In computational simulations, large heterogeneities in repolarization reserve produced ectopic focal torsade de pointes, while smaller heterogeneities produced re-entry-type torsade de pointes.
Does the degree of repolarization heterogeneity determine whether torsade de pointes is perpetuated by focal activity or re-entry in computational models?
In silico modeling reveals that the perpetuation mechanism of torsade de pointes—focal activity versus re-entry—is dictated by the degree of repolarization heterogeneity in the myocardium.
KEY POINTS: The underlying mechanism of torsade de pointes (TdP) remains of debate: perpetuation may be due to (1) focal activity or (2) re-entrant activity. The onset of TdP correlates with action potential heterogeneities in different regions of the heart. We studied the mechanism of perpetuation of TdP in silico using a 2D model of human cardiac tissue and an anatomically accurate model of the ventricles of the human heart. We found that the mechanism of perpetuation TdP depends on the degree of heterogeneity. If the degree of heterogeneity is large, focal activity alone can sustain a TdP, otherwise re-entrant activity emerges. This result can help to understand the relationship between the mechanisms of TdP and tissue properties and may help in developing new drugs against it. ABSTRACT: Torsade de pointes (TdP) can be the consequence of cardiac remodelling, drug effects or a combination of both. The mechanism underlying TdP is unclear, and may involve triggered focal activity or re-entry. Recent work by our group has indicated that both cases may exist, i.e. TdPs induced in the chronic atrioventricular block (CAVB) dog model may have a focal origin or are due to re-entry. Also it was found that heterogeneities might play an important role. In the current study we have used computational modelling to further investigate the mechanisms involved in TdP initiation and perpetuation, especially in the CAVB dog model, by the addition of heterogeneities with reduced repolarization reserve in comparison with the surrounding tissue. For this, the TNNP computer model was used for computations. We demonstrated in 2D and 3D simulations that ECGs with the typical TdP morphology can be caused by both multiple competing foci and re-entry circuits as a result of introduction of heterogeneities, depending on whether the heterogeneities have a large or a smaller reduced repolarization reserve in comparison with the surrounding tissue. Large heterogeneities can produce ectopic TdP, while smaller heterogeneities will produce re-entry-type TdP.
Vandersickel et al. (Tue,) conducted a other in Torsade de pointes. Heterogeneities with reduced repolarization reserve vs. Surrounding tissue was evaluated on Mechanism of TdP perpetuation (focal vs re-entry). In computational simulations, large heterogeneities in repolarization reserve produced ectopic focal torsade de pointes, while smaller heterogeneities produced re-entry-type torsade de pointes.