Systematic review, meta-analysis and economic modelling of ...

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1In addition to the measurement of cardiac troponin, other markers of the atherothrombotic process couldbe measured to allow earlier diagnosis. Markers of atheromatous plaque destabilisation or rupture havebeen proposed, including inflammatory markers [C-reactive protein (CRP), interleukin 6, interleukin 33/ST2and growth differentiation factor 15 (GDF-15)] and biomarkers considered to be associated with theplaque itself [myeloperoxidase (MPO), matrix metalloproteinases and pregnancy-associated plasma proteinA (PAPP-A)]. Alternatively, markers of myocardial dysfunction could be used, such as B-type natriureticpeptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), copeptin and adrenomedullin.A systematic review of 22 novel biomarkers, including CRP, MPO, BNP and H-FABP, 22 concluded thatthere was insufficient evidence to support the use of these biomarkers in ED assessment of suspectedACS. As this analysis was published, further studies have been undertaken to estimate the diagnosticand prognostic accuracy of alternative biomarkers, whereas other studies have suggested that moderntroponin assays have much improved early sensitivity. We therefore planned to synthesise the evidencerelating to the role of early biomarkers (including troponin) for identifying MI before 10–12 hours and therole of alternative biomarkers in providing additional risk stratification for troponin-negative patients withsuspected ACS.Exercise electrocardiography testingExercise ECG testing involves using exercise, typically walking on a treadmill or static cycling, toprovoke physiological stress, thus increasing heart rate and myocardial oxygen demand. ContinuousECG monitoring is used to identify changes that indicate myocardial ischaemia due to underlyingCAD. Development of cardiac-type pain on exercise, and other measurements such as blood pressurerecording, can also be used to indicate CAD or other heart disease. A conclusive test result requiresthe patient to achieve 85% of their predicted maximal heart rate. This may not be achievable if thepatient has neurological or musculoskeletal comorbidities. As a result, a proportion of exercise ECG testsare inconclusive.Exercise ECG has been widely used in the investigation of patients with stable chest pain due to suspectedCAD. Most studies of prognostic accuracy and all studies of diagnostic accuracy have involved patientswith stable symptoms and until recently suspected ACS was considered a contraindication to exercisetesting. The most recent meta-analysis 23 of the diagnostic accuracy of exercise ECG reported that themain diagnostic criterion (ST depression) performed only moderately well, with a positive likelihoodratio (PLR) of 2.79 for a 1-mm cut-off and 3.85 for a 2-mm cut-off. The negative likelihood ratios were0.44 and 0.72, respectively. Exercise ECG would therefore be expected to miss a significant proportionof patients with CAD, while subjecting others with normal coronary arteries to an unnecessary invasivecoronary angiogram.The role of exercise ECG has only recently developed in patients with suspected ACS. Biomarker testingwith a 10- to 12-hour troponin assay or alternative strategy is used to rule out MI before exercise testing,so it is effectively used only on those with troponin-negative suspected ACS. Also, as patients with knownCAD are unlikely to benefit from diagnostic assessment for CAD, use in those without known CAD islimited to providing prognostic information.Exercise ECG testing is not currently widely used in suspected ACS. When used it is typically in the contextof a standardised assessment alongside biomarker testing on a chest pain unit. These units are widespreadin the USA but have been established in only a few centres in the UK in the light of a cluster randomisedtrial that failed to show evidence of benefit. 24 European Society of Cardiology guidelines recommend usinga stress test (typically exercise ECG) to select patients for further investigation with coronary angiography, 15whereas NICE guidance does not recommend using exercise ECG in the context of suspected ACS. 11 Therole of exercise ECG testing in suspected ACS therefore remains unclear and involves extrapolating evidencefrom other settings. We therefore planned to synthesise the evidence relating to the role of exercise ECG inassessing patients with suspected ACS.© 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. 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