MitraClip Reaches Real-World Use in U.S., but Population Refinement Remains

The FDA’s approval last fall of Abbott Vascular’s minimally invasive, catheter-based MitraClip® therapy fills an important unmet need for patients with severe degenerative mitral regurgitation who are considered high-risk for surgery — and it holds out promise for those with functional mitral regurgitation who exhibit heart failure symptoms.

So say interventional cardiologists Samir Kapadia, MD, Amar Krishnaswamy, MD, E. Murat Tuzcu, MD, and Patrick Whitlow, MD, who are intimately involved in MitraClip implantation at Cleveland Clinic.

“MitraClip is an incredibly effective option — more so than expected,” says Dr. Kapadia, who directs the catheterization laboratory. “Most patients experience a significant decrease in regurgitation, their ventricle shrinks, heart failure symptoms resolve, medical management gets easier and hospital readmissions stop.”

Vetted in Europe

Much of the experience with MitraClip has been obtained in Europe, where the device has been used since 2008. A post-marketing study known as ACCESS-EU, released in June 2013, found low rates of adverse events at 30 days and 12 months. The mean age of enrolled patients was 74, and 45 percent were 75 or older. One year after implantation, 78.9 percent of patients had a mitral regurgitation (MR) severity score ≤ 2+, and 71.4 percent were in New York Heart Association functional Class I (normal) or Class II (mild), compared with 15 percent at baseline.

Two mechanisms, one indication (so far)

Mitral regurgitation is a common cause of heart failure. Data from Cleveland Clinic’s patient registry show that patients with mitral regurgitation and heart failure have higher rates of hospitalization and mortality when treated medically compared with patients whose mitral regurgitation is treated surgically. Treatment of mitral regurgitation is directed at improving lives as well as saving them.

Two different mechanisms can cause mitral regurgitation:

• In degenerative mitral regurgitation, the mitral valve itself is damaged.
• In functional mitral regurgitation, function of the mitral valve is adversely impacted by annular dilatation or abnormal tension on the chordae supporting the valve leaflets due to left ventricular dysfunction.

“For patients with degenerative mitral regurgitation, surgical repair is an excellent option, with an operative success rate of more than 99 percent and 10-year survival of more than 90 percent when performed in a center of excellence,” says Dr. Krishnaswamy.

Despite the success of surgery, however, an estimated 10 percent of patients with degenerative mitral regurgitation are not healthy enough to undergo the operation safely. In the U.S., those are the patients who are benefiting first from MitraClip, which was approved by the FDA for patients with significant symptomatic degenerative mitral regurgitation who are deemed high-risk for surgery.

Exploring utility in functional mitral regurgitation

Surgery yields a less durable response in patients with functional mitral regurgitation, and the benefits of surgery remain questionable in this population, particularly in patients who do not need coronary revascularization and have impaired left ventricular function. “Retrospective propensity-matched studies have shown no difference in mortality between medical management and valve repair in these patients,” says Dr. Tuzcu, Vice Chairman of Cardiovascular Medicine. “Therefore, surgery is not strongly recommended for this population.”

About 50 percent of patients with heart failure and severe functional mitral regurgitation are managed medically, as reported from Cleveland Clinic. These patients have high rates of recurrent congestive heart failure, hospital admissions and mortality. An ongoing clinical trial (detailed below) is investigating whether MitraClip will benefit these patients compared with medical management alone. Although a similar catheter-based device, the CARILLION® mitral contour system (Cardiac Dimensions® Inc., Kirkland, Wash.), is being tried in Europe and as many as 15 other devices are in the pipeline, none are likely to be approved in the near future.

Assessment continues in COAPT…

“The FDA has approved MitraClip for patients with severe regurgitation from degenerative mitral valve disease who are at prohibitive risk for surgery,” says Dr. Kapadia, “and it has approved the COAPT trial for patients with functional mitral regurgitation who are being managed by medical therapy but are still symptomatic.”

In its approval of MitraClip, the FDA requested a study in which eligibility for valve repair surgery will be determined by a heart team that includes cardiac surgeons and cardiologists specializing in heart failure management and interventional cardiologists specializing in the MitraClip procedure. Dr. Kapadia serves on the steering committee for this 420-patient, open-label randomized trial, known as COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High-Risk Surgical Patients). Enrollment began recently, but results are not expected until at least 2016.

…While real-world use begins

While refinement of the target patient population continues, Cleveland Clinic cardiologists are confident they have a good understanding of how MitraClip fits into the spectrum of treatment options for patients with mitral valve disease. “We understand it is not the answer for all patients with mitral regurgitation,” says Dr. Krishnaswamy. “But there’s no question that it’s the right treatment for some.”

Referrals of potential candidates for MitraClip are welcomed. The screening process involves an evaluation of cardiac anatomy, including the coronary arteries and valves, and a heart failure consultation. Patients who do not meet the FDA-approved indication for the device may potentially qualify for the COAPT study.

Importantly, the heart team approach identifies other treatment options. “When a patient is better suited for surgery or other conventional therapy such as biventricular pacing, it should be the first choice,” says Dr. Kapadia, noting that Cleveland Clinic performs more than 1,000 mitral valve repairs a year. “But if symptoms don’t improve or surgery is not indicated, then MitraClip should be considered. Awareness of evolving therapies for patients with heart failure and mitral regurgitation is critical and timely, because treatment options are evolving rapidly.”