title: Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.
abstract: BACKGROUND
  Pilsicainide, a pure Na+channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide.
  
  
  METHODS
  This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters.
  
  
  RESULTS
  Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1vs.68.4±22.1 mL/min,p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0,p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6vs.430.7±32.6 ms,p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments.
  
  
  CONCLUSIONS
  DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Fujino
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kitahara
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yuzawa
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Fukunaga
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Cardiovascular Medicine, Toho University, Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Kamata, Tokyo 143-8541, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
keywords: Pilsicainide; Proarrhythmia; QRS interval; QTc interval; Renal dysfunction