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.