Epicardial Ablation of Rotors Suppresses Inducibility of Acetylcholine-Induced Atrial Fibrillation in Left Pulmonary Vein–Left Atrium Preparations in a Beagle Heart Failure Model

Chou, Chung‐Chuan; Wen, Ming‐Shien; Lee, Hui‐Ling; Chen, Tse–Ching; Yeh, San‐Jou; Wu, Delon

doi:10.1016/j.jacc.2011.02.045

Cited by 35 publications

(23 citation statements)

References 13 publications

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“…Previous chronic AF dog models have demonstrated that without medication, the ventricular response rate is fast (Ͼ220 beats/min) and that heart failure develops unless AV nodal ablation or pharmaceutical interventions are used (4,23,35). Rapid ventricular pacing induces congestive heart failure in dogs when pacing rates are 220 -260 beats/min (10,28). In the present study, dogs developed significant heart failure even when the ventricular Ease of handling animals…”

Section: Discussionmentioning

confidence: 99%

Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs

Dosdall

Ranjan

Higuchi

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n ϭ 4), dogs (n ϭ 8), and goats (n ϭ 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50 -100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to Ͻ180 beats/min and to mitigate the effects of heart failure. The pacing leads in pigs became entirely encapsulated and lost the ability to excite the heart, often before the onset of sustained AF. LV EF in dogs dropped from 54 Ϯ 11% at baseline to 33 Ϯ 7% at 6 mo (P Ͻ 0.05), whereas LV EF in goats did not drop significantly (69 Ϯ 8% at baseline vs. 60 Ϯ 9% at 6 mo, P ϭ not significant). After 6 mo of AF, fibrosis levels in dog atria and ventricles increased, whereas only atrial fibrosis levels increased in goats compared with control animals. In our experience, the pig model is not appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF. animal models; chronic atrial fibrillation; fibrosis; heart failure; rapid atrial pacing ATRIAL FIBRILLATION (AF) is the most frequent chronic arrhythmia (22) and significantly increases the risk of stroke and mortality (7). AF currently affects ϳ3 million patients in the United States alone, and its prevalence is predicted to increase to Ͼ7.5 million by the year 2050 (20). Despite significant advances in treatment options, including rhythm and rate control techniques, AF is frequently recurrent and persistent.A significant limitation in the development of broadly effective treatments for AF is that the development of the substrate that leads to longstanding persistent AF is not well understood. It is well known that "AF begets AF," or, in other words, the longer AF persists, the more likely it is that a patient will experience more AF in the future (30). Numerous studies (1,8,24,29,33,34) have demonstrated that there are significant structural and electrophysiological substrate changes that accompany chronic AF.Recent studies (14,15,26,27) have shown that whereas electrical remodeling and sustained AF may be achieved in a matter of weeks, tissue levels and structural remodeling continue over months. Patients with longstanding persistent AF exhibit different activation patterns and have higher AF recurrence rates than patients with paroxysmal AF (11,25,31). Chronic large animal models of sustained AF provide the opportunity to study the development of the substrate that leads to AF persistence and recurrence. The purpose ...

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Section: Discussionmentioning

confidence: 99%

Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs

Dosdall

Ranjan

Higuchi

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…RF lesions were delivered point-by-point at the area covering the focal and reentrant drivers with the use of serial applications. 10,20 When drivers were seen in the PVs, circumferential ablation of ipsilateral PVs was undertaken. The end point of regional ablation was the slowing of local electric activity.…”

Section: Rf Ablationmentioning

confidence: 99%

“…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. [7][8][9] Wide-field mapping tools have been used to capture these sources with the use of balloon, multispline probes 5,[10][11][12][13][14] or electrode arrays enveloping the torso. [15][16][17][18] Recent developments have allowed biatrial AF mapping using activation or phase-based analysis of body surface potentials.…”

mentioning

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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“…The 2 prevailing hypotheses are, first, that AF is caused by spatially meandering electrical waves (the multiwavelet hypothesis (124)) and, second, that AF is caused by electrical spiral waves (rotors) or focal beat sources from which activity disorganizes to the surrounding atrium (the localized source hypothesis (125)). Chou et al (126) provided data to support the localized source hypothesis, in Langendorff-perfused LA-pulmonary vein preparations from 13 dogs. Sustained AF was induced by rapid pacing and acetylcholine infusion and was characterized by rotors in all animals with additional focal beat sources in just over one-half.…”

Section: Mechanisms Of Human Atrial Fibrillationmentioning

confidence: 94%

Highlights of the Year in JACC 2011

DeMaria

Bax

Ben‐Yehuda

et al. 2012

Journal of the American College of Cardiology

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Epicardial Ablation of Rotors Suppresses Inducibility of Acetylcholine-Induced Atrial Fibrillation in Left Pulmonary Vein–Left Atrium Preparations in a Beagle Heart Failure Model

Abstract: Epicardial ablation of the rotor anchoring sites suppresses AF inducibility. The arrhythmogenicity at the maximal dominant frequency sites is directly/indirectly suppressed by the rotor ablation.

Cited by 35 publications

References 13 publications

Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs

Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs

Driver Domains in Persistent Atrial Fibrillation

Highlights of the Year in JACC 2011

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