title: Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations.
abstract: BACKGROUND
  Andersen-Tawil syndrome (ATS) is an autosomal dominant genetic or sporadic disorder characterized by ventricular arrhythmias (VAs), periodic paralyses, and dysmorphic features. The optimal pharmacological treatment of VAs in patients with ATS remains unknown.
  
  
  OBJECTIVE
  We evaluated the efficacy and safety of flecainide for VAs in patients with ATS with KCNJ2 mutations.
  
  
  METHODS
  Ten ATS probands (7 females; mean age 27 ± 11 years) were enrolled from 6 institutions. All of them had bidirectional VAs in spite of treatment with β-blockers (n = 6), but none of them had either aborted cardiac arrest or family history of sudden cardiac death. Twenty-four-hour Holter recording and treadmill exercise test (TMT) were performed before (baseline) and after oral flecainide therapy (150 ± 46 mg/d).
  
  
  RESULTS
  Twenty-four-hour Holter recordings demonstrated that oral flecainide treatment significantly reduced the total number of VAs (from 38,407 ± 19,956 to 11,196 ± 14,773 per day; P = .003) and the number of the longest ventricular salvos (23 ± 19 to 5 ± 5; P = .01). At baseline, TMT induced nonsustained ventricular tachycardia (n = 7) or couplets of premature ventricular complex (n = 2); treatment with flecainide completely (n = 7) or partially (n = 2) suppressed these exercise-induced VAs (P = .008). In contrast, the QRS duration, QT interval, and U-wave amplitude of the electrocardiogram were not altered by flecainide therapy. During a mean follow-up of 23 ± 11 months, no patients developed syncope or cardiac arrest after oral flecainide treatment.
  
  
  CONCLUSIONS
  This multicenter study suggests that oral flecainide therapy is an effective and safe means of suppressing VAs in patients with ATS with KCNJ2 mutations, though the U-wave amplitude remained unchanged by flecainide.
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan. Electronic address: aiba@hsp.ncvc.go.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Cardiology, Omura Municipal Hospital, Omura, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Yasuoka
authors.affiliation: Department of Cardiology, Omura Municipal Hospital, Omura, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tanioka
authors.affiliation: EP Expert Doctors-Team Tsuchiya, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Pediatric Electrophysiology, Osaka City General Hospital, Osaka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Tsuboi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Ikutaro
authors.initials: I
authors.lastname: Nakajima
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kusano
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan. Electronic address: wshimizu@nms.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D050030:Andersen Syndrome / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D015716:Electrocardiography, Ambulatory; D005424:Flecainide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006323:Heart Arrest / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D013575:Syncope / Q000453:epidemiology / Q000517:prevention & control; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016896:Treatment Outcome; D018879:Ventricular Premature Complexes / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents; C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D005424:Flecainide
keywords: Andersen-Tawil syndrome; Flecainide; Long QT; Mutation; Ventricular arrhythmia