Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study

• Published in: European heart journal 2008-01, Vol.29 (2), p.185-190
• Main Authors: Hinterseer, Martin, Thomsen, Morten B., Beckmann, Britt-Maria, Pfeufer, Arne, Schimpf, Rainer, Wichmann, H.-Erich, Steinbeck, Gerhard, Vos, Marc A., Kaab, Stefan
• Format: Article
• Language: English
• Subjects: Aged; Arrhythmias, Cardiac - etiology; Beat-to-beat Variability of repolarization; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Case-Control Studies; Disease Susceptibility; Drug induced Long QT Syndrome; Electrocardiography - drug effects; Female; Heart; Heart Rate - drug effects; Heart Rate - physiology; Humans; Long QT Syndrome - chemically induced; Male; Medical sciences; Middle Aged; Pilot Projects; Predictive Value of Tests; Proarrhythmia; Torsades de Pointes; Torsades de Pointes - chemically induced; Torsades de Pointes - physiopathology
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehm586

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 = Σ|QTn+1 − QTn|/[30 × √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.