Transcatheter mitral valve replacement: A frontier in cardiac intervention
ABSTRACTAs transcatheter aortic valve replacement (TAVR) has become routine, device manufacturers and investigational cardiologists have set their sights on the mitral valve. Although transcatheter mitral valve replacement (TMVR) poses several technical challenges, they appear to be surmountable, and work is proceeding. Here we review the various devices being developed and preliminary results of trials in humans.
KEY POINTS
- Most TMVR procedures are performed by either a retrograde transapical approach or an antegrade transseptal approach.
- In the small number of patients who have undergone TMVR for native mitral valve regurgitation to date, mortality rates at 30 days have been high, reflecting the seriousness of illness in these patients.
- At present, none of the new devices for TMVR in patients with native mitral valve regurgitation are approved for general use, although some of them are being tested in phase 1 clinical trials that are enrolling patients.
- Valves made for TAVR have been used for TMVR in patients with degenerative mitral stenosis or failure of mitral bioprostheses; however, these are off-label uses of these devices.
The Intrepid valve
The Intrepid valve consists of an outer stent to provide fixation to the annulus and an inner stent that houses a bovine pericardial valve. The device is a self-expanding system that is delivered transapically.
In a series of 15 patients, 11 had functional mitral regurgitation (with an average left ventricular ejection fraction of 35%) and four had degenerative mitral regurgitation (with an average left ventricular ejection fraction of 57%).15 The device was successfully implanted in 14 patients, after which the average mitral valve gradient was 4 mm Hg. All patients but one were left with no regurgitation (the other patient had 1+ regurgitation).
,A trial is currently under way in Europe.
The CardiAQ valve
The CardiAQ is constructed of bovine pericardium and can be delivered by the transseptal or transapical route.
Of 12 patients treated under compassionate use,16 two-thirds (eight patients) had functional mitral regurgitation. Two patients died during the procedure, three died of noncardiac complications within 30 days, and one more died of sepsis shortly after 30 days. This early experience demonstrates the importance of careful patient selection and postprocedural management in the feasibility assessment of these new technologies.
Patients are being enrolled in phase 1 trials.
The Tiara valve
The Tiara valve, a self-expanding prosthesis with bovine pericardial leaflets, is delivered by the transapical route.
Eleven patients underwent Tiara implantation as part of either a Canadian special access registry or an international feasibility trial. Their average Society of Thoracic Surgeons score (ie, their calculated risk of major morbidity or operative mortality) was 15.6%, and their average left ventricular ejection fraction was 29%. Only two patients had degenerative mitral regurgitation. Nine patients had uneventful procedures and demonstrated no residual mitral regurgitation and no left ventricular outflow tract obstruction. The procedure was converted to open surgery in two patients owing to valve malpositioning, and both of them died within 30 days. One patient in whom the procedure was successful suffered erosion of the septum and died on day 4.17
Patients are being enrolled in phase 1 trials.
DEGENERATIVE MITRAL STENOSIS
In patients with degenerative mitral stenosis, extensive mitral annular calcification may provide an adequate “frame” to hold a transcatheter valve prosthesis (Figure 3). Exploiting this feature, numerous investigators have successfully deployed prosthetic valves designed for TAVR in the calcified mitral annulus via the retrograde transapical and antegrade transseptal routes.
Guerrero and colleagues presented results from the first global registry of TMVR in mitral annular calcification at the 2016 EuroPCR Congress.18 Of 104 patients analyzed, almost all received an Edwards’ Sapien balloon-expandable valve (first-generation, Sapien XT, or Sapien 3); the others received Boston Scientific’s Lotus or Direct Flow Medical (Direct Flow Medical, Santa Clara, CA) valves. With an average age of 73 years and a high prevalence of comorbidities such as diabetes, chronic obstructive pulmonary disease, atrial fibrillation, chronic kidney disease, and prior cardiac surgery, the group presented extreme surgical risk, with an average Society of Thoracic Surgeons risk score of 14.4%. Slightly more than 40% of the patients underwent transapical implantation, slightly less than 40% underwent transfemoral or transseptal implantation, and just under 20% had a direct atrial approach.
The implantation was technically successful in 78 of 104 patients (75%); 13 patients (12.5%) required a second mitral valve to be placed, 11 patients (10.5%) had left ventricular outflow tract obstruction, four patients (4%) had valve embolization, and two patients (2%) had left ventricular perforation. At 30 days, 11 of 104 patients (10.6%) had died of cardiac causes and 15 patients (14.4%) had died of noncardiac causes. When divided roughly into three equal groups by chronological order, the last third of patients, compared with the first third of patients, enjoyed greater technical success (80%, n = 32/40 vs 62.5%, n = 20/32), better 30-day survival (85%, n = 34/40 vs 62.5%, n = 20/32), and no conversion to open surgery (0 vs 12.5%, n = 4/32), likely demonstrating both improved patient selection and lessons learned from shared experience. At 1 year, almost 90% of patients had New York Heart Association class I or II symptoms. Prior to the procedure, 91.5% had New York Heart Association class III or IV symptoms.
At present, TMVR in mitral annular calcification is not approved in the United States or elsewhere. However, multiple registries are currently enrolling patients or are in formative stages to push the frontier of the currently available technologies until better, dedicated devices are available for this group of patients.
BIOPROSTHETIC VALVE OR VALVE RING FAILURE
Implantation of a TAVR prosthetic inside a degenerated bioprosthetic mitral valve (valve-in-valve) and mitral valve ring (valve-in-ring) is generally limited to case series with short-term results using the Edwards Sapien series, Boston Scientific Lotus, Medtronic Melody (Medtronic, Minneapolis, MN), and Direct Flow Medical valves (Figure 4).19–23
The largest collective experience was presented in the Valve-in-Valve International Data (VIVID) registry, which included 349 patients who had mitral valve-in-valve placement and 88 patients who had mitral valve-in-ring procedures. Their average age was 74 and the mean Society of Thoracic Surgeons score was 12.9% in both groups.24 Of the 437 patients, 345 patients (78.9%) underwent transapical implantation, and 391 patients (89.5%) received a Sapien XT or Sapien 3 valve. In the valve-in-valve group, 41% of the patients had regurgitation, 25% had stenosis, and 34% had both. In the valve-in-ring group, 60% of the patients had regurgitation, 17% had stenosis, and 23% had both.
Valve placement was successful in most patients. The rate of stroke was low (2.9% with valve-in-valve placement, 1.1% with valve-in-ring placement), though the rate of moderate or greater residual mitral regurgitation was significantly higher in patients undergoing valve-in-ring procedures (14.8% vs 2.6%, P < .001), as was the rate of left ventricular outflow tract obstruction (8% vs 2.6%, P = .03). There was also a trend toward worse 30-day mortality in the valve-in-ring group (11.4% vs 7.7%, P = .15). As with aortic valve-in-valve procedures, small surgical mitral valves (≤ 25 mm) were associated with higher postprocedural gradients.
Eleid and colleagues25 published their experience with antegrade transseptal TMVR in 48 patients with an average Society of Thoracic Surgeons score of 13.2%, 33 of whom underwent valve-in-valve procedures and nine of whom underwent valve-in-ring procedures. (The other six patients underwent mitral valve implantation for severe mitral annular calcification.) In the valve-in-valve group, 31 patients successfully underwent implant procedures, but two patients died during the procedure from left ventricular perforation. Of the nine valve-in-ring patients, two had acute embolization of the valve and were converted to open surgery. Among the seven patients in whom implantation was successful, two developed significant left ventricular outflow tract obstruction; one was treated with surgical resection of the anterior mitral valve leaflet and the other was medically managed.
CONCLUSION
Transcatheter mitral valve replacement in regurgitant mitral valves, failing mitral valve bioprosthetics and rings, and calcified mitral annuli has been effectively conducted in a number of patients who had no surgical options due to prohibitive surgical risk. International registries and our experience have demonstrated that the valve-in-valve procedure using a TAVR prosthesis carries the greatest likelihood of success, given the rigid frame of the surgical bioprosthetic that allows stable valve deployment. While approved in Europe for this indication, use of these devices for this application in the United States is considered “off label” and is performed only in clinically extenuating circumstances. Implantation of TAVR prosthetics in patients with prior mitral ring repair or for native mitral stenosis also has been performed successfully, although left ventricular outflow tract obstruction is a significant risk in this early experience.
Devices designed specifically for TMVR are in their clinical infancy and have been implanted successfully in only small numbers of patients, most of whom had functional mitral regurgitation. Despite reasonable technical success, most of these trials have been plagued by high mortality rates at 30 days in large part due to the extreme risk of the patients in whom these procedures have been conducted. At present, enrollment in TMVR trials for patients with degenerative or functional mitral regurgitation is limited to those without a surgical option and who conform to very specific anatomic criteria.
