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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

Objectives The purpose of this study was to determine the mechanistic overlap between paroxysmal and persistent forms of atrial fibrillation (AF), focusing on AF sources as a classification approach. Background The role of AF substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation. Methods In 175 patients at 11 centers, we compared AF substrates in both atria using 64-pole basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF. Results Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near pulmonary veins (PVs) than patients with redo PAF (47.4%; p = 0.005) or persistent AF (46.9%; p = 0.001). The total number of sources per patient (p = 0.444), and number of non-PV sources (p = 0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5 ± 9.5 mm vs. 49.0 ± 7.1 mm; p = 0.956) but was larger in patients with persistent AF (55.2 ± 8.4 mm; p = 0.001). Conclusions Patients with PAF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with PAF at first ablation. Notably, these subgroups of PAF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent PAF after PVI.

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.