Hwang Inseok, Park Je-Wook, Kwon Oh-Seok, Lim Byounghyun, Lee Jisu, Jin Ze, Yu Hee-Tae, Kim Tae-Hoon, Joung Boyoung, Pak Hui-Nam
Yonsei University Health System, Seoul, South Korea.
Front Physiol. 2021 Sep 24;12:733543. doi: 10.3389/fphys.2021.733543. eCollection 2021.
We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for evaluating multiple AADs in patients with atrial fibrillation (AF). We explored the anti-AF mechanisms of AADs and spatial change in the AF wave-dynamics by a realistic computational model. We used realistic computational modeling of 25 AF patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal AF) reflecting the anatomy, histology, and electrophysiology of the left atrium (LA) to characterize the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone). We evaluated the spatial change in the AF wave-dynamics by measuring the mean dominant frequency (DF) and its coefficient of variation [dominant frequency-coefficient of variation (DF-COV)] in 10 segments of the LA. The mean DF and DF-COV were compared according to the pulmonary vein (PV) vs. extra-PV, maximal slope of the restitution curves (Smax), and defragmentation of AF. The mean DF decreased after the administration of AADs in the dose dependent manner ( < 0.001). Under AADs, the DF was significantly lower ( < 0.001) and COV-DF higher ( = 0.003) in the PV than extra-PV region. The mean DF was significantly lower at a high Smax (≥1.4) than a lower Smax condition under AADs. During the episodes of AF defragmentation, the mean DF was lower ( < 0.001), but the COV-DF was higher ( < 0.001) than that in those without defragmentation. The DF reduction with AADs is predominant in the PVs and during a high Smax condition and causes AF termination or defragmentation during a lower DF and spatially unstable (higher DF-COV) condition.
我们之前报道过，计算模型引导的抗心律失常药物（AAD）测试对于评估房颤（AF）患者的多种AAD是可行的。我们通过一个真实的计算模型探索了AAD的抗AF机制以及AF波动力学的空间变化。我们对25例AF患者（68%为男性，年龄59.8±9.8岁，32.0%为阵发性AF）进行了反映左心房（LA）解剖、组织学和电生理学的真实计算建模，以表征五种AAD（胺碘酮、索他洛尔、决奈达隆、氟卡尼和普罗帕酮）的作用。我们通过测量LA的10个节段中的平均主导频率（DF）及其变异系数[主导频率-变异系数（DF-COV）]来评估AF波动力学的空间变化。根据肺静脉（PV）与肺静脉外、恢复曲线的最大斜率（Smax）以及AF的碎裂情况比较平均DF和DF-COV。给予AAD后，平均DF以剂量依赖性方式降低（<0.001）。在AAD作用下，PV区域的DF显著更低（<0.001），而COV-DF更高（=0.003）。在AAD作用下，高Smax（≥1.4）时的平均DF显著低于低Smax情况。在AF碎裂发作期间，平均DF更低（<0.001），但COV-DF高于无碎裂情况（<0.001）。AAD导致的DF降低在PV中以及高Smax情况下最为显著，并在较低DF和空间不稳定（较高DF-COV）状态下导致AF终止或碎裂。
