New analysis of the EARLY TAVR trial, in which investigators examined the prevalence of guideline indications for aortic valve intervention among patients enrolled in the trial, suggests that pre-emptive transcatheter aortic valve implantation (TAVI) may be an effective approach among patients with severe aortic stenosis, even if they have no symptoms or formal guideline recommendations for immediate treatment.
Initial results from EARLY TAVR were first released in late 2024. The trial, which enrolled more than 900 patients with severe asymptomatic aortic stenosis, compared early intervention with TAVI to clinical surveillance, demonstrating a reduction in a composite of death, stroke or unplanned cardiovascular hospitalisation between the two arms out to two years, driven largely by a reduction in hospitalisations in the TAVI group.
The latest study, presented by Allan Schwartz (Columbia University Irving Medical Center, New York, USA) at New York Valves 2025 (25–27 June, New York, USA), is one of a series of analyses from the trial’s investigators to have been released in recent months, and comes shortly after the device used in the study—Edwards Lifesciences’ Sapien 3 platform—was granted US Food and Drug Administration (FDA) approval for the treatment of severe aortic stenosis in asymptomatic patients.
In the latest study, investigators examined the prevalence of class II indications in accordance with the American College of Cardiology (ACC)/American Heart Association (AHA) guideline for the management of patients with valvular heart disease among patients enrolled in the trial and their associated impact on outcomes.
“The guidelines have a series of class II indicators that basically are indicators of rapid progression to a class I indication, or worse outcomes, and they are markers of either ventricular function or patient function drop on a stress test or biomarkers,” Schwartz outlined in his presentation.
For asymptomatic patients, the guidelines set out a class IIa recommendation if patients exhibit decreased exercise tolerance or a blood pressure drop of ≥10mmHg on a stress test, amongst other parameters, with a class IIb indication if they have a left ventricular ejection fraction (LVEF) measuring <60%. Surgical aortic valve replacement (SAVR) is favoured in the guidelines over TAVI.
“In the EARLY TAVR trial, 70% of the patients had no guideline recommendation to proceed with AVR,” Schwartz detailed, noting that 30% had either a class IIa or IIb recommendation and 7% had just a IIb with an ejection fraction <60%.
Outlining patient characteristics, Schwartz noted that patients in either of the class II categories typically had a slightly higher Society of Thoracic Surgeons’ (STS) risk score, and higher levels of B-type natriuretic peptide (BNP). In terms of echocardiographic characteristics, patients with a IIb classification typically had a lower ejection fraction, and IIa patients had more severe aortic stenosis with higher gradients.
“When you looked at the total calculation, it validated the guidelines, meaning that patients with a IIa or IIb indication at randomisation were indeed at significantly increased risk for death, stroke or heart failure hospitalisation,” he said.
Turning to the treatment effect of the trial, Schwartz said the analysis demonstrated the superiority of TAVI to clinical surveillance independent of guideline classification with a consistent benefit across all groups.
The analysis also took into account patients who converted from the surveillance group to undergo aortic valve replacement (AVR). Schwartz noted that there was a significant difference in terms of whether the patients had a IIa or IIb classification at randomisation. For patients with a class IIa recommendation, the median time to requiring replacement was 11.6 months, compared to 7.6 months for class IIb patients.
Added to this, as many as 50% of class II patients converted with an acute valve syndrome, and even among those with no guideline recommendation, up to a third presented with an acute valve syndrome.
“Given the overall positive outcomes of the EARLY TAVR trial, taking into account the extremely low procedural risk, the rapid progression to aortic valve replacement under very careful clinical surveillance, the risk of developing an acute valve syndrome even though you are under careful clinical surveillance and getting a worse outcome, and the real-world difficulties of detecting symptoms and the prompt performance of aortic valve replacement, the EARLY TAVR trial does support early intervention as the preferred strategy, independent of guideline indications,” said Schwartz, summing up the findings.
Prior to Schwartz’s presentation at New York Valves further data from the trial were released, detailing the incidence and impact of cardiac damage among patients enrolled in the study. These, presented at the 2025 EuroPCR congress (20–23 May, Paris, France), by Philippe Généreux (Morristown Medical Center, Morristown, USA) the EARLY TAVR principal investigator, suggest that in excess of 85% of patients enrolled in the trial had cardiac damage at baseline, with the extent of the damage associated with worse outcomes.
“Early TAVI patients were more likely to improve their stage of cardiac damage at two years compared to the clinical surveillance patients who were more likely to worsen their stage of cardiac damage,” Généreux reported. “When we looked more in detail among patients in the clinical surveillance group, who didn’t cross over to aortic valve replacement, they were less likely to improve their cardiac damage, but more likely to worsen, slightly, the extent of cardiac damage.”
According to Généreux, the findings support a strategy of early referral and prompt TAVI before the development of symptoms for patients with severe aortic stenosis to prevent worsening of cardiac damage. “For me, if you have damage, if you have biomarkers, if you have symptoms, you are too late. It is an alarm system,” he said.
