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.