EVOLVED Trial: Early Aortic Valve Replacement Fails to Show Mortality Benefit in Asymptomatic Patients with Fibrosis
Key Insights
The EVOLVED study found that early aortic valve replacement (search) (AVR) in asymptomatic patients with myocardial fibrosis did not reduce all-cause mortality or unplanned aortic stenosis (search)-related hospitalizations.
While the primary endpoint was not met, early intervention was associated with a significant reduction in unplanned hospitalizations for aortic stenosis (search)-related reasons.
Patients receiving early AVR reported improved NYHA symptom class at 12 months compared to those managed with guideline-directed conservative treatment.
WASHINGTON, DC—The EVOLVED trial, presented at TCT 2024, reveals that an early aortic valve replacement (search) (AVR) strategy, utilizing either transcatheter aortic valve implantation (TAVI (search)) or surgical AVR (SAVR), does not significantly decrease the risk of all-cause mortality or unplanned hospitalizations related to aortic stenosis (search) in asymptomatic patients who exhibit evidence of myocardial fibrosis.
The study, involving 244 patients, challenges the potential of using cardiac magnetic resonance (CMR) to identify and treat asymptomatic individuals with severe aortic stenosis (search) and early signs of structural remodeling. Despite the neutral outcome regarding the primary endpoint, researchers noted a positive trend in reducing unplanned hospitalizations due to aortic stenosis.
Key Findings and Interpretations
Marc Dweck, MBChB, PhD (University of Edinburgh, Scotland), a senior investigator in the EVOLVED trial, emphasized the importance of quality of life for patients. He stated, "Intervening early isn't necessarily going to make you live longer because there's other things that come into play, but it can make you live better. It keeps you out of hospital. Our patients were less symptomatic in a year—the people who had an early intervention, their symptomatic status was the same a year down the line as it was at baseline whereas the people who had delayed intervention were more symptomatic."
Chetan Huded, MD (Saint Luke’s Mid America Heart Institute/University of Missouri—Kansas City), who was not involved in the study, expressed surprise at the trial's negative outcome, considering previous smaller trials like RECOVERY and AVATAR had indicated benefits from early surgical AVR in asymptomatic patients with severe aortic stenosis (search). He noted that the EVOLVED trial included older patients with less severe aortic stenosis, which may account for the differing results. Huded also pointed out the difficulty in demonstrating significant differences in clinical events like mortality in smaller studies.
Benjamin Hibbert, MD, PhD (Mayo Clinic, Rochester, MN), another interventional cardiologist, suggested that using cardiac fibrosis to stratify asymptomatic patients for early AVR may not be an effective approach. He cautioned against investing further efforts into this strategy, stating, "It’s really hard to take someone who’s doing well and make them better."
Trial Design and Results
The EVOLVED trial randomized 224 patients (mean age 73 years, 28% female) with asymptomatic severe aortic stenosis (search) and midwall scarring to either early AVR or guideline-directed conservative management. The early intervention group saw 94% of patients undergoing AVR, with 86% receiving a new valve within 12 months (75% via SAVR). In the conservative treatment arm, 77% eventually received a new valve (55% via SAVR), with a median time to intervention of 20.2 months.
Early intervention did not significantly reduce the risk of all-cause mortality or unplanned hospitalization for aortic stenosis (search) (HR 0.79; 95% CI 0.44-1.43). However, it did show a 63% lower risk of unplanned hospitalizations (HR 0.37; 95% CI 0.16-0.88). Additionally, an improvement in NYHA symptom class from baseline to 12 months was more frequent in the early intervention group (80% and 18% in NYHA class I and II, respectively, compared to 62% and 29% in the conservative arm).
Limitations and Future Directions
The EVOLVED trial was initially planned for 356 patients but was underpowered due to recruitment challenges during the COVID-19 (search) pandemic. Despite this, Dweck believes that increasing the sample size would not alter the main findings, as mortality in this elderly population is influenced by factors beyond aortic valve disease.
Hibbert noted that the endpoint of aortic stenosis (search)-related hospitalizations was unusual and that the Kaplan-Meier curve flattened beyond one year, suggesting no further hospitalizations related to aortic stenosis, which he found difficult to reconcile.
Looking ahead, Dweck suggests that the decision to pursue early intervention should be individualized, considering patient preferences and proactive health management. Cardiothoracic surgeon Suyog Mokashi, MD (Temple University, Philadelphia, PA), advocates for close surveillance of asymptomatic patients with severe aortic stenosis (search) to detect any symptom onset promptly.
While CMR-assessed fibrosis may not directly influence AVR decisions based on EVOLVED, the collective data from EVOLVED, EARLY TAVR, RECOVERY, and AVATAR suggest potential benefits of early intervention in select asymptomatic patients.