Epicardial Fibrosis Explains Increased Endo–Epicardial Dissociation and Epicardial Breakthroughs in Human Atrial Fibrillation

Abstract

Background: Atrial fibrillation (AF) is accompanied by progressive epicardial fibrosis, dissociation of electrical activity between the epicardial layer and the endocardial bundle network, and transmural conduction (breakthroughs). However, causal relationships between these phenomena have not been demonstrated yet. Our goal was to test the hypothesis that epicardial fibrosis suffices to increase endo-epicardial dissociation (EED) and breakthroughs (BT) during AF. Methods: We simulated the effect of fibrosis in the epicardial layer on EED and BT in a detailed, high-resolution, three-dimensional model of the human atria with realistic electrophysiology. The model results were compared with simultaneous endo-epicardial mapping in human atria. The model geometry, specifically built for this study, was based on MR images and histo-anatomical studies. Clinical data were obtained in four patients with longstanding persistent AF (persAF) and three patients without a history of AF. Results: The AF cycle length (AFCL), conduction velocity (CV), and EED were comparable in the mapping studies and the simulations. EED increased from 24.1 ± 3.4 to 56.58 ± 6.2% (p < 0.05), and number of BTs per cycle from 0.89 ± 0.55 to 6.74 ± 2.11% (p < 0.05), in different degrees of fibrosis in the epicardial layer. In both mapping data and simulations, EED correlated with prevalence of BTs. Fibrosis also increased the number of fibrillation waves per cycle in the model. Conclusion: A realistic 3D computer model of AF in which epicardial fibrosis was increased, in the absence of other pathological changes, showed increases in EED and epicardial BT comparable to those in longstanding persAF. Thus, epicardial fibrosis can explain both phenomena.

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium

“…However, experimental recordings by Verheule et al [55,56], have demonstrated the existence of endomysial fibrosis which develops exclusively within the epicardial layer and accompanies the transition from persistent to permanent AF in goats. Moreover, a recent computational study by Gharaviri et al [57] in a human atrial model has proven that such fibrotic patterns could result in increased breakthroughs and endo-epicardial dissociations. In future studies, intramural fibrosis should be incorporated into atrial models to analyse its effects on the RD dynamics and CA strategy.…”

A Novel Tool for the Identification and Characterization of Repetitive Patterns in High-Density Contact Mapping of Atrial Fibrillation

“…Furthermore, electrode array resolution has been shown to significantly impact AF driver identification (Roney et al, 2017). Computation modeling of AF can help to investigate the effect of 3D conduction, dissociation and mapping device on pattern detection, providing that the model incorporates the 3D nature of the atrial anatomy and bundle structure, and exhibits epi-endocardial dissociation to an extent that 3D conduction patterns can be simulated [see for instance (Gharaviri et al, 2020)].…”

Long-standing Persistent Atrial Fibrillation Ablation: the Role of the Inter- and Intra-atrial Bundles

“…mostly over the areas of the Bachmann's and septopulmonary bundles 9,10 . The complexity of the interconnection between the right and left atriums, and between the epicardium and endocardium during atrial fibrillation partially explains the high rate of complex, reentrant, and recurrent atrial tachy-arrhythmias that are seen in patients with persistent atrial fibrillation after they have undergone catheter ablation, especially when single lines of ablation or focal lesions over fractionated potentials have been used as strategy.…”