Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype
Background: The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/−-deficient AF conditions by realistic in silico AF modeling.Me...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.650449/full |
| _version_ | 1811316290298576896 |
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| author | Inseok Hwang Ze Jin Je-Wook Park Oh-Seok Kwon Byounghyun Lim Myunghee Hong Min Kim Hee-Tae Yu Tae-Hoon Kim Jae-Sun Uhm Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak |
| author_facet | Inseok Hwang Ze Jin Je-Wook Park Oh-Seok Kwon Byounghyun Lim Myunghee Hong Min Kim Hee-Tae Yu Tae-Hoon Kim Jae-Sun Uhm Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak |
| author_sort | Inseok Hwang |
| collection | DOAJ |
| description | Background: The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/−-deficient AF conditions by realistic in silico AF modeling.Methods: We tested the V-AADs in AF modeling integrated with patients' 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/− deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications.Results: We compared the wild-type and PITX2+/− deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/−-deficient model exhibited a shorter APD90 (p < 0.001), a lower Smax (p < 0.001), mean DF (p = 0.012), PS number (p < 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose-dependent manner. AAD-induced AFCL lengthening (p < 0.001) and reductions in the CV (p = 0.033), peak DF (p < 0.001), and PS number (p < 0.001) were more significant in PITX2+/−-deficient than wild-type AF. PITX2+/−-deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018).Conclusions: The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamic and electrophysiological characteristics are different among the PITX2-deficient and the wild-type genotype models. |
| first_indexed | 2024-04-13T11:46:26Z |
| format | Article |
| id | doaj.art-b2b13787bce244b693568963dfbe3233 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T11:46:26Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-b2b13787bce244b693568963dfbe32332022-12-22T02:48:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-05-011210.3389/fphys.2021.650449650449Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to GenotypeInseok HwangZe JinJe-Wook ParkOh-Seok KwonByounghyun LimMyunghee HongMin KimHee-Tae YuTae-Hoon KimJae-Sun UhmBoyoung JoungMoon-Hyoung LeeHui-Nam PakBackground: The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/−-deficient AF conditions by realistic in silico AF modeling.Methods: We tested the V-AADs in AF modeling integrated with patients' 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/− deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications.Results: We compared the wild-type and PITX2+/− deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/−-deficient model exhibited a shorter APD90 (p < 0.001), a lower Smax (p < 0.001), mean DF (p = 0.012), PS number (p < 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose-dependent manner. AAD-induced AFCL lengthening (p < 0.001) and reductions in the CV (p = 0.033), peak DF (p < 0.001), and PS number (p < 0.001) were more significant in PITX2+/−-deficient than wild-type AF. PITX2+/−-deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018).Conclusions: The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamic and electrophysiological characteristics are different among the PITX2-deficient and the wild-type genotype models.https://www.frontiersin.org/articles/10.3389/fphys.2021.650449/fullatrial fibrillationmodelingantiarrhythmic drugsPITX2gene |
| spellingShingle | Inseok Hwang Ze Jin Je-Wook Park Oh-Seok Kwon Byounghyun Lim Myunghee Hong Min Kim Hee-Tae Yu Tae-Hoon Kim Jae-Sun Uhm Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype Frontiers in Physiology atrial fibrillation modeling antiarrhythmic drugs PITX2 gene |
| title | Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype |
| title_full | Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype |
| title_fullStr | Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype |
| title_full_unstemmed | Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype |
| title_short | Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype |
| title_sort | computational modeling for antiarrhythmic drugs for atrial fibrillation according to genotype |
| topic | atrial fibrillation modeling antiarrhythmic drugs PITX2 gene |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.650449/full |
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