Myocardial Fibrosis and Early Intervention in Asymptomatic Patients with Severe Aortic Stenosis Insights from The EVOLVED Randomized Controlled Trial

Importance. Myocardial fibrosis burden has been associated with adverse clinical outcomes in symptomatic patients with aortic stenosis.Objectives. To determine whether midwall myocardial fibrosis burden is associated with adverse clinical outcomes in asymptomatic patients, and whether those with more fibrosis derive greater benefit from early intervention.Design. Post-hoc analysis of a randomized controlled 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 midwall fibrosis on cardiac magnetic resonance.Intervention. Early intervention with transcatheter or surgical aortic valve replacement.Main Outcomes and Measures. Primary outcome was all-cause death or unplanned aortic stenosis-related hospitalization. Secondary outcomes included the individual components of the primary outcome.Results. In 224 trial participants (mean age 73 (standard deviation 9) years, 28% women and mean aortic valve peak velocity 4.3 (0.5) m/s) with median follow-up of 42 months, fibrosis burden (per 1% increase) was associated with an increase in the primary endpoint (hazard ratio (HR), 1.23 95% confidence interval 1.08-1.37) and its component of unplanned aortic stenosis-related hospitalizations (HR 1.22 1.03-1.40) but not all-cause death (HR 1.17 0.98-1.35). There were no interactions between randomization arm and the midwall fibrosis burden for the primary (Pinteraction=0.39) or secondary endpoints. In patients with high fibrosis burden above the median, the primary endpoint occurred in 12/59 (20%) of those randomized to early intervention and 17/53 (32%) of those randomized to guideline-directed conservative management (HR 0.62 0.29–1.28). For the individual components, all-cause death occurred in 9 (15%) and 10 (19%) patients respectively (HR 0.84 0.33-2.07), and unplanned aortic stenosis-related hospitalization in 4 (7%) and 13 (25%) patients respectively (HR 0.27 0.08-0.77). In patients with low fibrosis burden below the median, there were no differences in the primary outcome (HR 1.05 0.39-2.86) or its components between intervention groups.Conclusions and Relevance. In asymptomatic patients with severe aortic stenosis, higher midwall fibrosis burden was associated with adverse outcomes. There was no demonstrable heterogeneity by the degree of midwall fibrosis for the treatment effects of early surgical or transcatheter aortic valve replacement compared to clinical surveillance.Trial Registration:Clinicaltrials.gov Identifier: NCT03094143