VEITHSymposium: Percutaneous Mitral Valve Repair with the MitraClip

The catheter-based MitraClip therapy (Abbott Vascular) received U.S. Food and Drug Administration (FDA) approval on October 24, 2013. MitraClip has been approved for patients with significant symptomatic degenerative mitral regurgitation (MR) who are at prohibitive risk for mitral valve surgery. Ongoing prospective, randomized trials — COAPT in the United States and RESHAPE-HF in Europe — will evaluate the impact of MitraClip treatment on the progression of heart failure in patients with severe MR. Both studies are currently enrolling patients.

Dr. Ted Feldman served as co-principal investigator of EVEREST II (Endovascular Valve Edge-to-Edge REpair STudy), a multi-center, randomized clinical trial of 279 patients in the United States and Canada with moderate-to-severe (3+) or severe (4+) MR who were candidates for mitral valve surgery. EVEREST II was the first randomized clinical trial to compare a catheter-based mitral valve device to mitral valve surgery.

What did we learn about the MitraClip from EVEREST II?

EVEREST II, a trial comparing MitraClip to surgery, led us to understanding that the MitraClip was a more appropriate therapy for high-risk patients who are poor candidates for surgery.¹ The trial looked at both functional and degenerative mitral regurgitation (MR), but primarily degenerative, in about 75%. One of the key findings of the EVEREST II trial was that a subgroup analysis showed the results and outcome of MitraClip treatment were closest to surgery in older patients with poorer left ventricular function and functional MR. That led to the EVEREST II High Risk Registry^2-3, reported during the 2013 American College of Cardiology Scientific Sessions. This registry included 351 high-risk patients, of which 70% were functional MR patients, with an estimated STS (Society of Thoracic Surgeons) surgical risk score of 18%. This group had wonderful outcomes with the MitraClip, particularly considering that this is a group of patients for whom there had been no real therapy previously. A subgroup of 127 degenerative MR patients in that larger experience of high-risk cases was the basis of the FDA approval of the MitraClip for high-risk patients with degenerative MR. That approval came October 24, 2013. 

What remains to be addressed is the exact role of the MitraClip in high-risk, functional MR, leading to the COAPT trial. COAPT is a 1:1 randomization of MitraClip with optimal medical therapy for heart failure compared to optimal medical therapy for heart failure alone. The patients are high risk, and are not good candidates for surgery. Surgery as a standalone therapy for functional MR remains controversial, but has been shown to improve some secondary endpoints. Surgery definitely decreases the degree of regurgitation, but whether it has a mortality impact and what other clinical benefits it has are less clear. In fact, both the U.S. and European guidelines give surgery an Class IIb indication as a standalone therapy for functional MR, which is part of why MitraClip is still being looked at in this group. The COAPT trial is in this higher-risk population, so it is effectively a heart failure trial. 

What has your experience told you about the type of patient most likely to experience a positive outcome with the MitraClip?

Based on trial experience, it is the functional MR patients who get results closest to surgical results. Based on personal experience as a procedure operator, patients who have a focal prolapse also do very well. Although the recent FDA approval for high-risk prolapse does not make any anatomic distinctions as to the type of prolapse, a great deal of experience that has been accumulated in the international practice community tells us that the more focal the prolapse, the better the outcomes. Very specifically, many of the elderly patients with prolapse that are encompassed by this recent FDA approval, do have a localized area of prolapse. Maybe these patients have one cord that is broken, most commonly a central cord, where MitraClip is ideal, or they have a form of degenerative MR, fibroelastic deficiency (FED), the typical pathology in most of the older patients that is also well suited to MitraClip therapy. These patients are in contrast to the 45-year-old who presents with degenerative MR, who will more typically have Barlow’s disease with involvement of more leaflet segments, and for whom surgical repair is clearly the treatment of choice.

Does the process of percutaneous mitral valve repair have any similarities to aortic valve replacement (TAVR)? 

The therapies are not similar. The aortic valve is both anatomically and clinically very different from the mitral valve. There are huge differences in the technical issues involved with mitral compared to aortic therapy. The technologies are vastly different and developing on different pathways. 

What is the access for percutaneous mitral valve procedures?

Mitral repair with the MitraClip is all catheter-based. Access is transseptal. For percutaneous mitral valve replacement, the initial development is largely transapical, meaning surgical access, but beating heart, similar to TAVR in that regard. There are efforts to develop entirely percutaneous mitral valve replacement technologies. One point of distinction is that aortic valve replacement requires arterial access, or generally requires arterial access. Percutaneous mitral replacement is a transseptal procedure, and because it is unusual to have venous obstruction, the percutaneous access issues that have been part of the challenge of aortic valve replacement by TAVR are much less a part of the picture for mitral replacement.

Is this a procedure that would feel very natural for multidisciplinary heart teams to adopt?

The heart team process, i.e., having a team of interventional and surgical physicians and all of our other colleagues involved in these trial efforts, is critical and is part of the mitral therapy, just as it is part of the aortic valve therapy.  For MitraClip, pre-procedure screening is where the heart team has the greatest importance.

Figures are courtesy of and copyrighted by Abbott Vascular.

Disclosure: Dr. Ted Feldman reports research grants from and consultant to Abbott.

Dr. Ted Feldman can be contacted at tfeldman@tfeldman.org.

What is mitral valve regurgitation?

The mitral valve lies between the left atrium and the left ventricle, and its purpose is to support one-directional blood flow through the heart. A healthy functional valve will open just before and during atrial contraction, allow passive filling of the left ventricle with blood from the left atrium, and then close tightly during ventricular systole. This prevents blood from flowing backwards into the left atrium during ventricular contraction.

Mitral regurgitation occurs when the valve doesn’t completely close together during ventricular contraction, and a portion of the blood in the left ventricle is propelled back through the leaflets of the mitral valve into the left atrium. This reverse blood flow is known as a regurgitant jet and is graded according to its severity. It can occur as a result of valve degeneration, or be functional, where the valve itself appears normal in structure, but due to other changes in the heart’s structure such as a dilated left ventricle or a dilated mitral annulus, or even papilliary muscle displacement, the valve fails to close properly.

How are mitral regurgitation patients identified?

Initially, mitral regurgitation can be well tolerated, if the left ventricular function is preserved, so it can go undiagnosed for some years. However, once the left ventricle and atrium are involved, mitral regurgitation can give rise to symptoms of heart failure such as dyspnea, lethargy and fluid retention. Cardiac arrhythmias such as atrial fibrillation and chest discomfort may also result.

Mitral regurgitation may be discovered by chance, during a medical examination. On oscillation, the intensity and duration of systolic murmur, and the presence of a third heart sound, which is often heard loudest at the apex and radiates to the left lateral axilla, may be heard. The presence of a third heart sound can trigger further investigations of the patient, such as an echocardiogram.

How does the MitraClip help with mitral regurgitation?

When the leaflets of the mitral valve don’t fully close and a small orifice remains across the valve during ventricular systole, this allows a regurgitant jet to pass through into the left atrium. The MitraClip clips the portion of the mitral valve that is failing to close tightly together, so that during systole it reduces the level of mitral regurgitation from perhaps a grade of three or four, to a grade of one or two.

Source: 

Madden S. (interview) Transcatheter mitral valve repair: nursing considerations from a U.K. hospital. Cath Lab Digest online exclusive. Available online at https://www.cathlabdigest.com/Transcatheter-Mitral-Valve-Repair-Nursing-Considerations-UK-Hospital.

References

1. Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, et al; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011 Apr 14;364(15):1395-406. doi: 10.1056/NEJMoa1009355. 
2. Whitlow PL, Feldman T, Pedersen WR, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair. The EVEREST II (Endovascular Valve Edge-to-Edge Repair) high risk study. J Am Coll Cardiol. 2012;59:130-139.
3. Lim DS, Reynolds MR, Feldman T, Kar S, Herrmann HC, Wang A, et al. Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation following transcatheter mitral valve repair with the MitraClip^® system. J Am Coll Cardiol. 2013 Oct 24. doi:pii: S0735-1097(13)05864-6. 10.1016/j.jacc.2013.10.021.
4. Young A, Feldman T. Percutaneous mitral valve repair. Curr Cardiol Rep. 2014 Jan;16(1):443. doi: 10.1007/s11886-013-0443-6.