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\begin{document}

\title{Esophageal Cooling During Radiofrequency Ablation: Can Opposite
(Strategies) Attract?}



\author[1]{Cory Tschabrunn}%
\author[2]{Pasquale Santangeli}%
\affil[1]{Hospital of the University of Pennsylvania}%
\affil[2]{Cleveland Clinic Foundation}%


\vspace{-1em}



  
  \date{May 07, 2024}


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\selectlanguage{english}
\begin{abstract}
Catheter ablation has become the standard of care for the management of
antiarrhythmic drug-refractory atrial fibrillation (AF) in many
patients. The cornerstone of AF ablation includes pulmonary vein
isolation (PVI) and energy delivery can sometimes extend beyond the
atrial myocardium and result in collateral damage to adjacent
structures, include the esophagus.{[}1{]} While atrial esophageal
fistula (AEF) is a generally a rare complication, there have been
continued efforts aimed to reduce esophageal thermal injury during AF
ablation. While emerging energy sources such as irreversible
electroporation show exciting promise for selective, non-thermal
targeting of myocardial tissue, safety and efficacy clinical trial
evaluation is on-going.{[}2{]} Therefore, strategies that can prevent
esophageal thermal injury without adversely impacting lesion formation
using conventional ablation technologies are still needed.%
\end{abstract}%



\sloppy


\textbf{Esophageal Cooling During Radiofrequency Ablation: Can Opposite
(Strategies) Attract?}

Cory M. Tschabrunn, PhD\textsuperscript{1} and Pasquale Santangeli, MD,
PhD\textsuperscript{2}

\textsuperscript{1}Division of Cardiovascular Medicine, University of
Pennsylvania Perelman School of Medicine, Philadelphia, PA

\textsuperscript{2}Department of Cardiovascular Medicine, Cleveland
Clinic, Cleveland, OH

\textbf{Corresponding Author:}

Cory M. Tschabrunn, PhD

Hospital of the University of Pennsylvania

1 Convention Avenue -- Level 2

Philadelphia, PA 19104

Phone: 267-862-0110

Email: coryt@pennmedicine.upenn.edu

\textbf{Funding Sources}

Dr. Tschabrunn is supported by the Winkelman Family Fund in
Cardiovascular Innovation.

\textbf{Disclosures}

Dr. Tschabrunn receives research and educational grant support from
Biosense Webster, Abbott, Baylis Medical, and the National Institutes of
Health. Dr. Santangeli receives consulting fees from Biosense Webster,
Abbott, and Baylis Medical. Dr. Tschabrunn and Dr. Tschabrunn have also
received research grant support from Attune Medical and are actively
involved in leading a NIH funded clinical investigation investigating
the ensoETM device.

\textbf{Word count:} 1448

Catheter ablation has become the standard of care for the management of
antiarrhythmic drug-refractory atrial fibrillation (AF) in many
patients. The cornerstone of AF ablation includes pulmonary vein
isolation (PVI) and energy delivery can sometimes extend beyond the
atrial myocardium and result in collateral damage to adjacent
structures, include the esophagus.{[}1{]} While atrial esophageal
fistula (AEF) is a generally a rare complication, there have been
continued efforts aimed to reduce esophageal thermal injury during AF
ablation. While emerging energy sources such as irreversible
electroporation show exciting promise for selective, non-thermal
targeting of myocardial tissue, safety and efficacy clinical trial
evaluation is on-going.{[}2{]} Therefore, strategies that can prevent
esophageal thermal injury without adversely impacting lesion formation
using conventional ablation technologies are still needed.

Numerous studies have investigated the utility of esophageal cooling to
prevent or limit thermal injury during AF ablation. {[}3-8{]} While
various devices and techniques have been proposed, several of these
studies have demonstrated the feasibility and potential clinical utility
of esophageal cooling for the reduction of thermal injury during RF
ablation. Nonetheless the technique has not been widely adopted into
clinical practice, at least partly due to the lack of multi-center
randomized clinical trial data supporting the safety and efficacy of its
use, particularly regarding the potential impact of esophageal cooling
on left atrial lesion formation.

Towards this end, Leung and colleagues present data on acute
reconnection and first-pass isolation rates from patients enrolled in
their previously published prospective, randomized IMPACT study that
investigated whether active esophageal cooling during AF ablation can
reduce the incidence of esophageal thermal injury.{[}4{]} The authors
evaluated data available from 188 patients that were randomized to
undergo AF ablation with active esophageal cooling versus no cooling.
Esophageal cooling was performed using the FDA-cleared ensoETM device
(Attune Medical) and activated to 4\selectlanguage{ngerman}\textsuperscript{°}C at least 10
minutes before posterior wall ablation was started. The study included
both first time and redo AF ablations. Point by point ablation lesions
were guided by ablation index (AI) using a power of 40W on the anterior
segment and 30W on the posterior wall. The procedural strategy included
PVI or PVI combined with isolation of the posterior wall. The authors
compared biophysical parameters (catheter temperature, impedance drop)
during lesion delivery along with the incidence of first-pass isolation
and acute reconnection rate during a 20-minute waiting period in both
randomization groups. Provocation of acute reconnection with adenosine
was not routinely performed in all patients. In all but 6 cases, the
Thermocool Smart-Touch Surround Flow ablation catheter was used.

Impedance drop and ablation catheter tip temperature was similar across
groups in the entire cohort of patients. Assessment of first-pass
isolation and acute reconnection was performed in 132 patients that had
underwent first time AF ablation. First pass PVI was achieved in 51/64
(80\%) of patients randomized to receive activation esophageal cooling
group and 51/68 (75\%) patients in the control group. There was also no
significant difference in acute reconnection in first time ablation
patients (8\% in esophageal cooling group versus 10\% in control
patients). Furthermore, there was no difference in posterior wall
isolation success rates in patients between groups. During clinical
follow-up, arrhythmia recurrence rates were also similar within the
first year between cooling (21.1\%) and the control group (24.1\%).

The results from this study are valuable for several reasons. While
active esophageal cooling has been proposed as a potential strategy to
reduce esophageal thermal injury during RF ablation, it has been unclear
whether esophageal cooling can adversely impact posterior RF lesion
formation. This has not been systematically evaluated in a large group
of patients with available data only from mathematical modeling studies
and smaller clinical trials.{[}9{]} The authors' findings suggest that
active esophageal cooling does not significantly impact atrial tissue
lesion formation in a clinically significant way. The authors
appropriately recognize that their findings are inherently limited by
the single-center study design. In addition, the acute reconnection
assessment technique used was variable and it is likely that more
aggressive techniques such as isoproterenol and/or adenosine infusion
would likely unmask higher incidences of acute reconnection. The use of
adenosine provocation was limited to only 34 (18.1\%) of cases, and the
criteria adopted by the investigators to use adenosine were not
specified in the manuscript. In the eCool-AF pilot study that we
conducted which randomized 44 first-time AF ablation patients to active
cooling versus conventional temperature monitoring, we found a slightly
greater, but statistically non-significant rate of acute reconnections
in patients that underwent esophageal cooling when assessed with a
30-minute waiting period and additional pharmacological provocation in
all patients. We also found no difference in impedance drop and catheter
temperature in the eCool-AF study. However, it is important to point out
that the temperatures measured from a Thermocool Smart-Touch Surround
Flow catheter do not accurately reflect the actual temperature at the
tissue-catheter interface, as the thermocouple temperature sensor in
this catheter platform is displaced more proximally. The authors report
the use of a new generation ablation catheter (Qdot Micro, Biosense
Webster) with thermocouples located within the outer metal shell in a
small subgroup of 6 patients (4 randomized to active cooling and 2
control patients). It would have been of interest to evaluate the
recorded catheter tip temperatures in those patients to determine
whether esophageal cooling truly does not affect the temperature at the
LA tissue-catheter interface.

In summary, this additional analysis from Leung and colleagues
investigating acute reconnection, first-pass isolation rates, and AF
recurrence during follow-up is a welcomed addition to the literature and
provides further evidence that esophageal cooling may not have a major
impact on left atrial lesion formation. Of note, while the clinical
follow-up reported is encouraging regarding similar AF recurrence rates
within 1 year following ablation, AF recurrence assessment was limited
to data available from standard post-ablation clinical assessment as,
understandably, this was likely not part of the original study design.

While many of us remain cautiously optimistic in the promise of
electroporation in mitigating AEF risk, safety and efficacy clinical
investigation is on-going and it is unlikely to replace RF ablation in
the immediate short-term. As such, it is prudent that we continue to
investigate alternative techniques and technologies that can reduce AEF
risk during RF ablation. In this context, active esophageal cooling with
a dedicated device appears to provide protection from esophageal thermal
injury without significantly affecting LA lesion quality, and warrants
further evaluation in a multi-center clinical trial.



\textbf{References}

1. Calkins, H., et al., 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert
consensus statement on catheter and surgical ablation of atrial
fibrillation. Heart Rhythm, 2017. \textbf{14} (10): p. e275-e444.

2. Sugrue, A., et al., Cardiac ablation with pulsed electric fields:
principles and biophysics. Europace, 2022. \textbf{24} (8): p.
1213-1222.

3. Leung, L.W., et al., Esophageal cooling for protection during left
atrial ablation: a systematic review and meta-analysis. Journal of
Interventional Cardiac Electrophysiology, 2019.

4. Leung, L.W.M., et al., Randomized comparison of oesophageal
protection with a temperature control device: results of the IMPACT
study. Europace, 2021. \textbf{23} (2): p. 205-215.

5. Tschabrunn, C.M., et al., Active esophageal cooling for the
prevention of thermal injury during atrial fibrillation ablation: a
randomized controlled pilot study. J Interv Card Electrophysiol,
2022.\textbf{63} (1): p. 197-205.

6. Arruda, M.S., et al., Feasibility and safety of using an esophageal
protective system to eliminate esophageal thermal injury: implications
on atrial-esophageal fistula following AF ablation. J Cardiovasc
Electrophysiol, 2009. \textbf{20} (11): p. 1272-8.

7. John, J., et al., The effect of esophageal cooling on esophageal
injury during radiofrequency catheter ablation of atrial fibrillation. J
Interv Card Electrophysiol, 2020. \textbf{58} (1): p. 43-50.

8. Montoya, M.M., et al., Protecting the esophagus from thermal injury
during radiofrequency ablation with an esophageal cooling device. J Atr
Fibrillation, 2019. \textbf{11} (5): p. 2110.

9. Kulstad, E., M. Mercado-Montoya, and S. Shah, Influence of thermal
conductivity on esophageal protection with a cooling device during
high-power short-duration radiofrequency ablation - Abstract P1861.
European Heart Journal, 2019. \textbf{40} (Supplement\_1).

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