High Density Mapping of Atrial Fibrillation During Vagal Nerve Stimulation in the Canine Heart: Restudying the Moe Hypothesis

Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, M B S Celeen; Durand, Dominique M.; Waldo, Albert L.

doi:10.1111/jce.12032

Cited by 63 publications

(41 citation statements)

References 20 publications

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“…2,13,19 The study by de Groot et al 2 postulates transmural conduction of fibrillation waves as the leading mechanism of epicardial breakthrough, whereas many others use radial spread of activation as criterion to identify ectopic focal discharges during AF. [20][21][22][23][24] Using radial spread of activation and QS electrogram morphology as criterion for ectopy, Lee et al 25 recently demonstrate that AF in dogs undergoing vagal stimulation can be maintained by multiple ectopic foci.…”

Section: Discussionmentioning

confidence: 99%

Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation

Eckstein

Zeemering

Linz

et al. 2013

Circ: Arrhythmia and Electrophysiology

139

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Present hypotheses on mechanisms underlying breakthrough events include transmural conduction from the opposing layer of the atrial wall (endo-epicardial or vice versa), transmural microreentry, or ectopic focal discharges. 2,[5][6][7][8][9][10][11][12] Electric dissociation between the endocardial bundle network and the epicardial layer (EED) during AF is a prerequisite condition for transmural conduction of fibrillation waves because only in the presence of EED electric activity in 1 layer of the atrial wall can encounter excitable tissue in the opposing layer.We recently demonstrated that in goats EED increases during the first 6 months of AF, 13 which might well explain the higher incidence of breakthrough in complex substrates for AF. However, increasing evidence for altered intracellular Ca 2+ handling in atrial myocytes of AF patients supports the hypothesis that ectopic focal discharges because of triggered activity might also occur during AF and contribute to its perpetuation. 9,12,14 © 2013 American Heart Association, Inc. Background-Endo-epicardial dissociation (EED) of electric activations resulting in transmural conduction of fibrillation waves (breakthroughs) has been postulated to contribute to the complexity of the substrate of atrial fibrillation (AF). The aim of this study was to elucidate the correlation between EED and incidence of breakthrough and to test the plausibility of transmural conduction versus ectopic focal discharges as sources of breakthrough. Methods and Results-We analyzed high-resolution simultaneous endo-epicardial in vivo mapping data recorded in left atrial free walls of goats with acute AF, 3 weeks and 6 months of AF (all n=7). Waves were analyzed for number, size, and width and categorized according to their origin outside (peripheral wave) or within the mapping area (breakthrough). Breakthrough incidence was lowest (2.1±1.0%) in acute AF, higher (11.4±6.1%) after 3 weeks (P<0.01 versus acute AF) and highest (14.2±3.8%) after 6 months AF (P<0.001 versus acute AF) and similar in the epicardium and endocardium. Most of the breakthroughs (86%; n=564) could be explained by transmural conduction, whereas only 13% (n=85) could be explained by ectopic focal discharges. Transmural microreentry did not play a role as source of breakthrough. Conclusions-This is the first study to present simultaneous endo-epicardial in vivo mapping data at sites of breakthrough events. Breakthrough incidence and degree of EED increased with increasing AF substrate complexity. In goat left atrial free walls, most of the breakthroughs can be explained by transmural conduction, whereas ectopic focal discharges play a limited role as source of breakthrough. (Circ Arrhythm Electrophysiol. 2013;6:334-341.) Circ Arrhythm Electrophysiol

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Section: Discussionmentioning

confidence: 99%

Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation

Eckstein

Zeemering

Linz

et al. 2013

Circ: Arrhythmia and Electrophysiology

139

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“…24 A single relatively stable source in canine RA using a high concentration of acetylcholine by Schuessler et al, 8 and multifocal AF in the sterile pericarditis model by Waldo and colleagues, 6,25 as well, have been reported. Jalife and colleagues 4,26 used phase-based optical signal processing to demonstrate rotor activities with a spectrum of scenarios from single meandering rotor to multiple, periodic rotors giving rise to fibrillatory activation.…”

Section: Progressive Remodeling Of Atrial Tissue With Af Continuationmentioning

confidence: 99%

“…1,2 Multiple atrial wavelets, macroreentries, and localized (focal or reentrant) sources have been reported to contribute to the substrate of persistent AF. [3][4][5][6] For determining a therapeutic strategy in persistent AF (localized target versus global intervention), the key question is whether the multitude of activation waves that characterize persistent AF individually emanate from few, stable, periodic drivers or whether the waves are transitory, widely distributed, and self-perpetuating. Localized drivers are difficult to detect in persistent AF with conventional techniques because of sequential temporospatial mapping, lack of specificity of complex atrial electrograms, intermittent firing, and spatial meandering.…”

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confidence: 99%

Driver Domains in Persistent Atrial Fibrillation

et al. 2014

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Background-Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). Methods and Results-In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region.In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant. Conclusions-Persistent Methods Study PopulationThis is a hospital-based study of patients with persistent AF. All consecutive patients referred for ablation of persistent AF were enrolled between May 2012 and June 2013. Persistent AF was defined as continuous AF from 7 days to 12 months and long-lasting AF beyond 12 months. There were no exclusion criteria based on the left atrial size, ventricular ejection fraction, or structural heart disease. All patients gave written informed consent to participate in the study, which involved the use of an investigational system for mapping. The study protocol was approved by the institutional Clinical Research and Ethics Committee. Noninvasive MappingIf patients presented in ongoing AF, mapping was performed bedside, within 24 hours preceding the invasive procedure. For those presenting in sinus rhythm, AF was induced in the electrophysiological laboratory by rapid atrial pacing decrementing up to 200-ms cycle length at the beginning of the invasive procedure and before transseptal puncture. Induced AF was analyzed after >30 minutes of sustenance (during this time, intracardiac catheter placement and invasive mapping were undertaken). Isoproterenol was not used to facilitate induction.The noninvasive mapping techniq...

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“…Both experimental and human studies suggest rotor and ectopic activity to drive persistent AF. [7][8][9][10] However, detailed highdensity direct contact mapping studies in goat and humans identified multiple wavelets, increasing longitudinal dissociation and transmural conduction (epicardial breakthrough) as dominant AF mechanisms. [1][2][3][4][5] In these studies, stable rotors were rare and not sustained, and breakthroughs were largely because of transmural conduction rather than ectopic activity.…”

Section: Putative Af Mechanisms and Atrial Anatomymentioning

confidence: 99%

Rearrangement of Atrial Bundle Architecture and Consequent Changes in Anisotropy of Conduction Constitute the 3-Dimensional Substrate for Atrial Fibrillation

Maesen

Zeemering

Afonso

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background— Anisotropy of conduction facilitates re-entry and is, therefore, a key determinant of the stability of atrial fibrillation (AF). Little is known about the effect of AF on atrial bundle architecture and consequent changes in anisotropy of conduction and maintenance of AF. Methods and Results— Direct contact mapping was performed in left atria of goats with acute AF (n=6) or persistent AF (n=5). The degree and direction of anisotropic conduction were analyzed. Mapped tissue regions were imaged by high-resolution MRI for identification of endocardial and epicardial bundle directions. Correlation between endocardial and epicardial bundle directions and between bundle directions and anisotropic conduction was quantified. In persistent AF, epicardial bundles were oriented more perpendicularly to endocardial bundles than in acute AF (% angles <20° between epicardial and endocardial bundle directions were 7.63% and 21.25%, respectively; P <0.01). In acute AF, the direction of epicardially mapped anisotropic conduction correlated with endocardial but not with epicardial bundles. In persistent AF, the direction of anisotropic conduction correlated better with epicardial than with endocardial bundles (% angles <20° between direction of anisotropic conduction and bundle direction were 28.77% and 18.45%, respectively; P <0.01). Conclusions— During AF, atrial bundle rearrangement manifests itself in more perpendicular orientation of epicardial to endocardial bundles. Propagation of fibrillation waves is dominated by endocardial bundles in acute AF and by epicardial bundles in persistent AF. Together with the loss of endo-epicardial electrical connections, rearrangement of atrial bundles underlies endo-epicardial dissociation of electrical activity and the development of a 3-dimensional AF substrate.

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High Density Mapping of Atrial Fibrillation During Vagal Nerve Stimulation in the Canine Heart: Restudying the Moe Hypothesis

Abstract: In contrast to the prediction of the multiple wavelet hypothesis, during AF in the Moe model, multiple foci drove the atria, producing and maintaining AF. Reentry played little, if any, role.

Cited by 63 publications

References 20 publications

Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation

Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation

Driver Domains in Persistent Atrial Fibrillation

Rearrangement of Atrial Bundle Architecture and Consequent Changes in Anisotropy of Conduction Constitute the 3-Dimensional Substrate for Atrial Fibrillation

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