title: Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors.
abstract: BACKGROUND
  Among various cardiac autoantibodies (AAbs), those recognizing the β1-adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption.
  
  
  OBJECTIVE
  The goal of this study was to investigate the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy.
  
  
  METHODS
  Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months.
  
  
  RESULTS
  Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint.
  
  
  CONCLUSIONS
  IgG3-β1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Sakakibara Heart Institute, Fuchu, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagatomo
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
authors.affiliation: University of Rochester Medical Center School of Medicine and Dentistry, Rochester, New York.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Alexis
authors.affiliation: Mayo Clinic Florida, Jacksonville, Florida.
authors.forename: Leslie T
authors.initials: LT
authors.lastname: Cooper
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: G William
authors.initials: GW
authors.lastname: Dec
authors.affiliation: Truman Medical Centers, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.affiliation: Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Sheppard
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D020127:Recovery of Function; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1
keywords: IgG3; autoantibody; recent-onset cardiomyopathy; β-blocker