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Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach

Background: Antiarrhythmic drugs are the first-line treatment for atrial fibrillation (AF), but their effect is highly dependent on the characteristics of the patient. Moreover, anatomical variability, and specifically atrial size, have also a strong influence on AF recurrence. Objective: We perform...

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Autores principales: Sanchez de la Nava, Ana Maria, Arenal, Ángel, Fernández-Avilés, Francisco, Atienza, Felipe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685526/
https://www.ncbi.nlm.nih.gov/pubmed/34938202
http://dx.doi.org/10.3389/fphys.2021.768468
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author Sanchez de la Nava, Ana Maria
Arenal, Ángel
Fernández-Avilés, Francisco
Atienza, Felipe
author_facet Sanchez de la Nava, Ana Maria
Arenal, Ángel
Fernández-Avilés, Francisco
Atienza, Felipe
author_sort Sanchez de la Nava, Ana Maria
collection PubMed
description Background: Antiarrhythmic drugs are the first-line treatment for atrial fibrillation (AF), but their effect is highly dependent on the characteristics of the patient. Moreover, anatomical variability, and specifically atrial size, have also a strong influence on AF recurrence. Objective: We performed a proof-of-concept study using artificial intelligence (AI) that enabled us to identify proarrhythmic profiles based on pattern identification from in silico simulations. Methods: A population of models consisting of 127 electrophysiological profiles with a variation of nine electrophysiological variables (G(Na), I(NaK), G(K1), G(CaL), G(Kur), I(KCa), [Na](ext), and [K](ext) and diffusion) was simulated using the Koivumaki atrial model on square planes corresponding to a normal (16 cm(2)) and dilated (22.5 cm(2)) atrium. The simple pore channel equation was used for drug implementation including three drugs (isoproterenol, flecainide, and verapamil). We analyzed the effect of every ionic channel combination to evaluate arrhythmia induction. A Random Forest algorithm was trained using the population of models and AF inducibility as input and output, respectively. The algorithm was trained with 80% of the data (N = 832) and 20% of the data was used for testing with a k-fold cross-validation (k = 5). Results: We found two electrophysiological patterns derived from the AI algorithm that was associated with proarrhythmic behavior in most of the profiles, where G(K1) was identified as the most important current for classifying the proarrhythmicity of a given profile. Additionally, we found different effects of the drugs depending on the electrophysiological profile and a higher tendency of the dilated tissue to fibrillate (Small tissue: 80 profiles vs Dilated tissue: 87 profiles). Conclusion: Artificial intelligence algorithms appear as a novel tool for electrophysiological pattern identification and analysis of the effect of antiarrhythmic drugs on a heterogeneous population of patients with AF.
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spelling pubmed-86855262021-12-21 Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach Sanchez de la Nava, Ana Maria Arenal, Ángel Fernández-Avilés, Francisco Atienza, Felipe Front Physiol Physiology Background: Antiarrhythmic drugs are the first-line treatment for atrial fibrillation (AF), but their effect is highly dependent on the characteristics of the patient. Moreover, anatomical variability, and specifically atrial size, have also a strong influence on AF recurrence. Objective: We performed a proof-of-concept study using artificial intelligence (AI) that enabled us to identify proarrhythmic profiles based on pattern identification from in silico simulations. Methods: A population of models consisting of 127 electrophysiological profiles with a variation of nine electrophysiological variables (G(Na), I(NaK), G(K1), G(CaL), G(Kur), I(KCa), [Na](ext), and [K](ext) and diffusion) was simulated using the Koivumaki atrial model on square planes corresponding to a normal (16 cm(2)) and dilated (22.5 cm(2)) atrium. The simple pore channel equation was used for drug implementation including three drugs (isoproterenol, flecainide, and verapamil). We analyzed the effect of every ionic channel combination to evaluate arrhythmia induction. A Random Forest algorithm was trained using the population of models and AF inducibility as input and output, respectively. The algorithm was trained with 80% of the data (N = 832) and 20% of the data was used for testing with a k-fold cross-validation (k = 5). Results: We found two electrophysiological patterns derived from the AI algorithm that was associated with proarrhythmic behavior in most of the profiles, where G(K1) was identified as the most important current for classifying the proarrhythmicity of a given profile. Additionally, we found different effects of the drugs depending on the electrophysiological profile and a higher tendency of the dilated tissue to fibrillate (Small tissue: 80 profiles vs Dilated tissue: 87 profiles). Conclusion: Artificial intelligence algorithms appear as a novel tool for electrophysiological pattern identification and analysis of the effect of antiarrhythmic drugs on a heterogeneous population of patients with AF. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8685526/ /pubmed/34938202 http://dx.doi.org/10.3389/fphys.2021.768468 Text en Copyright © 2021 Sanchez de la Nava, Arenal, Fernández-Avilés and Atienza. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Physiology
Sanchez de la Nava, Ana Maria
Arenal, Ángel
Fernández-Avilés, Francisco
Atienza, Felipe
Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title_full Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title_fullStr Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title_full_unstemmed Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title_short Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: An in silico Population of Models Approach
title_sort artificial intelligence-driven algorithm for drug effect prediction on atrial fibrillation: an in silico population of models approach
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685526/
https://www.ncbi.nlm.nih.gov/pubmed/34938202
http://dx.doi.org/10.3389/fphys.2021.768468
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