People with bicuspid aortic stenosis and low surgical risk did not appear to be at a disadvantage for short-term outcomes after transcatheter aortic valve replacement (TAVR), though longer follow-up and randomized study were urged for such a relatively young cohort.

Drawing upon the Transcatheter Valve Therapies (TVT) Registry, investigators found no significant differences in clinical outcomes between 3,168 matched pairs of low-risk patients with bicuspid versus tricuspid anatomy who were implanted with the Sapien 3 and Sapien 3 Ultra valves:

• 30-day mortality: 0.9% vs 0.8% (HR 1.18, 95% CI 0.68-2.03)
• 1-year mortality: 4.6% vs 6.6% (HR 0.75, 95% CI 0.55-1.02)
• 30-day stroke: 1.4% vs 1.2% (HR 1.14, 95% CI 0.73-1.78)
• 1-year stroke: 2.0% vs 2.1% (HR 1.03, 95% CI 0.69-1.53)

Bicuspid and tricuspid groups shared similar procedural complications (e.g., new permanent pacemaker implantations 6.2% vs 5.2%) and valve hemodynamics over follow-up, according to Raj Makkar, MD, of Cedars-Sinai Heart Institute in Los Angeles, and colleagues in JAMA.

TVT captured the nearly 160,000 people who underwent TAVR nationwide from June 2015, when Sapien 3 hit the market, through October 2020. The newer Sapien 3 Ultra was FDA approved in December 2018.

Previous TVT Registry analyses on patients at higher surgical risk had reported higher rates of stroke, paravalvular regurgitation, and permanent pacemaker implantation after TAVR in patients with bicuspid aortic stenosis. In contrast, outcomes may be better in the low-risk population because of the availability of surgery as an option, evolving valve technology, and better procedural technique, the investigators noted.

The present analysis represents yet another observational study probing the safety and effectiveness of TAVR in the minority of people with bicuspid anatomy, a group for whom there is a paucity of data. To date, there are still no ongoing randomized trials trying to answer these questions, according to Makkar’s group.

“Because of the potential for selection bias and absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately assess the efficacy and safety of TAVR for bicuspid aortic stenosis in patients at low surgical risk,” they urged.

TAVR had officially expanded to the low-risk population in 2019 thanks to the successes of the pivotal PARTNER 3 and CoreValve Low Risk trials. However, those randomized trials had excluded patients with bicuspid anatomy.

“Clearly, TAVR is possible in patients with BAV [bicuspid aortic valve], although presumably only patients with otherwise favorable annular, valve, and aortic anatomy were offered this approach,” said Catherine Otto, MD, of University of Washington School of Medicine in Seattle, and David Newby, MD, of the University of Edinburgh.

“However, it is unclear whether TAVR is an appropriate option due to clinical concerns, such as valve durability and procedural risk, and anatomic challenges, such as asymmetrical valve anatomy, annular calcification, and associated aortic disease,” they cautioned in an accompanying editorial.

The chief issue is the relatively younger age at which bicuspid patients develop aortic stenosis. Regardless of surgical risk, it remains unclear how durable TAVR bioprosthetic valves can be in young patients with longer life expectancies.

Another group recently suggested that cerebral ischemic lesions may be a problem in particular for TAVR candidates with bicuspid aortic valves.

“TAVR in younger lower-risk patients may result in adverse outcomes and more complex surgery for later life. Therefore, physicians need to be mindful of these issues when considering patients for TAVR. More robust long-term durability data are needed for patients with either bicuspid or trileaflet aortic valve disease, but particularly for those with BAV,” Otto and Newby said.

American guidelines continue to recommend surgery over TAVR for patients younger than age 65 with severe aortic stenosis.

The TVT Registry identified 37,660 individuals with STS risk scores below 3% who underwent TAVR during the study period. The vast majority had tricuspid anatomy, leaving 3,243 individuals with bicuspid anatomy.

Makkar’s group reported that the proportion of TAVR patients at low surgical risk ballooned from 9.6% in 2015 to 43.8% in 2020, whereas patients with bicuspid aortic stenosis grew from 2.8% to 6.8%.

Propensity matching resulted in 3,168 matched bicuspid-tricuspid pairs. These patients averaged age 69, and 69.8% were men. Their mean STS score was 1.7%.

Besides its observational nature, the study was lacking in central adjudication of adverse events and independent core laboratory imaging. Furthermore, investigators noted patterns of incomplete follow-up that may be attributed in part to the COVID-19 pandemic.