Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation

Abstract

Background: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping. Methods: Patients with persistent atrial fibrillation (n=14; mean age, 61±8 years; ejection fraction, 59±10%) underwent simultaneous biatrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase, and subsequent spatiotemporal mapping was performed to identify phase singularities (PSs). RESULTS: PSs were located in both atria, but we observed more PSs in the left atrium compared with the right atrium (779±302, 552±235; P =0.015). Although some PSs of duration sufficient to complete >1 rotation were detected, the maximum PS duration was only 1150 ms, and the vast majority (97%) of PSs persisted for too short a period to complete a full rotation. Although in selected patients there was evidence of PS local clustering, overall, PSs were distributed globally throughout both chambers with no clear anatomic predisposition. In a subset of patients (n=7), analysis was repeated using an alternative established atrial PS mapping technique, which confirmed our initial findings. Conclusions: No sustained rotors or localized drivers were detected, and instead, the mechanism of arrhythmia maintenance was consistent with the multiple wavelet hypothesis, with passive activation of short-lived rotational activity. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01765075.

Prospective cross‐sectional study using Poisson renewal theory to study phase singularity formation and destruction rates in atrial fibrillation (RENEWAL‐AF): Study design

“…The exponential distribution is significant because it is the statistical signature of a Poisson stochastic renewal process 9 . The universality of this finding, in not only our data but observable in underlying phase singularity data from multiple other investigators, 8,12,13,18,24,25 supports the notion that the rate constants of rotor formation and destruction are fundamental properties of atrial fibrillation pathophysiology.…”

“…Electroanatomical data including electrograms, 3D data, and surface ECG will then be exported and processed using MATLAB. Signals will be filtered as previously described 12 . Phase singularity detection will be performed with an extended topological charge‐based approach 13 .…”

Challenges Associated with Interpreting Mechanisms of AF

“…Consequently, we recommend applying multiple analysis techniques to the same electrical dataset to increase confidence in the findings; for example, using both activation and phase mapping or using alternative phase mapping techniques. 3,87 Fibrosis Mapping Modelling studies may aim to select regions of fibrosis most likely to harbour re-entrant drivers. 96…”

“…The hierarchical theory of AF proposes a degree of organisation in AF, sustained by discrete electrical drivers, whereas the anarchical theory proposes that AF is sustained by a large number of randomly propagating, self-perpetuating activation wavelets without the presence of discrete electrical drivers. [ 1 – 3 ] Differences in reported AF mechanisms may be because AF is recorded across diverse models, investigational tools, spatial scales and clinical populations, ranging from paroxysmal to permanent AF.…”

Analytical approaches for myocardial fibrillation signals

“…Phase mapping was originally applied to transmembrane potential data. More recently, techniques have been developed for phase mapping of unipolar and bipolar electrogram data, during both VF [ 41 ] and AF [ 40 , 45 , 46 , 47 ]. The correct calculation of electrogram phase during AF is difficult due to several factors, including the non-sinusoidal and fractionated nature of the electrograms, and the direction-dependency of bipolar electrograms.…”