Mechanisms underlying the spontaneous termination of torsades de pointes in an experimental model of long QT syndrome

Abstract

Background: Torsades de pointes (TdP) represent a complex polymorphic ventricular tachycardia. While the triggering mechanisms of early afterdepolarization and increased dispersion of repolarization are well investigated, the sudden self-limiting termination remains poorly understood.

Objective: The purpose of this study was to perform analysis of TdP to investigate factors causing spontaneous termination.

Methods: We used a large data set from Langendorff experiments in isolated rabbit hearts in which drug-induced QT prolongation, bradycardia, and hypokalemia provoke TdP. We included 427 episodes with typical TdP characteristics of polymorphic self-terminating beats and twisting QRS complexes occurring in the presence of abnormal QT prolongation due to various different QT-prolonging drugs. The use of 8 monophasic action potential catheters allowed the characterization of action potential duration, configuration, and dispersion of repolarization beyond the capabilities of the surface electrocardiogram. To identify possible mechanisms of arrhythmia termination, the initial, midpoint, and terminal 3 ventricular complexes were analyzed for each episode.

Results: An abrupt decrease in spatial dispersion over the course of a TdP episode was identified as a precursor for termination of TdP. Within the last 3 beats, a sudden significant decrease in the dispersion of repolarization was observed as a predictor of termination. In parallel, there was a decrease in action potential duration (action potential duration at 90% repolarization) before termination. Also, a change in action potential configuration (action potential duration at 90% repolarization/action potential duration at 50% repolarization ratio) in terms of the loss of action potential dome with a restitution of action potential triangulation was observed.

Conclusion: In >400 TdP episodes, homogenization of myocardial repolarization with the recovery of an action potential configuration determines the termination of TdP episodes.

Keywords: Langendorff; Long QT syndrome; Termination; Torsades de pointes; Ventricular arrhythmia.