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Baseline Values and Sotalol-Induced Changes of Ventricular Repolarization Duration, Heterogeneity, and Instability in Patients With a History of Drug-Induced Torsades de Pointes

From the Heart Research Follow-Up Program, Cardiology Department, University of Rochester Medical Center, Rochester, New York (Dr Couderc, Mr McNitt, Mr Xia, Mr Polonsky, Dr Zareba); Ludwig-Maximilians-University, Munich, Klinikum Grosshadern, Department of Medicine 1, Munich, Germany (Dr Kaab, Dr Hinterseer, Dr Beckmann); and iCardiac Technologies Inc, Rochester, New York (Dr Fossa).

The authors investigated whether computerized parameters quantifying ventricular repolarization delay, heterogeneity, and instability characterize individuals who developed drug-induced Torsades de Pointes. Assessing an individual's 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 (ERD_30%: 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; LRD_70%: 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.

Key Words: QT interval • Torsades de Pointes • electrocardiogram • sotalol

Address for reprints: Jean-Philippe Couderc, PhD, MBA, Box 653, Heart Research Follow-Up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY 14642; e-mail: jean-philippe.couderc{at}heart.rochester.edu.

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				J.-P. Couderc Measurement and regulation of cardiac ventricular repolarization: from the QT interval to repolarization morphology Phil Trans R Soc A, April 13, 2009; 367(1892): 1283 - 1299. [Abstract] [Full Text] [PDF]