Transcatheter Mitral Valve Replacement

Learning Objectives

• While a transcatheter approach has become ubiquitous for aortic valve replacement, transcatheter mitral valve replacement has been slower to gain traction.

• The more complex anatomy and pathophysiology of mitral valve disease, in comparison to the aortic valve, complicates device design and deployment technique of transcatheter replacement for the mitral valve.

• TMVR is most likely to gain use in the near future as an alternative for prohibitively high-risk surgical patients with severe mitral regurgitation who are not suitable for repair with MitraClip.

INTRODUCTION

While surgical mitral valve repair or replacement remains the standard of care for symptomatic, severe mitral regurgitation, nearly 50% of these patients are not referred for conventional surgical mitral valve replacement (MVR) due to significant comorbidities and high surgical risk. Over the past few years, transcatheter mitral valve interventions using edge-to-edge repair have helped to address some of these high-risk patients. However, a significant group of patients are not candidates for this technique because of unsuitable mitral anatomy for clip repair. In addition, a substantial group of patients (10% to 20%) continue to have significant, moderate or severe, residual regurgitation after the clip repair. Transcatheter mitral valve replacement (TMVR) is a niche for those patients that are not currently served with the existing treatment options ( Table 24.1 ).

CURRENT INDICATIONS AND USE

TMVR is a novel option to treat both severe mitral regurgitation and mitral stenosis without the need for surgery. TMVR valves can be classified broadly based on whether the patient has had prior mitral valve intervention into valve-in-valve or native valve replacement. Valve-in-valve TMVR involves implanting a catheter expandable valve (usually an Edwards S3 valve) inside an existing prosthetic valve. This technique has gained food and drug administration (FDA) approval for patients with failing bioprosthetic valves who are too high risk for a surgical re-do MVR. Valve-in-valve TMVR has also been used for patients with prior mitral rings presenting with worsening mitral regurgitation (MR) or mitral stenosis (MS). Conversely, native TMVR involves replacement in patients with native mitral valve disease without prior interventions. As of today, TMVR for native mitral valve disease has not gained FDA approval.

TMVR can be done either via a transseptal or transapical approach. For native TMVR, the vast majority, over 80%, of valves implanted thus far today have been via the transapical approach. This approach is the most direct route to the mitral valve. Valve-in-valve TMVR has been performed mostly via the transseptal approach. A transseptal approach is also usually preferred in patients with extensive annular calcification.

While TMVR is a promising alternative option for mitral valve disease, it remains in a very early stage with many different types of valves, via both approaches, in development. The first dedicated device for TMVR was the CardiAQ self-expanding valve that was first used in 2014. This valve helped establish the feasibility of both transseptal and transapical delivery of a transcatheter mitral valve. Piggybacking on the success of transcatheter aortic valve replacement (TAVR), a modified Edwards SAPIEN 3 was then investigated via a transseptal approach for use in the mitral position. Early feasibility results first published in 2018 in 15 patients with severe 3+ native valve MR, New York Heart Association (NYHA) 2 symptoms, and high surgical risk showed 86.7% technical success and 0% 30-day mortality. There are now several different transseptal delivered valves in various stages of clinical investigation.

The Tendyne valve (Abbot Laboratories, Abbott Park, IL), likely the valve with the most clinical data thus far, is a transapically delivered TMVR that can be repositioned after initial deployment ( Fig. 24.1 ). It consists of a porcine trileaflet valve fixed to a one-size inner stent that maintains an effective orifice area of at least 3.2 cm ² . The outer stent is designed to match the D-shape of the native mitral annulus. Attached to the valve prosthesis is a tether that is secured to a pad resting on the apical epicardial surface. The system is delivered through a transapical sheath, accessed via a small left anterior thoracotomy. The device received the world’s first CE mark for transcatheter mitral valve implantation in Europe in January 2020.

Currently, several pivotal trials to assess long-term outcomes of TMVRs are underway ( Table 24.2 ). The APOLLO Trial is investigating a self-expanding, transapically delivered valve from Medtronic in patients with severe, symptomatic mitral regurgitation. Initial results in 50 patients published in 2019 showed a technical success rate of 96% with 14% 30-day mortality. The SUMMIT Trial is investigating the Abbott Tendyne valve for patients with symptomatic mitral regurgitation. Initial results in 100 patients demonstrated technical success in 96% with 6% 30-day mortality. Full results of this trial are expected in 2024.

TMVR has emerged as an alternative treatment option for patients with degenerated bioprosthetic mitral valves who are at high surgical risk for a re-do. A recent prospective cohort study assessing 1529 patients with failed surgical bioprosthetic mitral valves who underwent either transseptal or transapical SAPIEN 3 valve-in-valve replacement found all-cause mortality was low, with 5.4% at 30 days and 16.7% at 1 year. Patients at 1 year had a significant reduction in heart failure symptoms, with only 9.7% of patients being NYHA Class III/IV versus 87.1% prior to intervention. Of note, transseptal access was associated with lower 1-year mortality than transapical access (15.8% vs 21.7%).

Patients with significant mitral annular calcification represent one of the more challenging subsets of mitral disease to treat and are traditionally considered poor surgical candidates. A multicenter retrospective review of 116 patients with prohibitive surgical risk with severe mitral annular calcification (MAC) who underwent TMVR found high mortality (25% at 30 days and 53.7% at 1 year); however, patients had significant symptomatic improvement. Patients at 1 year were functionally improved with 71.8% improving to NYHA Class I or II. Seventy five percent of patients had zero or trace MR after the procedure. This is likely a group of patients who will be well suited with TMVR techniques in the future.

There are currently no large-scale randomized studies comparing TMVR with surgical MVR. Future studies will hopefully reveal improved long-term outcomes of prosthetic mitral valve replacements either percutaneously or with innovative surgical techniques and further define the role of TMVR in patients with mitral valve disease.

CHALLENGES WITH TRANSCATHETER MITRAL VALVE REPLACEMENT

The success of transcatheter valve replacement for aortic disease has paved the way for the use of this technique on other valvular pathology. However, while TAVR has become the standard of care for aortic stenosis, significant challenges still exist for the clinical adoption of TMVR for mitral regurgitation. The complicated pathophysiology and anatomy of the mitral valve render mitral valve replacement a much more difficult endeavor than transcatheter aortic valve replacement. The mitral valve, as described in earlier chapters, is a more intricate three-dimensional (3D) apparatus with several components, including valve leaflets, mitral annulus, chordal and papillary muscles, and a more variable size secondary to changes in the geometry of the left ventricle and atrium. All components of the apparatus may contribute to mitral regurgitation. Valve pathologies involving the structural integrity of the mitral leaflets, papillary muscle, or chords are considered primary. In contrast, secondary etiologies include mitral annular dilation, left ventricular (LV) dilatation, and papillary muscle and/or LV dysfunction. Left atrial dilatation due to chronic atrial fibrillation leading to mitral regurgitation is likely a third classification that has yet to be fully characterized. The heterogeneity of conditions that result in mitral regurgitation make a more challenging proposition for uniform treatment with valve replacement. All aspects of the mitral valve anatomy and adjacent chambers must be considered in TMVR.

While the aortic annulus is a rigid, elliptical structure, the mitral annulus is a much more variable and dynamic structure. The annulus is much larger, requiring larger valves with larger introduction devices. It is D-shaped and asymmetric and lacks a complete fibrous ring for prosthesis attachment. Achieving a uniform seal around the valve is thus very challenging with just a simple stenting structure like a TAVR valve. This could lead to a much higher incidence of paravalvular leak and migration than the TAVR valve if the same valve design was used in the mitral position. Furthermore, unlike aortic stenosis, which is primarily a calcific lesion, mitral regurgitation typically is not accompanied by extensive leaflet or annular calcification to hold a valve in place. These factors require different designs and implantation techniques for transcatheter mitral valves.

Outcomes research in regard to mitral valve replacement is more challenging than with aortic valve replacement as the patient population is more heterogeneous with more comorbidity and cardiac dysfunction. Aortic stenosis tends to be an isolated lesion in patients with either an intact ejection fraction or a reduced ejection fraction that can improve post-valve replacement. Severe mitral regurgitation, conversely, is often seen in sicker remodeled left ventricles with significant concurrent valvular dysfunction in other locations. Furthermore, the timing of mitral valve intervention is still evolving as early intervention on severe mitral regurgitation in asymptomatic patients has been shown to have better outcomes. Finally, while surgical mitral valve repair has been shown to have better outcomes than surgical valve replacement with favorable anatomy, whether replacement is better than repair with transcatheter options has yet to be determined.