Discussion
The current study in 84 patients with drug-induced QT interval prolongation and Torsades de Pointes showed lower diagnostic interpretability and shorter measured QT intervals in the limb leads in comparison to chest leads due to flattened T-waves. To the best of our knowledge, this is the largest study in this patient population to date.
We found that the QT interval was not reliably interpretable due to too flat T-waves in 11.9% of the patients with diLQTS with subsequent TdP, if only the limb leads were used. In comparison, the T-wave morphology in the chest leads was never a reason for non-interpretability of the QT interval. Therefore, approximately one out of nine patients with diLQTS and TdP might have been missed if only limb leads were used. Moreover QT duration was measured shorter in the limb leads compared to the chest leads though there was a high variability in the differences. Our results point out a possible limitation of QT interval monitoring in diLQTS with limb leads only, as for example by mobile ECG devices.
Prior studies on QT interval interpretation with mobile devices have mainly focused on the measurement of the QT interval and not on T-wave morphology. Garabelli et al. showed good agreement of the QTc interval between two limb leads by a mobile device compared to a 12-lead ECG in 99 healthy volunteers and patients loaded with dofetilide or sotalol up to a QT duration of 500ms, but with decreasing agreement above 500ms.9 Castelletti et al. investigated 351 measurements in 20 LQTS patients and 16 controls and also found good overall agreement between a single lead mobile ECG device and a 12-lead ECG. However, the range of disagreement also increased with increasing QTc duration.8 Moreover, two other studies in 381 and 94 subjects without known QT interval prolongation, respectively, showed relevant discrepancies in the QT interval between single lead mobile ECG devices and 12-lead ECGs.13,14 Malone et al. furthermore reported that the QT interval was not measureable in 9% of their study subjects due to low T-wave amplitudes.10Our results expand the current knowledge and suggest, that the interpretability of the limb leads further decreases with even longer QT intervals in patients experiencing TdP.
For optimal patient selection for mobile ECG monitoring, a screening 12-lead ECG before treatment initation might already identify some patients with non-interpretable QT intervals in the limb leads. However, T-wave morphology might only change with increasing QT interval prolongation, which would not be recognizable in the screening ECG. Of note, no patient in the above mentioned studies on mobile ECG QT monitoring has experienced TdP, therefore their true prognostic utility in those patients is not known. A possible solution to limited interpretability of the QT interval in the limb leads generated by mobile ECG devices could be the placement of the devices in different chest positions in order to get chest lead-like cardiograms. However, this promising approach has only been tested in a small patient population so far.11
Strengths of our study include the systematic assessment of a large number of patients with diLQTS and TdP. Limitations include the retrospective nature of our analyses of prior published cases with possible publication bias. However, due to the overall low occurrence of TdP in diLQTS, a prospective study would be unfeasible due to a large amount of participants needed. Furthermore, our study did not include a control group.
In conclusion, our results point out the limits of QT interval measurement using only the limb leads in patients with diLQTS experiencing TdP due to different T-wave morphologies in the limb and chest leads. Patients with diLQTS and high risk for TdP should probably undergo limb and chest lead ECG screening.