Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Research Center, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
PLoS One. 2024 Nov 22;19(11):e0314342. doi: 10.1371/journal.pone.0314342. eCollection 2024.
Transmural propagation and endoepicardial delays in activation observed in patients with atrial fibrillation are hypothesized to be associated with structural remodeling and endoepicardial dissociation. We aim to explore in a computational model how the distribution of delays and the rate of endo- and epicardial breakthrough activation patterns are affected by fibrosis and heterogeneous layer dissociation.
A bilayer interconnected cable model of the left atrium was used to simulate a total of 4,800 episodes of atrial fibrillation on 960 different arrhythmogenic substrates with up to 30% epicardium-only diffuse fibrosis. Endoepicardial connections were heterogeneously distributed following random spatial patterns (characteristic length scale from 1.6 to 11.4 mm). Intermediate nodes were introduced in the transmural connections to enable the simulation of weaker coupling. This heterogeneous interlayer dissociation divided the atrial bilayer into connected and disconnected regions (from 27 to 48,000 connected regions). Activation time series were extracted in both layers to compute endoepicardial delays and detect breakthrough patterns.
Because of epicardial fibrosis, fibrillatory waves were driven by the endocardium, which generated endoepicardial delays. The delays in the connected regions (up to 10 ms, but generally < 5 ms) were prolonged by higher fibrosis density and weaker coupling. Disconnected regions allowed longer delays (> 15 ms) and promoted the occurrence of breakthroughs. These breakthroughs had short lifespan (< 10-20 ms) and were more prevalent with higher fibrosis density and heterogeneous dissociation (larger disconnected regions). Severe remodeling (< 500 connected regions) was needed to produce clinically reported rates (> 0.1 breakthrough/cycle/cm2).
Heterogeneous endoepicardial dissociation aggravates activation delays and increases the prevalence of epicardial breakthroughs.
在心房颤动患者中观察到的跨壁传播和心内膜延迟激活被假设与结构重塑和心内膜分离有关。我们旨在通过计算模型探索延迟的分布以及内、心外膜突破激活模式的速率如何受到纤维化和异质层分离的影响。
使用左心房双层互联电缆模型，在 960 种不同的致心律失常基质上模拟了总共 4800 个心房颤动发作，其中多达 30%的心外膜仅弥漫纤维化。心内膜和心外膜连接呈随机空间模式（特征长度尺度为 1.6 至 11.4 毫米）不均匀分布。在贯穿壁连接中引入中间节点，以实现较弱的耦合模拟。这种不均匀的层间分离将心房双层分为连接和不连接区域（从 27 个到 48000 个连接区域）。在两个层中提取激活时间序列，以计算心内膜和心外膜延迟并检测突破模式。
由于心外膜纤维化，纤维颤动波由心内膜驱动，从而产生心内膜和心外膜延迟。在连接区域（最长 10 毫秒，但通常<5 毫秒）中，延迟随着纤维化密度的增加和耦合减弱而延长。不连接的区域允许更长的延迟（>15 毫秒），并促进突破的发生。这些突破的寿命较短（<10-20 毫秒），并且随着纤维化密度和异质分离（更大的不连接区域）的增加更为普遍。只有严重的重构（<500 个连接区域）才能产生临床报告的发生率（>0.1 突破/周期/平方厘米）。
不均匀的心内膜和心外膜分离会加重激活延迟并增加心外膜突破的发生率。
