First Published Report From MAC Global Registry Highlights Risks, Opportunities for Transcatheter Mitral Valve Replacement

Investigators leading the Mitral Annular Calcification (MAC) Global Registry examining the use of transcatheter mitral valve replacement via balloon-expandable valves designed for aortic stenosis have, for the first time, published the outcomes of the earliest-treated patients in a peer-reviewed journal. 

Mayra Guerrero, MD (Evanston Hospital, Evanston, IL), the lead author on the study, has provided updates from the registry at interventional cardiology meetings—as reported by TCTMD—and the number of patients in the report that appeared this week in JACC: Interventions is lower than that in Guerrero’s earlier presentations. As she pointed out, it’s common for published reports to lag behind data presented at meetings: this first published glimpse at the data should help interventionalists understand both the opportunities and substantial risks seen with this technology, in the specific setting of mitral annular calcification.

“What we wanted to show is that this is doable, that this is an option for patients who really need an intervention but are otherwise not candidates for surgery or for any other procedure available so far,” Guerrero told TCTMD. “So number one, yes, it’s doable. Number two, it’s not free of risk—we obviously found that there can be complications, and we need to be careful in selecting patients who would be at lower risk for the complications that we know of. Number three—and this is not in the manuscript, although we presented data at EuroPCR—we now have double the number of patients, and the important point is that outcomes get better as we learn and share our experience with others.”

Guerrero et al’s paper includes the first 64 patients treated between September 2012 and July 2015 at one of 32 centers. All of the patients were deemed inoperable and suitable for the procedure under compassionate use, not only by the treating hospital’s heart team but also by the MAC Global Registry investigators. Patients were a mean age of 73 years, with a mean STS score of 14, mean mitral gradient of 11.45 mm Hg, and mean mitral area of 1.18 cm². Two-thirds were women.

Similar to what Guerrero has presented previously, technical success—defined as no procedural mortality; successful access, delivery, and retrieval of the device delivery system; successful deployment/correct positioning of the first intended device; and freedom from emergent surgery or reintervention related to device or access—was achieved in 72% of patients. Need for a second valve was the number one reason for falling to meet this endpoint, they noted.

Six patients experienced left ventricular outflow tract (LVOT) obstruction, five of whom died. Better recognition of LVOT obstruction predictors, as well as ways of managing the complication when it occurs, have been key areas in which this procedure has improved. Indeed, in a separate publication this week in Catheterization and Cardiovascular Interventions, Guerrero and colleagues describe the use of percutaneous alcohol septal ablation to acutely reduce LVOT obstruction induced by transcatheter mitral valve replacement.

In all, the 30-day all-cause mortality rate was 29.7%—12.5% cardiovascular and 17.2% noncardiac. Among survivors, however, 84% were in NYHA class I or II heart failure at day 30; more than 90% had been NYHA class III or IV at baseline.

Transparency and Caution

Guerrero was careful to stress that she and her co-authors had ”tried to be as transparent as we could be” about the risks and complications. “Yes, we can do transcatheter mitral valve replacement in patients with MAC—it’s possible, but we have to be careful in whom we are using this for, in order to prevent complications,” she said.

She acknowledged the possible downsides of publishing this type of very early, feasibility data. “One bad thing is that someone reads this and sees the good results [in certain patients] and they think, I can do this, and they do a procedure and things go wrong,” Guerrero commented. “It would be better to produce the data we need, then do more analysis so we learn more and can [say]: these are the predictors of LVOT obstruction, these are the things we can do to treat this complication, and these are the things we can do to prevent it. I think this is what the MITRAL trial can help us with.”

MITRAL is the physician-sponsored, Food and Drug Administration (FDA)-approved investigational device exemption trial now underway. The trial includes 10 geographically dispersed sites in the United States and aims to enroll a total of 90 patients: 30 valve-in-MAC, 30 valve-in-ring, and 30 valve-in-valve. Both the ring and valve groups would enroll patients with previously implanted—now failing—surgical devices.

Guerrero hopes that physicians with inoperable patients with MAC will consider referring patients for enrollment in the trial, rather than attempting the kinds of procedures that make up the series published this week. “The quicker we learn, the quicker we can teach other sites, and the quicker others can benefit,” she said.

A Boundary Crossed

 “Guerrero et al are to be commended for developing a procedure for patients who had few, if any, surgical options,” Paul Sorajja, MD and Mario Gossl (Minneapolis Heart Institute, MN) write in an editorial accompanying the JACC: Cardiovascular Interventions paper. What’s needed next, they say, are further insights into patient selection, prosthesis landing zone, suitability of MAC pathology, and details on avoiding and treating LVOT obstruction—something albeit addressed now in the separate publication.

Still, the “remarkable progress” made by the MAC Global Registry deserves attention, they continued, calling it “a new boundary crossed.”

“One can . . . consider, with enthusiasm, the potential possibilities for success once dedicated prostheses become available,” Sorajja and Gossl write, “and how the unmet needs of many patients with mitral regurgitation will be finally addressed.”

Indeed, a relatively large number of companies, big and small, are racing to produce the first safe and effective fully transcatheter mitral valve, but these, Guerrero notes, are being developed almost exclusively for mitral regurgitation, not severely calcified mitral annuli. She predicts it will “be a while” before any dedicated mitral valves are developed for the treatment of MAC.

“The ones in our registry are super-super calcified, so even if I had the option to use a dedicated transcatheter mitral valve, because they are designed for a different pathology, they wouldn’t be suitable. And some of these MAC patients may not do as well with transapical access. At least, the balloon expandable aortic transcatheter valves can be delivered using a transseptal approach, which is a lot less invasive. So I think it’s going to be a while.”

The MITRAL trial is using exclusively the Sapien XT and Sapien 3 valves (Edwards Lifesciences), both of which are balloon expandable—the belief being that the self-expanding CoreValve (Medtronic) may not be as suited to the very thick calcified valve orifices being treated in the trial. The CoreValve is also too long in the mitral position, Guerrero added, although she noted that the Lotus and Direct Flow transcatheter aortic valves, which are shorter and repositionable, may be good options in the mitral position. They are currently not being studied in the FDA-approved trial.

 

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Disclosures:

 

• Guerrero reports serving as a proctor and consultant, and receiving research grant support, for Edwards Lifesciences. 
• Sorajja reports receiving consulting and speaking fees from Abbott Vascular; consulting fees from Medtronic; speaking fees from Boston Scientific; and consulting fees from Lake Region.  
• Gossl reports having no relevant conflicts. 

 

Related Stories:

 

• As Technique Inches Forward, Outcomes Improve for Transcatheter Treatment of Severe Calcific Mitral Disease
• Early Results for Transcatheter Mitral Valve Replacement Reveal Complications and Challenges for the Long Road Ahead