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\begin{document}

\title{``Searching for the team-dream: to whom the palms of victory?''}



\author[1]{Claudio Tondo}%
\affil[1]{Centro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
In the last few years novel ablative technologies featuring several
devices incorporating different energy sources and catheter design for
ensuring an effective PVI have been proposed. In particular, two
prominent technologies, such as the non-thermal ablation modality based
on pulsed field ablation (also defined as ``electroporation'') and radio
frequency balloon-based catheter has been introduced in the clinical
practice. The adoption of such technologies aims at simplifying PVI
procedures, improving efficacy, and increasing safety. Furthermore, the
evaluation of the extension of area of lesion promoted by the two
technologies might affect the clinical outcome%
\end{abstract}%



\sloppy


In this issue of the Journal, My and co-workers, in a single center
experience, report the comparison between two ablation modalities for
atrial fibrillation (AF), namely pulse field ablation (PFA) and
radiofrequency balloon ablation (RFB) in terms of acute extensive area
of lesion (1). Moreover, they also provide information about the release
of biomolecules as expression of the entity of cardiac tissue injury.
The study finds that PFA promotes larger acute lesion areas and higher
troponin release upon successful PVI than multi-electrode radiofrequency
balloon-based PVI

We acknowledge the advent of novel technologies in the last few years
featuring several devices which incorporate different energy sources and
catheter design for ensuring an effective PVI. The authors have elected
two prominent technologies for their investigation, such as the
non-thermal ablation modality based on pulsed field ablation (also
defined as ``electroporation'') and radiofrequency balloon-based
catheter. The adoption of such technologies aims at simplifying PVI
procedures, improving efficacy, reducing procedure time, and increasing
safety.

\textbf{The concept of area of lesion}

Assessment of the extension of area of lesion following PVI has been the
target of several previous studies both after RF current applications,
cryoballoon ablation and laser therapy (2-4). The general notion is that
the use of balloon-based ablation treatments usually provides larger
area of lesion as compared to conventional point-by-point catheter
ablation. On the other hand, this could be challenged by others who
argue that also with the completion of WACA modality of ablation is
feasible the creation of a large antral lesion. In this regard, it
appears easier to promote uniform antral lesion through the
balloon-based ablation than that created by conventional point-by-point
RF applications, due to the potential occurrence of lesion gaps along
the line.

One could raise the question whether a large area of lesion is really
required for achieving an effective PVI. Looking at previous studies the
wide antral approach is more effective than ostial PVI in achieving
freedom from atrial tachyarrhythmia recurrence at long-term follow-up
(3). The other side of the coin of the creation of an extended antral
lesion is the chance to favor macro-reentrant atrial tachycardia with a
critical isthmus in the posterior wall of left atrium (5). Anyhow, the
searching of novel catheter design associated to specific energy sources
and their different modalities of delivering (unipolar vs bipolar,..etc)
should yield higher acute success rate and better clinical outcome. In
this study, My et al. have selected two different energy sources coupled
with two novel catheter designs and compared their effects on the
extension of lesion and they found that PFA creates larger acute lesion
areas (20.7 \selectlanguage{ngerman}± 7.7 cm2) than RF balloon-based ablation (7.1 ± 2.09 cm2; p
\textless{} 0.001). Is this finding so crucial to support the hypothesis
that larger antral lesion facilitates a better clinical outcome? Of
course, there is no definite answer, due to the limited number of
patients included and the lack of data over the follow up. We might
anticipate that having a larger area of lesion could be more beneficial
for persistent AF than paroxysmal, due to the critical role played by
the posterior left atrial wall in the maintenance of AF.

\textbf{Catheter ablation design}

Catheter design is so critical when PVI is the main target of AF
ablation. In my view, the adoption of the complaint RF balloon implies a
more ostial lesion and, thus a more limited area of lesion is produced
at the PV antrum. As opposite, the pentaspline PFA catheter provides two
configurations (31 mm -- basket - and 35 mm flower) which can favor, in
eight setting of applications, ostial and antral lesions as well.
Therefore, it should not be a surprise to achieve a broad area of lesion
with PFA catheter than with RF balloon-based catheter, based on the
specific catheter design.

\textbf{Biochemical changes}

The two energy sources also differ in terms of the level of inflammation
produced, being the concentration of high sensitive Troponin 1 (hs TnI)
significantly higher after PFA applications than RF ablation (625 ± 138
pg/ml vs 148 ± 36 pg/ml). Unfortunately, the authors did not provide any
information about the Troponin concentration over time after the
ablation (time-related), which could have given additional and critical
data on the degree of inflammatory response. This is a reflection of the
entity of tissue disruption and parallels the demonstration of an
extended area of lesion. These data come from a minority of patients,
but they likely express the true scenario in relation to the specific
energy source applied. In this regard, similar results are achieved when
cryoenergy is applied to myocardial tissue, suggesting a more extensive
inflammatory process than that produced by point-by-point RF
applications (6), suggesting that energy sources with different
biochemical process than RF current produce a greater inflammatory
response. Again, is there any robust clinical data that an extensive
inflammatory process is followed by a better clinical outcome? Or the
hypothetical better clinical outcome could be achieved with an extensive
antral lesion regardless the modality of ablation employed?
Hypothetically, if the area of lesion provided by RF balloon is
comparable to that produced by PFA, will the clinical outcome be not
significantly different?

\textbf{Thus, do we care of energy source?}

Therefore, assuming the extension of area of lesion is comparable
between PFA and RF, could we foresee the same clinical behavior?
Electroporation is characterized by a nonthermal energy source in which
electrical fields are used to induce cardiomyocyte-specific cell death,
thus avoiding adjacent anatomical structures (7). Initial clinical
observations in controlled trials reported data on high degree of safety
and acute efficacy and follow-up data of PFA-based PVI not significantly
different from more conventional ablative therapy (8,9). On the other
hand, the RFB is a compliant balloon catheter compatible with a 3D
electroanatomical mapping system (CARTO 3, Biosense Webster, CA, USA)
and provides an established energy source. One of the main advantages of
this technology is the selective titration of RF energy delivery from
each surface electrode to reduce collateral damage and to apply energy
in a segmental area if needed (10). Multicenter trials (RADIANCE (10,11)
and SHINE (12)) demonstrated the feasibility, safety, and 12-month
outcome of this technology.

The wealth of clinical data collected from trials seems to indicate a
comparable outcome between the two modalities of ablation but higher
safety profile of electroporation over different energy sources (
especially RF current). How much crucial is the extension of area of
ablation towards the posterior wall in affecting the durability of
lesions produced is still unknown.

At the end of the day, we all dream to devise the most successful
ablative approach as to ensure a stable regular sinus rhythm to our AF
patients, but undoubtedly there still a need to gather additional
insights into these two novel strategies of treatment before declaring
the final winner.

\textbf{References}

1. My I, Lemoine MD, Butt M, et al. Acute lesion extension following
pulmonary vein isolation with two novel single shot devices: pulse field
ablation vs. multielectrode radiofrequency balloon. Journal of
Cardiovasc Electrophysiol 2023\ldots{}

2. Kawamura I, Neuzil P, Shivamurthy P, Kuroki K, Lam J, Musikantow D,
Chu E, Turagam MK, Minami K, Funasako M, Petru J, Choudry S, Miller MA,
Langan MN, Whang W, Dukkipati SR, Koruth JS, Reddy VY. How does the
level of pulmonary venous isolation compare between pulsed field
ablation and thermal energy ablation (radiofrequency, cryo, or laser)?
Europace. 2021 Nov 8;23(11):1757-1766. doi: 10.1093/europace/euab150.
PMID: 34151947; PMCID: PMC8576283.

3. Proietti R, Santangeli P, Di Biase L, Joza J, Bernier ML, Wang Y,
Sagone A, Viecca M, Essebag V, Natale A. Comparative effectiveness of
wide antral versus ostial pulmonary vein isolation: a systematic review
and meta-analysis. Circ Arrhythm Electrophysiol. 2014 Feb;7(1):39-45.
doi: 10.1161/CIRCEP.113.000922. Epub 2014 Jan 2. PMID: 24385448.

4. Sciacca V, Fink T, Ko\selectlanguage{english}rperich H, Bergau L, Guckel D, Nischik F,
Eckstein J, Braun M, Hamriti ME, Imnadze G, Piran M, Sommer P, Sohns C.
Magnetic resonance of left atrial scar a novel very for atrial
fibrillation ablation. Europace. 2023 Apr 15;25(4):1392-1399. doi:

5. Tohoku S, Chun KRJ, Bordignon S, Chen S, Schaack D, Urbanek L,
Ebrahimi R, Hirokami J, pulmonary vein isolation with pulsed field
ablation. Europace. 2022 Nov 25:euac211. doi: 10.1093/europace/euac211.
Epub ahead of print. PMID: 36427201.

6. Casella M, Dello Russo A, Russo E, Al-Mohani Ghaliah, Santangeli P,
Riva S, Fassini G, Moltrasio M, Innocenti E, Colombo D, Bologna F, Izzo
G, Gallinghouse JG, Di Biase L, Natale A, Tondo C. Biomarkers of
myocardial injury with different energy sources for atrial fibrilaltion
catheter ablation. Cardiol J.2014;21(5):516-23. Doi:
10.5603/CJ.a2013.0153

7. Koruth JS, Kuroki K, Kawamura I, et al. Pulsed Field Ablation Versus
Radiofrequency Ablation: Esophageal Injury in a Novel Porcine Model.
Circ Arrhythm Electrophysiol. 2020;13(3):e008303.
doi:10.1161/CIRCEP.119.008303

8. Reddy VY, Dukkipati SR, Neuzil P, et al. Pulsed Field Ablation of
Paroxysmal Atrial Fibrillation: 1-Year Outcomes of IMPULSE, PEFCAT, and
PEFCAT II. JACC Clin Electrophysiol. 2021;7(5):614-627.
doi:10.1016/j.jacep.2021.02.014

9. Lemoine MD, Fink T, Mencke C, et al. Pulsed-field ablation-based
pulmonary vein isolation: acute safety, efficacy and short-term
follow-up in a multi-center real world scenario {[}published online
ahead of print, 2022 Sep 22{]}. Clin Res Cardiol.
2022;10.1007/s00392-022-02091-2. doi:10.1007/s00392-022-02091-2

10. Reddy VY, Schilling R, Grimaldi M, et al. Pulmonary Vein Isolation
With a Novel Multielectrode Radiofrequency Balloon Catheter That Allows
Directionally Tailored Energy Delivery: Short-Term Outcomes From a
Multicenter First-in-Human Study (RADIANCE). Circ Arrhythm
Electrophysiol. 2019;12(12):e007541. doi:10.1161/CIRCEP.119.007541

11. Dhillon GS, Honarbakhsh S, Di Monaco A, et al. Use of a
multi-electrode radiofrequency balloon catheter to achieve pulmonary
vein isolation in patients with paroxysmal atrial fibrillation: 12-Month
outcomes of the RADIANCE study. J Cardiovasc Electrophysiol.
2020;31(6):1259-1269. doi:10.1111/jce.14476

12. Schilling R, Dhillon GS, Tondo C, et al. Safety, effectiveness, and
quality of life following pulmonary vein isolation with a
multi-electrode radiofrequency balloon catheter in paroxysmal atrial
fibrillation: 1-year outcomes from SHINE. Europace. 2021;23(6):851- 860.
doi:10.1093/europace/euaa382

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