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\begin{document}

\title{Estimation of Left Atrial Function Using Four-Dimensional Auto Left
Atrial Quantify Echocardiography in Patients with End-Stage Renal
Disease}



\author[1]{li zhao}%
\author[1]{xuan su}%
\author[1]{Lini Xian}%
\author[1]{Jian Chen}%
\author[1]{Xiaolei  Song}%
\author[1]{Qinghui  Wang}%
\author[2]{Yunchuan  Ding}%
\affil[1]{Yanan Hospital of Kunming City}%
\affil[2]{ Yanan Hospital of Kunming City}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
\let\center\flushleft
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\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: Cardiovascular impairment is an important complication of
end-stage renal disease (ESRD) undergoing hemodialysis (HD) therapy.
Left atrial (LA) deformation is closely related to left ventricular (LV)
filling pressure and dysfunction, but quantification of LA dysfunction
remains a challenge. The purpose of this study was to evaluate the LA
function in ESRD patients using four-dimensional(4D) auto left atrial
quantification(4D-LAQ). Methods: Thirty-seven ESRD patients (aged
51.68\selectlanguage{ngerman}±15.98 years; 43\% male) on HD and 34 healthy individuals (aged
42.03±11.50 years; 38\% male) were enrolled in the study. All
participants underwent conventional echocardiographic examinations and
4D-LAQ. The measurements of LA dimension, volume, emptying fraction, and
longitudinal/circumferential strain parameters during triphasic were
obtained from the LV long axis and apical 4-chamber views, which were
taken offline using software (GE EchoPac 203). Results: In patients with
ESRD, LA dimension and volume were higher than the healthy group, while
the LASr (22.54±6.14 vs 33.74±5.07; p\textless{}0.05), LAScd
(-12.54±5.83 vs -20.03±5.21;p\textless{}0.05), LASct (-10.00±4.93 vs
-13.56±5.17;p\textless{}0.05 ), LASr-c (28.00±6.61 vs
35.29±7.24;p\textless{}0.05), and LAScd-c (-13.27±5.58 vs -18.47±8.65;
p\textless{}0.05) were significantly lower. Furthermore, a good positive
correlation was observed between the LAEF, LASr, and LAScd-c values and
LV filling pressure, which reflect diastolic dysfunction. Conclusion: We
demonstrated that the LA strain in dialysis patients was impaired before
the occurrence of LA dilation. LA strain is more sensitive than
traditional echocardiographic parameters, and LASr and LAScd-c may be
useful to detect early myocardial involvement.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Estimation of Left Atrial Function Using Four-Dimensional Auto
Left Atrial Quantify Echocardiography in Patients with End-Stage Renal
Disease}

Li Zhao\textsuperscript{1,2,3}, Xuan Su\textsuperscript{1,2}, Lini
Xian\textsuperscript{1,2}, Jian Chen\textsuperscript{1,3}, Xiaolei
Song\textsuperscript{1}, Qinghui Wang\textsuperscript{1,2,3*}and
Yunchuan Ding\textsuperscript{1,2,3*}

\textsuperscript{1} Department of Ultrasound, Yanan Hospital of Kunming
City, the Affiliated Hospital of Kunming Medical University, Kunming,
Yunnan Province, 650051, China

\textsuperscript{2} Clinical Research Center of Cardiovascular
Ultrasound, Yunnan Province, 650051, China

\textsuperscript{3} Yunnan Province Key Laboratory of Cardiovascular
Diseases, Kunming, Yunnan Province, 650051, China

*Address correspondence to:Qinghui Wang, Department of Ultrasound,
Yanan Hospital of Kunming City, the Affiliated Hospital of Kunming
Medical University, Kunming, Yunnan Province, 650051, China, E-mail:
wqh962099@163.com.Yunchuan Ding, Department of Ultrasound, Yanan
Hospital of Kunming City, the Affiliated Hospital of Kunming Medical
University, Kunming, Yunnan Province, 650051, China, E-mail:
dd82109@163.com.

Funding information: Funds of Yunnan Province Science and Technology
Department, China, Grant/Award Number:2017NS331

\textbf{Background:} Cardiovascular impairment is an important
complication of end-stage renal disease (ESRD) undergoing hemodialysis
(HD) therapy. Left atrial (LA) deformation is closely related to left
ventricular (LV) filling pressure and dysfunction, but quantification of
LA dysfunction remains a challenge. The purpose of this study was to
evaluate the LA function in ESRD patients using four-dimensional(4D)
auto left atrial quantification(4D-LAQ).

\textbf{Methods:} Thirty-seven ESRD patients (aged 51.68\selectlanguage{ngerman}±15.98 years;
43\% male) on HD and 34 healthy individuals (aged 42.03±11.50 years;
38\% male) were enrolled in the study. All participants underwent
conventional echocardiographic examinations and 4D-LAQ. The measurements
of LA dimension, volume, emptying fraction, and
longitudinal/circumferential strain parameters during triphasic were
obtained from the LV long axis and apical 4-chamber views, which were
taken offline using software (GE EchoPac 203).

\textbf{Results:} In patients with ESRD, LA dimension and volume were
higher than the healthy group, while the LASr (22.54±6.14 vs 33.74±5.07;
p\textless{}0.05), LAScd

(-12.54±5.83 vs -20.03±5.21;p\textless{}0.05), LASct (-10.00±4.93 vs
-13.56±5.17;p\textless{}0.05 ), LASr-c (28.00±6.61 vs
35.29±7.24;p\textless{}0.05), and LAScd-c (-13.27±5.58 vs

-18.47±8.65; p\textless{}0.05) were significantly lower. Furthermore, a
good positive correlation was observed between the LAEF, LASr, and
LAScd-c values and LV filling pressure, which reflect diastolic
dysfunction.

\textbf{Conclusion:} We demonstrated that the LA strain in dialysis
patients was impaired before the occurrence of LA dilation. LA strain is
more sensitive than traditional echocardiographic parameters, and LASr
and LAScd-c may be useful to detect early myocardial involvement.

\textbf{Keywords: left atrial function; strain; end-stage renal disease;
hemodialysis}

\textbf{Introduction}

The occurrence and development of end-stage renal disease (ESRD) is
complex, which causes different degrees of damage in cardiac structure
and function. Cardiovascular complication is by far the most important
reason for death in patients with ESRD on hemodialysis (HD) therapy
{[}1{]}. In the past, the focus of clinical research has been on the
left ventricular morphology and function, but the change of left atrial
(LA) function was often overlooked. Previous studies have shown that LA
dilatation is closely related to the sustained volume and pressure
overload, which can predict left ventricular hypertrophy, high filling
pressure, and even mortality. {[}2{]} Thus, LA parameters have important
clinical value in assessing the risk and prognosis of cardiovascular
complications.

In clinical application, conventional echocardiography is the most
common noninvasive method of evaluating cardiac structure and function
in almost all patients with ESRD. However, it may not be sufficiently
sensitive to detect early and subtle changes in ESRD with preserved
ejection fraction, especially before serious cardiac involvement occurs.
The EACVI NORRE study recently recommended the use of LA deformation
imaging based on two-dimensional speckle tracking echocardiography
(2D-STE){[}3{]}. 2D-STE has been used in previous studies on LA function
of this triphasic nature to document subclinical dysfunction.

Four-Dimensional Auto Left Atrial Quantification (LAQ) is a new method
using three-dimensional(3D) data, which has a simple workflow and offers
a new diagnosis method, evaluating the value of LA volume and emptying
fraction aside from strain parameters analysis in the ESRD. LAQ can
directly show LA endocardial contraction and provide sensitive and
reproducible indices of myocardial dysfunction; thus, myocardial
deformation was assessed directly and angle-independently {[}4{]}.

The LA cavity volume is measured from a semi-automated segmentation
algorithm during the cardiac cycle. The method calculates the
deformation of the 3D model by solving a state estimation problem, which
was constructed from an extended Kalman filter combined with LA
geometry, a motion model, and edge detection algorithms. The strain is
calculated based on the length change of different lines in each
anatomical direction. The longitudinal strain is calculated by eight
longitudinal lines from an automatically constructed triangular grid,
which is connected to 2 opposite LA basal points (Figure 1). To
calculate circumferential strain, 7 circumferential lines are
equidistantly distributed between the LA base and apex (Figure 2).Then,
strain is calculated for each frame time according to the following
formula: s(t)=(L(t)-L(tref))/L(tref) X 100\%, where L(t) is the line
length at time t, and tref is set as the end diastolic time point of
left ventricular. Global strain in each direction is obtained by
calculating the average strain of the respective directional lines.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 1:} Points used to determine longitudinal
lines.\textbf{Figure 2:} Points used to determine circumferential lines.
Images were provided by GE Healthcare vendor.

\textbf{2.Materials and Methods}

\textbf{2.1 Study Population}

Every individual signed the informed consent forms approved by the
Ethics Committee of our hospital. Between August 2019 and April 2020, 37
patients with ESRD on regular HD aged 51.68\selectlanguage{ngerman}±15.98 years participated in
this study and compared with 34 healthy control subjects, matched for
sex and body surface area (BSA).

\textbf{Inclusion Criteria} : We used the modified National Kidney
Foundation Classification of Chronic Kidney Disease, with ESRD defined
as estimated glomerular filtration
rate(eGFR)\textless{}15mL/min/1.73m\textsuperscript{2}, and eGFR was
calculated by the MDRD formula. Adults\selectlanguage{english}[?]18 years old and
LVEF\selectlanguage{english}[?]50\%.\textbf{Exclusion Criteria:} Acute renal insufficiency,
significant valvular heart disease, arrhythmia, severe systemic
diseases, low ejection fraction (LVEF\textless{}50\%) and poor
echocardiographic image.

\textbf{2.2 Conventional Echocardiography}

Blood pressure, heart rate, and BSA measurements of all the individuals
were recorded before the examination. Echocardiography was performed by
an experienced cardiologist during the recovery period post-HD. Subjects
were in the left lateral decubitus position, aspirated calmly, and
connected with synchronous electrocardiogram. The measurements were
carried out using the echocardiography machine (Vivid E95; GE
Healthcare, Horten, Norway) and a 5S (3.5-5Mhz) probe.

Images included 2D, M-mode, pulsed-, and continuous-wave Doppler in
addition to Tissue Doppler Imaging (TDI) were obtained from the standard
parasternal and apical positions according to the guidelines of the
American Society of Echocardiography (ASE). Zoomed LA were obtained in
4-and 2-chamber views at high frame rates (60-80 frames/sec), and three
consecutive cardiac cycles were stored. LAV (maximum{[}max{]},
maximum{[}min{]}), 2D LAEF were measured by biplane Simpson's method. LA
diameter, including antero-posterior diameter (LAD1), medial-later
diameter (LAD2), and superior-inferior diameter (LAD3) were measured
from left ventricular long axis and apical 4 chamber. Left ventricle end
diastolic dimensions (LVEDd), interventricular septum diastolic
thickness (IVST), posterior wall diastolic thickness (PWT) and LVEF were
measured by M-mode method.

Left ventricle diastolic function was assessed: Peak E and A velocity
were measured by pulsed-wave doppler at the mitral leaflet tips in the
apical 4-chamber view, and the E/A ratio was calculated. TDI velocities
early diastole (e') were recorded with the sample volume placed on the
septal and lateral mitral annulus, and E/e' was calculated. Pulmonary
capillary wedge pressure (ePCWP) was calculated according to the
following formula: ePCWP = 1.25(E/E') + 1.9{[}5{]}. Pulmonary artery
systolic pressure(PASP) was estimated with the Bernoulli equation
formula: 4xTRv2 + RAP, where v is the peak tricuspid regurgitation
velocity, measured by continuous-wave Doppler, added to the estimated
right atrium pressure, which was calculated based on inferior vena cava
(IVC) diameter and the extent of its collapse during inspiration.
{[}6{]}

\textbf{2.3 Four-Dimensional(4D) Auto Left Atrial Quantify}

4D full volume data were acquired with a transthoracic 4D probe, and 4
consecutive cardiac cycle images from the apical 4ch view were stored in
digital format, and the measurements were analyzed offline using the
commercially available EchoPAC version 203 software (GE Healthcare).
During the acquisition process, it is necessary to ensure that the
complete LA is included, and the frame rate exceeds 12 volumes/second to
obtain adequate temporal assessment and volume/EF/strain calculation.

Open 4D LA image, select Measure/volume/4D Auto LAQ in turn. First,
adjust the frame control until the mitral valve closes at the Set
Landmark stage. Adjust the position and angle of image according to 4
pictograms in the upper right corner of each quadrant, so that the
vertical line intersects the MV center and the apex of the LA. Second,
at the Review stage, the system will segment the whole volume data set
to locate the endocardial borders for the LA. At the same time, the
editing function includes undo/redo to locate the time frame of mitral
valve opening (ES), end-diastole (ED) and preA accurately, which can be
adjusted manually when the automatic tracking is not accurate. In our
study, we exclude the pulmonary veins and the LA appendage. Finally, the
Results stage in the worksheet and volume provides various parameters
that have been calculated:

Volume and LAEF: LAVmin, LAVmax, left atrial volume at onset of
contraction (LA VpreA), and LAVImax was calculated by dividing the
LAVmax by BSA. Left atrial emptying volume (LAEV) was calculated by
LAVmax minus LAVmin. Left atrial emptying fraction (LAEF) was calculated
by dividing LA EV by LAVmax. The following left atrial strain parameters
are derived:

\textbf{1.Reservoir phase:} LA receive pulmonary veins during LV
contraction, and account for approximately 40\% of the atrium devoted to
stroke volume. Longitudinal strain (LASr) and circumferential strain
(LASr-c) are calculated by the difference of the strain value at ES
minus ventricular ED. The reservoir phase encompasses the time of left
ventricular isovolumic contraction, ejection and isovolumic relaxation.

\textbf{2.Conduit phase:} In normal subjects, LA passively transferring
blood to the LV during early diastole accounts for approximately 35\% of
the atrium contribution to stroke volume. Longitudinal strain (LAScd)
and circumferential strain (LAScd-c) are measured as the difference of
the strain value LA PreA minus ES.

\textbf{3.Contraction phase:} In normal subjects, LA passively
transferring blood to the LV in late diastole, account for approximately
25\% of the atrium contribution to stroke volume. longitudinal strain
(LASct) and circumferential strain (LASct-c) are measured as the
difference of the strain value at ventricular ED minus LA-PreA only in
patients in sinus rhythm.

In addition, radial strain is not involved in our study, which is
related to vendor-independent software, although radial strain may
account for a small proportion of LA function. We also used the global
strain rather than the segmental strain because of the thin wall, which
makes it difficult to obtain accurate results.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

\textbf{Figure 3:} Set landmark on the basis of the mitral valve

\textbf{Figure 4:} Edit left atrial endocardial border by review stage

\textbf{Figure 5:} The results are displayed in worksheet and volume

\textbf{2.4 Statistical Methods}

The SPSS 22.0 statistical package (IBM, Armonk, NY, USA) was performed
for data analyses. Continuous variables were expressed in our study as
mean \selectlanguage{ngerman}± standard deviation or median (interquartile range) values. Normal
distribution of the groups was tested using the Kolmogorov--Smirnov
test. Continuous variables were compared using an independent-samples
t-test between the 2 groups or adjusted t-test. The Pearson correlation
coefficient was used to identify the correlation between the groups.
Multiple linear regression analyses were performed to examine the
independent correlates between 3D left atrial function and 2D
conventional echocardiographic parameters in ESRD. Two-tailed P-values
\textless{}.05 were considered statistically significant.

\textbf{3.Results}

\textbf{3.1 Demographic characteristics of the study population}

A total of 71 patients were enrolled in the study, of whom 37 were ESRD
patients on regular HD and 34 were healthy controls. The systolic
(119.94±10.32 vs 150.76±19.67; p \textless{} 0.001) and diastolic
(76.68±7.03 vs 90.81±12.14; p \textless{}0.001) blood pressures were
found to be higher in the ESRD group. The mean age of the ESRD group was
found to be higher than the heathy group (42.03±11.50 vs 51.68±15.98,
p=0.005), while no difference was observed between the groups in terms
of BSA, gender, and heart rate. Laboratory tests showed an increase in
serum urea (5.00±0.84 vs 17.27±5.89; p\textless{}0.001) and creatinine
(63.41±12.29 vs 606.81±138.09;p\textless{}0.001) and a significant
decrease in eGFR(102.40±5.36 vs 7.87±1.93;p\textless{}0.001) in the ESRD
group. Among the ESRD patients, 30 had hypertension, 8 had diabetes
mellitus, and 5 had hyperlipidemia (Table1).\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Table 1} \textbf{Baseline characteristics of the study
population} & \textbf{Table 1} \textbf{Baseline characteristics of the
study population} & \textbf{Table 1} \textbf{Baseline characteristics of
the study population} & \textbf{Table 1} \textbf{Baseline
characteristics of the study population}\tabularnewline
\midrule
\endhead
& Control Group (n=34) & Dialysis Group (n=37) & p-value\tabularnewline
\textbf{Clinical Variable} & & &\tabularnewline
Age (years) & 42.03\selectlanguage{ngerman}±11.50 & 51.68\selectlanguage{ngerman}±15.98 & 0.005\tabularnewline
Gender, male & 13 & 16 & 0.673\tabularnewline
BSA (m2) & 1.62\selectlanguage{ngerman}±0.13 & 1.67\selectlanguage{ngerman}±0.21 & 0.223\tabularnewline
Systolic BP (mmHg) & 119.94\selectlanguage{ngerman}±10.32 & 150.76\selectlanguage{ngerman}±19.67 & 0.000\tabularnewline
Diastolic BP (mmHg) & 76.68\selectlanguage{ngerman}±7.03 & 90.81\selectlanguage{ngerman}±12.14 & 0.000\tabularnewline
Heart rate (bpm) & 71.03\selectlanguage{ngerman}±9.41 & 75.43\selectlanguage{ngerman}±11.44 & 0.082\tabularnewline
Hypertension & 0 & 30 &\tabularnewline
Diabetes mellitus & 0 & 8 &\tabularnewline
Hyperlipidemia & 0 & 5 &\tabularnewline
\textbf{Laboratory tests} & & &\tabularnewline
Urea (mmol/l) & 5.00\selectlanguage{ngerman}±0.84 & 17.27\selectlanguage{ngerman}±5.89 & 0.000\tabularnewline
Creatinine (lmol/l) & 63.41\selectlanguage{ngerman}±12.29 & 606.81\selectlanguage{ngerman}±138.09 & 0.000\tabularnewline
e GFR & 102.40\selectlanguage{ngerman}±5.36 & 7.87\selectlanguage{ngerman}±1.93 & 0.000\tabularnewline
\bottomrule
\end{longtable}

\textbf{3.2 Traditional Echocardiographic Parameters}

Of the ESRD patients on HD, 8 had mild to moderate mitral regurgitation,
12 had small pericardial effusion. Echocardiography revealed no
abnormality of congenital cardiac structure. LVEDd and LV wall thickness
were observed to be higher in the ESRD group while LAEF (63.41\selectlanguage{ngerman}±4.97 vs
67.47±3.96; p\textless{}0.001) was lower than the heathy control, but
still within in the normal range. There was a relationship between
conventional echocardiography and LV diastolic filling pressure. On the
one hand, mitral late diastolic flow velocity (A), E/e' ratio, ePCWP,
and PASP values were found to be higher in the ESRD group. On the other
hand, the E/A ratio, mitral annulus early diastolic velocities were
found to be lower in the ESRD group. In addition, no difference was
observed in terms of peak E and IVC values between the groups. The
results of the conventional echocardiographic parameters in both groups
are presented in Table 2.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Table 2 Conventional Echocardiography Variables of Healthy
Individuals and Dialysis Patients} & \textbf{Table 2 Conventional
Echocardiography Variables of Healthy Individuals and Dialysis Patients}
& \textbf{Table 2 Conventional Echocardiography Variables of Healthy
Individuals and Dialysis Patients} & \textbf{Table 2 Conventional
Echocardiography Variables of Healthy Individuals and Dialysis
Patients}\tabularnewline
\midrule
\endhead
\textbf{Echocardiography Parameters} & control group(n=34) & dialysis
group(n=37) & p-value\tabularnewline
\textbf{M-Mode and 2D} & \textbf{M-Mode and 2D} & \textbf{M-Mode and 2D}
& \textbf{M-Mode and 2D}\tabularnewline
LVEDd, mm & 44.09\selectlanguage{ngerman}±2.71 & 49.16\selectlanguage{ngerman}±4.28 & 0.000\tabularnewline
LV EF, \% & 67.47\selectlanguage{ngerman}±3.96 & 63.41\selectlanguage{ngerman}±4.97 & 0.000\tabularnewline
IVST, mm & 9.09\selectlanguage{ngerman}±0.83 & 11.03\selectlanguage{ngerman}±1.34 & 0.000\tabularnewline
LVPWT, mm & 9.24\selectlanguage{ngerman}±0.61 & 10.62\selectlanguage{ngerman}±1.09 & 0.000\tabularnewline
\textbf{Mitral inflow velocities} & \textbf{Mitral inflow velocities} &
\textbf{Mitral inflow velocities} & \textbf{Mitral inflow
velocities}\tabularnewline
E, cm/s & 0.87\selectlanguage{ngerman}±0.16 & 0.86\selectlanguage{ngerman}±0.22 & 0.824\tabularnewline
A, cm/s & 0.69\selectlanguage{ngerman}±0.19 & 0.87\selectlanguage{ngerman}±0.26 & 0.001\tabularnewline
E/A ratio & 1.37\selectlanguage{ngerman}±0.49 & 1.10\selectlanguage{ngerman}±0.51 & 0.022\tabularnewline
IVS e', m/s & 0.10\selectlanguage{ngerman}±0.02 & 0.06\selectlanguage{ngerman}±0.02 & 0.000\tabularnewline
LVLW e', m/s & 0.13\selectlanguage{ngerman}±0.03 & 0.08\selectlanguage{ngerman}±0.02 & 0.000\tabularnewline
\textbf{LV diastolic filling pressure} & \textbf{LV diastolic filling
pressure} & \textbf{LV diastolic filling pressure} & \textbf{LV
diastolic filling pressure}\tabularnewline
E/e' ratio & 7.85\selectlanguage{ngerman}±1.55 & 12.88\selectlanguage{ngerman}±4.71 & 0.000\tabularnewline
ePCWP, mmHg & 11.72\selectlanguage{ngerman}±1.93 & 18.00\selectlanguage{ngerman}±5.89 & 0.000\tabularnewline
PASP, mmHg & 27.62\selectlanguage{ngerman}±2.52 & 41.05\selectlanguage{ngerman}±11.44 & 0.000\tabularnewline
Inferior vena cava diameter, mm & 14.18\selectlanguage{ngerman}±1.03 & 14.62\selectlanguage{ngerman}±1.64 &
0.172\tabularnewline
\bottomrule
\end{longtable}

\textbf{3.3 LA structure and function parameters}

The diameter and volumes of the LA, including LAVImax, LA VpreA, and LA
EV by 2D- and 3D echocardiographic data were found to be higher in the
ESRD group(p\textless{}0.001). In addition, LAEF of ESRD patients was
within in the normal range, but still lower than the heathy controls.
Left atrial strain parameters, including longitudinal and
circumferential strain values through the 4D-LAQ were observed to be
lower in the ESRD group. Compared to the control group, the decrease of
longitudinal strain values occurred in triphasic functions of the LA,
whereas the decrease of the circumferential strain occurred in the
reservoir and conduit phase. (Table 3)\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Table 3 Left Atrium Functional and Structural Parameters} &
\textbf{Table 3 Left Atrium Functional and Structural Parameters} &
\textbf{Table 3 Left Atrium Functional and Structural Parameters} &
\textbf{Table 3 Left Atrium Functional and Structural
Parameters}\tabularnewline
\midrule
\endhead
& Control Group (n = 34) & Dialysis Group(n =37) &
P-Value\tabularnewline
\textbf{2D} & \textbf{2D} & \textbf{2D} & \textbf{2D}\tabularnewline
LAD1, cm & 29.91\selectlanguage{ngerman}±1.76 & 38.41\selectlanguage{ngerman}±4.11 & 0.000\tabularnewline
LAD2, cm & 37.65\selectlanguage{ngerman}±4.53 & 47.35\selectlanguage{ngerman}±6.77 & 0.000\tabularnewline
LAD3, cm & 45.38\selectlanguage{ngerman}±5.20 & 57.46\selectlanguage{ngerman}±6.14 & 0.000\tabularnewline
LAVmax, ml & 46.85\selectlanguage{ngerman}±10.38 & 85.84\selectlanguage{ngerman}±26.68 & 0.000\tabularnewline
LAVmin, ml & 19.18\selectlanguage{ngerman}±6.01 & 40.62\selectlanguage{ngerman}±17.59 & 0.000\tabularnewline
LAEF, \% & 59.47\selectlanguage{ngerman}±4.51 & 53.81\selectlanguage{ngerman}±5.71 & 0.000\tabularnewline
\textbf{3D} Left Atrial volume & \textbf{3D} Left Atrial volume &
\textbf{3D} Left Atrial volume & \textbf{3D} Left Atrial
volume\tabularnewline
LA Vmin,ml & 14.74\selectlanguage{ngerman}±3.58 & 26.14\selectlanguage{ngerman}±8.95 & 0.000\tabularnewline
LA Vmax,ml & 37.65\selectlanguage{ngerman}±6.46 & 56.08\selectlanguage{ngerman}±13.10 & 0.000\tabularnewline
LA VpreA,ml & 24.21\selectlanguage{ngerman}±6.93 & 41.16\selectlanguage{ngerman}±14.03 & 0.000\tabularnewline
LAVImax,ml/m2 & 23.12\selectlanguage{ngerman}±4.03 & 33.92\selectlanguage{ngerman}±8.54 & 0.000\tabularnewline
LA EV,ml & 22.79\selectlanguage{ngerman}±3.97 & 29.89\selectlanguage{ngerman}±5.37 & 0.000\tabularnewline
LA EF,\% & 61.09\selectlanguage{ngerman}±5.11 & 54.22\selectlanguage{ngerman}±5.97 & 0.000\tabularnewline
\textbf{3D} Left Atrial strain & \textbf{3D} Left Atrial strain &
\textbf{3D} Left Atrial strain & \textbf{3D} Left Atrial
strain\tabularnewline
LASr,\% & 33.74\selectlanguage{ngerman}±5.07 & 22.54\selectlanguage{ngerman}±6.14 & 0.000\tabularnewline
LAScd,\% & -20.03\selectlanguage{ngerman}±5.21 & -12.54\selectlanguage{ngerman}±5.83 & 0.000\tabularnewline
LASct,\% & -13.56\selectlanguage{ngerman}±5.17 & -10.00\selectlanguage{ngerman}±4.93 & 0.004\tabularnewline
LASr-c,\% & 35.29\selectlanguage{ngerman}±7.24 & 28.00\selectlanguage{ngerman}±6.61 & 0.000\tabularnewline
LAScd-c,\% & -18.47\selectlanguage{ngerman}±8.65 & -13.27\selectlanguage{ngerman}±5.58 & 0.004\tabularnewline
LASct-c,\% & -16.94\selectlanguage{ngerman}±7.62 & -13.76\selectlanguage{ngerman}±8.35 & 0.099\tabularnewline
\bottomrule
\end{longtable}

\textbf{3.4 Multivariate analysis for left atrial functions}\selectlanguage{english}
\begin{longtable}[]{@{}l@{}}
\toprule
We also performed multivariate analysis to determine 3D-LA volume and
strain in ESRD. The relationship between PASP, LAD3, and 2D-LAVmin
related to the 3D-LAVmin through the correlation analysis. LAD1,
2D-LAVmax, IVS, and LVPW were found to be associated with 3D-LAVmax.
LAVImax was related to LAD2. the relationship between the 3D-LAEF and
E/e', e PCWP, 2D-LAEF, IVC was observed closely. Multivariate analysis
showed a negative correlation between the LASr and E/e', ePCWP and
LVEDd, while it had a positive correlation with LVEF. The researchers
also found that LASct was relevant to LAVmax, E. LAScd-c was negatively
correlated to E/e', e PCWP, and IVC. Moreover, LASct-c was positively
correlated to E/A. The related analysis results are presented in Table
4.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\textbf{Table 4 Multivariate analysis for 3D left atrial function and 2D
conventional echocardiographic variables in ESRD} & \textbf{Table 4
Multivariate analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD} & \textbf{Table 4 Multivariate
analysis for 3D left atrial function and 2D conventional
echocardiographic variables in ESRD}\tabularnewline
\midrule
\endhead
& \textbf{2D conventional parameters} & \textbf{2D conventional
parameters} & \textbf{2D conventional parameters} & & \textbf{2D
conventional parameters} & \textbf{2D conventional parameters} &
\textbf{2D conventional parameters} &\tabularnewline
\textbf{3D variables} & \selectlanguage{greek}\textbf{β-coefficient ± SE}\selectlanguage{ngerman} &
\selectlanguage{greek}\textbf{β-coefficient ± SE}\selectlanguage{ngerman} & \textbf{P-value} & & \textbf{3D variables}
& \selectlanguage{greek}\textbf{β-coefficient ± SE}\selectlanguage{ngerman} & \selectlanguage{greek}\textbf{β-coefficient ± SE}\selectlanguage{ngerman} &
\textbf{P-value}\tabularnewline
LAVmin & & & & & LASr & & &\tabularnewline
& PASP & 0.609\selectlanguage{ngerman}±0.171 & 0.000 & & & E/e' & -0.373\selectlanguage{ngerman}±0.130 &
0.035\tabularnewline
& LAD3 & 0.713\selectlanguage{ngerman}±0.081 & 0.000 & & & e PCWP & -0.373\selectlanguage{ngerman}±0.162 &
0.035\tabularnewline
& LAVmin & 0.797\selectlanguage{ngerman}±0.201 & 0.000 & & & LVEDd & -0.675\selectlanguage{ngerman}±0.087 &
0.000\tabularnewline
LAVmax & & & & & & LVEF & 0.566\selectlanguage{ngerman}±0.113 & 0.000\tabularnewline
& LAD1 & 0.771\selectlanguage{ngerman}±0.034 & 0.000 & & LAScd & & &\tabularnewline
& LAVmax & 0.681\selectlanguage{ngerman}±0.223 & 0.000 & & LASct & & &\tabularnewline
& IVS & 0.450\selectlanguage{ngerman}±0.015 & 0.005 & & & LAVmax & 0.253\selectlanguage{ngerman}±0.593 &
0.027\tabularnewline
& LVPW & 0.427\selectlanguage{ngerman}±0.013 & 0.008 & & & E & 0.409\selectlanguage{ngerman}±0.007 &
0.012\tabularnewline
LAVpreA & & & & & & IVC & 0.299\selectlanguage{ngerman}±0.049 & 0.053\tabularnewline
LAVImax & & & & & LASr-c & & &\tabularnewline
& LAD2 & 0.733\selectlanguage{ngerman}±0.091 & 0.000 & & LAScd-c & & &\tabularnewline
LAEV & & & & & & E/e' & -0.669\selectlanguage{ngerman}±0.118 & 0.000\tabularnewline
LAEF & & & & & & e PCWP & -0.669\selectlanguage{ngerman}±0.148 & 0.000\tabularnewline
& E/e' & -0.471\selectlanguage{ngerman}±0.142 & 0.014 & & & IVC & -0.673\selectlanguage{ngerman}±0.046 &
0.000\tabularnewline
& e PCWP & -0.471\selectlanguage{ngerman}±0.178 & 0.014 & & LASct-c & & &\tabularnewline
& LAEF & 0.787\selectlanguage{ngerman}±0.100 & 0.000 & & & E/A & 0.489\selectlanguage{ngerman}±0.009 &
0.002\tabularnewline
& IVC & -0.384\selectlanguage{ngerman}±0.046 & 0.030 & & & & &\tabularnewline
\bottomrule
\end{longtable}

SE, standard error

\textbf{Discussion}

HD, as a common alternative treatment for ESRD patients, can prolong the
survival time of patients. Nevertheless, the high incidence of
cardiovascular disease, such as heart failure and coronary heart
disease, is the main cause of death. {[}7{]} Studies have shown the
relationship between increased LA size, volume, and major cardiovascular
events in ESRD {[}8{]}. There are many data available indicating that
the diastolic function of ESRD is damaged earlier than the change of LV
systolic function, and the change of LA function can more sensitively
reflect the change of diastolic function. {[}9{]} The LA function can
directly reflect the changes of atrioventricular pressure difference,
which is the direct embodiment of left atrial preload and afterload.
Thus, early detection of left atrial structural and functional
impairment is helpful for the selection of clinical treatment options in
the ESRD with preserved ejection fraction on HD. In the present study,
we demonstrated that LA dimension and volume increased in ESRD compared
to normal healthy groups, but the strain is lower. Additionally, the
strain parameters showed a better correlation with LV diastolic filling
pressure than conventional parameters.

\textbf{LA deformation in ESRD}

In accordance with previous studies, we found that LV dimension and wall
thickness increased in ESRD compared to normal healthy groups, and
hypertension was found in 81\% of HD group. LV hypertrophy, diastolic
dysfunction, and volume overload may lead to elevated LV filling
pressure and LA afterload in patients with ESRD {[}10{]} Therefore,
these alterations trigger a compensatory mechanism, which is
characterized by dilating and the stretching of the atrial myocardium.
This contributes to an enhanced LA emptying volume activation of the
Frank-Starling mechanism, which is partially responsible for the
maintenance of the stroke volume in ESRD patients. {[}4{]}

The dimension and volume of LA by 2D/3D echocardiography is
significantly increased, while LAEF is decreased but in the normal
range. The changes in the LA functional properties were accompanied by
an increase in E/e', ePCWP, PASP, and an decrease in E/A, velocities of
the septal and lateral mitral annulus, peak A, which is an
echocardiographic marker of LV dysfunction.

However, in the late stage of chronic renal diseases increases in the LA
afterload results in LA remodeling, which is featured by increases in
the LA wall thickness and focal collagen, as well as atrial myocardium
fibrosis. LA remodeling is also associated with atrial interstitial
fibrosis and cell hypertrophy, as well as impaired calcium uptake in the
cardiomyocytes, which may contribute to the LA systolic and diastolic
dysfunction {[}11{]}{[}12{]}{[}4{]} .With the deterioration of LA
deformation, lung vessel compliance is reduced and vascular remodeling
that can lead to right ventricular overload and dysfunction. {[}13{]}

\textbf{LA strain in ESRD}

LV diastolic dysfunction generated volume and pressure overload, which
can result in LA dilation and increased pressure in ESRD patients on
regular HD, may lead to a sustained elevation in LV filling pressure.
Mitral E/A and E/e' ratio used to evaluate LV diastolic dysfunction by
classical echocardiographers. However, they appeared late and showed
variations, depending on loading situations and other conditions, such
as heart rate, mitral regurgitation and so on. In addition, E/e' may be
elevated in ESRD due to extracellular volume expansion.{[}2{]}

Similar to LV function, LA strain can evaluate early subclinical
functional changes in ESRD. LA volume and pressure overload lead to
myocardial fibrosis and compliance reduction, and then lead to left
atrial remodeling and left atrial systolic function reduction, affecting
the reduction of myocardial strain. Our research was concordant with
other studies. The difference is the method of calculating strain.
Previous studies have reported that LA strain analysis using speckle
tracking echocardiography is useful for assessing LA function {[}14{]}.
3D-STI technology can track the motion track of myocardial ''spot'' in
3D space and construct 3D images of myocardial motion, including
longitudinal strain, circumferential strain and radial strain, but the
analysis of different phases is insufficient. At present, LA strain
calculation is based upon the length of different lines in each
anatomical direction during the three phases by 4D-LAQ.In addition, 4D
LAQ have brought new insights into particular situations, which
displayed LA myocardial volume and strain with high sensitivity and
repeatability.

The muscle fibers of LA are predominantly arranged in 2 layers: the deep
layer and the shallow layer. The shallow layer runs along the transverse
diameter. The deep layer contains two kinds of myocardium, longitudinal
and circular, which constitute the 3D spatial structure and complex
motion of the atrium. The LA strain parameters in this study are
longitudinal and circumferential strain with deep myocardial involvement
only, which undertakes the most of work and is related to the vendor.

During the cardiac cycle in normal subjects, the volume contribution of
ventricular filling (75-80\%) mainly comes from the reservoir and
conduit phase, while 20-25\% comes from atrial contraction. However, the
composition of these three phases has also been redistributed when
myocardial damage in ESRD. Reservoir function: In ESRD, the reduction of
LV relaxation and untwisting/reverse rotation possibly leads to elevated
LV filling pressure and LA pressure {[}15{]}, resulting in impairment of
LA compliance and relaxation. In our study, the LA longitudinal and
circumferential strain during reservoir phase significantly decreased in
ESRD. Moreover, the longitudinal strain revealed a strong connection
with LV filling by multivariate analysis. Conduit function: The
progressive worsening of LV diastolic delay and compliance reduction, LA
remodeling, and diastolic function worsening leads to the reduction in
the conduit phase. In our study, the LA longitudinal and circumferential
strain during conduit phase showed decrease significantly in ESRD.
Moreover, the circumferential strain reveals a strong connection with LV
filling by multivariate analysis. Contraction function: The volume
contribution of LA contraction at first compensates for the decrease in
the early diastolic and diastasis phase. Lon-term exposure to
accelerated volume and pressure will eventually affect the function of
LA pump. Compared with the control group, our findings show that LA
longitudinal strain during the contraction phase in ESRD was reduced
while circumferential strain showed no significant change.

When LV diastolic function is impaired early/mild, the conduit flow is
reduced while flow increases during the reservoir and pump phase
{[}16{]}. With progressive worsening of diastolic function, three phases
volume increases. The reason may be that RAAS system is activated to
increase myocardial contractility, which is responsible for the
compensation and maintenance of adequate ventricular filling through
Frank-Starling mechanism. With the worsening of LA enlargement and LV
diastolic dysfunction, LA strain during the three phases decreased due
to the LA and LV now acting as one chamber {[}15{]}. In our study, the
early damage of LA strain occurred during the reservoir and conduit
phase, and contraction damage may be associated with abnormal systolic
function. In conclusion, the change of LA strain is earlier than LA
dimension and volume; that is, the change of function is earlier than
the structuration. Moreover, LASr and LAScd-c may be associated with LV
diastolic filling pressure, which is an echocardiographic marker of LV
dysfunction.

\textbf{Limitations}

Our study has some limitations. The small size of the patient population
is the main limitation. Patients were not grouped by the duration of
dialysis time. This study is a single-center, small sample study; thus
the promotion of the conclusion needs further multicenter large sample
and long-term follow-up observation.

\textbf{Conclusion}

LA strain analysis may be more sensitive than conventional parameters to
detect early impairment of left atrial structure and function in ESRD
undergoing HD. 4D-LAQ provided a new and advanced method, we can further
demonstrate and quantify these changes, even in the early stage of the
disease process.

\textbf{Reference}

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risk factor for development of cardiovascular disease: a statement from
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{[}2{]} Hassanin N, Alkemary A. Detection of Left Atrium Myopathy Using
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Therapy.Echocardiography.2016.33(2)233-241.

{[}3{]}Sugimoto T, Robinet S, Dulgheru R, et al. Echocardiographic
reference ranges for normal left atrial function parameters: results
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{[}4{]}Altekin RE, Yanikoglu A, Karakas MS, et al. Evaluation of left
atrial function using two-dimensional speckle tracking echocardiography
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{[}5{]}Kurt M, Tanboga IH, Aksakal E, et al. Relation of left
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{[}6{]}Venkatachalam S, Wu G, Ahmad M. Echocardiographic Assessment of
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{[}7{]}Sun M ,Kang Y ,Cheng L ,et al .Global longitudinal strain is an
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{[}8{]}Chan MY, Wong HB, Ong HY, et al. Prognostic value of left atrial
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{[}9{]} Kadappu KK, Abhayaratna K, Boyd A, et al. Independent
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{[}10{]} Kim SJ, Han SH, Park JT, et al. Left atrial volume is an
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{[}11{]} .Losi MA, Memoli B, Contaldi C ,et al. Myocardial fibrosis and
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{[}12{]} Boyd AC, Richards DA, Marwick T, et al. Atrial strain rate is a
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{[}13{]} Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart
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{[}14{]} Shuji H, Hirotsugu Y, Mika B, et al: Optimal analysis of left
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SUPPORTING INFORMATION

Additional supporting information may be found online in the Supporting
Information section at the end of the article.

\textbf{Figure 1.} Points used to determine longitudinal lines.

\textbf{Figure 2.} Points used to determine circumferential lines.

\textbf{Figure 3.} Set landmark on the basis of the mitral valve

\textbf{Figure 4.} Edit left atrial endocardial border by review stage

\textbf{Figure 5.} The results are displayed in worksheet and volume

\textbf{Table 1.} Baseline characteristics of the study population

\textbf{Table 2.} Conventional Echocardiography Variables of Healthy
Individuals and Dialysis Patients

\textbf{Table 3.} Left Atrium Functional and Structural Parameters

\textbf{Table 4.} Multivariate analysis for 3D left atrial function and
2D conventional echocardiographic variables in ESRD\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

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\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

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