Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure class-III agent, nifekalant hydrochloride

Junko Ohashi, Satoshi Yasuda, Shunichi Miyazaki, Wataru Shimizu, Isao Morii, Takashi Kurita, Atsushi Kawamura, Shiro Kamakura, Hiroshi Nonogi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the Kchannel without inhibiting β-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/ fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 ± 17 (mean ± SD) years] at a dose of 0.19 ± 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 ± 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% ± 15% versus 5% ± 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% ± 49% versus 37% ± 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.

Original languageEnglish
Pages (from-to)274-279
Number of pages6
JournalJournal of cardiovascular pharmacology
Volume48
Issue number6
DOIs
Publication statusPublished - 2006 Dec

Keywords

  • Antiarrhythmia agents
  • Electrocardiography
  • Potassium
  • Tachyarrhythmia
  • Torsade de pointes

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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