Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study

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

Research output: Contribution to journalArticlepeer-review


Introduction: Atrial 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. Methods: We 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. Results: At 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). Conclusion: Consistent 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.

Original languageEnglish
Article number942998
JournalFrontiers in Cardiovascular Medicine
Publication statusPublished - 2022 Jul 19

Bibliographical note

Funding Information:
This work was supported by a grant [HI21C0011] from the Ministry of Health and Welfare, a grant [NRF-2020R1A2B5B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT & Future Planning (MSIP), and a grant [RS-2022-00141473] from Cross-ministerial tasks.

Publisher Copyright:
Copyright © 2022 Jin, Hwang, Lim, Kwon, Park, Yu, Kim, Joung, Lee and Pak.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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