The Electrophysiological Basis of Arrhythmogenicity of QT/T Alternants in the Long QT Syndrome

Abstract

Tachycardia-dependent QT/T alternans (A) occurs in patients with the congenital or idiopathic form of long QT syndrome (LQTS) and may presage the onset of polymorphic ventricular tachyarrhythmias (VT). We studied the electrophysiological basis of arrhythmogenicity of QT/T A in the anthopleurin-A model of LQTS, a surrogate for LQT3. in 7 anesthetized mongrel puppies, tridimensional repolarization and activation patterns were analyzed from 256-384 unipolar electrograms. Cardiac repolarization was evaluated as activation-recovery interval (ARI) of local electrograms. To induce QT/T A, the pacing cycle length (CL) was abruptly shortened in steps of 50 msec from a basic drive of 1000 msec. ARIs were calculated at epicardial (Epi), midmyiocardial (Mid), and endocardial (End) sites. ARI restitution at each site was assessed using single premature stimulation delivered after the basic drive. ARI A occurred at longer CLs at Mid sites compared to End and Epi sites and the magnitude of A at Mid sites was greater. This was due to differences in restitution kinetics at Mid sites, characterized by larger deltaARI and a slower time constant , and differences in diastolic intervals resulting in differetn input to restitution. The arrhythmogenicity of QT/T A was primarily due to the greater degree of spatial dispersion of repolarization during A compared to slower rates not associated with A. In 3 of 7 sxperiments, this resulted in funcional conduction block and reentrant VT during the fixed drive associated with