A Burning Success

Corresponding Author

Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia across the globe, and its invasive management, although widespread, poses a challenge when aiming for long-term freedom from AF. With success rates at approximately 60%, in absence of antiarrhythmic drugs, after a first procedure for paroxysmal AF (pAF) (1), we are yet to find the silver bullet for AF ablation.

In this issue of JACC: Case Reports, Kim et al. (2) describe the case of a 58-year-old lady with symptomatic pAF refractory to medical therapy and report the successful ablation of a single ganglionated plexus (GP), triggering ectopy causing AF, resulting in freedom from atrial arrhythmias. This proof-of-concept case describes an innovative potential strategy for ablation in patients with pAF, and we are grateful to the authors for sharing this case with the medical community.

There is a breadth of options for managing pAF and, as described in this case, antiarrhythmic medications, such as flecainide, are often used with a “pill in pocket” strategy. Use of many of the antiarrhythmic medications available is hindered by both side effects and contraindications in certain patient groups, notably those with structural or ischemic heart disease, which both have an increased incidence as people age. As AF disproportionately affects the elderly population, this poses challenges in clinical practice. It is clear that an ablative strategy over antiarrhythmic therapy is the preference for pAF management with regard to improvement in symptoms, maintaining sinus rhythm, and changing its natural history (3).

The history of AF ablation dates back to the 1980s, starting with surgical cut-and-sew techniques resulting in isolation of the atria (4), and as the authors note, it was not until 1998 that the landmark observation associating pulmonary veins to the origin and maintenance of AF was published (5). Subsequent extensive research into AF ablation has resulted in pulmonary vein isolation (PVI) becoming the established recommended procedure in all AF ablations. Following PVI, there are many targets for ablation that have been identified over the years (6): GPs are one of the most attractive among them, both on a pathophysiological and on a procedural standpoint.

Innervation of the heart occurs via the extrinsic (central) and intrinsic cardiac autonomic nervous system. The intrinsic cardiac autonomic nervous system is composed of GPs, which are the point of interest in this case. These GPs comprise afferent and efferent neurons, nerve axons, and ganglia clusters and are located on the epicardial surface of the heart, with the majority embedded in epicardial fat pads (7). The majority of neurons are located on the posterior atrial surface, and the 4 major atrial GPs are anatomically located in close proximity to the pulmonary veins and have projections to atrial tissue (8). These GPs have been found to play a role in the initiation and maintenance of AF (9). When performing wide PVI, the slowing of the RR interval is likely due to the interrupting axons of passage between ganglia.

As described in this case, the location of GPs are identified by delivering high-frequency stimulation (HFS) to the left atrial endocardium with the ablation catheter, and while the patient is in AF, this can identify an “atrioventricular dissociating GP,” should there be transient complete atrioventricular block or a >50% prolongation in the average RR interval (Central Illustration A). The majority of studies identify GP location this method or base GP ablation on known anatomy without prior identification using HFS.

Central Illustration.

High-Frequency Stimulation of Ganglionated Plexi in Atrial Fibrillation and Sinus Rhythm

(A) High-frequency stimulation of a ganglionated plexus when the patient is in atrial fibrillation leading to slowing of the RR interval and (B) high-frequency stimulation of a ganglionated plexus in sinus rhythm, which induces an atrial ectopic and leads to atrial fibrillation.

The novel approach proposed by Kim et al. (2) is to look for GPs also in sinus rhythm. The authors propose to perform synchronized HFS in the left atrium in sinus rhythm in order to identify specifically a particular type of GP, called ectopy-triggering GP (ET-GP) (Central Illustration B). HFS on these locations triggers short-cycle atrial ectopics and subsequently AF. The authors demonstrated that ablation on this site resulted in restoration of sinus rhythm during ablation and freedom from atrial arrhythmias at midterm follow-up.

GP ablation for the treatment of AF is not a novel technique: it has long been a controversial topic and is not recommended in current established guidance (10); however, this case describes the first ablation in humans, solely targeting the GP triggering AF, resulting in long-term freedom from AF, for which the authors must be applauded. The limitation of this technique stands in a potential lower reliability compared with PVI because localization of this particular type of GP could be cumbersome and time-consuming or not doable in patients in whom sinus rhythm cannot be restored with electrical or pharmacological cardioversion.

Furthermore, it is still debatable if GP ablation should be performed with or without PVI. Indeed, on the one hand, there is evidence that ablation of GPs in conjunction with traditional PVI confers a higher success rate when treating pAF (74% success, compared with 56% in PVI alone, in freedom from AF at 12 months) (11). On the other hand, when GPs were ablated without PVI, on an anatomical basis, this led to only 48% of success rate (11).

To confirm that when it rains it pours, there are data from canine studies suggesting that there could be not only no benefit in reduction of AF burden, but also proarrhythmic sequelae to GP ablation potentially secondary to reduction in the atrial effective refractory period in the long term, although all data are again based on anatomical ablation of GPs (12, 13, 14). On the clinical side, more recently the AFACT (Ganglionated Plexus Ablation in Advance Atrial Fibrillation) study showed no additional benefit to epicardial GP ablation when undergoing thoracoscopic ablation for advanced AF and indeed resulted in a higher proportion of adverse events (15). A theory behind the limitation of long-term success of GP ablation lies in the diverse effects of ablation on atrial tissue and nervous tissue. Localized ablation performed on atrial tissue results in the creation of infarction and scar; however, neural tissue can exhibit plasticity whereby, should cell bodies be preserved (which may occur after GP ablation), nerve sprouts can emerge from each parent axon, leading to regeneration. In this case, the limited ablation of only 1 ET-GP as opposed to widespread GP ablation may prevent the previously mentioned potential adverse consequences.

When considering an ablative strategy for patient with pAF, this case highlights that there may well be a focal ET-GP trigger to target in certain patients. More data are needed to demonstrate if this approach may prevent the need for further widespread ablation and if it may reduce procedure time, adverse events, and the need of redo procedures. Anyway, this patient-centered approach to ablation with such success should be encouraged and warrants further consideration.

Author Relationship With Industry

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.