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29.10.2018 | Original Article

Umbrella review and multivariate meta-analysis of diagnostic test accuracy studies on hybrid non-invasive imaging for coronary artery disease

Journal of Nuclear Cardiology
MD, MStat Giuseppe Biondi-Zoccai, MD Francesco Versaci, MD, MACC Ami E. Iskandrian, MD Orazio Schillaci, MD Alessandro Nudi, MD, MSc Giacomo Frati, MD Francesco Nudi
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12350-018-01487-w) contains supplementary material, which is available to authorized users.
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This work was supported by Replycare, Rome, Italy.



The diagnosis of coronary artery disease (CAD) remains challenging. It is uncertain whether hybrid imaging can improve diagnostic accuracy for CAD.


This is a systematic review and multivariate meta-analysis. We searched PubMed and The Cochrane Library for recent (≥ 2010) systematic reviews of diagnostic test accuracy studies on non-invasive imaging for CAD. Study-level data were extracted from them, and pooled with pairwise and multivariate meta-analytic methods, using invasive coronary angiography (ICA) or invasive fractional flow reserve (FFR) as reference standards, focusing on sensitivity and specificity.


Details from 661 original studies (71,823 patients) were pooled. Pairwise meta-analysis using ICA as reference showed that anatomic imaging was associated with the best diagnostic accuracy (sensitivity = 0.95 [95% confidence interval 0.94-0.96], specificity = 0.83 [0.81-0.85]), whereas using FFR as reference identified hybrid imaging as the best test (sensitivity = 0.87 [0.83-0.90], specificity = 0.82 [0.76-0.87]). Multivariate meta-analysis confirmed the superiority of anatomic imaging using ICA as reference (sensitivity = 0.96, specificity = 0.83), and hybrid imaging using FFR as reference (sensitivity = 0.88 [0.86-0.91], specificity = 0.82 [0.77-0.87]).


Non-invasive hybrid imaging tests appear superior to anatomic or functional only tests to diagnose ischemia-provoking coronary lesions, whereas anatomic imaging is best to diagnose and/or rule out angiographically significant CAD.

Systematic review registration

PROSPERO Registry Number CRD42018088528.

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