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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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). Conclusion: Our data suggest that β-blocker therapy might be more effective in CHF patients with autoantibodies targeting the β1-adrenergic receptor.

Original languageEnglish
Pages (from-to)224-232
Number of pages9
JournalJournal of Cardiac Failure
Volume15
Issue number3
DOIs
Publication statusPublished - 2009 Apr

Fingerprint

Autoantibodies
Adrenergic Receptors
Heart Failure
Therapeutics
Radionuclide Ventriculography
Metoprolol
Brain Natriuretic Peptide
Left Ventricular Function
Adrenergic Agents
Cardiac Arrhythmias
Norepinephrine
Heart Rate
Enzyme-Linked Immunosorbent Assay
Exercise
Antibodies

Keywords

  • Autoantibody
  • carvedilol
  • dilated cardiomyopathy
  • metoprolol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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.

In: Journal of Cardiac Failure, Vol. 15, No. 3, 04.2009, p. 224-232.

Research output: Contribution to journalArticle

Nagatomo, Yuji ; Yoshikawa, Tsutomu ; Kohno, Takashi ; Yoshizawa, Akihiro ; Baba, Akiyasu ; Anzai, Toshihisa ; Meguro, Tomomi ; Satoh, Toru ; Ogawa, Satoshi. / A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure. In: Journal of Cardiac Failure. 2009 ; Vol. 15, No. 3. pp. 224-232.
@article{449605652c484e5baf744c7db86568db,
title = "A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure",
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). Conclusion: Our data suggest that β-blocker therapy might be more effective in CHF patients with autoantibodies targeting the β1-adrenergic receptor.",
keywords = "Autoantibody, carvedilol, dilated cardiomyopathy, metoprolol",
author = "Yuji Nagatomo and Tsutomu Yoshikawa and Takashi Kohno and Akihiro Yoshizawa and Akiyasu Baba and Toshihisa Anzai and Tomomi Meguro and Toru Satoh and Satoshi Ogawa",
year = "2009",
month = "4",
doi = "10.1016/j.cardfail.2008.10.027",
language = "English",
volume = "15",
pages = "224--232",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "3",

}

TY - JOUR

T1 - A Pilot Study on the Role of Autoantibody Targeting the β1-Adrenergic Receptor in the Response to β-blocker Therapy for Congestive Heart Failure

AU - Nagatomo, Yuji

AU - Yoshikawa, Tsutomu

AU - Kohno, Takashi

AU - Yoshizawa, Akihiro

AU - Baba, Akiyasu

AU - Anzai, Toshihisa

AU - Meguro, Tomomi

AU - Satoh, Toru

AU - Ogawa, Satoshi

PY - 2009/4

Y1 - 2009/4

N2 - 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). Conclusion: Our data suggest that β-blocker therapy might be more effective in CHF patients with autoantibodies targeting the β1-adrenergic receptor.

AB - 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). Conclusion: Our data suggest that β-blocker therapy might be more effective in CHF patients with autoantibodies targeting the β1-adrenergic receptor.

KW - Autoantibody

KW - carvedilol

KW - dilated cardiomyopathy

KW - metoprolol

UR - http://www.scopus.com/inward/record.url?scp=62649147901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62649147901&partnerID=8YFLogxK

U2 - 10.1016/j.cardfail.2008.10.027

DO - 10.1016/j.cardfail.2008.10.027

M3 - Article

C2 - 19327624

AN - SCOPUS:62649147901

VL - 15

SP - 224

EP - 232

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 3

ER -