Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy

Abstract

Background: The aim of this study was to estimate the independent and incremental prognostic value of the presence of stimulating autoantibodies directed against the human beta1-adrenergic receptor (anti-beta1-AR) in patients with chronic heart failure.

Methods: One hundred five antibody-typed chronic heart failure patients with dilated cardiomyopathy (DCM, n = 65) or ischemic cardiomyopathy (ICM, n = 40) were prospectively followed for 10.7 +/- 2.5 years. Information on all-cause and cardiovascular mortality was collected throughout the observation period.

Results: Stimulating anti-beta1-AR were prevalent in 26% (17/65) of patients with DCM and 13% (5/40) with ICM. All-cause mortality in antibody-positive patients was 65% in those with DCM and 80% in those with ICM, and in antibody-negative patients 44% and 49%, respectively. In univariate and multivariable Cox regression analysis (P < .05), presence of stimulating anti-beta1-AR was associated with increased all-cause and cardiovascular mortality risk in DCM but not in ICM. Information on antibody status improved the prognostic capacity in models containing already extensive information on clinical profile, Holter electrocardiography, and invasive hemodynamic measurements (area under the receiver operating characteristic curve, 0.91; 95% confidence interval, 0.85-0.97; P < .05 for increase in receiver operating characteristic area).

Conclusion: The presence of stimulating anti-beta1-AR autoantibodies independently predicts increased all-cause and cardiovascular mortality risk in DCM conferring incremental prognostic value in addition to established risk predictors. Our data indicate a clinical relevance of stimulating anti-beta1-AR in DCM and encourage further research into antibody-directed strategies as a therapeutic principle.