Percutaneous repair of mitral regurgitation under study

It is hoped that alternative percutaneous strategies to standard surgical repair might be available to future patients.

Clinical trials testing many unique devices are now underway to demonstrate whether percutaneous treatment of mitral regurgitation can be done safely and successfully. Despite careful engineering and thoughtful application, it is not clear which devices will be successful in reducing mitral regurgitation long-term. This review outlines the current status.

Direct valvular repair

The Mitraclip (Evalve) is delivered via a steerable catheter which is introduced into the left atrium through a larger transseptal guiding catheter. Using transesophageal echocardiography (TEE), the delivery catheter is positioned so that the clip is at right angles to the mitral line of coaptation and centered over the regurgitant jet. The clip is then opened, advanced through the mitral valve, and pulled back in systole, capturing the edges of the anterior and posterior leaflets. A set of grippers then secures the leaflet edges inside the clip, producing a double orifice mitral valve.

Peter C. Block, MD

If mitral regurgitation as assessed by TEE is satisfactorily reduced, the clip is closed completely. Depth of leaflet tip capture, clip position, and residual mitral regurgitation are evaluated by TEE. If mitral regurgitation reduction is adequate (usually to about 1+) the clip is released. Patients are treated with antiplatelet agents and usually leave the hospital within days. Early follow-up data from the EVEREST (Evalve Mitral Endovascular Valve Edge-to-Edge Repair) I trial show that >80% of patients had mitral regurgitation reduced to <2+, and 70% had mitral regurgitation reduced to <1+. Of those followed as long as three years, >85% continued to have reduction of mitral regurgitation to <2+ and have not needed surgery.

The EVEREST I trial has been completed and a phase-2 trial (EVEREST II) is under way. In EVEREST II, patients are randomized 2-to-1 against standard surgical mitral valve repair or replacement. Candidates for the EVEREST II trial must meet the following criteria:

1. Moderately severe or severe mitral regurgitation.
2. Mitral regurgitation due to degenerative (prolapse), ischemic(+/-) with nondilated annulus, or functional (if annulus <4.5 cm) disease.
3. Central jet of mitral regurgitation (usually best at the A2/P2 position on the mitral leaflets).
4. Left ventricular ejection fraction >30%.
5. No left atrial thrombus.
6. Must have reason to repair mitral regurgitation: LV dilation, development of atrial fibrillation, symptoms.

In this landmark trial both surgical and percutaneous outcomes will be evaluated by an echocardiographic core laboratory. Will equivalence of percutaneous outcomes to surgery be enough to justify more widespread use of this device? If not equivalent, how much less reduction in mitral regurgitation will be acceptable for therapeutic strategies in the future? Is reduction of mitral regurgitation to <2+ enough to cause reversal of LV dilation and improve both ventricular function and symptoms? These and many other questions hopefully will be answered in EVEREST II.

Indirect devices to improve mitral valve coaptation

A number of devices that can be percutaneously anchored in the coronary sinus are under evaluation. Because of their stiffness or by shortening, they can move the posterior annular plane of the mitral valve toward the anterior leaflet, improving the line of coaptation. Examples are the Viacor, Carillon (Cardiac Dimension), and Monarch devices. These and similar devices rely on the coronary sinus and posterior annulus being in the same plane.

The circumflex coronary artery cannot course between the coronary sinus and the annulus in candidate patients since device deployment might cause circumflex coronary constriction or occlusion. Thus, pre-treatment evaluation by MRI, CT, and TEE to evaluate anatomic suitability is necessary.

Some devices are in early phase-1 trials. The Carillon Mitral Annuloplasty Device European Union Study (AMADEUS), evaluating the Carillon, is nearing completion in Europe. Its results will indicate what percentage of selected patients are improved, and whether there is durability of mitral regurgitation improvement as well as safety in device deployment. AMADEUS will surely be followed by trials of other coronary sinus devices since percutaneous access and suitability for device placement in the coronary sinus have already been proven in electrophysiological applications.

Two other novel devices directly affect the posterior annulus. The Ample device consists of a coronary sinus anchor to which a tether is connected that passes through the coronary sinus wall into the left atrium. The tether courses through another anchor in the interatrial septum and can be shortened. This pulls the posterior annulus (and the posterior leaflet) toward the anterior leaflet, improving the mitral line of coaptation and reducing mitral regurgitation.

Another device, the Mitralign device, is introduced through a retrograde arterial catheter passed into the left ventricle and positioned so that its tip lies against the posterior mitral annulus behind the posterior mitral leaflet. Three or more anchors are placed through the catheter in the annulus on its ventricular side. The anchors are connected, and when the connection is shortened the annulus is constricted. Both devices have been shown to reduce mitral regurgitation in early studies, and safety and efficacy trials are anticipated.

The myocardial problem

Ischemic myocardial disease or LV dilation because of cardiomyopathy have different effects on the mitral valve and annulus. Surgical experience has shown that structural mitral valvular disease (prolapse, cleft, etc.) is best treated with a combination of direct anatomic repair and placement of an annuloplasty device. Ischemic mitral regurgitation, due to annular dilation because of basal scarring or tethering of one or both mitral leaflets due to papillary muscle scarring or insufficiency, is produced by LV dysfunction, not valvular pathology. Hence a strategy to repair the valve and/or annulus may not be adequate.

The Coapsys (Myocor) device has the unique feature of supporting both the posterior annulus and the LV myocardium in the region of the posterior papillary muscle. The posterior support pad is attached to an anterior myocardial pad with a transventricular tether that is shortened by the surgeon under TEE guidance until mitral regurgitation is reduced. The surgical Treatment of Functional Mitral Regurgitation without Atriotomy or Cardiopulmonary Bypass Clinical Evaluation (TRACE) trial showed a reduction of mitral regurgitation from 3 to 1+ and also a persistent reduction of LV systolic and diastolic volumes out to one year.

The same device is now being tested in the larger Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve (RESTOR-MV) study, in which patients will randomly receive the Myocor device or standard surgical annuloplasty repair at the time of CABG.

The Myocor device is also about to be tested in percutaneous form (iCoapsys) in the Valvular and Ventricular Improvement Via iCoapsys Delivery (VIVID) phase-1 trial. As in the surgical application, the posterior pad is placed into the pericardial space. Coronary angiography is used to establish a position that does not impact the circumflex marginal arteries. A tether is then introduced through the posterior pad, through the left ventricle to an anterior myocardial pad placed to the right of the interventricular septum. Shortening the tether reduces the left ventricular and posterior-anterior annular dimensions, reducing mitral regurgitation. This percutaneous device focuses on the underlying pathology of both ischemic and cardiomyopathic LV function by supporting both the annulus and left ventricle. It is hoped that mitral regurgitation due to LV dilation as well as mitral regurgitation from coronary disease might be treated in this manner.

Percutaneous repair of mitral regurgitation is still in its early stages. Nevertheless, building on the promise of the completed EVEREST I trial and the acknowledged success of surgical therapy, it is hoped that percutaneous alternative strategies to standard surgical repair might be available to future patients. Stay tuned.

Peter C. Block, MD, is a Professor in the Department of Medicine, Division of Cardiology at Emory University Hospital, Atlanta, and a Member of the Cardiology Today Editorial Board.