Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide.

Abstract

BACKGROUND:

The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear.

OBJECTIVE:

Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies.

METHODS:

Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and T(peak)-T(end) intervals were analyzed before and during rufinamide treatment.

RESULTS:

The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). T(peak)-T(end) intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed.

CONCLUSION:

QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations notwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings.

• Authors: Rainer Schimpf, Christian Veltmann, Theano Papavassiliu, Boris Rudic, Turgay Göksu, Jürgen Kuschyk, Christian Wolpert, Charles Antzelevitch, Alois Ebner, Martin Borggrefe, Christian Brandt
• Journal: Heart rhythm (Heart Rhythm) Vol. 9 Issue 5 Pg. 776-81 (May 2012) ISSN: 1556-3871 [Electronic] United States
• PMID: 22245794 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticonvulsants
• Triazoles
• rufinamide

Topics

• Administration, Oral
• Adult
• Aged
• Anticonvulsants (adverse effects, therapeutic use)
• Arrhythmias, Cardiac (chemically induced)
• Death, Sudden, Cardiac (etiology)
• Electrocardiography
• Epilepsy (drug therapy)
• Female
• Follow-Up Studies
• Humans
• Intellectual Disability (drug therapy)
• Lennox Gastaut Syndrome
• Male
• Middle Aged
• Spasms, Infantile (drug therapy)
• Triazoles (adverse effects, therapeutic use)
• Young Adult