14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-149

Acquired QT syndrome. The mechanistic background

Wilhelm Haverkamp, Paulus Kirchhof, Lars Eckardt, Gerold Mönnig, Martin Borggrefe, Günter Breithardt.
Hospitalof the Westfälische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research, Münster, Germany

Mechanisms of torsade de pointes in acquired abnormal QT prolongation

Recently, in-vitro and in-vivo experimental studies have suggested that early afterdepolarizations (EADs) and triggered activity may play an important role in the genesis of ventricular tachyarrhythmias of the TDP-type. EADs are cellular depolarizations occurring either during phase 2 and 3 of the transmembrane potential before repolarization is completed. These depolarizations may give rise to a premature action potential or a train of action potentials when the threshold for activation is reached. The resulting depolarization has been referred to as “triggered activity” since it is caused by a second nondriven upstroke induced by an afterdepolarization. The induction of EADs in in-vitro preparations has been demonstrated for almost all drugs known to cause abnormal QT-prolongation and TDP. Most of them exert their QT prolonging effect which can be considered as a prerequisite for the development of EADs, by blocking the rapidly activating component of the delayed rectifier potassium current IKr. Some investigators have suggested that TDP may be initiated and also maintained by triggered activity simultaneously originating at several independent competing foci. However, others have suggested that TDP may be initiated by triggered activity but maintained by a circus movement reentry mechanism. El-Sherif and coworkers³ recently developed a canine in-vivo model of LQTS using anthopleurin-A, an agent that prolongs action potential duration by slowing inactivation of the sodium current. Using high-resolution tridimensional isochronal maps of activation and repolarization patterns, they showed that the initial beat of all episodes of polymorphic ventricular tachycardia consistently arose as a subendocardial focal activity whereas subsequent beats were due to successive reentrant excitation in the form of rotating scrolls. Increased transmural electrical heterogeneity resulting from spatial differences in action potential duration and morphology has been suggested as the substrate underlying reentrant activation.

TABLE I – Risk factors for drug-induced torsade de pointes