The Mechanism of Pause-Induced Torsade de Pointes in Long QT Syndrome

Jinqiu Liu, M.D.; Kenneth R. Laurita, Ph.D.

Disclosures

J Cardiovasc Electrophysiol. 2005;16(9):981-987. 

In This Article

Discussion

The short-long cycle length sequence has been recognized as a hallmark of TdP in congenital[22] and acquired[23] LQTS. Previous clinical studies have shown a close association between QT prolongation and pause-dependent TdP.[24,25] Dispersion of repolarization has also been shown to play an important role in the initiation of TdP.[8,26,14] El-Sherif et al.[8] used tridimensional activation and recovery interval (ARI) mapping in canine in vivo and demonstrated the occurrence of VT after one or more short-long cycle length sequences. They observed an increase in dispersion of recovery following a pause and ectopic activity originating primarily from the endocardium. In the present study, we observed a significant increase in dispersion of repolarization and mean APD following a pause under LQT2 and (to a greater extent) LQT3 conditions. This result is consistent with that reported by Ueda et al.[10] who demonstrated, using optical mapping in the left ventricular wedge preparation, M-cell behavior (i.e., prolonged APD) and dispersion of APD that dynamically forms with ATX-II ≥5 nmol/L. We also show detailed maps of APD before and after a pause (Fig. 3) that demonstrate discrete regions or "islands" of prolonged APD[9] that are enhanced by a pause and are causally related to intense local repolarization gradients and the formation of unidirectional block (Fig. 6). Interesting, the duration of the pause did not significantly affect APD prolongation and dispersion ( Table 1 ). Previously, we have shown the opposite result for a premature beat, where APD dispersion decreases and then increases as the duration of premature coupling interval is shortened.[27]

The pause associated with a short-long cycle length sequence can also promote the formation of EADs,[14–16,28] and the underlying mechanism may be related to pause-induced APD prolongation in M-cells.[29] Unlike the study by El-Sherif et al.,[8] we observed an increase in ectopic activity following a pause that breaks through in the midmyocardial region. One possible explanation for this difference is that in the present study pauses of longer duration occurred, which may preferentially prolong M-cell APD and enhance the formation of EADs.

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