Replacing the valve early beat watchful waiting in moderate aortic stenosis

Moderate aortic stenosis — a heart valve that has stiffened and narrowed, but not yet severely — sits in an awkward place in cardiology. Severe aortic stenosis has a clear fix: replace the valve. For moderate disease, guidelines advise watching and waiting, with an echocardiogram every year or two, until the narrowing becomes severe [s1]. A randomised trial published in the New England Journal of Medicine on 2 November tested whether acting earlier does better [s1].

The question

The valve in question is the aortic valve, the door the heart's main pumping chamber pushes blood through. When it narrows, the heart must work harder, and over time that strain can lead to heart failure. Transcatheter aortic-valve replacement, or TAVR, threads a replacement valve up to the heart through an artery in the leg, avoiding open-heart surgery [s1].

The established approach for moderate stenosis is surveillance — leave the valve alone until the narrowing crosses into severe, then replace it [s1]. The reasoning has been that any procedure, however safe, carries a risk not worth taking while the disease is only moderate. PROGRESS asked whether that caution costs patients — specifically those whose moderate stenosis already carries a warning sign of faster decline [s1].

How the trial was built

PROGRESS was an international, open-label, randomised trial, registered as NCT04889872 [s1][s2]. It enrolled patients with moderate aortic stenosis who had at least one "at-risk feature" — a symptom, or a structural or functional abnormality of the heart shown to track with faster progression or worse cardiovascular outcomes [s1]. A total of 744 patients were randomly assigned 1:1: 373 to transfemoral TAVR with a balloon-expandable valve and 371 to clinical surveillance [s1].

The patients were, on average, 78 years old; 39.1% were women and 45.6% were at low surgical risk [s1]. Their mean aortic-valve area was 1.2 cm² and mean peak velocity 3.3 m per second — numbers that place them squarely in the moderate range [s1]. The primary effectiveness endpoint was a composite of death from any cause or a heart-failure event, with or without hospitalisation, at two years, tested for superiority in the intention-to-treat population [s1].

What it found

Replacing the valve early reduced the combined endpoint. At two years, the Kaplan–Meier estimate of patients who had died or had a heart-failure event was 16.7% in the TAVR group versus 23.9% with surveillance — a risk difference of 7.2 percentage points (95% CI −13.1 to −1.3; p=0.02 for superiority) [s1].

The components show where the benefit came from. Death from any cause was 8.4% with TAVR and 7.3% with surveillance — essentially the same [s1]. The gap was in heart-failure events: 10.8% with TAVR against 19.0% with surveillance [s1]. In other words, replacing the valve early did not, in this trial, save lives over two years, but it roughly halved heart-failure events. The incidence of procedure-related adverse events did not differ meaningfully between the TAVR patients and the surveillance patients who went on to have their valve replaced [s1].

What is, and is not, established

What PROGRESS supports is that, among patients with moderate aortic stenosis and at least one at-risk feature, a strategy of early TAVR lowered the combined rate of death or heart-failure events at two years compared with waiting [s1]. For a condition usually managed by watching, that is a meaningful shift in the evidence.

The qualifications matter. The benefit was driven by fewer heart-failure events, not fewer deaths; survival at two years was essentially the same in both groups [s1]. The margin on the primary endpoint was modest and the p-value of 0.02 is not overwhelming, so this is one trial rather than a closed case [s1]. The trial was open-label — patients and doctors knew who had received a valve — though the endpoints are largely objective [s1]. Follow-up was two years; whether the early-TAVR advantage grows, holds, or fades over a longer horizon is not yet known [s1]. The results apply to patients with an at-risk feature, not to everyone with moderate stenosis, and the trial was funded by the maker of the valve used [s1].

Red flags: anyone with known aortic stenosis who develops breathlessness, chest tightness, fainting, or swelling of the legs should seek medical assessment, as these can signal the valve tightening or the heart beginning to struggle. This article describes research and is not medical advice. Whether and when to replace a moderately narrowed valve is a decision for patients and their cardiology team.