New TAVR research explores adverse outcomes, disease progression in patients with asymptomatic severe AS

At ACC.25, the annual conference of the American College of Cardiology, researchers presented two key follow-up studies focused on data from the EARLY TAVR trial.

Each analysis provided additional insights about the potential benefits of treating asymptomatic severe aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) as opposed to clinical surveillance (CS).

A bit of context about EARLY TAVR

EARLY TAVR was a randomized controlled trial comparing TAVR with a balloon-expandable Sapien valve from Edwards Lifesciences with CS in 901 patients. The mean patient age was 75.8 years old, 69% were men and the mean Society of Thoracic Surgeons risk score was 1.8%. While a vast majority (83.6%) of patients faced a low surgical risk, the mean Kansas City Cardiomyopathy Questionnaire (KCCQ) score was 92.7, suggesting the cohort presented with a relatively healthy, symptom-free quality of life. All CS patients were followed closely and converted to TAVR as soon as the first signs of clinical symptoms were identified.

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

Data from EARLY TAVR were presented by lead investigator Philippe Généreux, MD, director of the structural heart program at Morristown Medical Center’s Gagnon Cardiovascular Institute, at TCT 2024 and simultaneously published in The New England Journal of Medicine.[1]

“Given the benefits observed and the lack of harm, early TAVR may be preferred to clinical surveillance in patients with asymptomatic severe AS, especially when combined with the challenges of timely symptom recognition and prompt treatment in real-world settings,” Généreux said at the time.

What we learned at ACC.25

The first EARLY TAVR subanalysis at ACC.25 focused on patients who were originally just being watched with CS, but then developed symptoms and ended up undergoing TAVR. The goal was to learn how waiting before the eventual aortic valve replacement impacted patient outcomes—did that initial period of watchful CS do harm to the patient’s heart?

The study’s authors compared 444 patients who underwent TAVR right away with 388 patients who underwent delayed AVR after an initial period of CS. Overall, the study’s primary outcome—a composite of death, stroke or heart failure hospitalization after two years—was seen in 10.6% of delayed AVR patients and 6.8% of early TAVR patients. This was primary driven by a higher periprocedural stroke rate (1.8% vs. 0.9%) in addition to higher stroke rates after one year (2.6% vs. 1.4%) and after two years (4.5% vs. 2.7%).  

All-cause mortality and heart failure hospitalizations were also more common following delayed AVR.

Généreux presented these findings, noting that patients who underwent delayed AVR were much more likely to experience an adverse outcome if classified with acute valve syndrome, which the team defined as New York Heart Association III or IV heart failure, ventricular arrhythmia, syncope, atrial fibrillation, left ventricular ejection fraction less than 50% or other significant complications. 

It is these patients who go on to develop acute valve syndrome, it seems, who would benefit the most if treated with TAVR right away as opposed to waiting for the development of symptoms.

“These findings provide a strong rationale for prompt intervention in patients with asymptomatic severe AS, at least to prevent progression to acute valve syndrome and poor outcomes,” Généreux said.