Title: The Pre-hospital Evaluation of Sensitive Troponin (PRESTO) study
Funder: Department of Health and Social Care

Abstract: Background: Chest pain is the most second most common reason why people call for an emergency 999 ambulance and the most common reason for emergency hospital admission. Acute coronary syndrome (ACS) is suspected in approximately half of patients, which often requires prolonged evaluation in hospital. However, less than 20% of those patients actually have a diagnosis ACS, meaning that there is tremendous potential to reduce unnecessary resource utilisation. We developed the troponin-only Manchester ACS decision aid (T-MACS), which uses clinical information and a single blood test result from the time of arrival in the Emergency Department (ED), to calculate the probability of ACS. T-MACS identifies over 40% of patients as being 'very low risk' (~1% probability of ACS), 'ruling out' the diagnosis of ACS and enabling early reassurance. Another 5-10% of patients are identified as 'high risk' (~95% probability of ACS) and the diagnosis is 'ruled in', facilitating specialist treatment. The algorithm has been successfully validated in over 3,000 patients and has been used to treat another 3,000 patients in practice. In a multi-centre study, we recently showed that T-MACS has acceptable diagnostic accuracy when used with a portable point of care (POC) blood test. This opens up the possibility of using T-MACS in the pre-hospital environment to avoid unnecessary transfers to the ED. Objective: Our primary objective is to evaluate the diagnostic accuracy of T-MACS for ACS when applied in the pre-hospital setting. Plan of investigation: Design, setting and participants: In a prospective, observational diagnostic accuracy study involving three ambulance services, we will prospectively include patients who have called 999 for an ambulance for pain or discomfort that the treating paramedic suspects may have been caused by ACS. After consulting with a patient group and other key stakeholders, we will obtain initial verbal consent in the ambulance followed by subsequent written informed consent. Data collection: Paramedics will complete a simple questionnaire to calculate the outcome of T-MACS. A 12-lead electrocardiogram (ECG) will be recorded, as with routine care. Paramedics will then draw venous blood from all participants prior to transfer. After transfer, plasma will be extracted from the sample and stored, pending subsequent analysis for cardiac troponin using commercially available POC devices. Follow-up: In accordance with national guidelines, participants will undergo central laboratory cardiac troponin testing in hospital, which will form part of the reference standard. We will also obtain follow-up data after 30 days by chart review and by contacting participants. Outcomes: The primary outcome will be the diagnosis of ACS, which will be adjudicated by two independent investigators blinded to the assessment of T-MACS by paramedics. Discrepancies will be resolved by a third independent investigator. ACS will be defined as either (a) prevalent acute myocardial infarction (AMI), defined in accordance with the universal definition of AMI; or (b) incident major adverse cardiac events (cardiac death, AMI or non-elective coronary revascularization) within 30 days. Secondary outcomes will include healthcare resource utilisation and health status (EQ-5D). Primary analysis: We will calculate test characteristics of T-MACS for 'ruling in' and 'ruling out' ACS, together with 95% confidence intervals. Sample size: Based on feasibility data and allowing for attrition, including 700 participants will provide sufficient precision around measures of diagnostic accuracy. Potential benefits to patients and the NHS: This work will identify a novel means of delivering efficient pre-hospital emergency care to patients with chest pain. With a programme of training and dissemination and based on similar precedents, we aim to achieve clinical implementation within 2 years. This is likely to lead to substantial cost savings for the NHS and safe early reassurance for thousands of patients.

Lay abstract: The growing pressure on Emergency Departments ('A&E') and ambulance services is unsustainable. We must find new ways to deliver emergency healthcare without hospital treatment. Chest pain is the second most common reason why people call for an emergency ambulance. These people are routinely taken to hospital for tests, although most do not have a health problem that needs hospital treatment. With better tests we could avoid many unnecessary hospital attendances, easing pressure on emergency services and reassuring patients earlier. We developed the 'Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid', which calculates how likely it is that a patient has a serious heart problem by considering their symptoms and basic test results (including an electrocardiogram or 'heart tracing' and a blood test). Previous work has included: (1) Research involving >3,000 patients, showing that T-MACS could have safely avoided hospital admission for 4 out of 10 patients in 'A&E' (2) We started using T-MACS in 'A&E' and have safely treated another 3,000 patients (3) Further research in >700 patients showed that T-MACS is also accurate with a portable blood testing device. If used in an ambulance, T-MACS could avoid many unnecessary transfers to hospital. However, we must be sure that T-MACS remains accurate in this setting. This new research will include 700 patients who call 999 with chest pain in three ambulance services. After obtaining consent, we will draw blood samples in the ambulance, take a heart tracing and record patients' symptoms. We will review patients' medical records and contact them after 30 days to find out the final diagnosis. We will then calculate the accuracy of T-MACS. During the research, patients will still be transported to hospital for tests. However, if our results show that T-MACS is accurate, we can start to use it in practice to provide earlier reassurance.

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