Sarcoidosis is a multisystem inflammatory disease characterized by inflammation, characteristic noncaseating granuloma formation, and organ dysfunction [
We did not restrict the searches to particular study designs, or publication dates. We searched on PubMed from January 1, 1980, to March 28, 2018, on Embase from January 1, 1980, to March 29, 2018, and on the Cochrane Library from January 1, 1980, to April 1, 2018, using a strategy based on the search terms (sarcoidosis and magnetic resonance imaging) independently, detailed in Appendix 1, and included all studies of the accuracy of diagnostic tests. Studies were excluded if they did not contain sufficient information to complete a 2 × 2 table. For studies performed on the same population, we included the most recent results. The results of the literature search, literature screening, record eligibility, and study quality were assessed independently by 2 reviewers (J. Z. and Y. L.). Disagreements were resolved by adjudication by the other authors. Extracted data were used to create forest plots of sensitivity and specificity, with 95% confidence intervals (CIs), using Review Manager 5.3 (Nordic Cochrane Center, Copenhagen, Denmark). Given the data and diagnostic-threshold variability, a random-effects hierarchical summary receiver operating characteristic (SROC) model, fit the results onto an SROC curve using Stata 14.0 statistical software (Stata Corporation, College Station, TX, US).
The initial database created from the literature search was screened by two reviewers blindly. If the two reviewers had different opinions, disagreements were resolved by means of a discussion between them. Studies were included if they met the following criteria: (1) evaluation of the diagnostic accuracy of CMR for sarcoidosis; (2) use of a sample size of ≥20. Studies were excluded if they did not use CMR to evaluate cardiac sarcoidosis, or if they contained insufficient data.
Two reviewers collected data from the primary studies independently. For each test, the data were classified as positive or negative for the cardiac magnetic resonance imaging detection of cardiac sarcoidosis and sensitivity and specificity estimates were calculated. Data were recorded on a standard data extraction form. Two authors independently assessed the quality of each included study using the risk of bias tool in Review Manager 5.3 software.
We plotted study estimates of sensitivity and specificity on forest plots and in receiver operating characteristic (ROC) space. Because our focus of inference was summary points, we used a bivariate model to jointly summarize sensitivity and specificity, through the inclusion of random effects for the logit sensitivity and specificity parameters of the bivariate model [
We collected 449 records from PubMed, Embase, and the Cochrane Library. Titles were screened to exclude 162 duplicates from the initial 449 records. Screening of the titles, abstracts, study types, and full texts of the remaining 287 records resulted in the identification of 12 qualifying studies. Finally, we obtained 8 studies for the systematic review and meta-analysis [
The flow of the process of identifying eligible studies.
The main information and characteristics from the included studies are summarized in Table
Review of the literature.
Study | Year | Country | Study population | Standard clinical investigations | CMR diagnostic criteria | Reference test |
---|---|---|---|---|---|---|
Smedema et al. [ |
2005 | The Netherlands | 58 patients with histologically proven pulmonary sarcoidosis | ECGHolterUCGSPECT | Hyperenhancement on DE-MRI | JMHW |
Ohira et al. [ |
2008 | Japan | 21 consecutive patients with suspected cardiac sarcoidosis | ECGHolterUCG |
High signal intensity on T2WI hyperenhancement on DE-MRI | JMHW |
Patel et al. [ |
2009 | America | 81 consecutive biopsy-proven sarcoidosis patients | ECG cardiac-imaging study (at least one, non-CMR) cardiac biopsy (if performed) |
Hyperenhancement on DE-MRI | JMHW |
Manins et al. [ |
2009 | Australia | 20 consecutive biopsy-proven sarcoidosis patients with a suspicion of CS | ECGHolterUCGGallium |
Hyperenhancement on DE-MRI showed regional wall motion abnormalities with regional fibrosis and edema | JMHW |
Soussan et al. [ |
2013 | France | 35 consecutive biopsy-proven sarcoidosis patients with a suspicion of CS | ECGHolterUCGPET |
Hyperenhancement on DE-MRI spared the subendocardium and remained limited to the middle or epicardial portion of the myocardic wall or transmural | JMHW |
Yokoyama et al. [ |
2015 | Japan | 125 consecutive patients with suspected CS | sACE |
Hyperenhancement on DE-MRI | JMHW |
Kouranos et al. [ |
2017 | Greece and the United Kingdom | 321 consecutive biopsy-proven sarcoidosis patients (all Caucasians) | ECG |
Hyperenhancement on DE-MRI and regional wall motion abnormalities | HRS consensus criteria and JMHW |
Stanton et al. [ |
2017 | Australia | 46 consecutive patients with biopsy-proven sarcoidosis | ECG |
Hyperenhancement on DE-MRI | JMHW |
ECG: electrocardiogram; UCG: ultrasound cardiogram; SPECT: perfusion single photon emission computed tomography; DE-MRI: delayed enhancement magnetic resonance imaging; JMHW: the guidelines of the Japanese Ministry of Health and Welfare; sACE: serum angiotensin-converting enzyme; 18F-FDG: 18F-fluoro-2-deoxy-
Risk of bias of the 8 included studies.
This meta-analysis encompassed eight studies with a total of 649 participants; CMR had an overall sensitivity of 0.93 (95% CI, 0.87–0.97) and specificity of 0.85 (95% CI, 0.68–0.94) in the diagnosis of cardiac sarcoidosis (Figure
Forest plots of sensitivity and specificity. CMR had an overall sensitivity of 0.93 (95% CI, 0.87–0.97) and specificity of 0.85 (95% CI, 0.68–0.94) in the diagnosis of cardiac sarcoidosis.
SROC curve. A random-effect SROC model was used, given the data and diagnostic-threshold variability to fit a single symmetric SROC curve. The area under the SROC curve was 0.95 (95% CI, 0.93–0.97). The overall diagnostic odds ratio was 81 (95% CI, 20–332).
The Fagan plot analysis showed the pretest probability is 50, the positive likelihood is 6, the probability of posttest is 86, the negative likelihood ratio is 0.08, and the probability of the posttest is 7.
The Deeks funnel plot asymmetry test of publication bias of the diagnostic odds ratios revealed publication bias existed (
The Deeks funnel plot asymmetry test of publication bias. The Deeks funnel plot asymmetry test of publication bias of the diagnostic odds ratios revealed publication bias existed (
Forest plots of sensitivity and specificity, SROC curves, and the funnel plot asymmetry test based on the subgroup.
The diagnosis of CS lacks reliable and specific tools, particularly during the early stages of the disease [
The guidelines of JMHW are the worldwide standard used to diagnose CS [
Clinical assessment of cardiac sarcoidosis includes history, physical examination, electrocardiography, 24-h Holter monitoring, and echocardiography [
The typical pathology in CS is patchy edema and granulomatous infiltration of the myocardium. The inflammatory phase is characterized by focal wall thickening for infiltration or edema, combined with wall motion abnormalities, and focal myocardial thickening which can be seen as increased signal intensity on T2-weighted images and early gadolinium enhancement [
CMR has currently one limitation: it cannot be performed in patients with CS who carry cardiac devices, such as cardiac defibrillators (AICD) or pacemakers, which are contraindications to CMR [
PET can also be useful to diagnose CS, and studies indicated that PET could be useful as a marker of disease activity and adverse events and thus help guide therapy [
The results of this meta-analysis suggest that CMR could be used in the diagnosis of cardiac sarcoidosis and screening of the patients suspected with CS. With the improvement of the technique, the diagnostic accuracy of MRI improved. When cardiac involvement is suspected, it is crucial to thoroughly screen the patients. An early initiation of corticosteroid therapy can minimize adverse outcomes.
PubMed (2018-3-28), Embase (2018-3-29), and the Cochrane Library (2018-4-1) using the following search terms (sarcoidosis OR sarcoidoses OR “Besnier-Boeck-Schaumann Syndrome” OR “Besnier Boeck Schaumann Syndrome” OR “Syndrome, Besnier-Boeck-Schaumann” OR “Boeck Disease” OR “Schaumann's Syndrome” OR “Schaumann's Syndromes” OR “Syndrome, Schaumann's” OR “Boeck's Sarcoid” OR “Boeck Sarcoid” OR “Boecks Sarcoid” OR “Sarcoid, Boeck's” OR “Schaumann Disease” OR “Disease, Schaumann” OR “Schaumann Syndrome” OR “Syndrome, Schaumann” OR “Besnier-Boeck Disease” OR “Besnier Boeck Disease” OR “Boeck's Disease” OR “Boecks Disease”) AND (“Magnetic Resonance Imaging” OR “Imaging, Magnetic Resonance” OR “NMR Imaging” OR “Imaging, NMR” OR “Tomography, NMR” OR “Tomography, MR” OR “MR Tomography” OR “NMR Tomography” OR “Steady-State Free Precession MRI” OR “Steady State Free Precession MRI” OR “Zeugmatography” OR “Imaging, Chemical Shift” OR “Chemical Shift Imagings” OR “Imagings, Chemical Shift” OR “Shift Imaging, Chemical” OR “Shift Imagings, Chemical” OR “Chemical Shift Imaging” OR “Tomography, Proton Spin” OR “Proton Spin Tomography” OR “Magnetization Transfer Contrast Imaging” OR “MRI Scans” OR “MRI Scan” OR “Scan, MRI” OR “Scans, MRI” OR “fMRI” OR “MRI, Functional” OR “Functional MRI” OR “Functional MRIs” OR “MRIs, Functional” OR “Functional Magnetic Resonance Imaging” OR “Magnetic Resonance Imaging, Functional” OR “Spin Echo Imaging” OR “Echo Imaging, Spin” OR “Echo Imagings, Spin” OR “Imaging, Spin Echo” OR “Imagings, Spin Echo” OR “Spin Echo Imagings”) AND (“Sensitivity and Specificity” OR Sensitivity OR Specificity).
The meta-analysis data used to support the results of this study are included in the article.
The authors report no conflicts of interest.