The “Double Layer” Hypothesis Offers Alternative Explanation for Longstanding Persistent Atrial Fibrillation
Maurits Alessie, MD, PhD (Department of Physiology, Maastrict University, Maastrict, The Netherlands), Natasja de Groot, MD, PhD ) Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands), and Charles Kik, MD (Department of Cardiothoracic Surgery, Erasmus Medical Center, Rotterdam, The Netherlands) spoke with AF Symposium News about this fascinating presentation, which will take place during the group of sessions on “Rotors and Other Mechanisms in Persistent AF: Concepts and Controversies.”
Dr. Allessie and colleagues describe that in recent years, a growing number of scientists and physicians have started to believe that persistent atrial fibrillation (AF) is maintained by a single stable rotor somewhere in the atrial wall. This notion is primarily based on computer-generated fibrillation maps from low-resolution intracavitary electrograms, recorded with a basket catheter.2, 3 Reconstruction of the fibrillatory process by body surface mapping pointed to the presence of multiple unstable rotors.4 In great contrast, high-density contact maps recorded directly from the epicardium during cardiac surgery (spatial resolution 2 mm) failed to demonstrate any significance rotor activity.1, 5, 8
“Instead, fibrillation maps showed highly complex and continuously changing activation patterns by a multitude of narrow fibrillation waves,” said Dr. Allessie (See Figure 1.) The different fibrillation waves were separated by lines of conduction block oriented parallel to the atrial muscle bundles (longitudinal dissociation).5 Another striking feature of longstanding persistent AF was the high incidence of focal fibrillation waves (more than four times higher than in acutely induced AF).6 Focal waves were not repetitive but occurred predominately as solitary events (Figure 1). They were observed over the entire atrial surface (right and left alike), and unipolar electrograms recorded at their origin generally showed small R-waves. The cycle lengths of focal waves varied considerably and were often longer than the median AF cycle length.6 Dr. Allessie explained: “These characteristics make it not very likely that focal fibrillation waves are generated by ectopic focal discharges. On the other hand, they are in complete agreement with what one would expect if focal fibrillation waves were caused by endo-epicardial breakthroughs.”
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To obtain direct evidence that in patients with longstanding AF, the atrial wall is electrically dissociated, Allessie and colleagues performed simultaneous endo-epicardial mapping, using a clamp of two closely opposed electrode-arrays of 2 x 128 electrodes.9 One leg was introduces through the right atrial incision required for cardio-pulmonary bypass, and the clamp was gently closed. During persistent AF, asynchronous endo-epicardial activation (≥15ms) was frequently observed. Focal waves appeared equally frequent at the endocardial and epicardial side (11% vs. 13%, P=0.12). To assess the occurrence of endo-epicardial breakthrough, the opposite layer was examined for the presence of a fibrillation wave that could have served as a source for the focal wave (Figure 2). Using strict criteria for breakthrough (propogation of an opposite wavefront within 4mm distance and maximally 15ms before the appearance of a focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation by a fibrillation wave propagating in the opposite layer.9 However, not all focal waves were associated with endo-epicardial surface.
In patients with longstanding persistent AF, the total number of focal waves recorded during complete epicardial mapping was quite high, ranging between 3.000-5.000/minute (Figure 3). Dr. Allessie pointed out that “The actual incidence of focal waves is probably even higher since some (or all?) of the planar waves entering the periphery of the mapping array could also have originated form endo-epicardial breakthrough, outside the mapping area. Since endocardial breakthroughs occurred as frenquently as epicardial breakthroughs, we estimate that during persistend AF, the total number of focal fibrillation waves accounts for at least 8.000 per minute.”
He added: “This means that at a dominant AF-frequency of 400/minute, during each cycle and average of 20 new focal waves will arise, ten at the sub-epicardial and ten at the sub-endocardial layer. Since each breakthrough should be considered as a multiplication site (see Figure 4), together all breakthroughs form a huge reservoir of ‘new’ fibrillation waves. This is true even while breakthroughs are usually not repetitive and predominantly occur as solitary events at ever-changing sites.”
Dr. Allessie continued, “Thus, instead of being maintained by an eternal single source, the ‘double-layer’ hypothesis proposes that atrial fibrillation is perpetuated by the existence of two dissociated layers of multiple narrow wavelets that constantly ‘feed’ each other. Although the life span of fibrillation waves is rather short, the arrhythmia is sustained by the abundant offspring of new fibrillation waves at multiple breakthrough sites between the two layers. In such a substrate, there is no need for reentry or focal discharges to perpetuate atrial fibrillation. It adequately explains the high persistence of AF and the disappointing results of ablation procedures to restore and maintain sinus rhythm in patients with longstanding persistent AF.”
Allessie MA, de Groot NM, Cross-Talk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation. J Physiol. 2014;592:3167-3170.
Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (CONventional ablation for atrial fibrillation with or without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012;60:628-636.
Narayan SM, Shivkumar K, Krummen DE, Miller JM, Rappel WJ. Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms. Cin Arrhythm Electrophysiol. 2013;6:58-67.
Haissaguerre M, Hocini M, Denis A, et all. Driver Domains in persistent atrial fibrillation. Circulation. 2014;130:530-538.
Allessie MA, de Groot NM, Houben RP, et al. The electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation. Circ Arrhythm Electrophysiol. 2010;3:606-615.
de Groot NMS, Houben RP, Smeets JL, et al. The electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough. Circulation. 2010;122:1674-1682.
Lee G, Kumar S, Teh A, et al. Epicardial wave mapping in human long-lasting persistent AF: transient rotational circuits, complex wave fronts and disorganized activity. Eur Heart J. 2014;35:86-97.
Lee S, Sahadevan J, Khrestian CME, Cakulev I, Markowitz A, Waldo AL, Simultaneous bi-atrial high density (512) electrodes) epicardial mapping of persistent atrial fibrillation in patients: new insights into mechanism of its maintenance. Circ Arrhythm Electrophysiol. 2015 Oct 23;doi: 10.1161/CIRCULATIONAHA.115.017007.
de Groot NMS, van der Does L, Yaksh A, et al. Direct proof of endo-epicardial asynchrony of the atrial wall during atrial fibrillation in humans. Cir Arrhythm Electrophysiol. (under review)