Author + information
- Received April 28, 2017
- Accepted June 1, 2017
- Published online December 18, 2017.
- Nele Vandersickel, PhDa,∗ (, )
- Alexandre Bossu, Msb,
- Jan De Neve, PhDc,
- Albert Dunnink, PhDd,
- Veronique M.F. Meijborg, PhDd,
- Marcel A.G. van der Heyden, PhDb,
- Jet D.M. Beekmanb,
- Jacques M.T. De Bakker, PhDb,
- Marc A. Vos, PhDb and
- Alexander V. Panfilov, PhDa
- aDepartment of Physics and Astronomy, Ghent University, Ghent, Belgium
- bDepartment of Medical Physiology, University Medical Center Utrecht, Utrecht, the Netherlands
- cDepartment of Data Analysis, Ghent University, Ghent, Belgium
- dDepartment of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands
- ↵∗Address for correspondence:
Dr. Nele Vandersickel, Department of Physics and Astronomy, Ghent University, Krijgslaan 281, S9, Ghent, Oost-Vlaanderen 9000, Belgium.
Objectives This study investigated the arrhythmogenic mechanisms responsible for torsade de pointes (TdP) in the chronic atrioventricular block dog model, known for its high susceptibility for TdP.
Background The mechanism of TdP arrhythmias has been under debate for many years. Focal activity as well as re-entry have both been mentioned in the initiation and the perpetuation of TdP.
Methods In 5 TdP-sensitive chronic atrioventricular block dogs, 56 needle electrodes were evenly distributed transmurally to record 240 unipolar local electrograms simultaneously. Nonterminating (NT) episodes were defibrillated after 10 s. Software was developed to automatically detect activation times and to create 3-dimensional visualizations of the arrhythmia. For each episode of ectopic activity (ranging from 2 beats to NT episodes), a novel methodology was created to construct directed graphs of the wave propagation and detect re-entry loops by using an iterative depth-first-search algorithm.
Results Depending on the TdP definition (number of consecutive ectopic beats), we analyzed 29 to 54 TdP: 29 were longer than 5 beats. In the total group, 9 were NT and 45 were self-terminating. Initiation and termination were always based on focal activity. Re-entry becomes more important in the longer-lasting episodes (>14 beats), whereas in all NT TdP, re-entry was the last active mechanism. During re-entry, excitation fronts were constantly present in the heart, while during focal TdP, there was always a silent interval between 2 consecutive waves (142 ms) during which excitation fronts were absent. Interbeat intervals were significantly smaller for re-entry episodes—220 versus 310 ms in focal. Electrograms recorded in particular areas during NT TdP episodes had significantly smaller amplitude (0.38) than during focal episodes (0.59).
Conclusions TdP can be driven by focal activity as well as by re-entry depending on the duration of the episode. NT episodes are always maintained by re-entry, which can be identified in local unipolar electrograms by shorter interbeat intervals and smaller deflection amplitude.
Dr. Vandersickel is funded by Research Foundation–Flanders (FWO). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received April 28, 2017.
- Accepted June 1, 2017.
- 2017 American College of Cardiology Foundation
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