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.
Highlights
Atrial fibrillation (AF) is a common arrhythmia, with a prevalence of more than 1.6% of the total population, and the prevalence continues to increase in the aging society (Kim et al, 2018)
The patient group consisted of 25 atrial fibrillation (AF) patients (68.0% male, 59.8 ± 9.8 years old, 32.0% paroxysmal AF) who had undergone radiofrequency catheter ablation (Supplementary Table 3)
Antiarrhythmic drugs (AADs) dose-dependently changed the APD90 (p < 0.001), AFCL (p < 0.001), and CV (p < 0.001), and the dominant frequency (DF) reduction was more pronounced at high doses than low doses (p < 0.001, Table 1)
Summary
Atrial fibrillation (AF) is a common arrhythmia, with a prevalence of more than 1.6% of the total population, and the prevalence continues to increase in the aging society (Kim et al, 2018). Computational modeling can evaluate the efficacy of multiple AADs under the same condition and can quantify the mechanistic effects of AADs using very high-spatiotemporal resolution maps (Loewe et al, 2014; Li et al, 2016; Lim et al, 2020b; Bai et al, 2021; Hwang et al, 2021). This virtual AAD test does not have any ethical problems because it allows testing of multiple drugs with variable doses without the risk of adverse events (Hwang et al, 2021). We explored the anti-AF mechanisms of AADs and spatial change in the AF wave-dynamics by a realistic computational model
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