Title: Assessing the impact of early aortic valve replacement on irreversible heart damage and patient reported outcomes in asymptomatic Aortic Stenosis.
Funder: Department of Health and Social Care

Abstract: 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.

Lay abstract: Background: 'How does a patient's quality of life change following heart surgery?' is the number-one national priority in UK heart surgery, set by a collaborative piece of work done by the James Lind Alliance. This is a non-profit making initiative that brings patients, carers and clinicians together to identify the top-10 unanswered questions for healthcare research, and was recently conducted for heart surgery. 'When should heart valve intervention occur in asymptomatic patients?' is the number-five priority identified. This project will address these important questions in patients with aortic stenosis, the most common age-related valve problem requiring surgery in the western world. Aortic stenosis is narrowing of the aortic valve, and is associated with ageing. Current guidelines recommend waiting till patients develop symptoms (chest pain, breathlessness and dizzy spells/fainting) before possible open heart surgery to replace the valve is offered. However, studies using MRI scanning of the heart have shown that upto half of the patients already have 'scarring' in the heart by the time symptoms develop. Furthermore, scarring is not fully reversed even after surgery. This suggests that some patients are being offered treatment too late. There are two randomised trials in the UK (EASY-AS and EVOLVED) to see if valve replacement before symptoms will result in better survival. Aims: The aim of my project is to compare the effect of early valve replacement for patients with no symptoms versus waiting for symptoms, on the amount of scarring in the heart. We want to know if early treatment leads to less overall scarring at the end, and leads to better quality of life and recovery after surgery. We will also look at barriers to offering early open heart surgery to patients with no symptoms. Design and methods: The research will consist of two parts: A. MRI-We will invite participants of the EASY-AS and EVOLVED randomised trials to have 2 MRI heart scans: at recruitment and 3 years after being randomly allocated to early aortic valve replacement vs 'watchful waiting' (patients will not be able to choose). - The main outcome measure will be the difference in the amount of scarring in the hearts between the two groups. B. Patient experience-Qualitative study: I will work closely with research experts at the University of Sheffield to explore the views of participants and their carers, on potential open heart surgery before symptoms. -Patient Reported Outcome Measures: I will assess the impact of the different treatments on patients' quality of life, disability-free survival, and recovery after surgery, using questionnaires. Patient and public involvement (PPI): I have presented the study ideas at the local heart and heart surgery PPI groups and received positive feedback. This plain English summary was also circulated to the PPI group. I sent surveys to 19 previous participants of a research study, 15 of whom responded and 11 have agreed to be contacted for further help with the study. Going forwards, I plan to form a Project Advisory Group to help develop the topics to be addressed in the qualitative study, and help analyse and share its results. Dissemination: I will organise a 'conference' for those involved to share my findings with patient, clinicians and policy makers. I will ask the Project Advisory Group to help draft a plain English summary of findings, and ask them to prepare a statement for media. The results will be published in medical journals and presented at international conferences and communicated more widely by using media, social media and patient websites. The results from this project may also help the NHS plan future treatments for asymptomatic patients undergoing invasive treatments.

Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR