AUTHOR=Hwang Inseok , Jin Ze , Park Je-Wook , Kwon Oh-Seok , Lim Byounghyun , Lee Jisu , Yu Hee-Tae , Kim Tae-Hoon , Joung Boyoung , Pak Hui-Nam 

TITLE=Spatial Changes in the Atrial Fibrillation Wave-Dynamics After Using Antiarrhythmic Drugs: A Computational Modeling Study

JOURNAL=Frontiers in Physiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.733543

DOI=10.3389/fphys.2021.733543

ISSN=1664-042X

ABSTRACT=Background 
We previously reported that a computational modeling-guided anti-arrhythmic 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. 

Methods 
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 5 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 (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. 

Results 
The mean DF decreased after the administration of AADs in the dose dependent manner (p<0.001). Under AADs, the DF was significantly lower (p<0.001) and COV-DF higher (p=0.003) in the PV than extra-PV region. The mean DF was significantly lower at a high Smax (Over 1.4) than a lower Smax condition under AADs. During the episodes of AF defragmentation, the mean DF was lower (p<0.001), but the COV-DF was higher (p<0.001) than that in those without defragmentation. 

Conclusions 
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.