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.

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.

Keywords: IgG3; autoantibody; recent-onset cardiomyopathy; β-blocker.