Percutaneous Valve Therapies

The field of percutaneous valve replacement and repair has developed at a rapid pace, particularly in the last decade, and percutaneous treatment of valvular heart disease is one of the fastest evolving areas of cardiology.

Clinical strategies to advance and refine percutaneous catheter-based approaches to cardiac valve repair and replacementwere initiated as early as the 1950s with the introduction of simple catheter devices for treating pulmonic stenosis. In the early 1980s, treatment of stenotic lesions matured with the advent of balloon valvuloplasty, which has become the predominant therapy for primary pulmonic and mitral stenosis lesions. Percutaneous aortic balloon valvuloplasty, however, has yielded largely unfavorable results and is performed usually as a bridge to definitive treatment because of its short-lived benefits.

There have been advances over the last decade involving the two most frequent forms of valvular heart disease in the industrialized West, aortic stenosis and mitral regurgitation, which account for more than 70% of the cases of acquired valve disease in the United States and Europe. As the populations of the United States and other industrialized countries continue to age, the need for less invasive and safer methods of treating valvular disease will continue to grow. Careful evaluation comparing percutaneous approaches with conventional surgical approaches have extended the use of the new, less invasive techniques from high-risk patients to other, lower-risk patient groups. ^{[1, 2]}

Rationale for percutaneous approaches

The incidence of valvular heart disease is expected to increase over the next several decades. It is anticipated that treatment of heart disease—primarily valvular heart disease—will represent one of the main areas of focus for improving life expectancy and quality of life in an aging population.

With the increasing availability of cardiopulmonary bypass, surgical expertise, and intensive care facilities, valve repair and replacement are widely performed to relieve symptoms and improve prognosis of valvular heart disease, despite the associated morbidity and mortality. However, many patients with major comorbidities, particularly elderly patients, still do not undergo potentially beneficial interventions because of the high surgical risk.

Investigations into the current management of patients with valvular heart disease in Europe and the United States have shown that as many as one third of elderly patients with severe symptomatic aortic stenosis, and a similar number of patients with mitral regurgitation, were not referred for surgical management by the attending practitioner. The percentage of nonreferrals from the cardiologist’s office is likely to be even higher, and that from the general practitioner’s office may be higher still.

A catheter-based alternative to surgery allows treatment of higher risk patients with significantly reduced morbidity and mortality, thus making treatment available to patients not currently considered surgical candidates. Moreover, patients show a strong preference for minimally invasive therapies in general, especially those who have undergone many operations.

Finally, successful use of percutaneous approaches to valve replacement and repair could have a substantial positive economic impact by virtue of the associated reductions in intensive care unit (ICU) and hospital stays.

Realization of the potential benefits of percutaneous valve therapies continue to result in a paradigm shift, challenging long-standing traditional principles in the evaluation and treatment of valvular heart disease. Both short-term and long-term data are growing to assess percutaneous approaches compared with conventional surgical approaches with respect to superiority in safety and noninferiority in efficacy.

Patient selection

The excellent results of contemporary surgical approaches to valvular heart disease have set a high standard for any new treatment strategies under consideration. However, patients who are considered candidates for less invasive procedures may present a different risk profile than those who are currently referred for surgery (at both the high end and the low end of the risk spectrum); therefore, comparisons with current surgical outcome standards are not always appropriate.

Thus, it is essential to keep in mind that patients referred for valvular interventions today tend to be elderly and to have an increased surgical risk associated with congestive heart failure, the emergency nature of the operation, left ventricular (LV) dysfunction, coronary disease, previous operations, and (most important) severe comorbidities. Measures of invasiveness and effectiveness will also have to be weighed against the realities of patient expectations in potential patient candidate pools (those who currently may or may not be referred for surgery).

Although significant challenges in patient selection and clinical trial design remain to be solved, the patient populations who ultimately benefit most from treatment with these new technologies have become better defined through a rigorous clinical trial process. New transcatheter approaches have changed the face of valve therapy and extend treatment to a larger proportion of the population with valve disease.

Relevant anatomy

The normal human heart contains four valves that regulate blood flow into and out of the heart. The aortic and pulmonic valves are known as the semilunar valves, whereas the tricuspid and mitral valves are referred to as the atrioventricular valves. All the valves are trileaflet, with the exception of the mitral valve, which has two leaflets. All four cardiac valves are surrounded by fibrous tissue that form partial or complete valvular rings, or annuli. These annuli join the fibrous skeleton of the heart to anchor and support the valvular structures.

The aortic valve is located between the LV outflow tract (OT) and the ascending aorta. It forms the centerpiece of the heart and closely approximates many other important cardiac structures, specifically, the pulmonic valve anteriorly, mitral valve posterolaterally, and tricuspid valve posteromedially.

The mitral valve connects the left atrium (LA) and the LV. The mitral valve opens during diastole to allow the blood flow from the LA to the LV. During ventricular systole, the mitral valve closes and prevents backflow to the LA. The normal function of the mitral valve depends on its six components, which are (1) the LA wall, (2) the annulus, (3) the leaflets, (4) the chordae tendineae, (5) the papillary muscles, and (6) the LV wall (see Figure 1 below).

The pulmonic valve divides the right ventricular (RV) OT from the pulmonary artery. In normal conditions, the pulmonic valve prevents regurgitation of deoxygenated blood from the pulmonary artery back to the RV. It is a semilunar valve with three cusps, and it is located anterior, superior, and slightly to the left of the aortic valve.

The right atrioventricular valve complex (the tricuspid valve) is made up of the three valve leaflets, the annulus, the supporting chordae tendineae, and the papillary muscles. The atrial and ventricular masses, conduction system tissue, and support structure of the fibroelastic cardiac skeleton allow coordinated actions of the tricuspid valve.

For more information about the relevant anatomy, see Aortic Valve Anatomy, Mitral Valve Anatomy, Pulmonic Valve Anatomy, and Tricuspid Valve Anatomy.

Percutaneous balloon aortic valvuloplasty was developed after the successes achieved with mitral and pulmonary valvuloplasties in the 1980s. This procedure provides only modest hemodynamic improvement and is associated with a high incidence of restenosis. Long-term survival after this procedure is not significantly different from the natural history of aortic stenosis.

At present, percutaneous balloon aortic valvuloplasty is carried out primarily in inoperable patients for the purpose of achieving temporary improvement in quality of life before more definitive treatment can be performed. The current focus of treatment of aortic stenosis has shifted from balloon aortic valvuloplasty to percutaneous aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis over the past decade. The success of TAVR has led to great interest in treating other heart valve disease states with percutaneous approaches. Go to Transcatheter Aortic Valve Replacement (TAVR) for additional information.

Percutaneous mitral valvulopasty is a first-line procedure for the treatment of mitral valve stenosis. Of the percutaneous valve procedures, percutaneous mitral valvuloplasty has by far the longest track record; it has also been the subject of extensive clinical evaluation.

In properly selected patients, the rate of success—defined as a doubling of the baseline mitral valve area or an increase to at least 1.5 cm² without causing more than moderate mitral regurgitation or other significant complications—appears to be in the range of 85-99%.

Possible complications include mitral regurgitation, atrial septal defect, and left ventricular dysfunction. ^[3] For further information, see Mitral Valvuloplasty.

General considerations

For patients with mitral valve stenosis, percutaneous balloon mitral valvuloplasty (PBMV) is the first-line therapy for most patients with suitable anatomy. For some patients with mitral stenosis whose mitral valve anatomy is not well-suited for BMV, valve-in-mitral annular calcification (ViMAC) can be considered. There are significant anatomic constraints involved in this procedure, however. See the "Valve-in-MAC" sub-section under "Percutaneous Mitral Valve Replacement" (next section).

Until relatively recently, mitral regurgitation has been amenable only to surgical treatment with valve replacement or valve repair. Surgical valve repair is preferred over replacement, but neither procedure is suitable for patients with comorbidities and higher surgical risk. Myxomatous disease and functional regurgitation, which are the most common mechanisms of mitral valve dysfunction, are also the most amenable to valve repair. Various techniques have now been developed for reducing mitral regurgitation via a catheter-based approach in these circumstances.

Transcatheter edge-to-edge repair

Transcatheter edge-to-edge repair (TEER) involves percutaneous transcatheter repair of the mitral valve via a transeptal approach from a femoral vein. A clip device is used to bring the anterior and mitral leaflets together, which reduces mitral regurgitation. Mitraclip (Abbott) is currently the only transcatheter device approved by the US Food and Drug Administration (FDA) for use in the treatment of mitral regurgitation. The Pascal device (Edwards Lifesciences), which has CE (European conformity) mark in Europe, is currently being investigated in US clinical trials. The topic of TEER is covered extensively in Percutaneous Mitral Valve Repair.

Transcatheter annuloplasty

Mitral annuloplasty is a surgical mitral valve repair technique in which the surgeon directly sews a fixed ring to the atrial side of the mitral annulus. This is effective at treating secondary mitral regurgitation, which occurs as a result of annular dilatation, but is reserved for either patients with low surgical risk or those concomitantly undergoing another cardiothoracic surgery (such as coronary artery bypass grafting [CABG]).

Transcatheter techniques have been developed and are under investigation that allow percutaneous repair of the mitral valve in a similar fashion, with the goals of achieving similar success at reducing mitral valve regurgitation with a less invasive procedure. Theoretically, transcatheter annuloplasty could be used in conjunction with TEER. There are currently no transcatheter annuloplasty devices approved for commercial use in the United States. However, Cardioband, Carillon, and Mitralign have CE marks in Europe.

Cardioband

The Cardioband system (Edwards) is a transcatheter direct annuloplasty implant designed to improve mitral regurgitation by reducing mitral annular size. ^[4] The implant, delivered by a transeptal approach, consists of 12 to 17 (depending on device size) stainless steel anchors that are screwed into the posterior mitral valve annulus. The anchors are connected by a contraction wire covered with polyester fabric, which forms a ring and allows controlled reduction of the mitral annulus. The annulus size is reduced during visualization with transesophageal echocardiography until optimal reduction in mitral regurgitation is achieved.

Messika-Zeitoun et al reported 1-year outcomes in 60 patients with symptomatic mitral regurgitation from a multicenter, single-arm European trial. ^[5]  There was an immediate technical success of 97%, although the postprocedural acceptable device success according to the MVARC (Mitral Valve Academic Research Consortium) definition was only 72%. Immediate procedural complications included one each of stroke, myocardial infarction (due to left circumflex artery occlusion), pericardial effusion with tamponade, and cardiac arrest (due to circumflex obstruction). Anchor disengagement was reported in 10 patients; resultant device insufficiency was reported in 5 patients. Fifty-eight patients left the hospital alive. Survival at 1 year was 87%. Also at 1 year, 12% of patients had severe mitral regurgitation, 22% had moderate mitral regurgitation, and 65% had mild or less mitral regurgitation. At 1 year, 79% of patients reported New York Heart Association (NYHA) class I/II heart failure symptoms compared to 14% at baseline. ^[5]

The ACTIVE Trial (NCT 03016975) is a prospective, multicenter, randomized, controlled pivotal trial under way in the United States with a planned enrollment of 375 patients. The trial, comparing Cardioband to guideline-directed medical therapy (GDMT), aims to evaluate safety and efficacy in secondary mitral regurgitation.

Millipede

The Millipede angioplasty ring (Boston Scientific) is composed of a nitinol alloy ring fixed in place by stainless steel anchors. The device is deployed via a transeptal approach. The ring consists of eight stainless steel anchors that are individually attached to the atrial side of the mitral annulus. The anchors can be “unscrewed” and repositioned if their placement is deemed not optimal. Eight nitinol collars connect the anchors. The length of each collar can be individually adjusted during device deployment, allowing customization of the size and shape of the ring. By “fine tuning” the device during deployment while visualizing mitral regurgitation with transesophageal echocardiography, the annuloplasty can be optimized for each patient.

The first experience of the Millipede angioplasty ring in humans was in 2018, in which there was reported procedural success in two patients treated with a transeptal delivery approach. ^[6] An early feasibility trial  (NCT04147884) in Australia is currently enrolling, with an estimated enrollment of 75 patients.

Mitralign

Although initially developed and CE mark–approved for mitral regurgitation, more recent use of the Mitralign system has been focused on treatment of tricuspid regurgitation. See discussion of the Trialign device (Mitralign, Inc) under the Percutaneous Tricuspid Valve Repair/Replacement section.

Carillon

The Carillon system (Cardiac Dimensions Inc) is a percutaneous, indirect annuloplasty system that is placed in the coronary sinus to reshape the mitral annulus. Its placement does not require transeptal puncture. The device consists of a metal shaping ribbon, which has distal and proximal anchors to secure the device in the coronary sinus. The device is deployed via 9 French (9F) venous access and involves placing a distal anchor, cinching the device, and placing a proximal anchor. Care must be taken to avoid compression of the left circumflex coronary artery.

Several studies of the Carillon system have been published (AMADEUS, ^[7] TITAN I, ^[8] TITAN II, ^[9] REDUCE FMR ^[10] ). The TITAN II study used a newer iteration of the device, and enrolled 36 patients with symptomatic mitral regurgitation and reduced left ventricular (LV) function; it found no device-related major adverse events. ^[9] One-year mortality was 23%. At 12 months, 77% of patients had improvement in NYHA class from baseline. ^[9]

The REDUCE FMR trial was a sham-controlled trial that enrolled 120 patients randomized to GDMT or Carillon system. At 1 year, the treatment arm demonstrated a statistically significant reduction in mitral regurgitant volume compared with the control group. ^[10]

A pooled analysis of 74 patients treated with the Carillon system found that at 1 year, 64% of patients had decreased NYHA class and improved distance on the 6-minute walk test. ^[11]

There is an active US randomized, multicenter, double-blinded, sham-controlled trial (NCT03142152) with a target enrollment of 352 patients, but it is not currently enrolling.

Mitral chordal plasty

Although arguably not a catheter-based procedure, transapical chordal plasty for treatment of degenerative mitral regurgitation is worth mentioning. The procedure involves a surgical cutdown to the LV apex via left-lateral mini-thoracotomy. Using transesophageal echocardiography, the device is advanced from a surgical incision in the LV apex to the mitral valve, used to place a suture loop through the diseased part of the valve, brought back to the apex, and then sutured to create, in effect, a prosthetic mitral chordae. The procedure is repeated with multiple chords until the valve is adequately repaired. As with transapical valve replacement, this procedure is not fully percutaneous, but it does allow repair without a full midline sternotomy or cardiopulmonary bypass.

Two systems have been developed. The NeoChord (NeoChord, Inc) has CE mark with ongoing trials in the United States (NCT02803957). ^[12] The Harpoon (Edwards) has also received CE mark, but it is not yet commercially available. ^[13] A single-arm, open-label trial is currently enrolling up to 360 participants in the United States (NCT04375332).

Percutaneous mitral valve replacement is an evolving procedure that is continues to be developed and studied; there are several ongoing trials in the United States. The procedure is technically challenging due to several issues, including the asymmetric shape of the mitral annulus; concerns about cuff design or anchoring and accurate device sizing; mitral annular dilatation, which is frequently observed in patients with mitral regurgitation; and a foreshortened and restrictive subvalvular apparatus in rheumatic mitral stenosis and mitral annular calcification (MAC).

Transcatheter valve-in-valve (ViV), valve-in-ring (ViR), valve-in-MAC (ViMAC)

The Sapien 3 valve (Edwards Lifesciences) is a percutaneous balloon-expandable transcatheter valve replacement that was developed for use in the aortic position. Although this valve technology is not suitable for most patients in the mitral position, there are a few exceptions in which this valve has been implanted successfully: patients with degenerated bioprosthetic valve replacement, failed surgical annuloplasty ring, and severe MAC. The Sapien 3 is approved by the FDA for use in patients with degenerated bioprosthetic valves in the aortic or mitral position. ViR and ViMAC are off-label uses of the device.

A multicenter registry explored the use of the Sapien 3 in each of these scenarios in 521 patients. ^[14] Patients undergoing mitral ViV had a higher technical success rate (94.4%) compared with  those undergoing ViR (80.9%) and ViMAC (62.1%). At 30 days postprocedure, all-cause mortality was higher after ViMAC (34.9%) than with ViR (9.9%) or ViV (6.2%) (P < 0.001). Similarly, 1-year mortality was significantly higher after ViMAC (62.8%) compared with ViR (30.6%) and ViV (14.0%). ^[14] These data reflect the high morbidity in this patient population, which is at high risk for mitral valve surgery. Because reoperation for mitral valve replacement carries an increased risk, transcatheter ViV is likely to become the preferred treatment for patients with degenerated bioprosthesis.

Successful ViR and ViMAC require careful planning and patient selection. The type of annuloplasty ring does affect the procedural outcome. Additionally, though technically challenging, Mitraclip can be performed in some circumstances of failed annuloplasty ring. The greatest hurdle for ViMAC procedures is iatrogenic obstruction of the left ventricular (LV) outflow tract (OT), a situation that carries very high mortality. New techniques have been developed to plan and prevent neo-LVOT obstruction. One technique, in particular, is the LAMPOON technique in which the anterior mitral leaflet is split using transcatheter cautery prior to implanting the valve. This technique is currently being studied in an ongoing international registry (NCT03015194) (active, not recruiting).

Transapical valve replacement:

The transapical approach involves a surgical cutdown via left thoracotomy to the LV apex. A catheter is introduced via the LV apex and then advanced in retrograde fashion to the mitral valve. Although this is a surgical technique, the valve is deployed using catheter-based technology. The surgery is less invasive than a sternotomy and avoids cardiopulmonary bypass.

Intrepid

The Intrepid (Medtronic) valve is a self-expanding trileaflet bovine valve mounted on a nitinol frame that is manufactured in three sizes. The frame design includes an inner valve stent mount and an outer skirt, which seats the valve on the dynamic mitral valve annulus. ^[15] The outer frame is flexible and conforms to the shape of the mitral annulus.

An early feasibility study conducted in the United States and Europe enrolled patients from 2015 to 2017 with severe symptomatic mitral regurgitation who were at higher risk for surgery. ^[16] Successful implantation was achieved in 48 of 49 patients. At 1 year, survival was 77%, and 79% (P< 0.0001 vs baseline) of patients reported New York Hospital Association (NYHA) functional class I or II symptoms (ie mild or no symptoms).

The APOLLO trial (NCT03242642), a multicenter pivotal clinical investigation, is actively recruiting, with target enrollment of 1150 patients with severe symptomatic mitral regurgitation. The study will enroll two cohorts: a randomized arm that will compare the Intrepid valve to traditional open mitral valve surgery, and a single-treatment arm studying patients who are at prohibitive risk for open mitral valve surgery. A fully percutaneously deliverable transcatheter version of the Intrepid valve via transeptal approach is in development.

Tendyne

The Tendyne valve (Abbott) is a self-expanding trileaflet porcine valve delivered by transapical approach through a 34F sheath. ^[17] Whereas most prosthetic valves are circular, the Tendyne frame is asymmetrically shaped to fit the mitral annulus. The valve is unique in its anchoring via a cord tether from an epicardial pad at the LV apex. Tendyne is currently the only transcatheter mitral valve replacement system with CE Mark in Europe; it remains investigational in the United States.

An active international feasibility trial (NCT02321514) is estimating recruiting 350 patients with symptomatic mitral regurgitation.

Sorajja reported the first 100 patients’ long-term results with the Tendyne system. ^[18] Procedural success was obtained in 97% of patients, with 72% survival at 1 year. Freedom from mitral regurgitation was reported in 98% of survivors, with 86.5% of patients reporting NYHA class I or II symptoms. ^[18]

The SUMMIT trial (NCT03433274) is a pivotal clinical trial that will enroll patients from the United States, Europe, and Canada, with a target enrollment of 958 patients with symptomatic mitral regurgitation. The trial includes two arms: surgical and nonsurgical. Subjects in the surgical arm will be randomized to conventional open mitral surgery or Tendyne valve. Patients at prohibitive risk for surgery must be ineligible for edge-to-edge repair with Mitraclip.

Tiara

The Tiara transcatheter mitral valve (Neovasc) system consists of a bovine self-expanding prosthetic valve mounted on a nitinol frame. ^[19] The valve has a saddle shape intended to merge with the native mitral valve annulus. The frame incorporates a large atrial skirt and ventricular tabs to stabilize the valve. The valve is delivered via a 36 to 40F transapical sheath. Two early feasibility trials are unde rway: The TIARA-I early feasibility trial (NCT02276547) is a multinational trial that includes patients in the United States, and the TIARA-II performance clinical study (NCT03039855) is a European study.

HighLife

The HighLife transcatheter mitral valve replacement system (HighLife SAS) consists of a stented bovine valve that is delivered via a novel two-component system. ^[20] A subvalvular implant that consists of a loop placed on the ventricular side of the mitral valve apparatus stabilizes the valve and prevents migration of the valve into the ventricle or atrium. The subvalvular implant is placed via retrograde approach across the aortic valve from an 18F femoral arterial sheath. The valve itself is then delivered by a transapical 39F catheter.

Successful treatment of two patients was reported in a single-center early feasibility trial. ^[21]

Transeptal valve replacement:

Although transapical mitral valve replacement avoids cardiopulmonary bypass, it does require surgical cutdown to the LV apex and carries associated morbidity and recovery from surgery. Endeavors to develop an entirely percutaneous mitral valve replacement system are currently being pursued.

Transeptal mitral valve replacement involves a fully percutaneous, catheter-based valve replacement procedure in which the valve is delivered through a sheath that enters the femoral vein. The delivery system is advanced across the interatrial septum to approach the mitral valve in antegrade fashion from the left atrium. Most transcatheter mitral valve repair systems are large bore (< 45F), which is incompatible with percutaneous vascular access. Thus, significant engineering modifications are among the challenges to developing similar systems that can be deployed via a transseptal approach.

Sapien M3

The Sapien M3 device (Edwards) is a balloon-expandable transcatheter mitral valve replacement system delivered via transeptal approach. The M3 device is a modified version of the Sapien 3 valve in which the valve is seated in a “dock” that consists of a polytetrafluoroethylene–covered nitinol coil that wraps around the subvalvular chordae tendineae.

A first-in-human study conducted in 2017-2018 achieved procedural success in 9 of 10 patients. ^[22] At 30 days, 8 of 9 patients had mild or less mitral regurgitation. A safety and device performance study is currently under way; enrollment of 250 patients has been completed (NCT01808287).

Challenges to transcatheter mitral valve replacement:

With both transapical and transseptal approaches, neo-LVOT obstruction is a challenge. Careful preprocedural imaging, computed tomography modeling, and patient selection are important.

All of the mentioned technologies address the challenge of stability of the valve in the mitral position in various ways.

Balloon pulmonary valvuloplasty

Pulmonic stenosis is most commonly congenital. Acquired pulmonic stenosis occurs, but rarely, due to a variety of different etiologies. Similar to balloon aortic valvuloplasty and balloon mitral valvuloplasty, transcatheter balloon valvuloplasty (BPV) can be used to treat pulmonic stenosis with reasonable long-term results. The first BPV was performed in 1979, and it remains the first-line therapy for congenital pulmonic stenosis. ^[23]

Transcatheter valve replacement

Unlike pulmonic stenosis, pulmonic regurgitation is more often acquired than congenital. Severe pulmonic regurgitation is most frequently iatrogenic following surgical valvotomy, percutaneous BPV, or surgical repair of the right ventricular (RV) outflow tract (OT) for complex congenital heart disease such as tetralogy of Fallot. Congenital pulmonic regurgitation does occur, however; usually, these patients have dilated RVOTs, which are difficult to treat percutaneously.

Melody

The first transcatheter pulmonic valve available was the Melody valve (Medtronic), which was approved by the FDA for use in RV to pulmonary artery (RV-to-PA) conduits in 2010 and in failing bioprostheses in 2017. The valve is unique in that it is made from the valves of bovine jugular veins. Most commonly, a stent is placed in the conduit prior to deploying the Melody valve, as this reduces the risk of restenosis due to valve stent fracture. ^[24]

Sapien/Alterra

The Sapien valve (Edwards Lifesciences), discussed previously, received FDA approval in 2016 for use in RV-to-PA conduits. The Sapien valve can be used to treat larger native RVOTs and RV-to-PA conduits, and it is thus a useful complement to the Melody valve for treatment of patients with failing conduits.

The Alterra Adaptive Prestent is a novel device that can be implanted in a native RVOT to reduce the diameter of the vessel lumen in cases when the vessel is too large to accommodate a Sapien valve. Successful use in the first 15 patients was reported in 2020. ^[25] A US single-arm, nonrandomized, prospective trial is currently enrolling an estimated 85 participants (NCT03130777).

Harmony

The Harmony valve (Medtronic) is a porcine pericardial valve mounted on a self-expanding stent frame designed for transcatheter treatment of surgically repaired RVOTs with pulmonary valve regurgitation. The larger valve size aims to treat patients in whom the Melody valve is not an option. 

Three-year results in 20 patients were reported in early 2020 with encouraging results. ^[26] A prospective, nonrandomized, clinical experience trial is also under way in the United States and Canada (NCT02979587).

Percutaneous techniques to treat tricuspid valve regurgitation are in various stages of development and making rapid progress. Tricuspid annular devices must be correctly positioned to avoid obstruction of the coronary sinus ostium or damage to the atrioventricular node. Other technical challenges include the fragility of the tricuspid valve leaflets, the lack of firm surrounding tissue in the tricuspid annulus, and the frequent annular dilatation in patients with tricuspid regurgitation. Durable percutaneous tricuspid valve therapies must also prevent further annular dilatation; otherwise, the valves may be susceptible to future dehiscence or embolization.

Edge-to-edge repair

The Mitraclip and Pascal technologies have been successfully applied to the tricuspid valve in off-label procedures. Imaging the tricuspid valve by transesophageal echocardiography (TEE) as well as manipulating devices designed for delivery to the mitral valve can be challenging. A dedicated device based on the Mitraclip platform is under investigation in a multicenter randomized trial (NCT03904147) that is enrolling an estimated 700 participants with severe tricuspid regurgitation.

Annuloplasty

Cardioband

Described in the Percutaneous Mitral Valve Repair section, this technology has been successfully used to treat tricuspid regurgitation. ^[27] A US-based early feasibility trial is under way (NCT03382457).

Millipede

Also described under Percutaneous Mitral Valve Repair, the Milliped device has been considered for treatment of tricuspid regurgitation. A dedicated catheter for delivery to the tricuspid valve is in development.

Trialign

Performed via transjugular venous access, the procedure for the Trialign device (Mitralign, Inc) involves using a radiofrequency wire from the right ventricle (RV) advanced retrograde through the tricuspid annulus. Pledgets are placed at posteroseptal and anteroposterior commissures and then cinched to obliterate the posterior leaflet. This creates a “bicuspidization” of the tricuspid valve. A prospective, single-arm trial to explore safety and feasibility in patients with symptomatic chronic functional tricuspid regurgitation is enrolling in Europe (NCT03225612).

TriCinch

Performed via femoral venous access, the procedure for the TriCinch device (4Tech Cardio Ltd) involves placing a coil in the mid-anterior tricuspid annulus. This coil is connected by a Dacron band to a stent in the inferior vena cava to secure it in place. The procedure was studied in the PREVENT Trial, which enrolled 24 patients (NCT02098200), in which implantation was successful in 18 patients with a significant (≥1 grade) reduction of tricuspid regurgitation in 94% of these patients. ^[28]  At 6 months, there was significant improvement in 6-minute walking test and quality of life, with three quarters of patients in NYHA class I or II. ^[28] Two trials to study this device's safety and efficacy were terminated by the sponsor for unspecified reasons (NCT03294200 and NCT03632967).

Minimally Invasive Annuloplasty (MIA) 

The MIA technology (Micro Interventional Devices) is deployed by implanting multiple PolyCor anchors between the posteroseptal and anteroposterior commissures that are tensioned after deployment. The procedure is performed from the femoral vein using a 12F delivery system. The STTAR trial will enroll 60 patients with chronic functioning tricuspid regurgitation in a nonrandomized feasibility trial (NCT03692598).

Valve-in-ring (ViR)

Sapien

Similar to mitral ViR transcatheter valve replacement, percutaneous valve implantation has been performed in the tricuspid position in patients previously treated with surgical annuloplasty who have subsequent significant tricuspid regurgitation. Successful treatment has been reported, although residual paravalvular regurgitation is common. ^[29]

Transcatheter tricsupid valve replacement

NaviGate 

The Gate valve (NaviGate Cardiac Structures) consists of a 42F self-expanding valve with a tapered nitinol stent with atrial winglets and ventricular graspers. A first-in-human experience in five patients has been reported using surgical direct transatrial approach. ^[30] Percutaneous transjugular or transfemoral approach will require further device refinement and a small delivery system.

Forma

The Forma tricuspid repair system (Edwards Lifesciences) is a unique device consisting of a foam-filled spacer that creates a surface for valve leaflet coaptation. The device is inserted via the subclavian vein and anchored to the RV apex.

An early US feasibility study will enroll up to 60 patients (NCT02471807). The SPACER trial (NCT02787408) has enrolled 25 patients to date.

A newer iteration of the Forma device has improved anchoring, has a larger spacer for more severe tricuspid regurgitation, and has a radiopaque apposition indicator. ^[31]

Caval valve implantation

Sapien

Implantation of a transcatheter valve in the inferior vena cava conceptually offers an enticing novel treatment of tricuspid regurgitation while avoiding the challenge of placing a valve within the complex tricuspid valve anatomy. The TRICAVAL trial (NCT02387697) compared Sapien valve implantation in the inferior vena cava to optimal medical therapy. Unfortunately, the trial was halted prematurely at 3 months after eight patients showed no improvement.

TricValve 

The TricValve bicaval valves system (P+F Products + Features GmbH) consists of two self-expandable tissue valves, one in the superior vena cava and one in the inferior vena cava. Early in-human trials revealed immediate termination of caval backflow and improvement in NYHA class and 6-minute walk test. ^[28] The TRICUS study will enroll 10 patients with symptomatic tricuspid insufficiency and caval reflux (NCT03723239).