Assessing the impact of early aortic valve replacement on irreversible heart damage and patient reported outcomes in asymptomatic Aortic Stenosis.

Research questions: 1.

Does earlier aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) lead to less myocardial scar burden and better patient reported outcome measures (PROMs)? 2. Is myocardial scar burden related to long-term health outcomes? 3. What is the acceptability of early AVR for asymptomatic patients?

Background: The timing of intervention for severe AS is shifting, with cardiac magnetic resonance (CMR) imaging playing a crucial role in quantifying and tracking the variable remodelling response.

Focal fibrosis (late gadolinium enhancement, LGE) is present in asymptomatic AS, progresses rapidly within 12 months, is irreversible and remains a poor prognostic marker post-AVR. Randomised trials are therefore addressing whether earlier AVR in asymptomatic severe AS improves long-term outcomes.

However, the acceptability of invasive treatment to the asymptomatic patient and the effect of earlier AVR on residual scar burden and PROMs remains unknown.

Aims and objectives: To establish the effect of early AVR on myocardial scar burden and PROMs, and identify barriers to implementation of such a strategy, in a CMR and patient experience sub-study of randomised trials (EASY-AS/EVOLVED).

Methods: Workpackage-1: CMR sub-study -CMR sub-study in participants of EASY-AS/EVOLVED randomised trials of early AVR vs 'watchful waiting' in asymptomatic severe AS. -CMR at randomisation and at 3-year. -Primary outcome measure: difference in myocardial scar burden measured by late gadolinium enhancement (LGE) on CMR at 3-years between groups.

Workpackage-2: Patient Experience sub-study -Effect on PROMs will be assessed using: validated generic (EQ5D) and disease-specific (MLHF) questionnaires; disability-free survival (WHODAS-2); peri-operative recovery ('days at home within 30 days of surgery',DAH30). - A nested qualitative sub-study will explore views and barriers to implementation of invasive treatment whilst asymptomatic, from the perspective of participants of the trials, their carers and wider stakeholders. -A Patient Advisory Group will be formed to help co-develop this workpackage, and identify and prioritise important themes, as well as help with interpretation and disseminations of findings, adding rigour to its conclusions.

Timeline of delivery: Study set-up (6 months: including 4 months pre-Fellowship start date) Recruitment (18 months) Follow-up (overlapping with recruitment, including follow-up of some already recruited to EVOLVED, 44 months) Analysis and reporting (8 months) Future grant preparation (6 months) Anticipated impact and dissemination: This study will confirm whether early AVR reduces irreversible myocardial damage and provide strong evidence on whether LGE can be used as a risk-stratification tool in AS.

The nested qualitative study will provide valuable transferrable knowledge to help inform and implement future changes in clinical practice, and design future trials on intervention for other asymptomatic conditions.

The results of this study will be of interest to the wider clinical community, NHS commissioning groups and patients with AS (and their carers), as the results may change guidelines and help devise an implementation strategy. Findings will be published in high-impact journals and presented at medical conferences.

We will also organise a Stakeholders' Conference at the end of the study to communicate our results with all involved. Broader audiences will be reached through social media.