Baseline values and sotalol-induced changes of ventricular repolarization duration, heterogeneity, and instability in patients with a history of drug-induced torsades de pointes

J Clin Pharmacol. 2009 Jan;49(1):6-16. doi: 10.1177/0091270008325927. Epub 2008 Oct 28.


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 (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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Arrhythmia Agents / adverse effects*
  • Electrocardiography
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sotalol / adverse effects*
  • Torsades de Pointes / chemically induced
  • Torsades de Pointes / physiopathology*
  • Ventricular Dysfunction / chemically induced
  • Ventricular Dysfunction / physiopathology*


  • Anti-Arrhythmia Agents
  • Sotalol