Can Mitral Valve Innovators Dig Themselves Out of a Rut?

NEW YORK CITY — Mitral valve technology developers were urged to go back to the drawing board due to current-generation devices not meeting the needs of enough patients with mitral regurgitation (MR), some said.

With lots of devices in development — including transseptal devices Sapien M3, HighLife Valve, Cephea, Intrepid, and AltaValve — transcatheter mitral valve replacement (TMVR) is in theory poised to help those ill suited for transcatheter edge-to-edge repair (TEER) and surgery.

However, progress in TMVR continues to be hindered by slow trial enrollment. Every new TMVR device that comes out is met with some enthusiasm that is then dampened by higher-than-expected trial screen failures, lamented Gorav Ailawadi, MD, MBA, of the University of Michigan in Ann Arbor, at New York Valves, formerly known as the TVT conference, hosted by the Cardiovascular Research Foundation (CRF).

Screen failure rates haven’t changed much in the last 10 years, he said, noting that his center recently had 27 patients submitted for various TMVR trials, and none ended up being accepted.

The high TMVR screen failures are usually due to patients having poor left ventricular (LV) function, the prostheses being oversized relative to the ventricle, LV outflow tract (LVOT) limitations, anticoagulation challenges, and untreated concomitant disease such as coronary disease, Ailawadi explained.

Then there is the special population with mitral annular calcium (MAC), a poorly understood condition, which has an unmet clinical need and is often excluded from studies due to LVOT issues.

“When [the devices] work, they work really well,” said session co-moderator Michael Reardon, MD, a cardiac surgeon at Houston Methodist Hospital. “The issue is not do they work, the issue is can we give them to enough people … How do you expand out the population?”

D. Scott Lim, MD, of the University of Virginia in Charlottesville, noted that “we need to start thinking out of the box in terms of tools. We need patients. This is a long road. We’ve been doing this for a decade. Patient selection only grows as our awareness of who we can treat and technology evolve together.”

Industry leaders voiced their frustration during the session.

“Ten years ago, there was a lot of excitement for TMVR. We thought it would be like TAVR [transcatheter aortic valve replacement]. Despite a lot of great concepts, a lot of investment, the field hasn’t really moved as quickly as everyone expected,” said Lars Søndergaard, MD, of TMVR device maker Abbott.

Fellow industry representative Bill Shields, MBA, of Medtronic, pointed out that “we all dramatically underestimated the technical challenges of TMVR.”

This is a “much harder challenge than TAVR,” he added.

Recognizing the challenges, the FDA already softened its demands from industry by allowing the nonsurgical, non-clippable MAC patients to enter single-arm studies and performance goal-based registries after years of sluggish enrollment into randomized trials, said panelist Changfu Wu, PhD, an FDA scientific reviewer.

“Those will be the indications first out of the gate if everything goes all right in the next year or two. We will be able to see commercial approvals for those special patient populations,” he predicted.

Mayra Guerrero, MD, of the Mayo Clinic in Rochester, Minnesota, acknowledged the progress made in TMVR despite sharing her colleagues’ complaints.

“When I look back at the last 10 years, we have learned a lot about what works … My life in the clinic has changed,” she said, adding that one lesson learned is that the transfemoral transseptal approach — not the transapical approach requiring a minithoracotomy — is the path forward for TMVR. “These patients are old, with multiple comorbidities, so it has to be the least invasive option for the patient.”

Engineers are just realizing that the first-generation TMVR devices do not really fit or match what the clinical need is, said CRF President and CEO Juan Granada, MD, of Columbia University Medical Center in New York City, hence the “intense redesign phase” now.

It’s a stark contrast to the relatively smooth development of TEER for MR. The MitraClip is already approved for patients with degenerative MR at prohibitive surgical risk and select patients with functional MR who remain symptomatic despite medical therapy. A relative newcomer device, Pascal, is also indicated for TEER for degenerative MR.

For patients who can get TEER, just about half get a good result in terms of having residual mild MR or better, Ailawadi noted.

To that end, he said there is some enthusiasm for novel hemi-valves that, by mimicking a replacement approach, theoretically reduce MR better than repair and without as much impact on LV function.

In any case, “there’s definitely a need for TMVR,” he said.

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