ELECTROPHYSIOLOGICAL BASIS OF ARRHYTHMOGENICITY OF QT T ALTERNANS IN THE LONG-QT SYNDROME - TRIDIMENSIONAL ANALYSIS OF THE KINETICS OF CARDIAC REPOLARIZATION/

Tachycardia-dependent QT/T alternans occurs in patients with the conge nital or idiopathic form of long-QT syndrome (LQTS) and may presage th e onset of polymorphic ventricular tachyarrhythmias. To examine the el ectrophysiological basis of arrhythmogenicity of QT/T alternans in LQT S, the tridimensional repolarization pattern of QT/T alternans was stu died in the anthopleurin-A model of LQTS, a surrogate for LQT3. In 11 anesthetized mongreal puppies, tridimensional repolarization and activ ation patterns were analyzed from 256 to 384 unipolar electrograms. Ca rdiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. To induce QT/T alternans, the pacing cyc le length (CL) was abruptly shortened in steps of 50 ms from a basic d rive of 1000 ms, ARIs were calculated at epicardial (Epi), midmyocardi al (Mid), and endocardial (End) sites. ARI restitution at each site wa s assessed by using a single premature stimulation delivered after the basic drive. ARI alternans occurred at longer CLs at Mid sites compar ed with End and Epi sites, and the magnitude of alternans at Mid sites was greater. Two factors contributed to the modulation of ART during QT/T alternans: (1) differences in restitution kinetics at Mid sites, characterized by larger Delta ARI and a slower time constant ( tau), a nd (2) differences in diastolic intervals resulting in different input to restitution at the same constant CL, These 2 factors could explain not only the onset of alternans at Mid sites at longer CLs but also t he critical observation that ARI dispersion between Epi and Mid sites during alternans was greater than during the slower basic CL. Marked A RI alternans could be present in local electrograms without manifest a lternation of the QT/T segment in the surface EGG. The latter was seen at critically short CLs associated with reversal of the gradient of A RI between Epi and Mid sites, with a consequent reversal of polarity o f the intramyocardial QT wave in alternate cycles. The arrhythmogenici ty of QT/T alternans was primarily due to the greater degree of spatia l dispersion of repolarization during alternans than during slower rat es not associated with alternans. This could result in functional cond uction block and reentrant ventricular tachyarrhythmias during the fix ed drive associated with alternans.