Circ Arrhythm Electrophysiol Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial FibrillationClinical Perspective by Jens Eckstein, Stef Zeemering, Dominik Linz, Bart Maesen, Sander Verheule, Arne van Hunnik, Harry Crijns, Maurits A. Allessie, and Ulrich Schotten Circ Arrhythm Electrophysiol Volume 6(2):334-341 April 16, 2013 Copyright © American Heart Association, Inc. All rights reserved.

Example of a dissociated epicardial wave (left) and a nondissociated epicardial wave (right). Example of a dissociated epicardial wave (left) and a nondissociated epicardial wave (right). Two pairs of endo- and epicardial isochronal maps (time between isochrones 5 ms, red earliest, blue latest). Epicardial surfaces display a single wave. Outlines of the epicardial waves are projected on the endocardial maps. Waves were compared for their activation times and directions of propagation to the opposing layer. If the overlap in time and direction was <20% the wave was categorized as dissociated (example on the left), if it was >80% as nondissociated (example on the right). Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Identification of a putative source of a breakthrough. Identification of a putative source of a breakthrough. In this example, a breakthrough (indicated by a white star) was evaluated for preceding activations of the closest 25 opposing electrodes (grid, 5×5=64 mm2). Endocardial electric activity was preceding the epicardial breakthrough by 6 ms (red area within the transparent box in the endocardial isochronal map, time between isochrones 5 ms, red earliest, blue latest). The distance between endocardial and epicardial part of the mapping array was 2.7 mm, reflecting a conduction velocity of 45 cm/s. This breakthrough was, therefore, categorized as explainable by transmural conduction assuming a transmural conduction velocity of 45 cm/s and a source area in the opposing layer of 5×5 electrodes (64 mm2; space angle, ≈98°). Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Atrial remodeling leading to heterogeneous conduction and increasing incidence of breakthrough. Atrial remodeling leading to heterogeneous conduction and increasing incidence of breakthrough. Original tracings on top of the graph depict different extents of conduction alterations with electrogram fractionation with the increasing complexity of the atrial fibrillation (AF) substrate. Epicardial isochronal maps depict examples of increasing heterogeneity of activation with AF duration (time between isochrones 5 ms, earliest activations color coded in red, latest in blue, white stars representing sites of breakthrough). Graphs depict the increasing number of fibrillation waves/AF cycle length (AFCL), and decreasing size of fibrillation waves with AF duration (x-axis depicting number of electrodes activated by the same wave). *P<0.05 vs aAF; †P<0.05 vs 3 wk AF (same layer). Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Breakthrough incidence and degree of endo-epicardial dissociation (% dissociated waves) increase with increasing atrial fibrillation (AF) substrate complexity. Breakthrough incidence and degree of endo-epicardial dissociation (% dissociated waves) increase with increasing atrial fibrillation (AF) substrate complexity. Each mark represents the result of 1 episode of 4 s in each of the 21 goats investigated. Acute AF goats are represented by circles, 3 wk AF goats by triangles, and 6 months AF goats by dots. Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Three different categories of breakthrough. Three different categories of breakthrough. Three examples with consecutive endo-epicardial isochronal maps before and after a breakthrough event (indicated by white stars, time between isochrones 5 ms, red earliest, blue latest). Original endocardial and epicardial electrogram tracings from the site of breakthrough (depicting 3 beats before and 3 beats after the breakthrough) are depicted below the corresponding isochronal maps. Red lines in electrograms mark the time point of breakthrough. Top, Epicardial breakthrough with preceding endocardial activation classified as transmural conduction (86%). A fibrillation wave activating both the epicardial and the endocardial layer (entering from above) is slowed down in the epicardial layer (crowding of isochronal lines, upper left corner) but rapidly propagates in the endocardial layer from where it activates the epicardium and fuses with the delayed epicardial part of the initial wave. The corresponding local unipolar electrogram tracing shows an R/S morphology, which supports the hypothesis of putative transmural activation. Center, Simultaneous endocardial and epicardial radial activation pattern. Focal ectopic discharge activating endo- and epicardium simultaneously in the absence of endo-epicardial dissociation is assumed to underlie this conduction pattern. This activation pattern was present in 13% of all events. The corresponding local unipolar electrogram tracing showed small R-waves, which could point toward focal ectopic activity from the mid myocardium at this site. Bottom, Epicardial radial spread of activation preceding the endocardial activation. No clear mechanism explaining these events could be identified (only 1% of all events). Most likely mechanism seems focal ectopic discharge in the epicardial layer with transmural conduction block preventing propagation to the endocardium. Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Assessment of intramural micro reentry as mechanism underlying breakthrough. Assessment of intramural micro reentry as mechanism underlying breakthrough. Activation time differences between starting points of breakthrough and preceding breakthrough in the opposing layer of the atrial wall. Y-axis depicts the number of events, x-axis depicts time delay between starting points of successive breakthrough events. No increase in incidence of activations in the opposing layer possibly related to intramural reentry at AF cycle length/2 (≈60 ms; light grey bar) was present. Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.

Proposed positive feedback loop highlighting the contribution of endo-epicardial dissociation and transmural conduction to the progressive nature of atrial fibrillation. Proposed positive feedback loop highlighting the contribution of endo-epicardial dissociation and transmural conduction to the progressive nature of atrial fibrillation. Jens Eckstein et al. Circ Arrhythm Electrophysiol. 2013;6:334-341 Copyright © American Heart Association, Inc. All rights reserved.