In-Vivo Biphasic, Bipolar Pulsed Field Ablation Safety and
Efficacy
In this issue of The Journal of Cardiovascular Electrophysiology ,
Hsu et al. evaluated the safety and efficacy of delivering PFA left
atrial lesions in an in- vivo porcine model [22]. They
delivered PFA with a novel 10-electrode irrigated circular catheter and
pulse generator that is integrated with the CARTO mapping system
(Biosense Webster, Irvine, California). PFA was delivered in 8 swine and
included PFA delivered at (1) a PV ostium, (2) directly inside a PV to
assess for stenosis, (3) over the phrenic nerve in the right atrium to
assess for phrenic nerve injury, (4) lateral mitral valve annulus to
assess for valvular damage, and (5) in the aorta adjacent to the
esophagus to assess for esophageal injury. The swine were survived for
30 days and were remapped prior to being euthanized for histologic
examination.
The pulse field waveform was delivered in a bipolar configuration
alternating between different catheter electrodes in trains of biphasic
pulses with a total application duration of approximately 250 msec. The
authors report that the pulse generator was set to 1800V. However, it is
not clear if this represents the amplitude for each electrode pair or if
this is divided between multiple electrodes simultaneously. The pulse
width, duty cycle, and the voltage amplitude of the waveform between
each bipolar electrode pair are not described.
We congratulate the authors on this study, which adds to the growing
body of evidence supporting the safety and efficacy of PFA. Hsu et al.
showed that PFA did not cause collateral tissue damage acutely or at 30
days despite delivery of numerous PFA lesions to vulnerable areas. There
was no pulmonary vein stenosis, phrenic nerve injury, mitral valvular
damage, esophageal injury, or reduction in left ventricular function.
PFA lesions delivered at PV ostia demonstrated excellent efficacy with
PV isolation acutely and durable isolation at 30 days in all swine and
histology showing circumferential, transmural necrosis and repair.
Regarding safety, one of the potential issues with electroporation is
the phenomenon of arcing, where energy above a given threshold results
in rapid gas accumulation that results in a shock wave that can cause
significant barotrauma [23]. The arcing threshold may be different
for a given waveform and catheter design and should be carefully
evaluated for each PFA system. In the current study by Hsu et al, there
was no occurrence of thrombus and/or charring on the catheter tip,
pericardial effusion and/or cardiac tamponade, steam pop events, or
mural thrombus (on intracardiac echocardiography [ICE] during the
procedure nor during gross pathology), no incidence of clinically
significant mechanical tissue injury was noted from gross pathology, and
no incidence of clinically significant thrombo-emboli was found in
upstream and downstream organs nor within the heart. Silent cerebral
infarctions (SCI) have been described in up to 67% of patients
undergoing CA for AF and are defined as the presence of asymptomatic
cerebral lesions detected with imaging (i.e., magnetic resonance
imaging) studies (24). As PFA is associated with micro-bubble formation
(probably due to electrolysis), there is a concern of SCI associated
with these micro-bubbles. Nonetheless, a canine model failed to
demonstrate SCI after PFA was administered in the ascending aorta (25).
Moreover, Reddy et al failed to find SCI in the 13/81 patients who
underwent cerebral MRI after PFA in the IMPULSE/PEFCAT trial (26).
However,
using a lattice catheter, postprocedural brain MRI revealed
diffusion-weighted imaging+/fluid-attenuated inversion recovery- and
diffusion-weighted imaging+/fluid-attenuated inversion recovery+
asymptomatic lesions in observed in 9.8% and 5.9% of patients,
respectively (27). Further studies and trials are needed to clarify this
important dilemma.
The authors delivered supratherapeutic PFA lesions directly adjacent to
the phrenic nerve from the endocardium. No acute injury was seen, nor
was any injury found during gross pathology. This data is encouraging
and may allow ablation of cardiac tissue that previously would have been
prohibitively risky with RF, such as treating atrial tachycardias
originating from the Crista terminalis, which frequently are near the
right phrenic nerve. Currently, complex and risky procedures including
epicardial access with deviation/protection of the phrenic nerve using
air, saline, deflectable sheaths and balloons are the only option for
these patients.
There were no incidents of PV narrowing on the same day or 30 days post
PFA application when
the vein was targeted for isolation via ablation delivered to the
ostium, nor when ablation was performed directly inside of the vein, as
demonstrated by X-ray, ICE, and by flow velocity data. This corroborates
the work by Howard et al, hypothesized that pulsed field ablation (PFA)
would reduce PV stenosis risk and collateral injury compared with
irrigated radiofrequency ablation (IRF). A more precise method of
evaluating PV stenosis was developed that includes the use of
3-dimensional modeling based on computed tomography angiography with
triplicate measures of cross-sectional area at the distal PV and ostial
ablation sites. PV measurements were made pre-ablation and at 2-, 4-,
8-, and 12-weeks post-ablation to provide a detailed time course of the
progression of PV stenosis from radiofrequency ablations while showing
negligible changes in dimensions in pulsed field ablation treated sites
[28].
There was no evidence of esophageal injury despite delivery of
supratherapeutic PFA lesions adjacent to the esophagus from the aorta.
The esophagus in all animals showed no injury to the mucosa, muscularis
or serosa on histology after surviving the animal for 30 days. This is
consistent with prior in vivo studies showing no esophageal
injury despite administering high doses of PFA adjacent to the esophagus
and in human trials showing no evidence of esophageal lesions or
enhancement on EGD or chest CMR (26, 29).