Discussion
PFA is primarily a non-thermal ablative strategy that relies on pulsed applications of high-intensity electric fields for short durations which result in cellular and tissue electroporation.1 This phenomenon represents a process whereby the applied electric field results in the formation of pores within the cell membrane. Depending on the parameters of the applied electric fields, pore formation can lead to permeabilization which may be either reversible or irreversible. In reversible electroporation, cells remain viable and this process underlies the basis of electrochemotherapy and gene electrotransfer. Conversely, irreversible electroporation renders cells and tissues nonviable as a consequence of the programmed cell death cascade. Irreversible electroporation has recently been revisited in a number of preclinical and clinical studies with favorable outcomes for the treatment and ablation of atrial and ventricular tissues.4,5,7,8 Furthermore, irreversible electroporation can create lesions without tissue heating and is also believed to be tissue/cell selective enabling preservation of the adjacent or surrounding structures.
This initial in vivo study illustrates the safety and efficacy of a novel, bipolar, single-shot family of PFA catheters for the treatment and ablation of atrial tissue. The lesion durability and the histopathologic findings described in this report are highly consistent with prior reports using different biphasic waveforms delivered with other multipolar PFA catheters. Accordingly, the PFA catheters investigated in this study proved capable of creating large, transmural atrial lesions. The PFA applications were generally single-shot and did not require catheter repositioning resulting in acute marked reduction in post- versus pre-PFA electrogram amplitudes. Moreover, all PFA lesions were found to be completely durable up to 3 months of follow-up and despite minimal microbubbling observed during ablation, no discernable embolic events were encountered by MRI or careful histologic analysis of the brain, the rete mirabile, and the systemic organs.
Also, consistent with prior reports, PFA using the studied catheter system did not produce any collateral damage to the bronchi or PN, nor any long-term injuries to a manually-deviated, esophagus when performing ablations within the adjacent IVC. Though by design, the findings from such a simulation bear obvious limitations, this model does indeed offer certain clinical merits. As previously described,9 it involves manual deviation of the esophagus toward/against the PFA catheter placed transvenously within the IVC, to approximate the anatomical proximities required to simulate esophageal injury during LA ablation. The inherent advantage of this model is that it allows for delivery of the ablative energy over a large area of the esophageal tissue, within the blood pool as in the case of LA ablation, while affording placement of multiple ablation lesions for analysis.9 In addition, it represents ablation within an intra-vascular milieu similar to conventional clinical workflows allowing for assessment of PFA lesions delivered directly on a thin-walled structure (i.e., the IVC) similar to the posterior LA wall. Also, given that the posterior LA wall shares its embryologic origins with PV tissues11 and that the electrical conductivity of the IVC is similar to that of the posterior wall of the LA,12 these characteristics render this model both relevant and clinically suitable. Meanwhile, similar to previously published reports,13 the findings from this study showed evidence of acute, but transient PFA-related changes within the muscularis layer of the deviated esophagus when delivering PFA applications in the adjacent IVC, which completely resolved at 3 weeks of follow-up without any detectable long-term sequelae. Although these findings appear highly promising, future studies and clinical investigations are clearly warranted to further validate the safety and efficacy outcomes reported in this preclinical study.