Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study
IntroductionAtrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.942998/full |
| _version_ | 1818478597756682240 |
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| author | Ze Jin Inseok Hwang Byounghyun Lim Oh-Seok Kwon Je-Wook Park Hee-Tae Yu Tae-Hoon Kim Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak |
| author_facet | Ze Jin Inseok Hwang Byounghyun Lim Oh-Seok Kwon Je-Wook Park Hee-Tae Yu Tae-Hoon Kim Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak |
| author_sort | Ze Jin |
| collection | DOAJ |
| description | IntroductionAtrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2+/− deficient) using computational modeling.MethodsWe included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2+/− deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.ResultsAt the baseline AF, mean DF (p = 0.003), and Smax (p < 0.001) were significantly lower in PITX2+/− deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p < 0.001) without changing the DF or Smax. Although a PITX2+/− deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p < 0.001), and lower Smax (p = 0.001) in PITX2+/− deficient AF than in wild-type patients. In the clinical setting, the PITX2+/− genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273).ConclusionConsistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2+/− deficient patients. |
| first_indexed | 2024-12-10T09:49:40Z |
| format | Article |
| id | doaj.art-c0b76229e1404887a955e3c208ef6dae |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-10T09:49:40Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-c0b76229e1404887a955e3c208ef6dae2022-12-22T01:53:41ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-07-01910.3389/fcvm.2022.942998942998Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling studyZe JinInseok HwangByounghyun LimOh-Seok KwonJe-Wook ParkHee-Tae YuTae-Hoon KimBoyoung JoungMoon-Hyoung LeeHui-Nam PakIntroductionAtrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2+/− deficient) using computational modeling.MethodsWe included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2+/− deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.ResultsAt the baseline AF, mean DF (p = 0.003), and Smax (p < 0.001) were significantly lower in PITX2+/− deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p < 0.001) without changing the DF or Smax. Although a PITX2+/− deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p < 0.001), and lower Smax (p = 0.001) in PITX2+/− deficient AF than in wild-type patients. In the clinical setting, the PITX2+/− genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273).ConclusionConsistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2+/− deficient patients.https://www.frontiersin.org/articles/10.3389/fcvm.2022.942998/fullatrial fibrillationcomputational modelingPITX2dominant frequencyantiarrhythmic drug |
| spellingShingle | Ze Jin Inseok Hwang Byounghyun Lim Oh-Seok Kwon Je-Wook Park Hee-Tae Yu Tae-Hoon Kim Boyoung Joung Moon-Hyoung Lee Hui-Nam Pak Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study Frontiers in Cardiovascular Medicine atrial fibrillation computational modeling PITX2 dominant frequency antiarrhythmic drug |
| title | Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study |
| title_full | Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study |
| title_fullStr | Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study |
| title_full_unstemmed | Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study |
| title_short | Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study |
| title_sort | ablation and antiarrhythmic drug effects on pitx2 deficient atrial fibrillation a computational modeling study |
| topic | atrial fibrillation computational modeling PITX2 dominant frequency antiarrhythmic drug |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.942998/full |
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