Differences in Corrected QT Intervals at Minimal and Maximal Heart Rate May Identify Patients at Risk for Torsades de Pointes During Treatment with Antiarrhythmic Drugs

The mechanism of torsades de pointes as a proarrhythmic response to antiarrhythmic drugs is not clear. We hypothesized that the difference in the corrected QT interval (QTc, Bazett's formula) with varying autonomic tone and heart rate during 24-hour ambulatory ECG would help identify patients at risk. Ten patients with antiarrhythmic drug-induced torsades de pointes were compared with 28 controls. The QTc at maximal and minimal heart rate during antiarrhythmic drug-free ambulatory ECGs were measured. The mean QTc at minimal heart rates for patients was 0.413 +/- 0.102 seconds and 0.420 +/- 0.072 seconds and for controls (P = 0.715). The mean QTc at maximal heart rates for patients was 0.555 +/- 0.022 seconds and for controls was 0.439 +/- 0.011 seconds (P = 0.001). Mean QTc between minimal and maximal heart rates were significantly different for patients (P = 0.015) but were not for controls (P = 0.151). Using an arbitrary QTc difference cutoff of 0.075 seconds, this approach identified patients at risk for antiarrhythmic drug-induced torsades de pointes with a sensitivity of 70% (7 of 10) and a specificity of 89% (P < or = 0.003 by Chi-square analysis with Yates' correction). In conclusion, patients with antiarrhythmic drug-induced torsades de pointes had a greater rise in QTc from minimal to maximal heart rate during ambulatory ECG than controls. Further larger prospective trials will be required to establish the value of this approach to identify patients at risk for this type of proarrhythmia.