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(TAVI)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).