Biological Engineering of Atrial Fibrillation: Mechanisms and Treatments

Dear Colleagues,

Atrial fibrillation (AF) is a complex condition consisting of structural defects (fibrosis) [1], electrical dysfunction (ion channel and conduction defects) [2,3], metabolic insufficiency, anatomy [4] and non-atrial factors. While recent years have experienced impactful and almost paradigm changing developments in the understanding and treatment of AF [5,6,7], it still remains widely prevalent. A potential reason for this landscape is the sub-optimal translation of knowledge. This Special Issue is designed to bring together cutting-edge basic science research and informed treatment options.

This Special Issue invites original and review contributions from experimentalists, clinicians, and computational scientists. Novel insights such as the atrial wall being a bi-layer [8], a particular form of fibrosis [9], may impact pacemaker algorithms [10], cardioversion protocols [11], and ablation planning [12]. While contributions in the topics below are invited, other manuscripts will also be considered:

• Novel understanding of atrial excitation–contraction function;
• Role of fibrosis in the genesis of AF, and its treatment;
• Experimental and computational assessment of drug efficacy;
• Circadian effects on atrial activity;
• Artificial pacemaker, ablation, and cardioversion efficacy in light of recent developments;
• Role of metabolism in atrial physiopathology;
• Data driven computer modeling of AF treatments;
• Open source software and data repositories to assist the AF research community;
• Review articles.

References

1. Csepe, T.A.; Ekalyanasundaram, A.; Hansen, B.J.; Ezhao, J.; Fedorov, V.V. Fibrosis: a structural modulator of sinoatrial node physiology and dysfunction. Physiol. 2015, 6, 37, doi:10.3389/fphys.2015.00037.
2. Kharche, S.R.; Stary, T.; Colman, M.A.; Biktasheva, I.V.; Workman, A.J.; Rankin, A.C.; Holden, A.V. and Zhang, H. Effects of human atrial ionic remodelling by beta-blocker therapy on mechanisms of atrial fibrillation: a computer simulation. 2014, 16, 1524–1533.
3. Loewe, A.; Wilhelms, M.; Fischer, F.; Scholz, E.P.; Dössel, O.; Seemann, G. Arrhythmic potency of human ether-à-go-go-related gene mutations L532P and N588K in a computational model of human atrial myocytes. 2014, 16, 435–443, doi:10.1093/europace/eut375.
4. Dobrzynski, H.; Anderson, R.H.; Atkinson, A.; Borbas, Z.; D’Souza, A.; Fraser, J.F.; Inada, S.; Logantha, S.J.; Monfredi, O.; Morris, G.M.; et al. Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Ther. 2013, 139, 260–288, doi:10.1016/j.pharmthera.2013.04.010.
5. Macle, L. and Nattel, S. Arrhythmias in 2015: advances in drug, ablation, and device therapy for cardiac arrhythmias. Rev. Cardiol. 2016, 13, 67–68.
6. Nattel, S. How does fibrosis promote atrial fibrillation persistence: in silico findings, clinical observations, and experimental data. Res. 2016, 110, 295–297.
7. Nattel, S. and Dobrev, D. Electrophysiological and molecular mechanisms of paroxysmal atrial fibrillation. Rev. Cardiol. 2016, 13, 575–590.
8. Verheule, S.; Eckstein, J.; Linz, D.; Maesen, B.; Bidar, E.; Gharaviri, A.; Schotten, U. Role of endo-epicardial dissociation of electrical activity and transmural conduction in the development of persistent atrial fibrillation. Biophys. Mol. Biol. 2014, 115, 173–185, doi:10.1016/j.pbiomolbio.2014.07.007.
9. Kostin, S.; Klein, G.; Szalay, Z.; Hein, S.; Bauer, E.P.; Schaper, J. Structural correlate of atrial fibrillation in human patients. Res. 2002, 54, 361–379, doi:10.1016/s0008-6363(02)00273-0.
10. Zhang, Y.; Popović, Z.B.; Kusunose, K.; Mazgalev, T.N. Therapeutic Effects of Selective Atrioventricular Node Vagal Stimulation in Atrial Fibrillation and Heart Failure. Cardiovasc. Electrophysiol. 2013, 24, 86–91, doi:10.1111/j.1540-8167.2012.02405.x.
11. Kharche, S.R.; Biktasheva, I.V.; Seemann, G.; Zhang, H.G.; Zhao, J.C. and Biktashev, V.N. Computational Modelling of Low Voltage Resonant Drift of Scroll Waves in the Realistic Human Atria. Functional Imaging and Modeling of the Heart. 2015, 9126, 421–429.
12. Willems, S.; Khairy, P.; Andrade, J.G.; Hoffmann, B.A.; Levesque, S.; Verma, A.; Weerasooriya, R.; Novak, P.; Arentz, T.; Deisenhofer, I.; et al. Redefining the Blanking Period After Catheter Ablation for Paroxysmal Atrial Fibrillation. Arrhythmia Electrophysiol. 2016, 9, e003909, doi:10.1161/circep.115.003909.

Prof. Dr. Sanjay R. Kharche
Guest Editor

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• atrial fibrillation
• ablation
• atrial specific drugs
• in silico modeling of AF.
• open source data