Myval Noninferior to Other THVs at 1 Year, but Questions Persist

PARIS, France— Myval (Meril), a novel transcatheter heart valve that comes in a broad range of sizes, appears to be as safe and effective as contemporary balloon-expandable and self-expanding valves for the treatment of aortic stenosis, the LANDMARK study suggests.

In the randomized trial, the VARC-3-recommended composite endpoint of clinical efficacy (all-cause mortality, all stroke, and procedure- or valve-related hospitalization), was 13.0% among patients treated with Myval and 13.1% in the contemporary device group, which consisted of valves from Medtronic (Evolut R/Pro/Pro+/Flex) and Edwards Lifesciences (Sapien3/Ultra). This met the criteria for noninferiority (P < 0.0001).

The investigators further added quality of life, as captured by a 2.5-point or greater decrease on the Short Form-12 health survey, to the clinical efficacy endpoint and saw rates of 19.5% for Myval and 22.7% for the contemporary device group (P = 0.33).

“Follow-up of patients is planned for up to 10 years to evaluate the long-term performance and durability of the device, which is very important,” said Patrick Serruys, MD, PhD (University of Galway, Ireland), who presented the 1-year follow-up of LANDMARK here at EuroPCR 2025.

These data add to those Serruys presented here last year, showing that Myval met criteria for noninferiority against the same devices at 30 days. The primary composite safety endpoint using the VARC 3 definition was all-cause mortality, all-stroke, bleeding type 3 and 4, acute kidney injury stage 2-4, moderate or severe prosthetic valve regurgitation, new permanent pacemaker implantation, and major vascular complications (P < 0.0002, using an upper one-sided 95% confidence interval).

While Myval is not on the market in the United States, it was approved in India in 2018 and received CE Mark in 2019.

Speaking with TCTMD, Martin Leon, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), who served as anchor for the Hot Line session, said a main problem with LANDMARK from a US perspective is that it is short on data.

“We've estimated for an all-comer trial comparing two of these devices in the modern era, you need at least a thousand patients and a 1-year endpoint with careful hemodynamics to be able to justify that they are noninferior and that they can be used equivalently in the US,” he said. “We’re still a ways from seeing [Myval data] that would be acceptable to a US regulatory agency.”

One of Myval’s unique aspects is that it comes in more sizes than its competitors. In a press conference prior to his presentation, Serruys told TCTMD that one example where this would potentially be advantageous is when an operator must choose between two valves knowing they may be either under- or overestimating the aortic annulus. Thus, having an additional size to slip in between would be an advantage in the current era, Serruys noted.

While that may one day be the case if Myval can justify itself as an alternative to the available devices, Leon said more isn’t necessarily better in this case.

“If you're running a cath lab and you have to have an inventory of all these devices and they have only a lifespan that is so long, having too many sizes may create confusion, complexity, and expense,” he added. “Ultimately, they still have to prove that having multiple sizes makes a difference.”

LANDMARK at 1 Year

The trial randomized patients at 31 sites in 16 countries to one of seven Myval sizes (n = 384) or one of four Medtronic (Evolut R/Pro/Pro+/FX) or Edwards Lifesciences (Sapien 3/Ultra) sizes (n = 384). In the Myval group, the first 336 patients were treated with the first-generation device while the other 32 patients received the next-generation Myval Octacor (Meril).

The mean age of patients was 80 years, a little over 50% were women, and the median STS risk score was 3%. The mean aortic valve area was 0.7 cm², mean annulus area was 471 mm², and about 6.5% of patients had a bicuspid valve.

Echocardiographic outcomes at 1 year, available in 93% of patients, showed that the median effective orifice area was 2.09 cm² in the Myval group and 2.10 cm² in the contemporary aortic valve group. Similarly, the median aortic valve pressure gradient was 8.20 mm Hg and 7.60 mm Hg, respectively.

Total aortic regurgitation was mostly similar between both arms at 1 year, with rates of none to trace that were 60.4% in the Myval group and 66.4% in the contemporary aortic valve group. The rates of mild aortic regurgitation were 38% and 30.3%, respectively, and those of moderate aortic regurgitation were 1.6% and 3.3%.

Over follow-up, there were 27 deaths in each arm. For stroke, there were numerically more in the Myval group, but the difference was not statistically significant. Similarly, there were no differences between the groups for rehospitalization or clinical efficacy.

Valve Types and Echocardiographic Findings

Discussant Alexandre Abizaid, MD, PhD (Hospital das Clinicas Instituto do Coração, São Paulo, Brazil), said while LANDMARK shows similar clinical efficacy between Myval and the most commonly used valves in the world at both 30 days and 1 year, the rates of mild aortic regurgitation stood out to him.

“[It] surprised me a little bit since with all the intermediate sizes I wasn't expecting to have a little bit more PVL in the Myval group,” he said.

Ultimately, they still have to prove that having multiple sizes makes a difference. Martin Leon

Serruys noted that differences in how small annuli respond to treatment with specific valve platforms is an area of ongoing study that may ultimately explain some of this difference.

“Without telling you things that will be presented in the future, it's clear that the gradient and the effective orifice area, especially in the small orifice areas below 430 [mm²], is superior with Evolut,” he noted. “But what is amazing is that it does not apply for [valves] above 430.”

Serruys said at least 26 Evolut devices were implanted in small annuli in LANDMARK and analyses of patients by annulus size in relation to the echocardiographic follow-up data are ongoing.

These data would seem on track with recent data from the SMART trial of mostly women with small annuli. Both Myval and the Sapien devices are balloon-expandable, while the Evolut series are self-expanding. In SMART, both 1-year and 2-year data indicate less bioprosthetic valve dysfunction over time when using the self-expanding valves, though some say that not enough follow-up has yet accrued to reveal a link between early hemodynamics (which favor the self-expanding valves) and hard outcomes.