Answering key follow-up questions after the FDA approved TAVR in asymptomatic patients

EARLY TAVR’s primary endpoint—a composite of all-cause mortality, stroke or unplanned cardiovascular hospitalizations—was seen in 26.8% of patients treated with TAVR and 45.3% of patients monitored with clinical surveillance. This was primarily driven by a significant reduction in unplanned hospitalization—20.9% for TAVR, 41.7% for clinical surveillance—though early treatment was also linked to lower rates of all-cause mortality (8.4% vs. 9.2%) and stroke (4.2% vs. 6.7%). 

In addition, a favorable health status—defined as being alive with a Kansas City Cardiomyopathy Questionnaire score of at least 75 that had not decreased more than 10 points from baseline—was seen in 86.8% of TAVR patients and 68% of clinical surveillance patients.

When lead investigator Philippe Généreux, MD, first announced the EARLY TAVR findings in front of a packed audience at TCT 2024, he was met with cheers and applause; the crowd had clearly been anticipating these results, and they were excited about what this could mean for patient care going forward.

“A major reset in our approach to severe asymptomatic AS is now warranted,” Prof. Bernard Prendergast, chair of cardiology at Cleveland Clinic London and a consultant with St. Thomas’ Hospital in Westminster, England, said from the stage at TCT 2024. “The concept of watchful waiting is no longer appropriate and deserves re-examination. Patients require access to earlier diagnoses and they need to be prepared early for their interventional procedure.”

Généreux’s team has continued exploring the EARLY TAVR data. At ACC.25, for instance, he shared additional findings on the potential impact of early treatment, once again emphasizing the importance of taking care of these patients before the AS gets worse and worse. He shared even more EARLY TAVR data at SCAI Scientific Sessions 2025, tracking adverse event rates in patients who did and did not undergo TAVR for asymptomatic severe AS.

Additional data on treating asymptomatic patients

EARLY TAVR is not the first clinical trial to examine the potential treatment of asymptomatic severe AS. In fact, the RECOVERY, AVATAR and EVOLVED clinical trials explored the potential impact of early surgical aortic valve replacement (SAVR).[2, 3, 4]

RECOVERY is the oldest of these trials, first published in 2019. It included data from 145 patients with asymptomatic severe AS treated with either early surgical aortic valve replacement (SAVR) or conservative care. There was no operative mortality for the early SAVR patients, researchers noted, and the long-term risk of mortality was lower for patients who underwent SAVR.

AVATAR, meanwhile, found that early SAVR was associated with multiple long-term benefits compared to a more conservative approach. AVATAR included 157 low-risk patients randomized to either undergo early SAVR or clinical surveillance. The average age was 67 years old, 57% were men and the median estimated operative mortality risk according to the STS score was 1.7%. 

Original findings from AVATAR were published back in 2021. A follow-up analysis with a median follow-up period of 63 months, however, was released in 2024. Overall, the study’s authors found that early SAVR was linked to a significantly lower rate of the study’s primary endpoint—all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure—compared to conservative treatment. Early SAVR was also associated with a lower risk of all-cause mortality.

EVOLVED also evaluated early SAVR, tracking 224 patients who underwent early treatment or conservative management. The mean patient age was 73 years old and 28% of patients were women. 

The team behind EVOLVED reported that early treatment “had no demonstratable effect” on either all-cause mortality or unplanned hospitalizations related to AS. Early SAVR did appear to help lower the patient’s risk of developing New York Heart Association class II, III or IV symptoms, however. 

“The findings are not definitive, and further research will be required to confirm the trial findings,” the authors wrote at the time.

Back in 2023, meanwhile, the group behind a retrospective cohort study of more than 230,000 patients found that TAVR for “minimally symptomatic or asymptomatic” patients was safe, but only linked to “small improvements in health status.”[5]

“Randomized trial data are needed to confirm whether TAVR in asymptomatic AS improves outcomes compared with a conventional strategy of surveillance until symptoms develop,” the group said at the time, perhaps setting the table for these other studies.

Question 2: Will TAVR guidelines be changed?

TAVR guidelines from physician groups such as the American College of Cardiology (ACC) have never advocated for treating asymptomatic severe AS with TAVR. After the FDA’s approval, however, that could certainly change.

"The wait is over,” Généreux told Cardiovascular Business when discussing EARLY DATA at ACC.25. “It's time to change the guidelines. It's time to talk with our patients and to plan accordingly in a civilized way, and not wait until the patient falls off the cliff and then say, 'oh, let me help you.’” 

If guidelines do start to recommend TAVR for asymptomatic patients, it could result in many more patients undergoing the minimally invasive treatment than ever before. Instead of waiting to see if their symptoms will worsen, care teams could start recommending asymptomatic patients undergo treatment right away before anything escalates. Only time will tell what such a change would mean for established TAVR programs—or how reimbursement may be influenced—but this will be a space to watch closely in the years ahead.

Cardiologists will certainly be watching closely the next time the ACC or another major group announces new TAVR recommendations. 

Question 3: What do heart specialists think?

The FDA's decision is likely going to have a substantial impact on patient care going forward. So what do physicians think about AVR for asymptomatic patients? 

Exploring cardiologist opinions

Multiple commentary pieces published by cardiologists in the last year have explored the potential impact of early treatment for asymptomatic patients. 

In February, for example, first author Brian R. Lindman, MD, MSc, an associate professor and medical director of the Structural Heart and Valve Center at Vanderbilt University Medical Center, and colleagues wrote that both TAVR and SAVR should be start being used to treat asymptomatic severe AS.[6]

“We believe that the time has come to recommend AVR for asymptomatic patients with severe AS,” the group wrote. “This paradigm shift is anticipated to yield improved patient outcomes, public health, and resource utilization. It is time to act.” 

Just one month later, however, a group of cardiologists concluded that it was still too early to tell.[7]  

“The question for the community is whether we should intervene in all patients with severe AS, irrespective of symptoms or the status of the left ventricle,” wrote first author Rick A. Nishimura, MD, a veteran Mayo Clinic cardiologist, and colleagues. “Before routinely offering valve intervention to the asymptomatic patient with severe AS, it is important to pause and critically examine the reports of improved outcomes with early operation versus a more conservative strategy. If a patient is asymptomatic, an early intervention will not make them feel better. There is no definitive evidence that early intervention will improve survival, except perhaps for patients at the highest risk with very severe AS.”

Nishimura et al. did agree that aortic valve replacement is “inevitable” for a majority patients who present with severe asymptomatic AS. However, they want clinicians to exercise considerable caution and wait when appropriate. When a “wait and see” approach is chosen, they added, patients should be followed closely to ensure signs of symptom progression are identified right away.

Veteran surgeon shares his perspective

SAVR and TAVR are regularly compared to one another, especially in the last few years as TAVR has continued to grow and more popular among cardiologists and patients alike. With this close connection between the two treatment options in mind, Cardiovascular Business reached out to a leading voice in the cardiothoracic surgeon space, Vinay Badhwar, MD, for his own take on the FDA’s approval of the Sapien 3 platform for treating asymptomatic patients. 

Badhwar serves as the chair of the department of cardiovascular and thoracic surgery at West Virginia University (WVU) and executive chair of the WVU Heart and Vascular Institute. He is also a pioneer of robotic heart procedures, including robotic aortic valve replacement (RAVR), and a longtime member of STS, ACC and the American Association for Thoracic Surgery. He said he was speaking for himself only and not WVU or any other organization.

Badhwar’s first takeaway from this news was that clinicians cannot forget about the importance of stress tests. 

“Asymptomatic designations in the setting of severe AS with normal ejection fraction should be confirmed by exercise testing before recommending therapy,” he said. “Those with reduced ejection fraction at baseline or those who have provocative changes during stress testing (e.g. angina, significant dyspnea, ST changes, drop in ejection fraction, or ventricular arrhythmia) are not truly asymptomatic and should be managed by existing guidelines for symptomatic AS. For patients with elicitable symptoms or sequelae of AS that are at elevated premature risk, aortic valve replacement would of course be reasonable as a SAVR or TAVR based on age, valve anatomy, and risk.”

Badhwar also highlighted the many trials that have linked early SAVR to positive outcomes for asymptomatic patients, including AVATAR and others. These trials were not funded by a vendor, he added, and they included years of follow-up data. 

Badhwar did emphasize that he is a “firm believer in TAVR, particularly for the right patient at the right time.” However, his hope is that heart teams don’t forget about the value of SAVR when discussing possible treatment options—and that only older patients are being considered for early TAVR.

“For patients with severe AS with normal LV function deemed truly asymptomatic with negative stress testing, the heart team should be informed by all of the existing evidence as they carefully determine the appropriateness, timing, and type of intervention for either SAVR or TAVR based on age, valve anatomy, and risk,” he said.