Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

Drug-induced triangulation of the cardiac action potential is associated with increased risk of arrhythmic events. It has been suggested that triangulation causes a flattening of the electrocardiographic T-wave but the relationship between triangulation, T-wave flattening and onset of arrhythmia has not been studied in detail. In this paper, we have analyzed the simultaneous recordings of 10-lead electrocardiograms and monophasic action potentials (MAP) from the left ventricle of five dogs that were given supratherapeutic doses of the IKr inhibitor sertindole. All dogs developed Torsades de Pointes (TdP) arrhythmia. We show that MAP triangulation measured as the duration between 30% and 90% repolarization causes flattening of the electrocardiographic T-wave. Triangulation and flattening attain maximum values just before the onset ofTdP. A quantitative measurement of electrocardiographic flatness could present new opportunities in drug trials as a means to distinguish between safe and unsafe drugs.