University of Illinois Chicago
In this edition of JCE two papers focus on the thermal (1) and
pathological changes associated with the use of the Farapulse PFA
ablation system to isolate the PVs. The first study Bettina et al (1).
recorded the esophageal temperature changes using the Circa Scientific
temperature probe while
Meininghaus (2) used endoscopy,
endoscopic ultrasound, and electrogastrography before and after PVI to
define periesophageal injury (mucosal lesions, food retention,
periesophageal edema, or vagal nerve injury). Meininghaus et al.
compared the esophageal injury post PFA in 20 post PVI patients to
previously collected data from 24 radiofrequency (RF) and 33 cryoballoon
(CB) PVI.
In both studies, “PVI was performed with a 31 mm pentaspline
FARAWAVE-catheter (Farapulse, Boston Scientific, Marlborough, MA, USA).
For each vein, a minimum of eight pulsed field cycles (four in ‘flower’-
and four in ‘basket’-configuration of the catheter, respectively) were
applied in a train of five consecutive impulses for a total of 2.5
seconds and an energy of 2.0 kV If needed, additional cycles were
applied to fully isolate the veins.”
Luminal esophageal temperature (LET) was monitored using Circa
Scientific, LLC, Englewood, CO, USA. However, Meininghaus et al.
recorded the temperature in only four PFA-cases, and LET monitoring was
not done in the remaining procedures after documentation of the
“absence” of any LET rise.
While the first study investigated the impact of PFA on the esophageal
temperature and potential pathology the second study compared the
esophageal pathology to previous investigations using the same
examination of the esophagus post RFA and Cryo PVIs. The patients
underwent endoscopic evaluation within one week before and within two
working days after the PVI procedure.
Bettina et al. demonstrated a statistically significant increase in
luminal esophageal temperature of 0.8±0.6 ℃, p <0.001. The
temperature increase was ≥1 ℃ in 10/43 (23%) patients, and the maximum
was 40.3 ℃. Meininghaus et al. reported that PFA was not associated with
any mucosal esophageal lesions or signs of vagal nerve injury. Whereas
esophageal or peri esophageal injury was observed in 33/57 patients post
thermal ablation (58%) (CB: 21/33 [64%] and RF: 12/24 [50%])
In 30/57 patients (CB: 20/33, RF: 10/24) had endoscopically detected
pathology (ELs, edema, food retention). Mucosal lesions were more common
with RF, peri-esophageal edema was more frequently observed with CB, and
food retention was significantly more common following CB-PVI. Signs of
vagal nerve injury based on EGG were observed in 17/57 patients
following thermal ablation (30% [RF: 21%, CB: 36%]).
An unresolved observation in all of these ablation modalities is the
finding of periesophageal edema (RF: 30%; CB: 45% and in 25% with PFA
following ablation). The origin and pathophysiologic relevance of
periesophageal edema is unknown and the authors of the second paper
observe that so far it has not been shown to be associated with the risk
of progression to Atrio-esophageal fistula (AEF) and minimize this
finding to be a none specific response of the surrounding tissue. The
authors suggest that this observation may be due to preexisting
inflammation of esophageal tissue (i.e., chronic esophagitis or reflux)
and not due to the ablation itself. This explanation is not supported by
the fact that such edema was not reported to be present pre-ablation.
Furthermore, the authors minimize any possible adverse findings post PFA
PVI and have not reported any long-term complications associated with RF
or Cryo PVI.
It is concluded that “esophageal safety of PFA-PVI eliminates the key
safety obstacle to early interventional treatment of AF (2).”
While both studies provide a great deal of reassurance as to the
remarkable safety of using PFA regarding phrenic and esophageal
integrity at this time the findings are applicable only to Farawave
catheter and the pulse configuration used in both studies. Furthermore,
so far, the clinical efficacy of PFA has been found to be comparable to
RFA and Cryo (3).
Is PFA hot or cold
Fundamental to the dissipation of electrical energy across resistive
conductors is the induction of heat. In fact, as has been shown high
power and short duration of RF create effective lesions.
Given that the pulse configuration of high voltage short duration of the
electrical energy the temperature measurement requires temperature
sensors with a very high response time and sampling rate that is twice
the maximal rate of change of the temperature. In both studies, the
Circa temperature probe was used to assess the luminal temperature. The
Circa temperature probe delivers 240 data points per second; 12
thermocouple temperature sensors update 20 times per second. While these
specifications are appropriate for RF they will unlikely to record the
rapid rise of the temperature generated by PFA.
The Farapulse system delivers a minimum of eight 2.0 kV cycles in a
train of five consecutive impulses for a total of 2.5 seconds. The
electrical energy is delivered in a bipolar configuration to the
Farawave catheter electrodes spaced 2.5 mm, the electrode length is 2.5
mm, and the electrode diameter is 2.33 mm. The short-spacing small ring
electrodes the electrical energy dissipation remains in close proximity
to the two ring electrodes limiting the current density and the
electrical field to close proximity to the energy source. Furthermore,
the short application time minimizes the conductive heating. In
contrast, RF ablation electrical power is delivered to an irrigated
3.5-4mm long 2.66 mm diameter unipolar electrode with the reference
electrode being a large conductive patch placed on the patient’s skin.
High current density is near the ablation electrode the maximal heating
vector is radially and into the depth of the tissues. Furthermore,
application time may typically range from 4 sec (in the case of
high-power short duration application) to as long as 1 minute or more
which allows for conductive heating deep into tissues and thus the
potential of impacting the extracardiac tissues such as the esophagus.
In contrast to the thermal ablation modalities of RF and Cryo, PFA
primary ablative mechanism is irreversible electroporation. The exposure
of polypeptide polar membrane to a high electric field results in the
temporary appearance of pores within the cell lipid bilayer that
resolve. As the voltage amplitude increases as well as the pulse
duration, frequency, and the increasing number of delivered pulses the
membrane disruption becomes permanent leading to irreversible
electroporation and cell death (4 ).
As noted by Bettina et al. The detection of temperature rise using the
Circa esophageal temperature probe clearly suggests that Farapulse
recipe of high voltage short duration electrical sequential pulses
causes a temperature rise in the esophagus which is likely
under-estimated. Human cell proteins are generally the most sensitive to
temperature rise and start to denature at relatively small temperature
increases at ∼43–45◦ C (4).
Presently, the only means to assess lesion integrity is the elimination
of PV electrical activity and documentation of PVI. Furthermore, tissue
stunning has been reported (5).
In case of lack of isolation, PFA energy applications are repeated. LA
tissue thickness can vary from 2mm to 6mm and the only means to increase
the PFA lesion depth is to increase the pulse amplitude, pulse width,
number of pulses, and pulse cycle length (6). In such circumstances, the
likelihood of thermal injury would increase.
It can be concluded that:
- Using the Farapulse pulse configuration and ablation procedure results
in a significant esophageal temperature increase that is
underestimated using the Circa probe and it is likely significantly
higher temperature can be recorded at close proximity to the ablation
electrodes.
- A near-field tissue ablation is a mix of irreversible electroporation
and thermal injury.
- The bipolar energy delivery using the Farawave-catheter limits the
field and thermal ablation to close proximity to the bipolar ablation
electrodes limiting the impact on extracardiac tissues.
- In the two published papers accompanying this editorial, the Farapulse
PFA technology is shown to have no short or long-term adverse effect
on the esophagus. However, reported phrenic nerve conduction stunning
may occur (7,8).
It is also noted that while Meininghaus et al. reported significant
esophageal acute injuries using RF and Cryo no long-term data is
provided that these findings resulted in long-term disabilities.
- PFA is hampered by the inability to adequately assess irreversible
lesion formation in real-time.
- The advantage provided by using PFA ablation technology is added
safety and faster procedure time. These conclusions need further
affirmation when the technology is widely used.
References:
- Bettina et al. JCE-23-0416
- Meininghaus et al. JCE-23-0756
- Europace (2023) 25 , 1–11
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- Yarmush ML, Golberg A, Sersa G, Kotnik T, Miklavcic D.
Electroporation-based technologies for medicine: principles,
applications, and challenges. Annu Rev Biomed Eng. 2014;16:295-320.
- Pulsed-field ablation combined with ultrahigh-density mapping in
patients undergoing catheter ablation for atrial fibrillation:
Practical and electrophysiological considerations.
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- Sugrue A, Vaidya V, Witt C, DeSimone CV, Yasin O, Maor E, et al.
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- van Driel VJ, Neven K, van Wessel H, Vink A, Doevendans PA, Wittkampf
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