The State of Transcatheter Mitral Valve Implantation

Transcatheter interventions have become an alternative treatment option for patients with valvular heart disease who are high-risk candidates for surgery. The development of transcatheter aortic valve implantation (TAVI) has been the vanguard, and now transcatheter mitral valve implantation (TMVI) is following the same pathway. There are many conditions related to mitral valve disease where open heart surgery, even if required, is either refused by the patient or not performed by the surgeon because of increased associated perioperative risks. The development of TMVI has not seen as steep a rise as TAVI because of various epidemiologic-, anatomic-, and device-related factors. Despite this, trials are in progress for finding a solution for surgically ineligible patients.

BACKGROUND

The last 2 decades have seen an increase in transcatheter interventions for valvular heart disease. The invention of TAVI by Dr. Alain Cribier set a benchmark in this field. Approximately a decade after TAVI, TMVI was tried by Søndergaard et al.¹ However, the development of TMVI has been a very slow process compared with TAVI, leading to recurrent heart failure in many patients with mitral regurgitation (MR), which is the second most common valvular heart disease.² Approximately 50% of patients with MR either refuse surgery or are not eligible for surgery,³ which has propelled researchers to develop TMVI.

Although many trials have evaluated TMVI devices, none have been able to achieve FDA approval. Only one device, Tendyne (Abbott), has received CE Mark approval.⁴ Experience from trials has shown that the development of TMVI will not follow the course for TAVI because of various factors. First is the age of the patients, who are relatively younger and also have fewer comorbidities. For this reason, the surgical risks are less.⁵ Second, the anatomy of the mitral valve is more complex as compared to the aortic valve. There are five components of mitral valve structure, unlike the single component of the aortic valve. The shape is not uniformly circular, and the amount of calcification is much less. Due to less calcification, the concept of hinging (such as in the aortic valve) to the calcium cannot be applied here. Third is the fixation, which, unlike the aortic valve, must be an active process due to the risk of valve dislodgement. Also, the radial forces that help stabilize the valve in TAVI cause left ventricular outflow tract (LVOT) obstruction in TMVI. Finally, mitral valve regurgitation is more frequently associated with tricuspid regurgitation and atrial fibrillation compared to aortic stenosis. The presence of MR increases with age, and the most frequent etiology is degenerative, followed by functional MR.

Although surgery is the current treatment of choice, only 33% of patients fit the eligibility criteria for surgery.⁶ A subset of patients with mitral annular calcification (MAC) are poor candidates for surgery, but unlike in TAVI, this calcification that could be used as a hinge for the artificial valve is rarely circumferential, making the annular calcification not as useful in TMVI.⁷

Patients with heart failure should receive treatment prior to the procedure. Other comorbidities that should be considered during management are tricuspid regurgitation, right heart failure, aortic regurgitation or stenosis, associated coronary artery disease or chronic obstructive pulmonary disease, and ability to tolerate oral anticoagulation.

IMAGING NEEDS

Both transthoracic and transesophageal echocardiography should be performed to evaluate mitral valve disease in both two and three dimensions. Then, evaluation of the atrial and ventricular geometry is completed, and all the baseline data are recorded, as the patient is usually followed up after surgery using echocardiography. Detailed assessment of the LVOT is very important. Software is available that provides a virtual simulation of the neo-LVOT after device implantation.

CT scans are used to create a virtual three-dimensional model of the heart, with the artificial mitral valve in place so the results can be observed even before operating on the patient. CT scans also help with prosthesis sizing, evaluating calcium in the annulus, and evaluating the neo-LVOT (including the aorto-mitral angle), interventricular septal bulge, both mitral leaflets, thickness of the wall, best coaxial angle for implantation, and the access site over the chest wall or transeptal puncture site. The various software programs available for this reconstruction include 3Mensio (Pie Medical Imaging), Materialise (Materialise NV), and Circle CVI (Circle Cardiovascular Imaging).⁸

Screening failure for TMVI mainly occurs when there is a moderate and noncircumferential small left ventricle with an end-diastolic dimension of < 48 mm, severely impaired left ventricular function, anticipated neo-LVOT area < 170 mm², septal hypertrophy > 15 mm, long anterior mitral valve leaflet > 25 mm, and narrow aorta mitral angle < 115°.⁴

DEVICE TYPES

Two types of devices are currently under study, divided into single step and multistep based on the steps of device implantation. Single-step devices include Tendyne, Intrepid (Medtronic), AltaValve (4C Medical), Cardiovalve (Venus MedTech), Cephea (Abbott), and Evoque Eos (Edwards Lifesciences). Multistep devices include HighLife (HighLife Medical), Sapien M3 (Edwards Lifesciences), and Saturn (InnovHeart). The most common approach for TMVI has been transapical because of a large delivery system (> 35 F).⁹ While using this approach, one should keep in mind that in cases of MR the myocardium is thinned out. Determining the proper access site helps avoid entanglement with the chords and papillary muscles. Another approach is transseptal, in which percutaneous access is performed with devices > 30 F. A newer “transatrial” approach has been used in some patients with severe circumferential MAC in whom TAVI aortic devices have been tried using the passive fixation method by radial forces.¹⁰

Various anchoring techniques are used with the various devices. A tether and epicardial pad for coordination between axial forces are used in Tendyne.¹¹ Atrial and ventricular flanges for grasping the mitral annulus and leaflets are employed with the CardiAQ device (Edwards Lifesciences).¹ In the case of the Tiara valve (Johnson & Johnson MedTech), native leaflet grasping is used for fixating the prosthesis in place.¹² Docking systems that allow for sufficient radial forces for anchoring of the valve are used with HighLife¹² and Sapien M3.¹³ Subannular hooks that pierce the native mitral valve tissue or the annular winglet are used with NaviGate (NaviGate Cardiac Structures, Inc.).¹² Cork-like effects that produce radial forces that aid in anchoring of prosthesis are used in the Intrepid valve.¹² Lastly, an atrial cage that uses the entire anatomy of the left atrium to prevent valve migration is used with the AltaValve.¹⁴

The Tendyne and Tiara valves are exclusively delivered by the transapical route. The CardioValve, Cephea, Evoque, HighLife, and Sapien M3 valves are exclusively delivered by the transseptal route. Intrepid and AltaValve can be delivered by either route.¹⁵

DATA DISCUSSION

The most common cause of patient noneligibility for TMVI is neo-LVOT obstruction. Many techniques have been developed to deal with this issue. First is alcohol septal ablation, in which 0.5 to 1.0 mL of alcohol is injected slowly over a period of 3 to 5 minutes to reduce the risk of spillage into the cavity. Although the LVOT obstruction initially worsens for a transient period due to myocardial edema, the success rates are high.¹⁶ Another method is LAMPOON (laceration of the anterior mitral leaflet to prevent outflow obstruction), a transcatheter electrosurgical technique to split the anterior mitral valve leaflet immediately prior to TMVI.¹⁷ A third technique is SESAME (septal scoring along midline endocardium), in which a coronary catheter and guidewire enter the left ventricular cavity by traversing the basal interventricular septum up to the midventricular exit point. The wire is then energized to perform myotomy and relieve obstruction.¹⁸

A global feasibility trial showed technical success with use of the Tendyne mitral valve in 96% cases that met the primary endpoint of < 2+ MR at the end of 1 month. There was improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) score from 49 to 67 points.¹⁹ Based on these findings, the Tendyne valve has been evaluated in MAC patients in the MAC feasibility trial and MITRAL trial. Improvement in KCCQ score persisted in both trials.^20,21 The transfemoral Intrepid early feasibility study showed an improvement in Minnesota Living With Heart Failure Questionnaire score, with no mortality at the end of 30 days.²² The APOLLO trial of Intrepid for TMVI is enrolling patients who are not eligible for transcatheter edge-to-edge repair (TEER).²³ The ENCIRCLE trial using the Sapien M3 system is also enrolling candidates who are not eligible for TEER. ENCIRCLE also has an arm for failed TEER and MAC patients.²⁴

CONCLUSION

The development of TMVI has not been a smooth ride, and there are many obstacles that need to be overcome for TMVI use to be widespread and TMVI success to be reproduced. The shortcomings need to be addressed, such as the high failure rate of screening (up to 89%) and limited eligibility criteria. Patient- and device-related factors have delayed the progress of TMVI. Challenges like LVOT obstruction and MAC need to be addressed as these points are crucial for the success of a TMVI procedure. In addition to these, there are also challenges with respect to the durability of the device because our experience is limited. Adding to all this is the need for long-term anticoagulation after a successful TMVI, thus excluding patients who have any absolute contraindication for using long-term anticoagulation, even if they are candidates for TMVI. Further research and development in this field is a must to address the unmet need for transcatheter management of mitral valve disease.

1. Søndergaard L, De Backer O, Franzen OW, et al. First-in-human case of transfemoral CardiAQ mitral valve implantation. Circ Cardiovasc Interv 2015;8:e002135. doi: 10.1161/CIRCINTERVENTIONS.115.002135

2. Iung B, Delgado V, Rosenhek R, et al. Contemporary presentation and management of valvular heart disease: the EURObservational Research Programme Valvular Heart Disease II Survey. Circulation. 2019;140:1156-1169. doi: 10.1161/CIRCULATIONAHA.119.041080

3. Iung B, Delgado V, Lazure P, et al. Educational needs and application of guidelines in the management of patients with mitral regurgitation. A European mixed-methods study. Eur Heart J. 2018;39:1295-1303. doi: 10.1093/eurheartj/ehx763

4. Urena M, Lurz P, Sorajja P, et al. Transcatheter mitral valve implantation for native valve disease. EuroIntervention. 2023;19:720-738. doi: 10.4244/EIJ-D-22-00890

5. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro Heart survey on valvular heart disease. Eur Heart J. 2003;24:1231-1243. doi: 10.1016/s0195-668x(03)00201-x

6. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. EuroIntervention. 2022;17:e1126-e1196. doi: 10.4244/EIJ-E-21-00009

7. Carpentier AF, Pellerin M, Fuzellier JF, Relland JY. Extensive calcification of the mitral valve annulus: pathology and surgical management. J Thorac Cardiovasc Surg. 1996;111:718-729. doi: 10.1016/s0022-5223(96)70332-x

8. Blanke P, Modine T, Duncan A, et al. Anatomic suitability for transapical transcatheter mitral valve implantation using a tether-based device. Catheter Cardiovasc Interv. 2023;102:318-327. doi: 10.1002/ccd.30752

9. Bapat V, Rajagopal V, Meduri C, et al. Early experience with new transcatheter mitral valve replacement. J Am Coll Cardiol. 2018;71:12-21. doi: 10.1016/j.jacc.2017.10.061

10. Urena M, Vahanian A, Brochet E, et al. Current indications for transcatheter mitral valve replacement using transcatheter aortic valves: valve-in-valve, valve-in-ring, and valve-in-mitral annulus calcification. Circulation. 2021;143:178-196. doi: 10.1161/CIRCULATIONAHA.120.048147

11. Muller DWM, Farivar RS, Jansz P, et al. Transcatheter mitral valve replacement for patients with symptomatic mitral regurgitation: a global feasibility trial. J Am Coll Cardiol. 2017;69:381-391. doi: 10.1016/j.jacc.2016.10.068

12. Regueiro A, Granada JF, Dagenais F, Rodés-Cabau J. Transcatheter mitral valve replacement: insights from early clinical experience and future challenges. J Am Coll Cardiol. 2017;69:2175-2192. doi: 10.1016/j.jacc.2017.02.045

13. Yasmin F, Najeeb H, Fareed Siddiqui H, et al. Current practices and considerations for transcatheter mitral valve implantation based on risk stratification among patients with mitral valve regurgitation. Curr Probl Cardiol. 2023;48:101413. doi: 10.1016/j.cpcardiol.2022.101413

14. Nunes Ferreira-Neto A, Dagenais F, Bernier M, et al. Transcatheter mitral valve replacement with a new supra-annular valve: first-in-human experience with the AltaValve System. JACC Cardiovasc Interv. 2019;12:208-209. doi: 10.1016/j.jcin.2018.10.056

15. Hensey M, Brown RA, Lal S, et al. Transcatheter mitral valve replacement: an update on current techniques, technologies, and future directions. JACC Cardiovasc Interv. 2021;14:489-500. doi: 10.1016/j.jcin.2020.12.038

16. Wang DD, Eng MH, Greenbaum AB, et al. Validating a prediction modeling tool for left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR). Catheter Cardiovasc Interv. 2017;92:379-387. doi: 10.1002/ccd.27447

17. Case BC, Lisko JC, Babaliaros VC, et al. LAMPOON techniques to prevent or manage left ventricular outflow tract obstruction in transcatheter mitral valve replacement. Ann Cardiothorac Surg. 2021;10:172-179. doi: 10.21037/acs-2020-mv-25

18. Greenbaum AB, Khan JM, Bruce CG, et al. Transcatheter myotomy to treat hypertrophic cardiomyopathy and enable transcatheter mitral valve replacement: first-in-human report of septal scoring along the midline endocardium. Circ Cardiovasc Interv. 2022;15:e012106. doi: 10.1161/CIRCINTERVENTIONS.122.012106

19. Muller DWM, Sorajja P, Duncan A, et al. 2-year outcomes of transcatheter mitral valve replacement in patients with severe symptomatic mitral regurgitation. J Am Coll Cardiol. 2021;78:1847-1859. doi: 10.1016/j.jacc.2021.08.060

20. Gössl M, Thourani V, Babaliaros V, et al. Early outcomes of transcatheter mitral valve replacement with the Tendyne system in severe mitral annular calcification. EuroIntervention. 2022;17:1523-1531. doi: 10.4244/EIJ-D-21-00745

21. Guerrero M, Wang DD, Eleid MF, et al. Prospective study of TMVR using balloon-expandable aortic transcatheter valves in MAC: MITRAL trial 1-year outcomes. JACC Cardiovasc Interv. 2021;14:830-845. doi: 10.1016/j.jcin.2021.01.052

22. Zahr F, Song HK, Chadderdon SM, et al. 30-Day outcomes following transfemoral transseptal transcatheter mitral valve replacement: Intrepid TMVR early feasibility study results. JACC Cardiovasc Interv. 2022;15:80-89. doi: 10.1016/j.jcin.2021.10.018

23. Medtronic. The APOLLO trial. Accessed on August 28, 2024. https://www.medtronic.com/en-us/l/clinical-trials/apollo-intrepid-tmvr/about.html

24. Edwards. The ENCIRCLE trial. Accessed on August 28, 2024. https://www.edwards.com/healthcare-professionals/trial/encircle-hcp