Title: Novel Cardiac MRI methods for the diagnosis of coronary artery disease compared to PET imaging and Invasive Coronary Angiography: A cohort study and health economic evaluation for patient benefit.
Funder: Department of Health and Social Care

Abstract: Coronary artery disease (CAD) is the UK s second most common cause of death and hence important to identify in order to initiate management to prevent adverse events and guide clinical decision-making for coronary revascularisation. Various tests are recommended by National Institute for Health and Clinical Excellence (NICE) to investigate CAD. Positron Emission Tomography (PET) is the non-invasive gold standard, although is expensive and uses radioactive agents. Coronary angiography is invasive and expensive and provides anatomical rather than functional information of CAD unless additional Fractional-Flow-Reserve (FFR) measurements are obtained. Cardiac Magnetic Resonance (CMR) is advantageous as it is cheaper, safe and does not administer ionising radiation. Measurement of myocardial blood flow (MBF) improves diagnostic accuracy, provides prognostic information and risk stratification and can guide clinical decision-making for medical and expensive coronary revascularisation. PET is the gold standard to measure blood flow. Blood flow can be derived from CMR, although requires experts, is time consuming (>3 hours) and hence at present, not feasible for clinical practice. Previous studies that compared PET and CMR demonstrated only moderate agreement of blood flow values. Amongst other confounders, patients were scanned on separate PET and CMR scanners. Novelty of project: Using hybrid PET-MRI imaging, simultaneous blood flow with CMR and PET can be obtained. We will use state-of-the-art CMR perfusion methods which have demonstrated excellent correlations in phantom flow models, porcine models and volunteers. We have developed an automated user-independent software for MBF quantification using CMR which may be deployed for routine clinical use across the NHS at point-of-care. Aim To establish if novel CMR can be used as a valid and more cost-effective alternative to the non-invasive gold standard Position Emission Tomography (PET) to measure blood flow. Hypotheses 1. MBF measured with novel CMR agrees accurately with the non-invasive gold standard PET. 2. MBF measurement with novel CMR techniques is superior to standard visual CMR analysis for CAD detection and clinical decision-making. 3. Non-invasive novel CMR can detect significant CAD on invasive coronary angiography with a high precision. 4. Novel CMR methods to detect CAD is more cost-effective than PET. Methods Work package 1: 77 patients with stable angina and suspected CAD listed for diagnostic coronary angiography will undergo one additional PET-MRI scan. MBF with novel CMR techniques and PET will be measured simultaneously and findings compared to each other, and to invasive coronary angiography. Work package 2: A health economic evaluation will be performed for CMR and PET for the detection of CAD. This will comprise a short-term decision tree to model the impact of using CMR in the assessment of patients with suspected CAD compared to PET. Primary outcomes The agreement of MBF measured with novel CMR compared to the non-invasive gold standard of PET. The incremental cost-effective ratio of CMR versus PET for the detection of CAD (represented as cost per correctly identified case). Secondary outcome Sensitivity and specificity of novel CMR to detect significant CAD by coronary angiography. Trajectory for patient benefit: -CMR is a safer, cheaper and more widely available alternative to PET and hence an attractive alternative to patients if able to provide equivalent diagnostic information. -Novel CMR methods may be improve the diagnostic precision of CAD, which could avoid repeated testing or invasive angiography. -An automated tool to measure MBF has utility for clinicians and provides value in clinical decision-making to ensure patients receive appropriate therapy. -At the end of this project, we aim to have validated a tool for roll out to the NHS for routine clinical use at point of care.

Lay abstract: Coronary artery disease (CAD) is the UK's second most common cause of death. Therefore it is important to identify patients with CAD early so that prevention can be started before a heart attack occurs. CAD can be detected by a number of tests including a radioactive dye injection, ultrasound or Cardiac Magnetic Resonance (CMR). These are most commonly interpreted by simply looking at images on a computer screen which can be problematic as even with well-trained individuals scan reports can differ. Measuring the heart's blood flow provides more information and helps doctors treat patients better by identifying who may need expensive heart surgery or stents. The best method to do this is Positron Emission Tomography (PET), but this is expensive, not available widely and uses a radioactive agent and radiation. Coronary angiography (a test where a plastic tube is inserted into the body and dye is injected into the heart's arteries) can detect heart disease, but without further testing with special wires, it does not tell us whether treatment with stents or heart surgery is required. CMR can measure the heart's blood flow and is cheaper, widely available and no radiation is used. However measuring blood flow is time-consuming and therefore not used routinely by doctors. We have designed a tool to measure blood flow rapidly and precisely with CMR. We need to test if this is as good as PET for measuring the heart's blood flow. We will also test if this CMR tool can detect heart disease as well as coronary angiography. This tool will be beneficial for patients as CMR does not use radiation or radioactive agents, is safe and widely available and may be used in hospitals throughout the UK. Furthermore, this technique may detect heart disease earlier than other tests can.

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