Journal article
In-silico drug trials for precision medicine in atrial fibrillation: from ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria
- Abstract:
- Atrial fibrillation (AF) inducibility, sustainability and response to pharmacological treatment of individual patients are expected to be determined by their ionic current properties, especially in structurally-healthy atria. Mechanisms underlying AF and optimal cardioversion are however still unclear. In this study, in-silico drug trials were conducted using a population of human structurally-healthy atria models to 1) identify key ionic current properties determining AF inducibility, maintenance and pharmacological cardioversion, and 2) compare the prognostic value for predicting individual AF cardioversion of ionic current properties and electrocardiogram (ECG) metrics. In the population of structurally-healthy atria, 477 AF episodes were induced in ionic current profiles with both steep action potential duration (APD) restitution (eliciting APD alternans), and high excitability (enabling propagation at fast rates that transformed alternans into discordant). High excitability also favored 211 sustained AF episodes, so its decrease, through prolonged refractoriness, explained pharmacological cardioversion. In-silico trials over 200 AF episodes, 100 ionic profiles and 10 antiarrhythmic compounds were consistent with previous clinical trials, and identified optimal treatments for individual electrophysiological properties of the atria. Algorithms trained on 211 simulated AF episodes exhibited >70% accuracy in predictions of cardioversion for individual treatments using either ionic current profiles or ECG metrics. In structurally-healthy atria, AF inducibility and sustainability are enabled by discordant alternans, under high excitability and steep restitution conditions. Successful pharmacological cardioversion is predicted with 70% accuracy from either ionic or ECG properties, and it is optimal for treatments maximizing refractoriness (thus reducing excitability) for the given ionic current profile of the atria.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.1MB, Terms of use)
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- Publisher copy:
- 10.3389/fphys.2022.966046
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Physiology More from this journal
- Volume:
- 13
- Article number:
- 966046
- Publication date:
- 2022-09-15
- Acceptance date:
- 2022-08-23
- DOI:
- EISSN:
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1664-042X
- Language:
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English
- Keywords:
- Pubs id:
-
1278976
- Local pid:
-
pubs:1278976
- Deposit date:
-
2022-09-15
Terms of use
- Copyright holder:
- Dasí et al.
- Copyright date:
- 2022
- Rights statement:
- © 2022 Dasí, Roy, Sachetto, Camps, Bueno-Orovio and Rodriguez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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