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CLINICAL STUDY: CARDIOMYOPATHY

Autoantibodies against the second extracellular loop of beta₁-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy

^a Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

Manuscript received February 4, 2000; revised manuscript received August 12, 2000, accepted October 2, 2000.

Reprint requests and correspondence: Dr. Tsutomu Yoshikawa, Cardiology Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
tyoshi{at}mc.med.keio.ac.jp

OBJECTIVES

We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta₁-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC).

BACKGROUND

Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta₁-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder.

METHODS

Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta₁-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis.

RESULTS

Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low 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 <30% (p = 0.001).

CONCLUSIONS

Autoantibodies directed against the second extracellular loop of beta₁-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC.

Abbreviations and Acronyms   AR = adrenergic receptor   cAMP = cyclic adenosine monophosphate   ECG = electrocardiogram   ELISA = enzyme-linked immunosorbent assay   IDC = idiopathic dilated cardiomyopathy   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   PBS = phosphate-buffered saline   SVPC = supraventricular premature contractions   VPC = ventricular premature contractions   VT = ventricular tachycardia

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