\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}
\usepackage{CJKutf8}



\usepackage{float}








\begin{document}

\title{Catheter contact angle influences local impedance drop during
radiofrequency catheter ablation: Insight from a porcine experimental
study with 2 different LI-sensing catheters}



\author[1]{Gen Matsuura}%
\author[1]{Hidehira Fukaya}%
\author[1]{Emiyu Ogawa}%
\author[1]{Sota Kawakami}%
\author[2]{Hitoshi Mori}%
\author[1]{Daiki Saito}%
\author[1]{Tetsuro Sato}%
\author[1]{Hironori Nakamura}%
\author[1]{Naruya Ishizue}%
\author[1]{Jun Oikawa}%
\author[1]{Jun Kishihara}%
\author[1]{Shinichi Niwano}%
\author[1]{Junya Ako}%
\affil[1]{Kitasato University School of Medicine}%
\affil[2]{Saitama Medical University International Medical Center}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: Local impedance (LI) can indirectly measure catheter contact
and tissue temperature during radiofrequency catheter ablation (RFCA).
However, data on the effects of catheter contact angle on LI parameters
are scarce. This study aimed to evaluate the influence of catheter
contact angle on LI changes and lesion size with 2 different LI-sensing
catheters in a porcine experimental study. Methods: Lesions were created
by the INTELLANAV MiFi OI (MiFi) and the INTELLANAV STABLEPOINT
(STABLEPOINT). RFCA was performed with 30 watts and a duration of 30
seconds. The CF (0, 5, 10, 20, and 30 g) and catheter contact angle
(30\selectlanguage{ngerman}°, 45°, and 90°) were changed in each set (n=8 each). The LI rise, LI
drop, and lesion size were evaluated. Results: The LI rise increased as
CF increased. There was no angular dependence with the LI rise under all
CFs in the MiFi. On the other hand, the LI rise at 90° was lower than at
30° under 5 and 10 g of CF in STABLEPOINT. The LI drop increased as CF
increased. Regarding the difference in catheter contact angles, the LI
drop at 90° was lower than that at 30° for both catheters. The maximum
lesion widths and surface widths were smaller at 90° than at 30°,
whereas there were no differences in lesion depths. Conclusion: The LI
drop and lesion widths at 90° were significantly smaller than those at
30°, although the lesion depths were not different among the 3 angles
for the MiFi and STABLEPOINT.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Introduction}

Radiofrequency (RF) catheter ablation (CA) is an established treatment
for several types of cardiac arrhythmias.
\textsuperscript{{[}1{]}}Creating sufficient lesion formation is crucial
for successful ablation. In contrast, excessive RF delivery can lead to
steam pops or perforations;\textsuperscript{{[}2{]}} therefore, it is
paramount to energize without excess or deficiency.

Recently, contact force (CF) sensing catheters have become the standard
tools for RFCA,\textsuperscript{{[}3{]}} \textsuperscript{{[}4{]}
{[}5{]}} and CF parameter-integrated indices, such as the force-time
integral (FTI),\textsuperscript{{[}6{]}} ablation index
(AI),\textsuperscript{{[}7{]} {[}8{]}} and lesion size index
(LSI)\textsuperscript{{[}9{]}}, have been reported as effective
surrogate parameters for sufficient lesion creation, especially in
pulmonary vein isolation (PVI) for atrial fibrillation (AF). However,
these indices are provided only from the ablation parameters and do not
include the characteristics of the local myocardial tissue.

Historically, generator impedance change has been used as a surrogate
marker of lesion creation by an RF
application;\textsuperscript{{[}10{]}} however, since the absolute value
of the change is crude, it cannot be used as a definitive marker of
lesion formation. Recently, a local impedance (LI) detectable ablation
catheter (INTELLANAV MiFi OI, Boston Scientific, Maple Grove, MN, USA:
MiFi) was put on the market. This catheter has 3 microelectrodes
incorporated into the distal tip, and a more precise LI would be
detected with these microelectrodes. Since the LI would be changed by
tissue contact and temperature, this parameter allows us to speculate
about the CF and tissue temperature during the RF
application\textsuperscript{{[}11{]}}. In addition, both LI- and
CF-sensing ablation catheters (INTELLANAV STABLEPOINT Boston
Scientific, Maple Grove, MN, USA: STABLEPOINT) have recently become
available, and they will contribute to additional improvement in the
quality of RFCA.

Several studies have suggested that LI decreases reflect tissue
denaturation by RF applications, and the degree of LI drop is correlated
with the lesion size. \textsuperscript{{[}12{]}{[}13{]} {[}14{]}
{[}15{]}} However, although the LI can be changed by changing the
catheter contact angle to the tissue, data on the effects of the
catheter contact angle on LI parameters and lesion size are scarce.
Therefore, this study aimed to evaluate the relationships among the
catheter contact angles, LI parameters, and lesion size with 2 different
LI-sensing ablation catheters in a porcine experimental study.

\textbf{Methods}

Ablation catheter and local impedance measurements

An open-irrigated MiFi ablation catheter with a 4.5 mm distal tip and an
open-irrigated STABLEPOINT ablation catheter with a 4.0 mm distal tip
were used for the experiment. The MiFi has 3 microelectrodes
incorporated within the distal tip electrode, and there are 3 equally
spaced 0.8 mm diameter microelectrodes located 2 mm from the tip of the
catheter. First, LI was measured between each microelectrode and the
4\textsuperscript{th} ring electrode of the ablation catheter by a
driven nonstimulatory alternating current (5.0 ?A, 14.5 kHz) between the
distal tip electrode and the 4\textsuperscript{th} ring electrode to
create a local potential field. After that, only the maximum LI was
selected for the actual LI. Since the CF cannot be measured in the MiFi
catheter, it was measured using the pressure-current transducer (load
cell), as described in the next section. On the other hand, the
STABLEPOINT does not have microelectrodes, and the LI was measured
between the whole distal tip (4 mm length) and 2\textsuperscript{nd}ring
electrodes by being driven by a nonstimulatory alternating current (5.0
?A, 14.5 kHz) between the distal tip electrode and the
4\textsuperscript{th} ring electrode to create a local potential field.

In vitro experimental setup

Fresh porcine hearts were commercially obtained, which were extracted
within 48 hours of sacrifice. Porcine myocardial tissue was fixed on a
stage in a water pool (Figure 1). The saline solution was prepared for
the water pool with 20 g of salt to 7.8 L of water so that the baseline
LI was set at 90 ohms when using MiFi and 140 ohms when using
STABLEPOINT because blood pool data for those catheters in the clinical
setting were approximately 80--100 ohms for the MiFi and 130--150 ohms
for the STABLEPOINT. The saline solution in the water pool was kept at
37 \selectlanguage{ngerman}°C using a thermostatic system (Thermo-Mate BF-400, Yamato Scientific
Co., Ltd., Tokyo, Japan). The water bath was circulated across the
myocardial tissue surface at a flow rate of 5 L/min to simulate blood
flow. The shaft of the catheter was fixed to the pillar 10 mm from the
4\textsuperscript{th} ring electrode in the distal direction, and the CF
on the catheter tip was measured over time by connecting the pillar to a
load cell (DPU-2N, Imada Co., Ltd., Toyohashi, Japan). The voltage
waveform from the load cell was recorded by a 16-bit digital coder
(DP850, Yokogawa Electric Corp., Tokyo, Japan). A scale was used to
calibrate the CF at the tip of the catheter with the load cell voltage
value in a range of 0--30 g.

Ablation protocol

RF lesions were created on the LV epicardium with a Rhythmia HDx\selectlanguage{english}
Mapping System (Boston Scientific, Maple Grove, MN, USA). The RF
application was delivered with a constant power of 30 watts and a
duration of 30 seconds. CF (0, 5, 10, 20, and 30 g) and the catheter
contact angle (30deg, 45deg, and 90deg) were changed in each set (total 120
lesions, n=8 each, Figure 2). The same experiment was performed with 2
different ablation catheters. The LI increases as the catheter contacts
the tissue, and the LI decreases with the RF application. We defined the
value of the LI increase above the baseline LI by the catheter contact
as the LI rose and the absolute decrease in LI by the RF application as
the LI dropped. The proportional values of the LI parameters were also
evaluated to compare the 2 different catheters. The \%LI rise was
calculated as the LI rise divided by the baseline LI, and the \%LI drop
was calculated as the LI drop divided by the baseline LI.

RF lesion creation and measurement

After the RF application, the lesions were cut out and cross-sectioned
at the center of the surface lesion, and macro images were taken. The
maximum lesion width, surface width, and lesion depth were measured in
each lesion (Figure 3) by the image analysis software ImageJ (NIH Image,
Bethesda, MD). The average values measured by two persons were adopted
to ensure objectivity.

Statistical analysis

All statistical analyses were performed using JMP 14 software (SAS
Institute Inc., Cary, NC, USA). The data are presented as the mean +-
standard error (SE) for continuous variables. The differences in lesion
size (maximum lesion width, surface width, and lesion depth), LI rise,
and LI drop among the three catheter angles were assessed by the
analysis of variance in each CF, followed by post hoc analysis using the
Tukey HSD test. The level of statistical significance was set at p
\textless{}0.05.

\textbf{Results}

LI rise and LI drop at different catheter contact angles

Figures 4A and 4C show the correlation between the catheter contact
angle and the LI rise under each CF. The LI values increased as CF
increased for both catheters. Regarding the difference in the catheter
contact angles, there was no angular dependence for the LI rise under
all CFs in the MiFi (Figure 4A). On the other hand, the LI rise at 90deg
was lower than that at 30deg under 5 and 10 g of CF in STABLEPOINT (Figure
4C).

Figures 4B and 4D show the correlation between the catheter contact
angle and the LI drop by the RF application under each CF. The LI drop
values also increased as the CF increased for both catheters. Regarding
the difference in the catheter contact angles, the LI drop at 90deg was
significantly lower than that at 30deg under 10, 20, and 30 g of CF in the
MiFi (Figure 4B). Likewise, the LI drop at 90deg was significantly lower
than that at 30deg under 5, 10, 20, and 30 g of CF in STABLEPOINT (Figure
4D).

Relationship between catheter contact angle and lesion size

Figure 3 shows representative lesion images for each catheter angle RF
application (30 watts, 30 seconds, 30 g of CF). Although the lesion
depths were compatible, the maximum lesion widths and surface widths
were smaller at 90deg than at 30deg and 45deg. The summarized data of all
experiments are shown in Figure 5. In the MiFi group, the maximum lesion
widths under 20 and 30 g of CF were smaller at 90deg than at 30deg and 45deg
(CF 20 g: P = 0.003, CF 30 g: P = 0.011, respectively). Surface widths
under 5, 10, 20, and 30 g of CF were also smaller at 90deg than at 30deg (CF
5 g: P = 0.013, CF 10 g: P = 0.003, CF 20 g: P \textless{} 0.001, CF 30
g: P = 0.007, respectively). On the other hand, the lesion depths were
not significantly different among the three angles under any CF. For the
STABLEPOINT, the maximum lesion widths under 0, 5, 10, 20 and 30 g of CF
were smaller at 90deg than those at 30deg (CF 0 g: P = 0.001, 5 g: P
\textless{} 0.001, 10 g: P \textless{} 0.001, 20 g: P = 0.011, and 30 g:
P = 0.039, respectively). Surface widths under 0, 5, 10, 20, and 30 g of
CF were also smaller at 90deg than at 30deg (CF 0 g: P \textless{} 0.001, 5
g: P \textless{} 0.001, 10 g: P \textless{} 0.001, 20 g: P \textless{}
0.001, and 30 g: P = 0.032, respectively). The lesion depths were not
significantly different among the three angles under any CF.

Correlation between the LI drop and lesion size at each catheter contact
angle

Figure 6 shows the correlations between the LI drop and lesion size at
each catheter contact angle. The approximate curves were well fitted
with a natural logarithm equation at all angles on the LI drop vs. the
maximum lesion width (Figures 6A and 6C) and the lesion depth (Figure 6B
and 6D) in the MiFi (upper) and STABLEPOINT (lower) models. Thus, the LI
drops were correlated with maximum lesion widths and lesion depths at
any angle for both ablation catheters.

Differences in the impact of the LI drop and lesion size between MiFi
and STABLEPOINT

Comparing the 2 different catheters, the \% LI rise in the STABLEPOINT
was significantly higher than that in the MiFi under all CFs and all
contact angles (Supplemental Figures A, B, and C). The values of \% LI
drop in the STABLEPOINT were significantly higher than those in the MiFi
except for under 30 g of CF at 90deg and 45deg (Supplemental Figures D, E,
and F).

Figure 7 shows the correlations between the \%LI drop and lesion size
for the 2 catheters. The approximate curves were well fitted with a
natural logarithm equation on \%LI drop vs. maximum lesion width (Figure
7A) and lesion depth (Figure 7B) for both catheters. The absolute values
of the LI parameters were different, but the association between the
percent changes and lesion sizes were similar between the 2 catheters.

\textbf{Discussion}

In this in vitro study, we evaluated the impact of the catheter contact
angles on lesion formation, focusing on the LI parameters with different
CFs in the 2 different LI-sensing ablation catheters. The major findings
of our study are as follows: 1) the LI rose as CF increased, and the
degrees of LI rise were not significantly different among the 3 catheter
contact angles in the MiFi but it was lower at 90deg with the STABLEPOINT
than at 30deg; 2) the LI drop at 90deg was lower than at 30deg for both
ablation catheters; 3) the maximum lesion widths and surface widths were
smaller at 90deg than at 30deg, whereas there were no differences in the
lesion depths for both ablation catheters, 4) the actual value of the LI
drops by the RF application were well correlated with the lesion sizes
for each catheter angle, and 5) the \%LI drops were predictable for
lesion formation irrespective of the catheter angles for both ablation
catheters.

Correlation between the lesion size and the catheter contact angles

Several studies have demonstrated that the catheter contact angle is an
important factor in lesion
creation.\textsuperscript{{[}16{]}{[}17{]}{[}18{]}} In an in vitro
study, Calzolar et al. reported \textsuperscript{{[}17{]}} that the
superficial lesion widths were increased by shifting the catheter angle
from the perpendicular to the parallel orientation, and the intratissue
maximal lesion widths were greater with an oblique catheter orientation
than with a perpendicular position using a 3.5-mm tip, open-irrigated,
CF-sensing catheter (TactiCath\selectlanguage{english} SE; Abbott, St. Paul, MN, USA).
Conversely, they also reported that the lesion depths were not different
with different catheter orientations. In the present study, the maximum
lesion widths and surface widths were also smaller at 90deg than at 30deg,
whereas there were no differences in lesion depth. Although the distal
tip lengths of the ablation catheters are different (4.5 mm in
INTELLANAV MiFi\selectlanguage{english} OI, 4.0 mm in INTELLANAV STABLEPOINT\selectlanguage{english}, and 3.5 mm in
TactiCath\selectlanguage{english} SE), resulting in different sizes of the lesion
creation,\textsuperscript{{[}19{]}{[}20{]}} their impact on the catheter
angles are consistent with a previous study.

LI-guided RFCA considering the lesion size and interlesion distance

In RFCA for AF, PVI is the most effective
procedure,\textsuperscript{{[}1{]}} and the creation of secure RF
lesions avoiding conduction gaps is essential to achieve a durable
PVI.\textsuperscript{{[}21{]} {[}22{]}} Recently, the Rhythmia module
with an LI-sensing catheter was developed as a unique concept to
determine the lesion size by the RF application. LI drops have been
reported to be superior for predicting lesion size than FTIs
\textsuperscript{{[}12{]} {[}15{]}}, and LI-guided PVI can provide a
sufficient RF application along with the characteristics of the local
myocardial tissue. Das M et al. reported that the optimal threshold of
the LI drop for predicting gaps for anterior/roof segments was 16.1 ohms
(positive predictive value for block: 96.3\%) and for posterior/inferior
segments it was 12.3 ohms (positive predictive value for block: 98.1\%)
with MiFi.\textsuperscript{{[}23{]}} Our present study suggested that
the lesion formation and LI parameters were changed by the different
catheter angles (Figures 4 and 5). The LI drop and maximum lesion width
at 90deg were significantly lower and smaller than those at 30deg, although
lesion depths were not different among the three angles. This result
suggests that the LI drop accurately reflects the difference in the
lesion widths as the lesion volume changes with a perpendicular contact
angle. Although indices such as FTI, LSI, and AI have been reported as
useful parameters to predict RF lesion formation, it is impossible to
recognize the differences in actual lesion formation (depth and width)
by the catheter angle, which were observed in the present study.
Therefore, LI-guided RFCA would allow us to adjust the ablation
strategy, such as an optimal interlesion distance, to create continuous
linear lesions considering the lesion widths.

Differences in the impact of the contact angle between MiFi and
STABLEPOINT

In the present study, we evaluated 2 different LI-sensing ablation
catheters. Notable differences between the 2 catheters for the LI were
that the LI rise at 90deg was lower than at 30deg under 5 and 10 g of CF for
the STABLEPOINT (Figure 4C), while there were no angular dependences for
the LI rise under all CFs in the MiFi (Figure 4A). These results could
be explained by the differences in the features of the 2 electrodes
measuring the LI in each catheter. In the MiFi, the LI was measured
between 3 microelectrodes and the 2\textsuperscript{nd} ring electrode,
and only the maximum LI was selected as the actual LI. On the other
hand, the STABLEPOINT does not have a microelectrode, so the LI was
measured between the whole distal tip and the 2\textsuperscript{nd} ring
electrode. Therefore, the tissue contact area or distance from the
tissue to the LI measuring electrodes would be changed by the catheter
contact angles. Therefore, the LI in STABLEPOINT would be affected by a
larger area than for MiFi. In other words, the LI change affected by the
myocardial tissue would be relatively smaller, especially with the more
perpendicular catheter angle for STABLEPOINT, resulting in angular
differences in the LI rise. In contrast, LI in the MiFi would be
affected by a smaller area, i.e., the LI parameters in the MiFi would be
more sensitive to tissue information. As a result, it is considered
better to have a microelectrode to acquire more local LI information.

Since the size of the distal tips of STABLEPOINT was smaller (4 mm) than
that of the MiFi (4.5 mm), the lesion sizes were larger for STABLEPOINT.
Therefore, the \%LI drop and \%LI rise values (Supplemental Figure) were
due to the different features of the catheters. On the other hand, the
approximate curves were well fitted with the natural logarithm equation
of \%LI drop vs. maximum lesion widths (Figure 7A) and lesion depths
(Figure 7B) for the 2 catheters. The absolute values of the LI
parameters were different, but the association between the percent
changes of the LI drop and lesion size were similar between the 2
catheters; therefore, the \%LI drop can be a useful value for the
concept of an LI-guided RFCA.

\textbf{Clinical implications}

There are few studies on LI drops by RF applications and lesion size
considering the catheter contact angle. We found that the LI drop was an
important factor for creating an effective RF lesion with 2 different
LI-sensing catheters. In addition, we demonstrated that the catheter
contact angles affected the LI drop and lesion size. The results of this
study would be helpful to create effective RF lesions with a
comprehension of the LI drop at each catheter angle.

\textbf{Study limitations}

Our study has several limitations. First, the CF cannot be directly
measured with the INTELLANAV MiFi\selectlanguage{english} OI. Although the CF was measured with
a digital scale with a calibrated force-current transducer (load cell),
the actual CF might be different. Second, we evaluated the relationship
between the LI drop, LI rise, and lesion size at different catheter
angles under constant power and time; therefore, different settings were
not evaluated. In addition, there was no steam pop during this study, so
the predictive LI value for safety concerns could not be evaluated.
Finally, since this experiment was performed in porcine myocardial
tissues, the results may not be directly translated into clinical
practice. RF lesion size in a clinical setting might be affected by
multiple factors, such as stability, respiratory motion, or blood flow,
not only catheter orientation. Therefore, clinical studies are necessary
to assess lesion creation in a more clinically relevant setting.

\textbf{Conclusion}

The values of LI drop and lesion width at 90deg were significantly smaller
than those at 30deg at the same ablation setting, although the lesion
depths were not different among the 3 angles for the MiFi and the
STABLEPOINT. They were correlated with maximum lesion width and lesion
depth at any angle, which could be a good predictor of the lesion size
by RF applications.

\textbf{Acknowledgments}

We would like to thank Yoshiki Tasaki and Masaya Mizokami for their help
with this work.

\textbf{Disclosure}

This study received no financial support from commercial sources, and
the authors have no conflicts of interest to declare.

\emph{}

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Parkash R, Tang AS, Sapp JL, Wells G. Approach to the Catheter
  Ablation Technique of paroxysmal and Persistent Atrial Fibrillation: A
  Meta-Analysis of the Randomized Controlled Trials. J Cardiovasc
  Electrophysiol 2011;22:729-738.
\item
  Viles-Gonzalez JF, Berjano E, d'Avila A. Complications of
  Radiofrequency Catheter~Ablation:~Can We Prevent Steam Pops?. JACC
  Clin Electrophysiol 2018;4(4): 501-503.
\item
  Reddy VY, Shah D, Kautzner J, Schmidt B, Saoudi N, Herrera C, Jais P,
  Hindricks G, Peichl P, Yulzari A, Lambert H, Neuzil P, Natale A, Kuck
  KH. The relationship between contact force and clinical outcome during
  radiofrequency catheter ablation of atrial fibrillation in the TOCCATA
  study. Heart Rhythm 2012;9(11):1789-1795.
\item
  Kimura M, Sasaki S, Owada S, Horiuchi D, Sasaki K, Itoh T, Ishida Y,
  Kinjo T, Tomita H, Okumura K. Comparison of lesion formation between
  contact force-guided and non-guided circumferential pulmonary vein
  isolation: A prospective, randomized study. Heart Rhythm
  2014;11(6):984-991.
\item
  Neuzil P, Reddy VY, Kautzner J, Petru J, Wichterle D, Shah D, Lambert
  H, Yulzari A, Wissner E, Kuck KH. Electrical Reconnection After
  Pulmonary Vein Isolation Is Contingent on Contact Force During Initial
  Treatment: results from the EFFICAS I study. Circ Arrythm
  Electrophysiol 2013;6(2):327-333.
\item
  Shah DC, Lambert H, Nakagawa H, Langenkamp A, Aeby N, Leo G. Area
  under the real-time contact force curve (force-time integral) predicts
  radiofrequency lesion size in an in vitro contractile model. J
  Cardiovasc Electrophysiol 2010;21:1038-1043.
\item
  Phlips T, Taghji P, El Haddad M, Wolf M, Knecht S, Vandekerckhove Y,
  Tavernier R, Duytschaever M. Improving procedural and one-year outcome
  after contact force-guided pulmonary vein isolation: the role of
  interlesion distance, ablation index, and contact force variability in
  the 'CLOSE'-protocol. Europace 2018;20:419-427.
\item
  Hussein A, Das M, Chaturvedi V, Asfour IK, Daryanani N, Morgan M,
  Ronayne C, Shaw M, Snowdon R, Gupta D. Prospective use of ablation
  index targets improves clinical outcomes following ablation for atrial
  fibrillation. J Cardiovasc Electrophysiol 2017;28(9):1037-1047.
\item
  Calzolari V, De Mattia L, Indiani S, Crosato M, Furlanetto A,
  Licciardello C, Squasi P Antonio M, Olivari Z. In vitro validation of
  the lesion size index to predict lesion width and depth after
  irrigated radiofrequency ablation in a porcine model. JACC Clin
  Electrophysiol 2017;3(10):1126-1135.
\item
  Reichlin T, Kecht S, Lane C, Kuhne M, Nolf E, Chopra N, Tadros TM,
  Reddy VY, Schaer B, John RM, Osswald S, Stevenson WG, Sticherling C,
  Michaud GF. Initial impedance decrease as an indicator of
  good\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}catheter contact: Insights from radiofrequency ablation with
  force sensing catheters. Heart Rhythm 2014;11(2):194-201.
\item
  Garrott K, Gams A, Laughner J, Lehn L, Gutbrod S, Hamann J. Local
  impedance on a force sensing catheter predicts volumetric lesion
  temperature changes. EP Europace. 2020;22.
\item
  Sulkin MS, Laughner JI, Hilbert S, Kapa S, Kosiuk J, Younan P, Romero
  I, Shuros A, Hamann JJ, Hindricks G, Bollmann A. Novel measure of
  local impedance predicts and catheter-tissue contact and lesion
  formation. Circ Arrythm Electrophysiol 2018;11(4): 005831.
\item
  Martin CA, Martin R, Gajendragadkar PR, Maury P, Takigawa M, Cheniti
  G, Frontera A, Kitamura T, Duchateau J, Vlachos K, Bourier F, Lam A,
  Load S, Murray S, Shephard E, Pambrun T, Denis A, Derval N, Hocini M,
  Haissaguerre M, Jais P, Sacher F. First clinical use of novel ablation
  catheter incorporating local impedance data. J Cardiovasc
  Electrophysiol 2018;29(9):1197-1206.
\item
  Gunawardene M, M\selectlanguage{ngerman}ünkler P, Eickholt C, Akbulak RÖ, Jularic M, Klatt N,
  Hartmann J, Dinshaw L, Jungen C, Moser JM, Merbold L, Willems S, Meyer
  C. A novel assessment of local impedance during catheter ablation:
  initial experience in humans comparing local and generator
  measurements. Europace 2019;21:34-42.
\item
  Garrott K, Laughner J, Gutbord S, Sugrue A, Shuros A, Sulkin M, Yasin
  O, Bush J, Pottinger N, Meyers J, Kapa S. Combined~local~impedance~and
  contact force for radiofrequency ablation assessment. Heart Rhythm
  2020;17(8):1371-1380.
\item
  Kawaji T, Hojo S, Kushiyama A, Nakatsuma K, Kaneda K, Kato M,
  Yokomatsu T, Miki S. Limitation of lesion quality estimated by
  ablation index: an in vitro study. J Cardiovasc Electrophysiol
  2019;30(6):926-933.
\item
  Calzolari V, De Mattia L, Basso F, Crosato M, Scalon A, Squasi PAM,
  Del Favero S, Cernetti C. Ablation catheter orientation: In vitro
  effects on lesion size and in vivo analysis during PVI for atrial
  fibrillation. Pacing Clin Electrophysiol 2020;43(12):1554-1563.
\item
  Masnok K, Watanabe N. Relationship of Catheter Contact Angle and
  Contact Force with Contact Area on the Surface of Heart Muscle Tissue
  in Cardiac Catheter Ablation. Cardiovasc Eng Technol
  2021;12(4):407-417.
\item
  Kawano D, Mori H, Kato R, Tsutsui K, Ikeda Y, Sumitomo N, Fukaya H,
  Iwagana S, Nakano S, Muramatsu T, Matsumoto K. The optimal ablation
  setting for a local impedance guided catheter in an in vitro
  experimental model. J Cardiovasc Electrophysiol 2021;32(8):2069-2076.
\item
  Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, Ikeda A,
  Pitha JV, Sharma T, Lazzara R, Jackman WM. Novel contact force sensor
  incorporated in irrigated radiofrequency ablation catheter predicts
  lesion size and incidence of steam pop and thrombus. Circ Arrythm
  Electrophysiol 2008;1(5):354-362.
\item
  Nery PB, Belliveau D, Nair GM, Bernick J, Redpath CJ, Szczotka A,
  Sadek MM, Green MS, Wells G, Birnie DH. Relationship between pulmonary
  vein reconnection and atrial fibrillation recurrence: a systematic
  review and meta-analysis. JACC Clin Electrophysiol 2016;2(4):474-483.
\item
  Verma A, Kilicaslan F, Pisano E, Marrouche NF, Fanelli R, Brachmann J,
  Geunther J, Potenza D, Martin DO, Cummings J, Burkhardt JD, Saliba W,
  Schweikert RA, Natale A. Response of atrial fibrillation to pulmonary
  vein antrum isolation is directly related to resumption and delay of
  pulmonary vein conduction. Circulation2005;112(5):627-635.
\item
  Das M, Luik A, Shepherd E, Sulkin M, Laughner J, Oesterlein T, Duffy
  E, Meyer C, Jais P, Duchateau J, Yue A, Ullah W, Ramos P, García-Bolao
  I. 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;23(7):1042-1051.
\end{enumerate}

\textbf{Figure legends}

\textbf{Figure 1. In vitro experimental setup.}

(A) The saline solution in the water pool was kept at 37 °C using a
thermostatic system and it was driven across the surface of the
myocardial tissue at a flow rate of 5 L/min to simulate blood flow. The
solution in the water pool was adjusted to 90 and 140 ohms of baseline
LI for MiFi and STABLEPOINT, respectively. (B) Lesions were created on
the porcine myocardial left ventricles by 2 LI-sensing ablation
catheters. (C) RFCA was performed with a constant power of 30 watts and
a duration of 30 seconds. The CF and catheter contact angles were
changed in each set.

LI = local impedance, CF = contact force, RFCA = radiofrequency
ablation.

\textbf{Figure 2 Ablation protocol}

The study protocol is shown in Figure 2. A detailed explanation is given
in the main text.

CF = contact force, RF = Radiofrequency.

\textbf{Figure 3. RF lesion size measurement.}

Figure 3 shows the representative lesion images for each catheter angle
RF application (30 watts, 30 sec, CF = 30 g). MWs, SWs, and LDs were
evaluated for each lesion.

MW = maximum lesion width, SW = surface width, LD = lesion depth, RFCA =
radiofrequency ablation.

\textbf{Figure 4.} \textbf{Relationship between the catheter contact
angle and the LI rise and LI drop}

Figure 4 shows the correlation between the catheter contact angle and LI
rise (4A and 4C) and the LI drop (4B and 4D) under each CF in the MiFi
(upper panel) and the STABLEPOINT (lower panel).

LI = local impedance, CF = contact force.

\textbf{Figure 5. Relationship between the catheter contact angle and
lesion size}

Figure 5 shows the correlation between the catheter contact angle and
lesion size.

In the MiFi, (A) MWs at 90° were smaller than those at 30° under 20 g
and 30 g of CF; (B) SWs at 90° were smaller than those at 30° under 5,
10, 20, and 30 g of CF; (C) the LDs were not significantly different for
each of the three catheter angles. In the STABLEPOINT, (D) MWs at 90°
were smaller than those at 30° under 0, 5, 10, 20, and 30 g of CF; (E)
SWs at 90° were smaller than those at 30° under 0, 5, 10, 20, and 30 g
of CF; (F) LDs were not significantly different for each of the three
catheter angles.

MW = maximum lesion width, SW = surface width, LD = lesion depth.

\textbf{Figure 6. Correlation between the LI drop and lesion size at
each catheter contact angle}

The approximate curves were well fitted with a natural logarithm
equation on LI drop vs. lesion size at all catheter angles. Thus, the LI
drops by RF application were well correlated with the lesion sizes at
each catheter angle.

MW = maximum lesion width, SW = surface width, LD = lesion depth.

\textbf{Figure 7.}

\textbf{Differences in the impact of the contact angle between MiFi and
STABLEPOINT}

The approximate curves were well fitted with a natural logarithm
equation on \%LI drop vs. maximum lesion width (Figure 7A) and lesion
depth (Figure 7B) for both catheters. The absolute values of the LI
parameters were different, but the association between the percent
changes and lesion size was similar for both catheters.

CF = contact force, \%LI drop =LI drop/baseline LI.

\textbf{Supplemental Figure}

\textbf{The difference in the \%LI drop between the MiFi and
STABLEPOINT}

Comparing the 2 different catheters, the values of \%LI rise for the
STABLEPOINT were significantly higher than those for the MiFi under all
CF and contact angles. The \%LI drops for STABLEPOINT were significantly
higher than those for MiFi except for under 30 g of CF at 90° and 45°.

CF = contact force, \%LI rise =LI rise/baseline LI, \%LI drop =LI
drop/baseline LI.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-paper/LI-paper}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papes/LI-papes}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papet/LI-papet}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papeu/LI-papeu}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papev/LI-papev}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papew/LI-papew}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/LI-papex/LI-papex}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

