AUTHOR=Gharaviri Ali , Bidar Elham , Potse Mark , Zeemering Stef , Verheule Sander , Pezzuto Simone , Krause Rolf , Maessen Jos G. , Auricchio Angelo , Schotten Ulrich TITLE=Epicardial Fibrosis Explains Increased Endo–Epicardial Dissociation and Epicardial Breakthroughs in Human Atrial Fibrillation JOURNAL=Frontiers in Physiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00068 DOI=10.3389/fphys.2020.00068 ISSN=1664-042X 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.