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\begin{document}

\title{Local impedance to guide focal radiofrequency ablation: there is life in
the old dog yet}



\author[1]{Gavin S Chu}%
\author[2]{Dhiraj Gupta}%
\affil[1]{Liverpool Heart and Chest Hospital NHS Foundation Trust}%
\affil[2]{Liverpool Heart and Chest Hospital}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Despite being first described over 30 years ago, focal radiofrequency
(RF) continues to be the most widely used energy modality for catheter
ablation. The fact that it has managed to hold its own against stiff
competition from alternative energy sources used for pulmonary vein
isolation (PVI) is down to continuous evolution based on enhancements in
our understanding of its biophysical principles. In particular, the
advent of contact-force (CF) based integrated indices such as Ablation
Index have improved both efficacy and safety. However, a significant
limitation of this approach is the absence of tissue feedback during
lesion creation, which results in a blunt `one-size-fits-all' approach.
This limitation has been further brought into focus by the recent
appreciation of the much greater importance of circuit impedance rather
than delivered power as a fundamental determinant of RF lesion size.%
\end{abstract}%



\sloppy


Running Title: `Local Impedance for Atrial fibrillation ablation'

Gavin S Chu\textsuperscript{1}, Dhiraj Gupta\textsuperscript{1,2}

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool Centre for Cardiovascular Science, University of Liverpool, UK

\emph{Word count} : 1498 (including table and table legend, excluding
references)

\emph{Key words:} Local Impedance, Atrial fibrillation, Catheter
ablation

\emph{Funding:} None

Disclosures: DG is the recepient of institutional research grants from
Biosense Webster, Medtronic and Boston Scientific. GC: none

\emph{Correspondence}

Name: Professor Dhiraj Gupta, MD https://orcid.org/0000-0002-3490-090X

Address: Department of Cardiology, Liverpool Heart and Chest Hospital,
UK L14 3PE

Phone: +44 151 600 1793; Fax: +44 151 600 1696

Email: Dhiraj.gupta@lhch.nhs.uk

Despite being first described over 30 years ago, focal radiofrequency
(RF) continues to be the most widely used energy modality for catheter
ablation. The fact that it has managed to hold its own against stiff
competition from alternative energy sources used for pulmonary vein
isolation (PVI) is down to continuous evolution based on enhancements in
our understanding of its biophysical principles. In particular, the
advent of contact-force (CF) based integrated indices such as Ablation
Index has improved both efficacy and safety\textsuperscript{1}. However,
a significant limitation of this approach is the absence of tissue
feedback during lesion creation, which results in a blunt
`one-size-fits-all' approach. This limitation has been further brought
into focus by the recent appreciation of the much greater importance of
circuit impedance rather than delivered power as a fundamental
determinant of RF lesion size\textsuperscript{2}.

Historically, electrophysiologists have monitored the change in
generator impedance (GI) in real time as a surrogate of RF lesion
quality. However, GI is confounded by individual patient factors within
the ablation circuit including subcutaneous tissue and hydration
status\textsuperscript{2,3}. The large contribution of these variables
dwarfs the relatively low magnitude of GI change from ablation itself,
thereby limiting its clinical usefulness. Catheter local impedance (LI)
is a novel tool that attempts to minimize the influence of these
confounding variables in the impedance circuit, potentially offering a
more accurate representation of changes occurring close to the
catheter-myocardial interface. A local potential field is generated by
driving a non-stimulatory current between a distal and a more proximal
catheter electrode; proximity to physical structures such as myocardium
causes distortions in this local field which can be measured with one or
more intermediate electrodes, allowing derivation of a LI
value\textsuperscript{4}. Bench work has shown that during RF
application, LI drop dynamically follows the rate of intramural
temperature rise (Figure 1)\textsuperscript{5}. The resulting tissue
feedback can potentially allow operators to individualize each RF
application, and several groups have already reported on their clinical
experience (Table 1) with a LI-sensing catheter.

In this issue of the Journal, Francesco and colleagues present the
findings from the multicentre Italian CHARISMA registry, a study of 153
consecutive patients undergoing RF catheter ablation for AF using the
MiFi\textsuperscript{TM} OI catheter (Boston
Scientific)\textsuperscript{6}. Ablation lesions were delivered at 30-35
W, targeting a LI drop of at least 10 \selectlanguage{greek}Ω \selectlanguage{english}over 30 seconds, up to a maximum
of 40 \selectlanguage{greek}Ω, \selectlanguage{english}and an inter-lesion distance (ILD) of 6 mm or less. After
first-pass pulmonary vein encirclement, lesion success was defined by a
failure of pacing capture at the lesion site. Offline assessment of LI
and GI in 3556 first-pass ablation lesions showed that successful
lesions were associated with higher LI and GI drops than unsuccessful
ones, and ROC curve analysis found LI to be a far better discriminator
than GI. Every 5-point drop in LI had an OR of 3.1 (CI 2.7-3.6) for
lesion success, plateauing at 15 \selectlanguage{greek}Ω. \selectlanguage{english}No steam pops or ablation-related
adverse outcomes were observed. In their conclusions, the authors
suggest a 15 \selectlanguage{greek}Ω \selectlanguage{english}drop as an indicator of probable lesion effectiveness,
with an upper safety limit of 30 \selectlanguage{greek}Ω \selectlanguage{english}in order to avoid steam pops.

The authors should be congratulated for their study, which is the
largest reported to date using LI, and the first one to use a
LI-targeted approach for AF ablation. Although the study population was
heterogeneous, combining both first time and redo cases as well as both
paroxysmal and persistent AF, the low rate of arrhythmia recurrence on
follow up is encouraging, and suggests potential for real world use for
this novel technology.

It is notable that the results of the present study are consistent with
suggested LI targets from the recently published multicentre LOCALIZE
study, where the same catheter was used for first-time PVI in paroxysmal
AF patients whilst blinded to LI\textsuperscript{7}. Gaps in the ablated
segments were assessed after a protocol-mandated 20-minute wait
following first pass PV encirclement; a LI drop of 16.1 \selectlanguage{greek}Ω \selectlanguage{english}in the
anterior/roof segments had a positive predictive value (PPV) of 96.3\%
for absence of gap, while for posterior/inferior segments a LI drop of
12.3 \selectlanguage{greek}Ω \selectlanguage{english}had a PPV of 98.1\%. The largest LI drop associated with a
conduction gap when targeting an ILD of 6 mm or less was 20.1\selectlanguage{greek}Ω. \selectlanguage{english}The
threshold value of approximately 15-20 \selectlanguage{greek}Ω \selectlanguage{english}as being predictive of lack of
gap was also observed by other groups, and so it appears that the
technology is reproducible and predictive across a range of power and CF
values.

In addition to being a marker of lesion quality, LI may also serve as an
indicator of underlying substrate. LI is known to be independent of
catheter orientation\textsuperscript{4} and activation wavefront
direction\textsuperscript{8}, and yet has been shown in the present
study\textsuperscript{6} and others\textsuperscript{8,9} to be
positively correlated with electrogram amplitude. Lower baseline LI
values, as well as significantly lower response to RF ablation are seen
in scarred as opposed to healthy tissue\textsuperscript{10,11}. It is
notable that Solimene and colleagues also observed a lower baseline mean
LI in patients with persistent AF as compared to paroxysmal AF, although
there was no difference in mean LI values between de novo and redo
cases.

Successful evolution necessitates improvement beyond that which is
currently available. Particularly with a very well-established procedure
such as PVI, and with competition from single-shot and established RF
energy delivery techniques, procedural efficiencies such as first pass
PVI are very important. In this context, it would have been useful for
the current study to include such data, so that the effectiveness of
this technology could be put into context with that of other
contemporary techniques. For instance, a recent large multicentre study
systematically employing the CLOSE protocol reported a first-pass PVI
rate of 82.4\%\textsuperscript{1}. Whether a LI- based approach can
match such results, and preferably do so with more tailored but less
overall RF energy delivery remains to be determined.

In conclusion, Solimene and colleagues provide real world clinical
evidence in a sizeable multicentre real-life cohort of AF patients that
supports the use of local impedance in guiding RF ablation for PVI.
However as is often the case for such a rapidly evolving field,
obsolescence for the OI MiFi catheter may already be on the horizon in
the form of the recently released Stablepoint\textsuperscript{TM}(Boston
Scientific) catheter that has the ability to simultaneously measure both
CF and LI\textsuperscript{12}. It remains to be seen how our recently
acquired knowledge of LI will translate to this new platform, and
whether LI data provide incremental benefit beyond what can be achieved
already with standard composite metrics. Either way, it appears that
humble focal RF energy may still have a lot to offer
electrophysiologists, and its obituaries may be premature.

\emph{}

\emph{References}

1. Duytschaever M, Vijgen J, De Potter T, et al. Standardized pulmonary
vein isolation workflow to enclose veins with contiguous lesions: the
multicentre VISTAX trial. Europace. 2020;22(11):1645-1652.
doi:10.1093/europace/euaa157

2. Bourier F, Ramirez FD, Martin CA, et al. Impedance, power, and
current in radiofrequency ablation: Insights from technical, ex vivo,
and clinical studies. J Cardiovasc Electrophysiol.
2020;31(11):2836-2845. doi:10.1111/jce.14709

3. Piorkowski C, Sih H, Sommer P, et al. First in human validation of
impedance-based catheter tip-to-tissue contact assessment in the left
atrium. J Cardiovasc Electrophysiol. 2009;20(12):1366-1373.
doi:10.1111/j.1540-8167.2009.01552.x

4. Sulkin MS, Laughner JI, Hilbert S, et al. Novel Measure of Local
Impedance Predicts Catheter-Tissue Contact and Lesion Formation. Circ
Arrhythmia Electrophysiol. 2018;11(4):1-11.
doi:10.1161/CIRCEP.117.005831

5. Garrott K, Gams A, Laughner J, Lehn L, Gutbrod S, Hamann J. Local
impedance on a force sensing catheter predicts volumetric lesion
temperature changes. Europace. 2020;22(Supplement\_1).
doi:10.1093/europace/euaa162.248

6. Solimene F, Santoro MG, De Simone A, et al. Pulmonary vein isolation
in AF patients guided by a novel local impedance algorithm: 1-year
outcome from the CHARISMA study. J Cardiovasc Electrophysiol. 2021.

7. Das M, Luik A, Shepherd E, et al. Local catheter impedance drop
during pulmonary vein isolation predicts acute conduction block in
patients with paroxysmal atrial fibrillation: initial results of the
LOCALIZE clinical trial. Europace. 2021:1-10.
doi:10.1093/europace/euab004

8. Martin CA, Martin R, Gajendragadkar PR, et al. First clinical use of
novel ablation catheter incorporating local impedance data. J Cardiovasc
Electrophysiol. 2018;29(9):1197-1206. doi:10.1111/jce.13654

9. Gunawardene M, M\selectlanguage{ngerman}ünkler P, Eickholt C, et al. A novel assessment of
local impedance during catheter ablation: Initial experience in humans
comparing local and generator measurements. Europace. 2019;21:I34-I42.
doi:10.1093/europace/euy273

10. Barkagan M, Leshem E, Shapira-Daniels A, et al. Histopathological
Characterization of Radiofrequency Ablation in Ventricular Scar Tissue.
JACC Clin Electrophysiol. 2019;5(8):920-931.
doi:10.1016/j.jacep.2019.05.011

11. Tao S, Guttman MA, Fink S, et al. Ablation Lesion Characterization
in Scarred Substrate Assessed Using Cardiac Magnetic Resonance. JACC
Clin Electrophysiol. 2019;5(1):91-100. doi:10.1016/j.jacep.2018.11.001

12. Garrott K, Laughner J, Gutbrod S, et al. Combined local impedance
and contact force for radiofrequency ablation assessment. Heart Rhythm.
2020;17(8):1371-1380. doi:10.1016/j.hrthm.2020.03.016

Figure 1. Local impedance in action

A) Electric fish use sensors on their sides to feel the expansion and
compression of the field lines created between their head and tail. In
open ocean the field lines spread uniformly, but when an object enters
the field the field compresses. If that object's resistivity decreases
due to heat, the field expands proportional to volume heating. B) A
local electrical field (\textasciitilde{}) is created by driving
non-stimulatory current from the tip of the catheter to the proximal
ring electrode, while voltage (V) is measured from the tip to distal
ring electrode. This allows the catheter to sense changes in volumetric
dielectric properties surrounding the tip electrode. C) In this bench
study, temperature profiles at varying depths were correlated with the
local impedance measured during RF lesion creation. Thermocouples were
placed into the tissue at the surface, at 2 mm depth, and at 4 mm depth.
The local impedance drop was seen to dynamically follow the rate of
intramural temperature rise at both low and high powers.

\textbf{Hosted file}

\verb`JCE LI editorial image.pptx`  available at \url{https://authorea.com/users/407099/articles/517506-local-impedance-to-guide-focal-radiofrequency-ablation-there-is-life-in-the-old-dog-yet}

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