Latest EARLY TAVR data suggest it is time to update industry guidelines
A new analysis EARLY TAVR data presented at ACC.25 suggested that intervening before symptoms arise in asymptomatic severe aortic stenosis (AS) leads to better outcomes and lower stroke rates. The biggest takeaway was that 40% of patients who waited for symptoms to worsen before getting transcatheter aortic valve replacement (TAVR) rapidly declined without any warning. These patients were very difficult to manage due to cardiac arrest, heart failure hospitalization and pulmonary edema, and they were associated with elevated stroke rates.
Cardiovascular Business spoke with the trial's principal investigator, Philippe Genereux, MD, director of the structural heart program at Morristown Medical Center, to find out more details.
The trial divided about 900 asymptomatic patients between early TAVR interventions and a second arm for traditional clinical monitoring. Outcomes showed early TAVR intervention was clearly superior for death, stroke and unplanned hospitalizations. Early data were presented at TCT 2024. This latest data from ACC.25, meanwhile, looks at the remaining patients in the clinical surveillance arm who have all crossed over since the initial trial data were presented. A handful of these patients were still asymptomatic when converted to TAVR, and the rest converted with progressive valve syndrome, or the most severe classified as acute valve syndrome, which Genereux said are the "crash and burn" worst-case patients.
"While 60% of the patients will progress to mild symptoms, 40% of those patients crush and burn and have very poor outcomes for death and stroke because they develop a disease that is much more severe," Genereux explained.
Within the one or two years, he said they these patients had a much higher calcium score, more atrial fibrillation, more severe aortic stenosis and possibly more cardiac damage.
"So they come in a situation where they're more unstable and they have more strokes after the procedure. All those reasons led us to believe that a strategy of early intervention should be preferred compared to waiting and gambling with a patient that 40% of the time can really crush and burn within six months or 12 months," Genereux said.
Time to change the guidelines to favor early TAVR?
According to Genereux, the latest data combined with the initial TCT late-breaking data should be a wake-up for the industry that shows intervening early can make a big difference on patient outcomes.
"The wait is over. 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,'" Genereux explained
Predicting who will crash and burn with rapid AS decline
Importantly, Genereux noted that predicting which patients with asymptomatic will deteriorate rapidly is challenging. Traditional echocardiography indicators like peak valve velocity, left ventricular ejection fraction and stress test performance failed to reliably forecast acute decline. He noted that these key indicators remained somewhat consistent between baseline and just before a patient began their rapid decline. This uncertainty is another reason why a "wait and see" approach may not be the best for patients.
“Aortic stenosis is proving to be far more unpredictable than we thought. Our ability to risk-stratify is still quite limited,” he said.
AS may be an independent risk factor for stroke
Another groundbreaking takeaway from the EARLY TAVR data is the emerging evidence that severe aortic stenosis itself may be an independent risk factor for stroke. Stroke rates were nearly double in the delayed-intervention group compared to early TAVR, particularly after the two-year mark. Genereux pointed to factors such as progressive valve calcification, potential undetected atrial fibrillation and heightened inflammatory or thrombotic states in acutely decompensated patients as possible contributors.
"First of all, look at the calcium score on the valve. At the start, patients had a score of 1,000, and then when they crossover, it is 2,000, 3,000 or 4,000. So there's an increase of calcification of the valve that may explain stroke while waiting. I strongly believe that aortic stenosis is a risk factor for stroke and we've been sleeping on this for years. I think now it's time to better understand if this is true," Genereux explained. "There's a lot more research that's needed because it's not what we thought it was."
Data from EARLY TAVR helped influence the U.S. Food and Drug Administration (FDA) to approve a new indication for treating asymptomatic patients with the Edwards Lifesciences Sapien 3 TAVR platform on May 1, 2025. Read more about the FDA approval.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]