title: Beta-blocker decreases the increase in QT dispersion and transmural dispersion of repolarization induced by bepridil.
abstract: Bepridil is effective for intractable cardiac arrhythmia, but in rare cases will induce torsades de pointes (TdP) associated with QT interval prolongation. Beta-blockers will effectively prevent TdP in some clinical settings, so the effect of beta-blocker on the change in QT interval, QT dispersion and transmural dispersion of repolarization (TDR) induced by bepridil was investigated in 10 patients (7 male, 3 female; 62+/-6 years old) with intractable paroxysmal atrial fibrillation. The QTc interval, QTc dispersion and TDR were measured before and after 1 month of administration of bepridil, and then a beta-blocker was added and the QTc interval, QTc dispersion and TDR re-measured 1 month later. Bepridil significantly prolonged the QTc interval (0.42+/-0.05 to 0.50+/-0.08; p<0.01), and increased both the QT dispersion (0.07+/-0.05 to 0.14+/-0.08; p<0.01) and TDR (0.10+/-0.04 to 0.16+/-0.05; p<0.01). The addition of a beta-blocker decreased the QTc interval (0.50+/-0.08 to 0.47+/-0.04; p=0.09) and significantly decreased both the QTc dispersion (0.14 +/-0.08 to 0.06+/-0.02; p<0.01) and TDR (0.16+/-0.05 to 0.11+/-0.04; p<0.001). Compared with the control, the combination therapy significantly prolonged the QTc interval, but did not increase either QTc dispersion or TDR, and so was effective in all patients with intractable AF. The findings suggest that beta-blocker reduces the increase in QT dispersion and TDR induced by bepridil, and combined therapy with bepridil and beta-blocker might thus be useful for intractable atrial fibrillation.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical Bioregulation, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshiga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimizu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamagata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hayano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueyama
authors.forename: Masato
authors.initials: M
authors.lastname: Ohmura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Itagaki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kimura
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy; D015764:Bepridil / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D017298:Bisoprolol / Q000008:administration & dosage / Q000494:pharmacology; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D015764:Bepridil; D008790:Metoprolol; D017298:Bisoprolol