Keywords

Computerized tomography, coronary angiography, coronary artery disease, diagnostic test accuracy, sensitivity and specificity

 

Authors

  1. Mander, Gordon T.W.

ABSTRACT

Objective: The objective of this review is to determine the diagnostic accuracy of computed tomography coronary angiography (CTCA) using recent scan technologies for detecting coronary artery disease (CAD) in adults with high heart rates.

 

Introduction: Invasive coronary angiography is the gold standard for detecting significant CAD, but it is costly and carries risks of complications. Computed tomography coronary angiography has a high sensitivity for diagnosing CAD, although image quality may be affected by elevated heart rates. Recent technological advances in scanner design may increase the diagnostic accuracy of CTCA.

 

Inclusion criteria: This review will consider diagnostic test accuracy studies that include adults 18 years and older with a heart rate greater than 65 beats per minute who have undergone CTCA to diagnose CAD (greater than 50% stenosis). Eligible studies will compare invasive coronary angiography with computed tomography scanner technologies that use either single- or dual-source scanner configuration in prospective electrocardiogram scan acquisition mode, and with a total scanner coverage equal to or greater than 128 detector-rows. Studies published in English from 2007 will be considered.

 

Methods: PubMed, Embase, CINAHL and Scopus will be searched, along with Google Scholar, the NIHR-HTA register, computed tomography vendors and conference abstracts. Screening of potential titles and abstracts, retrieval of full-text studies, assessment of methodological quality and data extraction will be performed independently by two reviewers. Meta-analyses will be performed, if possible, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings presented.

 

Article Content

Introduction

Computed tomography coronary angiography (CTCA) has become an important test in the cardiovascular diagnostic armamentarium. The high sensitivity and associated negative predictive value have made CTCA a well-recognized diagnostic test for patients with low-intermediate risk of significant coronary artery disease (CAD).1 Furthermore, there is now strong evidence to support the use of CTCA in cases of stable angina likely associated with CAD to better stratify treatment options.2

 

Elevated heart rates (HR) are known to affect image quality, and therefore diagnostic performance in this examination.3 However, the relationship between HR, image quality and diagnostic test accuracy is complex due to multiple intermediary factors. The acquisition parameters, make and model of scanner, years of experience of the reader, as well as patient-specific factors, such as obesity and significant intraluminal calcium, all affect diagnostic accuracy.4,5 The operator's level of experience with the technology is also likely to be a contributing factor, but this has not been studied in detail. Despite the complexity of confounding factors, it is clear that motion artifacts have a deleterious effect on image quality. Previous CTCA studies have described poorer diagnostic accuracy in patients with HRs greater than 65 beats per minute (bpm).6 Guidelines, therefore, recommend a stable heart rate of less than 60 bpm in patients prior to imaging them with CTCA.7,8 Furthermore, where HRs are higher, a larger radiation exposure may be required to achieve results.9 Therefore, heart rates greater than 65 bpm, which may not be considered high in a clinical setting, are considered to be high in the CTCA context.

 

To combat high heart rates, patients are commonly prescribed beta-blockers or sinoatrial node inhibitors immediately prior to CTCA. This helps to ensure HRs are predictable enough to provide the greatest chance of a diagnostic result at the lowest practicable radiation exposure to the patient. Whilst HR control medications are usually effective and well tolerated, they are not without risks and are contraindicated in certain patients cohorts.10,11

 

Several advances in computed tomography (CT) scanner design and technology have been implemented to address the challenges in imaging patients with unsuitable HR. Recent important technological advances include: the introduction of dual-source systems, increased detector-row coverage in the patient direction, decreased tube rotation time, as well as novel computational algorithms.12-15 These advances are all designed to improve temporal resolution in order to reduce motion artifacts at high HRs and should therefore result in increased diagnostic accuracy.

 

Decreasing the time for rotation of the tube around the gantry reduces the amount of time needed to acquire projectional data and therefore reduces the incidence of heart related motion. The rotation time has a direct effect on the temporal resolution, which is commonly described as analogous to the shutter speed of a camera.

 

Dual-source CT (DSCT) systems (SOMATOM Definition, Siemens Healthcare, Forcheim, Germany) consist of two x-ray tubes and their corresponding detector array placed 90 degrees apart, which rotate concomitantly around the CT gantry. This technique allows twice the amount of data to be acquired in a single rotation, effectively halving the rotation time. This leads to a two-fold increase in temporal resolution compared to an equivalent single-source system.

 

Another method of reducing motion artifacts is by reducing the time taken to acquire data in the longitudinal (patient) direction. Increasing the detector-row coverage allows more data to be acquired in the z-direction in a single rotation compared with systems with lesser detector-row configurations. Whilst this does not reduce in-plane motion artifacts, it eliminates "stair step" artifacts caused by misalignment of consecutive scans that would otherwise be acquired sequentially, over more than one heartbeat.

 

Finally, computational algorithms have also been developed to reduce the effect of motion on image quality. These include two vendor-specific proprietary software algorithms: SnapShot Freeze (GE Healthcare, Waukesha, WI, USA) and adaptive motion correction (Canon Medical Systems, Tokyo, Japan), which utilize data from X-ray projections immediately prior to a specific reconstructed cardiac phase to correct the edge of structures, such as the coronary arteries, in an attempt to eliminate cardiac motion artifacts.14,16

 

Despite these important advances, and several primary studies that detail the veracity of diagnostic accuracy at higher HR,14,17-22 prominent international guidelines for performance of CTCA have not, as yet, increased baseline HR recommendations for newer generation scanners.20,23

 

Studies of the diagnostic accuracy of CTCA are commonly compared to invasive coronary angiography (ICA).4,24 Invasive coronary angiography is established as the reference test or "gold standard" imaging test in the detection of significant CAD. The spatial resolution of ICA is higher than that achievable in CTCA, therefore a more precise conclusion can be made about the severity of coronary artery stenosis.25 Additionally, more information can be readily attained regarding the functional flow of coronary arteries in ICA. However, its position as the "gold standard" has come under recent scrutiny by some, due to: substantial cost, the small but important risk of complications, and limited accuracy in demonstrating the functional importance of a coronary artery stenosis.26,27 Despite this, it is the recognized industry standard and will be used as the comparator in this review.

 

The American Heart Association (AHA) has described and recommends the use of a 15 segment model for the description of the coronary artery tree in ICA.28 More recently, the Society of Cardiovascular CT adapted this recommendation to a 17 coronary artery segment model in CTCA to standardize the reporting of the coronary tree.29 This is performed by expert readers and compared back to the ICA reference standard. Using this approach, the sensitivity and specificity can be appreciated at per patient, per vessel and per segment level.

 

An initial search of PubMed, PROSPERO, JBI Database of Systematic Reviews and Implementation Reports, and the Cochrane Library did not locate any systematic reviews that established the impact of recent advances in scan technology on the accurate diagnosis of patients with high HRs. The aim of this review is therefore to determine the diagnostic accuracy of CTCA utilizing recent scan technologies, specifically as they relate to adult patients with high HR. The influence of individual scan technologies on diagnostic accuracy will also be investigated.

 

Review question

The primary question to be considered in this review is: what is the diagnostic accuracy of a computed tomography coronary angiography scan utilizing recent advances in technology compared to invasive coronary angiography for the diagnosis of coronary artery disease in adult patients with high heart rates?

 

A secondary question will also be considered: what is the diagnostic accuracy of a computed tomography coronary angiography scan utilizing individual technologies compared with invasive coronary angiography for adult patients with high heart rates in the diagnosis of coronary artery disease?

 

Inclusion criteria

Population

The review will consider adult patients (18 years and over) with a high HR who have undergone a CTCA to diagnose CAD. High HR will be defined as >65 bpm.

 

The review will exclude patients with: coronary artery bypass grafts, a history of heart transplantation, intraluminal stents, obesity, atrial fibrillation or severe CAD (>75% stenoses). Studies that assess anthropomorphic or other phantoms, ex-vivo, or animal studies will also be excluded.

 

Index test

This review will consider studies that evaluate CT scanner technology that utilize either single- or dual-source scanner configuration in prospective electrocardiogram (ECG) scan acquisition mode, and with a total scanner coverage equal to or greater than 128 detector-rows. The review will not consider studies where retrospective gating is performed, or where ECG gating is not used.

 

Calcium score studies will be excluded, as will studies that investigate non-coronary examinations such as scans of the aorta, pulmonary veins or functional studies of the heart.

 

Reference test

This review will consider studies that compare the index test to ICA. Invasive coronary angiography may be performed before or after CTCA, but tests should be performed within one year of each other.

 

Diagnosis of interest

Clinically significant CAD will be defined as the presence of a stenosis measuring greater than 50% of the vessel lumen diameter. The review will consider diagnostic accuracy at: per patient, per vessel and per segment level. Any study that uses the AHA segmental coronary model, or similar, as a grading scale will be included.

 

Types of studies

This review will consider diagnostic test accuracy study types, specifically those with a cross sectional design. Case-control studies will also be included.

 

This review will consider studies that describe any of the following measures: the sensitivity, specificity, positive predictive value, negative predictive value, odds ratio, prevalence and receiver-operator characteristic (ROC) in the evaluation of CAD. Specific data for true positives, true negatives, false positives and false negatives will be sought wherever possible.

 

Studies published in English will be included. Studies published prior to 2007 will be excluded, as the technologies being investigated were not clinically available prior to this time.

 

Methods

The proposed systematic review will be conducted in accordance with the JBI methodology for systematic reviews of diagnostic test accuracy.30

 

Search strategy

A three-stage search strategy will aim to find published and unpublished studies. An initial limited search (Stage 1) of PubMed has been undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the articles. This informed the development of a search strategy which will be tailored for each information source (Stage 2). A full search strategy for PubMed is detailed in Appendix I. Methodological search filters or terms will not be applied to the search strategy as they are not recommended for reviews of diagnostic test accuracy.31 The reference lists of all studies selected for critical appraisal will be screened for additional studies (Stage 3).

 

Information sources

The databases to be searched include: PubMed, Embase, CINAHL and Scopus. A pragmatic search of the first five pages of Google Scholar will also be performed.

 

The following information sources will also be investigated:

 

* The National Institute for Health Research - Health Technology Assessment (NIHR-HTA) register

 

* CT vendors (Canon, GE Healthcare, Philips and Siemens)

 

* Conference abstracts

 

* Authors with a significant research output in the field of CTCA and diagnostic accuracy.

 

 

Study selection

Following the search, all identified citations will be collated and uploaded into Endnote V8.2 (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers (GTWM and CS) for assessment against the inclusion criteria for each component of the review. Studies that meet the inclusion criteria will be retrieved in full and their details imported into Cochrane's Review Manager, RevMan V5.3 (Copenhagen: The Nordic Cochrane Centre, Cochrane). The full text of selected studies will be retrieved and assessed in detail against the inclusion criteria. Full text studies that do not meet the inclusion criteria will be excluded and reasons for exclusion will be provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. The results of the search will be reported in full in the final report and presented in a PRISMA flow diagram.32 Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer (ZM).

 

Assessment of methodological quality

Selected studies will be critically appraised by two independent reviewers (GTWM and CS) at the study level for methodological quality and risk of bias in the review using the QUADAS-2 review tool.33 Any disagreements that arise will be resolved through discussion, or where this is not adequate via a third reviewer (ZM). Selected studies, regardless of their methodological quality, will undergo data extraction and synthesis (where possible).

 

Data extraction

Data will be extracted by the lead investigator (GTWM) from papers included in the review and entered into Microsoft Excel for Mac 2016 Version 14.7.1 (Redmond, Washington, USA). The data extracted will include specific details about the tests, populations, study methods and outcomes of significance to the review questions and specific objectives. Specifically, true positive, true negative, false positive and false negatives values from each study will be included. Where this is not available, sensitivity and specificity values will be extracted. Authors of papers will be contacted to request missing or additional data, where required.

 

Data synthesis

Where possible, the results of papers will be pooled in statistical meta-analysis using RevMan. If meta-analysis is possible, pooled sensitivity and specificity values will be presented with 95% confidence intervals. These will be displayed on paired forest plots if the same diagnostic threshold values are used across studies, or summary receiver operating characteristic curves (SROC) if they vary. Heterogeneity will be assessed visually based on how closely the studies on the paired forest plot align, or how closely they map to the curve of the SROC. The strategy for meta-analysis will be based on the guidance by Campbell et al.30 If heterogeneity is suspected it will be investigated through subgroup analysis. Subgroups that will be investigated potentially include: individual vendor-specific scan configurations and parameters, and stratification of high HR. Subgroup analysis will be undertaken, where required, to determine differences in methodological quality between studies. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate.

 

Assessing certainty in the findings

A Summary of Findings will be created using GRADEpro software (McMaster University, ON, Canada). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for grading the quality of evidence for diagnostic test accuracy reviews will be followed.34 The following outcomes will be included in the Summary of Findings: accuracy estimates (sensitivity and specificity), as well as positive and negative predictive values, area under the curve values and study-specific thresholds for CAD diagnosis.

 

Acknowledgments

This review will contribute toward partial fulfillment of the requirements of the Master of Clinical Science awarded by The University of Adelaide in conjunction with Joanna Briggs Institute. This program is being funded by the Australian Government through an Australian Government Research Training Program (RTP) Scholarship.

 

The input received from Dr. Loretta Carr, cardiologist, Darling Downs Hospital and Health Service, is acknowledged.

 

Appendix I: Search strategy

The following search strategy will be performed in a search of the PubMed database. Similar search strategies will be performed for other databases.

 

PubMed search string:

  
Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

("heart rate"[mh:noexp] OR "elevated heart rate"[tiab] OR "high heart rate"[tiab] OR "sinus tachycardia"[tiab]) AND ("cardiac computed tomography angiography"[tw] OR "Cardiac CT"[tw] OR "dual source CT"[tw] OR "DSCT"[tiab] OR "320 detector CT"[tw] OR "320 slice"[tw] OR "computed tomography coronary angiography"[tw] OR "computerized tomography coronary angiography"[tw] OR "coronary computerized tomography angiography"[tw] OR "coronary computed tomography angiography"[tw] OR "coronary CTA"[tw] OR "coronary CT angiography"[tw] OR "CT coronary angiography"[tw] OR "CTCA"[tw] OR "CCTA"[tw] OR "motion correction"[tw] OR "SSF"[tiab] OR "256-slice"[tw]) AND ("coronary angiography"[mh] OR ("coronary"[tw] AND "angiography"[tw]) OR "coronary angiography"[tw])

 

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