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BackgroundComputed tomographic coronary angiographyComputed tomographic coronary angiography uses computerised tomography (CT) scanning to allownon-invasive imaging of the coronary arteries. CT scanning involves an X-ray source and sensors mountedon opposite sides of a gantry that rotates around the patient to provide a computer-generated threedimensionalimage of the heart. Modern scanners have an array of X-ray detectors that collect data frommultiple ‘slices’ on each rotation of the scanner (multislice CT). Initially, scanners with four slices weredeveloped. Currently available scanners commonly use 16 or 64 slices.Computerised tomography can be used without intravenous contrast to quantify CAC (CT CAC scoring)and thus estimate the extent of coronary atheroma. Patients with a calcium score of zero are unlikely tohave CAD, whereas the higher the score the greater the probability of CAD. It can be used in conjunctionwith clinical assessment of CAD risk to select patients for invasive coronary angiography (ICA) or CTCA.However, CT coronary artery scoring does not determine whether or not coronary atheroma is obstructive.When patients present with suspected ACS it is usually considered more important to determine whethertheir symptoms are due to obstructive CAD than estimate the probability of CAD, so evaluation of the roleof CT in suspected ACS has focused on CTCA rather than CT coronary artery scoring.Computed tomographic coronary angiography involves injection of intravenous contrast medium with CTscanning timed to coincide with circulation of contrast through the coronary arteries. The scans are theninterpreted to determine the extent of coronary artery stenosis. As intravenous contrast is required, theprocedure is contraindicated in renal failure and allergy to contrast media, and is used with caution inpregnancy. The quality of imaging can be impaired by artefact due to inability to breath hold, tachycardiaor arrhythmia. Artefact may be reduced by using beta-blocking drugs to slow the patient’s heart rate.Computed tomographic coronary angiography may provide a more accurate and cost-effective alternativeto exercise ECG in troponin-negative patients with suspected ACS. As with exercise ECG, most studies haveevaluated CTCA in patients with stable symptoms rather than suspected ACS. A recent systematic reviewof 21 diagnostic accuracy studies of CTCA reported a pooled sensitivity of 99% and specificity of 89%for detection of CAD. 25 On the basis of this and similar analyses, NICE guidance has recommended thatCT calcium scoring with CTCA for selected patients should replace exercise ECG for patients with stablesymptoms. 11 There has been less research into the use of CTCA in suspected ACS. NICE guidance for chestpain of recent onset suggests that patients with suspected ACS in whom MI has been ruled out shouldbe risk stratified and those considered to be at risk of myocardial ischaemia managed according to theguidance for patients with stable symptoms. 11 The guidance highlighted that this contrasts with EuropeanSociety of Cardiology guidelines recommending stress testing, 15 and identified evaluation of the costeffectivenessof CTCA in troponin-negative patients with suspected ACS as being a research priority. Wetherefore planned to synthesise the evidence for the use of CTCA in patients with suspected ACS.6NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1Chapter 2 Research questionsRationale for the studyThis study aimed to reduce uncertainty around two issues highlighted in NICE guidance:1. The use of troponin and other biomarkers to diagnose MI at presentation to hospital.2. The use of other biomarkers, exercise ECG and CTCA to risk-stratify patients with acute chest pain anda negative troponin.Troponin measured at least 10–12 hours after symptom onset and using the 99th percentile as adiagnostic threshold, accurately diagnoses MI and identifies patients who are at high risk of adverseoutcome and who will benefit from hospital treatment. However, patients awaiting delayed testing arecurrently detained in hospital until 10–12 hours after symptom onset. This incurs health services costs andinconvenience for the patient. An earlier diagnostic assessment could allow earlier hospital discharge, thusdecreasing costs, but would risk missed MI and opportunity to benefit from treatment if sensitivity weresuboptimal. High-sensitivity troponin assays, either alone or in combination with other biomarkers, canbe used to diagnose MI before 10–12 hours, but the cost savings of this approach need to be weighedagainst the missed benefit (or, more rationally, the additional benefits of 10- to 12-hour troponin samplingneed to be weighed against the additional costs, compared with earlier diagnostic assessments). Wetherefore need to undertake evidence synthesis to estimate (1) the diagnostic accuracy of early biomarkersand (2) the cost-effectiveness of alternative diagnostic strategies for MI.Biomarkers may also provide benefits by risk-stratifying troponin-negative patients. A negative troponinassay at 10–12 hours (and potentially earlier) stratifies patients with acute chest pain to a low but notnegligible risk of subsequent MACEs. However, because the risk remains non-negligible there may still besome benefit in measuring other biomarkers that predict increased risk independent of troponin level.These biomarkers could be used to select higher risk troponin-negative patients for further investigationand treatment to reduce the risk of adverse outcome. We therefore need to undertake evidence synthesisto estimate (1) the prognostic accuracy of biomarkers other than troponin and (2) the cost-effectiveness ofusing these biomarkers to select patients for hospital treatment.Troponin-negative patients may also be investigated by exercise ECG or CTCA to identify those with CADand an increased risk of adverse outcome who may benefit from coronary intervention and medicaltreatment to reduce the risk. We therefore need to undertake evidence synthesis to estimate (1) thediagnostic accuracy of exercise ECG and CTCA for CAD, and the prognostic accuracy of exercise ECGand CTCA for MACEs and (2) the cost-effectiveness of using exercise ECG or CTCA to select patients forhospital treatment.Overall aims and objectives of assessmentThe overall aim was to evaluate the cost-effectiveness of various strategies for diagnosing MI and CAD inunselected populations with suspected ACS. More specifically, the objectives were:1. to undertake systematic reviews to determine:i. the diagnostic accuracy of early biomarkers (including troponin) for MI in patients withsuspected ACSii. the prognostic accuracy of biomarkers for predicting MACEs in troponin-negative patients© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.7
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