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\begin{document}

\title{The wall of unintended consequences: is the main benefit of posterior LA
wall isolation simply more durable pulmonary vein isolation?}



\author[1]{Paul Zei}%
\affil[1]{Brigham and Women's Hospital}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\textbf{The wall of unintended consequences: is the main benefit of
posterior LA wall isolation simply more durable pulmonary vein
isolation?}

Paul C. Zei, MD PhD FHRS

Department of Medicine

Brigham and Women's Hospital

Harvard Medical School

Boston, MA

Funding: None

Conflict of Interest: None



\textbf{The wall of unintended consequences: is the main benefit of
posterior LA wall isolation simply more durable pulmonary vein
isolation?}

Paul C. Zei, MD PhD FHRS

Medicine is rife with therapies originally developed for a specific
purpose, yet after some time, the true benefit is determined to lie
elsewhere - examples of the ``law of unintended consequences''. One
egregious example is aspirin, where the ``true'' benefit has shifted
several times over decades of use, from analgesic, to anti-inflammatory,
to anti-platelet, to anti-malignancy. In fact, our regulatory agencies,
including the FDA, allow off-label use of pharmaceuticals and devices in
large part to account for adaptation to changing indications based on
physician discretion. Invasive electrophysiology is no exception,
particularly with ablative approaches employed to treat atrial
fibrillation.

Durable pulmonary vein isolation (PVI) remains the primary goal of
effective catheter ablation for atrial fibrillation (AF), as multiple
high-quality studies over many years have demonstrated that PVI is one
of the strongest predictors of freedom from AF after ablation {[}1{]}.
However, despite our understanding of this seemingly straightforward
goal, we continue to struggle to achieve durable PVI. Unacceptably high
rates of PV electrical reconnection are seen in patients who return to
the EP lab for repeat AF ablation, driving clinical AF recurrence in
many patients after PVI {[}1{]}. Therefore, there is an ongoing need to
improve the ability to durably achieve PVI.

Today, we are in fact able to achieve acute PV isolation in most
procedures, highlighting a shortfall in the ability to predict long-term
durability of PVI {[}2{]}. Acute electrical isolation ideally
corresponds to permanent myocardial ablative injury, resulting in
permanent fibrosis, and as a result, permanent electrical block.
However, a subset of ablated tissues may appear acutely well-ablated by
intraprocedural measures but then eventually recover conduction, as
permanent myocardial injury is not achieved. Over time, multiple
strategies have been proposed and utilized to both better predict and
achieve lesion durability. Achieving transmural lesions likely remains
an important component of these strategies, but there remains an ongoing
concern for excessive ablation beyond the myocardium, with concern for
thermal injury to adjacent extracardiac structures including nerve
tissue and the esophagus.

Ablation guided by index estimates of energy delivery, such as Surpoint
Ablation Index (AI, Biosense Webster, Inc.) or lesion index (LSI,
Abbott), appears to result in improved durability of PVI without
increased risks of extra-cardiac collateral injury {[}3{]}. These
indices are an integration of multiple electrical and mechanical input
variables known to improve lesion formation predictability. With these
strategies, higher index values are typically targeted along the thicker
anterior segments, with lower target values along the thinner posterior
aspects of the PV wide-area circumferential ablation (WACA) lesion set.
Various strategies to create more shallow lesions along the thin
posterior aspects of the LA have been advocated.
High-power/short-duration (HPSD) ablation leverages the biophysical
principle that with shorter duration, higher power RF delivery, tissue
heating and injury occurs primarily through resistive heating, resulting
in more shallow and broad lesions {[}4{]}. In contrast, longer RF
delivery times allow the generation of conductive heating, resulting in
ablation lesions that are deeper. In the end, no matter what strategy
for RF delivery is employed, there remains inability to precisely tailor
ablation energy

delivery to the needs of the specific target tissue. In particular, the
posterior aspects of the PVI WACA set remain problematic, where the
thinner tissues reduce the margin of error between adequate transmural
ablation vs. excessive ablation that risks injury to extracardiac
structures.

Therefore, much focus has been centered on optimizing energy delivery
along the posterior aspects of the WACA. In this context, Li et al
report in this issue of the Journal of Cardiovascular Electrophysiology
their experience with targeting LA posterior wall isolation (PWI) in the
setting of AF catheter ablation and pulmonary vein isolation PVI
utilizing a specific technique of low-flow, medium power, short duration
(LFMPSD) ablation in a distributed fashion {[}5{]}. There is a fair
amount of information to unpack in this approach. The rationale for this
approach is that due to the presumed higher likelihood of electrical
reconnection along the posterior aspects of the WACA set, additional
ablation with a goal to electrically isolate the LA posterior wall may
improve the durability of PVI by broadly blocking posterior wall
electrical conduction. The authors utilize a distributive or
``peppering'' approach to RF lesions across the posterior wall to both
maintain chances of durable electrical block while minimizing risk of
injury to the

esophagus by decreasing chances of over-concentrated ablative energy. In
addition, the authors utilize a LFMPSD ablation strategy, which based on
preclinical data previously reported by the authors {[}6{]}, may result
in more shallow lesions, as reduced catheter irrigant rate may reduce
conductive heating.

In this study, consecutive patients with mostly persistent AF (79.6\%)
at a single center undergoing firsttime catheter ablation for AF were
included, with 137 out of 463 total patients undergoing LFMPSD PWI in
addition to PVI, with the remaining undergoing PVI alone. In all but 3
patients in the LFMPSD cohort, PW isolation was achieved acutely, with
atrial arrhythmia recurrence in 30.2\% of those followed up by 14
months. In the subset of patients who underwent repeat ablation in the
+PWI group, 16/18 (88.9\%) demonstrated durable PVI while in the PVI
alone group only 10/45 (23.9\%) patients demonstrated durable PVI.
Interestingly, in the +PWI group undergoing repeat ablation, only 7/18
(38.9\%) demonstrated durable posterior wall isolation. There are
several important caveats to this data, specifically potential patient
selection biases at the point of index ablation, the decision to perform
PWI (which was not predetermined), and the decision to perform repeat
ablation. Despite these caveats, these findings at face value suggest
that the addition of PWI increases the likelihood of durable PVI.

Interestingly, durable PWI is apparently not required to achieve this
increased rate of durable PVI. Hence, it can be concluded that
additional ablation along the PW specifically increases the durability
electrical block along the posterior segments of the WACA.

One wonders if these data may in part underpin the findings in several
studies demonstrating improved freedom from AF with the addition of PWI
to PVI {[}7{]}. The conventional wisdom is that PWI helps to exclude
additional AF drivers within the PW itself; but could it be that rather,
the primary effect of PWI is improving the likelihood of durable PVI?
This question clearly needs to be explored further. However, it remains
unclear whether the authors' approach is indeed the best strategy to
improve durable PVI rates. As the authors show, rates of durable
isolation of the PW itself are low, as these reconnections may increase
risk of PW-dependent atrial flutters. Moreover, additional ablation
along the PW may expose the esophagus to more risk of thermal injury
despite the LFMPSD approach employed here.

The described LFMPSD ablation approach remains squarely in the minority
of left atrial ablation approaches described and anecdotally utilized in
the community, as the ever more popular HPSD approach is quickly
becoming the dominant RF ablation strategy {[}8{]}. These two
diametrically opposite biophysical approaches have the same goal of
minimizing risk to adjacent extracardiac structures. It would therefore
stand to reason that evaluating whether PWI using an HPSD strategy
bolsters PVI durability is a clinically important. In the end, the
ultimate goal remains tailoring ablation energy to the appropriate
tissue characteristics, that is ablating ``just enough'' to achieve
durable PVI without increased risk of collateral injury. A missing
ingredient in this and other approaches remains accounting for
tissue-specific characteristics that may impact the ablation biophysical
characteristics. In the meantime, the findings in this paper suggest
that the commonly applied approach of PWI in addition to PVI,
particularly in persistent AF patients, may have the added, if not
primary benefit, of improving the durability of PVI. This perhaps
unintended consequence of posterior wall isolation may end up
benefitting AF ablation outcomes after all.

\textbf{References}

1. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar
JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Cosedis
Nielsen J, Curtis AB, Davies DW, Day JD, d'Avila A, Natasja de Groot
NMS, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT,
Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH,
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KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M,
Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K,
Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling
R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T; Document Reviewers:.
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PMC5834122.

2. Calvert P, Lip GYH, Gupta D. Radiofrequency catheter ablation of
atrial fibrillation: A review of techniques. Trends Cardiovasc Med. 2022
Apr 11:S1050-1738(22)00061-5. doi: 10.1016/j.tcm.2022.04.002. Epub ahead
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3. Das M, Loveday JJ, Wynn GJ, Gomes S, Saeed Y, Bonnett LJ, Waktare
JEP, Todd DM, Hall MCS, Snowdon RL, Modi S, Gupta D. Ablation index, a
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prediction of pulmonary vein reconnection at repeat electrophysiology
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differences in target values. Europace. 2017 May 1;19(5):775-783. doi:

10.1093/europace/euw105. PMID: 27247002.

4. Yavin HD, Leshem E, Shapira-Daniels A, Sroubek J, Barkagan M,
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10.1016/j.jacep.2020.04.023. PMID: 32819533.

\textbf{5. Li et al (this article)}

6. Kumar S, Romero J, Stevenson WG, Foley L, Caulfield R, Fujii A,
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Clinical Studies. JACC Clin Electrophysiol. 2017 Oct;3(10):1114-1125.
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10.1016/j.jacep.2017.09.001. Epub 2017 Oct 16. PMID: 29759494.

7. Kaba RA, Momin A, Camm J. Persistent Atrial Fibrillation: The Role of
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10.3390/jcm10143129. PMID: 34300301; PMCID: PMC8304563.

8. Kreidieh O, Varley AL, Romero J, Singh D, Silverstein J, Thosani A,
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