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. 2021 Sep 24:12:733543.
doi: 10.3389/fphys.2021.733543. eCollection 2021.

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

Inseok Hwang  1 , Je-Wook Park  1 , Oh-Seok Kwon  1 , Byounghyun Lim  1 , Jisu Lee  1 , Ze Jin  1 , Hee-Tae Yu  1 , Tae-Hoon Kim  1 , Boyoung Joung  1 , Hui-Nam Pak  1
Affiliations

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

Inseok Hwang et al. Front Physiol. .

Erratum in

Abstract

Background: 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. 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 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. 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 (≥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.

Keywords: antiarrhythmic drug; atrial fibrillation; computational modeling; dominant frequency; spatial changes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Computational modeling of the left atrium with atrial fibrillation (AF). Realistic left atrium (LA) modeling was conducted using an interpolation of the voltage map and merging with the CT images. Fibrosis and the fiber orientation were implemented. The LAT map synchronization and AF simulation protocol were conducted for the analyses.
FIGURE 2
FIGURE 2
The effects of antiarrhythmic drugs (AADs) on extra-PV and pulmonary vein (PV) regions. The 3D dominant frequency (DF) map indicated that the mean DF was higher in the PV regions. Electrograms demonstrated regional voltage changes in PV and extra-PV areas. Coefficient of Variation-Dominant Frequency (COV-DF) was higher in class IC and PV region.
FIGURE 3
FIGURE 3
Changes in the dominant frequency (DF) during a high and low Smax. The 3D DF map indicated that the mean DF was inversely related to the mean Smax. Regional voltage changes in pulmonary vein (PV) and extra-PV areas were demonstrated in electrograms.
FIGURE 4
FIGURE 4
Changes in the dominant frequency (DF) during Termination and Atrial Tachycardia. The 3D DF map indicated that the mean DF was lower during AT episodes, and AF termination episodes. Electrograms demonstrated AT and AF termination episodes.
FIGURE 5
FIGURE 5
Heterogeneity of dominant frequency (DF). Heterogeneity of DF was observed in overall defragmentation as well as termination group.
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