Perpetuation of Torsade de Pointes in heterogeneous hearts: competing foci or re-entry?

Abstract

Torsade de Pointes (TdP) can be the consequence of cardiac remodeling, drug effects or the 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 AV block dog model (CAVB) may have a focal origin or are due to reentry. Also it was found that heterogeneities might play an important role. In the current study we have used computational modeling 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 electrocardiograms with the typical TdP morphology can be both caused by multiple competing foci and re-entry circuits by the introduction of heterogeneities, depending on whether the heterogeneties 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 reentry type of TdPs.