ALIGN-AR Trial: Dedicated TAVI Device for Aortic Regurgitation Shows Strong Early Results

 In a Late-Breaking Clinical Trial at ACC 2025, investigators presented updated data from the ALIGN-AR trial, revealing that the Trilogy valve system (by JenaValve)—a TAVI device designed specifically for aortic regurgitation (AR)—has demonstrated promising safety, efficacy, and hemodynamic performance in high-risk surgical patients.

The new results, drawn from the first 500 patients, showed lower-than-expected mortality, excellent procedural success, and marked functional improvement—strengthening the case for a dedicated transcatheter option in patients with native AR, who have traditionally had few choices.

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Study Overview

• Trial: ALIGN-AR

• Device: Trilogy Valve System (self-expanding, designed for AR)

• Participants: 500 high-surgical-risk patients

• Mean age: 76.6 years

• Female: 46.2%

• Mean STS Score: 3.9

• Baseline NYHA Class III or IV: 61.6%

• Geography: Multicenter international trial

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Inclusion Criteria

• Severe native aortic regurgitation

• High surgical risk or contraindicated for surgery

• NYHA Class II–IV symptoms

• Anatomy suitable for TAVI using Trilogy valve

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Exclusion Criteria

• Active endocarditis

• Severe annular calcification

• Bicuspid aortic valve

• Life expectancy <12 months from non-cardiac causes

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Key Outcomes

Efficacy Endpoint (All-cause mortality at 1 year):

• Observed: 8.1%

• Noninferiority threshold: 25%

• P < 0.001

Primary Safety Endpoint (30-day composite):

• Includes death, stroke, bleeding, vascular complications, AKI, valve dysfunction, new pacemaker

• Observed rate: 26.2%

• Noninferiority margin: 40.5%

• P < 0.001

Disabling Stroke Rates:

• 1 year: 3.1%

• 2 years: 3.6%

Mortality:

• 1 year: 8.1%

• 2 years: 15.5%

• Rise primarily due to noncardiac causes

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Device Performance

• Mean effective orifice area (EOA): 2.8 cm²

• Mean gradient: 4.2 mm Hg

• Trace or no paravalvular leak:

  • 1 year: 93.4%

  • 2 years: 95.7%

• Procedural success: 95.2%

• Average procedure time: 69 minutes

• Pacemaker implantation:

  • 23–24% (higher than surgical AR treatment)

• Complications:

  • Valve embolization: 1.6%

  • Aortic dissection: 0.6%

  • No intraprocedural deaths or annular rupture

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Functional and Quality of Life Gains

• Significant LV remodeling with reduction in LV volume and mass

• KCCQ scores (quality of life) improved substantially

• NYHA Class III/IV patients:

  • 1 year: 8%

  • 2 years: 10%

More details on KCCQ can be found through the ACC’s documentation.

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What’s Next? The ARTIST Trial

With these strong results, the upcoming ARTIST trial will compare the Trilogy system directly to surgery in 1,110 lower-risk patients, with 10 years of follow-up. This marks a pivotal step in the evolution of TAVI beyond stenosis into the AR space.

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Take-Home Points

• The Trilogy valve, a dedicated TAVI device for AR, shows strong safety and performance in high-risk patients.

• Mortality, stroke, and valve complications are much lower than what’s historically seen with off-label devices used for AR.

• LV function, valve hemodynamics, and quality of life all improved post-TAVI.

• The need for pacemakers remains a challenge (23–24%), potentially linked to anatomical features unique to AR.

• The field is moving toward randomized trials in lower-risk populations—a possible paradigm shift in how AR is treated.