Percutaneous Mitral-Valve: 'Not Yet Ready for Prime Time'

November 03, 2011

November 2, 2011 (London, United Kingdom) — A percutaneous approach to the treatment of mitral regurgitation (MR) does have a future, but for now, surgery will remain the mainstay of treatment, surgeons and interventional cardiologists agreed at the recent PCR London Valves 2011 meeting.

When and whether a transcatheter approach will ever become a mainstream therapy for MR was the subject of a lively debate, with one speaker explaining that mitral-valve surgery is currently "close to perfect," setting a high bar for percutaneous access. "If you take the vast majority of patients with degenerative mitral regurgitation, they get a very good service from surgery," said Dr Francis Wells (Papworth Hospital, Cambridge, UK), a surgeon. "Is there a future for percutaneous mitral valves? Almost certainly, but for whom and when? Is it ready for prime time? Not yet.

"I'm not saying there is no place for this, but at the moment we must focus on the patient," Wells added. "Not the device, not the cardiologist, and not the firm producing the device. We've got to do the best for the patient, and right now the gold standard is surgery."

Interventional cardiologist Dr Ted Feldman (NorthShore University HealthSystem, Evanston, IL) argued that mitral-valve surgery is far from flawless for everyone: "We have to establish what is the real norm in the world of surgical therapy, because it's not perfection," he observed. He nevertheless agreed that identifying the best patients in whom to employ a transcatheter approach will be key. "There is a little bit of a future for percutaneous mitral therapy in 2011–2012. We are beginning to define some of the specific types of patients who will most benefit from these therapies, and I hope we'll soon be able to draw out a sharper beam on them as we go forward," he added.

Do Any of the Interventional Mitral Devices Work?

The subject of percutaneous mitral-valve therapy was also discussed during a focus session by Dr Michael Mack (University of Texas, Dallas) at last month's European Association of Cardio-Thoracic Surgery 2011 Annual Meeting in Lisbon, where he reviewed the whole field of interventional approaches to MR.

Initially, in the early 2000s, "it was felt that the mitral-valve space would grow much more rapidly from a transcatheter standpoint than the aortic-valve area," explained Mack. "However, the opposite has proven to be the case; the mitral-valve space has not grown rapidly from a transcatheter-valve standpoint and the aortic valve has, for the simple reason that it's not clear that any of these [mitral] devices work, work well, or work in the majority of patients," Mack noted.

The mitral valve has not grown rapidly from a transcatheter standpoint, for the simple reason that it's not clear that any of these devices work, work well, or work in the majority of patients.

He went on to summarize development in this field, noting that at least 23 companies have invented percutaneous mitral devices [1], and a number of these "have already come and gone out of business."

One of these devices, the MitraClip (Abbott, Abbott Park, IL), is really the only percutaneous device on which there is any significant clinical-trial data and any substantive use. Mack believes the MitraClip "has a narrow role, but it does work in functional MR," and therefore it may have a place in the treatment of high-risk, elderly, inoperable patients, including those with heart failure, he said.

But of all the percutaneous approaches for MR, Mack says he holds out most hope for mitral-valve replacement, in contrast to surgery (in which the pendulum has swung the other way, from valve replacement to repair, because the latter provides superior long-term outcomes and is now also starting to be performed with minimally invasive surgical techniques).

Are Coronary Sinus Annuloplasty Devices "All But Dead"?

Mack first discussed coronary sinus annuloplasty devices--deemed an "indirect annuloplasty approach"--of which three have been developed but only one remains. The overall clinical experience with these has been in a total of 259 patients, with about a 65% successful implantation rate, said Mack. "All three devices did show to some extent proof of concept that you could produce some degree of reduction of MR. There was a modest improvement in clinical outcomes, and the results appeared to last to up to two years."

But only the Carillon device (Cardiac Dimensions, Kirkland, WA) is still in development and has "the majority of positive experience," he noted. "However, one of the drawbacks of this device is that there were strut fractures associated with [long-term] implantation." As a result of this, the device has now been redesigned and reintroduced into clinical trials, he explained.

Nevertheless, it looks like only 50% to 60% of patients, based upon the coronary sinus anatomy, may be candidates for this type of device, he concluded. "So I don't hold out a whole lot of hope for the future." At the London meeting, Wells agreed, calling coronary sinus devices "all but dead."

But Feldman disagreed, noting that the redesigned Carillon system has recently "received a CE Mark in Europe and is in clinical use there" [2,3]. "There is a little bit of a future" for this approach, he believes.

Next up on Mack's list was direct annuloplasty devices delivered percutaneously; he discussed a number of examples, including the Accucinch device (Guided Delivery Systems, Santa Clara, CA) [4], which has first-in-human data and "does show proof of concept," but he concluded he was not overly inspired by this group of devices.

He then discussed what he called "a totally out-of-the-box way of thinking about correction of MR," the Percu-Pro System (Cardiosolutions, Stoughton, MA), which consists of a proprietary catheter system, a spacer device, and a reversible anchoring mechanism [5]. Dr Lars Svensson (Cleveland Clinic, OH) has done some animal work with this system, Mack noted, and the device is now in phase 1 trials.

MitraClip: Narrow Role in Functional High Risk Patients

On the subject of the MitraClip, there have been more than 3000 patients treated with this device, the majority in Europe in various trials, Mack noted, explaining there are 80 centers in Europe with clinical experience of this approach and 40 in the US.

While the landmark trial for this device, EVEREST II, was about 80% degenerative MR and about 20% functional MR, what is now becoming clear, said Mack, is that the MitraClip is suitable only for functional MR patients.

"There are a huge number of patients with this problem, and they are not referred for surgery. So I think that this is a viable technique for it," Mack added. "If we look at the experience in Europe, at the current time, we can see that 66% of patients are functional MR and another 6% are mixed functional and degenerative MR, so this is clearly the application for this device.

"I do have personal experience with this, and I am absolutely convinced it works. I think that there is a role for it in high-risk individuals, second- and third-time patients whom we don't want to operate on because they are in their 80s and have had two or three previous bypass operations," he added.

Speaking in London, Feldman, who was the lead investigator for the Everest II trial, agreed: "When we looked at subgroups, we found that the clip therapy was most equivalent to surgery in three patient groups: older patients, those with abnormal LV dysfunction, and those with functional rather than degenerative MR," he noted,

Feldman said that one-year data are now available with the MitraClip in just over 200 "truly high-risk" patients with MR and heart failure and provide "an inference that the MitraClip might improve survival"; there is also a "highly significant" reduction in the rate of rehospitalization with the clip, which is "a marker for symptom improvement," he said.

However, at the time these data were presented earlier this year, observers noted that it is not yet known whether the MitraClip is better than doing nothing in this group of patients. As such, a trial is now being designed in the US to randomize such patients to MitraClip or optimal standard therapy, including resynchronization therapy, Mack said.

No Long-Term Data on MitraClip

In London, Wells argued that "what is missing" here are "long-term follow-up data. We have got 20 to 30 years of follow-up for mitral repair surgery, and we are a long way from that with the devices we are talking about here. Most of us, when we think about mitral-valve surgery, think about the vast majority of patients in whom this is a one-off treatment for life."

However, Feldman argued there are 12-year follow-up data on the edge-to-edge surgical technique, on which the MitraClip is modeled, "so we are not without proof of concept," and he reminded the surgical audience that, prior to EVEREST I and II, there were no prospective randomized trials at all in the field of mitral-valve surgery. "The MitraClip trials represent a landmark in the study of therapy for mitral regurgitation," he observed.

And he stressed that the kind of patients Wells is talking about are not the same ones who are receiving the MitraClip. "These are not degenerative patients, they are high-risk, functional patients never referred to a surgeon or whom the surgeon wants nothing to do with," Feldman said.

Wells acknowledged that end-of-life, salvage patients "are something different" and added that the development of a staging for valve disease--in the same way that lung cancer is staged--might be helpful to define who the best patients for percutaneous procedures are.

Optimism for Percutaneous Mitral-Valve Replacement

But what Mack says he is most excited about is the concept of percutaneous mitral-valve replacement. "The reason I think it is intriguing is because, believe it or not--as difficult as this concept sounds--it probably is actually more doable than a lot of these repair techniques," he commented.

Percutaneous mitral-valve replacement, as difficult as this concept sounds, is probably more doable than a lot of these repair techniques.

"The challenges are the delivery of a relatively large prosthesis; fixation, because fixation of all these devices is easier in the aortic annulus than it is in the mitral annulus, so reliably fixing it in the mitral annulus is another challenge; and last, the valve itself may interfere with the subvalvular apparatus, and then paravalvular leak may also be an issue."

A number of companies are developing percutaneous mitral valves, including the CardiAQ prosthesis (CardiAQ Valve Technologies, Winchester, MA). But experience with these devices is so far limited to animal work, Mack noted, bemoaning the fact that animal models for this problem "are not closely aligned with the human model."

Wells reports consulting for St Jude Medical. Mack reports that some of his travel expenses have been paid by Edwards but has no other conflicts of interest. Feldman has served as an advisor or consultant for Abbott and Edwards and has received grants for clinical research from Abbott and Edwards. He has also been an investigator for the Carillon device.

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