Ibutilide-induced changes in the temporal lability of ventricular repolarization in patients with and without structural heart disease.
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.
Cheng
Alan
A
Section for Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. alcheng@jhmi.edu
Dalal
Darshan
D
Fetics
Barry J
BJ
Angkeow
Piamsook
P
Spragg
David D
DD
Calkins
Hugh
H
Tomaselli
Gordon F
GF
Berger
Ronald D
RD
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
D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide