Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model

Robin Van Den Abeele; Sander Hendrickx; Enid Van Nieuwenhuyse; Albert Dunnink; Alexander V Panfilov; Marc A Vos; Eike M Wülfers; Nele Vandersickel

doi:10.3389/fphys.2023.1201260

Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model

Front Physiol. 2023 Jul 26:14:1201260. doi: 10.3389/fphys.2023.1201260. eCollection 2023.

Authors

Robin Van Den Abeele¹, Sander Hendrickx¹, Enid Van Nieuwenhuyse¹, Albert Dunnink², Alexander V Panfilov^{1

3

4}, Marc A Vos², Eike M Wülfers¹, Nele Vandersickel¹

Affiliations

¹ Biophysics Group, Department of Physics and Astronomy, Faculty of Sciences, Ghent University, Ghent, Belgium.
² Department of Medical Physiology, University Medical Center Utrecht, Utrecht, Netherlands.
³ Laboratory of Computational Biology and Medicine, Ural Federal University, Yekaterinburg, Russia.
⁴ World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, Moscow, Russia.

Abstract

Torsade de Pointes is a polymorphic ventricular tachycardia which is as yet incompletely understood. While the onset of a TdP episode is generally accepted to be caused by triggered activity, the mechanisms for the perpetuation is still under debate. In this study, we analysed data from 54 TdP episodes divided over 5 dogs (4 female, 1 male) with chronic atrioventricular block. Previous research on this dataset showed both reentry and triggered activity to perpetuate the arrhythmia. 13 of those TdP episodes showed reentry as part of the driving mechanism of perpetuating the episode. The remaining 41 episodes were purely ectopic. Reentry was the main mechanism in long-lasting episodes (>14 beats), while focal sources were responsible for maintaining shorter episodes. Building on these results, we re-analysed the data using directed graph mapping This program uses principles from network theory and a combination of positional data and local activation times to identify reentry loops and focal sources within the data. The results of this study are twofold. First, concerning reentry loops, we found that on average non-terminating (NT) episodes (≥10 s) show significantly more simultaneous reentry loops than self-terminating (ST) TdP (<10 s). Non-terminating episodes have on average 2.72 ± 1.48 simultaneous loops, compared to an average of 1.33 ± 0.66 for self-terminating episodes. In addition, each NT episode showed a presence of (bi-)ventricular loops between 10.10% and 69.62% of their total reentry duration. Compared to the ST episodes, only 1 in 4 episodes (25%) showed (bi-)ventricular reentry, lasting only 7.12% of its total reentry duration. This suggests that while focal beats trigger TdP, macro-reentry and multiple simultaneous localized reentries are the major drivers of long-lasting episodes. Second, using heatmaps, we found focal sources to occur in preferred locations, instead of being distributed randomly. This may have implications on treatment if such focal origins can be disabled reliably.

Keywords: Torsade de Pointes; cardiac arrhythmias; chronic atrioventricular block; directed graph mapping; electrophysiological mapping; focal sources; reentry.

Grants and funding

This research was supported by a ‘Starting Grant’ from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant No. 900008), awarded to NV. In addition, research at Sechenov University was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World- Class Research Centers, “Digital Biodesign and Personalized Healthcare,” No. 075-15-2022-304.