Transcatheter Mitral Valve Replacement Therapies - American College of Cardiology (2023)

Transcatheter mitral valve replacement (MVR) has recently emerged as an exciting new frontier in the field of structural cardiac interventions. Although transcatheter aortic valve replacement (TAVR) is a well-established treatment option for patients with symptomatic severe calcific aortic stenosis, experience with transcatheter MVR is still at an early stage. There have been important challenges in developing this technology, including the complexity of the mitral valve anatomy with a saddle-shaped oval shape, the subvalvular apparatus, the interaction with the left ventricular outflow tract (LVOT) and the aortic valve, and the large size of transcatheter MVR devices and large catheters for implantation. At this stage of development, all of this limits the delivery approach to transapical in most cases. The wide variety of mitral pathology, from stenosis to multiple regurgitation mechanisms, also contributes to the difficulties in valve design. In addition, patients considered for transcatheter MVR are generally at high risk for multiple comorbidities, including frailty, pulmonary hypertension, or severe left ventricular systolic dysfunction, each of which negatively impacts the overall clinical outcome. Despite these technical, anatomical and clinical limitations, significant advances have been made in recent years.

Technology overview and first results with MVR transcatheter

The type of transcatheter heart valve that best suits a particular patient will vary depending on the underlying pathology being treated.

Transcatheter MVR in bioprosthetic or failed surgical rings

Patients with failing bioprostheses or surgical mitral rings have been treated with off-label use of standard transcatheter aortic heart valves. The pre-existing circular structure provided by a surgical bioprosthesis and some surgical rings can be used as a landing zone and provide anchorage for an expandable balloon or newer transcatheter aortic heart valve devices. Therefore, transcatheter aortic heart valve technology was used for this purpose before special transcatheter heart valve devices designed specifically for the mitral position were developed. Transcatheter mitral valve-in-valve and valve-in-ring have been successfully performed with transcatheter aortic heart valves in hundreds of patients worldwide. Most of the reported outcome data comes from case reports, case series, and the VIVID (Valve In Valve International Database) registry.^1-5The most commonly used transcatheter heart valves are the Edwards SAPIEN family valves (Edwards Lifesciences; Irvine, CA) (Figure 1). The administration approach was transapical in most patients. Although the transseptal approach was increasingly chosen, the apical approach was used in 80% of cases in the VIVID registry.⁵The composite endpoint of 30-day survival with no moderate or severe mitral regurgitation (MR) or clinically apparent LVOT obstruction was observed in 88.8% of 349 patients with valvular heart disease and 71% of 88 patients with annular heart valve function retrospectively evaluated in the VIVIDO registry became. The MITRAL (Mitral Implantation of Transcatheter Valves) study is a multicenter, prospective, Food and Drug Administration-approved, physician-sponsored study to evaluate the safety and feasibility of transcatheter MVR with the Edwards SAPIEN 3 valve in three patient populations: Natives with severe mitral valve regurgitation annulus calcification (MAC), failed surgical rings, and failed surgical bioprostheses.⁶The transvenous transseptal approach is the delivery method of choice in this study and is used successfully. Recruitment is ongoing and this study is expected to provide important information on the safety and outcomes of transseptal MVR with transcatheter. Table 1 summarizes the transcatheter MVR clinical trials enrolling patients at the time of publication of this review. These studies are currently in the proof-of-concept phase and are not randomized.

Table 1: Clinical studies with MVR transcatheter

Transcatheter MVR in native mitral valves

The implantation of a transcatheter heart valve in a native mitral valve is significantly more challenging than the valvular procedures in the mitral valve and the valve in the annulus, where there is a scaffold that the surgeon can use as a landing zone to anchor the new prosthesis. A major concern with transcatheter MVR in native mitral valves is obstruction of the LVOT by device encroachment into the LVOT and/or displacement of the anterior mitral leaflets. During MVR surgery, the anterior leaflet of the mitral valve is often removed to relieve LVOT obstruction. The type of transcatheter mitral valve design depends on the pathology. New self-expanding valves with a nitinol frame and an anchoring system are being used and developed in patients with MR. In contrast, in severe calcific mitral stenosis, balloon-expandable valves, mainly aortic transcatheter heart valves, are used.

Mitral insufficiency

Several transcatheter heart valve devices for treating MR are currently being developed. Most of them are in early stages of evaluation with mixed technical and clinical results. Some of them have been adopted by larger companies and are already being evaluated in early clinical proof of concept studies.

The CardiAQ-Edwards™ transcatheter mitral valve (Edwards Lifesciences; Irvine, CA) was the first transcatheter heart valve to be percutaneously implanted in a native mitral valve in humans.⁷The first generation consisted of porcine pericardium fixed on a self-expanding nitinol stent (Figure 1). The second generation CardiAQ can be administered via a transapical or transfemoral transseptal approach. Thirteen patients were treated in compassionate use: one with the first-generation device and the remaining 12 with the second-generation device. Technical success, defined as successful valve deployment, valve deployment, and recovery of the delivery system, was achieved in 92%. There were two procedure-related deaths: one due to interference with a pre-existing mechanical aortic valve and the other to poor positioning resulting from calcification of the inferior leaflets.⁸The RELIEF study was initiated (Table 1).

The Medtronic Intrepid™ Transcatheter Heart Valve (Medtronic; Minneapolis, MN) features an external self-expanding nitinol stent that provides fixation and sealing, and an internal circular stent that accommodates a three-leaf, 27-mm bovine pericardial valve with an effective opening accommodates area 2.4 cm²(Illustration 1). The valve is implanted transapically; a transseptal delivery approach is being developed. In a pilot study, 38 patients were treated. The valve was successfully implanted in 35 patients and there were 4 procedure-related deaths. MRI severity was reduced to 1 (+) in 3 patients and 0 in 32 patients, resulting in symptom improvement of 1 or more functional classes in 21 of 25 patients with available clinical follow-up data.⁹A clinical study was started (Table 1).

The Tendyne™ Mitral Valve System (Tendyne Holdings, LLC, a subsidiary of Abbott Vascular, Roseville, MN) features a self-expanding nitinol dual frame design. The internal structure of the stent is circular and supports a tri-leaflet porcine pericardial valve with an effective opening area of ​​3.2 cm². The outer structure of the stent is D-shaped to conform to the shape of the annulus of the mitral valve. The external stent has a polyterephthalate cuff for sealing in the annulus. Its anchoring mechanism is an apical cord (Figure 1). The valve is introduced via a transapical approach through a 34 Fr sheath. The results of the first 30 patients treated in the global feasibility study were recently published. The valve was successfully implanted in 28 patients (93.3%). Residual MRI was grade 1 in 1 patient and 0 in the remaining 27 patients. Despite a high-risk patient population with a Society of Thoracic Surgeons Mortality Risk Score of 7.3%, there were no cardiac deaths, strokes, or myocardial infarctions at 30 days. On postoperative day 13, there was one non-cardiac death from hospital-acquired pneumonia.¹⁰The expanded clinical study of the Tendyne Mitral Valve System is ongoing (Table 1).

illustration 1

Calcified mitral stenosis

Patients with severe calcified mitral stenosis who are not candidates for standard mitral valve surgery because of the surgical risk have been successfully treated with transcatheter MVR with compassionate use of transcatheter aortic heart valves. Most of these patients were treated with balloon expandable valves. Recently, newer transcatheter aortic heart valve devices such as the LOTUS Edge valve (Boston Scientific; Marlborough, MA) and Direct Flow (Direct Flow Medical; Santa Rosa, CA) have been used successfully to treat patients with severe MAC. However, this experience is currently limited to a few case reports,^11,12and the direct flow valve is no longer available. The TMVR in the MAC Global Registry was created to collect outcome data from similar procedures performed around the world to better understand their safety and efficacy in a larger patient population. The results of the first 64 patients were recently published. The transapical approach was used in 45.3% of patients, transseptal in 40.6% and transatrial in 14.1%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 of 64 patients (72%), limited primarily by the need for a second transcatheter heart valve in 11 (17.2%). At the end of the procedure, the mean VM gradient was 4 ± 2.2 mmHg, the VM aperture area was 2.2 ± 0.95 cm², and paravalvular regurgitation was mild or absent in all patients. Six patients (9.3%) had severe LVOT obstruction with hemodynamic compromise after valve implantation. The 30-day mortality was 29.7% (cardiovascular at 12.5% ​​and non-cardiovascular at 17.2%).¹³Results improved with increasing experience and more patients treated. A subsequent analysis of 104 patients evaluated the results in terms of experience, with patients divided into tertiles in chronological order by date of procedure. Most complications occurred in the first third of patients. Technical success was 62.5% in the first tertile, improving to 84.4% in the second tertile and 80% in the third tertile. The 30-day mortality was 37.5% in the first tertile and decreased to 21.9% in the second tertile and 15% in the last tertile. At 30 days, 29 of 37 patients (78%) with 30-day clinical follow-up data were NYHA Class I or II.¹⁴The MITRAL study is prospectively evaluating the safety and feasibility of Edwards SAPIEN XT and SAPIEN 3 in patients with severe native mitral disease with severe MAC who are not candidates for standard surgical MVR. Applications began in February 2015 and are ongoing at 10 participating locations.⁶

How are patients evaluated for transcatheter mitral valve repair or replacement?

Patients with symptomatic severe mitral valve disease who are not candidates for standard open mitral valve surgery may be candidates for transcatheter mitral valve repair or transcatheter MVR in a clinical trial. At this early stage of transcatheter MVR development, the safety and efficacy of transcatheter MVR remain uncertain. In contrast, transcatheter mitral valve repair with MitraClip (Abbott; Abbott Park, IL) has been shown to offer a similar improvement in symptoms and survival compared to surgery, despite higher rates of residual MI.¹⁵Therefore, given limited transcatheter MVR data at the time of publication of this review, MitraClip transcatheter mitral valve repair should be the first choice for patients with favorable anatomy who meet the clinical indication according to the guidelines. The underlying pathology plays a role in the decision between a transcatheter repair or replacement as the MitraClip repair is only approved for primary MR in the US. The role of catheter-assisted mitral valve repair in patients with secondary MI is being evaluated in the Cardiovascular Outcomes Assessment of the Percutan MitraClip Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) study. Therefore, secondary MR patients with favorable anatomy for MitraClip should be considered for participation in the COAPT study. Secondary MR patients with unfavorable anatomy for mitral valve reconstruction with MitraClip may be considered for participation in a transcatheter MVR clinical trial.

Once patients have been evaluated by a cardiac structural team and are considered poor candidates for surgery and poor candidates for transcatheter mitral valve repair, a cardiac CT scan is performed to carefully assess the size of the mitral valve annulus, the presence of MAC, and the valve implant evaluate modeling and risk assessment of transcatheter MVR-induced LVOT obstruction. Patients with severe calcifying mitral stenosis or regurgitation with severe MAC should be considered for enrollment in the MITRAL study or another study when available. Patients with MR without MAC may be considered for participation in one of the clinical studies evaluating transcatheter heart valve devices designed for the mitral position.

Next Steps

An important next step for clinicians is to refer patients to transcatheter MVR clinical trials. There are still no dedicated mitral prostheses in the world that are well developed or approved for use in practice. The development of transcatheter MVR will be more difficult than TAVR and will only be successful if we support clinical trials.

Conclusions

Transcatheter MVR is emerging as an alternative for patients with severe mitral valve disease who are poor candidates or at risk for conventional mitral valve surgery. This area is in its early stages and progress will be significantly slower than the development of TAVI due to the complexity of mitral valve anatomy and pathology. We learned important lessons during this first experience. There are important challenges with the currently available technology. Improved, less bulky valve designs and delivery methods can improve technical success. A better understanding of the type of anticoagulation required for transcatheter MVR is just beginning to emerge. Streamlining the patient selection process by using multimodal imaging tools to accurately measure ring size and assess risk of LVOT obstruction is essential to minimize complications.

references

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Keywords: aortenclap,Aortic stenosis,Bioprothese,comorbidity,pathological narrowing,heart failure,hemodynamics,pulmonary hypertension,Mitralklappe,Mitral Valve Annuloplasty,Mitralklappenstenose,mitral regurgitation,Heart attack,pericardium,Stents,AVC,surgeons,Tomography,Transcatheter Aortic Valve Replacement

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