European Heart Journal Advance Access originally published online on December 22, 2007
European Heart Journal 2008 29(2):185-190; doi:10.1093/eurheartj/ehm586
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Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study
1 Department of Medicine I, Klinikum Grosshadern, Ludwig Maximilians University Munich, Marchioninistrasse 15, D-81366 Munich, Germany
2 Department of Medical Physiology, Heart Lung Centre Utrecht, Utrecht, The Netherlands
3 Institute of Human Genetics and Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany
4 Institute of Human Genetics, Technical University Munich, Munich, Germany
5 1st Department of Medicine, Cardiology, University Hospital of Mannheim, Mannheim, Germany
6 Institute of Epidemiology, GSF, National Research Center, Neuherberg, Germany
Received 5 April 2007; revised 13 November 2007; accepted 22 November 2007; online publish-ahead-of-print 22 December 2007.
*Corresponding author. Tel: +49 89 7095 2251, Fax: +49 89 7095 5251, Email: martin.hinterseer{at}med.uni-muenchen.de
Aims: Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT intervals. Here, we evaluate variability of QT intervals in patients with a history of drug-induced long QT syndrome (dLQTS) and TdP in absence of a mutation in any of the major LQTS genes.
Methods and results: Twenty patients with documented TdP under drugs with QT-prolonging potential were compared with 20 matched control individuals. An observer blinded to diagnosis manually measured lead-II, RR, and QT intervals from 30 consecutive beats. BVR was determined from Poincaré plots of QT intervals as short-term variability (STVQT = 
|QTn+1 – QTn|/[30 x 
2]). QRS interval and cycle length was comparable between study groups and controls. No difference was found in QTc between dLQTS and controls (428 ± 25 vs. 421 ± 34 ms, P = 0.26), whereas STVQT was significantly higher in dLQTS when compared with controls (8.1 ± 3.7 vs. 3.6 ± 1.3 ms, P = 0.001). Proarrhythmic predictive power of STVQT was superior to that of the QTc interval (AUC: 0.89 vs. 0.57, 95% CI: 0.79–0.99 vs. 0.39–0.75).
Conclusion: In the absence of QTc prolongation, baseline STVQT characterized patients with documented drug-induced proarrhythmia. STVQT could prove to be a useful non-invasive, easily obtainable parameter aiding the identification of the patient at risk for potentially life threatening arrhythmia in the context of drugs with QT prolonging potential.
Key Words: Torsades de Pointes • Drug induced Long QT Syndrome • Beat-to-beat Variability of repolarization • Proarrhythmia
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