Erik Swain , 2025-04-15 13:18:00
April 15, 2025
3 min read
Key takeaways:
- A transcatheter aortic valve replacement system designed to treat aortic regurgitation exceeded its safety and performance goals.
- A randomized controlled trial comparing TAVR with surgery is planned.
CHICAGO — For patients with symptomatic aortic regurgitation at high surgical risk, a transcatheter aortic valve replacement system exceeded safety and performance goals, according to results of the ALIGN-AR trial.
If approved, the valve tested in ALIGN-AR (Trilogy THV, JenaValve) would be the first transcatheter therapy indicated to treat aortic regurgitation, Raj R. Makkar, MD, vice president of cardiovascular innovation and intervention at Cedars-Sinai and associate director of the Smidt Heart Institute, said during a press conference at the American College of Cardiology Scientific Session.
High-risk patients
For the single-arm, nonrandomized ALIGN-AR trial, Makkar and colleagues analyzed 500 patients with moderate to severe or severe aortic regurgitation (grade 3 or worse) and NYHA class II or worse HF who were determined to be at high surgical risk by a heart team (mean age, 76.6 years; 46.2% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality score, 3.9%). Guidelines currently recommend surgery for this population.
“This is a dedicated device designed to anchor in noncalcified aortic valve leaflets,” Makkar said during a press conference.
There were no procedural deaths, but 1.6% of patients had valve embolization and 0.6% had aortic dissection during the procedure, Makkar said, noting the technical success rate was 95.2% and the device success rate was 96.4%. He said the valve embolization rate was much lower than the rates observed — 10% to 15% — when TAVR valves designed to treat aortic stenosis are used off-label to treat aortic regurgitation.
producibly,” he said. “The procedural outcomes were excellent.”
The 30-day primary safety endpoint occurred in 26.2% of patients, with an upper one-sided 97.5% confidence interval of 30.1%, exceeding the prespecified noninferiority margin of 40.5% (P < .0001), Makkar said at the press conference.
Most of the safety events occurred because of new pacemaker implantation, which was needed in 23.3% of patients, he said. In other components of the safety endpoint, 1.4% of patients died (1.2% died from a CV cause), 2% had a stroke, 3.2% had major bleeding, 2.8% had a major vascular complication, 0.6% had acute kidney injury, 4.4% had a device-related surgery or intervention and 0.6% had regurgitation that was moderate or worse, according to the researchers.
“Pacemaker rates are an issue, and we are diligently working to understand more mechanisms that may be involved, and how to mitigate this,” Makkar said at the press conference.
The primary efficacy endpoint of all-cause mortality at 1 year occurred in 8.1% of patients, with an upper one-sided 97.5% confidence interval of 10.7%, exceeding the prespecified noninferiority margin of 25% (P < .0001), Makkar said at the press conference.
Favorable metrics
Effective orifice area was 2.7 cm2 at baseline at 2.8 cm2 at 1 year and 2 years, whereas mean gradient fell from 7.5 mm Hg at baseline to 4.2 mm Hg at 1 year and 2 years, he said.
The rate of no or trace paravalvular regurgitation rose from 82.6% at 30 days to 93.4% at 1 year and 95.7% at 2 years, according to the researchers.
No patients were NYHA class I at baseline, but 53% were at 30 days, 62% were at 1 year and 59% were at 2 years, Makkar said.
The Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) improved between baseline and 1 year and was sustained at 2 years (P < .0001 for both), and the rate of people alive and well, defined as a KCCQ-OSS of at least 60 with no decrease of more than 10, was 84% at 1 year and 79.8% at 2 years, he said.
“This is the largest series of high-risk patients with symptomatic aortic regurgitation that have been treated with the JenaValve,” Makkar said at the press conference. “The 30-day all-cause mortality was one-third of what was expected based on the STS score. The valve performance was favorable and we also saw improvement in functional status as well as … favorable [left ventricular] remodeling. This may be a valuable device in patients who are at high risk for surgery but symptomatic.”
A randomized controlled trial comparing TAVR to surgery in lower-risk patients with symptomatic aortic regurgitation is planned, he said.
Sources/Disclosures
Collapse
Makkar RR, et al. Joint American College of Cardiology/New England Journal of Medicine late-breaking clinical trials. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).
Disclosures:
The study was sponsored by JenaValve. Makkar reports receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, JenaValve and Medtronic.