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Background Ongoing advancements of coronary computed tomographic angiography (CTA) continue to challenge the role of invasive coronary angiography (ICA) as the gold standard for the evaluation of coronary artery disease (CAD). We sought to investigate the diagnostic accuracy of 320-slice CTA for detecting obstructive CAD in reference to ICA and nuclear myocardial perfusion imaging using single-photon emission computed tomography. Methods For the CORE320 study (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion), 381 patients at 16 centers underwent CTA, nuclear myocardial perfusion imaging by single-photon emission computed tomography, and ICA for the evaluation of CAD. Imaging studies were analyzed in blinded core laboratories, and a stenosis of ≥50% by quantitative coronary angiography was considered obstructive, whereas a stress difference score of ≥1 indicated inducible myocardial ischemia. The area under the receiver operating characteristic curve was used to evaluate diagnostic accuracy. Results Of 381 patients, 229 (60%) had obstructive CAD by quantitative coronary angiography. Diagnostic accuracy of CTA on a per-patient analysis revealed an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.87-0.93). Per-vessel and per-segment analysis revealed lower area under the receiver operating characteristic curve of 0.87 (0.84-0.90) and 0.81 (0.78-0.83), respectively. Median radiation dose was lower for CTA versus ICA: 3.16 (interquartile range, 2.82-3.59) versus 11.97 (interquartile range, 7.60-17.8) mSv ( P<0.001). Accuracy for identifying patients with inducible myocardial ischemia by SPECT-MPI was similar for CTA and ICA (area under the receiver operating characteristic curve, 0.68 versus 0.71 by quantitative coronary angiography and 0.68 by visual angiographic assessment; P>0.05). Furthermore, accuracy for identifying patients who subsequently underwent clinically driven coronary revascularization also was similar for CTA (0.76 [0.71-0.81]) and ICA (0.78 [0.74-0.83]; P=0.20). Conclusions Contemporary CTA accurately identifies patients with obstructive CAD by ICA at lower radiation exposure; however, agreement is lower in vessel- and segment-level analyses. Both CTA and ICA perform similarly for predicting clinically driven revascularization and for detecting myocardial ischemia by myocardial perfusion imaging using single-photon emission computed tomography, suggesting that limitations by both CTA and ICA contribute to variability of stenosis quantification. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00934037.

Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not significantly different for MACE or late MACE (P > .05 for all). The area under the receiver operating characteristic curve (AUC) for combined CT angiography and CT perfusion (AUC = 68; 95% confidence interval [CI]: 62, 75) was similar (P = .36) to that for combined ICA and single photon emission CT (AUC = 71; 95% CI: 65, 79) in the identification of MACE at 2-year follow-up. Conclusion Combined CT angiography and CT perfusion enables similar prediction of 2-year MACE, late MACE, and event-free survival similar to that enabled by ICA and single photon emission CT. © RSNA, 2017 Online supplemental material is available for this article.

Background: Coronary computed tomographic angiography (CTA) and myocardial perfusion imaging (CTP) is a validated approach for detection and exclusion of flow-limiting coronary artery disease (CAD), but little data are available on gender-specific performance of these modalities. In this study, we aimed to evaluate the diagnostic accuracy of combined coronary CTA and CTP in detecting flow-limiting CAD in women compared with men., Methods and Results: Three hundred and eighty-one patients who underwent both CTA-CTP and single-photon emission computed tomography myocardial perfusion imaging preceding invasive coronary angiography as part of the CORE320 multicenter study (Coronary Artery Evaluation Using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) were included in this ancillary study. All 4 image modalities were analyzed in blinded, independent core laboratories. Prevalence of flow-limiting CAD defined by invasive coronary angiography equal to 50% or greater with an associated single-photon emission computed tomography myocardial perfusion imaging defect was 45% (114/252) and 23% (30/129) in males and females, respectively. Patient-based diagnostic accuracy defined by the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone in females was 0.83 (0.75-0.89) and for CTA-CTP was 0.92 (0.86-0.97; P=0.003) compared with men where the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone was 0.82 (0.77-0.87) and for CTA-CTP was 0.84 (0.80-0.89; P=0.29)., Conclusions: The combination of CTA-CTP was performed similarly in men and women for identifying flow-limiting coronary stenosis; however, in women, CTP had incremental value over CTA alone, which was not the case in men., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037., (© 2016 American Heart Association, Inc.)

Background: Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis., Objectives: To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score., Methods: 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1., Results: In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020)., Conclusions: The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative., Methods and Results: We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001)., Conclusions: CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037., (© 2015 American Heart Association, Inc.)

OBJECTIVE. The purpose of this study was to comprehensively study estimated radiation doses for subjects included in the main analysis of the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (CORE320) study ( ClinicalTrials.gov identifier NCT00934037), a clinical trial comparing combined CT angiography (CTA) and perfusion CT with the reference standard catheter angiography plus myocardial perfusion SPECT. SUBJECTS AND METHODS. Prospectively acquired data on 381 CORE320 subjects were analyzed in four groups of testing related to radiation exposure. Radiation dose estimates were compared between modalities for combined CTA and perfusion CT with respect to covariates known to influence radiation exposure and for the main clinical outcomes defined by the trial. The final analysis assessed variations in radiation dose with respect to several factors inherent to the trial. RESULTS. The mean radiation dose estimate for the combined CTA and perfusion CT protocol (8.63 mSv) was significantly (p < 0.0001 for both) less than the average dose delivered from SPECT (10.48 mSv) and the average dose from diagnostic catheter angiography (11.63 mSv). There was no significant difference in estimated CTA-perfusion CT radiation dose for subjects who had false-positive or false-negative results in the CORE320 main analyses in a comparison with subjects for whom the CTA-perfusion CT findings were in accordance with the reference standard SPECT plus catheter angiographic findings. CONCLUSION. Radiation dose estimates from CORE320 support clinical implementation of a combined CT protocol for assessing coronary anatomy and myocardial perfusion.

Purpose: To compare the diagnostic performance of myocardial computed tomographic (CT) perfusion imaging and single photon emission computed tomography (SPECT) perfusion imaging in the diagnosis of anatomically significant coronary artery disease (CAD) as depicted at invasive coronary angiography., Materials and Methods: This study was approved by the institutional review board. Written informed consent was obtained from all patients. Sixteen centers enrolled 381 patients from November 2009 to July 2011. Patients underwent rest and adenosine stress CT perfusion imaging and rest and either exercise or pharmacologic stress SPECT before and within 60 days of coronary angiography. Images from CT perfusion imaging, SPECT, and coronary angiography were interpreted at blinded, independent core laboratories. The primary diagnostic parameter was the area under the receiver operating characteristic curve (Az). Sensitivity and specificity were calculated with use of prespecified cutoffs. The reference standard was a stenosis of at least 50% at coronary angiography as determined with quantitative methods., Results: CAD was diagnosed in 229 of the 381 patients (60%). The per-patient sensitivity and specificity for the diagnosis of CAD (stenosis ≥50%) were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95% confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion imaging for single- and multivessel CAD was higher than that of SPECT, with sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT., Conclusion: The overall performance of myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis ≥50%), as demonstrated with the Az, was higher than that of SPECT and was driven in part by the higher sensitivity for left main and multivessel disease.

Aims: To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT)., Methods and Results: We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels., Conclusions: The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Background: Computed tomography coronary angiography (CTA) has been shown to be accurate in detecting anatomic coronary arterial obstruction, but is limited for the detection of myocardial ischemia. The primary aim of this study was to assess the accuracy of 320-row computed tomography perfusion imaging (CTP) to detect atherosclerosis causing myocardial ischemia., Methods and Results: Fifty symptomatic patients with recent single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) underwent a comprehensive cardiac computed tomography (CT) protocol that included 320-CTA, followed by adenosine stress CTP. CTP images were analyzed quantitatively for the presence of subendocardial perfusion deficits. All analyses were blinded to imaging and clinical results. CTA alone was a limited predictor of myocardial ischemia compared with SPECT, with a sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of 56%, 75%, 56%, and 75%, and the area under the receiver operator characteristic curve (AUC) was 0.65 (95% CI, 0.51-0.78, P=0.07). CTP was a better predictor of myocardial ischemia, with a sensitivity, specificity, PPV, and NPV of 72%, 91%, 81%, and 85%, with an AUC of 0.81 (95% CI, 0.68-0.91, P<0.001), and was an excellent predictor of myocardial ischemia on SPECT-MPI in the presence of stenosis (≥50% on CTA), with a sensitivity, specificity, PPV, and NPV of 100%, 81%, 50%, and 100%, with an AUC of 0.92 (95% CI, 0.80-0.97, P<0.001). The radiation dose for the comprehensive cardiac CT protocol and SPECT were 13.8±2.9 and 13.1±1.7; respectively (P=0.15)., Conclusions: Computed tomography perfusion imaging with rest and adenosine stress 320-row CT is accurate in detecting obstructive atherosclerosis causing myocardial ischemia.

Background: Multidetector computed tomography coronary angiography (CTA) is a robust method for the noninvasive diagnosis of coronary artery disease. However, in its current form, CTA is limited in its prediction of myocardial ischemia. The purpose of this study was to test whether adenosine stress computed tomography myocardial perfusion imaging (CTP), when added to CTA, can predict perfusion abnormalities caused by obstructive atherosclerosis., Methods and Results: Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses > or =50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively., Conclusions: The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.