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EXPERIMENTAL STUDIES

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

^a Cardiology Division, Department of Medicine, State University of New York Health Science Center and Veterans Affairs Medical Center, Brooklyn, New York, USA

Manuscript received August 24, 1998; revised manuscript received November 6, 1998, accepted December 23, 1998.

Reprint requests and correspondence: Dr. Nabil El-Sherif, SUNY Health Science Center, Cardiology Division, Box 1199, 450 Clarkson Ave., Brooklyn, New York 11203.
el-sherif.nabil{at}brooklyn.va.gov

OBJECTIVES

The purpose of this study was to investigate the electrophysiologic 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 ventricular 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 transition 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. Activation–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 VT obtained from 12 experiments. The VT followed one S-L sequence (five episodes), two to five S-L sequences (12 episodes) and more than five S-L sequences (seven episodes). The single premature ventricular beats coupled to the basic beats were consistently due to a subendocardial focal activity (SFA). There were two basic mechanisms for the development of VT after one or more S-L sequences: 1) in 10 examples of a S-L sequence due to a stable unifocal bigeminal rhythm, the occurrence of a second SFA, which arose consistently from a different site, infringed on the pattern of dispersion of repolarization (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 ms) 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 prolongation of repolarization at midmyocardial and endocardial sites compared with epicardial sites with consequent increase of DR. The increased DR at key adjacent sites resulted in the development of de novo zones of functional conduction 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 was due to well defined electrophysiologic changes with predictable consequences that promoted reentrant excitation.

Abbreviations and Acronyms   APD = action potential duration   ARI = activation–recovery interval   CL = cycle length   DR = dispersion of repolarization   EAD = early afterdepolarization   ECG = electrocardiogram   End = endocardial   Epi = epicardial   LQTS = long QT syndrome   Mid = midmyocardial   SFA = subendocardial focal activity   S-L = short–long   VT = ventricular tachyarrhythmia

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