麻豆传媒

LOS ANGELES -- A number of novel transcatheter aortic valve implantation (TAVI) prostheses are proving their mettle in safety trials, groups reported here.

The next generation Medtronic Engager valve, for example, appeared to hold up fairly well at 6 months in the high-surgical-risk population in the pivotal trial for European regulatory approval, David Holzhey, MD, of Germany's University of Leipzig Heart Center, and colleagues found.

He pointed to the low incidence of paravalvular leak and positioning-related complications in a late-breaking presentation at the Society of Thoracic Surgeons meeting.

The Tech-Con portion of the meeting also outlined results with a number of other novel TAVI devices ranging in development from first-in-man to U.S. trials getting under way.

"It will not remain the same as it is where only two companies own the market," he said, referring to Edwards Lifesciences' Sapien and Medtronic's CoreValve as dominant on the European market.

The FDA has approved only the Sapien valve tested in the PARTNER trial cohorts.

The valve field appears to be heading down the same road as stents, Thor Sundt, MD, of Massachusetts General Hospital in Boston, agreed in an interview with 麻豆传媒.

"I'm sure that 5 years from now there will be half a dozen different transcatheter valves that one can chose from. It'll be a race to see which devices will be best. Many of them will fall off the track and never be heard from again," he said.

Each of the new valves has new design features to tackle positioning and leaks around the outside, which both impact patient outcomes.

The Engager valve, for example, has a self-expanding nitinol frame and polyester skirt with "control arms" that hug the native leaflets to the prosthesis in order to minimize paravalvular leaks.

The interim analysis of its pivotal European trial included the first 60 Engager recipients, with a previously reported initial device success rate of 94.3% by modified Valve Academic Research Consortium criteria.

Heart failure symptom improvements remained largely stable at the 6-month follow-up.

All-cause mortality went from 9.9% at 30 days to 16.9% at 6 months, and the stroke rate rose from 1.8% to 5.5% over that period.

But the MI rate remained unchanged at 1.8%, as did insertion of new pacemakers for third-degree atrioventricular block at 16.9%.

Paravalvular leak went from 24% at 30 days to 8% at 6 months having a trace of leakage, although mild (grade less than 2) leaks rose from none to 5%. No patient had moderate or severe paravalvular leak at either point.

The researchers concluded that this was a positive risk-to-benefit ratio for these high-surgical-risk, symptomatic patients.

After full enrollment, the trial will report follow-up annually for up to 5 years, which is the life expectancy of that population, Holzhey noted.

"No valve so far is perfect," he told 麻豆传媒. "We will see what the long term durability is."

Conventional Hourglass Designs

A number of TAVI prostheses on the horizon have kept more closely to the design of the first one out of the gate.

The latest revision to the balloon-expandable Sapien device will generally keep the same cobalt-chromium frame but will be taller and add a polyethylene terephthalate skirt to try to reduce paravalvular leaks, Anson Cheung, MD, of the University of British Columbia in Vancouver, explained.

In a 15-patient feasibility trial, the Edwards Sapien 3 was associated with no deaths at 30 days or any more than mild paravalvular leak and a 6.7% rate of pacemaker implantation. A 150-patient clinical trial designed to support European regulatory approval is under way.

Edwards is also developing the CENTERA valve, a self-expanding resheathable valve. The 15-patient feasibility trial had 80% survival at 1 year, one patient with more than mild paravalvular leak, and a 27% rate of new pacemaker insertion.

Along with the Engager valve, Medtronic is working on the CoreValve Evolut valve, Michael J. Reardon, MD, of the Methodist DeBakey Heart and Vascular Center in Houston, noted at the Tech-Con session.

Evolut is shorter than prior CoreValve versions but maintains the skirt length "with enhanced sealing," he explained.

St. Jude Medical's novel Portico valve features a large cell size in the annulus section to minimize risk of a strut resting on a calcified nodule, Gregory P. Fontana, MD, of Lenox Hill Heart and Vascular Institute in New York City, noted.

Its first-in-man transapical case, done last November on a small woman who had vascular injury after a failed attempt at transfemoral implantation of a Sapien XT valve, resulted in an "acceptable" mean gradient of 10 mm Hg across the new valve.

A U.S. trial should start later this year, Fontana noted.

Unconventional Designs

All those aortic valves feature a fairly similar upper and lower "crown" design, but several more unique alternatives are in the works as well.

Volkmar Falk, MD, of University Hospital Zurich, discussed two of these, the JenaValve and Symetis' Acurate Valve.

The self-expanding Symetis valve has flexible, self-aligning stabilization arches instead of an upper crown of metal cells to hold the valve in place.

In the 90 transapical cases that led to regulatory approval in Europe, the results were:

• 11.1% rate of new pacemakers
• 92.2% survival at 30 days, falling to 80% at 12 months
• 3.3% rate of stroke at 30 days, with another 1.1% at 6 months and at 12 months
• 2.2% rate of myocardial infarction at 30 days, with no further events
• 2.9% paravalvular leak of grade 2 or higher

The self-expanding JenaValve also has no uncovered metal upper crown; instead it has "feelers" for positioning and clips to attach to the native leaflets.

In the 73-patient trial that led to approval in Europe, results were:

• 92.5% survival at 30 days and 68.2% at 12 months
• 3.0% stroke at 30 days, 4.5% at 6 months, and 7.6% at 12 months
• No MIs
• 10.6% rate of new pacemakers at 30 days
• 13.6% rate of grade 2 or more paravalvular leak post procedure, falling to 8.8% at 12 months

The Direct Flow valve has a surgical valve design without any metal, which is hoped to extend its durability, Steven F. Bolling, MD, of the University of Michigan in Ann Arbor, explained at the session.

Instead of a metal cage, an upper and lower ring are filled with a hardening polymer compound after placement.

The 31-patient European feasibility study indicated 76% survival at 12 months, with fairly high gradients of 18 to 19 mm Hg after the procedure and through follow-up.

Clinical Implications

It's difficult to compare results across platforms at this point, Falk cautioned, especially with regard to mortality rates, given the small numbers.

The panel members agreed that sizing is less the target for development now, with paravalvular leak and need for pacemakers taking more of the focus.

Analysts project that the new features of these devices will expand the eligible TAVI population, Thomas Walther, MD, PhD, of the Kerckhoff Klinik Heart Center in Bad Nauheim, Germany, noted at the session.

But after having used a number of them, he was skeptical that the novel designs and features would have much impact.

"I think as a physician, you have to be a bit critical and keep the patient in focus," he told attendees.

Nevertheless, the European data is a sign of things to come for U.S. physicians, Sundt noted.

"From a practical standpoint, we look to Europe to see what's going to be in our future," he said.

From the American Heart Association:

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