MitraClip was approved by the U.S. Food and Drug Administration (FDA) in October 2013 for the limited indication of asymptomatic degenerative mitral regurgitation (MR) in patients considered prohibitive risk for surgical mitral valve repair surgery. The exact language of the label is, "The MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation." Surgical repair for degenerative mitral regurgitation (DMR) in suitable surgical candidates is well established. The outcomes of surgical repair therapy are both highly successful and durable. Thus, the recommendation for use of percutaneous mitral repair is restricted to poor surgical candidates with DMR etiology.

The evidence base for MitraClip includes a randomized comparison with surgery and also several registries for patients with high risk for surgery. The MitraClip device has been compared with surgery in a randomized trial.¹ After one year of follow-up, it was clear that the ability of MitraClip to reduce MR severity is less effective than standard surgery. It was also apparent that the less invasive procedure was safer, and that despite residual MR in many patients, reductions in left ventricular (LV) chamber volumes and clinical outcomes assessed by quality of life questionnaires were similar for MitraClip compared to surgery. Four- and five-year follow-up in these lower-risk patients has continued to verify the same findings.²

A registry including only patients with high surgical risk for mitral therapy has also been conducted prospectively in the U.S.³ The registry included patients with predominantly functional MR and demonstrated that the MitraClip procedure can be performed with acceptable safety in very ill patients with consistent improvements in LV chamber dimensions, symptoms, and heart failure hospitalizations.⁴ An analysis of the subgroup with DMR and prohibitive surgical risk similarly showed acceptable procedural safety and, importantly, improvements in LV dimensions and symptoms. The risk and comorbidity of this subgroup is reflected by the mean Sosciety of Transthoracic Surgeons (STS) Risk Score of 13.2%, higher even that the mean Risk Score of 11.2% in the Placement of Aortic Transcatheter Valves (PARTNER) trial, Cohort B inoperable patients. The most striking finding in the registry is that the rate of hospitalizations for heart failure in this group of patients was reduced by almost three-quarters with MitraClip therapy. Thus, the clinical impact of MitraClip in this elderly, high-risk group is highly significant.

A related Patient Case Quiz by Gin et al. highlights the use of MitraClip in a high-risk DMR patient. The case also identifies another important feature of the use of MitraClip therapy. The case describes evaluation by a "heart team." This is a multidisciplinary process involving case review by interventional cardiologists, cardiovascular surgeons, echocardiographers, and heart failure specialists. This rigorous evaluation determines not only the potential suitability for cardiovascular surgical repair or replacement therapy, but also the potential for percutaneous repair with the MitraClip device. The case vignette further notes that the patient was deemed suitable for MitraClip therapy after an extensive echocardiographic examination. This point deserves some amplification. The specific anatomy best suited for MitraClip therapy includes a relatively central MR jet origin, and a coaptation gap of less than 15 mm. MR that arises from the commissures is particularly difficult to treat with MitraClip. Similarly, large flail segments with an excess of coaptation gap have a high failure rate with MitraClip therapy. Many older patients with DMR have prolapse or localized flail of only the middle scallop of P₂, associated with a less severe form of the pathology, fibroelastic deficiency. Thus, in this particular patient with a more severely deformed valve and prolapse of multiple valve segments, it requires a critical examination of the echocardiogram to assess the potential for effective MR reduction with MitraClip.

The use for MitraClip to treat patients with functional MR is less well studied. There is substantial registry experience in the U.S. and internationally with high-risk patients with functional MR due to ischemic or dilated cardiomyopathy, but there are no randomized trials. The registry data generally include populations with mixed etiologies including both functional and degenerative MR. From one registry to another, there are no standard inclusion or exclusion criteria, so that evaluation of the results is challenging. Nonetheless, these experiences demonstrate similar findings to the initial randomized trial and the DMR registry group. Functional MR patients show similar improvements in LV chamber dimensions after MitraClip therapy, improved symptoms, and a similar reduction in rehospitalization rates.

To better define the outcomes in the functional MR group, a large multicenter randomized trial is being conducted in the U.S. The Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for Extremely High-Surgical-Risk Patients (COAPT) trial will randomize 430 patients to guideline-directed medical therapy (GDMT)⁶ compared to MitraClip therapy. The major inclusion criteria include symptomatic functional MR (≥3+) due to ischemic or nonischemic cardiomyopathy with a LV ejection fraction between 20% and 50%. Patients must have a heart failure hospitalization within the last 12 months and/or a corrected B-natriuretic peptide (BNP) level ≥300 pg/ml or NT-proBNP ≥1,500 pg/ml within 90 days. The qualifying transthoracic echocardiogram is performed on optimal therapy at least 30 days after any change in GDMT, revascularization, and/or implant of cardiac resynchronization therapy. This trial is the first randomized comparison of any form of valve repair with GDMT. Surgical mitral repair has developed with no such comparisons, and there is uncertainty about the role of isolated repair surgery, when not performed during CABG or other valve surgery, for patients who are not high-risk for surgery. Thus, COAPT will help define the role of MitraClip for high-risk patients, but the uncertainty of the role of surgery for lower risk patients will remain controversial.

References

1. Feldman T, Foster E, Glower D, et al. Percutaneous repair or surgery for mitral regurgitation. New Engl J Med 2011;364:1395-406,.
2. Mauri L, Glower DG, Apruzzese P, et al. Four-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol 2013;62:317-28.
3. Whitlow P, Feldman T, Pedersen W, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair. J Am Coll Cardiol 2012;59:130-9.
4. Glower D, Kar S, Lim DS, et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study. J Am Coll Cardiol 2014;64:172-81.
5. Lim DS, Reynolds MR, Feldman T, et al. Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation following transcatheter mitral valve repair. J Am Coll Cardiol 2014;64:182-92.
6. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.

Keywords: Aged, Cardiac Resynchronization Therapy, Cardiac Surgical Procedures, Cardiomyopathy, Dilated, Comorbidity, Geriatrics, Follow-Up Studies, Heart Failure, Hospitalization, Longitudinal Studies, Mitral Valve, Mitral Valve Insufficiency, Natriuretic Peptide, Brain, Outcome Assessment, Health Care, Pectinidae, Peptide Fragments, Prolapse, Registries, Specialization, Surgeons, Surgical Instruments, Uncertainty

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