title: Ibutilide-induced changes in the temporal lability of ventricular repolarization in patients with and without structural heart disease.
abstract: BACKGROUND
  Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease.
  
  
  METHODS
  Twenty-four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal.
  
  
  RESULTS
  Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 +/- 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: -7.4 +/- 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 +/- 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 +/- 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease.
  
  
  CONCLUSIONS
  Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.
authors.affiliation: Section for Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. alcheng@jhmi.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Fetics
authors.forename: Piamsook
authors.initials: P
authors.lastname: Angkeow
authors.forename: David D
authors.initials: DD
authors.lastname: Spragg
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use*; D013617:Tachycardia, Supraventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide