The use of transcatheter aortic valve replacement (TAVR) increased among healthier, lower-risk patients younger than 65 between 2012 and 2024, despite a lack of randomized data on this patient population, according to a new study.

The FDA in 2019 expanded its approval of TAVR to include some low-risk patients, although practice guidelines still recommend surgical aortic valve replacement (SAVR) for patients younger than 65.

The study “highlights that while procedural success is high, the patients being treated today are fundamentally different from those treated a decade ago,” said Sundos Alabbadi, PhD, a researcher at Icahn School of Medicine at Mount Sinai in New York and first author of the study published this month in the Journal of the American College of Cardiology.

Off-Guideline Concerns

Alabbadi and her collaborators were inspired to conduct their analysis by concerns about a rise in “off-guideline” use of TAVR among patients younger than 65. 

Her team analyzed 583,215 TAVR patients with aortic stenosis from the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry from 2012 to 2024. The analysis revealed the number of hospitals performing TAVR increased from 161 to 726 in 12 years and that the case mix shifted from high-risk patients with comorbidities to healthier, lower-risk patients.

During that time, low-risk cases grew from 2.7% to 35.7% of all cases. Alabbadi and her collaborators also saw a significant increase in bicuspid aortic valve prevalence among TAVR recipients, an anatomic defect that may complicate sealing of the device and affect its long-term durability.

“For these younger, lower-risk patients with decades of life expectancy ahead, the first intervention is no longer just a standalone procedure. It is a critical decision that must be made with a 20- to 30-year clinical horizon in mind.” Alabbadi said. There are no long-term data on TAVR durability and repeat TAVR procedures.

Parsing Risk

The study’s most striking finding was the inverse relationship between age and mortality, Alabbadi said. 

“For patients under 65, every 5-year increase in age actually decreased 1-year mortality by 10%,” she said. “This is the opposite of the trend seen in patients over 65, where mortality risk increases by 15% with every 5-year increase in age.”

The finding is in part attributable to the presence of patients with extreme-risk, non-calcific phenotypes or underlying conditions that made them poor surgical candidates to begin with, Alabbadi added.

Paul Michael Grossman, a professor of internal medicine in the Division of Cardiovascular Medicine at the University of Michigan in Ann Arbor, Michigan, said some of the increased risk in patients younger than 65 in this analysis may also be due to confounding factors such as comorbidities and socioeconomic factors not fully captured in the STS/ACC TVT Registry.

“In fact, many patients under 65 who undergo TAVR may be at higher risk for adverse, 1-year mortality due to these factors,” said Grossman, who was not involved in the study.

‘Reassuring’ outcomes

Grant Reed, MD, program director for the Interventional Cardiology Fellowship at Cleveland Clinic, noted that only about 5% of patients in the analysis were younger than 65, indicating that the majority were treated in alignment with US guidelines.

“Outcomes were reassuring and suggest that TAVR can be done safely in low-surgical risk patients, even among carefully selected patients with bicuspid [aortic valves],” said Reed, who didn’t work on the study. 

Reed and Grossman concurred with the study authors on the importance of a team approach for patients undergoing TAVR.

“Shared decision-making between the heart team and the patient, including a discussion of TAVR vs SAVR and long-term management of aortic valve disease, is routine practice at Michigan Medicine and should be standard across the United States, particularly for younger patients for whom lifetime valve strategy is especially important,” Grossman said.

The study was independently supported. The authors reported no relevant financial relationships.

Catherine Shaffer is a freelance science and medical writer with a background in molecular biology and pharmaceutical research. Her work has appeared extensively in scientific trade and mainstream publications and on public radio.