Abstract
BackgroundRecent researches have suggested that the complex three-dimensional structures caused by structural remodeling play a key role in atrial fibrillation (AF) substrates. Here we aimed to investigate this hypothesis using a multi-layer model representing intramural microstructural features.MethodsThe proposed multi-layer model was composed of the endocardium, connection wall, and epicardium. In the connection wall, intramural fibrosis was simulated using fibrotic patches randomly scattered in the myocardial tissue of fibrotic layers, while endo-epicardial dissociation was simulated using myocardial patches randomly scattered in the fibrotic tissue of isolation layers. Multiple simulation groups were generated to quantitatively analyze the effects of endo-epicardial dissociation and intramural fibrosis on AF stability, including a stochastic group, interrelated groups, fibrosis-degree-controlled groups, and dissociation-degree-controlled groups.Results1. Stable intramural re-entries were observed to move along complete re-entrant circuits inside the transmural wall in four of 65 simulations in the stochastic group. 2. About 21 of 23 stable simulations in the stochastic group were distributed in the areas with high endo-epicardial dissociation and intramural fibrosis. 3. The difference between fibrosis-degree-controlled groups and dissociation-degree-controlled groups suggested that some distributions of connection areas may affect AF episodes despite low intramural fibrosis and endo-epicardial dissociation. 4. The overview of tracking phase singularities revealed that endo-epicardial dissociation played a visible role in AF substrates.ConclusionThe complex intramural microstructure is positively correlated with critical components of AF maintenance mechanisms. The occurrence of intramural re-entry further indicates the complexity of AF wave-dynamics.
Highlights
Atrial fibrillation (AF) is a progressive supraventricular arrhythmia characterized by rapid and disorderly atrial electrical activity [1]
About 21 of 23 stable simulations in the stochastic group were distributed in the areas with high endoepicardial dissociation and intramural fibrosis
The difference between fibrosis-degreecontrolled groups and dissociation-degree-controlled groups suggested that some distributions of connection areas may affect AF episodes despite low intramural fibrosis and endoepicardial dissociation
Summary
Atrial fibrillation (AF) is a progressive supraventricular arrhythmia characterized by rapid and disorderly atrial electrical activity [1]. Gutbrod et al [12] acquired optical and electrical signals of endocardium and epicardium synchronously in sheep with acute AF and correlated across imaging planes to gauge the synchrony of the activation patterns compared with paced rhythms, suggesting that AF substrates are dynamic three-dimensional (3D) structures with a range of discordance between endocardium and epicardium. A recent study by Hansen and colleagues [13] found that the intramural re-entry projected differently on endocardium and epicardium using high-resolution optical mapping in ex vivo preparations from diseased hearts, revealing the critical importance of better understanding the role of complex atrial microstructure in AF maintenance. Recent researches have suggested that the complex three-dimensional structures caused by structural remodeling play a key role in atrial fibrillation (AF) substrates. We aimed to investigate this hypothesis using a multi-layer model representing intramural microstructural features
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