title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Ist Department of Medicine-Cardiology, University Medical Centre Mannheim, Mannheim, Germany. rainer.schimpf@umm.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Schimpf
authors.forename: Christian
authors.initials: C
authors.lastname: Veltmann
authors.forename: Theano
authors.initials: T
authors.lastname: Papavassiliu
authors.forename: Boris
authors.initials: B
authors.lastname: Rudic
authors.forename: Turgay
authors.initials: T
authors.lastname: Göksu
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kuschyk
authors.forename: Christian
authors.initials: C
authors.lastname: Wolpert
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
authors.forename: Alois
authors.initials: A
authors.lastname: Ebner
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy*; D065768:Lennox Gastaut Syndrome; D008297:Male; D008875:Middle Aged; D013036:Spasms, Infantile / Q000188:drug therapy*; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide