A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure

Nagatomo, Yuji; Yoshikawa, Tsutomu; Kohno, Takashi; Yoshizawa, Akihiro; Baba, Akiyasu; Anzai, Toshihisa; Meguro, Tomomi; Satoh, Toru; Ogawa, Satoshi

doi:10.1016/j.cardfail.2008.10.027

« Previous Next »Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 224-232, April 2009

A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure

Yuji Nagatomo, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Tsutomu Yoshikawa, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
- Reprint requests: Tsutomu Yoshikawa, MD, Cardiology Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan.
Takashi Kohno, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Akihiro Yoshizawa, MD
- Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Japan
Akiyasu Baba, MD
- Kitasato Institute Hospital, Tokyo, Japan
Toshihisa Anzai, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Tomomi Meguro, MD
- Tokyo Electric Power Company Hospital, Tokyo, Japan
Toru Satoh, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Satoshi Ogawa, MD
- Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

Received 26 January 2008; received in revised form 21 October 2008; accepted 22 October 2008. published online 24 December 2008.

Abstract

Background

Autoantibodies directed against the β1-adrenergic receptor exert agonistlike actions by inducing receptor uncoupling and cause myocardial damage as well as fatal ventricular arrhythmias. Previous studies have shown that β-blockers can modulate these actions of the autoantibodies. We investigated the influence of such autoantibodies in patients with congestive heart failure (CHF) receiving β-blocker therapy.

Methods and Results

Eighty-two CHF patients were randomly assigned to treatment with metoprolol or carvedilol for 16 weeks. Autoantibodies were detected in 20 patients (24%) by enzyme-linked immunosorbent assay. Left ventricular function in response to β-blocker therapy did not differ significantly by the presence of the autoantibody in global analysis. However, changes of the left ventricular end-diastolic dimension (P = .04), end-systolic dimension (P < .01), and ejection fraction on radionuclide ventriculography (P = .02) were significantly larger in autoantibody-positive patients than antibody-negative patients. Changes in the plasma level of brain natriuretic peptide tended to be larger in autoantibody-positive patients (P = .09). The increase of heart rate normalized by the increase of plasma norepinephrine during exercise (an index of adrenergic responsiveness) showed a greater decrease in autoantibody-positive patients than autoantibody-negative patients (P = .035).