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\begin{document}

\title{PROGNOSTIC VALUE OF DIASTOLIC FUNCTION PARAMETERS IN SIGNIFICANT AORTIC
REGURGITATION. THE ROLE OF THE LEFT ATRIAL STRAIN.}



\author[1]{Ana Garcia-Martin}%
\author[2]{María Abellás}%
\author[3]{Ariana González Gómez}%
\author[4]{Luis Rincon Diaz}%
\author[2]{Juan Manuel Monteagudo-Ruiz}%
\author[5]{Rocio Hinojar-Baydes}%
\author[6]{Jose Luis Moya Mur}%
\author[5]{Jose Zamorano}%
\author[5]{Covadonga Fernandez-Golfin}%
\affil[1]{Affiliation not available}%
\affil[2]{Hospital Universitario Ramon y Cajal}%
\affil[3]{University Hospital Ramón y Cajal}%
\affil[4]{Hospital Clinico de Salamanca}%
\affil[5]{Ramon y Cajal University Hospital}%
\affil[6]{Hospital Universitario Ramón y Cajal}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Aims. The management of patients with asymptomatic significant aortic
regurgitation (sAR) is often challenging and appropriate timing of
aortic valve surgery remains controversial. Prognostic value of
diastolic parameters has been demonstrated in several cardiac diseases.
In particular, left atrial (LA) function has been shown to be an
important determinant of morbimortality. The purpose of this study was
to analyze the prognostic significance of diastolic function in
asymptomatic patients with sAR. Methods and results. A total of 126
patients with asymptomatic sAR were included. Conventional
echocardiographic systolic and diastolic function parameters were
assessed. LA auto-strain analysis was performed in a subgroup of 57
patients. During a mean follow up of 33\selectlanguage{ngerman}±19 months, 25 (19,8\%) patients
reached the combined end-point. Univariate analysis showed that LV
volumes, LVEF, E wave, E/e' ratio, LA volume and LA reservoir strain
(LASr) were significant predictors of events. Multivariate model 1 that
tested all echocardiographic variables statistically significant in the
univariate model showed that LVEDV {[}HR=1,02;95\% CI:1,01-1,03
(p\textless{}0,001){]} and E/e' ratio {[}HR=1,12;95\% CI:1,03-1,23
(p=0,01){]} were significant predictors of events. In the subgroup of
patients with LA auto-strain analyzed, a second multivariate model
including the previous significant variables for the first model as well
as LASr, showed that LVEDV {[}HR=1,05;95\% CI:1,01-1,08 (p=0,016){]} and
LASr {[}HR=0,8;95\% CI:0,65-0,98 (p\textless{}0,035){]} were the most
significant predictors of cardiovascular events. Conclusions. In this
population of asymptomatic patients with sAR and normal LV systolic
function, baseline diastolic parameters were prognostic markers of
cardiovascular events; among them, LASr played a strong independent
predictor role.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{PROGNOSTIC VALUE OF DIASTOLIC FUNCTION PARAMETERS IN SIGNIFICANT
AORTIC REGURGITATION. THE ROLE OF THE LEFT ATRIAL STRAIN.}

Ana Garc\selectlanguage{ngerman}ía Martín MD, PhD\textsuperscript{1}, María Abellás Sequeiros
MD\textsuperscript{1}, Ariana González Gómez MD\textsuperscript{1}, Luis
Miguel Rincón Díaz MD\textsuperscript{2}, Juan Manuel Monteagudo Ruiz
MD\textsuperscript{1}, Rocío Hinojar Baydés MD, PhD\textsuperscript{1},
Jose Luis Moya Mur MD, PhD\textsuperscript{1}, José Luis Zamorano Gómez
MD, PhD\textsuperscript{1}, Covadonga Fernández-Golfín MD,
PhD\textsuperscript{1}.

\textsuperscript{1}Department of Cardiology. Ramón y Cajal University
Hospital. Madrid. Spain. CIBER CV.

\textsuperscript{2}Department of Cardiology. University Hospital.
Salamanca. Spain.

Address:

Ana García Martín. Department of Cardiology. Ramón y Cajal University
Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain. Telephone
number: +34913368259. E-mail:\emph{aggarciamartin@gmail.com}

María Abellás Sequeiros. Department of Cardiology. Ramón y Cajal
University Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain.
Telephone number: +34913368259. E-mail: maine.iaca@gmail.com

Ariana González Gómez. Department of Cardiology. Ramón y Cajal
University Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain.
Telephone number: +34913368259. E-mail: arianaglz@hotmail.com

Luis Miguel Rincón Díaz. Department of Cardiology. University Hospital.
Salamanca. Spain. E-mail:\emph{lmrincondiaz@hotmail.com}

Juan Manuel Monteagudo Ruiz. Department of Cardiology. Ramón y Cajal
University Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain.
Telephone number: +34913368259. E-mail: j5469m@gmail.com

Rocío Hinojar Baydés. Department of Cardiology. Ramón y Cajal University
Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain. Telephone
number: +34913368259. E-mail: rociohinojar@gmail.com

José-Luis Moya-Mur. Department of Cardiology. Ramón y Cajal University
Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain. Telephone
number: +34913368259. E-mail: joseluis.moya@salud.madrid.org

Covadonga Fernández-Golfín. Department of Cardiology. Ramón y Cajal
University Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain.
Telephone number: +34913368259. E-mail: covagolfin@yahoo.es

José Luis Zamorano-Gómez. Department of Cardiology. Ramón y Cajal
University Hospital. Ctra. Colmenar Km 9,100. 28034 Madrid, Spain.
Telephone number: +34913368259. E-mail: zamorano@secardiologia.es

\textbf{ABSTRACT.}

\textbf{Aims.}

The management of patients with asymptomatic significant aortic
regurgitation (sAR) is often challenging and appropriate timing of
aortic valve surgery remains controversial. Prognostic value of
diastolic parameters has been demonstrated in several cardiac diseases.
In particular, left atrial (LA) function has been shown to be an
important determinant of morbimortality. The purpose of this study was
to analyze the prognostic significance of diastolic function in
asymptomatic patients with sAR.

\textbf{Methods and results.}

A total of 126 patients with asymptomatic sAR were included.
Conventional echocardiographic systolic and diastolic function
parameters were assessed. LA auto-strain analysis was performed in a
subgroup of 57 patients. During a mean follow up of 33±19 months, 25
(19,8\%) patients reached the combined end-point. Univariate analysis
showed that LV volumes, LVEF, E wave, E/e' ratio, LA volume and LA
reservoir strain (LASr) were significant predictors of events.
Multivariate model 1 that tested all echocardiographic variables
statistically significant in the univariate model showed that LVEDV
{[}HR=1,02;95\% CI:1,01-1,03 (p\textless{}0,001){]} and E/e' ratio
{[}HR=1,12;95\% CI:1,03-1,23 (p=0,01){]} were significant predictors of
events. In the subgroup of patients with LA auto-strain analyzed, a
second multivariate model including the previous significant variables
for the first model as well as LASr, showed that LVEDV {[}HR=1,05;95\%
CI:1,01-1,08 (p=0,016){]} and LASr {[}HR=0,8;95\% CI:0,65-0,98
(p\textless{}0,035){]} were the most significant predictors of
cardiovascular events.

\textbf{Conclusions.}

In this population of asymptomatic patients with sAR and normal LV
systolic function, baseline diastolic parameters were prognostic markers
of cardiovascular events; among them, LASr played a strong independent
predictor role.

\textbf{KEYWORDS.}

Echocardiography, aortic regurgitation, diastolic function, strain.

\textbf{ABBREVIATIONS.}

AUC: Area under the curve.

LA: Left Atrial.

LASct: Left atrial strain contractile.

LASr: Left atrial strain reservoir.

LAScd: Left atrial strain conduit.

LV: Left ventricle.

LVEF: Left ventricle ejection fraction.

sAR: Significant aortic regurgitation.

SPAP: Systolic pulmonary artery pressure.

TTE: Transtoracic echocardiography.

TR: Tricuspid regurgitation.

\textbf{INTRODUCTION.}

The management of patients with asymptomatic significant aortic
regurgitation (sAR) is often challenging and appropriate timing of
aortic valve surgery remains controversial.

According to the latest guidelines, among patients with sAR, surgery is
formally recommended when it causes symptoms, left ventricular ejection
fraction (LVEF) \selectlanguage{english}[?]50\% or if there is a concomitant indication for
cardiac surgery (i.e. significant enlargement of ascending aorta). In
addition, surgery should be considered in asymptomatic patients with
severe LV dilation (end-diastolic diameter \textgreater{}70mm or
end-systolic \textgreater{}50mm) (1).

There are no strong indicators to recommend early surgery in patients
with sAR, however delaying the time for the intervention could bring
potential negative consequences, such as the risk of permanent LV
dysfunction, heart failure or sudden cardiac death (2). In this context,
the identification of markers that are early altered in the natural
history of the sAR, could be useful in order to improve the management
of these asymptomatic patients.

The prognostic value of diastolic parameters has been demonstrated in
several cardiac diseases. In particular, left atrial (LA) function has
been shown to be an important determinant of morbimortality. More
specifically, LA strain is a promising tool for the detection of
subclinical cardiac dysfunction (3).

The purpose of this study was to analyze the prognostic significance of
diastolic function parameters, included LA strain, in asymptomatic
patients with sAR and to evaluate whether these parameters could help to
identify patients at high risk of adverse events that could benefit from
early cardiac surgery.

\textbf{METHODS.}

From February 2013 to November 2019 consecutive asymptomatic patients
with chronic sAR evaluated in the Heart Valve Clinic with a
comprehensive transthoracic echocardiogram (TTE) were included.

Exclusion criteria included patients who already met criteria for
cardiac surgery at the time of the inclusion (presence of symptoms, LV
dilation or dysfunction, indication for other cardiac surgery), other
concomitant significant valve disease (more than mild degree evaluated
with echocardiography), LV dysfunction, the presence of atrial
fibrillation or pacemaker rhythm.

Local Ethical Committee approved the study.

\textbf{Echocardiogram protocol analysis.}

The closest TTE study to the first medical visit in the Heart Valve
Clinic was used as baseline analysis. TTE was performed using the
commercially available echo systems in the Imaging Unit, according to
the standard protocol (7,8). Measurements were reviewed and reperformed
by trained echocardiographers.

The severity of AR was assessed using an integrated method including a
combination of several measurements (vena contracta width, pressure
half-time of the AR jet, the presence of diastolic retrograde flow in
aorta, and the LV size) according to the established practice guidelines
(9). Aortic regurgitation was considered significant by the presence of
the following criteria: the width of the vena contracta \textgreater{}
6mm, pressure half-time \textless{} 200ms, the presence of diastolic
retrograde flow in aorta and some degree of LV enlargement.

LV size was evaluated by its diameters from the parasternal long axis
view and by its volumes from the apical four chamber view. LVEF was
measured using Teicholz method and apical biplane Simpson's method.

LV diastolic function was evaluated following the established
recommendations from the American Society of Echocardiography and the
European Association of Cardiovascular Imaging (10), that included the
following parameters:

Transmitral flow was recorded by pulsed wave Doppler echocardiography,
from apical four chamber view, by placing the sample volume at the tips
of the mitral leaflets. Peak E wave velocity, peak A wave velocity, E to
A wave ratio (E/A) and E wave deceleration time were determined.

Tissue Doppler imaging was performed in the apical four chamber view and
pulsed wave Doppler sample volume was place in the septal and lateral
mitral annulus. The peak annular systolic wave velocities were recorded
(e' septal and e' lateral). From these measurements, the mitral E/e'
septal and E/e' lateral ratios were calculated, as well as the mean of
both results (E/e' ratio).

The severity of tricuspid regurgitation (TR) was assessed using an
integrated method, according to the established practice guidelines (9).
The systolic pulmonary artery pressure (SPAP) was estimated using TR
peak velocity and right atrial pressure, which was estimated by the
inferior vena cava diameter from long-axis subxiphoid view and its
response to inspiration.

LA size was measured at its antero-posterior diameter from the long axis
parasternal view in the end-systolic period, and by LA volume, that was
measured using the biplane area length method.

In a subgroup of patients with TTE performed in the Philips stations, LA
auto-strain analysis was performed with an offline workstation
(autostrain TOMTEC). From the apical four chamber view focus in the LA
with a minimum loop length of 2 beats; the software uses Advanced
Automatic View Recognition technology to identify LA and automatic
contour placement, which automatically detects and places the LA border.
The software automatically provides the measurement of the average
strain for the three major LA function throughout the cardiac cycle:
reservoir (LASr), conduit (LAScd) and contractile (LASct) values. The
reference point for deformation analysis was at end diastole (Figure 1).

\textbf{Clinical outcomes.}

Combined clinical endpoint included hospital admission due to heart
failure, cardiovascular mortality, or aortic valve surgery due to have
reached the indications for surgery and excluding those undergoing
surgery due to aortic dilatation or dissection. Clinical data was
obtained from hospital's records.

\textbf{STATISTICAL ANALYSIS.}

Continuous variables were expressed as mean +- SD. Categoric variables
were described as number and percentage. For comparison 2 normally
distributed variables, Student t test for continuous variables and
chi-squared test for categorical variables were used. The analysis was
adjusted for age and sex.

In order to evaluate diastolic parameters that could serve as early
markers of cardiovascular outcome, several statistical analyses were
performed. The following Cox regression models were constructed: a) a
univariate model with all the variables of interest collected; b) a
multivariate model including parameters currently used to indicate
surgery (LVEDV, LVESV and LVEF) and the most relevant conventional
diastolic function parameters that were statistically associated with
the composite endpoint in the univariate analysis (E, E/e' ratio and LA
volume; SPAP was excluded in the analysis because its echocardiographic
evaluation was only possible in 39 patients). The backward elimination
method was used for selection of covariates; c) for the subgroup of
patients with TTE performed in a Philips station, a second multivariate
model, including the significant variables in the previous model and LA
strain, was constructed. LASr was the LA strain parameter used for the
analysis for being the strongest LA strain parameter available with more
reliable scientific evidence.

Area under the receiver-operating characteristic curve (AUC) was used to
evaluate LASr accuracy~to predict cardiovascular events.~The
Kaplan-Meier survival curves for patients above and below the median
value of LASr were performed to summarize the follow-up experience of
the study population. Interaction was studied. This was a
hypothesis-generating and exploratory study; therefore, no formal sample
size calculation was performed in advance.

The statistical analyses were performed using SPSS software version 26.0
(SPSS Inc, Chicago, Illinois, United States) and R version 3.3.2.

\textbf{RESULTS.}

A total of 126 patients were included. Mean age of the patients was 70 +-
17,0 years. Among them, 25 (19,8\%) had bicuspid valve, 75 (59,5\%) were
men, 78 (62,4\%) had hypertension, 44 (35,3\%) suffered from
dyslipidemia and 11 (9,6\%) had concomitant coronary artery disease with
preserve LVEF.

During a mean follow up of 33+-19 months, 25 (19,8\%) patients reached
the combined endpoint (n= 5 developed heart failure, n= 25 underwent
surgery, and n= 4 died due to cardiovascular etiology).~Another 3
patients that had undergone valve surgery exclusively due to aortic
dilatation and another 7 patients that had died from an extracardiac
etiology were not included in the cardiovascular event group. Clinical
and echocardiographic characteristics of both groups (control and
cardiovascular event group) are displayed in table 1.

Univariate analysis showed that LV volumes, LVEF, E wave, E/e' ratio, LA
volume, PSAP and LASr were significant predictors of events, whereas LA
diameter and LV diastolic diameter were not. Statistical significance
was maintained in the analysis adjusted for age and sex (Table 2).
Multivariate model 1 that tested all echocardiographic variables
statistically significant in the univariate model showed that the E/e'
ratio (p= 0,01) and LVEDV (p\textless{} 0,001), were significant
predictors of events (Table 2).

In a sub-group of 57 patients LA auto-strain analysis was obtained.
During the same follow-up period, 8 (14\%) patients developed the
combined endpoint (7 patients underwent surgery, one of them developed
previous heart failure and died due to cardiovascular etiology). Another
3 patients that underwent valve surgery exclusively due to aortic
dilatation were excluded from the cardiovascular event group. In this
subgroup of patients with LA autostrain analyzed, a second multivariate
model was built, including the previous significant variables for the
first model (LVEDV and E/e' ratio) and the LASr. This model showed that
LVDEV (p= 0,016) and LASr (p= 0,035) were the most significant
predictors of cardiovascular events (Table 2).

Area under the receiver-operating characteristic (AUC) curve was used to
evaluate LASr accuracy to predict cardiovascular events (AUC= 0,78 p=
0,012) (Figure 2). Kaplan Meier curve, stratified by median value of
LASr, showed that lower LASr values (less than median of 34\%) were
associated with higher rates of events (p= 0,013) (Figure 3).

\textbf{DISCUSSION.}

In this population of asymptomatic patients with sAR and normal LV
systolic function, baseline diastolic parameters were prognostic markers
of cardiovascular events; among them, LASr played a strong independent
predictor role. In addition, our results also showed that LV volumes had
greater prognostic value that LV diameters in patients with asymptomatic
sAR.

In accordance with current clinical practice guidelines (1), aortic
valve replacement in patients with sAR should be limited to symptomatic
patients or those with LV dysfunction. However, there are possible
advantages of an early surgery in valvular heart disease in order to
prevent sudden cardiac death, persistent LV systolic dysfunction or
worse perioperative and postoperative outcomes. In addition, considering
the development of new percutaneous treatments less aggressive than
cardiac surgery, identifying those conditions associated with a worse
prognosis and who may benefit from an early intervention, seems
important.

Previous studies have analyzed the role of the diastolic function in sAR
undergoing aortic valve replacement. \emph{Ma et al} described that LV
diastolic disfunction, analyzed by the integration of 2
echocardiographic parameters (LA volume index and E/e' ratio) is highly
prevalent in patients undergoing aortic valve replacement and might
improve after surgery (11). In a similar way, \emph{Cayli et al} (12)
reported that diastolic function is a reliable parameter in predicting
outcomes in patients with sAR and LV dysfunction. They found that
preoperative diastolic disfunction had an adverse impact on the recovery
of the cardiac function after surgery and justify this finding due to
the correlation of the myocardial fibrosis and worse diastolic function.
K\emph{im et al} , also found that preoperative E/e' ratio was
correlated with postoperative improvement of LVEF (13).

To the best of our knowledge, this study is the first to evaluate the
clinical relevance of baseline diastolic function parameters in patients
with asymptomatic sAR. In our sample, E wave, E/e'ratio, SPAP and LA
size and function, have significant prognostic value in these patients.
Among the analyzed diastolic function parameters, we found that LASr
played a strong independent predictor role in outcomes, stronger than LA
diameter and LA volume. In patients with sAR, the volume and pressure
overload promote LV dilatation and eccentric hypertrophy; in this
context, LA function estimated by strain can be reduced even in the
absence of LA dilatation, mainly due to interstitial fibrosis, and
reflects LV filling pressure. In fact, LA volume has been shown to have
low sensitivity in the early detection of LA dysfunction in the setting
of LV diastolic dysfunction (14).

There are few data available on AR and LA function and its prognosis
implications. \emph{Salas Pacheco et al} (15) demonstrated that in
patients with severe aortic disease (AR and aortic stenosis) LASr was
the main variable associated with pulmonary hypertension, they
considered that the maintenance of LASr function may be one explanation
for the absence of pulmonary hypertension in some patients with severe
aortic disease. In isolated aortic stenosis, LA enlargement is
recognized as a marker of aortic stenosis severity as well as predictor
of postoperative clinical outcomes independently of mean transaortic
gradient and LV mass (16). Even more, LASr has been shown as an
independent predictor of prognosis in patients with aortic stenosis
(17).

We used automated quantification technique for the LA strain assessment,
which has the potential advantages of time saving and greater accuracy
and reproducibility of the measurements (18). Its implementation could
lead to simplify these measurements, making it possible to obtain the
deformation parameters in the daily clinical practice.

Finally, although the objective of the study was to analyze diastolic
function in patients with sAR, an interesting finding has been that LV
volumes have more prognostic value than LV diameters. This finding is in
accordance with current guidelines (8) that considered the LV size
should be routinely assessed by calculating volumes and the biplane
method as the currently recommended 2D method to assess LVEF, however
the indications for valve replacement in sAR are still based on LV
diameters (1). Previous studies described that LV long axis diameter is
closely related with LV systolic and diastolic function in patients with
chronic severe AR and that LV long axis function is impaired prior to
deterioration of LV global systolic function in these patients, which
might indicate subclinical LV dysfunction (19). Therefore, a global
assessment of the LV size and function seems necessary, beyond that
provided by the determination of isolated diameters.

Although further studies, with large sample size, are required to
stablish cut off points, we believe that careful assessment of diastolic
function including LA strain, could be useful to identify high risk
patients who could benefit from shortening follow up periods and early
aortic surgery.

\textbf{LIMITATIONS.}

Our study was an analysis from clinical database, from single referral
center with limited number of patients and cardiovascular events.
Diastolic parameters are difficult to assess in valvular patients with
volume overload; however, they have been analyzed in other volume
overload valvulopathies, such as mitral regurgitation, with confirmed
prognostic value. Due to the retrospective nature of the study, LA
auto-strain was not available throughout the sample. Thus, further
prospective studies are required to validate our findings.

\textbf{CONCLUSION.}

In patients with asymptomatic sAR, baseline diastolic parameters were
significant predictors of cardiovascular events in the follow-up. LA
reservoir strain was a strong independent prognostic marker. LV volumes
had greater prognostic value that LV diameters in patients with
asymptomatic sAR.

Conflict of interest: none declared.

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  Ventricular Diastolic Dysfunction. JACC Cardiovasc Imaging. 2018
  Oct;11(10):1405-1415.
\item
  Salas-Pacheco JL, \selectlanguage{ngerman}Ávila-Vanzzini N, Eugenia RM, Arias-Godínez JA. Left
  atrium function by 2D speckle tracking in aortic valve disease.
  Echocardiography. 2016 Dec;33(12):1828-1834.
\item
  Rossi A, Tomaino M, Golia G, Santini F, Pentiricci S, Marino P, et al.
  Usefulness of left atrial size in predicting postoperative symptomatic
  improvement in patients with aortic stenosis. Am J Cardiol. 2000 Sep
  1;86(5):567-70, A9-10.
\item
  Galli E, Fournet M, Chabanne C, Lelong B, Leguerrier A, Flecher E, et
  al. Prognostic value of left atrial reservoir function in patients
  with severe aortic stenosis: a 2D speckle-tracking echocardiographic
  study. Eur Heart J Cardiovasc Imaging. 2016 May;17(5):533-41.
\item
  Nolan MT, Thavendiranathan P. Automated Quantification in
  Echocardiography. JACC Cardiovasc Imaging. 2019 Jun;12(6):1073-1092.
\item
  Cayli M, Kanada\selectlanguage{polish}ş\selectlanguage{english}i M, Akpinar O, Usal A, Poyrazo\selectlanguage{polish}ğ\selectlanguage{english}lu H. Relationship
  between left ventricular geometry and left ventricular systolic and
  diastolic functions in patients with chronic severe aortic
  regurgitation. Echocardiography. 2008 Jul;25(6):562-8.
\end{enumerate}

\textbf{FIGURE LEGENDS.}

\textbf{Figure 1.}

Left atrial (LA) auto-strain analysis. From the apical four chamber view
focus in the LA. The software automatically detects and places the LA
border and provides the measurement of the average strain for the three
major LA function throughout the cardiac cycle: reservoir (LASr),
conduit (LAScd) and contractile (LASct) values. The reference point for
deformation analysis was at end diastole.

\textbf{Figure 2.}

Receiver operating characteristic (ROC) curves. Area under curve (AUC)
was used to evaluate LASr accuracy to predict cardiovascular events
(AUC= 0,78 p= 0,012).

\textbf{Figure 3.}

Kaplan-Meier analysis for cardiovascular events. Kaplan-Meier analysis
stratified by median value of LASr (less than median of 34\%) showed
that lower LASr values were associated with significantly higher rates
of cardiovascular event (p= 0,013).

\textbf{Table 1.}

Baseline patient characteristics according to the occurrence of the
composite outcome during follow-up (n = 125).

Values are expressed as mean \selectlanguage{ngerman}± standard deviation for continuous
variables and No. (\%) for categorical variables. * Adjusted for age and
sex.

CV, cardiovascular; BMI, Body mass index; BNP, B type natriuretic
peptide; TR, tricuspid regurgitation; SPAP, Systolic pulmonary artery
pressure; LVEDD, left ventricular end diastolic diameter; LVESD, left
ventricular end systolic diameter; LVEDV, left ventricular end diastolic
volume; LVESV, left ventricular end systolic volume; LVEF, left
ventricular ejection fraction; LASct, left atrial strain contractile;
LASr, left atrial strain reservoir; LAScd, left atrial strain conduit.

\textbf{Table 2.}

Cox Regression Analysis between echocardiographic parameters and outcome
events.

Univariate analysis: All the echocardiographic systolic and diastolic
function parameters assessed.

Multivariate Model 1: Parameters currently used to indicate surgery
(LVEDV, LVESV and LVEF) and conventional diastolic variables
statistically significant in the univariate model (E, E/e' ratio, LA
volume) except SPAP because it is available only in 39 patients.

Model 2: In LA autostrain group. Significant parameters in the Model 1
(LVEDV, E/e' ratio) and LASr.

CI, confidence interval; HR, hazard ratio; LVEDV, left ventricular
end-diastolic volume, LVESV, left ventricular end-systolic volume, LVEF,
left ventricular ejection fraction; and TR, tricuspid regurgitation.

\textbf{FIGURES}

Figure 1.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 3.

\textbf{TABLES.}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Group 1} \textbf{(no CV events)} \textbf{N=101}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Group 2} \textbf{(CV events)} \textbf{N=25}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
P*\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Clinical characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Clinical characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Clinical characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Clinical characteristics}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Age (years)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
70,8\selectlanguage{ngerman}±17,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
67,0\selectlanguage{ngerman}±15,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,40\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Female sex (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
44 (43,6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7 (28,0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,14\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{BMI}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1,8\selectlanguage{ngerman}±0,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1,8\selectlanguage{ngerman}±0,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,65\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Dyslipidemia (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
39 (38,6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (24,0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,31\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Diabetes (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8 (7,9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,98\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Hypertension (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
62 (61,4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
16 (64,0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,81\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Bicuspid valve (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
19 (18,8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (24\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,59\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{BNP}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
197,2 (233,5)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
83,3 (116,7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Echocardiographic characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Echocardiographic characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Echocardiographic characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Echocardiographic characteristics}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Vena contracta (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5,7\selectlanguage{ngerman}±1,4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6,3\selectlanguage{ngerman}±1,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,84\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Left atrial diameter (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
37,0\selectlanguage{ngerman}±6,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
37,0\selectlanguage{ngerman}±7,1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,99\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Left atrial diameter (index, mm/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20,8\selectlanguage{ngerman}±3,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20,0\selectlanguage{ngerman}±3,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,94\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Left atrial volume (ml)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
53,3\selectlanguage{ngerman}±19,1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
66,7\selectlanguage{ngerman}±32,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Left atrial volume (index. ml/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29,8\selectlanguage{ngerman}±10,1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35,6\selectlanguage{ngerman}±16,1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
63,5\selectlanguage{ngerman}±22,4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
72,0\selectlanguage{ngerman}±26,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,03\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{A}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
79,4\selectlanguage{ngerman}±20,8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
86,2\selectlanguage{ngerman}±32,8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E/a}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,8\selectlanguage{ngerman}±0,4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,9\selectlanguage{ngerman}±0,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,28\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E' lat}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7,9\selectlanguage{ngerman}±3,3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7,4\selectlanguage{ngerman}±2,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E' med}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6,3\selectlanguage{ngerman}±2,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6,1\selectlanguage{ngerman}±2,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,09\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E/e' lat}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9,3\selectlanguage{ngerman}±4,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10,4\selectlanguage{ngerman}±5,3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{E/e' med}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10,8\selectlanguage{ngerman}±4,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13,5\selectlanguage{ngerman}±9,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0,001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{TR grade}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,3\selectlanguage{ngerman}±0,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,5\selectlanguage{ngerman}±0,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{SPAP (mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29,8\selectlanguage{ngerman}±8,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35,6\selectlanguage{ngerman}±10,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,03\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{TR (mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21,6\selectlanguage{ngerman}±7,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28,1\selectlanguage{ngerman}±5,8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEDD (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
52,1\selectlanguage{ngerman}±7,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
54,4\selectlanguage{ngerman}±8,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,23\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVESD (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31,8\selectlanguage{ngerman}±5,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35,3\selectlanguage{ngerman}±8,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEDDi (mm/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29,2\selectlanguage{ngerman}±4,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29,5\selectlanguage{ngerman}±4,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,91\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVESDi (mm/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17,8\selectlanguage{ngerman}±3,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
19,0\selectlanguage{ngerman}±4,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,13\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEDV (ml)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
112,6\selectlanguage{ngerman}±42,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
153\selectlanguage{ngerman}±55,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0,01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVESV (ml)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
42,4\selectlanguage{ngerman}±24,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
64,8\selectlanguage{ngerman}±37,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0,01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEDVi (ml/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
62,0\selectlanguage{ngerman}±19,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
81,9\selectlanguage{ngerman}±25,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0,001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVESVi (ml/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
23,2\selectlanguage{ngerman}±11,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
34,6\selectlanguage{ngerman}±20,1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0,01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEF (\%, Teicholz)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
67,5\selectlanguage{ngerman}±9,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
65,9\selectlanguage{ngerman}±10,4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,13\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LVEF (\%, Simpson)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
64,0\selectlanguage{ngerman}±7,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
61,5\selectlanguage{ngerman}±8,4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LASr}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
23,9\selectlanguage{ngerman}±9,0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35,6\selectlanguage{ngerman}±12,5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LAScd}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-13,3\selectlanguage{ngerman}±4,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-17,6\selectlanguage{ngerman}±12,3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,15\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{LASct}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-11,4\selectlanguage{ngerman}±7,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
-18,9\selectlanguage{ngerman}±6,6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,01\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 1.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& \textbf{HR (95\% CI)} & P & \textbf{HR (95\% CI)} & P & \textbf{HR
(95\% CI)} & P\tabularnewline
\midrule
\endhead
\textbf{LVEDV (ml)} & 1,01 (1,01 -- 1,02) & \textless{}0,001 & 1,02
(1,01 -- 1,03) & \textless{}0,001 & 1,05 (1,01-1,08) &
0,016\tabularnewline
\textbf{LVESV (ml)} & 3,85 (1,44 -- 10,33) & 0,007 & & & --- &
---\tabularnewline
\textbf{LVEF -- biplane (\%)} & 0,95 (0,90 -- 1,00) & 0,053 & & & --- &
---\tabularnewline
\textbf{E} & 1,02 (1,00 -- 1,03) & 0,015 & & & --- & ---\tabularnewline
\textbf{A} & 1,01 (1,00 -- 1,03) & 0,128 & --- & --- & --- &
---\tabularnewline
\textbf{E/e' ratio} & 1.10 (1.04 -- 1.17) & 0,002 & 1,12 (1,03 -- 1,23)
& 0,01 & &\tabularnewline
\textbf{TR (grade)} & 1,63 (0,77 -- 3,44) & 0,200 & & & --- &
---\tabularnewline
\textbf{SPAP (mmHg)} & 1,10 (1,02 -- 1,16) & 0,008 & & & --- &
---\tabularnewline
\textbf{LA volume (ml)} & 1,02 (1,00 -- 1,04) & 0,013 & & & --- &
---\tabularnewline
\textbf{LASr\_ED} & 0,93 (0,87 -- 0,99) & 0,021 & --- & --- & 0,80 (0,65
-- 0,98) & 0,035\tabularnewline
\textbf{LA diameter (mm)} & 1,02 (0,94 -- 1,10) & 0,637 & & &
&\tabularnewline
\textbf{LVEDD (mm)} & 1,03 (0,97-- 1,10) & 0,377 & & & &\tabularnewline
\bottomrule
\end{longtable}

Table 2.\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}

