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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

SS Abdelmoneim, A Dhoble, M Bernier, PJ Erwin, G Korosoglou, R Senior, S Moir, I Kowatsch, S Xian-Hong, T Muro, D Dawson, R Vogel, K Wei, CP West, VM Montori, PA Pellikka, SS Abdel-Kader, and SL Mulvagh.

Review published: 2009.

CRD summary

This generally well-conducted review concluded that there was evidence to support use of quantitative myocardial contrast echocardiography as a non-invasive test for detection of coronary artery disease. Although the reliability of the pooled results was uncertain due to substantial heterogeneity and evidence of a threshold effect, the conclusions are likely to be reliable.

Authors' objectives

To evaluate the accuracy of quantitative stress myocardial contrast echocardiography in coronary artery disease.


MEDLINE, EMBASE, Web of Science, DARE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL) were searched without language restrictions from inception to January 2008; search terms were reported. Bibliographies of retrieved articles were searched.

Study selection

Studies that compared accuracy of measuring the peak plateau of video intensity (A reserve; myocardial capillary blood volume), rate of rise in signal intensity (β reserve; microbubble velocity) and Aβ reserves (myocardial blood flow) of quantitative stress myocardial contrast echocardiography compared to coronary angiography or single-photon emission computed tomography for assessment of coronary artery disease in those with known or suspected disease were eligible for inclusion. The primary outcome was diagnostic odds ratio (DOR). Studies in patients who presented with acute coronary syndrome were excluded.

Stress test agents used were adenosine, dipyridamole, and dobutamine. Most studies used coronary angiography as the reference standard. Where reported, mean age of participants ranged from 56 to 67 years and prevalence of coronary artery disease was from 17% to 72%. Most participants had no history of invasive coronary interventions. The proportion of patients with a history of myocardial infarction ranged from 0% to 100%, diabetes mellitus from 0% to 52%, hypertension from 0% to 85% and hyperlipidaemia from 0% to 68%.

Two reviewers independently selected studies for the review; disagreements were resolved by consensus.

Assessment of study quality

Two reviewers independently assessed study quality using the 14-criteria QUADAS tool; disagreements were resolved by consensus.

Data extraction

Two independent reviewers extracted data in order to construct 2x2 tables of test performance from which diagnostic odds ratio and positive and negative likelihood ratios (LR+/-) were calculated. Mean values and standard deviations for A, β and Aβ reserves in patients with and without coronary artery disease were extracted and from these mean differences and 95% confidence intervals (CI) were calculated. Authors were contacted for individual patient data when these were missing. Disagreements were resolved by consensus.

Methods of synthesis

Pooled estimates of the diagnostic odds ratio and likelihood ratios and weighted mean differences (WMD) for A, β and Aβ reserves, with 95% CI, were calculated using a random-effects model. Summary receiver operating characteristic curves were produced using the Moses linear model. Heterogeneity was assessed using the I2 statistic (low 25%, moderate 50% and high 75%). Subgroup/sensitivity analyses were conducted to investigate: prior medical history; reference standard used; stress agent used; mechanical index; contrast agent used; prevalence of coronary artery disease; cut-offs used for a positive test; and level of analysis. Analyses were also conducted using a fixed-effect model.

Results of the review

Thirteen studies met the inclusion criteria (n=627; successful myocardial contrast echocardiography in 574 patients). All studies adequately reported methods for the index and reference standard tests, and avoided progression, incorporation and partial verification biases. Seven recruited a representative patient spectrum, nine reported uninterpretable/intermediate results, eight reported on withdrawals and 12 avoided differential verification bias. Blinding and avoidance of clinical review bias were poorly reported.

For A reserve (nine RCTs), diagnostic odds ratio was 2.09 (95% CI 1.42 to 3.07), LR+ was 1.33 (95% CI 1.13 to 1.57) and LR- was 0.68 (95% CI 0.55 to 0.83).

For β reserve (13 RCTs), diagnostic odds ratio was 15.11 (95% CI 7.90 to 28.91), LR+ was 3.76 (95% CI 2.43 to 5.80), and LR- was 0.30 (95% CI 0.24 to 0.38).

For Aβ reserves (13 RCTs), diagnostic odds ratio was 14.73 (95% CI 9.61 to 22.57), LR+ was 3.64 (95% CI 2.87 to 4.78), and LR- was 0.27 (95% CI 0.22 to 0.34).

Myocardial contrast echocardiography parameters were significantly lower in patients with confirmed coronary artery disease: A reserve WMD 0.12 (95% CI 0.06 to 0.18; 11 RCTs); β reserve WMD 1.38 (95% CI 1.28 to 1.52; 12 RCTs); and Aβ reserves WMD 1.47 (95% CI 1.18 to 1.76; 12 RCTs).

Substantial heterogeneity was observed for all analyses of β and Aβ reserves. Results of subgroup and sensitivity analyses were presented; the only subgroup with a statistically significant test for interaction was presence/absence of previous myocardial infarction or coronary artery bypass graft (p=0.001).

Authors' conclusions

Evidence supported use of quantitative myocardial contrast echocardiography as a non-invasive test for detection of coronary artery disease.

CRD commentary

The review addressed a clear research question supported by appropriate inclusion criteria. Several relevant sources were searched without language restrictions. There was no specific search for unpublished studies and so studies may have been missed. Each stage of the review was conducted in duplicate, which reduced risk of error and bias. Study quality was assessed using appropriate criteria and results were presented for each criterion. There was substantial heterogeneity observed for many analyses and there was some evidence of a threshold effect, which made the reliability of pooled results uncertain. However, heterogeneity was investigated extensively. This was a generally well-conducted review and the conclusions are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that appropriate training and education must be provided for accurate performance and analysis of contrast perfusion imaging studies. More effort was needed to standardise methods and interpretation of quantitative myocardial contrast echocardiography to increase test reliability and reproducibility, and its integration into clinical practice.

Research: The authors stated that future studies needed to evaluate patients who had a lower risk of coronary artery disease, An adequately powered multicentre study that recruited a broad spectrum of patients with acute and chronic coronary artery disease to establish valid and reliable cut-offs would be beneficial.


One author was supported by grants from Lantheus Medical Imaging and Astellas Pharma, USA.

Bibliographic details

Abdelmoneim SS, Dhoble A, Bernier M, Erwin PJ, Korosoglou G, Senior R, Moir S, Kowatsch I, Xian-Hong S, Muro T, Dawson D, Vogel R, Wei K, West CP, Montori VM, Pellikka PA, Abdel-Kader SS, Mulvagh SL. Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies. European Journal of Echocardiography 2009; 10(7): 813-825. [PubMed: 19549700]



Indexing Status

Subject indexing assigned by NLM


Adult; Aged; Contrast Media /diagnostic use; Coronary Artery Disease /diagnosis; Coronary Circulation; Echocardiography; Exercise Test; Female; Heart /radionuclide imaging; Humans; Male; Microcirculation; Middle Aged; Radiopharmaceuticals /diagnostic use



Date bibliographic record published


Date abstract record published


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19549700

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