Aortic Regurgitation Device Passes in Pivotal Trial

— JenaValve device hits benchmarks with improvement in pacemaker rates

Last Updated October 26, 2023

SAN FRANCISCO -- Aortic valve regurgitation treated with the investigational JenaValve Trilogy appeared safe and effective in the ALIGN AR trial.

The device met the safety benchmark, with a 26.7% rate of combined 30-day all-cause mortality, all stroke, life-threatening or major bleeding, major vascular complications, acute kidney injury or dialysis, valve intervention, new permanent pacemaker, and moderate or worse paravalvular leak (P<0.0001 for noninferiority to the prespecified margin of 40.5%).

JenaValve also met the primary efficacy endpoint for 1-year all-cause mortality, with a rate of 7.8% that was significantly noninferior compared with the prespecified margin of 25%, reported Vinod Thourani, MD, of Piedmont Heart Institute in Atlanta, at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation.

New pacemaker implantation rates were high in the trial, at 24.0%, but steadily declined to a "respectable" 14% by the last tertile of treated patients. Thourani chalked this up to a change in insertion technique placing locators above the nadir of native valve cusps, reduction in oversizing, and evolution in management of periprocedural conduction abnormalities.

TCT press conference panelist Kendra Grubb, MD, surgical director of the Emory Structural Heart and Valve Center in Atlanta, called the 14% rate on par with or better than what's been seen with use of self-expanding valves.

"I think this is very encouraging," she said. "You're talking about a high-risk patient population that didn't have surgical options, and what you're seeing here are very excellent results."

Moderate to severe paravalvular regurgitation occurred in only 0.6% of patients at 30 days and 6 months and was not seen at 1 year. Mild regurgitation declined from 18.0% at 30 days to 5.2% at 6 months and 7.8% at 1 year, which Thourani emphasized as "very low" rates that are "really some of the best in class for paravalvular regurgitation ever shown" from a transcatheter heart valve (THV) prosthesis.

Press conference panelist Bernard Prendergast, MD, of Cleveland Clinic London, noted that these patients are different and have different anatomy than aortic stenosis patients, so using a transcatheter aortic valve replacement (TAVR) device approved for aortic stenosis off label for aortic regurgitation "can be successful, but it is fraught with risk of embolism and other adverse consequences."

He noted the long journey for this valve after a pivot from transapical-only access and from going from an aortic stenosis TAVR population to aortic regurgitation. "Although it's a less common disease, it's one with major needs," Prendergast said. "I'm very excited by these results."

Device developer JenaValve Technologies said in a that the results are intended to support an application to the FDA for an indication. "If approved, the Trilogy THV System would become the first and only TAVR system in the U.S. indicated for the treatment of symptomatic, severe AR [aortic regurgitation]."

Another TCT press conference panelist Pinak Shah, MD, director of the Cardiac Catheterization Lab at Brigham and Women's Hospital in Boston, predicted no hesitation in interventionalists switching from current TAVR devices, should it be approved.

"There will be no inertia, because we don't have an alternative. And I'm not so worried about the pacemaker rate. I don't think we were worried about pacemaker rates in the first PARTNER trial [with TAVR in prohibitive surgical risk patients] because we had no alternative," he said. "I am very excited to put this to use because we have an unmet need."

The trial included 180 patients with high surgical risk and symptomatic, severe aortic regurgitation at 20 sites. Exclusion criteria included valve calcification and unsuitable anatomy, notably bicuspid valves or more than moderate mitral regurgitation. Slightly more than half of the patients screened were excluded.

As another factor that would rule out the procedure, "a lot of these patients have abnormal aortas that need to be replaced," noted TCT press conference co-moderator David Cohen, MD, MSc, of Saint Francis Hospital in Roslyn, New York.

Even so, Thourani argued that it's a "huge patient population, quite honestly. People talk about tricuspid regurgitation being forgotten; I actually have rethought about that over the last 5 years. AR is a forgotten disease," he said. "It is staggering that the number of these patients are starting to come out of the woodwork because people know that it's there. ... Once we open this up, I think we'll see this proliferation of a disease management that we normally have ignored."

Commenting on the study, Clyde Yancy, MD, of Northwestern University in Chicago, cautioned that the noninferiority thresholds were "quite generous."

Another concern is long-term durability of the valves, he told app.

Nevertheless, he concluded, "There are so many patients that have aortic insufficiency in whom surgery is high risk because they're older, and we haven't had this transcatheter approach to address AR. ... But this really could be a significant step forward. The alternative is evidence-based medical therapy for reduced ejection fraction heart failure with no real evidence other than empiricism that it ought to work in a dilated ventricle based on regurgitation."

"This is the first step, I hope, of more refinement in the technology and more precision in candidate selection," he said, "but this is a missing area in clinical cardiovascular medicine. We don't have this."

Correction: An earlier version of this story stated that the study investigated treatment of tricuspid valve regurgitation; this has been corrected.


Thourani disclosed relationships with Abbott, Edwards Lifesciences, Boston Scientific, and DASI Simulations.

Grubb disclosed relationships with Boston Scientific, Edwards Lifesciences, Medtronic, and Ancora Heart.

Shah disclosed relationships with Edwards Lifesciences.

Primary Source

Transcatheter Cardiovascular Therapeutics

Thourani VH "ALIGN-AR trial: Initial outcomes of the JenaValve Trilogy transcatheter aortic valve replacement in high risk patients with symptomatic severe native aortic regurgitation" TCT 2023.