Dr. Ayşe Nur Özkaya İbiş

Title:

Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Left Ventricular Myocardial Fibrosis (EVOLVED Trial)

Presentation at: TCT 2024

Link: https://jamanetwork.com/journals/jama/fullarticle/2825540

Introduction

Aortic stenosis (AS) is the most common valvular heart disease in developed countries, with increasing prevalence among aging populations. Current guidelines recommend aortic valve replacement (AVR) primarily for patients with severe symptomatic AS or those with a left ventricular ejection fraction (LVEF) below 50%. In asymptomatic patients, watchful and waiting until symptom onset is generally advised. Emerging evidence suggests that early AVR could improve clinical outcomes for younger, asymptomatic patients with severe AS and preserved ejection fraction. The potential benefits of early intervention may be particularly significant for patients at high risk of AS-related complications, necessitating the identification of reliable biomarkers for risk stratification. Cardiac magnetic resonance imaging (MRI) provides a robust marker for myocardial fibrosis, as mid-wall late gadolinium enhancement indicates fibrosis, which is associated with the transition from left ventricular hypertrophy to heart failure in AS.

Objective

This study investigates whether early valve intervention reduces the incidence of death or unplanned AS-related hospitalizations in asymptomatic patients with severe AS and myocardial fibrosis.

Methods

The EVOLVED trial is a parallel-group, multicenter, prospective, randomized, open-label, blinded endpoint study conducted across 24 centers in the United Kingdom and Australia between August 2017 and October 2022. The study enrolled asymptomatic patients aged 18 and older with severe AS, confirmed as asymptomatic through exercise stress testing or, if not feasible, based on detailed clinical history. Exclusion criteria included symptomatic AS, LVEF below 50%, significant aortic or mitral regurgitation, estimated glomerular filtration rate below 30 mL/min/1.73 m², or contraindications for MRI.

All participants underwent cardiac MRI, and those with mid-wall myocardial fibrosis were randomized 1:1 to early aortic valve intervention or guideline-directed medical management. In the early intervention group, the choice between surgical AVR (SAVR) and transcatheter aortic valve implantation (TAVI) was determined by the heart team. The primary endpoint was a composite of all-cause mortality and unplanned AS-related hospitalizations. Secondary endpoints included the individual components of the primary endpoint, symptom burden (assessed by NYHA classification), and development of LVEF dysfunction (defined as LVEF <50%) at 12 months post-randomization.

Results

During the study period, 427 asymptomatic severe AS patients were screened, with 224 identified as having myocardial fibrosis via MRI. Of these, 113 patients were randomized to early valve intervention, and 111 to conservative management. The mean patient age was 73 years, with 28% female and 29% having bicuspid aortic valves.

In the early intervention group, 106 patients (94%) underwent AVR, of which 80 (75%) received SAVR and 26 (25%) received TAVI. In the conservative group, 85 patients (77%) eventually required AVR during follow-up, with 47 (55%) undergoing SAVR and 38 (45%) undergoing TAVI.
The primary composite endpoint of all-cause mortality or unplanned AS-related hospitalization occurred in 20 patients (18%) in the early intervention group and 25 patients (23%) in the conservative group (HR, 0.79; 95% CI, 0.44–1.43; p=0.44). Analysis of the components revealed no significant difference between groups in all-cause mortality or AS-related mortality. For unplanned AS-related hospitalizations and symptom burden, seven patients (6%) in the early intervention group and 19 patients (17%) in the conservative group experienced unplanned AS-related hospitalizations (HR, 0.37; 95% CI, 0.16–0.88). At 1-year follow-up, NYHA class II-IV symptoms were observed in 21 patients (20%) in the early intervention group and 39 patients (38%) in the conservative group (OR, 0.37; 95% CI, 0.20–0.70).

Conclusions

The study found that early aortic valve intervention in asymptomatic patients with severe AS and myocardial fibrosis did not significantly affect overall mortality or unplanned AS-related hospitalizations.

Commentary

The optimal timing of AVR in severe AS remains a major clinical question. Current guidelines recommend intervention as a Class I indication for symptomatic patients, but for certain asymptomatic patients with elevated BNP levels, reduced exercise tolerance, rapid disease progression, or very severe AS, intervention is a Class IIa consideration. Hence, identifying biomarkers for cardiac deterioration in asymptomatic patients with severe AS is a clinical priority. Myocardial fibrosis, detectable by cardiac MRI, is an early marker of left ventricular dysfunction, making the EVOLVED trial highly anticipated within biomarker research. However, the trial results temper expectations for MRI’s role in guiding early intervention in this context.
While the AVATAR and RECOVERY trials showed benefits of early SAVR in younger, asymptomatic patients, the EVOLVED trial, with 224 participants, did not demonstrate a primary endpoint benefit of early AVR. This difference may stem from EVOLVED’s older patient cohort and less severe AS profiles.

The authors note that while early intervention may not reduce mortality, it appears to improve symptom burden, an important outcome for the geriatric population where quality of life and symptom management are key due to comorbidities. Further studies are necessary to determine if early intervention could become standard practice for this patient subset.