Mechanism of arrhythmogenicity of the short-long cardiac sequence that precedes ventricular tachyarrhythmias in the long QT syndrome

OBJECTIVES The purpose of this study was to investigate the electrophysiolo gic mechanism(s) that underlie the transition of one or more short-long (S- L) cardiac, sequences to ventricular tachyarrhythmias (VTs) in the long QT syndrome. BACKGROUND One or more S-L cardiac cycles, usually the result of a ventricu lar bigeminal rhythm, frequently precedes the onset of VT in patients with either normal or prolonged QT interval. Electrophysiologic mechanisms that underlie this relationship have not been fully explained. METHODS We investigated electrophysiologic changes associated with the tran sition of a S-L cardiac sequence to VT in the canine anthopleurin-A model, a surrogate of LQT3. Experiments were performed on 12 mongrel puppies after administration of anthopleurin-A. Correlation of tridimensional activation and repolarization patterns was obtained from up to 384 electrograms. Acti vation-recovery intervals were measured from unipolar electrograms and were considered to represent local repolarization. RESULTS We analyzed 24 different episodes of a S-L sequence that preceded V T obtained from 12 experiments. The VT followed one S-L sequence (five epis odes), two to five S-L sequences (12 episodes) and more than five S-L seque nces (seven episodes). The single premature ventricular beats coupled to th e basic beats were consistently due to a subendocardial focal activity (SFA ). There were two basic mechanisms for the development of VT after one or m ore S-L sequences: 1) in 10 examples of a S-L sequence due to a stable unif ocal bigeminal rhythm, the occurrence of a second SFA, which arose consiste ntly from a different site, infringed on the pattern of dispersion of repol arization (DR) of the first SFA to initiate reentrant excitation; 2) in the remaining 14 episodes of a S-L sequence, a slight lengthening (50 to 150 m s) in one or more preceding cycle lengths (CLs) resulted in alterations of the spatial pattern of DR at key sites to promote reentry. The lengthening of the preceding CL produced differentially a greater degree of prolongatio n of repolarization at midmyocardial and endocardial sites compared with ep icardial sites with consequent increase of DR. The increased DR at key adja cent sites resulted in the development of de novo zones of functional condu ction block and/or slowed conduction to create the necessary prerequisites for successful reentry. CONCLUSIONS The occurrence of VT after one or more S-L cardiac sequences wa s due to well defined electrophysiologic changes with predictable consequen ces that promoted reentrant excitation. (C) 1999 by the American College of Cardiology.