Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis: The EVOLVED Randomized Clinical Trial

Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis.

Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

Design: Prospective randomized open label blinded endpoint trial conducted between August 2017 and October 2022.

Setting: Twenty-four Cardiac Centers across the United Kingdom and Australia.

Participants: Asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

Interventions: Early valve intervention with transcatheter or surgical aortic valve replacement.

Main Outcomes and Measures:
The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first event intention-to-treat analysis. There were 9 secondary outcomes including the components of the primary outcome and symptom status at 12 months.

Results:
The trial enrolled 224 eligible patients (mean age 73 (standard deviation 9) years, 28% women and mean aortic valve peak velocity 4.3 (0.5) m/s) of the originally planned sample size of 356 patients. The primary endpoint occurred in 20/113 (18%) patients in the early intervention group and 25/111 (23%) patients in the guideline-directed conservative management group (hazard ratio, 0.79 [95% confidence interval 0.44 to 1.43], P=0.44; between-group difference -4.82 [95% confidence interval -15.31 to 5.66]). Of 9 prespecified secondary endpoints, 7 showed no significant difference. All-cause death occurred in 16/113 (14%) and 14/111 (13%) patients (hazard ratio, 1.22 [95% confidence interval 0.59 to 2.51]) and unplanned aortic stenosis hospitalization occurred in 7/113 (6%) and 19/111 (17%) patients (hazard ratio, 0.37 [95% confidence interval 0.16 to 0.88]) respectively. Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 (19.7%) versus 39 (37.9%); odds ratio 0.37 [95% confidence interval 0.20 to 0.70]).

Conclusions and Relevance:
In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% confidence interval around the primary endpoint, with further research needed to confirm these findings.