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

INTRODUCTION: Torsade de pointes (TdP), is often preceded by a short-long cycle length sequence. However, the causal relationship between the pause associated with a short-long cycle length sequence and TdP is not completely understood. This study tests the hypothesis that a pause enhances both dispersion of repolarization and EAD formation; however, EADs that form where APD is longest will be less likely to initiate TdP. METHODS AND RESULTS: We used optical mapping to measure transmural action potentials from the canine left ventricular wedge preparation. D-sotalol and ATX-II were used to mimic LQT2 and LQT3, respectively. The pause significantly enhanced mean APD (from 356 +/- 20 to 381 +/- 25 msec in LQT2, P < 0.05; from 609 +/- 92 to 675 +/- 98 msec in LQT3, P < 0.05) and transmural dispersion (from 35 +/- 9 to 46 +/- 11 msec in LQT2, P < 0.05; from 121 +/- 85 to 171 +/- 98 msec in LQT3, P < 0.05) compared to steady state pacing. Under LQT3 condition EADs, EAD-induced triggered activity, and TdP were more likely to occur following a pause. Interestingly, the triggered beat following a pause always broke through at the region of maximum local repolarization gradient. CONCLUSION: These data suggest that a pause accentuates transmural repolarization gradients and facilitates the formation of EADs and EAD-induced triggered activity. In contrast to our hypothesis, the findings of this study support the concept that M-cells (where APD is longest) can play an important role in both the origination of EAD-induced triggered activity and unidirectional block associated with TdP.