The ALIGN-AR (TAVR With JenaValve for Symptomatic Aortic Regurgitation in High Surgical Risk Patients) trial findings demonstrated that, among patients with symptomatic moderate-to-severe or severe native aortic regurgitation (AR) at high surgical risk, transcatheter aortic valve implantation (TAVI) using the Trilogy valve (JenaValve Technology, Inc.) met prespecified safety and efficacy endpoints. The procedure achieved high technical success, significant AR reduction, favorable hemodynamic profiles, and sustained clinical improvements over a 2-year period.¹

This prospective, multicenter, single-arm investigational device exemption study encompassed 700 patients at 30 US centers between June 2018 and July 2025. The co-primary endpoints were a 30-day composite safety outcome consisting of all-cause death, stroke, life-threatening or major bleeding, acute kidney injury, major vascular complications, need for further device-related intervention, new permanent pacemaker implantation, or moderate or severe residual AR (24% vs. 40.5% prespecified performance goal; noninferiority met) and the primary efficacy endpoint of 1-year all-cause death (7.7% vs. 25% prespecified performance goal; superiority met). Technical success was achieved in 95% of cases. At 30 days, mortality was 1.6%, stroke 1.7%, and pacemaker implantation 21.6%, declining from 29% to 14% over time (p = 0.043). At 1 year, stroke incidence was 4.8% and heart failure hospitalization occurred in 5.1% of patients. By up to 2 years, mortality reached 13.3% (median follow-up 472 days), with stable hemodynamics (mean gradient 4.27 mm Hg, effective orifice area 2.75 cm²), minimal residual AR (moderate or severe in ~2%), and sustained clinical improvement, as evidenced by New York Heart Association (NYHA) functional class improvement in >80% of patients and a mean Kansas City Cardiomyopathy Questionnaire score increase of 21.6 points (exceeding the prespecified superiority threshold) at 1 year.

Symptomatic native AR remains challenging in patients who are not surgical candidates, with prior registries of off-label TAVI devices showing variable outcomes and high complication rates.² The ALIGN-AR trial provided the strongest prospective evidence to date supporting a leaflet-anchoring TAVI platform that addresses device instability associated with the absence of annular calcification.

The ALIGN-AR trial had several limitations, including its single-arm design, which precluded direct comparison with surgical or medical therapy; incomplete 2-year follow-up for the entire cohort; and relatively high pacemaker implantation rates despite observed improvement over time. Within these constraints, the results support the Trilogy valve as a promising therapeutic option for patients with native AR at high risk.

References

1. Makkar RR, Thourani VH, Vahl TP, et al. Transcatheter aortic valve implantation with the Trilogy valve for symptomatic native aortic regurgitation (ALIGN-AR): a pivotal, multicentre, single-arm, investigational device exemption study. Lancet. 2025;406(10521):2757-2771. doi:10.1016/S0140-6736(25)02215-9
2. Poletti E, De Backer O, Scotti A, et al. Transcatheter aortic valve replacement for pure native aortic valve regurgitation: the PANTHEON international project. JACC Cardiovasc Interv. 2023;16(16):1974-1985. doi:10.1016/j.jcin.2023.07.026