Gharaviri, A., Pezzuto, S., Potse, M., Conte, G., Zeemering, S., Sobota, V., Verheule, S., Krause, R., Auricchio, A., & Schotten, U. (2021). Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation. Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, 23(Suppl 1), i161-i168. https://doi.org/10.1093/europace/euaa413, https://doi.org/10.1093/europace/euaa413

@article{e7f56602e96d4959b8a9120a1f2f40f3,
title = "Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation",
abstract = "AimsRecent clinical studies showed that antiarrhythmic drug (AAD) treatment and pulmonary vein isolation (PVI) synergistically reduce atrial fibrillation (AF) recurrences after initially successful ablation. Among newly developed atrial-selective AADs, inhibitors of the G-protein-gated acetylcholine-activated inward rectifier current (IKACh) were shown to effectively suppress AF in an experimental model but have not yet been evaluated clinically. We tested in silico whether inhibition of inward rectifier current or its combination with PVI reduces AF inducibility.Methods and resultsWe simulated the effect of inward rectifier current blockade (IK blockade), PVI, and their combination on AF inducibility in a detailed three-dimensional model of the human atria with different degrees of fibrosis. IK blockade was simulated with a 30% reduction of its conductivity. Atrial fibrillation was initiated using incremental pacing applied at 20 different locations, in both atria. IK blockade effectively prevented AF induction in simulations without fibrosis as did PVI in simulations without fibrosis and with moderate fibrosis. Both interventions lost their efficacy in severe fibrosis. The combination of IK blockade and PVI prevented AF in simulations without fibrosis, with moderate fibrosis, and even with severe fibrosis. The combined therapy strongly decreased the number of fibrillation waves, due to a synergistic reduction of wavefront generation rate while the wavefront lifespan remained unchanged.ConclusionNewly developed blockers of atrial-specific inward rectifier currents, such as IKAch, might prevent AF occurrences and when combined with PVI effectively supress AF recurrences in human.",
keywords = "Anti-Arrhythmia Agents/therapeutic use, Atrial Fibrillation/drug therapy, Catheter Ablation, Computer Simulation, Humans, Pulmonary Veins/surgery, Recurrence, Treatment Outcome",
author = "Ali Gharaviri and Simone Pezzuto and Mark Potse and Giulio Conte and Stef Zeemering and Vladim{\'i}r Sobota and Sander Verheule and Rolf Krause and Angelo Auricchio and Ulrich Schotten",
note = "Published on behalf of the European Society of Cardiology. All rights reserved. {\textcopyright} The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.",
year = "2021",
month = mar,
day = "4",
doi = "10.1093/europace/euaa413",
language = "English",
volume = "23",
pages = "i161--i168",
journal = "Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology",
issn = "1099-5129",
publisher = "Oxford University Press",
number = "Suppl 1",
}