ABSTRACTS  & OBJECTIVES
 

The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetector row coronary computed tomographic angiography (CCTA) in individuals without known coronary artery disease (CAD).

Background:

CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no prospective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populations with intermediate prevalence of CAD.

Methods:

We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronary angiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluated for coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baseline coronary artery calcium score or body mass index.

Results:

A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 ± 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect 50% or 70% stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively.

No differences in sensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates 65 beats/min compared with >65 beats/min, whereas calcium scores >400 reduced specificity significantly.

Conclusions:

In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA possesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and 70% stenosis.

Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as an effective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomography [CT] for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569 [ClinicalTrials.gov] )

Key Words: computed tomography • coronary artery disease • angiography

Abbreviations and Acronyms   AUC = area under the receiver-operating characteristic curve   CAC = coronary artery calcium   CAD = coronary artery disease   CCTA = coronary computed tomographic angiography   ICA = invasive coronary angiography   MDCT = multidetector (row) computed tomography   NPV = negative predictive value   PPV = positive predictive value   QCA = quantitative coronary angiography

Coronary computed tomographic angiography (CCTA) has emerged as a promising noninvasive method for the detection and exclusion of obstructive coronary artery disease (CAD) (1).

However, widespread clinical applicability of CCTA remains limited, because earlier studies have excluded subjects based on baseline coronary artery calcium (CAC) score or heart rate and have assessed diagnostic performance of CCTA after exclusion of nonevaluable coronary artery segments.

In addition, these studies were largely performed in patients with high prevalence (high clinical pre-test likelihood), which can potentially skew the results when applied to other pre-test likelihood groups. Recent studies evaluating the diagnostic performance of newer 64-multidetector (row) computed tomography (MDCT) scanners have shown further potential for an improvement in CCTA diagnostic accuracy and reduction in the number of nonevaluable coronary artery segments compared with older-generation CT scanners (2).

However, these studies have been limited to single centers for patients with primarily high prevalence of obstructive coronary artery stenoses. To our knowledge, to date, no prospective multicenter trial for CCTA efficacy in patients without known CAD or with intermediate prevalence of CAD has yet been reported.

The aim of the present prospective blinded multicenter study was to test the ability of current-generation 64-multidetector row CCTA to detect or exclude significant coronary artery stenosis in chest pain subjects without known CAD, using an American Heart Association (AHA) classification of coronary artery segments (3).

We assessed the diagnostic performance of 64-multidetector row CCTA on a per-patient and -vessel basis, including all patients and all vessels for final efficacy analysis.

Methods

Patients.  

The ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) study was designed to prospectively evaluate adult subjects with chest pain who were being clinically referred for nonemergent invasive coronary angiography (ICA).

Potential study subjects were screened and enrolled by a site research coordinator if they met both inclusion and exclusion criteria.

Study subjects were asked to undergo a research CCTA, as well as data and blood collection as specified by a pre-defined research protocol.

Individuals were eligible for participation in the ACCURACY trial if they were 18 years of age, experienced typical or atypical chest pain, and were being referred for nonemergent ICA.

Individuals were excluded from participation in the ACCURACY trial for the following reasons: known allergy to iodinated contrast; baseline renal insufficiency (creatinine 1.7 mg/dl); irregular cardiac rhythm; resting heart rate >100 beats/min; resting systolic blood pressure <100 mm Hg; contraindication to beta-blocker, calcium-channel blocker, or nitroglycerin; pregnancy; and known history of CAD (prior myocardial infarction, percutaneous transluminal coronary angioplasty or intracoronary stent, or coronary artery bypass surgery). Importantly, patients were not excluded for an elevated CAC score or body mass index.

The study was performed at 16 centers in the U.S. (Online Appendix). Before the study commenced, each Institutional Review Board had reviewed and approved the study protocol and patient safety monitoring plan. Protocols associated with patient enrollment, safety analysis, image acquisition, image interpretation, and statistical analysis were developed by a Steering Committee.

GE Healthcare (Milwaukee, Wisconsin) performed study monitoring, data management, and quality control. Adverse and serious adverse events were determined for follow-up by a Data and Safety Monitoring Board.

Sample size.  

Estimation of sample sizes using a binary end point for each subject (e.g., agreement between CCTA and ICA, whether sensitivity or specificity) gave a conservative estimate of the required sample size.

Based on historical data, we assumed values for sensitivity and specificity of 0.88 (standard deviation: 0.045) at the patient level, which required a minimum of 173 subjects to reject the null hypothesis that either sensitivity or specificity is 0.80 in favor of the alternative >0.80.

CCTA image acquisition.  

Study subjects underwent CCTA before conventional ICA. All CCTA scans were performed with a 64-multidetector row Lightspeed VCT scanner (GE Healthcare). All patients were in normal sinus rhythm at the time of the CCTA scan. Individuals presenting with baseline heart rates >65 beats/min were administered oral beta-blocker therapy as the preferred method for slowing down the heart rate. Intravenous administration was allowed in the protocol, using metoprolol at 5 mg increments to a total possible dose of 25 mg to achieve a resting heart rate <65 beats/min.

All patients eligible for CCTA were scanned, whether or not the goal of a heart rate <65 beats/min was achieved.

Following a scout radiograph of the chest (anteroposterior and lateral), a timing bolus (using 10 to 20 ml contrast) was performed to detect time to optimal contrast opacification in the axial image at a level immediately superior to the ostium of the left main artery. Nitroglycerine 0.4 mg sublingually was administered immediately before contrast injection.

During CCTA acquisition, 80-ml iodinated contrast (Visipaque, GE Healthcare, Buckinghamshire, United Kingdom) was injected using a triple-phase contrast protocol: 60-ml iodixanol, followed by 40 ml of a 50:50 mixture of iodixanol and saline, followed by a 50-ml saline flush. Retrospective electrocardiogram-gated helical contrast-enhanced CCTA was performed, with scan initiation 20 mm above the level of the left main artery to 20 mm below the inferior myocardial apex.

The scan parameters were 64 x 0.625 mm collimation, tube voltage 120 mV, and effective mA 350 to 780 mA. Radiation reduction algorithms using electrocardiography modulation were used, which reduce radiation exposure (mA) during systole and end-diastole.

After scan completion, multiphasic reconstruction of the CCTA scans was performed, with reconstructed images from 70% to 80% by 5% increments and 5% to 95% by 10% increments.

CCTA interpretation.  

The CCTA images were interpreted separately by 3 readers (M.J.B., D.D., and J.K.M.) blinded to all patient characteristics and ICA results. All CCTA images were evaluated on a 3-dimensional image analysis workstation (GE Advantage Workstation, GE Healthcare, Milwaukee, Wisconsin).

The CCTA readers were permitted to use any or all of the available post-processing image reconstruction algorithms, including 2-dimensional axial and 3-dimensional maximal intensity projection, multiplanar reformat, cross-sectional analysis, and volume-rendered technique.

Coronary arteries were scored using a 15-segment AHA coronary artery classification, as previously described (3). An overall assessment of image quality and coronary supply dominance was performed on the subject level (4,5).

For each coronary segment, readers assessed whether coronary segments were evaluable. For any coronary artery segments considered to be nonevaluable, stenosis severity was assigned based on the outcome of the most adjacent proximal and identifiable segment, as previously described (6).

A semiquantitative scale was used by the CCTA readers to grade extent of luminal stenosis as a percentage of the vessel diameter using visual estimations.

Stenosis severity was recorded in the following manner: no stenosis; 1% to 29% stenosis; 30% to 49% stenosis; 50% to 69% stenosis; 70% to 99% stenosis; and 100% stenosis.

For coronary artery segments considered to have 100% stenosis by CCTA, all segments distal to the occlusion were excluded from analysis (Fig. 1).

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  Figure 1 Computed Tomographic Angiogram and Invasive Angiogram Demonstrating Significant Left Anterior Descending Artery Disease

(A) Right anterior oblique orientation of left anterior descending artery with quantitative coronary angiography. (B) Multiplanar reformation and short-axis cross-sectional view (inset) of the left anterior descending artery demonstrating obstructive coronary artery stenosis. (C) Curved multiplanar reformat of the left anterior descending artery demonstrating obstructive coronary artery stenosis. (D) Volume-rendered view of the left anterior descending artery. Arrows indicate the significant stenosis present on the computed tomographic angiogram and corresponding invasive angiogram.

ICA image acquisition and interpretation.   Selective ICA was performed by standard transfemoral arterial catheterization. A minimum of 8 projections were obtained (minimum of 5 views for the left coronary artery system and minimum of 3 views for the right coronary artery system). Because of differences in cardiac position, angles of projection for ICA differed slightly among study subjects.

All ICA images were interpreted by an independent ICA reader (J.G.J.) blinded to all patient characteristics and CCTA results. The ICAs were quantitatively evaluated for coronary artery stenosis with quantitative coronary angiography (QCA) software (CAAS, Pie Medical Imaging, Maastricht, the Netherlands). Any segment deemed visually to have >15% stenosis was quantified.

Coronary artery segments by QCA were also evaluated using a 15-segment AHA coronary tree model and were judged as having significant stenosis at 2 levels (i.e., if 50% or 70% luminal narrowing of the coronary artery diameter was present).

Data analysis.  

In all analyses, all patients and all vessels were included. Analyses were performed separately for 2 distinct conditions—50% and 70% luminal diameter narrowing—that defined obstructive coronary artery stenosis.

For the patient-based analysis, a true-positive was defined as the presence of 1 coronary artery segment considered to have an obstructive stenosis by both CCTA and ICA, irrespective of location.

For the vessel-based analysis, a true-positive was defined as the presence of 1 coronary artery segment considered to have an obstructive stenosis by both CCTA and ICA in a single arterial system.

Four arterial systems were predefined and consisted of the:

• 1) left main artery;
• 2) left anterior descending artery inclusive of diagonal branches; 3) left circumflex artery inclusive of obtuse marginal and left-sided posterolateral branches; and
• 4) right coronary artery inclusive of posterior descending artery and right-sided posterolateral branches.

Ramus intermediate arteries were considered to be the first obtuse marginal branch for per-vessel analyses.

Statistical analysis.  

Categorical variables are presented as frequency and percentage, continuous variables as mean ± SD.

The area under the receiver operating characteristic curve (AUC) was calculated for CCTA to identify obstructive coronary artery stenosis at either 50% or 70% threshold.

All statistical analyses were performed using SAS Proprietary Software, version 9.1 (SAS Institute, Cary, North Carolina).

SEE FULLTEXT http://content.onlinejacc.org/cgi/content/full/52/21/1724?

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