Repolarization effects of sertindole manifest as T-wave flatness on the ECG

Flattening of the electrocardiographic T-wave has been associated with proarrhythmic risk. It has also been demonstrated that triangulation of the monophasic action potential (MAP) manifests on the ECG as a flattened T-wave. In this study we investigate the effects of sertindole on the electrocardiographic T-wave using a recently developed ECG marker of T-wave flatness which is directly correlated with sertindole-induced triangulation of the MAP prior to Torsade de Pointes arrhythmia in dogs. The effect of sertindole on T-wave flatness was compared with the effects of moxifloxacin and placebo on the T-wave. Sertindole caused more flattening of the T-wave compared to moxifloxacin and placebo. Effect sizes also revealed that flattening of the T-wave after sertindole was a more prominent finding compared to QT interval prolongation. An electrocardiographic measurement linking MAP triangulation and T-wave flatness could potentially used for cardiac safety assessment in drug trials along with other safety measures.