Award Title: First-phase ejection fraction guided management of aortic stenosis
Funder: Health Education England

Abstract: Background Aortic stenosis (AS) is the most common form of primary heart valve disease in moreeconomically developed countries, with a prevalence of moderate or severe disease of approximately 3% in those aged 75 years.It is often asymptomatic but when symptoms develop and/or there is a reduction in left ventricular (LV) ejection fraction (EF), survival without intervention is poor. Symptoms or reduced EF are thus Class I indications for aortic valve replacement (AVR) in severe AS. However, the management of asymptomatic severe AS with preserved EF is challenging and a measure that would accurately predict survival in asymptomatic AS would be invaluable with regard to decisions on expectant management or elective AVR. We have developed a novel measure of early systolic function: first phase ejection fraction (EF1) that shows promise in robustly predicting outcomes in patients with asymptomatic AS.Aims and objectives To examine whether patients with lower EF1 are more likely to develop symptoms and need more intensive clinical monitoring or early surgical intervention than those with preserved EF1. In addition, in an exploratory study in patients proceeding to AVR, we will assess whether EF1 is predictive of outcomes after AVR since this is another potential use of EF1. Methods Patients with asymptomatic severe AS (n=300) will be recruited from Guy's and St Thomas' NHS Foundation Trust and King's College London NHS Foundation Trust. Patients will have clinical examination, medical history review, echocardiography, central blood pressure measurements, blood test for biochemical biomarkers, a 6 minute walk test and, if clinically indicated to clarify symptom status, an exercise tolerance test. EF1 will be measured by an automated method developed in collaboration with Tomtec. Patients will be followed-up at 6 monthly intervals according to standard care for a minimum of 12 months or until AVR or death by a clinician blinded to the value of EF1. The primary outcome will be a composite event of: indication for AVR (based on a reduction in EF Timeline for delivery Milestone 1: setup imaging analysis workstations with Tomtec on both sites (Months 1-2) Milestone 2: patient recruitment (Months 3-21) Milestone 3: patient monitoring and follow up (Months 3-33) Milestone 4: Data analysis, conference presentation and publication (Months 30-36) Anticipated impact and dissemination The findings of this fellowship will benefit patients and service delivery in the NHS by establishing EF1 guided management of patients with AS. This will determine which patients need close monitoring or immediate valve replacement and which patients can be reassured and monitored less frequently.

Lay Abstract: A new test (called EF1) may tell us which patients with a narrowed heart valve need an operation. Aim: I think a new way of measuring how well the heart pumps (called EF1) will help to provide the best care for patients with a narrowed heart valve. I will see if the test can tell which patients need an operation to replace the narrowed valve. I will improve the test so that it can be made automatically during a standard heart scan. Background: Sometimes a valve at the top of the heart becomes narrower with age. It stops pumping properly and prevents the blood being pumped out of the heart from returning into the heart. This is known as 'aortic stenosis'. The narrowed valve makes the heart work harder to pump blood and puts a strain on the heart. Some people with this condition don't notice anything wrong until it is too late. In these people, the heart suddenly gives up from the strain and they may die. I have developed a new test called EF1 that measures how well the heart is pumping under the strain of the narrowed valve. I think this will tell which patients should have an operation to keep them feeling well. I will see if the test can tell which patients need an operation to replace the narrowed valve and which patients can be safely seen by doctors once or twice a year. Design and methods: Patients with a narrowed valve who have not developed symptoms, such as feeling short of breath, will be asked to volunteer to have the new test. About 300 patients will have the new test so that I have enough people to make a decision whether this test works or not. The test will be done during the ultrasound heart scan that is done in all patients with suspected heart problems. As part of the project I will test an automatic computer system for measuring EF1. If this works well, then all doctors and clinical care workers will be able to use the test easily and reliably. After patients have the test, I will see them regularly to find how well the test can predict which patients develop symptoms. Potential benefits to patients and the NHS: I hope the results of this research will help patients and improve clinical services in the NHS by helping us give the right treatment at the right time. Patient and public involvement: The patient and public review panel from our Cardiovascular Imaging group helped me to write this summary. This group will be helping me to explain to patients what will happen if they volunteer for this research and explain the results at the end of the project.

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: CARDIOVASCULAR