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Mechanisms sustaining atrial fibrillation are yet to be clarified. This article focuses on milestones in the theory of atrial fibrillation and addresses the different leading hypotheses concerning atrial fibrillation mechanisms. We start off with electric potential originating from the pulmonary vein, which triggers atrial fibrillation, discuss classic activation mapping and phase mapping as well as computer models, which have contributed to the our understanding of atrial fibrillation, and end with new mapping methods and studies highlighting the advantages and disadvantages of current mechanistic hypotheses. The technical evolution of mapping atrial fibrillation has led to new insights into the potential mechanisms underlying atrial fibrillation. A comparison between methods is essential for understanding the advantages and disadvantages of each method when mapping atrial fibrillation. Ultimately, the combination of several methods might shed light on the underlying mechanisms of atrial fibrillation and lead to a better understanding of atrial fibrillation and subsequently improve treatment of this condition.

BACKGROUND: Cryoballoon apposition is crucial for durable pulmonary vein isolation (PVI) in atrial fibrillation, yet the balloon is difficult to visualize by conventional mapping systems, and pulmonary venography may miss small or out-of-plane leaks. We report a novel imaging system that offers real-time 3D navigation of the cryoballoon within atrial anatomy that may circumvent these issues. METHODS AND RESULTS: A novel overlay guidance system (OGS) registers already-acquired segmented atrial cardiac tomography (CT) with fluoroscopy, enabling real-time visualization of the cryoballoon within tomographic left atrial imaging during PVI. Phantom experiments in a patient-specific 3D printed left atrium showed feasibility for confirming PV apposition and leaks. We applied OGS prospectively to 68 PVs during PVI in 17 patients. The cryoballoon was successfully reconstructed in all cases, and its apposition was compared to concurrent PV venography. The OGS uncovered leaks undetected by venography in nine veins (eight cases), which enabled repositioning, confirming apposition in remaining 68 veins. Concordance of OGS to venography was 83.8% (χ(2), P < .01) CONCLUSIONS: We report a new system for real-time imaging of cryoballoon catheters to ensure PV apposition within the tomography of the left atrium. While providing high concordance with other imaging modalities for confirming balloon apposition or leak, the system also identified leaks missed by venography. Future studies should determine if this tool can provide a new reference for cryoballoon positioning.

OBJECTIVE To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). INTRODUCTION It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods. METHODS We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. RESULTS In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n = 20) and focal (n = 2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P

Pulmonary vein isolation (PVI) is central to ablation approaches for atrial fibrillation (AF), yet many patients still have arrhythmia recurrence after one or more procedures despite the latest technology for PVI. Ablation of rotational or focal sources for AF, which lie outside the pulmonary veins in many patients, is a practical approach that has been shown to improve success by many groups. Localized sources lie in atrial regions shown mechanistically to sustain AF in optical mapping and clinical studies of human AF, as well as computational and animal studies. Because they arise in localized atrial regions, AF sources may explain central paradoxes in clinical practice – such as how limited ablation in patient specific sites can terminate persistent AF yet extensive anatomical ablation at stereotypical locations, which should extinguish disordered waves, does not improve success in clinical trials. Ongoing studies may help to resolve many controversies in the field of rotational sources for AF. Studies now verify rotational activation by multiple mapping approaches in the same patients, at sites where ablation terminates persistent AF. However, these studies also show that certain mapping methods are less effective for detecting AF sources than others. It is also recognized that the success of AF source ablation is technique dependent. This review article provides a mechanistic and clinical rationale to ablate localized sources (rotational and focal), and describes successful techniques for their ablation as well as pitfalls to avoid. We hope that this review will serve as a platform for future improvements in the patient-tailored ablation for complex arrhythmias. Keywords: Atrial fibrillation, Ablation, Rotors, Computer, Mapping

The mechanisms for atrial fibrillation (AF) are unclear in part because diverse mapping techniques yield diverse maps ranging from stable organized sources to highly disordered waves. We hypothesized that AF mechanisms may be clarified if mapping techniques were compared in the same patients, and referenced to a clinical endpoint. We compared 2 independent AF mapping techniques in patients in whom local ablation terminated persistent AF before pulmonary vein isolation (PVI). Techniques and Results We identified 12 patients with persistent AF (61.2±10.8 years, 4 female) in whom mapping with 64 pole baskets and technique 1 (activation/phase mapping, FIRM) identified rotational activation patterns during at least 50% of the 4-second mapping interval and targeted ablation at these rotational sites terminated AF to sinus rhythm (n = 10) or atrial tachycardia. We analyzed the unipolar electrograms of these patients to determine phase maps of activation by an independent technique 2 (Kuklik, Schotten et al., IEEE Trans Biomed Eng 2015). Compared to technique 1, technique 2 revealed a source in 12/12 (100%) cases with spatial concordance in all cases (p

Aims Focal Impulse and Rotor Modulation (FIRM) uses 64-electrode basket catheters to identify atrial fibrillation (AF)-sustaining sites for ablation, with promising results in many studies. Accordingly, new basket designs are being tested by several groups. We set out to determine the procedural safety of adding basket mapping and map-guided ablation to conventional pulmonary vein isolation (PVI). Methods and results We collected 30 day procedural safety data in five US centres for consecutive patients undergoing FIRM plus PVI (FIRM-PVI) compared with contemporaneous controls undergoing PVI without FIRM. A total of 625 cases were included in this analysis: 325 FIRM-PVI and 300 PVI-controls. FIRM-PVI patients were more likely than PVI-controls to be male (83% vs. 66%, P

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 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.

Background: The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure. Methods: Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I 2 statistic. Results: Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%–81.8%; P P P =0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2–2.7; P P Conclusions: In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.

Background: The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation. Methods and Results: We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum –dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms. Conclusions: Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation.

There is considerable interest in identifying potential drivers for human atrial fibrillation (AF), in order to improve therapy. Ablation via pulmonary vein isolation (PVI) is broadly used, yet is insufficient in many patients yet its outcomes are unimproved by adding extensive ablation of lines or complex electrogram sites, particularly in patients with persistent AF. Rotational and focal sources for AF represent novel mechanistic and therapeutic targets, often remote from the PVs and proven to drive AF in many studies. This chapter discusses this issue. AF sources can now routinely be identified clinically by many methods, yet discrepant results have been reported. AF drivers identified by Focal Impulse and Rotor Mapping (FIRM), the most widely applied method, are also seen in simultaneous optical maps of human atria and have now been detected by other mapping methods applied to the exact same signals. In proof-of-concept studies, ablation of drivers can terminate persistent AF and, in over a thousand patients reported thus far, yield favorable long-term outcomes versus PVI alone. Nevertheless, some centers show disappointing results. This review focuses on discrepant results, which may reflect challenging patients, operator unfamiliarity with basket catheter use, or the technical ablation of drivers, amongst other factors. We discuss challenges, potential solutions, and future directions for map-guided AF driver ablation including basket-data collection, interpreting AF maps, ablation guidance, and extent. Mapping and ablation of AF drivers is a rapidly growing field which, with continued scientific discovery and procedural advances, offers a strong mechanistic foundation to improve patient-tailored ablation for complex arrhythmias.