Technology promising for percutaneous mitral valve replacement

A randomized trial of the percutaneous mitral clip vs. standard surgical therapy is now underway.

Percutaneous repair of mitral regurgitation continues to evolve as new technologies are developed.

The leader in this area is Evalve, which has now completed its phase-1 trial of clip delivery to the central portion of the anterior and posterior mitral leaflets in patients with central MR, mimicking the Alfieri surgical approach and producing a double orifice valve without stenosis.

EVEREST trials

Recent updates of the EVEREST I and EVEREST II trials now include 97 nonrandomized patients. The results are gratifying and demonstrate that in carefully selected patients, this concept improves MR to ≤2+ in 68/82 (83%) and to ≤1+ in about 70% of successfully completed procedures. MR reduction is durable up to 36 months, and surgical options seem to be preserved. In patients who had unsuccessful procedures, insufficient reduction of MR with the clip (or clips) or recurrence of MR requiring mitral valve surgery, about 70% had mitral valve repair.

Peter C. Block

Acute procedural success has now reached 90% and complications in this first group of patients have been gratifyingly low. Not all patients treated with this technology have had degenerative (mostly prolapse) disease: 20% had functional MR due to mild annular dilation with resultant central MR.

The EVEREST II trial, a randomized trial of the percutaneous mitral clip against standard surgical therapy, is now underway. About 20% of patients anticipated for this trial were randomized. The results are awaited with interest, since a core echocardiographic review of each patient will be done and information about one-year follow-up for patients treated percutaneously and surgically will be collected.

Coronary sinus route

Edwards Lifesciences has developed technology that more closely mimics the Alfieri operation. A transcatheter stitch, rather than a clip, placed in the mitral leaflet tips, also produces a double orifice valve. The phase-1 trial is under way in European centers.

Unfortunately, in most patients treatment of MR is not that simple. Surgeons have long recognized the need for placement of an annuloplasty device in association with any direct mitral valve repair. Other transcatheter technologies have been devised to treat functional causes of MR such as annular dilation and left ventricular dilation with an otherwise structurally normal mitral valve.

Attempts to mimic surgical annuloplasty have focused on the coronary sinus (CS) as a transcatheter route, which lies behind the posterior mitral annulus. Currently, CS devices in early human trials include the Viacor, Cardiac Dimensions, St. Jude and Edwards Lifesciences devices.

Either through an increasingly rigid series of CS rods that move the posterior annulus forward or the use of two anchors connected by a bridge that can be shortened (“cinching” the posterior annulus), these devices improve the line of coaptation and reduce MR by moving the posterior leaflet toward the anterior leaflet.

Use of the CS as a conduit raises a number of issues: The CS is often superior to the mitral annulus, and movement of the CS might not affect the posterior annulus except in the short term before stretching of the atrial muscle occurs. Also, the circumflex coronary artery traverses the distal CS, and might be compressed by such devices. Thus, careful selection of patients for such therapy is necessary, and pre-procedure imaging of the relationships of the CS to the mitral structures will be an important part of that process.

Other technologies, problems

Other concepts, such as from Ample Medical, attempt to move the posterior annulus forward by placing a tether between the CS and an atrial septal anchor. Shortening the tether moves the posterior annulus forward and mitral coaptation is restored. Mitralign technology employs a novel transventricular approach to the posterior mitral annulus from below and behind the posterior mitral leaflet. Transcatheter sutures are placed directly into the annulus, and a shortening tether between the sutures cinches the annulus.

Ischemic MR poses even more complex problems. Surgical annuloplasty has been inadequate to treat this entity, with early recurrence of MR and ongoing clinical deterioration because of ventricular dilation and ongoing papillary muscle dysfunction. Myocor’s device, currently in a surgical trial, combines moving the annulus forward and buttressing the posterior ventricular myocardium to the level of the papillary muscles. The mitral supporting structures are thus restored to their proper position within the virtual cylinder defined by the mitral annulus. If the surgical trial results are as promising as the original phase-1 trial, a percutaneous version of this device may well be a therapeutic option for some patients with moderate to severe ischemic MR whose surgical options are limited.

Evolving percutaneous strategies for the treatment of MR is taking many paths due to its complex causes. Direct leaflet repair is already a reality, and some of the multiple annuloplasty-like devices will certainly be useful in selected patients. Other devices still in early development will offer even more promise for the percutaneous treatment of patients with this complex pathophysiology. Interventionalists may well use more than one strategy to help patients in the future, combining direct leaflet repair with an annuloplasty device, for example, as surgeons routinely do.

There are lots of possibilities, and if a percutaneous mitral valve replacement becomes reality, the future for interventionalists is bright.

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