Introduction: The understanding of atrial fibrillation (AF) mechanisms and success of its treatments remain suboptimal. Various electrophysiological phenomena seen experimentally, such as rotors and breakthroughs, have been proposed as drivers sustaining AF. This work aims to elucidate the mechanistic links between rotors and breakthroughs by demonstrating that the architecture of atrial pectinate muscles (PM) can act as a hidden pathway for rotors to evolve into breakthroughs.
Method: A computational model was created using a 3D canine atrial geometry and fibre orientation obtained from contrast-enhanced micro-computed tomography (micro-CT). The action potentials (AP) were computed using canine-specific electrophysiology models. The 3D models included ionic and structural heterogeneities in the atria, and specifically between the right atrium (RA) and pectinate muscles (PM). Sustained AF was generated by rapid ectopic pacing in the pulmonary veins (PV). Results were visualized through 3D atrial voltage maps (VM), 2D isochronal maps (IM), and wave maps (WM). Pharmacological effects of 10µM Amiodarone were modelled by reducing the relevant ionic currents.
Results: AF episodes were initiated in the entire atria and initially maintained by several epicardial rotors around the PVs and in the RA. Transmural rotors were then observed to propagate through the PM and re-emerge at the RA epicardium later during these episodes. IM and WM revealed multiple breakthroughs at the region where the PM connect to the RA. The presence of Amiodarone caused the both the transmural and epicardial rotors to be terminated, leaving only a single rotor in the PV.
Conclusion: The modelling showed that the complex activation patterns in AF can be determined by the interactions of epicardial and transmural rotors. Breakthroughs seen in such patterns can be explained by transmural waves propagating from the depth of 3D atrial tissue. These results can reconcile controversial viewpoints on AF mechanisms and lead to mechanism-based AF treatments.