Title: What is the best test for the non-invasive diagnosis of significant coronary artery disease?
Funder: Department of Health and Social Care

Abstract: Research question: Which achieves superior diagnostic accuracy in suspected stable coronary artery disease (CAD): non-invasive imaging with (1) cardiovascular magnetic resonance, or (2) computed tomography coronary angiography (CTCA) with fractional flow reserve (FFRCT)? BackgroundCAD is the leading cause of death and disability in the UK. Despite major international guidelines recommending the diagnostic use of non-invasive functional imaging in patients with suspected CAD, the 2016 NICE update recommends anatomical imaging with CTCA. Despite its excellent negative predictive value (enabling the safe exclusion of significant CAD), positive predictive value remains suboptimal (c.50%), potentially leading to the exposure of substantial numbers of individuals to unnecessary invasive coronary angiography (ICA). Hence, the optimum management of patients with a positive CTCA remains uncertain. FFRCT is a novel technique affording functional data from routinely acquired CTCA scans (without additional imaging or pharmacological stress). Preliminary studies indicate a reduction in unnecessary ICA with CTCA/FFRCT relative to CTCA alone. However, it is yet to be evaluated in real-world situations or be compared with the current non-invasive gold standard, cardiovascular magnetic resonance (CMR), whose excellent diagnostic performance may itself be further enhanced by recent technical innovation (involving quantitative analysis). Hence, before NICE-recommended adoption of CTCA [with additional FFRCT], requiring major changes to the structure of UK imaging services, it is appropriate that CTCA/FFRCT be rigorously compared with CMR. The possibility of hybrid approaches should also be evaluated.Aims and objectives: to determine the optimum non-invasive diagnostic strategy in patients with suspected CAD, specifically whether: 1) CTCA/FFRCT achieves non-inferior accuracy compared with CMR 2) Quantitative CMR achieves superior accuracy compared with qualitative CMR and CTCA/FFRCT 3) Hybrid CMR/CT approaches achieve superior accuracy compared with individual modalities MethodsProspective single-centre diagnostic accuracy study involving 300 patients with suspected CAD referred for ICA. Prior to ICA, subjects will undergo CTCA/FFRCT and CMR, with evaluation of diagnostic accuracy for identifying significant CAD (defined by invasive fractional flow reserveTimelines for delivery: Study setup - 6m Recruitment -h; 3y Analysis and reporting -h; 18m Future grant preparation -h; 12mAnticipated impact and dissemination The proposed study will provide robust comparative performance data for CTCA/FFRCT, CMR and potential hybrid imaging strategies. Determining the optimum diagnostic strategy will improve the targeting of invasive procedures, in turn improving service delivery and cost-effectiveness. Importantly, the avoidance of unnecessary ICA will improve patient outcomes in the management of CAD (an established goal of NHS England). Hence, this study will be of direct relevance to NHS organisations, informing decisions regarding the structuring of cardiac imaging services in the next 5-10 years. It is anticipated that our findings will be of significant interest to NHS commissioning groups (as outlined above), wider scientific communities and the general public. Study findings will be published in high impact scientific journals, being presented at national and international meetings, and communicated with NHS commissioners. Broader audiences will be reached through the hospital website. The results may also interest media outlets, and we will liaise with the NIHR and local institutional communications teams.

Lay abstract: Aim To determine the best way to diagnose patients with severely narrowed heart arteries. Background Coronary heart disease is the leading cause of death and disability in the UK (2.3 million affected individuals, 70,000 deaths annually). Like all muscles, the heart has a blood supply. Narrowed blood vessels restrict blood flow to the heart, causing chest pain or sometimes a heart attack. Good treatments are available but we first need to identify who has a problem. We can use a test called a 'coronary angiogram': this involves inserting a flexible tube into a person's groin or arm, and passing it to the heart. We then inject a dye and take X-ray pictures. Although this clearly shows any blood vessel narrowings or blockages, the test can be painful, and there is a risk of things going wrong. Therefore, guidelines recommend using scans first, as they are safer and less unpleasant. Recently, national guidelines were changed to recommend a specific scan called 'computed tomography coronary angiography', or CTCA. This helps to rule out disease in some patients who don't have a problem. However, about half the patients who don't have a problem will also seem to have something wrong according to this scan. This can be very worrying for patients, especially as they may then need a 'coronary angiogram' test to check if they really do have a narrowing . We think we can help by using different scans instead, meaning more people can be reassured they are healthy and don't need an unpleasant test. Fractional flow reserve with computed tomography (FFRCT) is an exciting new test which uses a supercomputer to analyse the CTCA scan pictures. A few studies involving carefully selected patients show that this is more accurate than using a CTCA scan alone. However, before we start using it more widely (which means the NHS needs many more scanners), we need to compare it with other types of scans. Currently, the best performing is a heart magnetic resonance imaging (MRI) scan. A bonus with MRI is that it doesn't use radiation, and recent innovations may make it even more accurate. Deciding which approach is more accurate will benefit patients and the NHS by helping to avoid unnecessary unpleasant tests which require hospital admission. Design and methodsThe study will involve 300 patients with chest pain who have been referred to hospital for a coronary angiogram. Before this, they will have both types of scan. We will then compare the results to decide which is more accurate. We will also ask patients their opinion and which they prefer. Patient and public involvement Patient involvement is an integral part of our study. Its design was strongly influenced by a patient experience survey and discussions with the Leicester Biomedical Research Centre Cardiovascular PPI group, which has approved the final study design. They will also help write the study documents (e.g. patient information leaflet). The study steering group will include lay members. We envisage that patient groups will play a key role in promoting the study. Social media resources (Facebook/Twitter) will provide peer support, tell participants about study progress, and help publicise our findings. Dissemination Our findings will be of significant interest to NHS commissioning groups, wider scientific communities and the general public. Study findings will be published in scientific journals, being presented at national and international meetings, and communicated with NHS commissioners to help inform the design of future cardiac services. Broader audiences will be reached through the hospital website. The results may be of interest to media outlets, and we will talk to the NIHR and local institutional communications teams.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR