Computational Modeling for Antiarrhythmic Drugs for Atrial Fibrillation According to Genotype

• Published in: Frontiers in physiology 2021-05, Vol.12, p.650449-650449
• Main Authors: Hwang, Inseok, Jin, Ze, Park, Je-Wook, Kwon, Oh-Seok, Lim, Byounghyun, Hong, Myunghee, Kim, Min, Yu, Hee-Tae, Kim, Tae-Hoon, Uhm, Jae-Sun, Joung, Boyoung, Lee, Moon-Hyoung, Pak, Hui-Nam
• Format: Article
• Language: English
• Subjects: antiarrhythmic drugs; atrial fibrillation; gene; modeling; Physiology; PITX2
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2021.650449

The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF), and the gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and -deficient AF conditions by realistic AF modeling. We tested the V-AADs in AF modeling integrated with patients' 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications. We compared the wild-type and deficiency in terms of the action potential duration (APD ), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The -deficient model exhibited a shorter APD ( < 0.001), a lower Smax ( < 0.001), mean DF ( = 0.012), PS number ( < 0.001), and a longer AF cycle length (AFCL, = 0.011). Five V-AADs changed the electrophysiology in a dose-dependent manner. AAD-induced AFCL lengthening ( < 0.001) and reductions in the CV ( = 0.033), peak DF ( < 0.001), and PS number ( < 0.001) were more significant in -deficient than wild-type AF. -deficient AF was easier to terminate with class IC AADs than the wild-type AF ( = 0.018). The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamic and electrophysiological characteristics are different among the -deficient and the wild-type genotype models.