Direct Proof of Endo-Epicardial Asynchrony of the Atrial Wall During Atrial Fibrillation in Humans

Abstract

Background-The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo-and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo-and epicardial wall during AF in humans. Method and Results-Intraoperative mapping of the endo-and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; P=0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions-We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans.Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails. (Circ Arrhythm Electrophysiol. 2016;9:e003648.

Ablating atrial fibrillation: A translational science perspective for clinicians

“…Although intriguing, the extent to which these findings from this study of AF induced by a rotor-stabilizing drug in denervated ex vivo human lateral right atrial wall preparations can be extrapolated to in vivo left and right atria in healthy patients at different settings/stages of AF remains to be established. Indeed, in contrast to the ex vivo study, the recent study by de Groot et al 19 documenting endo-epicardial asynchrony with high density electrode mapping during human AF failed to identify quasi-stable rotors or reentry on either the endocardial or epicardial surfaces.…”

“…In 3D tissue, activation patterns on the endocardial and epicardial surfaces can appear dissociated and asynchronous if scroll wave filaments are not aligned transmurally. Endo-epicardial asynchrony during human AF has been recently demonstrated by de Groot et al 19 . These authors characterized the arrhythmia mechanism as multisite endo-epicardial reexcitation in which wavefronts propagating on one surface cross-over and break through to excite recovered regions on the opposite surface, and vice versa in a reciprocating manner.…”

“…Simulations have also shown the false positive detection of phase singularities can be a significant problem 13 . Although quasi-stable rotors have been observed during AF in some animal models, rotors that complete one or many full rotations have only rarely been identified during AF in patients using high density epicardial mapping during heart surgery 12, 19, 29–31 . More commonly, focal excitations (target waves), breakthroughs and multiple broken colliding waves have been described.…”

16th Atrial Fibrillation Symposium

“…A recently published paper delineates the zones of epicardial and endocardial dissociation along the opposite surface, resulting in breakthrough activity. 6 Thus, focal firing on the endo-or epicardial surface may be due to breakthrough instead of ectopy, and endo-epicardial interaction may multiply AF-maintaining sources. This may be a form of AF-maintaining activity that does not involve true ectopy or re-entry.…”

Evolution of AF ablation strategies-Role of PVI?

“…These two proposed mechanisms have been shown to appear in isolation and also simultaneously, resulting in a much more complex pattern of AF [8]. More recently in 2010, Allessie proposed 'the double layer hypothesis' adding a third dimension to the complexity of AF in which endo-epicardial dissociation plays a major role in maintaining AF [9,10].…”