This work was supported by NIH grant P50 HL52307, and partially supported by the D.W. Reynolds Foundation to Drs. Tomaselli and Berger.
Ibutilide-Induced Changes in the Temporal Lability of Ventricular Repolarization in Patients with and without Structural Heart Disease
Article first published online: 30 APR 2009
© 2009 Wiley Periodicals, Inc.
Journal of Cardiovascular Electrophysiology
Volume 20, Issue 8, pages 873–879, August 2009
How to Cite
CHENG, A., DALAL, D., FETICS, B. J., ANGKEOW, P., SPRAGG, D. D., CALKINS, H., TOMASELLI, G. F. and BERGER, R. D. (2009), Ibutilide-Induced Changes in the Temporal Lability of Ventricular Repolarization in Patients with and without Structural Heart Disease. Journal of Cardiovascular Electrophysiology, 20: 873–879. doi: 10.1111/j.1540-8167.2009.01476.x
Dr. Berger holds a patent on technology for measurement of the QT variability index. Mr. Fetics is an employee of Robin Medical Inc., which has limited rights to this technology. Dr. Tomaselli is the Michel Mirowski Professor of Cardiology. All other authors have nothing to disclose.
- Issue published online: 28 JUL 2009
- Article first published online: 30 APR 2009
- Manuscript received 9 November 2008; Revised manuscript received 24 February 2009; Accepted for publication 25 February 2009.
- ventricular repolarization;
- monophasic action potential;
- QT interval;
- torsades de pointes
Introduction: 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.
Conclusion: 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.