Current ESC guidance for asymptomatic severe aortic stenosis suggests that in the absence of a reduction in left ventricular ejection fraction (LVEF) or a positive exercise test, a strategy of watchful waiting is recommended (1). The AVATAR (2) and RECOVERY (3) trials have suggested benefit to early surgical aortic valve replacement in this population, but the role of TAVI remains unclear.

The EARLY-TAVR trial was published in the New England Journal of Medicine in October 2024 (4). This trial aimed to explore the role for early TAVI as compared to clinical surveillance. Patients were deemed asymptomatic by a negative treadmill test and excluded if they had a LVEF <50% or a Society of Thoracic Surgeons (STS) adult cardiac surgery risk score >10%. 901 patients from 75 centres across the United States and Canada were randomised in a 1:1 ratio to TAVI or clinical surveillance. Those in the clinical surveillance arm were offered TAVI when they developed symptoms or any other indication for TAVI. The primary end point was a composite of all-cause mortality, stroke or unplanned hospitalisation for cardiovascular cause. Secondary endpoints included change in LVEF, new onset atrial fibrillation, a composite of death or disabling stroke, a favourable outcome at 2 years (defined as being alive with a Kansas City Cardiomyopathy Questionnaire (KCCQ) score >75 that had not decreased more than 10 points) and a composite measure of left ventricular and atrial health (defined as LV global longitudinal strain >15% and a left atrial volume index of 34ml/m2 or less).

The primary composite endpoint occurred in 122 patients (26.8%) in the early TAVI group as compared to 202 patients (45.3%) in the surveillance group (hazard ratio 0.50, p<0.001). Death from any cause occurred in 38 patients (8.4%) in the TAVR group and 41 (9.2%) of the surveillance group, whilst stroke occurred in 19 patients (4.2%) vs 30 (6.7%) and unplanned hospitalisation in 95 patients (20.9%) vs 186 patients (41.7%) of the two groups respectively. 87% in the clinical surveillance group underwent aortic valve replacement during follow-up. A favourable outcome defined by KCCQ occurred in 86.6% of the TAVR group and 68% of the surveillance group. Left ventricular and atrial health was better in the TAVR group, and there was no difference in LVEF or onset of atrial fibrillation. Death or disabling stroke occurred in 9.7% of the TAVR group and 11.2% of the surveillance group.

This is the first trial exploring the role of TAVI in asymptomatic severe aortic stenosis. Early TAVI resulted in a lower incidence of the primary composite end point, primarily driven by fewer unplanned hospitalisations. Since most patients in the surveillance group eventually underwent valve replacement, the trial essentially compared early versus delayed TAVI, with all outcomes favouring early intervention. However, interpretation is limited by the unblinded design and composite endpoints, with early hospitalisations possibly influenced by “subtraction anxiety” (5). It also remains unclear why the TAVR arm had a statistically significantly lower rate of stroke. Nonetheless, this

trial will help shape future guideline recommendations for the management of asymptomatic severe aortic stenosis.

References

1. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J [Internet]. 2022 Feb 12 [cited 2025 Aug 7];43(7):561–632. Available from: https://academic.oup.com/eurheartj/article/43/7/561/6358470

2. Banovic M, Putnik S, Penicka M, Doros G, Deja MA, Kockova R, et al. Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: The AVATAR Trial. Circulation [Internet]. 2022 Mar [cited 2025 Aug 7];145(9):648–58. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057639

3. Kang DH, Park SJ, Lee SA, Lee S, Kim DH, Kim HK, et al. Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis. N Engl J Med [Internet]. 2020 Jan 9 [cited 2025 Aug 7];382(2):111–9. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1912846

4. Généreux P, Schwartz A, Oldemeyer JB, Pibarot P, Cohen DJ, Blanke P, et al. Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis. N Engl J Med [Internet]. 2025 Jan 16 [cited 2025 Aug 7];392(3):217–27. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2405880

5. Rajkumar CA, Nijjer SS, Cole GD, Al-Lamee R, Francis DP. ‘Faith Healing’ and ‘Subtraction Anxiety’ in Unblinded Trials of Procedures: Lessons from DEFER and FAME-2 for End Points in the ISCHEMIA Trial. Circ Cardiovasc Qual Outcomes. 2018 Mar;11(3):e004665