Journal
JOURNAL OF CARDIAC FAILURE
Volume 22, Issue 6, Pages 417-422Publisher
CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
DOI: 10.1016/j.cardfail.2016.03.005
Keywords
Autoantibody; IgG3; beta 1-adrenergic receptor; beta-blocker
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Funding
- National Institutes of Health [1R01HL103931]
- Cleveland Clinic Clinical Research Unit of the Case Western Reserve University CTSA [UL1TR 000439]
- Cleveland Clinic Research Programs Committee [2013-1059]
- Myocarditis Foundation [MYF1401MF]
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Objective: To elucidate the prevalence and role of beta(1) adrenergic receptor autoantibodies (beta(1)AR-AAb) belonging to the immunoglobulin (Ig)G3 subclass in patients with heart failure (HF) treated with beta-adrenergic blockers. Background: Several cardiac AAbs have been reported to be present in sera from patients with dilated cardiomyopathy and other etiologies. Among AAbs, those recognizing beta(1)AR-AAbs show agonist-like effects, have detrimental effects on cardiomyocytes, and may induce persistent myocardial damage. Methods: We quantify total IgG and IgG3 subclass beta(1)AR-AAb in subjects with chronic stable HF with long-term follow-up. Results: In our study cohort of 121 subjects, non-IgG3-beta(1)AR-AAb and IgG3-beta(1)AR-AAb were found to be positive in 20 (17%) and 26 patients (21%), respectively. The positive rate of IgG3-beta(1)AR-AAb was significantly higher for those with nonischemic compared with ischemic HF etiology (27% vs 8%, P = .01), but the positive rate for non-IgG3-beta(1)AR-AAb was similar between the 2 groups (18% vs 16%, respectively, P = NS). There were no significant differences in clinical and echocardiographic measures among total beta(1)AR-AAb negative, non-IgG3-beta(1)AR-AAb positive, and IgG3-beta(1)AR-AAb positive groups at baseline. During 2.2 +/- 1.2 years of follow-up, we observed similar rates of the composite endpoint of all-cause mortality, cardiac transplantation, or hospitalization resulting from HF between total IgG-beta(1)AR-AAb negative and positive patients. However, the composite endpoint events were significantly more common in the patients without than in those with IgG3-beta(1)AR-AAb (P = .048, log-rank test). Conclusions: Presence of IgG3-beta(1)AR-AAb, not total IgG, was associated with paradoxically more favorable outcomes in our cohort of patients with chronic systolic HF largely treated by beta-blockers.
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