For decades, electrical activity recorded has been investigated to unravel pathophysiology of cardiac arrhythmias, such as atrial fibrillation (AF). Particularly high-resolution mapping studies have significantly contributed to novel insights into AF mechanisms. From these mapping studies, it appeared that persistence of AF is associated with a high incidence of focal patterns of activation. Features of these focal activation patterns indicated that they could be attributed to transmural propagation of fibrillation waves. However, "focal fibrillation waves" can only appear when there is electrical asynchrony between the endocardial and epicardial layer. By performing simultaneous high-resolution mapping of the endo- and epicardial wall of the right atrium in humans during AF, the existence of electrical asynchrony (endo-epicardial asynchrony [EEA]) between the endo- and epicardial layer was indeed confirmed. During sinus rhythm, focal patterns of activation are most frequently observed at the right atrium and a considerable degree of EEA-as large as 50 ms-may occur. Furthermore, prematurely aberrant atrial extrasystoles emerging as focal waves caused the highest degree of conduction disorders, particularly in patients with left atrial dilatation and diabetes mellitus. These observations emphasize the contribution of atrial anatomy to EEA and the role of focal patterns of activation in development AF.
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