A multicenter, randomized clinical trial has found that early aortic valve intervention did not significantly improve clinical outcomes compared to guideline-directed conservative management in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. The study, conducted across 24 cardiac centers in the UK and Australia between August 2017 and October 2022, enrolled 224 patients and followed them until July 2024. The findings, published in JAMA, suggest that the strategy of watchful waiting remains a reasonable approach for these patients.
The primary outcome, a composite of all-cause death or unplanned aortic stenosis-related hospitalization, occurred in 18% of patients in the early intervention group and 23% in the conservative management group (hazard ratio, 0.79; 95% CI, 0.44-1.43; P = .44). This indicates no statistically significant difference between the two approaches. The trial was designed to investigate whether early aortic valve intervention could improve clinical outcomes in patients with asymptomatic severe aortic stenosis and myocardial fibrosis, hypothesizing that it would reduce the incidence of the primary composite outcome.
Trial Design and Key Findings
The EVOLVED trial was a parallel-group, multicenter, prospective, randomized, open-label, masked end point trial. Patients aged 18 years or older with severe aortic stenosis, defined as aortic valve peak velocity ≥4.0 m/s or aortic valve peak velocity ≥3.5 m/s with an indexed aortic valve area <0.6 cm²/m², and without symptoms attributable to their valve disease were included. Participants were screened for adverse left ventricular remodeling using plasma cardiac troponin I concentration and electrocardiography. Those meeting the criteria underwent cardiac magnetic resonance imaging to assess for midwall late gadolinium enhancement, indicative of myocardial fibrosis.
While the primary endpoint was not met, early intervention was associated with a lower 12-month rate of New York Heart Association (NYHA) class II-IV symptoms compared to conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]). Additionally, there were fewer unplanned aortic stenosis-related hospitalizations in the early intervention group (6%) compared to the conservative management group (17%) (hazard ratio, 0.37 [95% CI, 0.16-0.88]).
Implications and Context
Aortic stenosis is the most common heart valve disease in high-resource countries, with prevalence increasing in the aging population. Current guidelines recommend that asymptomatic patients be observed, with aortic valve intervention deferred until symptom onset. However, symptom assessment can be challenging due to limited mobility or comorbidities.
The potential benefits of early aortic valve intervention are most likely to be apparent in patients at the highest risk of aortic stenosis-related clinical events. Myocardial fibrosis, identified via cardiac magnetic resonance imaging, is a strong independent predictor of heart failure and mortality in aortic stenosis patients. This study aimed to determine if early intervention could improve outcomes in this high-risk group.
Expert Commentary
"In this study that compared early aortic valve intervention with guideline-directed conservative management in asymptomatic patients with severe aortic stenosis and subclinical evidence of cardiac decompensation, there was no demonstrable difference in the primary composite end point of all-cause mortality or unplanned aortic stenosis–related hospitalization," the authors wrote. They also noted, "However, the 95% CI around the primary end point is wide and encompasses potential clinically meaningful benefits or harms from early intervention. The findings are not definitive, and further research will be required to confirm the trial findings."
Limitations
The trial faced limitations, including recruitment challenges due to the COVID-19 pandemic, which prevented achievement of the original sample size. The authors also noted that because the primary end point is null, any conclusions about the secondary end points must be designated as hypothesis-generating. The rate of transcatheter aortic valve intervention was higher in the guideline-directed conservative management group than the early intervention group, reflecting better access to transcatheter aortic valve intervention during study conduct and urgent intervention following unplanned aortic stenosis-related hospitalizations. Finally, the percentage of female participants in this trial was low (28%), which could reflect that female patients may have less advanced myocardial remodeling than males in response to the same level of valvular stenosis, and this limits the generalizability of the trial findings.
Conclusion
While early aortic valve intervention did not demonstrate a significant impact on the primary composite outcome, the study suggests potential benefits in reducing heart failure symptoms and unplanned hospitalizations. Further research, including the ongoing EASY-AS trial, is needed to confirm these findings and refine treatment strategies for asymptomatic patients with severe aortic stenosis and myocardial fibrosis.
