Mechanism of discordant T wave alternans in the in vivo heart

Introduction: Compared to concordant T wave alternans (CA), discordant T wave alternans (DA) may be associated with an increased dispersion of repolarization (DR) and a greater propensity to develop reentrant ventricular tachyarrhythmias. The electrophysiologic mechanisms of DA in the in vivo heart are not well understood. Methods and Results: The mechanisms of DA were investigated in the canine anthopleurin-A surrogate model of long QT3 syndrome using tridimensional analysis of activation and repolarization patterns from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. Two mechanisms for the development of DA were observed. (1) Stepwise shortening of cycle length (CL) superimposed on preexisting DR resulted in different diastolic intervals (DI) at midmyocardial sites compared to epicardial and endocardial sites. The dispersion of DI coupled with different restitution kinetics at those sites induced DA. (2) The dependence of conduction velocity on DI as the CL is abruptly shortened could result in differential conduction delays at mid sites. This enhanced the dispersion of DI between sites and, coupled with the different restitution kinetics, induced DA. The critical step for the development of DA in both mechanisms was the occurrence of short ARI in two consecutive beats either at epicardial sites in the first mechanism or at mid sites in the second mechanism. Sites with DA had significantly more DR compared to sites with concordant T wave alternans, and ventricular tachyarrhythmias developed mainly in the presence of DA. Conclusion: In the in vivo heart, DA developed due to critical interaction between dispersion of DI and differences in restitution kinetics at different myocardial sites. The dispersion of DI could result from preexisting DR or differential conduction delay at a critical short CL. DA is critically linked to the development of malignant tachyarrhythmias.