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Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype

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dc.contributor.author권오석-
dc.contributor.author김태훈-
dc.contributor.author박제욱-
dc.contributor.author박희남-
dc.contributor.author엄재선-
dc.contributor.author유희태-
dc.contributor.author이문형-
dc.contributor.author정보영-
dc.contributor.author권오석-
dc.contributor.author임병현-
dc.contributor.author홍명희-
dc.contributor.author김민-
dc.date.accessioned2021-09-29T01:47:08Z-
dc.date.available2021-09-29T01:47:08Z-
dc.date.issued2021-05-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184548-
dc.description.abstractBackground: 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.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherFrontiers Research Foundation-
dc.relation.isPartOfFRONTIERS IN PHYSIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleComputational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorInseok Hwang-
dc.contributor.googleauthorJe-Wook Park-
dc.contributor.googleauthorOh-Seok Kwon-
dc.contributor.googleauthorByounghyun Lim-
dc.contributor.googleauthorMyunghee Hong-
dc.contributor.googleauthorMin Kim-
dc.contributor.googleauthorHee-Tae Yu-
dc.contributor.googleauthorTae-Hoon Kim-
dc.contributor.googleauthorJae-Sun Uhm-
dc.contributor.googleauthorBoyoung Joung-
dc.contributor.googleauthorMoon-Hyoung Lee-
dc.contributor.googleauthorHui-Nam Pak-
dc.identifier.doi10.3389/fphys.2021.650449-
dc.contributor.localIdA06119-
dc.contributor.localIdA01085-
dc.contributor.localIdA04574-
dc.contributor.localIdA01776-
dc.contributor.localIdA02337-
dc.contributor.localIdA02535-
dc.contributor.localIdA02766-
dc.contributor.localIdA03609-
dc.relation.journalcodeJ02868-
dc.identifier.eissn1664-042X-
dc.identifier.pmid34054570-
dc.subject.keywordPITX2-
dc.subject.keywordantiarrhythmic drugs-
dc.subject.keywordatrial fibrillation-
dc.subject.keywordgene-
dc.subject.keywordmodeling-
dc.contributor.alternativeNameKwon, Oh-Seok-
dc.contributor.affiliatedAuthor권오석-
dc.contributor.affiliatedAuthor김태훈-
dc.contributor.affiliatedAuthor박제욱-
dc.contributor.affiliatedAuthor박희남-
dc.contributor.affiliatedAuthor엄재선-
dc.contributor.affiliatedAuthor유희태-
dc.contributor.affiliatedAuthor이문형-
dc.contributor.affiliatedAuthor정보영-
dc.citation.volume12-
dc.citation.startPage650449-
dc.identifier.bibliographicCitationFRONTIERS IN PHYSIOLOGY, Vol.12 : 650449, 2021-05-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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