\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,greek,english]{babel}



\usepackage{float}








\begin{document}

\title{Predictive factors for increase in pacing threshold after transcatheter
pacing system implantation owing to micro-dislodgement}



\author[1]{Motoaki Higuchi}%
\author[1]{Yuki Kawahara}%
\author[2]{Yasutoshi Shinoda}%
\author[3]{Tomoaki Hasegawa}%
\author[4]{Mayu Ishibashi}%
\author[1]{Norihiro Yamada}%
\author[1]{Yoshiro Chiba}%
\author[1]{Koji Ohira}%
\author[1]{Minoru Murata}%
\author[1]{Kazutaka Aonuma}%
\affil[1]{Mito Saiseikai General Hospital}%
\affil[2]{University of Tsukuba}%
\affil[3]{Yokohama-city Bay Red Cross Hospital}%
\affil[4]{Ibaraki Prefectural Central Hospital}%


\vspace{-1em}



  
  \date{May 15, 2024}


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





\selectlanguage{english}
\begin{abstract}
Introduction: Achievement of a favorable pacing threshold with a Micra
transcatheter pacing system (Micra-TPS) is important for reducing
battery depletion; in some cases, the threshold increases shortly after
the device is implanted, and a higher pacing threshold may be required.
This study aimed to define the causes and predictors of the increase in
pacing threshold observed shortly after Micra-TPS implantation. Methods
and Results: The study included 64 consecutive patients who underwent
Micra-TPS implantation between 2017 and 2020. Patients were divided into
two groups depending on their pacing threshold, namely, the increased
pacing threshold (IPT) group (threshold increased by [?]0.5 V/0.24 msec
within 1 month of implantation) and the stable pacing threshold (SPT)
group. Excluding 4 patients we were unable to conduct follow-up on, 9 of
the 60 remaining patients (15\%) were in the IPT group and 51 (85\%)
were in the SPT group. The IPT group had significantly lower implant
impedance values and higher implant thresholds than the SPT group: 582 \selectlanguage{ngerman}±
59 vs 755 ± 167 \selectlanguage{greek}Ω \selectlanguage{english}(P \textless{}0.001) and 1.29 \selectlanguage{ngerman}± 0.87 vs 0.71 ± 0.40
V/0.24 msec (P =0.014), respectively. Implant impedance and threshold
may serve as predictors of a threshold increase after implantation (area
under the curve: 0.737--0.943 and 0.586--0.926, respectively).
Conclusion: An increased pacing threshold was noted shortly after
Micra-TPS implantation owing to micro-dislodgement because of
insufficient anchoring of the device on the myocardium. Impedance
\textgreater{}660 \selectlanguage{greek}Ω \selectlanguage{english}and threshold \textless{}1.0 V/0.24 msec may be
predictive factors for an increased pacing threshold.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

Permanent pacemaker implantation is the only established treatment for
bradyarrhythmia that contributes to improved life prognosis as well as
quality of life. In the last 10 years, 50,000 implantable pacemakers
have been introduced in Japan every year, and more than 60,000 cases
have been recorded annually in recent years. In the United States, more
than 350,000 pacemakers are implanted annually, and this number has
doubled in the last 30 years.\textsuperscript{1} Elderly people are more
prone to bradyarrhythmias, and it is estimated that more patients will
need more pacemaker implants as the aging society advances. On the other
hand, it has been reported that lead trouble and subcutaneous pocket
complications, which are complications of conventional transvenous
pacemakers, are present in 7\% and 11\% of cases at 5 years after
implantation, respectively.\textsuperscript{2} The introduction of
transcatheter pacing systems (TPSs) was expected to reduce lead and
pocket complications. In previous studies, the TPS was shown to be an
effective and safer option, reducing the common complications from
conventional pacemakers and providing a more stable pacing
threshold.\textsuperscript{3-6} However, some cases require a higher
pacing threshold, because the latter increases post-implantation, which
subsequently decreases battery longevity and increases the risk of an
adverse heart event due to pacing issues. Predictors that require
long-term high pacing thresholds have been
reported,\textsuperscript{6}but the cause of increased thresholds after
implantation has not been clarified. Most of the rapid increases in
pacing threshold occurred within one month of implantation, but there
were few cases where the threshold was increased in the medium-to-long
term.\textsuperscript{7-9}Therefore, we hypothesized that it would be
possible to obtain a stable pacing threshold in the long term if the
increase could be avoided in the short term.

In this study, we investigated the clinical significance of early
increased pacing threshold by comparing patient background
characteristics, procedure-related indications, and threshold
transition.

\textbf{METHODS}

\textbf{Subjects}

The study included 64 consecutive patients who underwent Micra-TPS
(Medtronic, Dublin, Ireland) implantation using the transfemoral vein
approach at our hospital between October 2017 and April 2020. The
inclusion criteria were successful placement of the TPS, no clear
dislodgement of the device, and patient consent to use their data. The
exclusion criterion was missing data owing to patient loss to follow-up.
Micra-TPS implantation was performed by two cardiologists; one conducted
35 implantation procedures and the other 29 procedures. The
pull-and-hold method was used for all subjects during implantation to
confirm that the device was hooked onto the myocardium, followed by
extension of at least two of the four tines on the TPS. Pacemaker
impedance, threshold, and sensitivity were measured at the time of
discharge from the hospital and postoperative follow-up examinations at
1, 3, 6, 12, and 24 months. Additionally, chest radiography (CXR) was
also performed during each follow-up examination to assess whether the
position of the Micra-TPS device had changed from that at implantation.
The Micra-TPS output pacing threshold setting was initially set to +1.5
V during implantation and for 1 month postoperatively. Thereafter, the
output setting was set by the Micra-TPS Capture Management system
(Medtronic). This study was approved by the Mito Saiseikai General
Hospital ethics committee.

\textbf{Endpoints}

After subsequent pacemaker examinations and CXR procedures showing no
clear dislodgement of the Micra-TPS, we divided the patients into the
following two groups based on their pacing threshold: (1) the increased
pacing threshold (IPT) group where the pacing threshold increased by
[?]0.5 V/0.24 msec within 1 month after implantation and (2) the stable
pacing threshold (SPT) group where the pacing threshold increased by
\textless{}0.5 V/0.24 msec within 1 month of implantation.

The IPT and SPT groups were compared with respect to the following
variables:

(a) Patient demographics and clinical characteristics: age, sex, body
mass index (BMI), monitoring period, indication for TPS implantation,
underlying diseases, B-type natriuretic peptide (BNP) level at
hospitalization, left ventricular ejection fraction (LVEF),
hypertension, diabetes, and blood dialysis.

(b) Procedure-related indicators: Implantation position, implantation
time, number of deployments, number of tines hooked, electrical
impedance immediately after implantation, and threshold at a pulse width
of 0.24~msec.

(c) Transition of pacing threshold: Changes in the individual thresholds
were measured in both groups, while the mean threshold values were
measured in the SPT group.

(d) Event: (1) Adverse events: all deaths and cases of
rehospitalization; (2) device dysfunction: pacing issues, device
reimplantation, and device infection; and (3) complications during
device implantation: major complications (cardiac injury requiring
therapeutic intervention, access trouble, and dislodgment associated
with embolization) and minor complications (pericardial effusion not
requiring therapeutic intervention, and complications associated with
puncture sites).

\textbf{Statistical analysis}

For continuous variables, the Shapiro-Wilk test was used to determine
the normality of the data of the IPT and SPT groups. If the distribution
was normal, Levene's test was used to confirm equal variance between the
two groups. When the distribution did not follow a normal distribution,
the Mann-Whitney U test was used. If the variance was uniform, the
Student's t-test was used, and if not, the Welch t-test was used. In
addition, Fisher's exact probability test was used to compare
categorical variables between the two groups. Furthermore, when
statistically significant differences were found, a receiver operating
characteristic (ROC) curve was generated to determine the cut-off value
for assessing the pacing threshold increase. All analyses were performed
using EZR version~1.42 (Saitama Medical Center, Jichi Medical
University, Saitama, Japan), a graphical user interface for R 2.13.0 (R
Foundation for Statistical Computing, Vienna, Austria). In all tests,
the significance level was set at \emph{P} ~[?]~0.05.

\textbf{RESULTS}

\textbf{Patient demographics and clinical characteristics}

Excluding 4 patients that could not be followed up, of the 60 remaining
patients, 9 (15\%) were in the IPT group and 51 (85\%) were in the SPT
group. We found no significant differences between the two groups with
respect to the patient demographics and clinical characteristics (Table
1).

\textbf{Procedure-related indicators}

We also observed no differences in the number of deployments, number of
tines, or the indwelling site; however, a significantly longer
implantation time, lower impedance, and higher pacing threshold were
observed in the IPT group than in the SPT group
(\emph{P}\textless{}0.05; Table 2).

\textbf{Transition of the pacing threshold}

We found that 44\% (4/9) of the patients in the IPT group did not have
improved pacing thresholds after 3 months and required a higher pacing
threshold of [?]2.0 V/0.24 msec (Figure 1). In the SPT group, the pacing
thresholds for most patients improved after implantation. The pacing
threshold was [?]1.0 V/0.24 msec in all cases after 3 months (Figure 2).

The ROC curves for impedance and the pacing threshold at implantation
are shown in Figures 3A and 3B. The area under the curve (AUC) for
impedance and pacing threshold was 0.756 (95\% confidence interval
{[}CI{]}: 0.586--0.926) and 0.840 (95\% CI: 0.737--0.943), respectively.
Comparison of the AUC for the two ROC curves showed no significant
difference (\emph{P} ~=~0.364; Figure~3C). The cut-off values based on
the ROC curve were 660~\selectlanguage{greek}Ω \selectlanguage{english}for impedance and 1.0~V/0.24~msec for the
pacing threshold. The sensitivity and specificity cut-off values for
impedance were 100\% and 66.7\%, respectively, and those for the pacing
threshold were 66.7\% and 78.4\%, respectively.

\textbf{Events}

There were no cases of cardiovascular mortality or rehospitalization due
to cardiac events. We observed two cases of pacing failure in the IPT
group; however, the devices were not re-implanted. There were only two
cases of complications: one case of lymph leakage at the puncture site
in the IPT group and one case of pericardial effusion not requiring
intervention in the SPT group. No other major complications were noted
in either group.

\textbf{DISCUSSION}

This study compared patients with an increased pacing threshold shortly
after TPS implantation with those who maintained a stable pacing
threshold. Our results suggest that impedance and threshold at the time
of implantation may serve as predictive factors for an increased pacing
threshold (AUC: 0.737--0.943 and 0.586--0.926, respectively). All
patients requiring a higher pacing threshold were in the IPT group,
suggesting that if a threshold increase can be avoided within the first
month after TPS implantation, a stable threshold may be obtained in the
medium-to-long term.

Impedance is the sum of resistance in the electrode lead and the
myocardium owing to contact between the two. Therefore, the difference
in impedance is a measure of whether the TPS is sufficiently anchored to
the myocardium. To anchor the device, four nitinol tines at the tip of
the TPS are hooked to the myocardium. It has been shown that at least
two tines must be applied to minimize dislodgement of the device, which
may occur due to the cardiac rhythm.\textsuperscript{10} However, there
are conflicting reports where, despite two tines being anchored to the
myocardium, the TPS tail was reported to shift, leading to an increase
in the threshold with a changing bodily
position.\textsuperscript{11,12}To achieve sufficient fixation to the
myocardium with two tines, the tines must be attached perpendicular to
the myocardial wall.\textsuperscript{10} If the tines are leaning
against the myocardial wall, they do not provide enough force to secure
the device; thus, the device may shift with an increase in the cardiac
rhythm during exercise conditions. Therefore, a slight movement between
the heart muscle and the device could result in micro-dislodgement. In
this study, at least two or more tines were anchored by the
pull-and-hold method in all patients. However, the low impedance at the
time of implantation in the IPT group meant that the tines were not
sufficiently anchored to the myocardial wall, resulting in
micro-dislodgement. We observed that the pacing threshold increases
shortly after implantation in this group, suggesting that additional
investigations are required for the evaluation of adequate anchoring of
the TPS to the myocardium other than the number of tine connections.
While it was expected that impedance at the time of implantation would
function as a predictive factor for the altered threshold status, it was
also observed that the pacing threshold at the time of implantation
served as a predictor in that it tended to be low if the device was
well-anchored. This finding is similar to a report by Tolosana et al.,
who showed that impedance and threshold at the time of implantation play
important roles in achieving a pacing threshold of [?]2.0 V/0.24
msec.\textsuperscript{7}

We observed that the pacing threshold improved in the majority of cases
in the IPT group, while a higher threshold was maintained in a few
cases. This may be due to fixation and adhesion of the dislodged device.
However, we do not have sufficient evidence to support this claim, and
further studies are needed.

We experienced two cases of pacing failure in the IPT group. This may be
because the pacing threshold was higher than the initial pacing
threshold (+ 1.5 V) set at implantation. Our results suggest that if the
electrode impedance is low and the pacing threshold level is high
immediately after TPS implantation, maintenance of a sufficient margin
to the established output with periodic monitoring will help lower the
risk of pacing failure. The results of this study indicate that if the
electrode impedance is low or the pacing threshold is high at the time
of TPS implantation, it is better to maintain a sufficient margin of the
set output.

In addition, pericardial effusion was observed in one case in the SPT
group. In this case, the Micra-TPS was attached to the inferior wall.
When positioning the Micra-TPS, the thickness of the myocardium should
be considered to ensure safety of the right ventricular
septum.\textsuperscript{13} To achieve sufficient compression fitting of
the Micra-TPS and myocardium, it is necessary to press the Micra-TPS
with adequate force onto the myocardium. It is, therefore, recommended
that the Micra-TPS be positioned on the right ventricular septum, if
possible.

\textbf{Limitations}

There are several limitations to this study. First, the Micra-TPS was
implanted by two different cardiologists, which may have led to
technical differences in implantation. As the procedure was performed on
consecutive patients, the degree of proficiency of the cardiologists in
performing the procedure may have slightly varied. Second, there is a
limit in accurately determining the number of tines stably anchored to
the myocardium by the pull-and-hold method. Currently, some
facilities\textsuperscript{13} are making efforts to investigate tine
anchoring to the myocardium using intracardiac echo. If it is possible
to accurately evaluate the number of anchored tines, the number of tines
may potentially function as another predictor. Third, the follow-up
period for the SPT group was short, approximately 7 months on average,
and there is a possibility that a threshold increase may occur beyond
the follow-up period. Long-term continuous follow-up is, therefore,
necessary. We aim to clarify the involvement of threshold rise and
impedance by conducting a prospective study on the transition of the
pacing threshold according to implant impedance.

\textbf{CONCLUSIONS}

The pacing threshold increased shortly after Micra-TPS implantation due
to micro-dislodgement of the device because of insufficient anchoring of
the device to the myocardium. Our results suggest that if an early
threshold increase can be avoided after implantation, a stable threshold
can be potentially reached in the medium-to-long term. When implanting
the Micra-TPS, we showed that impedance \textgreater{}660 \selectlanguage{greek}Ω \selectlanguage{english}and
threshold \textless{}1.0 V/0.24 msec may be good indicators that the
device is sufficiently anchored to the myocardium. We intend to evaluate
the increase in the threshold by assessing implant impedance in a
further study.

\textbf{Acknowledgments}

We would like to thank Editage (www.editage.com) for English language
editing

\textbf{REFERENCES}

1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke
statistics - 2012 update: a report from the American Heart Association.
Circulation 2012;125:e2-e220.

2. Udo EO, Zuthoff NP, van Hemel NM, et al. Incidence and predictors of
short- and long-term complication in pacemaker therapy: the FOLLOWPACE
study. Heart Rhythm 2012;9:728-735.

3. Reynolds D, Duray GZ, Omar R, et al. A leadless intracardiac
transcatheter pacing system. N Engl J Med 2016;374:533-541.

4. El-Chami MF, Al-Samadi F, Clementy N, et al. Updated performance of
the Micra Transcatheter Pacemaker in the real-world setting: A
comparison to the investigational study and a transvenous historical
control. Heart Rhythm 2018;15:1800-1807.

5. Roberts PR, Clementy N, Al-Samadi F, et al. A leadless pacemaker in
the real-world setting: The Micra Transcatheter Pacing System
Post-Approval Registry. Heart Rhythm 2017;14:1375-1379.

6. Duray GZ, Ritter P, El-Chami M, et al. Long-term performance of a
transcatheter pacing system: 12-Month results from the Micra
Transcatheter Pacing Study. Heart Rhythm 2017;14:702-709.

7. Tolosana JM, Guasch E, San Antonio R, et al. Very high pacing
thresholds during long-term follow up predicted by a combination of
implant pacing threshold and impedance in leadless transcatheter
pacemakers. J Cardiovasc Electrophysiol 2020;31:868-874.

8. Piccini JP, Stromberg K, Jackson KP, et al. Long-term outcomes in
leadless Micra transcatheter pacemakers with elevated thresholds at
implantation: Results from the Micra Transcatheter Pacing System Global
Clinical Trial. Heart Rhythm 2017;14:685-691.

9. Grubman E, Ritter P, Ellis CR, et al. To retrieve, or not to
retrieve: System revisions with the Micra Transcatheter Pacemaker. Heart
Rhythm 2017;14:1801-1806.

10. Eggen MD, Grubac V, Bonner MD. Design and evaluation of a novel
fixation mechanism for a Transcatheter Pacemaker. IEEE Trans Biomed Eng
2015;62:2316-2323.

11. Morani G, Bolzan B, Tomasi L, Corrado Vassanelli. A case of removal
of a ``dancing'' Micra. Europace 2017;19:2000

12. Yoh M, Tageki M, Takahashi H, Yoshio T, Shiojima I. The unstable
pacing thresholds of the leadless transcatheter pacemaker affected by
body positions in subacute phase after implant. Eur Heart J Case Rep
2019;3:1-6.

13. Vamos M, Erath JW, Benz AP, Bari Z, Duray GZ, Hohnloser SH.
Incidence of cardiac perforation with conventional and with leadless
pacemaker systems: A systematic review and meta-analysis. J Cardiovasc
Electrophysiol 2017;28:336-346.

\textbf{Figure Legends}

\textbf{Figure 1. Graph showing time-course of threshold changes in the
increased pacing threshold (IPT) group.} The change in the pacing
threshold for nine patients in the IPT group is shown. Patients who
required a threshold [?]2.0 V at 3 months after implantation are shown in
red lines, and patients who had a threshold of [?]2.0 V at 3 months after
implantation are shown in gray lines.

\textbf{Figure 2} : \textbf{Graph showing time-course of the pacing
threshold in the stable pacing threshold (SPT) group} . Each boxplot
represents the total number of patients assessed at each time point. The
upper and lower whiskers show the maximum and minimum values (excluding
outliers), respectively, and the line that divides the box represents
the median threshold value.

\textbf{Figure 3} : \textbf{The receiver operating characteristic (ROC)
curves for impedance and the pacing threshold at implantation.} A) ROC
curve of implant pacing threshold to determine the probability of
increased pacing threshold shortly after Micra-TPS implantation. B) ROC
curve of implant impedance to determine the probability of increased
pacing threshold shortly after Micra-TPS implantation. C) Comparison of
the area under the curve (AUC) for the two ROC curves. The numbers in
the graphs in 3A and 3B represent the cutoff values with the best
sensitivity and specificity. The numbers in parentheses indicate the
rates of sensitivity and specificity. The p-value in 3C was obtained
using the chi-square test.

\textbf{Tables}

\textbf{Table 1. Patient baseline demographics and clinical
characteristics grouped according to pacing threshold}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& & & SPT group (n=9) & IPT group (n=51) & IPT group (n=51) &
\emph{P}-value\tabularnewline
\midrule
\endhead
Monitoring period (months) & Monitoring period (months) & Monitoring
period (months) & 13.8 \selectlanguage{ngerman}± 6.9 & 7.0 \selectlanguage{ngerman}± 5.7 & 7.0 \selectlanguage{ngerman}± 5.7 &
0.009*\tabularnewline
Age (years) & Age (years) & Age (years) & 89.1 \selectlanguage{ngerman}± 4.4 & 85.9 \selectlanguage{ngerman}± 7.6 & 85.9
\selectlanguage{ngerman}± 7.6 & 0.303\tabularnewline
Sex: Female, n (\%) & Sex: Female, n (\%) & Sex: Female, n (\%) & 5
(56\%) & 27 (53\%) & 27 (53\%) & 1.000\tabularnewline
BMI (kg/m\textsuperscript{2}) & BMI (kg/m\textsuperscript{2}) & BMI
(kg/m\textsuperscript{2}) & 20.0 \selectlanguage{ngerman}± 3.8 & 21.9 \selectlanguage{ngerman}± 3.5 & 21.9 \selectlanguage{ngerman}± 3.5 &
0.125\tabularnewline
Indication for implantation & Indication for implantation & Indication
for implantation & Indication for implantation & Indication for
implantation & Indication for implantation & Indication for
implantation\tabularnewline
& SSS, n (\%) & SSS, n (\%) & 2 (22\%) & 12 (24\%) & 12 (24\%) &
0.482\tabularnewline
& CAVB, n (\%) & CAVB, n (\%) & 5 (56\%) & 32 (63\%) & 32 (63\%)
&\tabularnewline
& Type II AVB, n (\%) & Type II AVB, n (\%) & 0 & 3 (6\%) & 3 (6\%)
&\tabularnewline
& AF bradycardia, n (\%) & AF bradycardia, n (\%) & 2 (22\%) & 4 (7\%) &
4 (7\%) &\tabularnewline
Underlying disease & Underlying disease & Underlying disease &
Underlying disease & Underlying disease & Underlying disease &
Underlying disease\tabularnewline
& & IHD & 1 (11\%) & 2 (4\%) & 2 (4\%) & 0.056\tabularnewline
& & Valvular disease & 3 (33\%) & 11 (22\%) & 11 (22\%) &\tabularnewline
& & Cardiomyopathy & 1 (11\%) & 0 & 0 &\tabularnewline
& & Others & 4 (44\%) & 38 (74\%) & 38 (74\%) &\tabularnewline
BNP & BNP & BNP & 707 \selectlanguage{ngerman}± 729 & 434 \selectlanguage{ngerman}± 427 & 434 \selectlanguage{ngerman}± 427 &
0.382\tabularnewline
LVEF & LVEF & LVEF & 57.2 \selectlanguage{ngerman}± 11.2 & 57.2 \selectlanguage{ngerman}± 11.2 & 59.8 \selectlanguage{ngerman}± 7.4 &
0.477\tabularnewline
HT, n (\%) & HT, n (\%) & HT, n (\%) & 5 (56\%) & 5 (56\%) & 28 (56\%) &
1.000\tabularnewline
DM, n (\%) & DM, n (\%) & DM, n (\%) & 4 (44\%) & 4 (44\%) & 11 (23\%) &
0.218\tabularnewline
HD, n (\%) & HD, n (\%) & HD, n (\%) & 0 (0\%) & 0 (0\%) & 1 (2\%) &
1.000\tabularnewline
\bottomrule
\end{longtable}

In the increased pacing threshold (IPT) group, the pacing threshold
increased by [?]0.5 V/0.24 msec within 1 month after implantation, and in
the stable pacing threshold (SPT) group, the pacing threshold increased
by \textless{}0.5 V/0.24 msec within 1 month after implantation.
Abbreviations: AF: atrial fibrillation; BNP: B-type natriuretic peptide;
CAVB: complete atrial ventricular block; DM: diabetes mellitus; HD:
hemodialysis; HT: hypertension; IHD: ischemic heart disease; LVEF: left
ventricular ejection fraction; SSS: sick sinus syndrome; Type II AVB:
type second-degree atrioventricular block. *P-values\textless{}0.05 were
considered statistically significant.

\textbf{Table 2. Procedure-related indicators grouped according to
pacing threshold}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& & SPT group (n=9) & IPT group (n=51) & \emph{P}-value\tabularnewline
\midrule
\endhead
Implantation time (minutes) & Implantation time (minutes) & 52\selectlanguage{ngerman}±25 &
35\selectlanguage{ngerman}±18 & 0.029*\tabularnewline
Number of deployments & Number of deployments & 2.2\selectlanguage{ngerman}±1.7 & 1.6 &
0.259\tabularnewline
Implantation site & Implantation site & Implantation site & Implantation
site & Implantation site\tabularnewline
& Mid-septal, n (\%) & 6 (67\%) & 45 (88\%) & 0.127\tabularnewline
& Apical septal, n (\%) & 2 (22\%) & 5 (10\%) &\tabularnewline
& Inferior, n (\%) & 1 (11\%) & 1 (2\%) &\tabularnewline
Tines & Tines & 2.3 \selectlanguage{ngerman}± 0.5 & 2.4 \selectlanguage{ngerman}± 0.5 & 0.585\tabularnewline
Sensitivity & Sensitivity & 5.1 \selectlanguage{ngerman}± 1.9 & 8.3 \selectlanguage{ngerman}± 4.1 & 0.220\tabularnewline
Impedance & Impedance & 582 \selectlanguage{ngerman}± 59 & 756 \selectlanguage{ngerman}± 167 &
\textless{}0.001*\tabularnewline
Threshold & Threshold & 1.29 \selectlanguage{ngerman}± 0.87 & 0.71 \selectlanguage{ngerman}± 0.40 &
0.014*\tabularnewline
\bottomrule
\end{longtable}

In the increased pacing threshold (IPT) group, the pacing threshold
increased by [?]0.5 V/0.24 msec within 1 month after implantation, and in
the stable pacing threshold (SPT) group, the pacing threshold increased
by \textless{}0.5 V/0.24 msec within 1 month after implantation.
*P-values\textless{}0.05 were considered statistically significant.

\textbf{Table 3. Patient outcomes grouped according to pacing threshold}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& & IPT group (n = 9) & SPT group (n = 51) &
\emph{P-}value\tabularnewline
\midrule
\endhead
Adverse events, n (\%) & Adverse events, n (\%) & 6 (66\%) & 10 (20\%) &
0.005*\tabularnewline
All deaths, n (\%) & All deaths, n (\%) & 1 (11\%) & 5 (10\%) &
1.000\tabularnewline
& Cardiovascular deaths & 0 & 0 &\tabularnewline
& Others & 1 & 2 &\tabularnewline
& Unknown & 0 & 3 &\tabularnewline
Rehospitalization n (\%) & Rehospitalization n (\%) & 5 (55\%) & 7
(14\%) & 0.011*\tabularnewline
& Due to heart failure & 0 & 2 &\tabularnewline
& Others & 5 & 5 &\tabularnewline
Device dysfunction, n (\%) & Device dysfunction, n (\%) & 2 (22\%) & 0
(0\%) & 0.020*\tabularnewline
& Pacing issue & 2 & 0 &\tabularnewline
& Device reimplantation & 0 & 0 &\tabularnewline
& Infection & 0 & 0 &\tabularnewline
Complications, n (\%) & Complications, n (\%) & 1 (11\%) & 1 (2\%) &
0.275\tabularnewline
& Major complications & 0 (0\%) & 0 (0\%) &\tabularnewline
& Minor complications & 1\textsuperscript{+} (11\%) &
1\textsuperscript{++} (2\%) &\tabularnewline
\bottomrule
\end{longtable}

In the increased pacing threshold (IPT) group, the pacing threshold
increased by [?]0.5 V/0.24 msec within 1 month after implantation, and in
the stable pacing threshold (SPT) group, the pacing threshold increased
by \textless{}0.5 V/0.24 msec within 1 month after implantation.
*P-values\textless{}0.05 were considered statistically
significant.\textsuperscript{+}Puncture site lymphatic
leakage.\textsuperscript{++}Pericardial effusion.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}

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

