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In-silico modeling of atrial repolarization in normal and atrial fibrillation remodeled state

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Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.

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Acknowledgments

The authors would like to thank Mathias Wilhelms for the extraction of restitution curves from the literature. The research leading to these results has received funding from the European Communitys Seventh Framework Programme (FP7/2007-2013) under grant agreement no 224495 (euHeart project).

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Authors and Affiliations

  1. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131, Karlsruhe, Germany

    Martin W. Krueger, Andreas Dorn, David U. J. Keller, Gunnar Seemann & Olaf Dössel

  2. Department of Cardiology and Center for Integrative Electrocardiology, Lund University, Lund, Sweden

    Fredrik Holmqvist, Jonas Carlson & Pyotr G. Platonov

  3. Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, UK

    Kawal S. Rhode & Reza Razavi

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  1. Martin W. Krueger
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  2. Andreas Dorn
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  3. David U. J. Keller
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  9. Gunnar Seemann
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  10. Olaf Dössel
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Correspondence to Martin W. Krueger.

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Krueger, M.W., Dorn, A., Keller, D.U.J. et al. In-silico modeling of atrial repolarization in normal and atrial fibrillation remodeled state. Med Biol Eng Comput 51, 1105–1119 (2013). https://doi.org/10.1007/s11517-013-1090-1

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