Pulsed field ablation: have we finally found the holy grail?

This editorial refers to ‘Pulsed field ablation prevents chronic atrial fibrotic changes and restrictive mechanics after catheter ablation for atrial fibrillation’ by Y. Nakatani et al., pages 1767--1776. Pulsed field ablation (PFA) is rapidly emerging as a novel energy source. The latter is a non-thermal ablation method in which high voltage ultra-short pulses are delivered in order to create lesions on the targeted tissue. The mechanism by which PFA leads to permanent cellular damage is based on the formation of nano-scale pores in the cellular membrane. This leads to leakage of cellular content with the end result of death by apoptosis.1,2 This ablation modality is particularly attractive due to the speed with which it creates a lesion but more importantly to its intrinsic capacity of being ultraselective in targeting a specific tissue. Conversely, thermal ablation methods invariably create collateral damage to neighbouring structures. This can lead to a number of potential complications such as pericardial effusion, pulmonary vein stenosis, phrenic nerve palsy, or the dreaded atrio-oesophageal fistula.3,4 These are just a few examples of adverse events and are typically encountered during atrial fibrillation (AF) ablation. Therefore, a safe and effective energy source would be more than welcome in electrophysiology laboratories all around the world in which most procedures consist of pulmonary vein (PV) isolation to treat AF. A recent publication by Reddy et al.,5 analysed the impact of PFA in 81 patients affected by paroxysmal AF. At 12 months roughly 90% of individuals did not experience recurrence of any atrial arrhythmias. Furthermore, the rate of procedural complications was considerably low if compared to reports focusing on thermal ablation. Interestingly, the authors also observed that electrical isolation chronically persisted at an antral level at repeat invasive procedures. The authors concluded that PFA led to rapid and efficient PV isolation with a degree of tissue selectivity and a safety profile previously not described for cardiac ablation. Another recent article regarding PFA ablation in persistent AF underlined6 the outstanding safety profile of this ablation modality. In fact, post-procedure oesophagogastroduodenoscopy and repeat cardiac computed tomography revealed no mucosal lesions or PV narrowing. In an animal model paper by Koruth et al.,7 PFA induced no damage to the oesophagus, while radiofrequency (RF) ablation led to a spectrum of oesophageal lesions including fistula and deep oesophageal ulcers. In this issue of EP Europace, Nakatani et al.8 analysed the impact of PFA during AF ablation on the left atrial tissue composition and subsequent mechanics of the left atrial chamber by the use of cardiac magnetic resonance imaging. The authors elegantly compared their findings to a cohort of patients having undergone the same procedure with thermal ablation. The authors observed that late gadolinium enhancement (LGE) was present in both cohorts after ablation. However, PFA was associated with significantly larger areas of LGE, homogeneously and densely distributed around the PV antra without signs of microvascular damage or intramural haemorrhage. Conversely, LGE images following thermal ablation were significantly less homogeneous and showed reproducibly areas of structural damage to the tissue. Most interestingly, in the chronic stage most of the LGE observed in the acute phase after PFA had disappeared. Interestingly, no patient in this group showed PV reconnection at the repeat invasive 3D mapping procedure at 3 months after the index ablation. The authors hypothesized that the lack of chronic fibrosis might be due to the mechanism of cellular death induced by PFA, which is apoptosis. Conversely, thermal ablation, leads to necrosis which causes fibrosis through an inflammatory reaction. The latter is especially true when dealing with RF energy. Additionally, acute alterations in atrial mechanics, such as atrial strain, seemed to also recover after PFA. This interesting report underlines once more the safety and efficacy profile of this novel ablation technology. In fact less (if none) fibrosis in the left atrium would mean no post-procedural PV stenosis or even left atrial stiff syndrome which in some cases can lead to disastrous consequences. Performing ablation in the left atrium without fearing collateral damage to neighbouring anatomical structures without jeopardizing clinical outcome is the dream come true of every electrophysiologist. Considering the main goal of treating symptoms related to the arrhythmia in otherwise healthy patients (certainly in paroxysmal AF) and the elective nature of AF ablation, safety is imperative when approaching these procedures. Pulsed field ablation also has the capacity of isolating the PVs extremely rapidly. In fact, all reports comparing procedural times between thermal ablation and PFA clearly show that the latter is significantly faster. And with experience, these will further increase in speed and lead to unprecedently low left atrial dwelling times. In addition, this might lead to the abatement of waiting lists in many electrophysiology laboratories. However, although extremely promising, one could argue that important structures such as the ganglionated plexi or the perivenous innervation might not be targeted by PFA due to the ultraselective nature. Multiple reports have studied the importance of these nervous structures in the maintenance of AF,9,10 and modulation of the latter by ablation might be needed to guarantee freedom from AF in the long term. Therefore, although extremely promising, only studies with longer clinical follow-up will tell if PFA will become the new gold standard of ablation and if thermal energy will remain only a distant memory of the past. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.