The EVOLVED trial found that early aortic valve intervention in patients with asymptomatic severe aortic stenosis (AS) and mid-wall myocardial fibrosis on magnetic resonance imaging did not reduce the incidence of the composite primary endpoint of all-cause death or unplanned aortic stenosis hospitalization compared with guideline-directed conservative management.
Findings were reported today at TCT 2024, the annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The results were also published simultaneously in the Journal of the American Medical Association.
Aortic valve replacement via surgical or transcatheter approaches is the primary treatment for severe AS but it is reserved for those with symptomatic disease or those with asymptomatic disease and a left ventricular ejection fraction less than 50 percent. Myocardial fibrosis is a key driver of left ventricular decompensation in AS and is a powerful predictor of patient mortality.
Late gadolinium enhancement on cardiac magnetic resonance imaging can directly visualize myocardial fibrosis, providing an objective marker that the left ventricle is starting to decompensate. Whether early intervention for asymptomatic severe AS in patients with myocardial fibrosis can improve outcomes is unknown.
The EVOLVED trial was an international multicenter prospective randomized open-label blinded-endpoint trial, conducted at 24 sites in the United Kingdom and Australia. Participants were asymptomatic with severe AS (aortic valve peak velocity ≥ 4.0 m/s, ≥ 3.5 m/s with an indexed aortic valve area <0.6 cm2/m2). Key exclusion criteria included left ventricular ejection fraction less than 50%, concomitant severe aortic or mitral regurgitation, eGFR greater than 30 mL/min/1.73 m2, contraindications to magnetic resonance, or patients deemed unfit for intervention.
A total of 427 participants were screened. Of these subjects, 278 were eligible for cardiac magnetic resonance and the 224 participants with myocardial fibrosis were randomized to early intervention (n=113) or guideline-directed conservative management (n=111). The 49 participants without myocardial fibrosis were entered into an observational registry to maintain blinding. In addition, the choice of surgical or transcatheter valve replacement was determined by the local heart valve team.
The median time-to-intervention was 15 months shorter among patients randomized to valvular intervention. The primary end point, consisting of the composite of all-cause death or unplanned aortic stenosis-related hospitalization, was not met [Hazard Ratio 0.79 (95% CI 0.44 to 1.43, p=0.44)]. The secondary endpoint of all-cause death was also not met [Hazard Ratio 1.22 (95% CI 0.59 to 2.51)]. However, unplanned aortic stenosis-related hospitalization was less in the early intervention group [Hazard Ratio 0.37 (95% CI 0.16 to 0.88)]. In addition, NYHA Symptom Class at 12 months favored the early intervention group [Odds Ratio 0.37 (95% CI 0.20 to 0.70).
Although early intervention did not reduce the incidence of the composite primary endpoint of all-cause death or unplanned aortic stenosis hospitalization, our study did find other benefits The principal benefit of early intervention appears to be in the reduction of emergency hospitalization and in preventing the development of limiting symptoms. This appears to be a consistent finding across all the trials to date and an important outcome for patients with this condition."
Mark R. Dweck, MD, PhD, Chair of Clinical Cardiology, University of Edinburgh
Dweck was also a British Heart Foundation Senior Clinical Research Fellow and a Consultant Cardiologist at the University of Edinburgh.
The study was funded by Sir Jules Thorn Charitable Trust.
Dr. Dweck reported the following disclosures: consulting fees/honoraria from Novartis, AstraZeneca, Pfizer, Bristol Myers Squibb, Amarin, Jupiter Bioventures, Beren and Silence Therapeutics.
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