Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for patients with severe aortic stenosis. Although the prevalence of aortic stenosis is similar in both sexes, women have historically been underrepresented in clinical trials, potentially leading to an oversight of anatomical and pathophysiological differences unique to female patients. Specifically, women tend to have a smaller aortic annulus compared to men, which increases their risk of hemodynamic valve dysfunction following TAVR. This knowledge gap was addressed in 2024 by the SMART trial, a randomized clinical study that compared the hemodynamic performance and clinical outcomes of the two most widely used valve systems: the EVOLUT self-expanding supra-annular device and the SAPIEN balloon-expandable valve.
“The SMART study finally gives us female-specific data that allows us to more effectively treat women with aortic stenosis. It’s a critical step forward in treating women with heart disease,” says Roxana Mehran, MD, Professor of Medicine (Cardiology), and Director of Interventional Cardiovascular Research and Clinical Trials at the Icahn School of Medicine at Mount Sinai, who was co-Principal Investigator of the study, along with Howard C. Herrmann, MD, Director of Interventional Cardiology, and the John Winthrop Bryfogle Professor of Cardiovascular Diseases at the Perelman School of Medicine at the University of Pennsylvania.
The study, which included an 87 percent female cohort, was published in April 2024 in The New England Journal of Medicine. Dr. Mehran presented its findings, along with a secondary analysis of the women-only cohort—simultaneously published in JAMA Cardiology—in May 2024 as a late-breaker at the EuroPCR conference.
“Though clinical endpoints between the two valves were similar through the first year, the benefit in hemodynamic performance was pronounced for patients with a small annulus who received a self-expanding valve,” Dr. Mehran says. “Within this cohort, there was much less bioprosthetic valve dysfunction, less prosthesis-patient mismatch, less aortic regurgitation, and better quality of life. The composite picture is thus decidedly more favorable for the self-expanding valve vs. balloon-expandable when it comes to informing device selection for patients with small aortic annuli.”
“The SMART study finally gives us female-specific data that allows us to more effectively treat women with aortic stenosis. It’s a critical step forward in treating women with heart disease.”
Roxanna Mehran, MD
Graphic abstract of the study.
The SMART (Small Annuli Randomized to Evolut or SAPIEN) trial was conducted at 83 sites across North America, Europe, and the Middle East. It found that bioprosthetic valve dysfunction through 12 months for patients with the self-expanding valve was 9.4 percent, compared to 41.6 percent for patients with the balloon-expandable valve. The coprimary clinical endpoint at one year—defined as death, disabling stroke or rehospitalization for heart failure—was similar for the two types of valves (9.4 percent for self-expanding vs. 10.6 percent for balloon-expandable).
Consistent findings were observed in the prespecified secondary analysis of women, which included 621 female patients. The analysis demonstrated similar clinical outcomes (9.4 percent vs. 11.8 percent) but significantly less bioprosthetic valve dysfunction (8.4 percent vs. 41.8 percent) with the self-expanding valve, which also resulted in superior hemodynamic performance, including a lower incidence of prosthesis-patient mismatch. The trial was funded by Medtronic, maker of the Evolut platform.
Individuals with small annuli are an important subgroup of symptomatic patients with aortic stenosis undergoing TAVR, though they are understudied, accounting for only about a third of participants in randomized clinical trials. Predominantly women, these patients are at greater risk for impaired valve hemodynamics, including high gradients, prosthesis-patient mismatch, reduced exercise capacity, and impaired prosthesis durability. The SMART trial was designed to correct that imbalance by randomizing 716 patients who had a valve annulus ≤430 mm2 to either the self-expanding Evolut valve or the balloon-expandable SAPIEN valve.
At the end of a year, the study found the self-expanding supra-annular valve to be noninferior to the balloon-expandable valve in clinic outcomes, and superior in bioprosthetic valve dysfunction. The self-expanding valve was also found to be superior in terms of mean gradient, effective orifice area, hemodynamic structural valve dysfunction, and bioprosthetic valve dysfunction. Second-year results from the study will be available in 2025, shedding additional light on the durability of the valve as well as clinical outcomes.
“TAVR is life-saving, and interventional cardiologists need to inform patients undergoing the procedure that they may do better with a self-expanding valve because of their annulus size,” Dr. Mehran says. “In a broader context, results from the first-of-its-kind SMART study are extremely important to women’s health overall, since women are under-recognized and undertreated for conditions like aortic stenosis, and underrepresented in clinical trials. These shortcomings need to be recognized and addressed at the highest levels of government, along with the need for a joint public-private partnership to ensure women get the treatment they deserve.”
Dr. Mehran is internationally known for her leadership in cardiovascular clinical trials and in women’s cardiovascular health. She is Chair of The Lancet Women and Cardiovascular Disease Commission, whose members from 11 countries in 2021 released the first-ever global report and recommendations for decreasing the burden of cardiovascular disease in women. In March 2025, Dr. Mehran will become Vice President of the American College of Cardiology, one of the world’s premier cardiovascular organizations, with more than 56,000 members.