Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques

Abstract

Background: Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods.

Methods: We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360±45 cycles using (1) a published phase method and (2) a commercial activation/phase method.

Results: Patients were 62.2±9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6±23.9% and 70.6±20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition.

Conclusions: Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

Keywords: atrial fibrillation; mapping; network; patients; pulmonary vein; registries; tachycardia.

Conflict of interest statement

Disclosures

Dr Brachmann reports modest honoraria from Medtronic, Bayer, and Biotronik. Dr Miller reports consulting fees from Biosense Webster and Abbott Electrophysiology (both modest); honoraria from Biosense Webster, Medtronic Inc, and Boston Scientific (all modest); fellowship support from Biosense Webster, Medtronic Inc, and Boston Scientific (all significant). Dr Krummen reports consulting for Abbott Laboratories (modest) and fellowship support from Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. Dr Narayan reports consulting compensation from Up to Date, Abbott Laboratories, American College of Cardiology Foundation (all modest); speaking/consulting fees from Medtronic, Inc (modest), and St. Jude Medical (modest); equity interests from Topera Medical (significant); and intellectual property rights from University of California Regents (significant). Dr Wang reports honoraria/consultant from Janssen, St. Jude Medical, Amgen, and Medtronic; (all modest) fellowship support from Biosense Webster (moderate), Boston Scientific (moderate), Medtronic, and St. Jude Medical (all modest); clinical studies from Medtronic, Siemens, Cardiofocus, and ARCA Biopharma (all modest); and stock options from VytronUS (modest). The other authors report no conflicts.

© 2018 American Heart Association, Inc.

Figures

Figure 1.. Rotational activity at atrial fibrillation (AF) termination site, revealed by 2 mapping systems for most AF cycles over a minute.

In a 67-year-old woman with persistent AF, (A) atrial shell, where ablation at site A, (B) terminated persistent AF via atrial tachycardia (AT) to sinus rhythm (SR). C, Counterclockwise rotation at site A by both methods. Another site B showed clockwise rotation that was also continuous but did not perturb site A. Randomly selected control site C showed no rotations. D, Prevalence of rotations at site A for successive 4-s windows over 1 min of AF by both methods. At arrowed time points; Movie I in the Data Supplement shows continuous rotations at site A by both methods, and Movie II in the Data Supplement shows interrupted rotations by method 1 but continuous rotations by method 2. FIRM indicates focal impulse and rotor modulation; LAA, left atrial appendage; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; and RSPV, right superior pulmonary vein.

Figure 2.. At atrial fibrillation (AF) termination site, rotational activity without competing organized sites.

In a 78-year-old man with persistent AF, (A) atrial shell on which ablation at site A, (B) terminated persistent AF. C, Clockwise rotation at site A by both mapping methods. No rotations are seen at control site C. D, Prevalence of rotations at site A for successive 4-s windows over 1 minute of AF by both methods. At arrowed time points, Movie III in the Data Supplement shows continuous rotations at site A by both methods; Movie IV in the Data Supplement shows interrupted rotations by method 1 but continuous rotations by method 2. FIRM indicates focal impulse and rotor modulation; LAA, left atrial appendage; LIPV, left inferior pulmonary vein; RIPV, right inferior pulmonary vein; and RSPV, right superior pulmonary vein.

Figure 3.. Phase singularities in similar locations on automatic tracking.

A, Automatic phase singularity tracking along its atrial path for methods 1 (red) and 2 (blue). B, Area enclosed by the meandering path of both methods showed a proportional overlap of 65.7% between methods. C, Area overlap of phase singularities between both methods for the entire cohort was 79.6±23.1%. Four patients did not show organized activity by method 1.

Figure 4.. Fluctuating rotational activation at atrial fibrillation (AF) termination site, because of intermittent reciprocal activity from competing organized site.

In a 49-year-old woman with persistent AF, (A) Atrial shell on which ablation at Site A, (B) terminated persistent AF. C, Clockwise rotational activation at site A by method 1 (phase). D, Inspection of separate time windows revealed clear focal activity emerging from site B. Randomly selected control site C showed no rotational activation. E, Prevalence of rotational activation at sites A (blue) and B (orange) for successive 4-s windows for 1 min of AF. Sites A/B were reciprocal, high prevalence at site A at times of low prevalence at site B and vice versa. Movie V in the Data Supplement shows a transition from rotations at site A to focal activation at site B. Abl indicates ablation; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; PVI, pulmonary vein isolation; RIPV, right inferior pulmonary vein; and RSPV, right superior pulmonary vein.

Figure 5.. Patient-level prevalence of organized activity patterns over 1 min for the entire cohort.

Columns indicate median presence for all 4-s windows during the minute. Error bars represent interquartile range. Forty-seven of 55 patients showed organized activity for >50% of 1 min at the site of atrial fibrillation (AF) termination by ablation.

Figure 6.. Recording duration to detect potential atrial fibrillation (AF) drivers at sites of termination varies with definition.

Ordinate shows detection rate of organized AF patterns, abscissa shows increasing cumulative durations of recording time as randomly selected (nonduplicated) 4-s windows for up to 1 min. Distributions are shown for 4 definitions of potential AF drivers. For definition 1 (≥66% prevalence), 32 s of AF achieves a 90% probability of detecting a potential AF driver. For definition 2 (≥50% prevalence), definition 3 (≥33% prevalence), and definition 4 (≥10% prevalence), 4 to 8 s of recording is sufficient