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\begin{document}

\title{Left Ventricular Strain in Neonates using 2-dimensional speckle
tracking: Normal range and relation with bi-plan Ejection fraction.}



\author[1]{Khaled Al Nahili}%
\author[1]{Irfan Saleem}%
\author[1]{Salim Ahmad}%
\author[1]{El Tayeb Ahmed}%
\author[1]{Najlaa Al Rajaa}%
\affil[1]{Prince Sultan Cardiac Center}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Objectives:} Echocardiographic assessment of Left ventricular
systolic function is traditionally being performed by estimation of
fractional shortening and Ejection fraction. Speckle tracking
echocardiography (STE) is a promising tool for assessment of myocardial
function. The aim of this study is to evaluate the global longitudinal
strain (GLS) using 2D-STE in healthy neonates to establish normal
reference ranges. \textbf{Method:} it is a retrospective study through
an analysis of transthoracic echocardiogram of normal healthy neonates.
We enrolled all neonates in our institution from 1 \textsuperscript{st}
January 2021 to 28 \textsuperscript{th} February 2021. 2-D STE was used
to assess left ventricular global longitudinal strain from the apical
views. \textbf{Results:} 185 neonates were enrolled. Mean value for left
ventricle GLS (\%) was -19.9 \selectlanguage{ngerman}± 1.2, GLS-derived ejection fraction (\%)
was 60.0 ± 2.7; while the left ventricle ejection fraction by biplane
Simpson's method (\%) was 61.0 ± 3. There is a good positive correlation
between the Left Ventricle EF by biplane Simpson's method and EF by 2-D
STE, which was statistically significant ( \emph{r} = 0.294,~ \emph{n}~=
102,~ \emph{p}=0.003). Apical 4-chamber longitudinal strain and strain
derived EF is significantly correlated with GLS and bi-plan EF
respectively. \textbf{Conclusion:} 2-STE is feasible technique for
analyzing newborn myocardial systolic function. The normal range of GLS
in neonates is not much different than reported for the pediatric. There
is a good positive correlation between the Left Ventricle EF by 2-D STE
and EF by biplane method.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Left Ventricular Strain in Neonates using 2-dimensional speckle
tracking: Normal range and relation with bi-plan Ejection fraction.}

\textbf{Authors}

Khaled Al Nahili\textsuperscript{1,2}, Irfan Saleem\textsuperscript{1}.
Salim Ahmad\textsuperscript{1}, El Tayeb Ahmed\textsuperscript{1},
Najlaa Al Rajaa\textsuperscript{1}.

\textbf{Affiliations}

\textsuperscript{1} Pediatric cardiology Department, Prince Sultan
Cardiac Center, Riyadh, KSA

\textsuperscript{2} Khamis Mushait maternity and children hospital,
Aseer, KSA

\textbf{Corresponding Author:}

Khaled Al Nahili

Pediatric cardiology Department

Prince Sultan Cardiac Center

Riyadh, KSA

Email: khaled.059@hotmail.com

Tel:+966114783000- Ext:88793

Number of text pages: 25

Number of words: 4210

Reference pages: 3

Tables: 4

Figures\textbf{:} 3

All data of this study are available on Xcelera R3.3 cardiology PACS
system at Prince Sultan Cardiac Center, Riyadh, KSA

\textbf{Abstract:}

\textbf{Objectives:} Echocardiographic assessment of Left ventricular
systolic function is traditionally being performed by estimation of
fractional shortening and Ejection fraction. Speckle tracking
echocardiography (STE) is a promising tool for assessment of myocardial
function. The aim of this study is to evaluate the global longitudinal
strain (GLS) using 2D-STE in healthy neonates to establish normal
reference ranges.

\textbf{Method:} it is a retrospective study through an analysis of
transthoracic echocardiogram of normal healthy neonates. We enrolled all
neonates in our institution from 1\textsuperscript{st} January 2021 to
28\textsuperscript{th} February 2021. 2-D STE was used to assess left
ventricular global longitudinal strain from the apical views.

\textbf{Results:} 185 neonates were enrolled. Mean value for left
ventricle GLS (\%) was -19.9 \selectlanguage{ngerman}± 1.2, GLS-derived ejection fraction (\%)
was 60.0 ± 2.7; while the left ventricle ejection fraction by biplane
Simpson's method (\%) was 61.0 ± 3. There is a good positive correlation
between the Left Ventricle EF by biplane Simpson's method and EF by 2-D
STE, which was statistically significant (\emph{r} = 0.294,~\emph{n} ~=
102,~\emph{p} =0.003). Apical 4-chamber longitudinal strain and strain
derived EF is significantly correlated with GLS and bi-plan EF
respectively.

\textbf{Conclusion:}

2-STE is feasible technique for analyzing newborn myocardial systolic
function. The normal range of GLS in neonates is not much different than
reported for the pediatric. There is a good positive correlation between
the Left Ventricle EF by 2-D STE and EF by biplane method.

\textbf{Key words:} Infant myocardial strain, global longitudinal
function, left ventricular function, echocardiography

\textbf{1 Introduction:}

With advancement in technology, echocardiographic evaluation of cardiac
function is rapidly changing, and newer promising techniques are being
identified. The traditional tools for assessment of left ventricular
function are fractional shortening (FS) and ejection fraction (EF).

Fractional shortening (FS) includes assessment of maximum dimensional
changes of the left ventricular cavity in diastole and systole in
relation to the end diastolic dimension. Normal values for FS in infants
and pediatrics has been established and are typically between
28-46\%\textsuperscript{(1, 2)}

Ejection fraction, on the other hand, is calculated via assessing
volumetric changes of the left ventricular cavity between diastole and
systole in relation to end diastolic volume.

Both modalities (FS and EF) encounter several challenges related to
assumption of left ventricular geometry. Both are pressure dependent,
and they are not accurate in estimating LV function in case of
myocardial regional dyskinesia and in case of paradoxical motion of the
interventricular septum. Moreover, FS and EF mainly assess
circumferential fiber shortening and did not consider the longitudinal
motion of the LV.

Myocardial strain is a relatively new echocardiographic tool using
speckle tracking echocardiography (STE). It has been successfully used
in adult population to evaluate the regional and global systolic
function of the left ventricle. This technique consists of
frame-by-frame tracking of the ultrasound signals of the myocardial
speckles. Strain is a dimensionless parameter representing the
deformation of an object, in relation to its original shape. It is
expressed as percent change from the original dimension.

\(Strain\ (s)=\frac{L1-L0}{L0}\)

Where S is the longitudinal strain, L1 is the length at a given point of
time, and L0 is the baseline length.

Adapting this ultrasound tool in pediatrics and particularly in neonates
faces many problems including small heart size and fast heart rate.
Nevertheless, some studies have been performed in pediatrics and showed
relatively good reproducibility and feasibility. This is mainly due to
the fact that the investigation could be adjusted at higher frame rate
and the independency of the STE from the angle of incidence in contrast
to tissue Doppler derived signals which have shown to be angle
dependent. \textsuperscript{(3)}

Another advantage of STE is the ability to assess longitudinal motion of
the left ventricle, in contrast to fractional shortening and ejection
fraction which assess only the circumferential fiber shortening and
radial thickening. This is particularly important, as some cardiac
lesions are known to affect longitudinal motion of the left ventricle
before it progress to global systolic dysfunction \textsuperscript{(4,
5)} Therefore, it is important to establish a diagnostic tool to assess
longitudinal function of the LV to detect early signs of functional
impairment. The utility of STE in assessing the left ventricular
longitudinal motion was studied in adult and pediatric population,
however, only few studies with small patient number have documented the
utility of speckle tracking echocardiography in assessment of myocardial
longitudinal strain in neonates. \textsuperscript{(6, 7, 8)} The aim of
our study is to evaluate 2-DTE longitudinal strain of the left ventricle
in neonates, to establish the reference values for our population and to
compare the global longitudinal strain-derived EF to the commonly used
tools for assessment of left ventricular systolic function (FS and EF).

\textbf{2: Method:}

\textbf{2. 1: Study design:}

We conducted a retrospective study through analysis of the offline
measurements obtained from 2D transthoracic echocardiographic images of
normal healthy neonates. We enrolled all neonates from the post -natal
ward in Prince Sultan Military Medical city (PSMMC) in Riyadh who were
referred to pediatric cardiology service for evaluation over the period
from 1\textsuperscript{st} January 2021 to
28\textsuperscript{th}February 2021.

\textbf{2. 2: Study population:}

A total of 185 neonates were eligible for study enrollment during this
period. Subjects were eligible for inclusion if they were born term
(37-42 weeks), birth weight above 2.2 kg, normal vital signs and
12-leads ECG for age and normal cardiac structure on echocardiography
examination except for hemodynamically insignificant small patent ductus
arteriosus or small atrial septal defect /patent foramen ovalle.
Exclusion criteria are neonates with significant structural heart
lesions or abnormal cardiac rhythm on 12-leads ECG. Seventeen babies
were excluded due to presence of significant congenital heart lesion and
three babies were excluded due to abnormal electrical cardiac rhythm.
(Figure 1). Another 63 patients were excluded due to suboptimal
echocardiographic image quality i.e. ECG not connected during the study
or missing of any of the required apical views: apical 4-chamber view,
apical 3 chamber view and apical 2 chamber view.

Demographic data for the participants were documented and complete
transthoracic echocardiography study was done for each of them.

\textbf{2. 3: Echocardiography:}

Transthoracic echocardiographic study was performed for the neonates
using IE 33 platform scanner (Philips Medical ultrasound systems,
Washington, USA). Matrix-array transducer (S12) and (S8) were used for
the 2D, M Mode and Doppler study. The studies were performed without
sedation with babies asleep or suckling on bottle of milk.

Studies included recording of apical four chamber, three chamber and two
chamber 2D views for quantification of global longitudinal strain and
calculating ejection fraction. M-mode was used in parasternal short axis
views for calculating fractional shortening. Images were stored in
digital format for off-line analysis. The echocardiograms were
downloaded to Xcelera R3.3 Cardiology PACS system (Philips Medical
ultrasound systems, Washington, USA) and were analyzed and reported
offline.

\textbf{2.3.1: Speckle tracking strain imaging:}

Speckle tracking strain analysis was used to assess left ventricular
longitudinal strain. We performed the offline analysis using 2-D images
from apical four chamber, three chamber and two chamber views to
quantify the global longitudinal strain (GLS) using the Xcelera Q-Lab
software. Images were selected to find clear myocardial border with
frame rate between 100-140 fps. The echo contrast for the selected
images was adjusted and manual tracing of the endocardial border at end
diastole was performed to set the region of interest (ROI). The operator
identifies and selects the hinge points of the mitral valve annulus and
LV apex. The software allows a semi-automated detection of the LV
borders. The system allows manual adjustment of the endocardial and
epicardial surfaces.

Initially a 3-chamber view is selected; the first step is to select a
point just below the aortic valve, then lateral hinge point of the
mitral valve annulus and lastly the LV apex. The ROI is then
automatically analyzed by the software and divided into six segments as
well as the Aortic valve closure time for further analysis. The process
is followed for the apical 4-chamber view with 3 points selections at
the hinge points of the MV annulus and LV apex. In the 4-ch view, the
six segments represent the basal, mid and apical segments of the left
ventricular lateral wall and inter ventricular septum. Similar steps
were applied to obtain speckle tracking of apical two chamber views.

Data from speckle tracking were displayed in longitudinal time-strain
curves for each of the six segments and segmental peak strain was
obtained from each curve. The peak longitudinal strain was defined as
the most negative strain value at any time point during cardiac cycle.
The mean strain of the of six segments were calculated to yield the
strain value of that specific view. Aortic valve closure time and GLS is
obtained in the apical 3-chamber view while GLS and EF are displayed
numbers from the 4-chamber and 3-chamber views. The software then
calculates the cumulative GLS as the average longitudinal strain value
for the readings obtained from all the three views; and is displayed as
bull eye pattern with 16 segment distributions.\textsuperscript{(12,13)}
(Figure 2)

\textbf{2.3.2: Ejection fraction:}

Left ventricular ejection fraction was calculated from apical four and
two chamber views using biplane disc summation method (Modified Simpsons
method) by tracing the endocardial border manually at end-diastole and
end-systole (planimetry). Ejection fraction was calculated using the
following formula:

\begin{equation}
\text{EF}=\ \ \frac{EDV-ESV}{\text{EDV}}\text{\ \ }X\ \ \ 100\nonumber \\
 \end{equation}

Where EDV represent left ventricular end-diastolic volume, ESV
represents left ventricular end-systolic volume

\textbf{2.3.3: M-mode:}

\begin{equation}
FS\ \%=\ \ \frac{EDD-ESD}{\text{EDD}}\text{\ \ }X\ \ \ 100\nonumber \\
 \end{equation}

\textbf{3. Statistical Analysis:}

The data was analyzed using SPSS software version---- . Descriptive
analysis was used to summarize data. Continuous variables were expressed
as means \selectlanguage{ngerman}± standard deviation with their minimum and maximum values.
Categorical variables were presented as counts and percentages.
Comparison between groups was performed by independent Students T-test
for continuous data or Pearson's chi-square test for categorical data.

\textbf{4. Results:}

The study population comprised of 102 neonates; mean age 1.5±0.8 days
(Min:1 day, Max:5 days), 65 (63.7\%) were age 1 day old at time of echo
and 59 (57.8\%) neonates were males. Atrial septal defect vs. patent
foramen ovale were found in 67 neonates (65.7\%) (Table 1).

Averaged GLS (\%) was -19.9 ± 1.2 while GLS-derived ejection fraction
(\%) was 60.0 ± 2.7(Table 2).

Fractional shortening (\%) was 34± 3. EF using Biplane Simpsons method
(\%) 61.0 ± 3,

A Pearson correlation was used to determine the relationship between LV
EF by biplane Simpson's method and Left Ventricle EF by strain. There is
a small positive correlation between the LV EF by biplane and LV EF by
strain which was statistically significant (\emph{r} ~= 0.294,~\emph{n}
~= 102,~\emph{p} =0.003). On the other hand, there is a small negative
correlation between the FS and LV EF by strain which shows inconclusive
evidence about the significance of the association between the variables
(\emph{r} ~= -0.142,~\emph{n} ~= 102,~\emph{p} =0.). Apical 4-chamber
strain and 4-chamber strain-derived EF was significantly correlated with
GLS and GLS-derived EF (\emph{r} ~= 0.756 ,~\emph{n} ~=102,
p\textless{}0.001) and (r = 0.735 , n = 102, p\textless{}0.001.)
respectively . Additionally, there is weak but statistically significant
correlation between 4-ch strain-derived EF and biplane Simpson EF (r =
0.204 , n = 102, p=0.039) (Table 3). Comparison of demographic data and
echo variables showed no significant difference between male and female
(Table 4). By using linear regression analysis, there was a small
positive correlation between average EF by biplane method and EF by
strain, which was statistically significant (\emph{R\textsuperscript{2}}
~= 0.087,~\emph{p} =0.003) (Figure 3)

\textbf{5. Discussion:}

The deformation imaging using speckle tracking echocardiography is used
as tool of assessment of the LV function in the diagnosis and management
of several cardiopulmonary diseases in children. The ASE and EACVI
guidelines consider STE derived GLS as feasible and reproducible for
routine clinical use.

The normal reference range of values for 2DSTE-derived LV LS in
pediatric and adult population has been described by many
authors\textsuperscript{.} The reference range of values for 2DSTE and
3DSTE derived LV LS, in neonatal age has been reported in few studies
and that with limited enrollment. \textsuperscript{(13)} This study
establishes reference ranges of values of LV global LS in a cohort of
102 normal full-term neonates.

This is a retrospective study, and we enrolled all neonates with
transthoracic echocardiograms during the period of study. These were all
routine 2-d echocardiographic studies and some of them did not have all
the three apical views in particular the 2-chamber view which is
sometimes technically demanding. Therefore, we had to drop many studies
from inclusion. We performed the M-Mode analysis to get FS and EF and
also the EF by bi-plan Simpson's method to make sure that all the
enrolled population have normal function by conventional methods, so
that our 2DSTE analysis would truly indicate a dependable reference for
normal neonates.

Our study revealed fractional shortening that ranges between 27 and 42
\% (mean 34± 3) which is correlated well with several studies performed
in neonates. Similarly, Biplane Simpson method-derived ejection fraction
was ranging between 55 and 73\% (mean 61± 3).

The volume-based measurements of left ventricular function are different
from direct measurement of myocardial motion by myocardial deformation
(strain) using speckle tracking echocardiography. Our study revealed
myocardial global longitudinal strain in normal healthy neonates ranging
from -13.5 to -22.9 \% (mean -19.9- ± 1.2), (Table 3). These values are
correlated well with the values presented by Jashari et al, in their
meta-analysis for normal ranges of left ventricular strain in children
and neonates when they found normal values between --12.9 and 26.5\%
(mean -20.5\%).\textsuperscript{(9,14)}

Most of the studies reported longitudinal strain, an extremely sensitive
sign of deteriorating LV systolic function especially in neonates with
aortic valve stenosis, aortic coarctation or hypertrophic obstructive
cardiomyopathy. Therefore, establishing normal values and routine
performance of myocardial longitudinal strain is crucial on those
patients to predict the early signs of myocardial
dysfunction.\textsuperscript{(9, 15)}

Our study shows that 2D-STE analysis is feasible in neonatal period. We
observed a positive correlation between Biplane Simpson method-derived
ejection fraction and myocardial strain-derived ejection fraction in
healthy neonates (Table 3). This may suggest potential advantage of
using myocardial strain-derived EF over the volumetric-based EF which is
load dependent as well as geometry-dependent compared to myocardial
strain.

Performing GLS for the left ventricle necessitate assessment of LV
myocardial strain in all the three views for the LV; 4-ch, 3-ch and 2
chambers views which is felt by some practitioners to be time consuming
process. Despite all the advantages of the technique for performing LV
myocardial strain assessment, we modeled to evaluate whether apical
4-chambers view alone could be a reasonable reflector for the LV global
longitudinal strain. We observed a statistically significant correlation
between 4-ch longitudinal strain and the cumulative GLS for the left
ventricle, (Table 3)

Moreover, 4ch 2DSTE derived EF was significantly correlated with
GLS-derived EF as well as the EF calculated by biplane Simpson method.
These observations of the 2DSTE apical 4-chambers values may suggest the
usefulness of 4 chamber view alone to be a good reflector for the GLS
instead of performing all the three views for the left ventricle (in
patients with missing 3 chamber or 2 chamber apical views). This would
make it possible to get the quantification of LV longitudinal strain
from the apical 4 chamber view alone and then to follow that very
patient with the same parameters to detect any change in myocardial
function. It is easy to perform, and post-processing time has decreased
with the newer automated systems.

\textbf{6. Limitations:}

Our study is a single-center experience. Although our study of left
ventricular GLS has the largest of the published neonatal cohort, still
the limited number of participants would have been acceptable.

We analyzed the apical views only to assess Global Longitudinal Strain.
Assessing left ventricular circumferential and radial strain would add
more information to the understanding the LV strain.

\textbf{7. Ethical Standard:}

An ethical approval for this study was approved from ethical approval
committee in PSCC research department. All authors had no conflict of
interest. This research did not receive any funds.

\textbf{8. Conclusion:}

Speckle tracking echocardiography is feasible technique for analyzing
newborn myocardial systolic function. This study revealed the mean
reference value for GLS -19.9 ± 1.2 and strain-derived EF 60 ±
2.7.Apical 4-chamber 2DSTE derived values for LV -LS and LV-EF may be
used as a reasonable representative of the GLS and EF. Further
prospective studies that include larger number of patients is needed to
evaluate this novel modality and to compare the reference ranges to
pediatric and adult population. follow up for those newborns is needed
to evaluate the changes of myocardial strain as they grow up.

\textbf{Authors contributions:} Dr. K. Alnahili performed data
collection and acquisition. Dr. S. Ahmad conceived the idea of the
project and designed the final revision of the manuscript. Dr. N. Al
raja assigned for data analysis and interpretation. Dr. E. Ahmed and Dr.
I. Saleem contributed in writing and editing the manuscript.

\textbf{References:}

(1) Gutgesell HP, Paquet M, Duff DF, McNamara DG: Evaluation of left
ventricular size and function by echocardiography. Results in normal
children. \emph{Circulation} (1977) 56:457--62. Doi: Doi:
10.1161/01.CIR.56.3.457

(2) , L.I.H. Overbeek, L. Kapusta: New reference values for
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(3) Matsui H, Germanakis I, Kulinskaya E, Gardiner HM: Temporal and
spatial performance of vector velocity imaging in the human fetal heart.
Ultrasound Obstet Gynecol 2011 ;37 :150--7.

(4) Marcus KA, de Korte CL, Feuth T, et al: Abnormal two-dimensional
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(5) Marcus KA, de Korte CL, Feuth T, et al: Persistent reduction in left
ventricular strain using two-dimensional speckletracking
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25:473--485.

(6) C Bussadori, A Moreo, M Di Donato: A new 2D-based method for
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doi:10.1186/1476-7120-7-8

(7) Annelies E van der Hulst\textsuperscript{~},~Victoria Delgado:
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(8) Marcus KA, Mavinkurve-Groothuis AM, Barends M,van A Dijk, et al:
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(9) Haki Jashari, Annika Rydberg, Pranvera Ibrahimi, et al: Normal
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Cardiovascular Ultrasound (2015). DOI: 10.1186/s12947-015-0029-0

(10) Lang RM, Badano LP,Mor-Avi V, et al: Recommendations for cardiac
chamber quantification by echocardiography in adults: An update from the
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(11) Lai WW, Geva T, Shirali GS, et al: Guidelines and standards for
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(12) Jens-Uwe Voigt, Gianni Pedrizzetti, Peter Lysyansky, et al:
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1-11.Doi.org/10.1093/ehjci/jeu184

(13) Holly Geyer, Giuseppe Caracciolo, Haruhiko Abe, et al: Assessment
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http://dx.doi.org/10.1016/j.echo.2015.11.016

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10.1186/1476-7120-11-34

\textbf{Table} \textbf{I:} Baseline demographic and clinical
characteristics of 102 neonates enrolled in this study:\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Variables} & \textbf{Values}\tabularnewline
\midrule
\endhead
\textbf{Demographic Data} &\tabularnewline
Age (days) & 1.5 \selectlanguage{ngerman}± 0.8\tabularnewline
Male, n\% & 59 (57.8)\tabularnewline
Female, n\% & 43 (42.2)\tabularnewline
Weight (kg) & 3.2 \selectlanguage{ngerman}± 0.5\tabularnewline
Height (cm) & 50.0 \selectlanguage{ngerman}± 2\tabularnewline
BSA (m\textsuperscript{2}) & 0.2 \selectlanguage{ngerman}± 0.08\tabularnewline
\textbf{Reason for referral} &\tabularnewline
FH CHD & 23 (22.5)\tabularnewline
IDM & 14 (13.7)\tabularnewline
Murmur & 64 (62.7)\tabularnewline
Fetal echo showing echogenic foci & 2 (2.0)\tabularnewline
\textbf{Findings} &\tabularnewline
ASD vs. PFO & 67 (65.7)\tabularnewline
Closing PDA & 30 (29.4)\tabularnewline
Normal & 5 (4.9)\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table} \textbf{II:} Echocardiographic characteristics of the
study population\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\textbf{Variables} & \selectlanguage{ngerman}\textbf{Mean ± SD} & \textbf{SEM} &
\textbf{Variance} & \textbf{Minimum} & \textbf{Maximum}\tabularnewline
\midrule
\endhead
End diastolic diameter (cm) & 1.62 \selectlanguage{ngerman}± 0.23 & 0.022 & 0.052 & 1.12 &
2.35\tabularnewline
End systolic diameter (cm) & 1.10 \selectlanguage{ngerman}± 0.16 & 0.016 & 0.027 & 0.64 &
1.7\tabularnewline
Fractional shortening (\%) & 34 \selectlanguage{ngerman}± 3 & 0.339 & 0.1 & 27 &
42\tabularnewline
Biplane Simpson method EF (\%) & 61.0 \selectlanguage{ngerman}± 3 & 0.326 & 0.1 & 55 &
73\tabularnewline
LV 4ch strain & -20.03 \selectlanguage{ngerman}± 1.43 & 0.141 & 2.038 & -23.8 &
-13.5\tabularnewline
LV 3ch strain & -19.4 \selectlanguage{ngerman}± 3.6 & 0.357 & 12.977 & -22.5 &
-14.4\tabularnewline
LV 2ch strain & -19.60 \selectlanguage{ngerman}± 4.1 & 0.406 & 16.814 & -25.0 &
-17.4\tabularnewline
LV GLS & -19.9 \selectlanguage{ngerman}± 1.2 & 0.115 & 1.362 & -22.9 & -13.5\tabularnewline
Ejection fraction strain (\%) & 60.0 \selectlanguage{ngerman}± 2.7 & 0.265 & 0.1 & 52 &
67\tabularnewline
Strain rate & -0.050 \selectlanguage{ngerman}± 0.003 & 0.0003 & 0.00 & -0.074 &
-0.044\tabularnewline
\bottomrule
\end{longtable}

\textbf{LV} left ventricle, \textbf{GLS} global longitudinal
strain,\textbf{SEM} standard error of the mean

\textbf{Table III:} Correlations between Fractional shortening (FS),
ejection fraction (EF) and longitudinal strain EF:\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{A)}

A Pearson correlation was used to determine the relationship between
fractional shortening and left ventricular ejection fraction by strain.
There is a small negative correlation between the FS and LV EF by strain
which shows inconclusive evidence about the significance of the
association between the variables (\emph{r} ~= -0.142,~\emph{n} ~=
102,~\emph{p} =0.).

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

\end{center}
\end{figure}

A Pearson correlation was used to determine the relationship between LV
EF by biplane Simpsons method and LV EF by strain. There is a small
positive correlation between the LV EF by biplane and LV EF by strain
which was statistically significant (\emph{r} ~= 0.294,~\emph{n} ~=
102,~\emph{p} =0.003).

\textbf{C)}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

A Pearson correlation was used to determine the relationship between LV
4 chamber strain versus LV global longitudinal strain. There is a
moderate positive correlation between the LV4 chamber strain and LV GLS
which is statistically significant (\emph{r} ~= 0.756 ,~\emph{n} ~=
102,~\emph{p} \textless{}0.001.).

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

\end{center}
\end{figure}

A Pearson correlation was used to determine the relations hip between 4
chamber EF and LV EF by strain. There is a moderate, positive
correlation between the two variables which was statistically
significant. (\emph{r} ~= 0.735 ,~\emph{n} ~= 102,~\emph{p}
\textless{}0.001.).

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

\end{center}
\end{figure}

A Pearson correlation was used to determine the relationship between 4
chamber EF and LV EF by biplane. There is weak, positive correlation
between the two variables which is statistically significant (\emph{r}
~= 0.204,~\emph{n} ~= 102,~\emph{p} =0.039.).

\textbf{Table IV:} Comparison of demographic data and echo variables
between male and female:\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Variable} & \textbf{Male (n=59)} & \textbf{Female (n=43)} &
\textbf{p-value}\tabularnewline
\midrule
\endhead
Age (days) & 1.51 \selectlanguage{ngerman}± 0.751 & 1.45 \selectlanguage{ngerman}± 0.861 & 0.729\tabularnewline
Male, n\% & & &\tabularnewline
Female, n\% & & &\tabularnewline
Weight (kg) & 3.246 \selectlanguage{ngerman}± 0.479 & 3.078 \selectlanguage{ngerman}± 0.582 & 0.113\tabularnewline
Height (cm) & 50.1 \selectlanguage{ngerman}± 1.98 & 49.81 \selectlanguage{ngerman}± 1.98 & 0.470\tabularnewline
BSA (m\textsuperscript{2}) & 0.211 \selectlanguage{ngerman}± 0.097 & 0.187 \selectlanguage{ngerman}± 0.042 &
0.136\tabularnewline
\textbf{Echo variables} & \textbf{Echo variables} & \textbf{Echo
variables} & \textbf{Echo variables}\tabularnewline
End diastolic diameter (mm) & 1.62 \selectlanguage{ngerman}± 0.242 & 1.61 \selectlanguage{ngerman}± 0.208 &
0.745\tabularnewline
End systolic diameter (mm) & 1.07 \selectlanguage{ngerman}± 0.171 & 1.04 \selectlanguage{ngerman}± 0.155 &
0.336\tabularnewline
Fractional shortening (\%) & 33.78 \selectlanguage{ngerman}± 3.348 & 33.58 \selectlanguage{ngerman}± 3.554 &
0.774\tabularnewline
Biplane Simpson EF (\%) & 60.92 \selectlanguage{ngerman}± 3.454 & 61.20 \selectlanguage{ngerman}± 3.725 &
0.681\tabularnewline
LV 4ch strain & -19.90 \selectlanguage{ngerman}± 1.57 & -20.21 \selectlanguage{ngerman}± 1.209 & 0.284\tabularnewline
LV 3ch strain & -19.20 \selectlanguage{ngerman}± 4.603 & -19.65 \selectlanguage{ngerman}± 1.355 & 0.544\tabularnewline
LV 2ch strain & -19.58 \selectlanguage{ngerman}± 5.30 & -19.62 \selectlanguage{ngerman}± 1.278 & 0.962\tabularnewline
LV GLS & -19.93 \selectlanguage{ngerman}± 1.37 & - 19.81 \selectlanguage{ngerman}± 0.81 & 0.614\tabularnewline
Ejection fraction strain (\%) & 59.79 \selectlanguage{ngerman}± 2.530 & 60.26 \selectlanguage{ngerman}± 2.879 &
0.393\tabularnewline
Strain rate & -0.051 \selectlanguage{ngerman}± 0.004 & -0.051 \selectlanguage{ngerman}± 0.002 & 0.920\tabularnewline
\bottomrule
\end{longtable}

\textbf{FIGURE 1:} Cohort flowchart of neonates assessed in the study.

\textbf{Inclusion criteria:}

Full term (37-41weeks)

Birth weight \textgreater{} 2.2 kg

Normal vital signs for age

Normal ECG

Normal cardiac structure

\textbf{Figure 2:} Demonstration of longitudinal strain using 2D-Speckle
Tracking Echocardiography.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

\end{center}
\end{figure}

\textbf{Figure 3:} Relationship between average EF by strain and by
biplane method among all patients included in the study.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

\end{center}
\end{figure}\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}

