Embattled TAVR Device Myval Meets Expectations in Trial, but Trouble Still Ahead

For a balloon-expandable transcatheter aortic valve replacement (TAVR or TAVI) platform, the much-litigated Myval performed well enough in the COMPARE-TAVI 1 randomized trial, but its rates of pacemakers and paravalvular leaks raised red flags.

Pitted against more established balloon-expandable Sapien 3 valves in TAVR for severe aortic stenosis, the Myval devices (Myval or Myval Octacor) were able to meet noninferiority with respect to the composite primary endpoint (13% for Sapien vs 14% for Myval, P=0.019 for noninferiority).

The individual outcomes in the composite endpoint consisted of:

• Death: 6% vs 5% (P=0.52)
• Stroke: 5% vs 5% (P=0.76)
• Moderate or severe aortic regurgitation: 1% vs 4% (P=0.0051)
• Moderate or severe hemodynamic transcatheter heart valve (THV) deterioration: 2% vs 1% (P=0.19)

"The finding of more moderate or severe aortic regurgitation with Myval THVs than Sapien 3 THVs, despite the opportunity for more precise sizing and a higher average degree of oversizing with Myval THVs, might indicate that the skirt used for the Sapien 3 THVs provides better sealing against paravalvular leakage," acknowledged the study investigators led by Christian Juhl Terkelsen, MD, PhD, DMSc, of Aarhus University Hospital in Denmark in The Lancetopens in a new tab or window.

What's more, the exploratory endpoint of new pacemaker implants at 30 days also put Myval at a disadvantage against Sapien (19% vs 10%), with first-time pacemaker implantations in particular reaching as high as 21% vs 12% (P=0.0002).

This had not been observed in last year's LANDMARK trialopens in a new tab or window report, which showed that Myval (mostly Myval proper, not the Myval Octacor) met noninferiority criteria against Sapien and Evolut valves for safety and effectiveness in severe symptomatic native aortic stenosis.

Terkelsen and colleagues noted that both Myval and Myval Octacor differ in design and implantation technique when compared with the Sapiens. "The differences in pacemaker rates might be associated with variations in the design of skirts used, delivery systems leading to deeper implants, implantation balloons, or increased oversizing with Myval THVs than Sapien 3 THVs."

"More first-time pacemakers were implanted in patients who received Octacor Myval THVs than in patients who received Myval THVs, which explains some of the increased pacemaker rates in COMPARE-TAVI 1 compared with the LANDMARK trial that mainly used first-generation Myval THVs," they suggested.

Mariama Akodad, MD, PhD, of Institut Cardiovasculaire Paris Sud, Ramsay Santé in Massy, France, nevertheless commended the COMPARE-TAVI 1 group for enrolling an "unprecedented" all-comers population with representation of complex anatomies.

"Yet, long-term advantages of the more recent Myval THVs over the well-established Sapien 3 platform requires more data, especially in a younger population for whom lifetime management of aortic stenosis is crucial," she cautioned in an accompanying editorialopens in a new tab or window.

Indeed, the study cohort tended towards older age (median 81.6 years), making the trial less generalizable to the younger, low-risk patients with aortic stenosis for whom it is still a toss-up in the choice of TAVR versus surgeryopens in a new tab or window.

"Future post-TAVI studies with CT analysis might provide insightful data on expansion of THV frames, implantation depth, and commissural alignment that was intended with the Octacor THV and might affect repeatability, future coronary access, and THV expansion. Further analyses are required to elucidate whether Myval THV might provide favorable hemodynamics in small annuli regarding its unique design and sizing features," Akodad added.

While CE markedopens in a new tab or window in Europe, the Myval line remains investigational and not for commercial use in the U.S. Among its selling points are the availability of intermediate sizes to better match patient anatomy, a higher skirt, wider stent frame, and shorter frame height.

Notably, the maker of the Sapien 3, Edwards Lifesciences, had sued India-based Meril Inc. in 2019, claiming patent infringement in the Myval line of THVs. Meril subsequently defended itself successfullyopens in a new tab or window in U.S. courts, and the European Patent Office revoked Edwards' patentopens in a new tab or window for a prosthetic heart valve.

However, Europe's Unified Patent Court (UPC) did find the Myval Octacor to infringe on another Edwards patent -- ruling to take it off shelves in UPC territoryopens in a new tab or window this past November.

The Denmark-based COMPARE-TAVI 1 trial therefore had to pause enrollment twice because of patent-related legal proceedings, according to Terkelsen's group.

The noninferiority trial ended up with 1,031 adult participants who got transfemoral TAVR and were enrolled from 2020 to 2023. Patients were randomized 1:1 to groups receiving the Sapien 3 THV or a Myval/Myval Octacor.

Median age was 81.6 years, and 40% of patients were women. About 40% were categorized as having New York Heart Association class III/IV symptoms. Median Society of Thoracic Surgeons Predicted Risk of Mortality was 2.3%.

Study authors stressed that this was an all-comers cohort, with about 10% undergoing TAVR on bicuspid valves, and 4% a valve-in-valve procedure.

One thing Myval had going for it were better favorable hemodynamic outcomes compared with Sapien 3: at 30 days, the Myval was associated with a significantly greater median effective orifice area (1.9 vs 1.7 cm², P<0.0001) and a lower frequency of moderate or severe patient-prosthesis mismatch (19% vs 30%, P<0.0001), for example.

However, the authors acknowledged that the trial had not included the newest-generation Sapien 3 THVs with Resilia technology, which are known for better hemodynamics than its predecessors.

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