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\begin{document}

\title{Effect of sacubutril/valsartan and dapagliflozin on athletic
performance; Can the popular cardiac medications of recent years be used
as doping agents?}



\author[1]{Akin Torun}%
\author[1]{Sahhan Kilic}%
\author[1]{Suha Asal}%
\author[1]{Mert Babaoglu}%
\author[1]{Samet Yavuz}%
\author[1]{Cumaali Demirtaş}%
\author[2]{Serkan Dilmen}%
\author[1]{Ahmet Lutfullah Orhan}%
\author[1]{Mehmet Uzun}%
\affil[1]{Istanbul Sultan 2 Abdulhamid Han Egitim ve Arastirma Hastanesi}%
\affil[2]{Izmir Il Saglik Mudurlugu}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
Studies conducted in recent years have demonstrated the positive effects
of sacubitril/valsartan and dapagliflozin on cardiac prognosis and
performance. These drugs can potentially be abused as doping agents by
professional athletes. In our study, we evaluated the effects of
sacubitril/valsartan and dapagliflozin on athletic performance. In the
study, the swimming performances of three groups of rats were evaluated
by dividing them into control, sacubitril/valsartan and dapagliflozin
groups. Additionally, echocardiography, weight and rotarod data were
evaluated during follow-up. In the comparison of sacubitril/valsartan
and control groups, a statistical difference was seen in the 13th, 19th
and 20th swimming sessions, and when the total and average swimming
times were compared, the p values were 0.115 and 0.015. In the
comparison of dapagliflozin and control groups, a statistical difference
was observed starting from the 10th swimming session, and when the total
and average swimming times were compared, the p values were
\textless{}0.001 and \textless{}0.001. In triple analysis, a statistical
difference was seen from the 9th swimming session until the end of the
experiment. Furthermore, a statistical difference was observed in
rotarod results for sacubitril/valsartan and dapagliflozin compared to
baseline. (p value \textless{}0.001 and 0.011 respectively) Our study
showed a limited positive effect of sacubitril/valsartan on athletic
performance. The impact of dapagliflozin on athletic performance was
shown to be particularly significant.%
\end{abstract}%



\sloppy


\textbf{Title} : Effect of sacubutril/valsartan and dapagliflozin on
athletic performance; Can the popular cardiac medications of recent
years be used as doping agents?

\textbf{Short title:} Effect of sacubutril/valsartan and dapagliflozin
on athletic performance

\textbf{Keywords:} dapagliflozin, sacubutril/valsartan, athletic
performance, sports cardiology, doping agents, performance enhancing

\textbf{Authors:}

\textsuperscript{1} Akin Torun, MD / 0000-0003-2791-9538

\textsuperscript{1} Sahhan Kilic , MD / 0000-0002-3524-5396

\textsuperscript{1} Suha Asal, MD / 0000-0002-3709-2506

\textsuperscript{1} Mert Babaoglu, MD / 0000-0003-4544-9584

\textsuperscript{1} Samet Yavuz, MD / 0000-0002-1913-3001

\textsuperscript{2} Cumaali Demirta\selectlanguage{polish}ş, \selectlanguage{english}PhD / 0000-0001-5226-6730

\textsuperscript{3} Serkan Dilmen, MD / 0009-0008-2498-6958

\textsuperscript{1} Ahmet Lutfullah Orhan, Prof. / 0000-0002-8617-3281

\textsuperscript{1} Mehmet Uzun Prof. /\emph{0000-0003-2999-489X}

\textsuperscript{1} Sultan II. Abdulhamid Han Training and Research
Hospital, Department of Cardiology, Istanbul, T\selectlanguage{ngerman}ürkiye

\textsuperscript{2} Sultan II. Abdulhamid Han Training and Research
Hospital, Veterinary Medicine, Istanbul, Türkiye

\textsuperscript{3} Izmir Bayrakl\selectlanguage{polish}ı \selectlanguage{english}City Hospital, Department of
Cardiology, Izmir, T\selectlanguage{ngerman}ürkiye

\textbf{Corresponding Author:}

Akin Torun

Sultan II. Abdulhamid Han Training and Research Hospital, Uskudar,
Istanbul, Turkey, 34668

Communication number: +90 537 986 15 51

\textbf{E-mail} :\emph{torunakin@hotmail.com}

\textbf{Abstract}

Studies conducted in recent years have demonstrated the positive effects
of sacubitril/valsartan and dapagliflozin on cardiac prognosis and
performance. These drugs can potentially be abused as doping agents by
professional athletes. In our study, we evaluated the effects of
sacubitril/valsartan and dapagliflozin on athletic performance. In the
study, the swimming performances of three groups of rats were evaluated
by dividing them into control, sacubitril/valsartan and dapagliflozin
groups. Additionally, echocardiography, weight and rotarod data were
evaluated during follow-up. In the comparison of sacubitril/valsartan
and control groups, a statistical difference was seen in the 13th, 19th
and 20th swimming sessions, and when the total and average swimming
times were compared, the p values were 0.115 and 0.015. In the
comparison of dapagliflozin and control groups, a statistical difference
was observed starting from the 10th swimming session, and when the total
and average swimming times were compared, the p values were
\textless{}0.001 and \textless{}0.001. In triple analysis, a statistical
difference was seen from the 9th swimming session until the end of the
experiment. Furthermore, a statistical difference was observed in
rotarod results for sacubitril/valsartan and dapagliflozin compared to
baseline. (p value \textless{}0.001 and 0.011 respectively) Our study
showed a limited positive effect of sacubitril/valsartan on athletic
performance. The impact of dapagliflozin on athletic performance was
shown to be particularly significant.

\textbf{Keywords:} dapagliflozin, sacubitril/valsartan, athletic
performance, sports cardiology, doping agents, performance enhancing

\textbf{Key points:}

\begin{itemize}
\tightlist
\item
  Dapagliflozin and sacubitril/valsartan are cardiac medications that
  have an effect on athletic performance.
\item
  The athletic performance effect of sacubitril/valsartan is limited,
  but this effect is more pronounced with dapagliflozin.
\item
  These medications, which have become very popular among cardiac
  medication options in recent years, can be abused as doping agents.
\end{itemize}

\textbf{Introduction}

Athlete's heart is a definition used for the physiological adaptation of
the heart to repetitive exercise. Different physiological adaptation
mechanisms may develop depending on the content of the exercise
performed {[}1{]}. Elite athletes aim to improve their cardiac fitness
at an optimal level through training for the best athletic performance.
Training is a structured procedure in which athletes are subjected to
consistent and recurrent exercise stimuli in order to induce adaptations
that align with a desired function. These functions may include delaying
the onset of tiredness, enhancing power output, improving motor
coordination, or minimizing the likelihood of injury. The boundaries of
athletic performance have been a topic of speculation and discussion for
a significant period of time. Nevertheless, there appears to be a
noticeable plateau in sports performance in recent years, indicating
that the potential for further enhancement of individuals' physical
capabilities may be limited {[}2{]}. Therefore, doping substances are
becoming a suspicious factor among elite athletes. Due to the extensive
range chemicals and the continual emergence of novel designer
pharmaceuticals on the market, the World Anti-Doping Agency (WADA)
annually revises its list of substances and methodologies that are
forbidden in the realm of sports. One of the most fundamental elements
of sports performance is undoubtedly cardiac function. This raises
serious doubts about the use of some heart medications as doping agents.
The addition of trimetazidine to WADA's Prohibited List as a doping
substance in 2014 can be considered the beginning of this era {[}3,4{]}.
The combination of sacubitril and valsartan, as well as dapagliflozin,
which effectively improves cardiac performance and has a positive
prognostic effect on heart failure, has been particularly notable in
recent years in the existing literature {[}5,6{]}. These may potentially
be abused as doping substances in elite athletes. Therefore, in our
study, we aimed to observe the effects of these drugs on athletic
performance.

\textbf{Methods}

A swimming experiment was designed in rat to objectively observe
exercise capacity. The Sprague-Dawley male rat were obtained from the
Animal Center of Health Science University. Based on the findings of the
G power 3.1 analysis, it was determined that a minimum of six rat per
group would be necessary to achieve the desired experimental power.
Consequently, the study was designed to include a total of 24 animals,
following the appropriate ethical procedures by seeking approval from
the animal experiments ethics committee.

The subjects were accommodated in a controlled environment with a
12-hour light and dark cycle, at a temperature of 25 °C, and a relative
air humidity of 40\%. They were provided with ad libitum access to water
and feed, and were allowed unrestricted activity within a laboratory
animal room for a minimum duration of one week. Then, 3-month-old rat
were randomly divided into three groups. The Rota-Rod test was employed
to measure the motor coordination and antifatigue ability of rat at the
beginning of the study. The Rota-Rod test consists of a cylindrical rod
with a diameter of 3\selectlanguage{english} cm, which has been partitioned into five tracks
each with a width of 6\selectlanguage{english} cm. Additionally, the apparatus includes an
infrared detector and a computer. The Rota-Rod test comprises a rotating
rod with a diameter of 3\selectlanguage{english} cm (this rod was divided into 5 tracks with a
width of 6\selectlanguage{english} cm), an infrared detector, and a computer. In the test, rat
were positioned on the horizontally oriented, rotating rod. It was
ensured that there were no differences between groups.

In the first group, 60 mg/kg/1ml dose of sacubitril/valsartan was
administered every day by oral gavage. In the second group, 1,5mg/kg/1ml
dose of dapagliflozin was administered every day by oral gavage. The
third group was the control group. The researchers who administered the
drug and the researchers who performed the swim test were different
people. The researcher who performed the swim test was unaware of the
groups' information.

Initially, before the experiment, each group had swimming training in
the water tank for three days. Each mouse was placed in a different
water tank. The water tank was designed with a size of 40x40 cm and a
height of 50 cm. The swimming tank was maintained at a temperature of
28oC throughout the swimming process. The endurance of each mouse was
assessed by measuring the swimming time from the start of the activity
until exhaustion, which was determined by observing uncoordinated
movements and the inability to resurface within a period of 7 seconds.
The maximum swimming seconds of each mouse were recorded daily. In
addition, echocardiography (ECHO) and heart rate measurements were
performed in each mouse at the beginning of the experiment, on the 15th
day and at the end of the experiment.

\textbf{Statistical analysis}

The research analysis was conducted utilizing the Statistical Package
for Social Science (SPSS) version 27.0 program. Continuous variables are
given with median (minimum-maximum) values. Kruskal Wallis test was used
to determine differences between groups. Mann-Whitney U test was used
and bonferroni correction was applied in post hoc intergroup pairwise
analyses. Friedman test was applied to determine intragroup differences.
Wilcoxon test was applied and bonferroni correction was applied in post
hoc intragroup pairwise comparison. The significance level for
statistical analyzes was set as p\textless{}0.05. determined.

\textbf{Results}

A total of 24 rat, divided into 3 groups of 8 rat each, were observed
throughout the duration of the experiment. Table 1 shows the baseline
ECHO parameters of the three groups. There is no difference between the
groups when comparing echo parameters at baseline. Table 2 shows the
echo parameters of the control group on days 0, 15 and 30, table 3 shows
the dapagliflozin and table 4 shows the sacubitril/valsartan group.

When comparing baseline data, there was no significant difference
observed in the performance of rotarods and their corresponding weights.
Table 5 shows the change in the rat's weight over the course of the
experiment, and Table 6 shows the results from the rotarod follow-ups.

Table 7 shows the median swimming times of each group during the
swimming sessions throughout the experiment. Starting from the 9th
swimming session, there was a noticeable difference in the swimming
times between the groups. Figure 1 displays the average swimming
performance of the three groups. Table 8 shows the comparison of
sacubitril/valsartan with the control group, and table 9 shows the
comparison of dapagliflozin with the control group.

\textbf{Discussion}

Instances of doping, as well as other forms of cheating, have been
documented throughout the history of sports. The utilization of
performance-enhancing drugs in sports is an obvious crisis. The
utilization of substances in professional sports and competitions has
significantly damaged the reputation of numerous athletes worldwide,
while also posing a threat to their health. {[}7{]} The pharmaceutical
industry has had significant expansion in the past decade, in tandem
with advancements in technology. This growth has resulted in key
advancements, particularly in the field of cardiac medications. The
recently introduced cardiac medications may enhance sports performance
and therefore may be abused as a form of doping. Therefore, our study
aimed at examining the impact of dapagliflozin and sacubitril/valsartan,
known for their significant symptomatic alleviation and favorable
prognosis, particularly in heart failure, on sports performance. Both
drugs have proved the ability to improve athletic performance, The
impact on improving athletic performance was significantly more
prominent for dapagliflozin.

The effect of exercise on the heart can be observed more quickly in rat.
{[}8{]} The change seen in the echo data of the control group regarding
the left ventricle is compatible with the development of an athlete's
heart. This demonstrates the methodological reliability of the
experiment. In both medical approaches, there was a significant increase
in antegrade flow of the pulmonary artery, compared to baseline. This
may be related to an increase in right ventricular functions. Another
notable feature is the increase of ejection fraction (EF) observed in
the sacubitril/valsartan group. The increase in EF with
sacubitril/valsartan use can also be seen in heart failure patients.
{[}9{]} The effect of dapagliflozin on athletic performance was assessed
independently from its impact on EF.

There was a decrease in the weight of the rat in all three groups due to
intense exercise throughout the experiment. But there was no significant
difference between the groups in this decrease. The decrease in weight
is related to both the direct effect of physical activity on energy
expenditure and the increase in metabolic rate during the resting
period. {[}10{]} The rat were not under any calorie restriction. They
had unrestricted access to food. If the experimental period was
extended, a plateau in their weight could be observed. {[}11{]}

We observed an increase in rotarod results compared to baseline data in
both medication groups. There was no significant difference compared to
the control group. The adaptation of rat should not be ignored. However,
while there is a statistical difference in the medication groups,
although there is an increase in the control group, it is not
statistically significant. These results may be the beginning of more
comprehensive studies. Because the positive effect of dapagliflozin and
sacubitril/valsartan on the rotarod may provide an advantage in skill
sports (golf, table tennis, shooting, curling, bowling etc.). {[}12{]}

The primary objective of our investigation was to reveal the improvement
in athletic performance. After similar results were obtained during the
first 9 swimming sessions of exercise, we observed a significant
difference in the athletic performance of rat with both medications.
This effect of sacubitril/valsartan was generally observed parallel to
the control group and slightly better. Sacubitril/valsartan, an
angiotensin receptor-neprilysin inhibitor, enhances the natriuretic
peptide system~by suppressing the neprilysin enzyme and inhibits the
renin-angiotensin-aldosterone system by inhibiting the angiotensin II
receptor. Evidence demonstrates that it improves mortality~and reduces
hospitalization rates in individuals with heart failure caused by
impaired left ventricular systolic performance. {[}13{]} Also
sacubitril/valsartan augments~the effects of bradykinin, substance P,
and adrenomedullin, which are other hormones that may contribute to the
cardiac efficacy of the medication. {[}14{]} The positive effect of
sacubitril/valsartan on athletic performance may be related to increased
cardiac efficiency and slightly improved left ventricular function.
However, this effect was observed to be limited and there was a relative
increase in athletic performance.

The effect of dapagliflozin was observed remarkably. Sodium-glucose
cotransporter-2 (SGLT) inhibitors reduce the risk of hospitalization for
heart failure in patients with either preserved or reduced ejection
fraction. However, the specific hemodynamic processes responsible for
these advantages are not yet fully understood. {[}15{]} A research
conducted on rat has demonstrated that dapagliflozin has a vasodilatory
impact on the thoracic aorta, which is dependent on the voltage of
potassium channels. {[}16{]} This demonstrated a direct effect on
vascular cells for both acute and chronic treatment. {[}17{]} Therefore,
it is reasonable to observe that the improvement in performance begins
during the initial periods and thereafter advances throughout time.
Another possible mechanism of action may be related to its positive
microvascular and endothelial activity. {[}18{]} SGLT-2 inhibitors,
currently the only option in preserved EF heart failure, may have as yet
undisclosed abilities regarding possible cellular myocardial efficiency.
However, our study showed that dapagliflozin has an obvious doping
effect on athletic performance. Future studies on the mechanism of
action may reveal the reasons for this effect more clearly.

\textbf{Conclusion}

The development of studies in cardiac treatment provides novel and
efficacious alternatives. The heart, which is the center of high-level
athletic performance, and its related medications can be abused as
doping agents. Our study showed a limited positive effect of
sacubitril/valsartan on athletic performance. The impact of
dapagliflozin on athletic performance was shown to be particularly
significant.

\textbf{References}

\begin{enumerate}
\tightlist
\item
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\textbf{Figure legend:} Improvement of median swimming times of the
groups during the experiment

Table 1: Comparison of baseline echocardiography parameters\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Echo parameters}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Control}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Dapagliflozin}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Sacubitril / valsartan}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{P value*}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Heart rate (beat/min)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
245 (223-261)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
243 (225-255)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
244 (213-262)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.996\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
IVSD (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,8-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,7-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,8-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.980\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
IVSS (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,7 (2,6-2,8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,7 (2,4-2,8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,7 (2,6-2,8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.899\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
LVDD (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
7,4 (7,1-8,3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
8 (6,6-8,1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
7,55 (7,1-8,2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.648\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
LVSD (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
5,2 (4,5-6,1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
5,6 (4,1-6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
5,3 (4,6-5,9)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.723\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
LVPWD (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,8-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,7-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,9 (1,8-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.495\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
LVPWS (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,7 (2,5-2,7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,6 (2,6-2,8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2,7 (2,6-2,8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.350\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
AoS (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,6 (3,5-3,7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,6 (3,4-3,9)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,55 (3,4-3,7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.560\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
AoD (mm)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,2 (3,1-3,3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,1 (3,1-3,4)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3,1 (3-3,3)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.577\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Aortic strain (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
12,9 (12,12-16,12)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
13,8 (9,6-16,1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
12,7 (9,6-16,6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.940\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
AV Vmax (m/sn)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,29 (1,1-1,54)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,43 (1,14-1,56)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,39 (1,14-2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.467\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
PV Vmax (m/sn)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,77 (0,63-0,91)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,74 (0,58-0,91)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,73 (0,6-1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.828\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
EF (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
69 (60-74)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
67 (56-79)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
64 (59-72)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.828\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
F shortening (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
32,9 (26,5-36,6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
30,8 (24-40,5)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
29,3 (25,9-35,2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.828\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
EDV (mL)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,468 (0,374-0,598)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,53 (0,30-0,55)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,45 (0,37-0,57)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.648\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
ESV (mL)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,147 (0,095-0,237)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,18 (0,07-0,22)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0,15 (0,11-0,21)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.723\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Cardiac output (mL/min)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
80 (65-88)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
82,7 (51,8-95)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
71 (62-85)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.471\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
LV mass (g)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,94 (1,87-1,97)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,93 (1,84-1,97)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1,94 (1,89-1,99)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.607\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Kruskal Wallis test

AoD;aortic diastole, AoS;aortic systole, AV; aortic valve, EDV; end
diastolic volume, ESV; end systolic volume, EF; ejection fraction, F;
fractional, IVSD; inter ventricular septum diastolic, IVSS; inter
ventricular septum systolic, LV; left ventricle, LVDD; left ventricle
diastolic diameter, LVSD; left ventricle systolic diameter, LVPWD; left
ventricle posterior wall diastolic, LWPWS: left ventricle posterior wall
systolic, PV; pulmonary valve

Table 2: Follow-up of echocardiography parameters of the control group\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Echo parameters} & \textbf{Day 0} & \textbf{Day 15} &
\textbf{Day 30} & \textbf{P value*}\tabularnewline
\midrule
\endhead
Heart rate (beat/min) & 245 (223-261) & 231 (208-254) & 238,5 (221-266)
& \textbf{0,010}\tabularnewline
IVSD (mm) & 1,9 (1,8-2) & 1,9 (1,8-2) & 1,95 (1,8-2) &
\textbf{0,022}\tabularnewline
IVSS (mm) & 2,7 (2,6-2,8) & 2,7 (2,7-2,9) & 2,75 (2,7-3) &
\textbf{0,006}\tabularnewline
LVSD (mm) & 7,4 (7,1-8,3) & 7,45 (7,0-8,2) & 7,4 (6,9-8,1) &
\textbf{0,003}\tabularnewline
LVSD (mm) & 5,2 (4,5-6,1) & 5,1 (4,5-6) & 5,05 (4,4-6,1) &
\textbf{0,034}\tabularnewline
LVPWD (mm) & 1,9 (1,8-2,0) & 1,9 (1,8-2,0) & 2 (1,8-2,1) &
0,280\tabularnewline
LVPWS (mm) & 2,7 (2,5-2,7) & 2,7 (2,5-2,8) & 2,7 (2,6-2,7) &
0,646\tabularnewline
AoS (mm) & 3,6 (3,5-3,7) & 3,65 (3,4-3,7) & 3,7 (3,5-3,9) &
0,059\tabularnewline
AoD (mm) & 3,2 (3,1-3,3) & 3,1 (3-3,2) & 3,1 (3,1-3,3) &
0,401\tabularnewline
Aortic strain (\%) & 12,9 (12,12-16,12) & 15,62 (9,67-23,3) & 17,15
(12,5-22,58) & 0,179\tabularnewline
AV Vmax (m/sn) & 1,29 (1,1-1,54) & 1,41 (1,18-1,52) & 1,49 (1,18-1,83) &
0,115\tabularnewline
PV Vmax (m/sn) & 0,77 (0,63-0,91) & 0,80 (0,69-1,05) & 0,88 (0,73-1,14)
& 0,250\tabularnewline
EF & 69 (60,74) & 70 (60,74) & 68 (57,74) & 0,325\tabularnewline
F shortening & 32,9 (26,5-36,6) & 33,1 (26,8-36,4) & 32 (24,6-36,2) &
0,325\tabularnewline
EDV & 0,468 (0,374-0,598) & 0,432 (0,359-0,577) & 0,424 (0,343-0,556) &
\textbf{0,003}\tabularnewline
ESV & 0,147 (0,095-0,237) & 0,138 (0,095-0,226) & 0,134 (0,089-0,237) &
\textbf{0,034}\tabularnewline
Cardiac output (mL/min) & 80 (65-88) & 70 (60-78) & 69 (58,82) &
\textbf{0,010}\tabularnewline
LV mass (g) & 1,94 (1,87-1,97) & 1,96 (1,89-1,99) & 1,96 (1,92-2,02) &
\textbf{0,024}\tabularnewline
\bottomrule
\end{longtable}

*Friedman Test

AoD;aortic diastole, AoS;aortic systole, AV; aortic valve, EDV; end
diastolic volume, ESV; end systolic volume, EF; ejection fraction, F;
fractional, IVSD; inter ventricular septum diastolic, IVSS; inter
ventricular septum systolic, LV; left ventricle, LVDD; left ventricle
diastolic diameter, LVSD; left ventricle systolic diameter, LVPWD; left
ventricle posterior wall diastolic, LWPWS: left ventricle posterior wall
systolic, PV; pulmonary valve

Table 3: Follow-up of echocardiography parameters of the dapagliflozin
group\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Echo parameters} & \textbf{Day 0} & \textbf{Day 15} &
\textbf{Day 30} & \textbf{P value*}\tabularnewline
\midrule
\endhead
Heart rate (beat/min) & 243 (225-255) & 221 (184-253) & 240 (210-282) &
0,197\tabularnewline
IVSD (mm) & 1,9 (1,7-2) & 1,8 (1,8-1,9) & 1,85 (1,7-2) &
0,368\tabularnewline
IVSS (mm) & 2,7 (2,4-2,8) & 2,75 (2,2-2,9) & 2,75 (2,4-2,9) &
0,268\tabularnewline
LVSD (mm) & 8 (6,6-8,1) & 7,85 (6,7-8,0) & 7,9 (7,2-8,3) &
0,191\tabularnewline
LVSD (mm) & 5,6 (4,1-6) & 5,45 (3,8-5,8) & 5,5 (4-6,1) &
\textbf{0,042}\tabularnewline
LVPWD (mm) & 1,9 (1,7-2) & 1,9 (1,8-2) & 1,95 (1,9-2,1) &
\textbf{0,012}\tabularnewline
LVPWS (mm) & 2,6 (2,6-2,8) & 2,7 (2,6-2,8) & 2,7 (2,3-2,9) &
0,229\tabularnewline
AoS (mm) & 3,6 (3,4-3,9) & 3,55 (3,4-4) & 3,6 (3,5-3,8) &
0,882\tabularnewline
AoD (mm) & 3,1 (3,1-3,4) & 3,1 (2,9-3,4) & 3,1 (3-3,3) &
0,891\tabularnewline
Aortic strain (\%) & 13,8 (9,6-16,1) & 13,1 (12,1-20,6) & 15,6 (9,1-20)
& 0,748\tabularnewline
AV Vmax (m/sn) & 1,43 (1,14-1,56) & 1,38 (1,19-1,68) & 1,54 (1,37-1,99)
& 0,417\tabularnewline
PV Vmax (m/sn) & 0,74 (0,58-0,91) & 0,92 (0,74-1,25) & 0,89 (0,77-1,04)
& \textbf{0,05}\tabularnewline
EF & 67 (56-79) & 66 (61-81) & 69 (58-82) & 0,648\tabularnewline
F shortening & 30,8 (24-40,5) & 30,5 (27,5-43,3) & 30,8 (25,3-44,4) &
0,648\tabularnewline
EDV & 0,53 (0,30-0,55) & 0,50 (0,31-0,53) & 0,51 (0,39-0,59) &
0,191\tabularnewline
ESV & 0,18 (0,07-0,22) & 0,16 (0,06-0,20) & 0,17 (0,07-0,23) &
\textbf{0,042}\tabularnewline
Cardiac output (mL/min) & 82,7 (51,8-95) & 72 (52,7-91) & 79 (65-94) &
0,197\tabularnewline
LV mass (g) & 1,93 (1,84-1,97) & 1,96 (1,82-1,99) & 1,93 (1,84-2,02) &
0,119\tabularnewline
\bottomrule
\end{longtable}

*Friedman Testi

AoD;aortic diastole, AoS;aortic systole, AV; aortic valve, EDV; end
diastolic volume, ESV; end systolic volume, EF; ejection fraction, F;
fractional, IVSD; inter ventricular septum diastolic, IVSS; inter
ventricular septum systolic, LV; left ventricle, LVDD; left ventricle
diastolic diameter, LVSD; left ventricle systolic diameter, LVPWD; left
ventricle posterior wall diastolic, LWPWS: left ventricle posterior wall
systolic, PV; pulmonary valve

Table 4: Follow-up of echocardiography parameters of the
sacubitril/valsartan group\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Echo parameters} & \textbf{Day 0} & \textbf{Day 15} &
\textbf{Day 30} & \textbf{P value*}\tabularnewline
\midrule
\endhead
Heart rate (beat/min) & 244 (213-262) & 230 (184-266) & 232 (219-252) &
0,325\tabularnewline
IVSD (mm) & 1,9 (1,8-2) & 1,9 (1,8-2,1) & 1,9 (1,8-1,9) &
0,202\tabularnewline
IVSS (mm) & 2,7 (2,6-2,8) & 2,6 (2,4-2,9) & 2,7 (2,6-2,8) &
0,878\tabularnewline
LVSD (mm) & 7,55 (7,1-8,2) & 7,55 (7,2-8,2) & 7,55 (7,3-8,4) &
0,779\tabularnewline
LVSD (mm) & 5,3 (4,6-5,9) & 5,3 (4,6-5,7) & 4,6 (4-5,5) &
0,061\tabularnewline
LVPWD (mm) & 1,9 (1,8-2) & 1,9 (1,8-2) & 1,9 (1,7-2) &
0,186\tabularnewline
LVPWS (mm) & 2,7 (2,6-2,8) & 2,75 (2,6-2,8) & 2,7 (2,6-2,8) &
0,417\tabularnewline
AoS (mm) & 3,55 (3,4-3,7) & 3,5 (3,3-3,7) & 3,55 (3,4-3,9) &
\textbf{0,013}\tabularnewline
AoD (mm) & 3,1 (3-3,3) & 3,05 (2,9-3,2) & 3,1 (2,9-3,2) &
0,167\tabularnewline
Aortic strain (\%) & 12,7 (9,6-16,6) & 12,9 (10-20,6) & 15,8 (9,6-25,8)
& 0,227\tabularnewline
AV Vmax (m/sn) & 1,39 (1,14-2) & 1,49 (1,34-1,61) & 1,67 (1,52-2,23) &
\textbf{0,030}\tabularnewline
PV Vmax (m/sn) & 0,73 (0,6-1) & 0,8 (0,66-1,25) & 1,09 (0,89-1,72) &
\textbf{0,010}\tabularnewline
EF & 64 (59-72) & 67 (60-75) & 74 (69-83) &
\textbf{0,002}\tabularnewline
F shortening & 29,3 (25,9-35,2) & 31,3 (26,6-37,8) & 36,9 (32,9-45,2) &
\textbf{0,002}\tabularnewline
EDV & 0,45 (0,37-0,57) & 0,45 (0,39-0,57) & 0,45 (0,41-0,62) &
0,779\tabularnewline
ESV & 0,15 (0,11-0,21) & 0,16 (0,11-0,19) & 0,11(0,7-0,17) &
0,061\tabularnewline
Cardiac output (mL/min) & 71 (62-85) & 75 (52-101) & 80 (66-111) &
\textbf{0,034}\tabularnewline
LV mass (g) & 1,94 (1,89-1,99) & 1,93 (1,84-2,02) & 1,96 (1,92-1,97) &
0,891\tabularnewline
\bottomrule
\end{longtable}

*Friedman Testi

AoD;aortic diastole, AoS;aortic systole, AV; aortic valve, EDV; end
diastolic volume, ESV; end systolic volume, EF; ejection fraction, F;
fractional, IVSD; inter ventricular septum diastolic, IVSS; inter
ventricular septum systolic, LV; left ventricle, LVDD; left ventricle
diastolic diameter, LVSD; left ventricle systolic diameter, LVPWD; left
ventricle posterior wall diastolic, LWPWS: left ventricle posterior wall
systolic, PV; pulmonary valve

Table 5: Follow-up data of the weights of the groups and comparison
between groups\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Group} & \textbf{Day 0} & \textbf{Day 15} & \textbf{Day 30} &
\textbf{P value**}\tabularnewline
\midrule
\endhead
\textbf{Control} & 430 (370,450) & 405 (350,430) & 385 (330,400) &
\textbf{0.002}\tabularnewline
\textbf{Dapaglifozin} & 420(390,470) & 380 (360,430) & 361 (344,407) &
\textbf{\textless{}0.001}\tabularnewline
\textbf{Sacubitril/Valsartan} & 435 (380,460) & 397 (340,435) & 377
(319,410) & \textbf{\textless{}0.001}\tabularnewline
\textbf{P value*} & 0.996 & 0.889 & 0.826 &\tabularnewline
\bottomrule
\end{longtable}

*Kruskal Wallis

**Friedman

Table 6: Rotarod follow-up data of the groups and comparison between
groups\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Gruop} & \textbf{Day 0} & \textbf{Day 15} & \textbf{Day 30} &
\textbf{P value**}\tabularnewline
\midrule
\endhead
\textbf{Control} & 31 (14,131) & 67,5 (27,129) & 67,5 (38,131) &
0.115\tabularnewline
\textbf{Dapaglifozin} & 43,5 (17,103) & 60 (41,132) & 88 (38,148) &
\textbf{0.011}\tabularnewline
\textbf{Sacubitril/Valsartan} & 45 (30,70) & 74 (58,103) & 89 (75,157) &
\textbf{\textless{}0.001}\tabularnewline
\textbf{P value*} & 0.750 & 0.652 & 0.278 &\tabularnewline
\bottomrule
\end{longtable}

* Kruskal Wallis

**Friedman

Table 7: Comparison of swimming times of groups\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Swimming session} \textbf{(Second)} \textbf{Median
(Min-Max)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Control group}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Dapagliflozin} \textbf{group}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Sacubitril/Valsartan} \textbf{group}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{P value*}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
188 (165,297)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
203 (171,293)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
203 (182,244)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,671\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
339 (290,510)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
345 (270,590)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
394 (288,420)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,655\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
728 (688,910)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
808 (654,950)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
767 (555,954)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,777\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1154 (966,1245)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1180 (945,1365)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1194 (765,1362)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,760\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1269 (1100,1330)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1402 (1189,1490)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1370 (1143,1613)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,072\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1532 (1214,1974)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1722 (1600,1910)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1827 (1464,2026)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,165\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1680 (1430,2050)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1906 (1653,2170)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1764 (1385,2184)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,68\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1746 (1480,2496)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2170 (1790,2450)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1866 (1685,2252)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0,52\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1889 (1478,2210)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2144 (1986,2387)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2044 (1800,2387)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1955 (1551,3455)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2724 (2625,2939)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2085 (1686,2533)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,009}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2110 (1810,2280)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2407 (2190,3001)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2238 (2022,2464)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2261 (2054,2320)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2787 (2620,3160)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2354 (2104,2773)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2103 (2037,2276)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3055 (3004, 3274)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2350 (2247,2656)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2304 (2060,2474)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3037 (2798,3345)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2677 (2136,2950)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2299 (2100,2382)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2630 (2229,3141)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2435 (2110,2187)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,039}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
16.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2314 (2245,2405)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2710 (2340,3312)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2407 (2135,2173)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,011}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
17.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2371 (2214,2472)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3006 (2360,3140)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2480 (2179,2895)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,046}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
18.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2372 (2256,2492)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3372 (2480,4130)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2397 (2284,2980)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
19.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2343 (2272,2424)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3500 (2630,4003)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2470 (2320,29559\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
20.\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2382 (2300,2467)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3580 (2914,4212)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2591 (2457,3002)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Total time\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
35654 (32315,38332)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
45406 (39839,49157)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38105 (34423,42696)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Median\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1782 (1615,1916)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2270 (1991,2457)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1905 (1721,2134)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{\textless{}0,001}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Kruskal Wallis

Table 8: Comparison of swimming times of the control group and
sacubitril/valsartan group\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Swimming session} \textbf{(Second)} \textbf{Median
(Min-Max)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Control group}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Sacubitril/Valsartan} \textbf{Group}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{P value*}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
188 (165,297)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
203 (182,244)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.431\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
339 (290,510)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
394 (288,420)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.528\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
728 (688,910)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
767 (555,954)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.344\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1154 (966,1245)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1194 (765,1362)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.462\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1269 (1100,1330)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1370 (1143,1613)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.115\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1532 (1214,1974)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1827 (1464,2026)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.172\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1680 (1430,2050)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1764 (1385,2184)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.600\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1746 (1480,2496)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1866 (1685,2252)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.248\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1889 (1478,2210)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2044 (1800,2387)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.141\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1955 (1551,3455)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2085 (1686,2533)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.401\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2110 (1810,2280)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2238 (2022,2464)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.115\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2261 (2054,2320)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2354 (2104,2773)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.172\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2103 (2037,2276)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2350 (2247,2656)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.002}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2304 (2060,2474)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2677 (2136,2950)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.46\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2299 (2100,2382)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2435 (2110,2187)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.093\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
16.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2314 (2245,2405)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2407 (2135,2173)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.462\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2371 (2214,2472)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2480 (2179,2895)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.401\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2372 (2256,2492)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2397 (2284,2980)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.462\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
19.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2343 (2272,2424)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2470 (2320,29559\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.009}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2382 (2300,2467)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2591 (2457,3002)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.002}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Total time\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35654 (32315,38332)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
38105 (34423,42696)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.115\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Median\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1782 (1615,1916)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1905 (1721,2134)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.115\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Mann-Whitney U testi

Table 9: Comparison of swimming times of the control group and
dapagliflozin group\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Swimming session} \textbf{(Second)} \textbf{Median
(Min-Max)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Control group}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Dapagliflozin group}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{P value*}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
188 (165,297)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
203 (171,293)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.462\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
339 (290,510)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
345 (270,590)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.916\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
728 (688,910)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
808 (654,950)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.793\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1154 (966,1245)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1180 (945,1365)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.636\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1269 (1100,1330)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1402 (1189,1490)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1532 (1214,1974)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1722 (1600,1910)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.059\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1680 (1430,2050)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1906 (1653,2170)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1746 (1480,2496)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2170 (1790,2450)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.046\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1889 (1478,2210)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2144 (1986,2387)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.021\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1955 (1551,3455)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2724 (2625,2939)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.012}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2110 (1810,2280)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2407 (2190,3001)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2261 (2054,2320)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2787 (2620,3160)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2103 (2037,2276)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3055 (3004, 3274)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2304 (2060,2474)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3037 (2798,3345)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2299 (2100,2382)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2630 (2229,3141)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
16.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2314 (2245,2405)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2710 (2340,3312)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2371 (2214,2472)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3006 (2360,3140)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2372 (2256,2492)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3372 (2480,4130)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
19.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2343 (2272,2424)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3500 (2630,4003)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2382 (2300,2467)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3580 (2914,4212)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Total time\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35654 (32315,38332)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
45406 (39839,49157)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Median\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1782 (1615,1916)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2270 (1991,2457)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Mann-Whitney U testi\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig-1/fig-1}

\end{center}
\end{figure}

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

