TAVR With JenaValve for Symptomatic Aortic Regurgitation in High Surgical Risk Patients - ALIGN-AR

Mar 30, 2025
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Author/Summarized by Author:
Yasser Jamil, MD
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; Hooman Bakhshi, MD, FACC
Trial Sponsor:
JenaValve Technology
Date Presented:
03/30/2025
Date Updated:
03/30/2025
Original Posted Date:
03/30/2025
References

Contribution To Literature:

The ALIGN-AR trial contributes to the literature by demonstrating high technical success, a reassuring safety profile, and favorable clinical outcomes in high-risk patients with aortic regurgitation and NYHA class II or greater symptoms.

Description:

Currently, no device is approved for the transcatheter treatment of native aortic regurgitation, and off-label TAVR use remains suboptimal. To address this unmet need, this single-arm, prospective, multicenter study was designed to evaluate the efficacy and safety of the JenaValve Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) in patients with symptomatic, greater-than-moderate native aortic regurgitation who were deemed high risk for surgery by heart teams.

Study Design

Patients enrolled at 28 U.S. sites between 2018 and 2024 with moderate-to-severe or severe symptomatic aortic regurgitation underwent TAVR with the JenaValve Trilogy transcatheter heart valve.

  • Total number of enrollees: 500 patients
  • Duration of follow-up: 2 years
  • Mean patient age: 76.6 years
  • Percentage female: 46.2%

Inclusion criteria:

  • Age ≥18 years
  • Moderate-to-severe or severe (grade ≥3) native aortic regurgitation using the multiparametric approach defined by the American Society of Echocardiography
  • NYHA class II or greater symptoms
  • High-risk for surgery defined by the heart team

Exclusion criteria:

  • Congenital unicuspid or bicuspid aortic valve
  • Ascending aorta diameter >5.0 cm
  • Previous prosthetic aortic valve
  • Mitral regurgitation > moderate
  • Coronary artery disease requiring revascularization

Principal Findings:

Primary outcome:

  • Among 500 enrolled patients in the ALIGN-AR trial, the composite safety endpoint occurred in 131 patients (26.2%, upper 1-sided 97.5% CI, 30.1%) at 30 days, demonstrating noninferiority to the prespecified safety performance margin of 40.5% (p for noninferiority < 0.0001). In addition, the primary efficacy endpoint was met, with an all-cause mortality rate of 8.1% (upper 1-sided 97.5% CI, 10.7%) at 1 year and a prespecified noninferiority margin of 25% (p for noninferiority < 0.0001).

Secondary outcomes:

  • Key echocardiographic parameters indicative of valve hemodynamics showed favorable changes at the 2-year follow-up. The effective orifice area increased slightly from 2.7 cm² at baseline to 2.8 cm² at 2 years, while the mean gradient improved from 7.5 mm Hg to 4.2 mm Hg. 
  • At 2 years, paravalvular regurgitation was absent or trace in 95.7% of patients, and the incidence of mild or mild-to-moderate regurgitation decreased from 17.4% to 4.3% compared to 30 days. 
  • Paired analyses revealed significant left ventricular (LV) remodeling over the 2-year period. The mean LV mass index declined from 152.3 g/m² to 114.3 g/m² (p<0.0001). The LV end-systolic volume index decreased from 38.4 mm/m² to 30.5 mm/m², and the LV end-diastolic volume index decreased from 82.2 mm/m² to 65.0 mm/m² (p<0.0001). 
  • At baseline, among the 500 patients, NYHA functional class distribution was as follows: 38% were in class II, 58% in class III, and 4% in class IV. At 2 years, among 125 patients, NYHA class improved markedly, with 59% in class I, 31% in class II, and 10% in class III.
  • The mean Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-OS) score increased by 19.4 points (SD 25.5) from a baseline mean of 58.5 to 79.1 at 2 years (p<0.0001). Among those who were alive and well at 2 years, 79.8% achieved a KCCQ-OS score ≥60 without a decline of 10 points.
  • Pacemaker implantation rates varied by valve size: 16.8% for 23 mm valves, 18.3% for 25 mm valves, and 28.9% for 27 mm valves. Predictors of new pacemaker implantation included the presence of baseline right bundle branch block (odds ratio [OR], 6.66; 95% CI, 3.48–12.75; p<0.0001), an annular perimeter ≥85 mm (OR, 2.08; 95% CI, 1.24–3.46; p=0.005), as well as a history of congestive heart failure and severe aortic regurgitation compared with moderate-to-severe regurgitation.

Interpretation:

In this multicenter, nonblinded, single-arm evaluation of high-risk patients with symptomatic (≥3+) aortic regurgitation undergoing TAVR with the JenaValve Trilogy System, both the primary safety and efficacy endpoints met the prespecified performance goals. The study demonstrated high device success alongside acceptable complication rates, including a 0% procedural death rate, 1.4% 30-day mortality, 1.6% valve embolization, and 0.8% 30-day disabling stroke. Moreover, favorable valve performance was evident by consistently low transvalvular gradients, large effective valve areas, and minimal regurgitation. These results were associated with sustained improvements in functional status and patient-reported quality of life, as well as significant LV remodeling at 2 years.

References:

Presented by Dr. Raj R. Makkar at the American College of Cardiology Annual Scientific Session (ACC.25), Chicago, IL, March 30, 2025.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound

Keywords: ACC25, ACC Annual Scientific Session, Aortic Valve Insufficiency, Echocardiography, Heart Valve Diseases, Transcatheter Aortic Valve Replacement


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