Panoramic Electrophysiological Mapping but not Electrogram Morphology Identifies Stable Sources for Human Atrial Fibrillation

Narayan, Sanjiv M.; Shivkumar, Kalyanam; Krummen, David E.; Miller, John M.; Rappel, Wouter Jan

doi:10.1161/circep.111.977264

Cited by 162 publications

(160 citation statements)

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“…55 Given the predominantly functional nature of CFAEs, however, this explanation seems unlikely, and Narayan's group has demonstrated that CFAEs are largely spatially unrelated to sites of rotors or other focal AF drivers. 70 Nevertheless, all CFAEs may not be equivalent, 71 and fractionation may evolve over time as AF transitions from paroxysmal to persistent. 72 Ablation of fractionated electrograms which demonstrate continuous activity or temporal activation gradients have been shown to be more strongly associated with AF slowing or termination, 73 and the subset of CFAEs that persist in AF, sinus rhythm or with atrial pacing might also be important in the pathophysiology of AF, with a potential role as an ablation target.…”

Section: Complex Fractionated Electrograms Are Passive Bystanders In Afmentioning

confidence: 99%

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Waks

Josephson²

2014

Arrhythmia &Amp; Electrophysiology Review

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Atrial fibrillation (AF), the most common sustained arrhythmia, is a leading cause of stroke, and is associated with significant morbidity and mortality worldwide. Despite its frequency, clinical importance, and advances in technology and our knowledge of the molecular, ionic and physiological fundamentals of cardiac electrophysiology, our limited understanding of the mechanisms that initiate and sustain AF has prevented us from being able to truly cure this arrhythmia with antiarrhythmic drugs and/or ablation. This contrasts with other arrhythmias, such as AV nodal tachycardia or circus movement tachycardia using an accessory pathway, which have well-defined mechanisms and circuits that can be safely targeted with high rates of cure. The observations that AF may have different mechanisms in different patients, and that paroxysmal, persistent and permanent forms of AF may differ in how they are initiated and sustained, only serves to reinforce our lack of understanding of this ubiquitous arrhythmia. Historical Mechanisms of Atrial Fibrillation and the Multiple Wavelet HypothesisInterest and understanding of the mechanism of AF began to take form in the early 1900s. Given the chaotic and irregular nature of AF on the surface electrocardiogram, rapid firing of automatic atrial foci was considered a potential mechanism. However, after the seminal work of Mayer 1 , Mines 2 and Garrey 3 in laying the foundation for describing and understanding reentrant arrhythmias, atrial reentrant circuits emerged as the likely drivers of AF.4-7 Although these theories were conceptually sound, it was impossible to prove a specific mechanism with the technology of the time. Moe et al. demonstrated that it was probabilistically unlikely that a large number of simultaneous wavefronts would all die out simultaneously, and AF would therefore perpetuate. However, if the number of simultaneous wavelets were small and/or below a critical value (between 15 and 30 in Moe's computer model), 9 at some point all reentrant wavefronts would be simultaneously extinguished, and AF would therefore terminate. 8,9 Allessie et al. provided experimental evidence supporting this mechanism in a canine heart model of AF where four to six simultaneous reentrant wavelets were needed to sustain arrhythmia. 10 Further evidence supporting multiple wavelets in AF was demonstrated in a separate model, which evaluated the effect of various antiarrhythmic drugs on canine myocardium. This model demonstrated that termination of AF was associated with a reduction AbstractAtrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, yet our understanding of the mechanisms that initiate and sustain this arrhythmia remains quite poor. Over the last 50 years, various mechanisms of AF have been proposed, yet none has been consistently observed in both experimental studies and in humans. Recently, there has been increasing interest in understanding how spiral waves or rotors -which are specific, organised forms of functional reentry -su...

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Section: Complex Fractionated Electrograms Are Passive Bystanders In Afmentioning

confidence: 99%

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Waks

Josephson²

2014

Arrhythmia &Amp; Electrophysiology Review

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“…In cell monolayers, rotor meandering causes fusion of action potentials to produce fractionated electrograms, 28 that in clinical studies is further confused by the multiple technical causes of fractionated electrograms. 29 These mechanisms may obscure rotors or give the illusion of rotors that are 'unstable' in activation maps, but are continuous if appropriate signal processing techniques are used.…”

Section: Signal Processing Approaches To Identify and Track Precessinmentioning

confidence: 99%

“…In FIRM maps, precessing rotors in human AF produce electrograms that are regular in some cases and 'fractionated' in others. 29 …”

Section: Conventional Ablation For Atrial Fibrillation With or Withoumentioning

confidence: 99%

“…Accordingly, direct source ablation has become the default method, to cover the rotor precession areas of 2-3 cm 2 (or 6-10 non-overlapping lesions of ~5-7 mm diameter). 29 Many catheters have been used, including 3.5 mm tip open-irrigated radiofrequency (Thermocool, BiosenseWebster, Diamond Bar, CA), 8 mm tip non-irrigated radiofrequency (Blazer, Boston Scientific, Natick, MA), or cryoablation 44 and robotic navigation. 45 Typically two to three simultaneous rotors are identified within a given patient, requiring ~15-20 minutes of ablation covering 5-10 cm 2 of atrial tissue.…”

Section: Ablation Of Atrial Fibrillation Sourcesmentioning

confidence: 99%

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Role of Rotors in the Ablative Therapy of Persistent Atrial Fibrillation

Schricker¹,

Zaman²,

Narayan³

2015

Arrhythmia &Amp; Electrophysiology Review

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Catheter ablation is more effective than pharmacological therapy for the secondary prevention of patients with paroxysmal 1,2 and persistent 3,4 atrial fibrillation (AF) and has an emerging role in the primary prevention of paroxysmal AF. 5,6 Nevertheless, in randomised clinical trials (RCTs) its success in treating patients with paroxysmal AF is 40-60 % for a single procedure and 70 % for multiple procedures at one year, 1,2 and results for persistent AF are lower. 7,8 Thus, there is an urgent unmet need to improve our understanding of mechanistic targets for AF in each patient, to match recent advances in ablation energy delivery and catheter positioning.This report reviews mechanistic data on human AF, mapping technologies that provide the opportunity to reconcile fundamental mechanisms in individual patients and their therapeutic application. Atrial Fibrillation MechanismsAF is initiated by triggers predominantly near the pulmonary veins (PV), 9 with increasingly recognised sites outside the PVs. [10][11][12] To improve success, ablation to eliminate AF triggers should thus also target non-PV triggers, although they are transient and difficult to locate. Another potential ablative target is the mechanistic cascade by which triggers initiate AF, yet this is relatively unstudied. We recently showed -using wide-area mapping during spont aneous and induced AF -that the first cycles of AF after a trigger exhibit a single organised re-entrant spiral wave or focal driver (see Figure 1) that subsequently disorganises. 13 Remarkably, these AF-initiating mechanisms may be relatively spatially fixed for each patient -even for different triggers from both atria -separated by 2.1 ± 1.7 cm from trigger sites (see Figure 1). 13 Thus, AF initiation is likely to be a two-step mechanistic process, in which 1) a trigger initiates an organised spiral wave or focal source at patient-specific anatomical sites that 2) lead rapidly to disorganisation to produce the classical AF phenotype. This begs the question of whether AF maintenance is driven by self-sustaining disorganisation, or whether disorganisation is actually sustained by localised AF drivers (rotors or focal drivers).Self-sustaining disorganisation was traditionally considered the mechanism of AF maintenance. This mechanism is supported by computational models in which multiple wavelets sustain AF if there is enough room in the atrium ('critical mass'), 14 proposals that dissociation between the epicardium and endocardium may be contributory 15 and plaque recordings from the atria of patients in the operating room showing re-entry without apparent organisation. Limitations to these studies are that fibrillatory maps are based upon recordings that poorly represent local activation;16 only small areas of the atria were mapped (<10-20 %) and while these studies show that disorganisation exists they did not test if it self-sustains. The success of widespread ablation or Maze surgery supports the concept of self-sustaining disorganisation, but are also consistent with coinci...

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“…Elimination of these targets terminated persistent and paroxysmal AF, which also became noninducible. 9, 10 The following reports from that study group emphasized the importance of patient-specific AF mapping. 11 Further studies with long-term follow-up are required, though ablation for persistent AF will shift from empirical to novel mapping-based approaches in the near future.…”

Section: Article P 1416mentioning

confidence: 99%