T-wave morphology as a covariate in drug-induced QTc prolongation

QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a role in differentiating between safe and unsafe drugs. We used moxifloxacin and d,l-sotalol to investigate whether concurrent changes for QTc and T-wave morphology could be used to describe the discrepancy in proarrhythmic risk between the two drugs. Our results provide evidence that these drugs have significantly different morphology-duration profiles at similar QTc prolongations. We propose to investigate whether concurrent assessment of QTc and T-wave morphology has general validity for drug safety evaluation.