difference was seen in the composite end point (all-cause mortality and hospitalization for cardiovascular diseases or heart failure). However, in patients with dilated cardiomyopathy, it was more common in the 2.5 mg group than in the other groups in N, and it was similar among the 3 groups in P.
  
  
  CONCLUSIONS
  Our data suggest that the presence of β1-AAb is associated with favorable response to carvedilol in CHF.
authors.affiliation: Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagatomo
authors.affiliation: Department of Cardiology, Sakakibara Heart Institute, Fuchu, Japan. Electronic address: tyoshi@shi.heart.or.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Cardiovascular Medicine, National Hospital Organization, Hokkaido Medical Center, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1
chemical_list: D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D002227:Carbazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D000077261:Carvedilol
keywords: Autoimmunity; responder; reverse remodeling; β-blocker