Sensitivity of T-wave morphology and the QT interval to small drug-induced electrocardiographic changes

Abstract

The electrocardiographic QT interval is the only widely used surrogate marker of repolarization abnormality in drug trials. However, numerous basic and clinical studies have provided evidence that disturbed ventricular repolarization is reflected not only in the duration of the QT interval but also in the shape of the electrocardiographic T-wave. Thus, in order to elucidate the full spectrum of drug-induced repolarization changes, it is pertinent to perform a thorough analysis of T-wave morphology changes in addition to measuring the QT interval. We present a computerized method for quantification of drug-induced T-wave morphology changes. Our results provide evidence that the shape of the T-wave can be a more sensitive marker of disturbed repolarization than QT interval prolongation. Effect sizes for T-wave morphology changes, 1.58plusmn0.30 (meanplusmnSD) were 1.8 times larger than those for QTcF, 0.87plusmn0.14, p=0.0013.