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Discussionspecificity were 62% (95% predictive interval 35% to 83%) and 83% (95% predictive interval 35% to 98%),respectively. These findings suggest inadequate diagnostic accuracy to act as a single diagnostic test for MIat presentation.A few studies reported the accuracy of alternative biomarkers in combination with troponin atpresentation, with the combination being positive if either marker were positive. H-FABP, copeptin,IMA and myoglobin improved sensitivity for MI at presentation but at the expense of loss of specificity.However, the estimates of diagnostic accuracy for presentation troponin alone varied substantially inthese studies and used an unclear threshold for positivity in some cases. Our meta-analysis suggests thathigh-sensitivity troponin assays can achieve similar sensitivity to the biomarker and troponin combinationwith a similar loss of specificity. Future evaluations of alternative biomarkers at presentation should includemeasurement of a high-sensitivity troponin assay to determine whether or not the biomarker still producesan incremental improvement in sensitivity.Prognostic accuracy of biomarkers for predicting major adverse cardiac eventsThe prognostic value of troponin is well established 8 and elevated troponin levels is associated withincreased potential to benefit from treatment. 9,155 As a result, troponin is established as an essentialbiomarker in the assessment of suspected ACS. We identified a large number studies evaluating the abilityof other biomarkers to predict MACEs in patients with suspected ACS. However, many of these simplyevaluated whether there was an association between biomarker levels and risk of MACEs. In clinicalassessment, the ECG and troponin are already established in routine practice on the basis of value inpredicting adverse outcome, so any new biomarker would need to demonstrate additional prognosticvalue beyond routine assessment. We found some evidence that BNP, NT-pro-BNP, MPO and H-FABPcould predict MACEs even after adjustment for troponin and other variables in multivariate analysis.However, results were sometimes inconsistent and it was not always clear whether or not all potentiallyimportant covariates had been included in analysis. We also found evidence that CRP, PAPP-A and H-FABPcould predict MACEs in troponin-negative patients. These findings were based on a small number ofheterogeneous studies with differing methods of analysis and there was some inconsistency in thefindings. Meta-analysis was not possible so the estimates of RR were based on single studies and should beinterpreted with caution.Diagnostic accuracy of computed tomographic coronary angiography andexercise electrocardiography for coronary artery diseaseThe diagnostic accuracy of CTCA and exercise ECG for identifying CAD in patients with stable symptomshas been extensively studied and summarised in previous meta-analyses. We aimed to determine whetheror not similar estimates existed in patients presenting to hospital with suspected ACS.We identified eight studies comparing CTCA to conventional coronary angiography in patients presentingwith suspected ACS, reporting sensitivities ranging from 83% to 100% and specificities ranging from 54%to 100%. The summary estimates for sensitivity and specificity were 93% (95% predictive interval 61%to 99%) and 87% (95% predictive interval 16% to 100%), respectively. The studies were relatively small,evaluated various different techniques and used different methods of analysis, so there are a number ofpotential explanations for the variation in results. Only one study 126 used 64-slice CT and this reported thehighest sensitivity and specificity (both 100%). The other studies used 16- or 4-slice CT and reported lowersensitivity and specificity.Our findings are similar to other published reviews. Mowatt et al. 25 sought all diagnostic studies of CTCAand included 18 studies with 1286 patients in the meta-analysis. Most of the included studies were ofpatients with stable symptoms rather than suspected ACS. Sensitivity ranged from 94% to 100%, with apooled sensitivity of 99% (95% CrI 97% to 99%). Specificity ranged from 50% to 100%, with a pooledspecificity of 89% (95% CrI 83% to 94%). Athappan et al. 167 included 16 studies of CTCA in acute chestpain. The pooled sensitivity and specificity for ACS were 0.96 (95% CI 0.93 to 0.98) and 0.92 (95% CI108NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 10.89 to 0.94), respectively. There was surprisingly little overlap between this review and ours. The studiesof Sato et al., 129 Tsai et al. 130 and Olivetti et al. 128 were included in both reviews. The other five studies weidentified 123–127 were not included in the Athappan review. We excluded four studies 131,135,168,169 becauseonly those with positive CTCA underwent ICA as the reference standard test, two studies 170,171 because thereference standard was not based on ICA, and two studies 172,173 because the study population were notpatients with suspected ACS. We excluded studies that used reference standards other than CAD on ICAand studies that confirmed only CAD on ICA in those with a positive CTCA result because these studieswill be prone to work-up bias and will overestimate diagnostic parameters. This probably explains why ourestimates of sensitivity and specificity (albeit for CAD rather than ACS) were lower than those reported byAthappan et al. 167The most recent meta-analysis 23 of the diagnostic accuracy of exercise ECG reported that the maindiagnostic criterion (ST depression) performed only moderately well, with a PLR of 2.79 for a 1-mm cut-offand 3.85 for a 2-mm cut-off. The negative likelihood ratios were 0.44 and 0.72, respectively. All of theincluded studies were of patients with chronic chest pain. We identified no studies that compared exerciseECG to ICA for the diagnosis of CAD in patients presenting with acute symptoms due to suspected ACS.We are therefore unable to determine whether the diagnostic accuracy of exercise ECG estimated inpatients with stable symptoms can be extrapolated to those presenting with suspected ACS.Prognostic accuracy of computed tomographic coronary angiography andexercise electrocardiography for predicting major adverse cardiac eventsWe identified seven studies that evaluated the prognostic accuracy of CTCA for major cardiac events inpatients with suspected ACS. MACE rates were generally very low in patients with a negative CTCA butthis may reflect selection of low-risk patients rather than accurate risk stratification by CTCA. Most of theevents reported in patients with positive CTCA findings were process events (i.e. PCI or CABG), which, inan unblinded study, may simply reflect physicians acting on CTCA findings. However, one study 136 reportedan association between positive CTCA and MACEs (including revascularisation) despite patients andcarers being blind to CTCA results. Furthermore, this study used multivariate analysis to show that CTCAfindings predicted MACEs even after adjustment for a clinical risk score incorporating ECG and troponin.This study therefore shows that CTCA can provide potentially useful additional prognostic information,beyond routine clinical assessment with ECG and troponin. Despite this, the overall findings of our reviewsuggested only weak evidence that CTCA findings predicted MACEs in patients with suspected ACS. The95% CrIs of estimates of the RR of MACEs associated with positive CTCA were wide and included thepossibility of no association.A previous systematic review and meta-analysis by Hulten et al. 174 sought all prognostic studies of CTCArather than just studies of patients with suspected ACS. Most studies included patients with stablesymptoms rather than suspected ACS. Only the study by Rubinshtein et al. 135 was included in this reviewand ours. Hulten et al. 174 included 18 studies evaluating 9592 patients with a median follow-up of20 months. The pooled annualised event rate for obstructive (any vessel with 50% luminal stenosis)compared with normal CTCA was 8.8% compared with 0.17% per year for MACEs (p < 0.05) and 3.2%compared with 0.15% for death or MI (p < 0.05). These findings suggest that abnormalities on CTCApredict an increased risk of a MACE in patients with suspected CAD and that the risk of MACEs is very lowif CTCA is normal. Our review confirms that the low risk of a MACE associated with CTCA is also seen inpatients with suspected ACS but the low overall rate of adverse outcome means that we cannot be surewhether this reflects low-risk patient selection or effective risk stratification by CTCA.We identified 13 studies reporting risk of MACEs after ETT for patients presenting to hospital withsuspected ACS. Overall, MACE rates were generally low among patients with negative ETT results.There was some evidence that positive tests identified higher-risk patients and were associated with aneightfold increase in the risk of a MACE. However, as with CTCA, in unblinded studies higher rates ofrevascularisation among patients with positive ETT may reflect physician awareness and expectation of a© 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.109
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DOI: 10.3310/hta17010 Health Techno
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ContentsAppendix 5 Expected discoun
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BackgroundTABLE 1 Hospital admissio
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Background2. investigation of the c
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BackgroundComputed tomographic coro
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Research questionsiii. the diagnost
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Assessment of diagnostic and progno
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Appendix 9respectively. Exercise EC
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Appendix 9ES (Information Resources
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Appendix 923. Westwood ME, Whiting
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