A robust method for quantification of IKr-related T-wave morphology abnormalities

The QTc interval plays an important role in premarket testing of new drugs, but the intrinsic variability of the measurement is critical. Most arrhythmogenic drugs inhibit the I_Kr current and cause both QTc prolongation and changes in T-wave morphology. Quantification of T-wave morphology may be useful in drug testing, but no robust method exists for this purpose. We present a method for quantification of I_Kr-related T-wave morphology changes: T-wave asymmetry, flatness and the presence of notches on the T-wave combined to an overall morphology combination score (MCS). In a population of 30 LQT2-subjects (congenital I_Kr inhibition) and 1096 healthy subjects, both QTcF and MCS yield clear separation between the groups (p<0.001), sensitivity 90%, specificity 95%.