Ganesh Athappan, Paul Sorajja, and Mario Gössl (2017) Percutaneous Treatment of Mitral Regurgitation: Present and Future. Journal of the Minneapolis Heart Institute Foundation: Fall/Winter 2017, Vol. 1, No. 2, pp. 113-123.
Ganesh Athappan, MD
Paul Sorajja, MD
Mario Gössl, MD, PhD
Abbott Northwestern Hospital, Minneapolis, MN
Disclosures: The authors have no funding or other disclosures to make.
Address for correspondence:
Mario Gössl, MD, PhD
Director, Transcatheter Research and Education
Valve Science Center
Minneapolis Heart Institute® at Abbott Northwestern Hospital
Minneapolis, MN, 55407
Mitral valve regurgitation poses a significant public health burden, with more than 3 million people in the US alone suffering from moderate or severe mitral valve regurgitation. Surgical correction with mitral valve repair or replacement is the mainstay of therapy. However, a significant proportion of elderly patients are not eligible for mitral valve repair or replacement due to prohibitive surgical risk from increased age, poor ventricular function, or associated comorbidities. Percutaneous mitral valve repair/replacement techniques have been developed to fill this void. The most advanced percutaneous technique with the highest safety and efficacy to date is the edge-to-edge MitraClip repair system. The majority of other catheter-based mitral valve repair/replacement devices are at early developmental stages, but have shown encouraging initial results in feasibility trials. Transcatheter mitral valve replacement holds promise to emerge as the leading transcatheter treatment of choice in the future.
Keywords: degenerative MR, functional MR, MitraClip, TMVR
Mitral valve regurgitation (MR) poses a significant public health burden, with more than 3 million people in the US alone suffering from moderate or severe MR.1 Left untreated, chronic MR results in heart failure symptoms, left ventricular cavity dilation and systolic dysfunction, left atrial enlargement, atrial fibrillation (AF), and pulmonary hypertension. In patients with severe primary/degenerative MR, an early repair of the structural defect is crucial to avoid irreversible sequela.2 In patients with secondary/functional MR, optimal medical therapy is a key component in the treatment of the underlying cardiomyopathy and may provide relief from symptoms. However, unless the cardiomyopathy and secondary/functional MR improves significantly under therapy, surgical or interventional options need to be considered.3 Surgical correction with mitral valve repair (MVRe) or replacement (MVR) remain the mainstay of therapy for primary and secondary MR. Even so, because of the invasive nature of open-heart surgery (OHS) and the frequent presence of comorbidities in this group, up to 50% of patients with severe MR may not be offered surgery.4 This is especially true for older patients with multiple comorbidities and those with impaired left ventricular function. As a result, percutaneous technology is poised to significantly alter the treatment paradigm for chronic MR. Percutaneous MVRe or MVR offers the potential benefit of decreased morbidity, improved recovery time, and shorter hospital stays compared with OHS. In this review we summarize the devices that have been developed for percutaneous transcatheter mitral valve repair or replacement and their preliminary clinical results.Anatomy of the Mitral Valve Complex
An appreciation of the complex anatomy of the mitral valve is of importance to understand the challenges in development of percutaneous MVRe or MVR technologies and for selection of the most optimal repair/replacement technique.
The mitral valve is a complex functional unit composed of the mitral annulus; anterior and posterior leaflets; subvalvular apparatus (chordae tendineae and papillary muscles [PMs]); left ventricular (LV) myocardium (attachment of the papillary muscles); and left atrial wall (Figure 1A). These individual structures work synchronously to open during diastole and close during systole.
A. Components of the mitral valve complex unit. B. Anatomic relations of the mitral valve. C. Carpentier’s surgical classification of MR: type I MR, normal leaflet length and motion but with either annular dilation or leaflet perforation; type II MR, leaflet prolapse, usually from myxomatous disease, or by PM rupture or elongation; type IIIa MR, restricted leaflet motion in systole and diastole; and type IIIb MR, restricted leaflet motion in systole only.
Mechanisms of Mitral Regurgitation
Abnormalities of the mitral valve complex that affect closure during systole cause MR that can be either functional/secondary or degenerative/primary.
Alain Carpentier proposed a morphologic classification (Figure 1B) based on leaflet motion to describe the pathophysiologic changes that contributed MR from either etiology.5 This simplification has usefulness in terms of both the surgical approach and the percutaneous approach, as the goal of therapy is to restore normal leaflet function but not necessarily normal valve anatomy.Functional/Secondary Mitral Regurgitation
Functional mitral regurgitation (FMR) occurs from geometric derangement of the mitral valve functional unit subsequent to LV remodeling in the setting of regional or global LV dysfunction from any cause. Notably there is an absence of primary leaflet pathology in FMR. Alterations in LV geometry and function lead to annular dilation and flattening, decreased annular contraction, and papillary muscle displacement with attendant chordal tension and leaflet tethering. This results in an imbalance between the closing (LV contractility, LV electrical synchrony, and annular contraction) and tethering (papillary muscle displacement, LV remodeling, annular dilation) forces of the functional mitral unit leading to FMR.6 The 2 most common etiologies of FMR are nonischemic and ischemic dilated cardiomyopathy.Degenerative/Primary Mitral Regurgitation
Unlike FMR, primary leaflet pathology leading to Carpentier class II with or without class III dysfunction is the hallmark of degenerative mitral regurgitation (DMR). It is often due to either Barlow’s disease (myxomatous valve disease), mitral valve prolapse, or fibroelastic deficiency.7 Rare causes of DMR include Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta.Timing of Intervention
The natural history of patients with chronic MR depends on the degree of regurgitation, the cause of the underlying disorder, and the degree of LV dysfunction. When severe MR is present, approximately 5% to 10% of patients per year develop (a) significant symptoms (LV failure, pulmonary hypertension, atrial fibrillation, and stroke); (b) clinical indications for surgery; (c) death; or all of these.8,9
The optimal timing for corrective intervention in chronic mitral regurgitation is widely debated (Table 1). For degenerative MR in asymptomatic individuals, this depends upon a balance between the risk of early surgery and rates of successful repair, with the potential risk of irreversible left ventricular dysfunction if the intervention is performed too late after either the development of symptoms or the fall in left ventricular ejection fraction.
Current indications for surgical mitral valve repair/replacement.
In secondary MR, the indications and timing of surgery are even more uncertain and are being actively explored. Secondary MR is considered severe when the effective regurgitant orifice (ERO) > 0.20 cm2 or effective regurgitant volume (ERV) > 30 mL10–12 due to doubling of mortality with even moderate regurgitant volumes. Nevertheless, correction of a MR as a therapeutic target to reduce mortality and improve functional status has not been proven. Percutaneous mitral repair/replacement techniques are uniquely suited to answer this question.Corrective Interventions for Mitral Regurgitation
Surgical mitral valve repair or replacement is currently the mainstay of corrective treatment for severe MR. Compared to mitral valve replacement, mitral valve repair lowers early and late mortality, preserves left ventricular contractility, eliminates the need for long-term anticoagulation, and decreases the risk of infective endocarditis. These advantages were established by several observational studies conducted in the 1970s.13–15 However, successful mitral valve repair may be impossible in ≈10% of surgical cases requiring valve replacement. Unlike for degenerative MR, the advantages of mitral valve repair over replacement are not established for FMR. Due to the progressive nature of the underlying ventricular disease recurrence, an FMR is common after mitral valve repair.16
The European Heart Survey showed that up to 50% of patients with severe symptomatic MR are not referred for surgery due to advanced age, other comorbidities, and operative risk.4 Patients with severe MR who are not offered surgery due to high operative risk (STS risk score >12 and logistic EuroScore >20) and are medically treated have a 50% mortality at 5 years.17 Catheter-based mitral valve repair has been developed to expand treatment options to such patients who are deemed at high risk for conventional mitral valve surgery (repair or replacement).Transcatheter Treatment Options in Degenerative Mitral Regurgitation
Showing promise in their various stages of evolution from preclinical to randomized trials, several percutaneous techniques (Table 2) have been developed adapting surgical principles and are being tested.
Transcatheter mitral valve repair/replacement therapies.
Catheter-based interventions targeting the mitral leaflet coaptation have been designed to mimic the Alfieri stitch operation that creates a double mitral orifice.18 In the Alfieri procedure, the edges of the mitral leaflet are sutured at the site of regurgitation in order to reduce leaflet motion and to force coaptation, both of which reduce the degree of regurgitation.MitraClip.
The MitraClip system (Evalve, Inc., Menlo Park, CA) is the best studied of the options for percutaneous mitral valve repair with >40,000 procedures worldwide. The system uses a 24-French steerable delivery guide catheter and a transseptal approach to place a v-shaped clip (MitraClip) on the mitral leaflets, effectively achieving a double-orifice repair similar to the Alfieri stitch (Figure 2). A second or third clip can be delivered adjacent to the first clip in cases with significant residual MR. The device is approved by the FDA (October 23, 2013) for use in patients with 3+ or 4+ degenerative MR and with prohibitive risk of surgery. The approval came in the wake of safety and efficacy data from several registries, observational studies, and pooled analyses in high-risk patients.19,20
Fluoroscopic images postimplantation of a deployed Tendyne valve (open arrows in A,B,D,F) in the mitral position in the A. right anterior oblique projection and B. left anterior oblique projection. C. Systolic frame of a midesophageal, two-dimensional (2D) transesophageal echocardiogram (TEE) long axis view of the left ventricular outflow tract showing severe central MR in a patient with ischemic cardiomyopathy. D.Post-Tendyne valve implantation, there is no MR. E. Preimplant LV angiography showing a severe mitral regurgitation with contrast filling up the entire LA (white outline identifies the borders of the LA) with similar density as seen in the LV. F. Postimplant LV angiography showing no mitral regurgitation.
An integrated high surgical risk primary MR cohort was formed by pooling patients enrolled in the EVEREST (feasibility study of a percutaneous mitral valve repair system) II high-risk study and the later REALISM (real-world expanded multicenter study of the MitraClip system) continued-access registry and was pivotal in FDA approval of the device. A total of 127 patients with primary MR and prohibitive surgical risk (Society of Thoracic Surgeons [STS] risk >8) were identified by pooling the 2 registries. Enrolled patients were elderly with a mean age of 82.4 years and with a mean prohibitive STS score of 13.2% ± 7.3%. The MitraClip device was successfully implanted in 95.3% of patients (121 of 127). There were 8 deaths (6.3%); 3 strokes (2.4%); 16 major bleeding complications (12.6%); 7 major vascular complications (5.5%); 1 myocardial infarction (0.8%); 2 acute kidney injuries (1.6%); and 2 atrial septal defects (1.6%). A total of 4 patients (3.1%) required ventilation beyond 48 hours. The average length of hospital stay was 2.9 ± 3.1 days, with 88% of the patients discharged home.
The observed 30-day mortality rate was 6.3% (8 patients), substantially lower than the study population’s mean STS-predicted surgical mortality of 13.2% with surgical mitral valve replacement. In 91 patients, MR ≤2+ was observed at discharge. At 12 months, 70.3% of patients maintained MR ≤2+, 11% experienced worsening MR grade of 3+ or 4+, and 18.7% died. Notably, rehospitalization for heart failure was significantly reduced (73%) during the 12-month post-MitraClip implantation, compared to the 12 months prior to implantation (0.67 [95% confidence interval (CI): 0.54–0.83] to 0.18 [95% CI: 0.11–0.28] per patient year).
Most recently Sorajja et al.21 reported acute, 30-day, and 1-year clinical outcomes of commercial transcatheter mitral valve repair with the MitraClip in the US on 2,952 high-risk patients (median age of 82 years and median STS score of 9.2%). Degenerative MR was found in 85.9% of the patients. The device was successfully implanted with acute procedural success in 91.8% of patients with an in-hospital mortality of 2.7%. Survival was 74.1% at 1 year and freedom from heart failure hospitalization was 79.8% at 1 year.
It is noteworthy that the favorable outcomes following MitraClip therapy is associated with a very low procedural mortality. In the EVEREST and EVEREST II trials that included patients with low surgical risk, the observed mortality post-procedure was only 1%. In the integrated high-risk cohort, procedural mortality was seen in 6.3% of patients. A recent large meta-analysis of 2,980 patients that pooled patients from 16 studies reported a procedural mortality of only 0.1% with the MitraClip procedure.
The anatomic subset of degenerative MR tested in the EVEREST trials was confined to Carpentier type II central MR (lesions in anterior [A2]/posterior [P2] segment), with a flail leaflet gap of <10 mm and flail width of <15 mm.19 In the ACCESS-EU trial,22 there was a broader spectrum of enrolled valve morphologies with inclusion of noncentral MRs and flail leaflets, with a flail gap >20 mm or flail width >25 mm. These indications have been further expanded in the U.S. Compassionate Use Pathway and with evolving operator experience (Figure 3).
The MitraClip device and procedure (upper two rows). Also depicted is the surgical Alfieri stitch.18Lower row: midesophageal 2D TEE view (bicommissural view, 60°) showing flail (open arrow in A,B) A. P1 segment and B. associated severe eccentric MR on color Doppler. C. A single MitraClip was placed laterally to anchor the flail P1 segment with successful reduction in MR from severe to mild.
Chordal rupture and chordal elongation are common findings in patients with degenerative MR. In the chordal techniques, defective chords can be replaced with artificial chords implanted either from a transapical or transseptal approach to achieve optimal leaflet coaptation.
The NeoChord (NeoChord, Inc., Minnetonka, MN) has the largest clinical experience worldwide (Figure 4A). It involves a mini-thoracotomy,23 off-pump, transapical access to implant neochords that stabilize the prolapsing segments of the mitral valve. Outcomes from the Neochord Independent International Registry on 247 patients showed a 97.6% success rate with reduction in MR to mild or less in 87% of patients at discharge. The majority of patients selected for enrollment included those with severe MR from either isolated P2 flail/prolapse or multisegmented flail/prolapse of the posterior leaflet (83.4%). The remaining patients had anterior, bileaflet or paracommissural pathology. The U.S. pivotal trial RECHORD (randomized trial of the Neochord DS1000 system versus open surgical repair) is currently underway at up to 20 U.S. centers with a projected enrollment of 585 patients. Eligibility for inclusion is limited to those with severe MR and isolated segmental prolapse of the A2 or P2 segment with the anterior leaflet covering at least 65% of anterior-posterior annular distance.
A. Neochord DS1000 for transapical implantation of artificial chords. B,C. The Carillion mitral contour system for indirect mitral annuloplasty via the coronary sinus. D,E,F. The Mitralign system for direct annuloplasty through pledgets delivered via a deflectable retrograde transaortic catheter. G,H,I. The Cardioband system for direct annuloplasty via a transseptal approach.
Transcatheter Therapies for Functional/Ischemic Mitral Regurgitation
In functional MR, it is well appreciated that despite the use of evidence-based pharmacotherapies to counteract neurohumoral activation, progression of heart failure is rarely halted, but rather slowed.24 Moreover, with disease progression, patients become intolerant or refractory to pharmacotherapy. This supports the concept that at some point, heart failure progresses independently of neurohumoral activation, but due to an abnormal LV geometry (shape and size) from remodeling: the biomechanical model of heart failure.25 Therefore, the biomechanical model of heart failure introduces the need for surgical and percutaneous strategies to reverse abnormal LV geometry by direct or indirect restoration of mitral valve function beyond guideline-based therapies for heart failure. In line with the above concept, existing literature on surgical correction by repair or replacement of severe MR in advanced heart failure has consistently shown an improvement in MR functional class, quality of life, and consistent reverse remodeling of the LV. There has, however, been a persistent lack of demonstrable mortality benefit in all reports. In a direct comparison of percutaneous MitraClip to conventional surgery for severe MR, the composite of death, stroke, MI, need for urgent reoperation, blood transfusion, and renal failure occurred in 15% of those in the percutaneous arm versus 48% of those in the surgical arm. The associated high procedural morbidity, together with a lack of mortality benefit from conventional surgery for functional MR, has led to an overwhelming interest in catheter-based techniques.Coaptation TechniquesMitraClip.
The MitraClip has been successfully used to treat FMR with a favorable safety profile. In the EVEREST II REALISM study, 439 high surgical risk FMR patients were treated with the MitraClip procedure with a 96% implant rate. Freedom from mortality at 12 months was 76%.26 At 12 months, 83% of patients achieved MR <2+. Also noted were improvements in LV volume and New York Heart Association (NYHA) functional class. There was also a 30% reduction in annual rates of hospitalization. Similar results have been reported by large-scale registry studies on patients with FMR. The prerequisites for successful edge-to-edge repair in FMR are a coaptation depth <11 mm and coaptation segment >2 mm.19
The ongoing Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for heart failure patients with functional mitral regurgitation (COAPT) trial is designed to confirm the safety and effectiveness of the MitraClip System compared to the medical standard of care in patients with functional MR for the treatment of moderate-to-severe or severe FMR in symptomatic heart failure subjects. Similar trials, RESHAPE HF (a randomized study of the MitraClip device in heart failure patients with clinically significant functional mitral regurgitation) and MITRA-FR (multicentre study of percutaneous mitral valve repair MitraClip device in patients with severe secondary mitral regurgitation), are randomized studies of the MitraClip device in heart failure patients that are ongoing in Europe and France. MATTERHORN (a multicenter, randomised, controlled study to assess mitral valve reconstruction for advanced insufficiency of functional or ischaemic origin), another trial of patients with FMR, will compare the MitraClip against surgery. The results of the above trials will define the true benefit of MitraClip in patients with FMR.Annuloplasty Techniques
Annular dilation and shape are important contributors to the severity of FMR. Progressive dilation of the mitral annulus in dilated cardiomyopathy reduces coaptation of the leaflets leading to mitral regurgitation. Annular re-shaping by indirect and direct annuloplasty techniques is currently under clinical investigation as either a stand-alone procedure or as an adjunctive therapy to leaflet repair.
In indirect annuloplasty, the close proximity of the coronary sinus to the annulus is exploited to reshape the annulus by applying a constricting force through a device deployed in the coronary sinus. The Carillon Mitral contour developed by Cardiac Dimensions (Kirkland, WA) is currently the only available indirect annuloplasty device (Figure 4B,C). The procedure is performed percutaneously via internal jugular vein access. After the device is deployed and locked into position, tension applied to the anchors of the device results in tissue plication and reduces the mitral valve annular diameter and MR. The REDUCE FMR (Carillon mitral contour system for reducing functional mitral regurgitation) study is an ongoing, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume in patients with functional MR. Patients to be enrolled are those with functional MR (grades 2+ to 4+) and symptomatic congestive heart failure (NYHA classes II–IV) with an impaired 6 minute walk test of 150 to 450 m. Eligibility requirements are objective evidence for LV systolic dysfunction with a LV ejection fraction ≤50, as well as an enlarged LV, with an LV end-diastolic diameter >55 mm and stable heart failure medication regimen for at least 3 months prior to index procedure.
Percutaneous direct annuloplasty via a retrograde transventricular approach or antegrade via a transseptal approach is an exciting area of development. Two devices, the Mitralign (Mitralign, Tewksbury, MA) and the Cardioband System (Valtech Cardio Ltd., Or-Yehuda, Israel) have CE mark approval.
The Mitralign system is designed to deliver pledgets in the region of the posterior annulus at P1 and P3 via a retrograde transaortic route to achieve direct annuloplasty (Figure 4D,E,F). Pulling the pledgets together causes plication of the posterior annulus, emulating the results of a surgical, suture-based annuloplasty. Several device iterations have been incorporated, and clinical testing has continued and completed, albeit slowly in the Mitralign Percutaneous Annuloplasty First in Man Study.27 Patients with symptomatic chronic functional MR, MR grade ≥2+, LVEF of 30% to 60%, structurally normal mitral valve, and a mitral plane to apex dimension of ≥5 cm were recruited for this study.
The Cardioband System is a transcatheter-implantable adjustable annuloplasty ring system (Figure 4G,H,I). Different from the previous devices, it is delivered anterogradely via the right femoral vein and through a transseptal puncture. The Cardioband is a polyester prosthetic tube (band) sequentially fixed by multiple helical anchors, from the anterolateral to the posteromedial trigone. Larger scale European trials are currently underway with active enrollment of patients with symptomatic moderate to severe functional MR despite optimal medical therapy and LVEF ≥25% and left ventricular end diastolic dimension ≤65 mm.Transcatheter Mitral Valve Replacement
Transcatheter mitral valve replacement (TMVR) is an attractive option, as it targets the mitral valve complex as a whole, thereby eliminating the need for a combination of percutaneous approaches to achieve results on par with surgical repair/replacement. However, the complex structural and functional anatomy of the mitral unit makes this a formidable challenge. Specifically, they include the lack of a complete annulus, saddle-shaped geometry that changes throughout the cardiac cycle, a very large size, and an aortomitral geometry that lends to left ventricular outflow obstruction. Despite the challenges, several valves have been developed and are currently in various phases of pre-clinical or clinical testing.
The Tendyne valve (Abbott Vascular, Abbott Park, IL) is a self-expanding, trileaflet porcine valve mounted within the inner stent of a double frame design (1 stent inside the other) developed for transapical implantation.28 The D-shaped outer stent with atrial flanges provides anchoring on the atrial side while an apical fixation pad allows for LV tethering (Figure 2). The global feasibility trial to evaluate the safety and performance of the device on 30 patients was recently completed.29 Patients with both symptomatic primary and secondary MR grade 3 or 4 were enrolled. Exclusion criteria for enrollment included LVEF <30%, LV end-diastolic diameter >70 mm, severe mitral annular or leaflet calcification, left atrial or LV thrombus, prior mitral or aortic valve surgery, prior transcatheter mitral intervention, pulmonary artery systolic pressure ≥70 mm Hg, severe tricuspid regurgitation, and severe right ventricular dysfunction with evidence of right heart failure. Successful device implantation was achieved in 93.3% of patients with no intraprocedural adverse outcomes. There was no device embolization, cardiac perforation or LV outflow tract obstruction. There were also no strokes, no myocardial infarctions, and no device-related complications during hospitalization. At 30 days, all patients except 1 had no residual MR and none had paravalvular regurgitation. Favorable left ventricular echocardiographic performances indices were also noticed during follow-up. There was 1 death at 30 days that occurred 13 days postoperatively due to hospital acquired-pneumonia, 4 rehospitalizations for heart failure, and 1 patient with leaflet thrombosis. An expanded early feasibility trial currently underway is projected to enroll 110 patients and be complete by May 2018.
The Intrepid valve (Medtronic, Minneapolis, MN) is a double-frame, self-expanding valve again designed for transapical implantation (Figure 5). The inner stent houses the trileaflet bovine pericardial valve. A flexible brim aids in fixation to the mitral annulus. An early feasibility trial is currently actively enrolling30 patients with severe symptomatic grade 3 to 4+ MR (primary and secondary) that have a suitable transapical access as well as native valve geometry and size compatible with the Intrepid device. Early results appear promising. Thus far, in a series of 27 patients (21 patients with FMR), successful device implantation was achieved in 92.3% with reduction in MR to 0/1+ in all. A total of 14 deaths were reported at 30 days, of which 4 were procedure related, 6 due to major bleeding, 3 from renal failure, and 1 due to reoperation.
A. Systolic frame of a midesophageal 2D TEE long axis view of the left ventricular outflow tract showing severe MR in a patient with nonischemic cardiomyopathy. B. Post-Intrepid valve (open arrow) implantation there is no MR. C. Three-dimensional TEE enface view of the implanted valve showing the trileaflet morphology mounted on the inner-stent, also visible is the outer stent. D.Fluoroscopic images showing the transapical delivery of the valve through the delivery sheath (arrowhead) with partially deployed valve (open arrow) and postimplant images in the E. right anterior oblique projection and F. left anterior oblique projection.
The CardiAQ (Edwards Lifesciences, Irvine, CA) is the first of its kind for the mitral valve. It is a transseptally delivered, trileaflet bovine pericardial valve mounted on a nitinol frame that self-anchors without the need of radial force. The feasibility study has paused clinical enrollment at the time of this writing and is expected to restart in the second quarter of 2017.
Percutaneous mitral valve repair is an exciting new field with many devices at early stages of preclinical and clinical evaluation. The most advanced technique with the highest safety and efficacy to date is the edge-to-edge MitraClip repair system. The majority of other catheter-based mitral valve repair devices are at early developmental stages and will have to undergo further feasibility/pilot studies and ultimately well-designed clinical trials before their widespread application. Therefore, at present, the first treatment of choice in high surgical risk patients with primary MR should be the MitraClip, with the other transcatheter approaches confined to those with an unfavorable anatomy for the use of the MitraClip. In high surgical risk patients with secondary MR, the MitraClip again remains the procedure of choice pending results of the COAPT trial and other feasibility trials of TMVR devices. Looking forward, it seems likely that the role of percutaneous repair or replacement will expand in the future with more novel device designs, advances in existing devices, improvements in imaging techniques and operator experience.
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