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\begin{document}

\title{The feasibility evaluation of transapical saddle-shaped valved stent for
transcatheter mitral valve implantation}



\author[1]{Kaiqin Wu}%
\author[1]{Shaorui Gu}%
\author[1]{Tiancheng Lu}%
\author[1]{Shengting Dong}%
\author[1]{Chenglai Dong}%
\author[2]{Haitao Huang}%
\author[1]{Zhenchuan Liu}%
\author[1]{Xin Zhang}%
\author[1]{Yongxin Zhou}%
\affil[1]{Department of Thoracic-Cardiovascular Surgery Tongji Hospital School of Medicine Tongji University Shanghai 200065 China}%
\affil[2]{Department of Thoracic and Cardiovascular Surgery Nantong First People's Hospital Nantong 226001 China}%


\vspace{-1em}



  
  \date{June 08, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Background:} Transcatheter mitral valve implantation (TMVI) is a
promising and minimally invasive treatment for high-risk mitral
regurgitation (MR). The purpose of this study was to investigate the
feasibility of a novel self-expanding valved stent for transcatheter
mitral valve implantation via apical access. \textbf{Methods:} A novel
self-expanding mitral valved stent system was designed and fabricated
for the in vivo evaluation. It is consists of an atrial flange and a
saddle-shaped ventricular body connected by two opposing anchors and two
opposing extensions. During the valve deployment, each anchor is
controlled by a recurrent string. TMVI was performed in ten pigs using
the valve prosthesis through the apical access to verify technical
feasibility. Echocardiography and ventricular angiography were used to
assess hemodynamic data and valve function. The surviving pigs were
sacrificed four weeks later to confirm stent deployment.
\textbf{Results:} Ten animals underwent transapical mitral valve
implantation with the novel mitral valved stent. Optimal valve
deployment and accurate anatomical adjustment were obtained in nine
animals. Implantation failed in one case, and the animal died one day
later due to stent mismatch. After stent implantation, the hemodynamic
parameter of other animals was stable and valve function was normal. The
mean pressure across the mitral valve and left ventricular outflow tract
(LVOT) were 2.98\selectlanguage{ngerman}±0.91mmHg and 3.42±0.66 mmHg, respectively. The
macroscopic evaluation confirmed the stable and secure positioning of
the stents in the mitral valve. No obvious valve displacement, embolism,
and paravalvular leakage were observed four weeks after valve
implantation. \textbf{Conclusions:} This study proved that the novel
mitral valved valve stent is technically feasible in animals. This
device features opposing anchors, opposing recurrent strings, and
saddle-like ventricular portions, providing structural design details
for reducing TMVI complications. However, the long-term feasibility and
durability of this valved stent need to be improved and verified.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Paper Title} :

The feasibility evaluation of transapical saddle-shaped valved stent for
transcatheter mitral valve implantation

\textbf{Authors} :Kaiqin Wu\textsuperscript{1}, Shaorui
Gu\textsuperscript{1}, Tiancheng Lu\textsuperscript{1}, Shengting
Dong\textsuperscript{1}, Chenglai Dong\textsuperscript{1}, Haitao
Huang\textsuperscript{2}, Zhenchuan Liu\textsuperscript{1}, Xin
Zhang\textsuperscript{1}, Yongxin Zhou\textsuperscript{1}*

\textbf{Affiliations:} 1 Department of Thoracic-Cardiovascular Surgery,
Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065,
China; 2 Department of Thoracic and Cardiovascular Surgery, Nantong
First People's Hospital, Nantong 226001, China

\textbf{Corresponding author information} :Yongxin Zhou, Department of
Thoracic-Cardiovascular Surgery, Tongji Hospital, School of Medicine,
Tongji University, 389 Xincun Road, Shanghai 200065, China. Telephone
number: +8613681666828;

Email: zhou6302@tongji.edu.cn

Keywords: Transcatheter mitral valve implantation, Mitral Regurgitation,
Valve Prosthesis

Running title: feasibility of TMVI stent

\textbf{Abstract}

\textbf{Background:}Transcatheter mitral valve implantation (TMVI) is a
promising and minimally invasive treatment for high-risk mitral
regurgitation (MR). The purpose of this study was to investigate the
feasibility of a novel self-expanding valved stent for transcatheter
mitral valve implantation via apical access.

\textbf{Methods:} A novel self-expanding mitral valved stent system was
designed and fabricated for the in vivo evaluation. It is consists of an
atrial flange and a saddle-shaped ventricular body connected by two
opposing anchors and two opposing extensions. During the valve
deployment, each anchor is controlled by a recurrent string. TMVI was
performed in ten pigs using the valve prosthesis through the apical
access to verify technical feasibility. Echocardiography and ventricular
angiography were used to assess hemodynamic data and valve function. The
surviving pigs were sacrificed four weeks later to confirm stent
deployment.

\textbf{Results:}Ten animals underwent transapical mitral valve
implantation with the novel mitral valved stent. Optimal valve
deployment and accurate anatomical adjustment were obtained in nine
animals. Implantation failed in one case, and the animal died one day
later due to stent mismatch. After stent implantation, the hemodynamic
parameter of other animals was stable and valve function was normal. The
mean pressure across the mitral valve and left ventricular outflow tract
(LVOT) were 2.98\selectlanguage{ngerman}±0.91mmHg and 3.42±0.66 mmHg, respectively. The
macroscopic evaluation confirmed the stable and secure positioning of
the stents in the mitral valve. No obvious valve displacement, embolism,
and paravalvular leakage were observed four weeks after valve
implantation.

\textbf{Conclusions:}This study proved that the novel mitral valved
valve stent is technically feasible in animals. This device features
opposing anchors, opposing recurrent strings, and saddle-like
ventricular portions, providing structural design details for reducing
TMVI complications. However, the long-term feasibility and durability of
this valved stent need to be improved and verified.

INTRODUCTION

Mitral regurgitation(MR) is one of the most prevalent valvular diseases
in the world. (1) Surgical mitral replacement is the golden treatment
for patients with severe MR, but nearly half of patients with severe MR
are rejected. (2) Due to lack of surgical treatment, severe MR patients
have a high mortality rate. (3) Transcatheter mitral valve implantation
(TMVI) is a minimally invasive treatment for severe MR patients with
high surgical risk. (4) The clinical effect of the TMVI device is
promising. The Tendyne TMVI system has been approved by the European
administration for the treatment of MR(5). Several TMVI devices are
undergoing preclinical evaluation or clinical trials, including CardiAQ,
Twelve, Tiara, and Fortis. (6) Our team designed a novel TMVI valve
stent, which is characterized by two opposing anchors points for
grasping native leaflets and two recurrent strings points for accurate
valve deployment. A coherent delivery system was designed for the
tri-step implantation of the TMVI valve stent through transapical
access. The feasibility of the technique was verified by in vivo
experiments.

MATERIALS AND METHODS

\textbf{The novel mitral valved stent system}

The valved stent is a self-expanding nitinol stent with bovine
pericardial tissue leaflets and biocompatible silicone membrane.
(Figure1 A-D) The nitinol stent frame was divided into four parts:
atrial side, ventricular body, extensions, and anchors. The height of
the valved stent is 20mm and the longest diameter of its ventricular
body is 27, 30, 33, and 35mm. The ventricular body is like an inverted
cone or saddle, attached by two opposing extensions and two opposing
anchors. The extension is triangular, opposed with another, and combined
with the ventricular body to reduce the paravalvular leakage. The flange
of the atrial side is located at the base of the left atrium and
prevents the prosthesis from migrating into the ventricle. The anchor
can be abducted by the string while the valve deployment. Two opposing
strings stabilize the stent and retrieve it for valve redeployment and
readjustment. The structure of the stent is fitted into the complexity
of the mitral valve. One anchor is opposite the other and is controlled
by a recurrent string, functioning to grasping, engaging, and preserving
the native mitral leaflet to avoid valve displacement. The tricuspid
pericardial heart valve is mounted on the ventricular body. The nitinol
frame is covered with an ultra-thin biocompatible membrane to reduce
valve regurgitation.

The valved prosthesis is compressed at the front end of the 28fr
delivery system. Each string was loaded inside the delivery system and
hung on the anchor in a recurrent direction to control the anchor
abduction and stent retrieving. (Figure 1E) Only qualified valve stents
are used in animal studies. The releasing and retrieving process of the
valved stent system was tested before sterilization.

\textbf{Animal preparation}

The animal study was approved by the local hospital's ethics committee
with a project license (NO.2018-DW-006). All animal procedures were
completed under the ''Guide for the Care and Use of Laboratory Animals''
issued by the Ministry of Science and Technology of China. Pigs weighing
55-75Kg were selected for the valve intervention. All animals were
fasted and deprived of water eight hours before surgery. Transthoracic
cardiac echocardiography was performed to measure mitral anatomy before
valved stent deployment. The maximum diameter of the mitral annulus and
mitral area were accurately measured for subsequent study. (Figure 2
A\&B)

\textbf{TMVI procedure}

Experimental pigs were anesthetized with 4-10mg propofol for induction
and maintained with 4-12mg/kg/h propofol. A left anterolateral
thoracotomy was performed minimally in the fifth intercostal space for
access to the left ventricle (LV) apex. Echocardiography and fluoroscopy
were utilized as intraoperative guidance. Heparin (200 IU/kg) was
administered intravenously before apical catheterization. An LV apex
incision was performed following the echocardiographic measurement and
sutured with two box stitches (Polyprolene2-0). A 0.035-inch J-shaped
guidewire was inserted into the LV and retrograded across the mitral
valve into the left atrium under the guidance of epicardial
echocardiography and fluoroscopy. Then it was manipulated into the left
inferior pulmonary vein and exchanged with a super-stiff guidewire.
After the LV apex incision was dilated, a delivery system with a crimped
valve prosthesis and two recurrent strings was introduced into the LV.
The prosthesis was rotated to fit the anatomical position (one anchor
matched anterior leaflet and another matched and posterior leaflet) and
deployed following the tri-step implantation process. If the stent
deployment is found to be inappropriate, the mitral stent was retrieved
and redeployed. After valve implantation, intraoperative
echocardiography was performed to confirm and evaluate the position and
function of the implanted valve. (Figure 4) The delivery system was
subsequently removed and replaced with a pigtail catheter for
fluoroscopy to identify valvular insufficiency, paravalvular leakage
(PVL), and left ventricular outflow tract (LVOT) obstruction, and
coronary artery obstruction. (Figure 3) Finally, the chest incision was
processed routinely. After implantation, all experiment animals received
standardized care. All surviving pigs were monitored clinically and then
sacrificed for four weeks. All the hearts were explanted for macroscopic
evaluation. (Figure 5)

\textbf{Statistical analysis}

The data was recorded, analyzed, and presented as means±SD by SPSS 17.0
software.

RESULTS

Ten pigs received the TMVI procedures using the novel valved stent
system. The mean weight of animals was 62.90±5.80Kg, and the mean
diastolic diameter of the mitral annulus was 29.30±2.05mm, ranging from
26-33mm. The diameter of the mitral valved stent was 32.00±3.10mm,
ranging from 27-35mm. All but one valved stent was larger than the
measured mitral annulus. (Table 1)

The mitral stent was deployed successfully in all experiments. The
operation time and deployment time were 77.33±11.58 minutes and
27.44±6.99 minutes respectively. The blood loss volume averaged
351.78±41.54 ml. And the transvalvular pressure across the mitral valve
and left ventricular outflow tract (LVOT) were 2.98±0.91mmHg versus
3.42±0.66mmHg, respectively. (Table 2)

One animal died after a failed valve implantation and the necropsy found
that the novel prosthesis valve immigrated because its size was smaller
than the mitral annulus. The hemodynamic parameter was stable in the
remaining animals and valve function was normal after stent
implantation. The macroscopic evaluation confirmed the stable and secure
positioning of the stents in the mitral valve. No obvious valve
displacement, embolization, and paravalvular leakage were observed four
weeks after valve implantation. However, there were some metallic
fractures at the ventricular partial margin of the mitral valve stent in
three cases.

DISCUSSION

The surging success of transcatheter aortic valve replacement\selectlanguage{english}(TAVI\selectlanguage{english})is
speeding up the innovation and transformation in valve disease
treatment. (7) The shift from valve replacement with sternotomy to
catheter-based valve implantation has been encouraging. (8) The
application of TAVI has revolutionized the treatment of symptomatic
severe aortic valve stenosis in the past decade. Though most of the
patients who received TAVI were elderly, high-risk, and unsuitable for
surgical valve replacement, the risk of TAVI was proved to be tolerable
and its outcomes are promising. (9) However, transcatheter mitral valve
implantation (TMVI) is still at dawn. (10) Though the first-in-man case
of TMVI was reported in 2012, the total reported cases in current
literature were approximately 300. (11) The Tendyne valve system, the
first approved TMVI device, was a great breakthrough. (5) However, many
challenges still delay and render the clinical application of TMVI,
including the asymmetrical mitral annulus, high-pressure gradients, and
lack of secure anatomic structure for valve fixation. Paravalvular
leakage or valvular regurgitation should be minimized, and fatal LVOT
obstruction should be avoided. (12-14)

We have designed and fabricated a novel catheter-based mitral stent for
TMVI that features in saddle-like ventricular portion, two anchors, and
two recurrent strings. This main portion of the valved stent valve was
saddle-like, which means that the upper sectional (atrial side) area is
smaller than the bottom sectional (ventricular side) area. This design
was special and conducive to resisting the high-pressure blood by
expanding the stress area and then transferring the compression force to
the surrounding structure. Besides, the ventricular body is attached by
two opposing extensions, thus fitting to the sub-valvular structure,
enhancing the valve stability and reducing the paravalvular leakage. The
anchoring mechanism was the combination of the atrial flange, two
opposing anchors, and suitable radial force. The design of the anchor is
significantly important for the TMVI device as the anterior leaflet is a
part of the left ventricular output tract. To increase the grasping
angle of the anchor, two strings were specifically designed for the
anchor abduction. Two strings were previously loaded inside the delivery
system in a recurrent direction and hung on paired anchors. During the
valve deployment, two strings also keep the stent remaining inside the
delivery system and thus make stent retrieving possible. The string can
be remained as the artificial chordae tendineae to sustain the stent or
be removed easily (because it's placed in a recurrent direction).

In this study, we focus on the technical feasibility of the valve
prosthesis. We performed animal experiments to investigate the in-vivo
function of the stent and evaluate the possible complications, such as
LVOT obstruction, valve regurgitation, paravalvular leakage. Ten animal
experiments were undergone TMVI using the valve prosthesis. All valve
prosthesis deployments were successful in the animals. In the surviving
cases, intraoperative echocardiography and fluoroscopy show the stable
hemodynamic function of the Mitral stent without LVOT obstruction or
severe paravalvular leakage. These results indicated the technical
feasibility of the Mitral stent system in transcatheter mitral valve
implantation. According to the TAVI practice, paravalvular leakage was
prevalent after valve implantation and remains an unsolved problem. (16)
Trace or mild paravalvular leakages were found in all surviving animals,
which were caused by high-pressure blood during the diastolic phase.
Clinical paravalvular leakage should be followed up in the long-term
evaluation.

One pig died one day after valve replacement. Necropsy found that the
diameter of the valve prosthesis was smaller than the maximum diameter
of the mitral ring, resulting in stent displacement. These results
suggest that the size of the mitral stent should be larger than, but not
equal to, the native mitral valve to avoid valve displacement. The
mitral valve anatomy, especially the maximum diameter of the mitral
annulus, should be accurately evaluated before surgery. In order to make
more accurate preoperative imaging evaluation and avoid the possible
errors of a single imaging method, a combination of multiple imaging
methods should be considered for the anatomic evaluation of the mitral
valve. Preoperative imaging results show that the mean diameter of the
diastolic mitral ring was 29.33+-2.05mm. The mean diameter of the valved
stent used in this study was 32.00+-3.10mm. The diameter of the valve
prosthesis exceeds the maximum diameter of the mitral annulus by
10\%-15\%, which means that the size of the valve prosthesis was larger
than the mitral valve orifice.

The mitral valved stent produced in this study for TMVI was designed to
validate the feasibility and concept of the new fixation system. In
three cases, some nitinol fractures were found along partial ventricular
margins of stents. The main causes of metal fatigue are high ventricular
pressure and frequent heart contractions. Finite element analysis and
durability tests are needed to improve the structural strength of the
valved stent in further research.

Limitations

There are several limitations to our animal experiment. This is a
feasibility preclinical study on a specifically designed transcatheter
mitral prosthesis. Given the pathological change of acute MR are
different from chronic MR, we have not performed the TMVI in an acute MR
animal model. In this study, the transapical approach provides direct
access to the native mitral leaflets. However, retrograde access was at
times difficult because of the blood flow interference or sub-valvular
structure obstacle. Moreover, this animal experiment was a short-term
evaluation for the TMVI prosthesis without the ability to evaluate for
long-term mitral device durability. Animal experiments in chronic MR
models and subsequent long-term evaluation should be considered in
further research.

CONCLUSION

The experiment results demonstrated that the novel transapical mitral
valved stent was technically feasible. This device was designed with
several structure innovations like strings-controlling-anchor and
saddle-like ventricular body to reduce the complications of TMVI,
providing a novel potential TMVI device design. However, its durability
should be enhanced and the long-term evaluation should be considered in
further research.

Funding

This work was supported by the National Natural Science Foundation of
China (No.81670463, No.81974053) and the Shanghai Science and Technology
Committee Foundation (No.16441907800).

\textbf{Acknowledgments}

We thank the help from the staff of Tongji hospital affiliated with
Tongji University, including the department of cardiac echocardiography,
the department of cardiac angiography, and the animal laboratory
management office. Without their help and professional guidance, we
can't finish this tough research project.

\textbf{Conflicts of interest}

The authors declare that there is no conflict of interest.

Author contribution

Yongxin Zhou supervised the research project, designed the Mitral stent
system, executed the animal experiment, and modified the manuscript.
Kaiqin Wu executed the animal experiment and wrote the manuscript.
Shaorui Gu, Ttiancheng Lu, Zhenchuan Liu, Chenglai Dong, Xin Zhang, and
Haitao Huang were involved in the animal experiments. Shaorui Gu and
Tiancheng Lu also recorded and evaluated the experimental data.

Reference

1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG,
Enriquez-Sarano M. Burden of valvular heart diseases: a population-based
study. The Lancet 2006;368(9540):1005-1011.

2. Mirabel M, Iung B, Baron G, Messika-Zeitoun D, Detaint D,
Vanoverschelde J-L, Butchart EG, Ravaud P, Vahanian A. What are the
characteristics of patients with severe, symptomatic, mitral
regurgitation who are denied surgery? European heart journal
2007;28(11):1358-1365.

3. Iung B, Vahanian A. Epidemiology of valvular heart disease in the
adult. Nat Rev Cardiol 2011;8(3):162-72.

4. Patel A, Bapat V. Transcatheter mitral valve replacement: device
landscape and early results. EuroIntervention 2017;13(Aa):Aa31-aa39.

5. Duncan A. Transcatheter Mitral Valve Replacement: The Tendyne Device.
Transcatheter Mitral Valve Therapies 2021:261-275.

6. Tabata N, Sinning JM, Kaikita K, Tsujita K, Nickenig G, Werner N.
Current status and future perspective of structural heart disease
intervention. J Cardiol 2019;74(1):1-12.

7. Iyer R, Chalekian A, Lane R, Evans M, Yi S, Morris J. Transcatheter
Mitral Valve Replacement: Functional Requirements for Device Design,
Bench-Top, and Pre-Clinical Evaluation. Cardiovasc Eng Technol
2018;9(3):301-338.

8. Van Linden A, Doss M, Arsalan M, Kim WK, Walther T. Transcatheter
aortic valve implantation--update and evidence. Minim Invasive Ther
Allied Technol 2015;24(5):255-63.

9. Rahhab Z, El Faquir N, Tchetche D, Delgado V, Kodali S, Mara Vollema
E, Bax J, Leon MB, Van Mieghem NM. Expanding the indications for
transcatheter aortic valve implantation. Nat Rev Cardiol
2020;17(2):75-84.

10. Kheiwa A, Divanji P, Mahadevan VS. Transcatheter pulmonary valve
implantation: will it replace surgical pulmonary valve replacement?
Expert review of cardiovascular therapy 2018;16(3):197-207.

11. Saccocci M, Taramasso M, Maisano F. Mitral Valve Interventions in
Structural Heart Disease. Current cardiology reports 2018;20(6):49-49.

12. Urena M, Vahanian A, Sondergaard L. Patient selection for
transcatheter mitral valve implantation: why is it so hard to find
patients? EuroIntervention 2018;14(Ab):Ab83-ab90.

13. Urena M, Vahanian A, Sondergaard L. Patient selection for
transcatheter mitral valve implantation: why is it so hard to find
patients? EuroIntervention: journal of EuroPCR in collaboration with the
Working Group on Interventional Cardiology of the European Society of
Cardiology 2018;14(AB): AB83-AB90.

14. Vogelhuber J, Weber M, Sinning JM, Nickenig G. Transcatheter mitral
valve replacement: current status. Herz 2019;44(7):602-610.

15. Bapat V, Buellesfeld L, Peterson MD, Hancock J, Reineke D, Buller C,
Carrel T, Praz F, Rajani R, Fam N and others. Transcatheter mitral valve
implantation (TMVI) using the Edwards FORTIS device. EuroIntervention
2014;10 Suppl U: U120-8.

16. Schewel D, Frerker C, Schewel J, Wohlmuth P, Meincke F, Thielsen T,
Kreidel F, Kuck KH, Schafer U. Clinical impact of paravalvular leaks on
biomarkers and survival after transcatheter aortic valve implantation.
Catheterization and Cardiovascular Interventions 2015;85(3):502-514.

Figure Legends

Figure 1 Novel mitral valved stent for transcatheter implantation.

(A) Atrial side view of the valve prosthesis. (B) Ventricular side view
of the valve prosthesis. (C-D) Lateral side view of the valve
prosthesis. The main structure of the valve prosthesis was mainly
divided into four parts, including the atrial flange and the ventricular
portion, which are attached to two opposing extensions (star marker) and
two opposing anchors (rectangular dotted lines). (E) The valve
prosthesis is compressed within a delivery system, with recurrent
strings (red arrow) hanging from each pair of anchors. Anchor (red
triangle) is abducted at an angle by the string for grasping.

Figure 2 Preoperative echocardiography evaluation before the animal
experiment

(A) The native mitral valve opening during the left ventricular
diastole. (B)The native mitral valve closed during the left ventricular
systole without valve regurgitation.

Figure 3 Representative fluoroscopy images after valved stent deployment

(A) The valve prosthesis was successfully deployed in the heart
(asterisk labeled prosthesis), and the delivery system was removed and
the ventricular angiography was performed with a pigtail catheter (arrow
pointing to the pigtail catheter).

(B) Ventricular angiography showed that the valve prosthesis was closed
normally in diastole. There is trace paravalvular leakage in this case.
No obvious LVOT obstruction was observed. MV=Mitral valve, LV=Left
ventricle, LA= Left atrium, Ao= Aorta.

Figure 4 Representative echocardiography images after valve deployment

The valve prosthesis was closed well during the left ventricular
systole. (B) Valve prosthesis was opening during the left ventricular
diastole. (LV=Left Ventricle, LA= Left Atrium)

Figure 5 Representative images of necropsy

(A)The pig heart atrium was removed to expose the valve prosthesis. The
atrial flange of the valved stent is located on the mitral annulus.

(B) The left ventricle tissue was dissected to reveal the valve
prosthesis and subvalvular structure. Both anchors successfully clamped
the native leaflet (green arrow) and the valve prosthesis was stable in
the mitral position. There were no LVOT obstruction, valve displacement,
rupture of chordae tendineae or papillary muscle ischemia, or other
subvalvular structural injury. The native mitral leaflets are sandwiched
between anchors and the ventricular body of the stent.

(C) Careful examination of the valve prosthesis revealed no embolism or
nitinol fracture. No leaflets rupture or dislocating was observed.

Tables

Table 1 Procedural data of animal experiments\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
No. & Weight & Mitral annulus diameter & Mitral valve area & Stent size
& Stent area & Operation time & Intervention time & Blood loss
volume\tabularnewline
\midrule
\endhead
& (Kg) & (mm) & (cm2) & (mm) & (cm2) & (min) & (min) &
(ml)\tabularnewline
1 & 55 & 26 & 676 & 27 & 729 & 92 & 39 & 353\tabularnewline
2 & 64 & 27 & 784 & 27 & 900 & NA & NA & NA\tabularnewline
3 & 56 & 28 & 729 & 30 & 729 & 75 & 25 & 304\tabularnewline
4 & 59 & 28 & 784 & 30 & 900 & 76 & 21 & 365\tabularnewline
5 & 62 & 30 & 900 & 33 & 1089 & 65 & 35 & 300\tabularnewline
6 & 69 & 29 & 841 & 33 & 1089 & 70 & 29 & 433\tabularnewline
7 & 70 & 32 & 1024 & 35 & 1225 & 93 & 31 & 310\tabularnewline
8 & 72 & 30 & 900 & 35 & 1225 & 90 & 25 & 394\tabularnewline
9 & 60 & 33 & 1089 & 35 & 1225 & 77 & 28 & 365\tabularnewline
10 & 62 & 30 & 900 & 35 & 1225 & 58 & 14 & 342\tabularnewline
mean\selectlanguage{ngerman}±SD & 62.90\selectlanguage{ngerman}±5.8 & 29.30\selectlanguage{ngerman}±2.05 & 862.70\selectlanguage{ngerman}±121.24 & 32.00\selectlanguage{ngerman}±3.10 &
1066.60\selectlanguage{ngerman}±193.37 & 77.33\selectlanguage{ngerman}±11.58 & 27.44\selectlanguage{ngerman}±6.99 & 351.78\selectlanguage{ngerman}±41.54\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

Note: No.2 Pig died of failed valve implantation after one day and its
data was not applicable and excluded. NA: Not available/applicable.

Table 2 Hemodynamic data during TMVI\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
No. & Before TMVI & Before TMVI & After TMVI & After TMVI &
Transvalvular Pressure & Transvalvular Pressure\tabularnewline
\midrule
\endhead
& Blood Pressure & Heart Rate & Blood Pressure & Heart Rate & Mitral
valve & LVOT\tabularnewline
& (mm Hg) & (bpm) & (mm Hg) & (bpm) & (mm Hg) & (mm Hg)\tabularnewline
1 & 122/75 & 57 & 116/67 & 48 & 2 & 3\tabularnewline
2 & 99/60 & 61 & NA & NA & NA & NA\tabularnewline
3 & 118/68 & 70 & 126/80 & 43 & 4 & 3.3\tabularnewline
4 & 130/69 & 71 & 117/75 & 97 & 3 & 2.9\tabularnewline
5 & 133/66 & 79 & 128/79 & 70 & 2.5 & 3.2\tabularnewline
6 & 108/59 & 80 & 123/61 & 71 & 2.4 & 2.5\tabularnewline
7 & 115/75 & 71 & 133/85 & 95 & 4 & 3.9\tabularnewline
8 & 108/64 & 60 & 135/86 & 82 & 1.6 & 3.8\tabularnewline
9 & 113/78 & 81 & 123/85 & 69 & 3 & 3.3\tabularnewline
10 & 135/68 & 76 & 119/68 & 97 & 4.4 & 4.9\tabularnewline
mean\selectlanguage{ngerman}±SD & 118.10\selectlanguage{ngerman}±11.26/68.20±6.03 & 70.6\selectlanguage{ngerman}±8.28 & 126.2\selectlanguage{ngerman}±8.41/77.5±9.45 &
74.7\selectlanguage{ngerman}±20.1 & 2.98\selectlanguage{ngerman}±0.91 & 3.42\selectlanguage{ngerman}±0.66\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

LVOT: Left Ventricular Outflow Tract. NA: Not available/applicable.\selectlanguage{english}
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