Key Points:
- Transcatheter aortic valve replacement for aortic valve disease has largely focused on those with aortic stenosis. In pure, native-valve aortic regurgitation, there remains a paucity of options beyond surgical correction or medical management.
- The ALIGN-AR trial evaluated the JenaValve Trilogy, a dedicated transcatheter heart valve for treating moderate to severe, symptomatic aortic regurgitation (AR), in 500 high surgical risk patients.
- At one year, the all-cause mortality rate was 8.1%, significantly outperforming the prespecified non-inferiority goal of 25%. Device success was 96.4%, with excellent hemodynamic performance and low rates of regurgitation.
- This findings support the JenaValve Trilogy as a safe and effective treatment for symptomatic, moderate to severe AR and provide strong evidence for expanding transcatheter therapies beyond aortic stenosis.
Transcatheter aortic valve replacement (TAVR) has become an increasingly popular treatment strategy for aortic valve disease, but its application in patients with pure native aortic regurgitation (AR) has remained limited due to anatomical challenges. The ongoing, multicenter, non-blinded, single arm, ALIGN-AR trial evaluates a novel transcatheter heart valve (JenaValve Trilogy) specifically engineered for AR, offering new possibilities for patients previously relegated to high-risk surgical options or medical therapy alone.
The trial enrolled 500 adults patients across 28 U.S. sites between 2018 and 2024= with moderate to severe AR with NYHA Class II or greater symptoms and were deemed high-risk for surgery by a multi-disciplinary heart team. Median patient age was 76.6 years; 46% were female. STS score was 3.9, NYHA class III/IV symptoms were present in 62% of participants, and 12% had existed RBBB or bifascicular block.
Device success was achieved in 96.4% of cases with 98% deployment success. At 30 days, the all-cause mortality rate was 1.4%, stroke 2.0% (0.8% disabling), and valve embolization occurred in 1.6%. New pacemaker implantation was high at 23.3%. Only 0.6% of patients had more than mild residual valve regurgitation. The primary safety endpoint (26.2%) met the trial’s non-inferiority margin of 40.5% (p<0.0001).
At one year, all-cause mortality was 8.1% — well below the prespecified non-inferiority benchmark of 25%. Beyond survival, the trial also demonstrated reverse ventricular remodeling. Left ventricular volumes and mass significantly declined, while mean valve gradients remained under 5 mmHg through two years. NYHA functional class improved as well: the proportion of patients in class III/IV dropped from 61.6% at baseline to just 10% at one year. Quality-of-life measures (KCCQ scores) rose from 58.5 to 79.1.
Considerations of this trial include its non-randomized nature and the high rates of new pacemaker implantation. Risk factors predicting need for new pacemaker implantation include existed right bundle branch block, implanted valve size, annular size, and severe (as opposed to moderate to severe) AR.
Speaking at the late breaking clinical trial session at the American College of Cardiology Conference on March 30, 2025, lead investigator Dr. Raj Makkar stated that “not only did we meet our prespecified safety and efficacy endpoint, we also saw excellent valve hemodynamics and valve function, and there was a very low rate of leakage across and around the valve.” He hopes that “These findings represent significant progress in overcoming the historical limitations associated with using off-label TAVR devices for aortic regurgitation.” A randomized trial (ARTIST) comparing the Trilogy system to surgery is now underway to evaluate outcomes in operable patients.