QT Prolongation Is a Poor Predictor of Proarrhythmia Liability: Beyond QT Prolongation!

Abstract

Prolongation of the APD, as reflected by QT prolongation in the ECG, was introduced as a major antiarrhythmic mechanism [1, 2], but soon QT prolongation became instead a liability [3,4]. QT prolongation even graduated to a surrogate [5] for Torsade de Pointes (TdP): what a paradox! It is then not surprising that QT prolonging drugs range from potently torsadogenic to antiarrhythmic agents [6]. Thus, QT interval alone can clearly not satisfactorily identify anti-and proarrhythmic actions.In this chapter, cardiac wavelength (l) and TRIaD (Triangulation, Reverse use dependence, Instability and Dispersion) are described with respect to proarrhythmia. The QT paradox is resolved: it is emphasized that QT prolongation by itself (i.e., in the absence of disturbances of l-TRIaD) can be antiarrhythmic. In contrast, QT prolongation alone (i.e., without consideration of l-TRIaD) yields false positives (depriving patients from valuable drugs) and false negatives (exposing patients to preventable risks). ProarrhythmiaArrhythmias can result from disturbances in automaticity, disturbances of conduction, disturbances of repolarization and mechanical disturbances. The present chapter will be limited to disturbances of conduction and repolarization (which does not mean that the others cannot also contribute) and focus upon TdP and VF.