Breaking News: New 2-Year Results for the SMART Clinical Trial

Over the last ten years, transcatheter aortic valve replacement (TAVR) has emerged as a safe and effective treatment for symptomatic severe aortic stenosis. In that time, more than 15,000 patients have been enrolled in nine clinical trials to evaluate the safety of the valves and overall patient outcomes.¹  The SMall Annuli Randomized To Evolut^TM or Sapien^TM* Trial (SMART) is a clinical trial that focuses specifically on patients with a small heart valve. The study is particularly unique because, unlike other TAVR trials, it focuses mainly on women, who are more likely to have a smaller heart valves.²  The two-year results were recently published with promising findings.³

Adam Pick, the patient who founded HeartValveSurgery.com, spoke with Dr. Angela Lowenstern in an exclusive interview to learn more about women with severe aortic stenosis^† and small heart valves and the implications of the SMART Trial results for this specific patient population. Dr. Lowenstern is a leading interventional cardiologist at Vanderbilt Health in Nashville, Tennessee. During her extraordinary career, she has performed thousands of minimally invasive cardiac procedures, including more than 500 TAVRs.

Key Findings of the Two-Year SMART Trial Results

Here are the principal insights shared by Dr. Lowenstern:

• Can you address the current state of the diagnosis and treatment of symptomatic severe aortic stenosis for women? “Absolutely,” said Dr. Lowenstern. “What we know is that among all patients with symptomatic severe aortic stenosis, patients are undertreated and that we need to do a better job.”⁴ Dr. Lowenstern explained that undertreatment is more prominent among females.^5-6 “Women are frequently diagnosed later, which may be related to anatomic characteristics such as less valve calcification, different flow characteristics, and also related to different symptoms. We also know that once women are diagnosed with symptomatic severe aortic stenosis, they’re less likely to undergo treatment. They’re often deemed frail by the heart team, and when they are treated, there is usually a longer time to treatment as compared with male patients.”⁷

• What is the SMART Clinical Trial, and why is it so unique and important for women? Dr. Lowenstern explained, “The SMART Clinical Trial is a randomized clinical trial examining the treatment of patients with symptomatic severe aortic stenosis and a small annulus or valve size. This is particularly relevant for women and helps in addressing some of the undertreatment since women are much more likely to have a small annulus. The trial examined the use of TAVR with a self-expanding Medtronic Evolut valve compared with a balloon-expandable Edwards SAPIEN valve in patients with a small annulus. Most notably, the trial included 87 percent women, which is really unheard of in cardiovascular disease trials.”²

• What were the results from the two-year study? According to Dr. Lowenstern, the SMART Trial showed similar clinical outcomes at two years among patients with severe aortic stenosis and a small annulus who underwent TAVR with either a self-expanding or a balloon-expandable valve. These outcomes were related to death, disabling stroke, or rehospitalization for heart failure. “However, there were significant implications for valve performance^‡ between the two groups,” she said. “Patients who underwent TAVR with a self-expanding valve were more likely to have better hemodynamics, or blood flow, through the valve and less likely to have valve dysfunction^‡, which can have long-term implications for valve durability.”³

• What are the risks of patients undergoing TAVR? “I have this conversation with my patients every day,” said Dr. Lowenstern. “Anytime we are working in the heart or doing a procedure, there are associated risks, and we always want to make sure that the benefit of the procedure outweighs those risks.” She explained that the select risks associated with TAVR include bleeding and infection from the access site, stroke, heart attack, pacemaker placement, or dying during the procedure.”

• What is your number one piece of advice for a woman with symptomatic severe aortic stenosis who may need her valve replaced? “We know that when patients with severe symptomatic aortic stenosis do not undergo any treatment, there is very high mortality,”^*8  Dr. Lowenstern said. “It’s important to be proactive, seek treatment, monitor your symptoms, and discuss these with your doctor.” She also stressed that it’s essential for women to be honest with themselves and their physicians. “What I frequently see is that women will attribute their symptoms to aging, but this is often not the entire picture. Women should feel empowered. Ask the hard questions, discuss valve choice with your physician based on your unique anatomy, and determine the best solution for you. Do your homework and get educated. Read about TAVR and what that looks like so you can have that discussion with your physician.”

Thanks Dr. Lowenstern and Medtronic!

On behalf of all the patients in our community, thank you, Dr. Angela Lowenstern, for everything you and your team are doing at Vanderbilt Health in Nashville, Tennessee. And, many thanks to Medtronic for conducting this very important research for the Evolut TAVR!

Related Links:

• Explore TAVRforWomen.com
• Low-Risk TAVR: What Should You Know?
• Free Patient eBook: Top 7 Facts About Medtronic Evolut TAVR

Keep on tickin,
Adam

P.S. For the deaf and hard-of-hearing members of our patient community, we have provided a written transcript of our interview with Dr. Lowenstern below.

†Medtronic TAVR is indicated to treat patients who have been diagnosed with symptomatic severe aortic stenosis.
^‡ Valve performance is as defined as freedom from bioprosthetic valve dysfunction (BVD) through 24 months. BVD is defined as a composite including any of the following: hemodynamic structural valve dysfunction (mean gradient ≥ 20 mmHg), non-structural valve dysfunction (severe prothesis-patient mismatch or ≥ moderate aortic regurgitation), clinical thrombosis, endocarditis, and aortic valve reintervention.
*Once severe symptoms develop, mortality is 50%.

References:

1. Al-Azizi K, Hamandi M, Mack M, Clinical trials of transcatheter aortic valve replacement, Heart 2019;105:s6-s9.
2. Herrmann HC, Mehran R, Blackman DJ, Bailey S, et al, SMART Trial Investigators, Self-Expanding or Balloon Expandable TAVR in Patients with a Small Annulus. N Engl J Med. 2024 Apr 7.
3. Herrmann HC. SMART 2-year data update. Presented at: CRT 2025; March 9, 2025; Washington, D.C.
4. Brennan JM. Under-treatment of aortic stenosis in the United States: a coordinated path forward. Presented at: TVT Conference; June 13, 2019; Chicago, IL.
5. Nau DP , Ellis JJ , Kline-Rogers EM, Mallya U, Eagle KA, Erickson SR. Gender and perceived severity of cardiac disease: evidence that women are “tougher.” Am J Med. November 2005;118(11):1256–1261.
6. Iribarren AC, AlBadri A, Wei J, et al. Sex differences in aortic stenosis: Identification of knowledge gaps for sex specific personalized medicine. Am Heart J Plus. September 2022;21:100197.
7. Rice CT, Barnett S, O’Connell SP, et al. Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England. Open Heart. September 2023;10(2):e002373.
8. Ross J Jr, Braunwald E. Aortic stenosis. Circulation. July 1968;38(1 Suppl):61-67.

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