Figure 8.

Applying Coumel's triangle of arrhythmogenesis to the actions of dofetilide. To develop life-threatening arrhythmia such as TdP, this agent would require (i) an electrophysiological substrate, that is APD prolongation and APD_i; (ii) a primary trigger factor, that is enhancement of HR HF oscillations; and (iii) a modulator factor, the ANS which modulates both APD and endogenous HF oscillations. The combination of these three ingredients leads to increasing of ventricular repolarization STV (STVQT), so creating favourable conditions for expression of cellular triggering factors such as re-entries or early after depolarizations. In the context of these drug-induced arrhythmias, STVQT is a biomarker of the arrhythmic threshold above which probability for arrhythmia occurrence is high. PVB, premature ventricular beats.