Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors

Yuji Nagatomo, Dennis M. McNamara, Jeffrey D. Alexis, Leslie T. Cooper, G. William Dec, Daniel F. Pauly, Richard Sheppard, Randall C. Starling, W. H.Wilson Tang, Karen Janosko, Charles McTiernan, Barry London, Karen Hanley-Yanez, John Gorcsan, Hidekazu Tanaka, Mathew Suffoletto, Cynthia Oblak, Annette McNallan, Lu Anne Koenig, Paul MatherNatalie Pierson, Sharon Rubin, Yanique Bell, Alicia Ervin, John Boehmer, Patricia Frey, Jeffrey Alexis, Janice Schrack, Pam LaDuke, Guillermo Torre-Amione, Jeannie Arredondo, Pamela C. Smith, Stephanie Fuoco, Ilan S. Wittstein, Elayne Breton, Vinay Thohan, Deborah Wesley, Diane Cocca-Spofford, David W. Markham, Lynn Fernandez, Colleen Debes, Mark J. Zucker, Laura Adams, Peter Liu, Judith Renton, Jagat Narula, Byron Allen, Elizabeth Westberg

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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. Objectives 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.

Original languageEnglish (US)
Pages (from-to)968-977
Number of pages10
JournalJournal of the American College of Cardiology
Volume69
Issue number8
DOIs
StatePublished - Feb 28 2017

Keywords

  • IgG3
  • autoantibody
  • recent-onset cardiomyopathy
  • β-blocker

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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