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      Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis

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          Abstract

          Aims

          The aim of this study was to determine the diagnostic performance of single-photon emission computed tomography (SPECT), stress echocardiography (SE), invasive coronary angiography (ICA), coronary computed tomography angiography (CCTA), fractional flow reserve (FFR) derived from CCTA (FFR CT), and cardiac magnetic resonance (MRI) imaging when directly compared with an FFR reference standard.

          Method and results

          PubMed and Web of Knowledge were searched for investigations published between 1 January 2002 and 28 February 2015. Studies performing FFR in at least 75% of coronary vessels for the diagnosis of ischaemic coronary artery disease (CAD) were included. Twenty-three articles reporting on 3788 patients and 5323 vessels were identified. Meta-analysis was performed for pooled sensitivity, specificity, likelihood ratios (LR), diagnostic odds ratio, and summary receiver operating characteristic curves. In contrast to ICA, CCTA, and FFR CT reports, studies evaluating SPECT, SE, and MRI were largely retrospective, single-centre and with generally smaller study samples. On a per-patient basis, the sensitivity of CCTA (90%, 95% CI: 86–93), FFR CT (90%, 95% CI: 85–93), and MRI (90%, 95% CI: 75–97) were higher than for SPECT (70%, 95% CI: 59–80), SE (77%, 95% CI: 61–88), and ICA (69%, 95% CI: 65–75). The highest and lowest per-patient specificity was observed for MRI (94%, 95% CI: 79–99) and for CCTA (39%, 95% CI: 34–44), respectively. Similar specificities were noted for SPECT (78%, 95% CI: 68–87), SE (75%, 95% CI: 63–85), FFR CT (71%, 95% CI: 65–75%), and ICA (67%, 95% CI: 63–71). On a per-vessel basis, the highest sensitivity was for CCTA (pooled sensitivity, 91%: 88–93), MRI (91%: 84–95), and FFR CT (83%, 78–87), with lower sensitivities for ICA (71%, 69–74), and SPECT (57%: 49–64). Per-vessel specificity was highest for MRI (85%, 79–89), FFR CT (78%: 78–81), and SPECT (75%: 69–80), whereas ICA (66%: 64–68) and CCTA (58%: 55–61) yielded a lower specificity.

          Conclusions

          In this meta-analysis comparing cardiac imaging methods directly to FFR, MRI had the highest performance for diagnosis of ischaemia-causing CAD, with lower performance for SPECT and SE. Anatomic methods of CCTA and ICA yielded lower specificity, with functional assessment of coronary atherosclerosis by SE, SPECT, and FFR CT improving accuracy.

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          Most cited references14

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          Meta-DiSc: a software for meta-analysis of test accuracy data

          Background Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Results Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Conclusion Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at .
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            Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses.

            The clinical significance of coronary-artery stenoses of moderate severity can be difficult to determine. Myocardial fractional flow reserve (FFR) is a new index of the functional severity of coronary stenoses that is calculated from pressure measurements made during coronary arteriography. We compared this index with the results of noninvasive tests commonly used to detect myocardial ischemia, to determine the usefulness of the index. In 45 consecutive patients with moderate coronary stenosis and chest pain of uncertain origin, we performed bicycle exercise testing, thallium scintigraphy, stress echocardiography with dobutamine, and quantitative coronary arteriography and compared the results with measurements of FFR. In all 21 patients with an FFR of less than 0.75, reversible myocardial ischemia was demonstrated unequivocally on at least one noninvasive test. After coronary angioplasty or bypass surgery was performed, all the positive test results reverted to normal. In contrast, 21 of the 24 patients with an FFR of 0.75 or higher tested negative for reversible myocardial ischemia on all the noninvasive tests. No revascularization procedures were performed in these patients, and none were required during 14 months of follow-up. The sensitivity of FFR in the identification of reversible ischemia was 88 percent, the specificity 100 percent, the positive predictive value 100 percent, the negative predictive value 88 percent, and the accuracy 93 percent. In patients with coronary stenosis of moderate severity, FFR appears to be a useful index of the functional severity of the stenoses and the need for coronary revascularization.
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              Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

              We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least-squares regression line), with V - U as the dependent variable. (iv) Back-transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates.
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                Author and article information

                Journal
                Eur Heart J
                Eur. Heart J
                eurheartj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                01 April 2017
                02 May 2016
                02 May 2016
                : 38
                : 13
                : 991-998
                Affiliations
                [1 ]Department of Radiology, Weill Cornell Medical College, New York, NY, USA
                [2 ]Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA
                [3 ]Department of Epidemiology and Biostatistics, VU University Medical Center, VU University, Amsterdam, The Netherlands
                [4 ]Department of Cardiology, Aarhus University Hospital Skejby, Aarhus, Denmark
                [5 ]Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
                [6 ]HeartFlow, Inc., Redwood City, CA, USA
                [7 ]Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands
                Author notes
                [* ]Corresponding author. Tel: +1-646-962-6192; Email: jkm2001@ 123456med.cornell.edu

                See page 999 for the editorial comment on this article (doi: [Related article:]10.1093/eurheartj/ehw123)

                Article
                ehw095
                10.1093/eurheartj/ehw095
                5381594
                27141095
                c4407127-a752-4da2-be71-0c8a2cc72267
                © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 19 June 2015
                : 26 January 2016
                : 18 February 2016
                Page count
                Pages: 9
                Funding
                Funded by: National Heart Lung and Blood Institute
                Award ID: R01 HL111141, R01 HL115150 and >R01 HL118019
                Categories
                Meta-Analysis
                Imaging

                Cardiovascular Medicine
                meta-analysis,diagnostic accuracy,cardiac imaging,fractional flow reserve

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