\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[T2A]{fontenc}
\usepackage[ngerman,greek,polish,english]{babel}



\usepackage{float}








\begin{document}

\title{The association between epicardial adipose tissue thickness and left
atrial phasic function in patients with non-valvular atrial fibrillation}



\author[1]{You Yang}%
\author[1]{Biaohu Liu}%
\author[1]{Wenyan Ji}%
\author[1]{Jing Ding}%
\author[1]{Shanqiang Tao}%
\author[1]{Feifei Lian}%
\author[1]{Deguo Wang}%
\affil[1]{Wannan Medical College}%


\vspace{-1em}



  
  \date{May 24, 2024}


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





\selectlanguage{english}
\begin{abstract}
\textbf{Abstract} \textbf{Purpose:} The purpose of our study was to
explore the relationship between EAT thickness and left atrial phasic
function in patient with non-valvular atrial fibrillation (NVAF).
\textbf{Methods:} 100 NVAF patients were enrolled, including 50 patients
with paroxysmal AF and 50 patients with persistent AF. Another 50
patients without AF in sinus rhythm were selected as the control group.
EAT thickness in front of the right ventricular free wall was measured
using transthoracic echocardiography(TTE) at end-systole, while left
atrial phasic function parameters were measured by Real-time
three-dimensional echocardiography(RT-3DE) and two-dimensional speckle
tacking imaging(2D-STI), including left atrial total emptying
fraction(LATEF), left atrial active emptying fraction(LAAEF), left
atrial passive emptying fraction(LAPEF), left atrial reservoir
strain(LASr), left atrial contraction strain(LASct) and left atrial
conduit strain(LAScd). Subsequently, we compared EAT thickness and left
atrial phasic function parameters in each group, and analyzed the
relationship between EAT thickness and left atrial phasic function
parameters. \textbf{Results:} Compared with control group, patients with
paroxysmal AF and persistent AF groups had sequentially greater EAT
thickness and left atrial diameter (LAD), but sequentially lower left
atrial phasic function parameters (LATEF, LAAEF, LAPEF, LASr, LASct,
LAScd) (all p\textless{}0. 001). By Pearson and Spearman Correlation
Coefficient, EAT thickness was significantly positively correlated with
LAD and negatively correlated with left atrial phasic function
parameters (all p\textless{}0. 001). \textbf{Conclusions:} EAT thickness
in front of the ventricular free wall measured by TTE was significantly
correlated with left atrial phasic function in patients with NVAF, which
could effectively reflect the trend of left atrial function changes,
thus providing some reference for clinical practice and early
intervention of left atrial remodeling.%
\end{abstract}%



\sloppy


The association between epicardial adipose tissue thickness and left
atrial phasic function in patients with non-valvular atrial fibrillation

You Yang\textsuperscript{a}, Biaohu Liu\textsuperscript{a}, Wenyan
Ji\textsuperscript{a}, Jing Ding\textsuperscript{a}, Shanqiang
Tao\textsuperscript{a}, Feifei Lian\textsuperscript{a}, Deguo
Wang\textsuperscript{b}

\textsuperscript{a} Department of Ultrasonic Medicine, The First
Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China

\textsuperscript{b} Department of Geriatrics Medicine, The First
Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China

Corresponding Author: Biaohu Liu, Department of Ultrasonic Medicine, The
First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui,
241000, China

Tel:86-13515538949 E-mail: lbhwuhu@163.com

\textbf{A} \textbf{cknowledgement}

I, YY, particularly thank my partners and funding agencies who helped me
in this study.

\textbf{Data Availability Statement}

All data generated or analyzed during this study are included in this
article. Further enquiries can be directed to the corresponding author.

\textbf{Funding Sources}

This study was supported by the Effect and Mechanism of Bidirectional
Precise Regulation of Cardiac Sympathetic Nerve Discharge by
Photogenetic Technology on Ventricular Arrhythmia after Myocardial
Infarction, the National Natural Science Foundation of China (no.
81670301). This study was also supported by the Provincial Quality
Engineering Project of Colleges and Universities in Anhui in 2020(no.
2020xskt525).

\textbf{Conflict of Interest Statement}

The authors have no conflicts of interest to declare.

\textbf{Statement of Ethics}

Since this study did not involve operations such as drugs that may
affect the human body and ultrasonography is a non-invasive test, we
followed the principles of the Declaration of Helsinki, and the
echocardiography and clinically relevant data were collected after
informed consent of patients.

Author Contributions

You Yang and Biaohu Liu made significant contributions to the design,
data acquisition, statistical analysis and data interpretation. You Yang
drafted this study and completed the manuscript. And further improved
and revised the article under the guidance of Biaohu Liu. Biaohu Liu and
Deguo Wang made significant contributions to the funds collection of the
study. Jing Ding, Shanqiang Tao and Feifei Lian contributed to data
acquisition and statistical analysis. Wenyan Ji made significant
contributions to the literature search and revision of the important
content of this study.

\textbf{Abstract}

\textbf{Purpose:} The purpose of our study was to explore the
relationship between EAT thickness and left atrial phasic function in
patient with non-valvular atrial fibrillation (NVAF).

\textbf{Methods:} 100 NVAF patients were enrolled, including 50 patients
with paroxysmal AF and 50 patients with persistent AF. Another 50
patients without AF in sinus rhythm were selected as the control group.
EAT thickness in front of the right ventricular free wall was measured
using transthoracic echocardiography(TTE) at end-systole, while left
atrial phasic function parameters were measured by Real-time
three-dimensional echocardiography(RT-3DE) and two-dimensional speckle
tacking imaging(2D-STI), including left atrial total emptying
fraction(LATEF), left atrial active emptying fraction(LAAEF), left
atrial passive emptying fraction(LAPEF), left atrial reservoir
strain(LASr), left atrial contraction strain(LASct) and left atrial
conduit strain(LAScd). Subsequently, we compared EAT thickness and left
atrial phasic function parameters in each group, and analyzed the
relationship between EAT thickness and left atrial phasic function
parameters.

\textbf{Results} \textbf{:} Compared with control group, patients with
paroxysmal AF and persistent AF groups had sequentially greater EAT
thickness and left atrial diameter (LAD), but sequentially lower left
atrial phasic function parameters (LATEF, LAAEF, LAPEF, LASr, LASct,
LAScd) (all p\textless{}0. 001). By Pearson and Spearman Correlation
Coefficient, EAT thickness was significantly positively correlated with
LAD and negatively correlated with left atrial phasic function
parameters (all p\textless{}0. 001).

\textbf{Conclusions:} EAT thickness in front of the ventricular free
wall measured by TTE was significantly correlated with left atrial
phasic function in patients with NVAF, which could effectively reflect
the trend of left atrial function changes, thus providing some reference
for clinical practice and early intervention of left atrial remodeling.

\textbf{Keywords}

Epicardial Adipose Tissue, Atrial Fibrillation, Left Atrial

\textbf{1 Introduction}

The relationship between epicardial adipose tissue (EAT) and atrial
fibrillation (AF) has become a topic of great interest. Previous studies
have demonstrated that EAT is associated with the development of AF
{[}1,2{]}. Excessive EAT promotes adipose infiltration and fibrosis of
myocardial, and affects cardiac electrophysiological function through
pathophysiological processes such as inflammation and oxidative stress,
thus contributing to the occurrence and development of AF {[}3{]}.
Magnetic resonance imaging (MRI) and computed tomography (CT) can be
used for EAT examination, but their examination time is long and cost is
high, and CT has certain radiation, so it is difficult to be popularized
in clinical practice. The use of ultrasound to measure EAT thickness is
a more convenient and economical method, that is easy to be promoted and
has good reliability compared with MRI in measuring EAT thickness
{[}4{]}. To further explore the relationship between EAT and AF, our
study applied TTE to measure EAT thickness anterior the right
ventricular free wall in NVAF patients and analyzed its relationship
with left atrial phasic function to explore the possible mechanism
between EAT and AF.

\textbf{2 Materials and Methods}

\textbf{2.1 Study population}

From January 2021 to April 2022, 100 patients with NVAF who were treated
at the First Affiliated Hospital of Wannan Medical College were
selected. Among them, there were 68 males and 32 females with an average
age of 59.36\selectlanguage{ngerman}±7.70 years. They were divided into paroxysmal AF group and
persistent AF group according to the duration of AF, with 50 patients in
each group. The inclusion criteria were as follows: (1) NVAF; (2) good
image quality. And the exclusion criteria included rheumatic heart
disease, heart failure (left ventricular ejection fraction,
LVEF\textless{}50\%), cardiac valve repair or replacement, AF
radiofrequency ablation, hyperthyroidism, and severe liver and kidney
dysfunction. In addition, 50 non-AF patients in sinus rhythm treated in
our hospital during the same period were selected as the control group,
and the exclusion criteria were consistent with the case group. Among
them, there were 34 males and 16 females with an average age of
59.34±7.05 years. The basic clinical information of the above 150
patients was recorded, such as age, gender, body mass index (BMI), body
surface area (BSA), smoking and drinking history, some comorbidities,
and some laboratory parameters. Ultimately, 150 patients were included
in our study (shown in Fig. 1). Since this study did not involve
operations such as drugs that may affect the human body and
ultrasonography is a non-invasive test, we followed the principles of
the Declaration of Helsinki, and the echocardiography and clinically
relevant data were collected after informed consent of patients.

\textbf{2.2 Echocardiographic image acquisition}

All patients were examined with the Philips EPIQ 7C ultrasound system,
and the require image were collected by S5-1 and X5-1 probes. During the
examination, all patients in the control and paroxysmal AF groups had
sinus rhythm and heart rate \textless{}100 beats/min, while the average
ventricular rate \textless{}100 beats/min in the persistent AF group.
First, after connecting the ECG, the patient was placed in the left
lateral position, and the S5-1 probe was used to observe the
parasternal-long axis view. Subsequently, the near-field area was
enlarged and the image gain was appropriately adjusted to fully display
EAT, which located in front of the right ventricular free wall and
beneath the pericardium. Using the aortic annulus as a reference, the
reference line was placed across the aortic annulus and the right
ventricular free wall, and EAT thickness was measured vertically in
front of the right ventricular free wall at end-systole. Then, the
parasternal-long axis view and apical two-chamber and four-chamber views
were collected, and four cardiac cycles were continuously recorded to
obtain LAD and LVEF which was analyzed by the biplane Simpson's method.
Finally, the X5-1 probe was used to display the apical four-chamber
view, and the ``full-volume'' mode was selected to record four cardiac
cycles continuously to obtain the three-dimensional volume of left
atrium.

\textbf{2.3 Echocardiographic image analysis}

(1) RT-3DE: Philips Qlab 10. 4 software was used to off-line analyze the
full-volume image. In the 3DQA mode, the left atrial volume curve was
obtained, and we recorded the maximal, minimal and pre-atrial
contraction left atrial volume (LAVmax, LAVmin, LAVp). Then, each left
atrial volume index (LAVImax, LAVImin, LAVIp) was obtained by
normalizing BSA. Finally, we calculated LATEF, LAAEF and LAPEF. the
calculation method was as follows: LATEF=
(LAVImax-LAVImin)/LAVImax×100\%; LAAEF= (LAVIp-LAVImin)/LAVIp×100\%;
LAPEF= (LAVImax-LAVIp)/LAVImax×100\%. (2) 2D-STI: Off-line analysis of
apical two-chamber and four-chamber images of four consecutive cardiac
cycles using Philips Qlab 10. 4 software. In the aCMQ mode, we recorded
the intima of the left atrium and plotted the region of interest to
obtain the left atrial strain curve. LASr, LASct and LAScd were recorded
respectively, and the strain values of the the two views were added
together and included in the analysis after averaging. The mean peak
strain during left atrial systole, late diastole and early diastole
respectively represents LASr, LASct and LAScd. Where LASr is positive,
LASct and LAScd are both negative, so the absolute value was taken and
analyzed.

\textbf{2.4 Statistical analysis}

Statistical analysis of all data was performed using SPSS 25. 0. The
continuous variables were tested for normality using the Shapiro-Wilks
test. When the continuous variables were conformed to normal
distributions, they were expressed as mean±SD, and the date with skewed
distributions were expressed as medians with 25\% and 75\% interquartile
ranges. Categorical variables were expressed as numbers with
percentages. The continuous variables conforming to normal distribution
between three groups were compared by F-test or Welch's test. When at
least one of three groups of continuous variables conforms to skewed
distribution, the kruskal-Wallis test was used. Then, we performed
multiple comparisons between groups. Categorical variables between three
groups were compared by Chi-square test. Pearson and Spearman
Correlation Coefficient were used to determine the correlation between
EAT thickness and LAD, as well as the correlation between EAT thickness
and left atrial phasic function in patients with AF. Intra-class
correlation coefficient (ICC) was used to test the reproducibility of
measurement of EAT thickness and left atrial phasic function parameters
within and between operators. For all tests, a p\textless{}0. 05 was
defined as statistically significant.

\textbf{3 Results}

\textbf{3.1 Baseline clinical and echocardiographic characteristics}

All baseline parameters are summarized in Table 1. A total of 150
patients were included in our study, with 50 patients in each group. 16
(32\%) were female in control group with an average age of 59.34±7.05
years, 17 (34\%) were female in paroxysmal AF group with an average age
of 57.78±8.36 years and 15 (30\%) were female in persistent AF group
with an average age of 60.94±6.70 years. In our study, EAT thickness
differed significantly among control group (3.51±0.29mm), paroxysmal AF
group (5.11±0.84mm) and persistent AF group (6.26±0.80mm). And compared
with control group, LAD in paroxysmal AF group and persistent AF group
increased in turn. However, there was no significant difference in LVEF
among three groups. The baseline clinical characteristics among three
groups also had no statistical difference, such as age, gender, BMI, BSA
and so on.

\textbf{3.2 RT-3DE and 2D-STI parameters}

The parameters obtained by RT-3DE are shown in Table 2. Compared with
control group, LAVImax, LAVIp and LAVImin in paroxysmal AF group and
persistent AF group increased in turn, but LATEF, LAAEF and LAPEF
decreased in turn. The left atrial volume curves obtained by RT-3DE
among the three groups are shown in Figure 2.

Left atrial strain measured by 2D-STI among the three groups are shown
in Table 2. The LASr, LASct and LAScd of patients in persistent AF group
were significantly lower than those in paroxysmal AF group, while the
left atrial strain of patients in paroxysmal AF group were significantly
lower than those in control group. Figure 3 shows the left atrial strain
curves obtained by 2D-STI among the three groups.

\textbf{3.3 The correlation analysis of EAT thickness with LAD and left
atrial phasic function in patients with AF}

EAT thickness was significantly positively correlated with LAD, LAVImax,
LAVIp and LAVImin (r= 0.676, 0.694, 0.735 and 0.799 , all
p\textless{}0.001).

EAT thickness was significantly negatively correlated with LATEF, LAAEF
and LAPEF (r=-0.802, -0.768 and -0.681, all p\textless{}0.001;). And EAT
thickness was significantly negatively correlated with LASr, LASct and
LAScd (\selectlanguage{greek}ρ\selectlanguage{english}=-0.778, -0.697 and -0.726, all p\textless{}0.001)

\textbf{3.4 Reproducibility analysis of EAT thickness and left atrial
phasic function parameters}

15 patients were randomly selected for reproducibility analysis of EAT
thickness and left atrial phasic function parameters. Two experienced
ultrasound physicians used TTE to measure the images respectively, and
analyzed the Interobserver agreement. One week later, the images were
measured again by one of the physicians and analyzed the Intraobserver
agreement. The analysis results are shown in Table 3.

\textbf{4 Discussion}

Our study mainly found that EAT thickness in front of the right
ventricular free wall measured by TEE was significantly positively
correlated with left atrial size, but significantly negatively
correlated with left atrial phasic function.

EAT is biologically active tissue that is unevenly distributed between
the myocardial and the visceral pericardium. There is no fascial barrier
between EAT and myocardial, so local EAT can slow down conduction
through fat infiltration, damage to the myocardial interstitium, and
self-tissue fibrosis, thereby affecting myocardial electrophysiology
{[}5{]}. EAT also promotes adjacent myocardial fibrosis by paracrine
release of multiple adipose cytokines {[}6{]}. Similarly, there are no
fascial boundaries between the atrium and the ventricles, thus, multiple
adipose cytokines secreted by EAT around the left ventricle can reach
the atrium and affect atrial fibrosis {[}7{]}. A variety of inflammatory
mediators secreted by EAT are also closely related to the occurrence of
AF {[}8{]}. In addition, EAT is rich in autonomic ganglion plexus, and
the excitation of sympathetic and parasympathetic nerves can increase
intracellular calcium concentration and shorten action potential
duration, thus promoting the occurrence and development of AF {[}9{]}.
Left atrial remodeling is crucial in the occurrence and development of
AF, and EAT participates in this process through the above various
pathophysiological mechanisms. Moreover, left atrial remodeling is also
an important indicator of the prognosis of AF {[}10{]}. Therefore, early
identification of left atrial remodeling and timely intervention may
slow or even reverse this pathophysiological process, while improving
prognosis. Our study found that compared with control group, EAT
thickness in paroxysmal AF group and persistent AF group increased
sequentially, and the difference was statistically significant. This is
consistent with the findings of previous studies {[}11{]}. Similarly,
van Rosendael et al. {[}12{]}applied CT to quantitatively assess EAT
around the left atrium and found that it was independently associated
with AF. Through above studies, we found that EAT was closely related to
the occurrence and development of AF.

In the occurrence and development of AF, the pathological changes caused
by initial trigger factors cause atrial remodeling through the formation
of functional AF matrix {[}13{]}. The enlargement of left atrium
indicates that atrium has remodeled. Wong et al. {[}14{]} found that
pericardial fat volume by MRI was positively correlated with left atrial
volume in patients with AF. Yorgun et al. {[}15{]} used CT to measure
EAT thickness and found that it was correlated with the presence and
type of AF, and significantly related to the LAD. Our study showed that
LAD, LAImax, LAVIp and LAVImin increased sequentially in control group,
paroxysmal AF group and persistent AF group, and EAT thickness was
significantly positively correlated with left atrial size. Those results
were consistent with previous studies. According to our studies, the
increase of EAT thickness may cause structural changes in left atrium,
which can reflect the structural change trend of left atrium.

Left atrial phasic function is a sensitive parameter that reflects the
changes in left atrial structure and function, and can early detect
myocardial motion changes caused by left atrial remodeling. It mainly
includes reservoir function, booster function and conduit function.
LATEF and LASr represent reservoir function; LAAEF and LASct represent
booster function; LAPEF and LAScd represent conduit function. Our study
demonstrated that the left atrial reservoir function, booster function
and conduit function were sequentially decreased in control group,
paroxysmal AF group and persistent AF group. Hopman et al. {[}16{]}
found that compared with the control group, the left atrial reservoir
strain, conduit strain and systolic strain in AF group were
significantly reduced, and the left atrial strain in the persistent AF
group was lower than in paroxysmal AF group, but there was no
significant difference between the two groups, which is slightly
different from the results of our study, and may be affected by
different subjects. In addition, in order to further study the
relationship between EAT and left atrial, and to deeply explore the
mechanism of EAT leading to left atrial remodeling. Our study attempted
to analyze the correlation between EAT thickness and left atrial phasic
function. The results showed that EAT thickness was significantly
negatively correlated with left atrial reservoir function, booster
function and conduit function. The above studies all confirmed that with
the increase of EAT thickness, left atrial function showed a downward
trend. Compared with LAD, our study comprehensively assessed the left
atrial phasic function by RT-3DE and 2DD-STI, which more accurately
reflected the changes of left atrial structure and function. And the
results of our study showed that both LAD and more sensitive left atrial
phasic function were significantly correlated with EAT thickness.
Combined with the results of our study and previous studies, it is
further confirmed that there is a certain connection between EAT and
left atrium of patient with AF. The increased thickness of EAT may be
one of the important mechanisms of left atrial remodeling.

The result of this study showed that EAT thickness measured by TTE and
left atrial phasic function assessed by RT-3DE and 2D-STI had good
reproducibility and reliability. At present, the evaluation of left
atrial size is generally based on LAD measured by TTE, but the irregular
remodeling of left atrium makes it difficult to accurately assess left
atrial size. With the development of three-dimensional technology,
RT-3DE has achieved accurate assessment of left atrial structure and
function. MRI is the gold standard to evaluate left atrial structure and
function. Mor-Avi et al. {[}17{]} used the left atrial function
parameters measured by MRI as reference, and found that RT-3DE and MRI
had a better correlation in evaluating left atrial function, and they
were more accurate than two-dimension echocardiographic parameters. In
addition, 2D-STI is also widely used in the evaluation of early changes
in myocardial function, which can sensitively detect myocardial strain
damage in the early stage of the disease and quantitatively evaluate the
changes in left atrial function. Therefore, our study selected RT-3DE
and 2D-STI to comprehensively assess left atrial phasic function. With
the deepening of research on EAT, noninvasive examination has become the
main way to evaluate EAT, mainly including MRI, CT and TTE. Compared
with MRI and CT, TTE is more convenient, economical, and easier to
popularize in clinical practice.

Our study also has a few limitations. First, the research subjects
included in this study were relatively small. Second, EAT thickness
measured by TTE was not compared with other techniques, such as MRI and
CT. Therefore, the follow-up will continue to expand the sample size and
combine other techniques to further explore the mechanism of EAT on the
left atrial structure and function in patients with AF.

\textbf{5 Conclusion}

Our study found that left atrial phasic function was significantly
impaired in patients with AF, and patients with persistent AF were more
severely damaged than those with paroxysmal AF. The combination of
RT-3DE and 2D-STI can more comprehensively evaluate left atrial
structure and function. EAT thickness was significantly negatively
correlated with left atrial reservoir function, booster function and
conduit function. EAT thickness measured by TTE can effectively reflect
the change trend of left atrial structure and function in patients with
AF, thereby providing a certain reference for clinical practice.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Oba K, Maeda M, Maimaituxun G, et al. Effect of the Epicardial Adipose
  Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial
  Fibrillation. Circ J. 2018;82(7):1778-87.
\item
  Shaihov-Teper O, Ram E, Ballan N, et al. Extracellular Vesicles from
  Epicardial Fat Facilitate Atrial Fibrillation. Circulation.
  2021;143(25):2475-93.
\item
  Couselo-Seijas M, Rodr\selectlanguage{ngerman}íguez-Mañero M, González-Juanatey JR, et al.
  Updates on epicardial adipose tissue mechanisms on atrial
  fibrillation. Obes Rev. 2021;22(9): e13277.
\item
  Iacobellis G, Assael F, Ribaudo MC, et al. Epicardial fat from
  echocardiography: a new method for visceral adipose tissue prediction.
  Obes Res. 2003;11(2):304-10.
\item
  Nalliah CJ, Bell JR, Raaijmakers AJA, et al. Epicardial Adipose Tissue
  Accumulation Confers Atrial Conduction Abnormality. J Am Coll Cardiol.
  2020;76(10):1197-1211.
\item
  Venteclef N, Guglielmi V, Balse E, et al. Human epicardial adipose
  tissue induces fibrosis of the atrial myocardium through the secretion
  of adipo-fibrokines. Eur Heart J. 2015;36(13):795-805a.
\item
  Hatem SN. Is epicardial adipose tissue an epiphenomenon or a new
  player in the pathophysiology of atrial fibrillation? Arch Cardiovasc
  Dis. 2014;107(6-7):349-52.
\item
  Petraglia L, Conte M, Comentale G, et al. Epicardial Adipose Tissue
  and Postoperative Atrial Fibrillation. Front Cardiovasc Med.
  2022;9:810334.
\item
  Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating
  cardiac arrhythmias. Circ Res. 2014;114(6):1004-21.
\item
  Thomas L, Abhayaratna WP. Left Atrial Reverse Remodeling: Mechanisms,
  Evaluation, and Clinical Significance. JACC Cardiovasc Imaging.
  2017;10(1):65-77.
\item
  Acet H, Erta\selectlanguage{polish}ş \selectlanguage{english}F, Ak\selectlanguage{polish}ı\selectlanguage{english}l MA, et al. New inflammatory predictors for
  non-valvular atrial fibrillation: echocardiographic epicardial fat
  thickness and neutrophil to lymphocyte ratio. Int J Cardiovasc
  Imaging. 2014;30(1):81-9.
\item
  van Rosendael AR, Dimitriu-Leen AC, van Rosendael PJ, et al.
  Association Between Posterior Left Atrial Adipose Tissue Mass and
  Atrial Fibrillation. Circ Arrhythm Electrophysiol. 2017;10(2):
  e004614.
\item
  Iwasaki YK, Nishida K, Kato T, et al. Atrial fibrillation
  pathophysiology: implications for management. Circulation.
  2011;124(20):2264-74.
\item
  Wong CX, Abed HS, Molaee P, et al. Pericardial fat is associated with
  atrial fibrillation severity and ablation outcome. J Am Coll Cardiol.
  2011;57(17):1745-51.
\item
  Yorgun H, Canpolat U, Aytemir K, et al. Association of epicardial and
  peri-atrial adiposity with the presence and severity of non-valvular
  atrial fibrillation. Int J Cardiovasc Imaging. 2015;31(3):649-57.
\item
  Hopman LHGA, Mulder MJ, van der Laan AM, et al. Impaired left atrial
  reservoir and conduit strain in patients with atrial fibrillation and
  extensive left atrial fibrosis. J Cardiovasc Magn Reson.
  2021;23(1):131.
\item
  Mor-Avi V, Yodwut C, Jenkins C, et al. Real-time 3D echocardiographic
  quantification of left atrial volume: multicenter study for validation
  with CMR. JACC Cardiovasc Imaging. 2012;5(8):769-77.
\end{enumerate}

\textbf{Figure}

Fig. 1. Flowchart of patient enrollment in the study.

Fig. 2. Left atrial volume curves. a control group, b paroxysmal AF
group, c persistent AF group.

Fig. 3. Left atrial strain curves. a control group, b paroxysmal AF
group, c persistent AF group.

Fig. 4. The scatterplot and regression lines of individual values of EAT
thickness(x-line) and corresponding values of left atrial phasic
function parameters(y-lines) in patients with AF. LATEF and LASr
represent reservoir function; LAAEF and LASct represent booster
function; LAPEF and LAScd represent conduit function.

\textbf{Table}

Table 1. Baseline clinical and echocardiographic characteristics.

Table 2. RT-3DE and 2D-STI parameters.

Table 3. Intraobserver and Interobserver variability of EAT thickness
and left atrial phasic function parameters.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-2-3/Figure-1-2-3}
\caption{{This is a caption
{\label{242406}}%
}}
\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Table-1-2-3/Table-1-2-3}
\caption{{This is a caption
{\label{986571}}%
}}
\end{center}
\end{figure}

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

