Autoantibodies against the second extracellular loop of beta(1)-adrenergicreceptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy

Objectives We sought to define the clinical and long-term prognostic implic ations of autoantibodies that act against the second extracellular loop of beta(1)-adrenergic receptors (ARs) in patients with idiopathic dilated card iomyopathy (IDC). Background Although autoantibodies directed against various domains of beta -ARs are found in patients with IDC, only a subgroup against the second ext racellular domain of beta(1)-ARs exerts intrinsic sympathomimetic-like acti ons on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of LDC and may affect long-term prognosis of patients with this disorder. Methods Sera from 104 patients with IDC were screened for autoantibodies th at act against the second extracellular loop of beta(1)-ARs by enzyme-linke d immunosorbent assay, using a synthetic peptide corresponding to the domai n. Relations of the autoantibodies to clinical variables and long-term prog nosis were assessed by multivariate analysis. Results Autoantibodies were detected in 40 patients (38%). Multifocal ventr icular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in antibody-negativ e patients, although no differences in cardiac function or neurohormonal le vels were demonstrated. The presence of autoantibodies (p = 0.001) and a lo w left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <300% (p = 0.001). Conclusions Autoantibodies directed against the second extracellular loop o f beta(1)-ARs were closely related to serious ventricular arrhythmias in pa tients with LDC, and the presence of autoantibodies independent predicted s udden death. These autoantibodies may contribute to electrical instability in patients with IDC. (C) 2001 by the American College of Cardiology.