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).