©© 2008 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270008325927
Baseline Values and Sotalol-Induced Changes of Ventricular Repolarization Duration, Heterogeneity, and Instability in Patients With a History of Drug-Induced Torsades de Pointes
Jean-Philippe Couderc 1*,
Stefan Kaab 2,
Martin Hinterseer 2,
Scott McNitt 1,
Xiaojuan Xia 1,
Anthony Fossa 3,
Britt M. Beckmann 2,
Slava Polonsky 1,
and
Wojciech Zareba 1
1 University of Rochester
2 Ludwig-Maximilians-University
3 iCardiac Technologies Inc
* To whom correspondence should be addressed. E-mail: heartjpc{at}heart.rochester.edu.
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Abstract |
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The authors investigated whether computerized parameters quantifying ventricular repolarization delay, heterogeneity, and instability characterize individuals who developed drug-induced Torsades de Pointes. Assessing an individuals propensity to Torsades de Pointes when exposed to a QT-prolonging drug is challenging because baseline QT prolongation has limited predictive value. Five-minute digital 12-lead electrocardiograms were acquired at baseline and after a sotalol challenge in 16 patients who had a history of Torsades de Pointes in the context of a QT-prolonging drug and 17 patients who did not have such history. Computerized measurements of QTc, T peak to T end intervals (TpTe), TpTe/QTc, and QT variability were implemented, and novel quantifiers of ventricular repolarization heterogeneity from the early (ERD) and late (LRD) part of the T wave were investigated. Compared with electrocardiograms of patients without a history of Torsades de Pointes, the baseline electrocardiograms of patients with a history of Torsades de Pointes had a longer QTc and an increased repolarization heterogeneity of the early part of the T wave (ERD30%: 44 ± 13 vs 35 ± 8 ms, P = .02). On sotalol, the electrocardiograms from individuals with Torsades de Pointes revealed a delay of the terminal part of the T wave that was not present in patients without Torsades de Pointes (TpTe: 27 ± 40 vs –2 ± 21 ms, P = .02; LRD70%: 20 ± 29 vs 2 ± 4 ms, P = .04). Results suggest that the electrocardiogram abnormalities characterizing patients with a history of Torsades de Pointes are (1) an increased repolarization heterogeneity at baseline and (2) a sotalol-induced prolongation of the terminal part of the T wave.