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CONTRIBUTION TO LITERATURE - The RECOVERY trial showed that early surgery among patients with asymptomatic but very severe aortic stenosis results in improved survival out to 8 years compared with watchful waiting.

DESCRIPTION - The goal of the trial was to assess the safety and benefit of surgery vs. watchful waiting among patients with asymptomatic very severe aortic stenosis.

STUDY DESIGN

Eligible patients with very severe asymptomatic aortic stenosis were randomized in a 1:1 open-label fashion to either early surgical aortic valve replacement (AVR) (n = 73) or watchful waiting (n = 72).

- Total screened: 273

- Total number of enrollees: 145

- Duration of follow-up: 6.2 years

- Mean patient age: 64.2 years

- Percentage female: 51%

INCLUSION CRITERIA:

- Age 20-80 years

- Very severe aortic stenosis (aortic valve area [AVA] 0.75 cm2, peak velocity ≥4.5 m/sec, or mean gradient ≥50 mm Hg)

- Lack of symptoms

EXCLUSION CRITERIA:

- Exertional dyspnea, syncope, presyncope, or angina

- Left ventricular ejection fraction (LVEF) <50%

- Clinically significant aortic regurgitation or mitral valve disease

- Prior cardiac surgery

- Positive cardiac stress test

- Medical conditions such as cancer

OTHER SALIENT FEATURES/CHARACTERISTICS:

- Body mass index: 24.5 kg/m2

- Coronary artery disease: 4-5%

- Mean EuroSCORE II: 0.9%

- Cause of aortic stenosis: bicuspid valve: 60%, degenerative: 33%, rheumatic: 6%

- Peak velocity: 5.1 m/sec, mean gradient 64 mm Hg, AVA 0.64 cm2

- Mean LVEF: 65%

PRINCIPAL FINDINGS -

The primary outcome of operative mortality or cardiovascular mortality at 4 years, for early surgery vs. watchful waiting, was 1% vs. 6% (p < 0.05). At 8 years: 1% vs. 26% (p = 0.003).

- Cardiovascular mortality at 4 years: 1% vs. 15% (hazard ratio 0.09, 95% confidence interval 0.01-0.67, p < 0.05)

SECONDARY OUTCOMES FOR EARLY SURGERY VS. WATCHFUL WAITING:

- All-cause mortality at 8 years: 10% vs. 32% (p < 0.05)

- Heart failure hospitalization: 0% vs. 11% (p < 0.05)

- Any secondary endpoint or AVR in watchful waiting group: 62% at 4 years, 92% at 8 years

INTERPRETATION - The results of this trial indicate that early surgery among patients with asymptomatic but very severe aortic stenosis (AVA 0.75 cm2, mean gradient ≥50 mm Hg, peak velocity ≥4.5 m/sec) results in improved survival out to 8 years compared with watchful waiting. These are important findings, and will likely change guidelines on this topic. Currently, surgery for asymptomatic aortic stenosis has a Class IIb indication in the American Heart Association/American College of Cardiology valvular heart disease guideline. There are observational data that patients with peak velocity >5 m/sec may particularly benefit, especially if they are low-surgical risk candidates.

A few noteworthy points: Although the surgical risk of these patients was low, there were zero operative deaths, which is likely a reflection of experienced operators/institutions. The generalizability of these findings may thus be harder in a more heterogeneous landscape such as in the United States. Also, it is interesting to note that patients in the watchful waiting arm could go as long as 8 years without crossing over (only two cross-overs to surgery), despite having such severe aortic stenosis. Other studies have suggested this “latent” period (i.e., no symptoms despite severe aortic stenosis) to be about 1-2 years. This cohort had a very high proportion of bicuspid aortic stenosis patients, which may be a partial reason for this. Also, exercise testing was only selectively employed; thus, some patients could have “hidden” symptomatic aortic stenosis, which would have been unmasked with a stress test. The EARLY-TAVR trial is looking to enroll a similar asymptomatic population – all patients are required to undergo exercise testing for this reason. Finally, these results are not applicable to TAVR; EARLY-TAVR and other studies will help inform this question.