2.1 EARLY TAVR: Sure. Moderate AS: Not So Sure?

Problem Presenter: Molly Szerlip

These proceedings summarize the educational activity of the 18th Biennial Meeting of the International Andreas Gruentzig Society held January 27 to 30, 2026, in Puerto Ayora, Santa Cruz, Ecuador.

Faculty Disclosures     Sponsors

2026 IAGS Summary Document

Statement of problem or issue

In the United States, transcutaneous aortic valve replacement (TAVR) is approved for patients with symptomatic severe aortic stenosis (AS). For patients with asymptomatic severe aortic stenosis, current guidelines recommend optimal medical therapies and clinical surveillance (CS) every 6 to 12 months. Whether these asymptomatic patients with severe AS might benefit from TAVR before symptoms develop has been tested recently in two large randomized clinical trials, which unfortunately reached different conclusions (see below).[1,2] Additionally, patients with symptomatic but only moderate AS are known to be at higher risk for adverse events.[3] Whether these moderate AS patients might benefit from TAVR is of great clinical interest yet there are few data available at present for guidance.

Gaps in current knowledge

1. Asymptomatic severe AS

The EARLY TAVR trial enrolled 901 patients (455 randomly assigned TAVR and 446 assigned CS). The primary endpoint at a minimum of 2 years follow-up was a composite of death from any cause, stroke, or unplanned hospitalization for cardiovascular causes. Median follow-up was 3.8 years and Kaplan-Meier curves were extended to 5 years. A primary endpoint event occurred less frequently in the TAVR group compared with the CS group (26.8% versus 45.3%, HR=0.50, P<.001). The investigators concluded that early TAVR was a superior strategy compared with CS.[1]

The EVOLVED trial enrolled 224 patients (113 randomly assigned TAVR and 111 assigned to conservative management). Additionally, all enrolled patients had to have evidence of myocardial fibrosis on gadolinium-enhanced cardiac MRI scans. The planned enrollment of 356 patients was not achieved due to COVID restrictions. The primary endpoint was a composite of all-cause death or unplanned AS–related hospitalization. Median follow-up was 3.5 years (42 months) and Kaplan-Meier curves were extended to 5 years. Occurrence of a primary endpoint event was not significantly different in the TAVR group compared with the conservative management group (18% versus 23%, HR=0.79, P=.44). The investigators concluded that in asymptomatic patients with severe AS and myocardial fibrosis, early TAVR had no demonstrable effect on all-cause death or unplanned AS–related hospitalization. [2]

The differing conclusions reached by these 2 randomized trials leaves a large gap in our knowledge base that will need to be filled in.

2. Moderate AS

A recent meta-analysis of five observational studies of early aortic valve replacement (AVR, including both TAVR and SAVR) compared with CS, in patients with moderate AS and reduced LVEF, concluded that early AVR might be associated with improved survival.[4] Given the limited nature of the data, however, larger, appropriately designed randomized trials with long term follow-up are needed.

Possible solutions or future directions

There are two large trials currently underway that are examining early TAVR in patients with moderate AS and reduced LVEF. These are the PROGRESS trial (NCT 04889872) and the EXPAND TAVR II trial (NCT 05149755). More fundamentally, though, there are several areas of investigation for future research studies:

• One is the intriguing question of the definitions of ‘moderate’ and ‘severe’ AS, and the precise role of symptoms: Is it possible that we are dealing only with subsets of the same clinical phenomenon?
• Just how important are structural changes in the myocardium, for example, myocardial fibrosis, across the entire spectrum of AS?
• With earlier implantation of these valves, how important is valve durability? Are we trading one set of problems for another set? For example: paravalvular leak, endocarditis, reintervention, need for permanent pacemaker, etc?

References

1. Généreux P, et al. Transcatheter aortic-valve replacement for asymptomatic severe aortic stenosis. N Engl J Med. 2025;392(3):217-227. doi: 10.1056/NEJMoa2405880. Epub 2024 Oct 28. PMID: 39466903.
2. Loganath K, et al. Early intervention in patients with asymptomatic severe aortic stenosis and myocardial fibrosis: the EVOLVED Randomized Clinical Trial. JAMA. 2025 Jan 21;333(3):213-221. doi: 10.1001/jama.2024.22730. PMID: 39466640; PMCID: PMC11519785.
3. Jacquemyn X, et al. Moderate aortic valve stenosis is associated with increased mortality rate and lifetime loss: systematic review and meta-analysis of reconstructed time-to-event data of 409 680 patients.J Am Heart Assoc. 2024;13(9):e033872. doi: 10.1161/JAHA.123.033872. Epub 2024 May 3. PMID: 38700000; PMCID: PMC11179918.
4. Abdelfattah OM, et al. Early aortic valve replacement in moderate aortic stenosis. JACC Adv. 2024;3(9):101190. doi: 10.1016/j.jacadv.2024.101190. PMID: 39253710; PMCID: PMC11381792.