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Aims: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF., Methods and Results: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance., Conclusion: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP., Competing Interests: Conflict of interest: M.B.M. received personal grants from the Rigshospitalets Research Foundation and the Heart Center Research Council, Rigshospitalet. J.J.L. has received grants from the Danish Research Foundation and the Research Council of Rigshospitalet during the conduct of the study. A.F. reports no conflicts of interest. B.G.N. has received consulting fees or honoraria for presentations by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Kowa, Denka Seiken, Amarin, Novartis, Novo Nordisk, Abbott, and Silence Therap. L.V.K. has received grants from the Danish Research Foundation during the conduct of the study. K.F.K. has received grants from Sygeforsikring ‘Danmark’, The Danish Agency for Science, Technology and Innovation, The Danish Council for Strategic Research, The University of Copenhagen, The Danish Heart Foundation, The Danish Research Foundation, The Research Council of Rigshospitalet, AP Moller og hustru Chastine McKinney Mollers Fond, The John and Birthe Meyer Foundation, The Lundbeck Foundation, and Canon Medical Systems Corporation. K.F.K. is on the Speakers Bureau of Canon Medical Systems Corporation. The funding sources did not have any role in the study design, conduct of the study, data analysis, data interpretation, or writing of this report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status., Materials and Methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications)., Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy., Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers., Clinical Relevance Statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status., Trial Registration: ClinicalTrials.gov NCT02400229., Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain., Methods: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris., Results: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48)., Conclusions: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.)., (Copyright © 2022 Massachusetts Medical Society.)

Purpose: To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD)., Methods: We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction., Results: Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization., Conclusions: Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures., Clinical Trial Registration: NCT00934037.

Background: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease., Objectives: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS., Methods: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard., Results: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group., Conclusions: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background CT allows evaluation of atherosclerosis, coronary stenosis, and myocardial ischemia. Data on the characterization of ischemia and no obstructive stenosis (INOCA) at CT remain limited. Purpose This was an observational study to describe the prevalence of INOCA defined at coronary CT angiography with CT perfusion imaging and associated clinical and atherosclerotic characteristics. The analysis was also performed for the combination of invasive coronary angiography (ICA) and SPECT as a secondary aim. Materials and Methods The prospective CORE320 study ( ClinicalTrials.gov : NCT00934037) enrolled participants between November 2009 and July 2011 who were symptomatic and referred for clinically indicated ICA. Participants underwent CT angiography, rest-adenosine stress CT perfusion, and rest-stress SPECT prior to ICA. For this ancillary study, the following three phenotypes were considered, using either CT angiography/CT perfusion or ICA/SPECT data: (a) participants with obstructive (≥50%) stenosis, (b) participants with no obstructive stenosis but ischemia (ie, INOCA) on the basis of abnormal perfusion imaging results, and (c) participants with no obstructive stenosis and normal perfusion imaging results. Clinical characteristics and CT angiography atherosclerotic plaque measures were compared by using the Pearson χ 2 or Wilcoxon rank-sum test. Results A total of 381 participants (mean age, 62 years [interquartile range, 56-68 years]; 129 [34%] women) were evaluated. A total of 31 (27%) of 115 participants without obstructive (≥50%) stenosis at CT angiography had abnormal CT perfusion findings. The corresponding value for ICA/SPECT was 45 (30%) of 151. The prevalence of INOCA was 31 (8%) of 381 (95% confidence interval [CI]: 5%, 11%) with CT angiography/CT perfusion and 45 (12%) of 381 (95% CI: 9%, 15%) with ICA/SPECT. Participants with CT-defined INOCA had greater total atheroma volume (118 vs 60 mm 3 , P = .008), more positive remodeling (13% vs 1%, P = .006), and greater low-attenuation atheroma volume (20 vs 10 mm 3 , P = .007) than participants with no obstructive stenosis and no ischemia. Comparisons for ICA/SPECT showed similar trends. Conclusion In CORE320, ischemia and no obstructive stenosis (INOCA) prevalence was 8% and 12% at CT angiography/CT perfusion and invasive coronary angiography/SPECT, respectively. Participants with INOCA had greater atherosclerotic burden and more adverse plaque features at CT compared with those with no obstructive stenosis and no ischemia. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by François in this issue.

Computed tomography derived fractional flow reserve (FFR CT ) and computed tomography stress myocardial perfusion imaging (CTP) are techniques to assess haemodynamic significance of coronary stenosis. To compare the diagnostic performance of FFR CT and static rest/stress CTP in detecting fractional flow reserve (FFR) defined haemodynamically-significant stenosis (FFR ≤ 0.8). Fifty-one patients (96 vessels) with suspected coronary artery disease from a single institution planned for elective invasive-angiography prospectively underwent research indicated 320-detector-CT-coronary-angiography (CTA) and adenosine-stress CTP and invasive FFR. Analyses were performed in separate core-laboratories for FFR CT and CTP blinded to FFR results. Myocardial perfusion was assessed visually and semi-quantitatively by transmural perfusion ratio (TPR). Invasive FFR ≤ 0.8 was present in 33% of vessels and 49% of patients. FFR CT , visual CTP and TPR analysis was feasible in 96%, 92% and 92% of patients respectively. Overall per-vessel sensitivity, specificity and diagnostic accuracy for FFR CT were 81%, 85%, 84%, for visual CTP were 50%, 89%, 75% and for TPR were 69%, 48%, 56% respectively. Receiver-operating-characteristics curve analysis demonstrated larger per vessel area-under-curve (AUC) for FFR CT (0.89) compared with visual CTP (0.70; p < 0.001), TPR (0.58; p < 0.001) and CTA (0.70; p = 0.0007); AUC for CTA + FFR CT (0.91) was higher than CTA + visual CTP (0.77, p = 0.008) and CTA + TPR (0.74, p < 0.001). Per-patient AUC for FFR CT (0.90) was higher than visual CTP (0.69; p = 0.0016), TPR (0.56; p < 0.0001) and CTA (0.68; p = 0.001). Based on this selected cohort of patients FFR CT is superior to visually and semi-quantitatively assessed static rest/stress CTP in detecting haemodynamically-significant coronary stenosis as determined on invasive FFR.

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe. Materials and Methods This was a prospective 16-center trial in 381 study participants undergoing coronary CT angiography with stress perfusion, SPECT, and invasive coronary angiography (ICA). Patient preferences were collected by using a previously validated questionnaire translated into eight languages. Responses were converted to ordinal scales and were modeled with generalized linear mixed models. Results In patients in whom at least one test was associated with pain, CT and SPECT showed reduced median pain levels, reported on 0-100 visual analog scales, from 20 for ICA (interquartile range [IQR], 4-50) to 6 for CT (IQR, 0-27.5) and 5 for SPECT (IQR, 0-25) ( P < .001). Patients from Asia reported significantly more pain than patients from other continents for ICA (median, 25; IQR, 10-50; P = .01), CT (median, 10; IQR, 0-30; P = .02), and SPECT (median, 7; IQR, 0-28; P = .03). Satisfaction with preparation differed by continent and test ( P = .01), with patients from Asia reporting generally lower ratings. Patients from North America had greater percentages of "very high" or "high" satisfaction than patients from other continents for ICA (96% vs 82%, respectively; P < .001) and SPECT (95% vs 79%, respectively; P = .04) but not for CT (89% vs 86%, respectively; P = .70). Among all patients, CT was preferred by 54% of patients, compared with 18% for SPECT and 28% for ICA ( P < .001). Conclusion For cardiac imaging, patients generally favored CT angiography with stress perfusion, while study participants from Asia generally reported lowest satisfaction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Woodard and Nguyen in this issue.

Background The predictive value of coronary artery calcium ( CAC ) has been widely studied; however, little is known about specific characteristics of CAC that are most predictive. We aimed to determine the independent associations of Agatston score, CAC volume, CAC area, CAC mass, and CAC density score with major adverse cardiac events in patients with suspected coronary artery disease. Methods and Results A total of 379 symptomatic participants, aged 45 to 85 years, referred for invasive coronary angiography, who underwent coronary calcium scanning and computed tomography angiography as part of the CORE 320 (Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) study, were included. Agatston score, CAC volume, area, mass, and density were computed on noncontrast images. Stenosis measurements were made on contrast-enhanced images. The primary outcome of 2-year major adverse cardiac events (30 revascularizations [>182 days of index catheterization], 5 myocardial infarctions, 1 cardiac death, 9 hospitalizations, and 1 arrhythmia) occurred in 32 patients (8.4%). Associations were estimated using multivariable proportional means models. Median age was 62 (interquartile range, 56-68) years, 34% were women, and 56% were white. In separate models, the Agatston, volume, and density scores were all significantly associated with higher risk of major adverse cardiac events after adjustment for age, sex, race, and statin use; density was the strongest predictor in all CAC models. CAC density did not provide incremental value over Agatston score after adjustment for diameter stenosis, age, sex, and race. Conclusions In symptomatic patients, CAC density was the strongest independent predictor of major adverse cardiac events among CAC scores, but it did not provide incremental value beyond the Agatston score after adjustment for diameter stenosis.

Purpose: Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS., Methods: Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen's kappa., Results: A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64-0.66, 0.69-0.76, 0.46-0.48, and 0.41-0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile., Conclusions: Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile., Competing Interests: Martina de Knegt has received research grants from The Danish Heart Foundation; The Danish Agency for Science, Technology and Innovation by The Danish Council for Strategic Research; and the Department of Cardiology, Hvidovre Hospital and has previously received lecturing fees from Toshiba Medical Systems. Lars Køber has received has received research grants from the Danish Research Council. Klaus Kofoed has received research grants from AP Møller og hustru Chastine McKinney Møllers Fond, The John and Birthe Meyer Foundation, Research Council of Rigshopitalet, The University of Copenhagen, The Danish Heart Foundation, The Lundbeck Foundation, The Danish Agency for Science, Technology and Innovation by The Danish Council for Strategic Research; is principle investigator of the investigator initiated CATCH-2 trial, CSub320 trial and at the steering committee of the CORE320 trial –supported in part by Toshiba Medical Corporation; and is on the Speakers Bureau of Toshiba Medical Systems, Advisory board work for VITAL Images Inc. All other authors report no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. These declarations of interest do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes., Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure., Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023)., Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Objectives: The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone., Background: Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease., Methods: Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization., Results: Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups., Conclusions: A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery calcification (CAC) is commonly assessed with Agatston score (AS). A higher sensitivity and precision for the detection of CAC has been demonstrated with calibrated mass score (cMS). We hypothesized that cMS would detect low-level CAC not detectable with AS in a large asymptomatic background population., Methods: Participants (N = 2985) from the Copenhagen General Population Study were evaluated for CAC using both conventional AS and cMS. The population was grouped according to number of traditional risk factors and heart score was used to assess the risk of event for those with no CAC, those with only cMS > 0 and those with both AS and cMS > 0., Results: In participants with an AS = 0, 11% had cMS > 0. The risk profile of this cMS-only group was between that of the CAC-negative participants and those with AS > 0 and cMS > 0. Overall, 6% of the population belonged to the cMS-only group independent of the number of risk factors., Conclusion: In individuals with AS = 0, a fraction was found to have cMS > 0. Based on traditional risk factors, this group has a higher 10-year risk than individuals with both AS = 0 and cMS = 0; cMS might offer very early cardiovascular risk assessment in asymptomatic individuals., Key Points: • In individuals with AS=0, a fraction has CAC with highly sensitive cMS. • This fraction has a higher 10-year risk of cardiovascular disease. • Regardless of risk factors, 6% has CAC detectable only with cMS. • cMS might offer very early cardiovascular risk assessment in asymptomatic individuals.

Objectives: Diagnostic accuracy of conventional coronary CT angiography (CCTA conv ) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTA sub ) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTA sub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTA conv ., Methods: In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTA conv , and CCTA sub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTA sub reconstruction process, in which case evaluation was omitted. CCTA sub and CCTA conv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTA conv versus CCTA sub to identify > 50% coronary stenosis by ICA on a per-segment level., Results: After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTA conv to 33% (CI:25-42%) in CCTA sub , at the expense of 7% (CI:3-14%) false negatives in CCTA sub ., Conclusions: In severely calcified coronary arteries or stents, CCTA sub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTA conv . Nevertheless, misregistration artifacts are frequent in CCTA sub ., Key Points: • A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT. • These patients would normally need an invasive angiogram for diagnosis. • In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations. • Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing.

Aims: To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging., Methods: The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC)., Results: Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(p > 0.05 for all)., Conclusion: Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease., Design: The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed., Results: CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of "no or medical treatment", "referral to percutaneous coronary intervention" or to "coronary artery bypass graft surgery" and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome., Conclusion: CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population.

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: Signs of pulmonary congestion obtained from cardiac computed tomography angiographic (coronary CTA) images have not previously been related to clinical congestion or outcome and the clinical value is, therefore, unknown. Our objective was to test the hypothesis that signs of pulmonary congestion predict clinical heart failure and adverse outcome in patients with myocardial infarction., Methods: Coronary CTA was performed before invasive treatment in 400 prospectively included patients with non ST segment elevation myocardial infarction in an observational study. Using a previously described chest computed tomography evaluation algorithm, patients were classified as having "no congestion", "mild to moderate congestion" or "severe congestion"., Results: Using multivariate analyses, presence of pulmonary congestion on coronary CTA images was associated with age, female gender, left ventricular ejection fraction (LVEF) and left atrial size. The diagnostic accuracy for predicting clinical heart failure, defined as Killip class >1, was: sensitivity: 83%, specificity: 69%, positive predictive value: 25%, and negative predictive value: 97%. The median follow-up time was 50 months and the study end-point of death or hospitalization due to heart failure was reached in 68 (16%) patients. In a Cox proportional hazards model with adjustments for known risk factors and Killip class, the presence of "mild to moderate congestion" and "severe congestion" was independently associated with adverse outcome (Hazard ratio: 2.6 (95% CI:1.3-5.0) and 3.2 (1.3-7.5))., Conclusion: Signs of pulmonary congestion on coronary CTA images are closely correlated to cardiac dysfunction, predict clinical heart failure, and provide prognostic value independent of LVEF and Killip class., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

To evaluate the interobserver agreement of visual coronary plaque characteristics by 320-slice multidetector computed tomography (MDCT) in three populations with low, intermediate and high CAD prevalence and to identify determinants for the reproducible assessment of these plaque characteristics. 150 patients, 50 asymptomatic subjects from the general population (low CAD prevalence), 50 symptomatic non-acute coronary syndrome (non-ACS) patients (intermediate CAD prevalence), and 50 ACS patients (high CAD prevalence), matched according to age and gender, were retrospectively enrolled. All coronary segments were evaluated for overall image quality, evaluability, presence of CAD, coronary stenosis, plaque composition, plaque focality, and spotty calcification by four readers. Interobserver agreement was assessed using Fleiss' Kappa (κ) and intra-class correlation (ICC). Widely used clinical parameters (overall scan quality, presence of CAD, and determination of coronary stenosis) showed good agreement among the four readers, (ICC = 0.66, κ = 0.73, ICC = 0.74, respectively). When accounting for heart rate, body mass index, plaque location, and coronary stenosis above/below 50 %, interobserver agreement for plaque composition, presence of CAD, and coronary stenosis improved to either good or excellent, (κ = 0.61, κ = 0.81, ICC = 0.78, respectively). Spotty calcification was the least reproducible parameter investigated (κ = 0.33). Across subpopulations, reproducibility of coronary plaque characteristics generally decreased with increasing CAD prevalence except for plaque composition, (limits of agreement: ±2.03, ±1.96, ±1.79 for low, intermediate and high CAD prevalence, respectively). 320-slice MDCT can be used to assess coronary plaque characteristics, except for spotty calcification. Reproducibility estimates are influenced by heart rate, body size, plaque location, and degree of luminal stenosis.

Aims: Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP., Methods: Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded., Discussion: The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.)

Objectives: The aim of the CATCH (CArdiac cT in the treatment of acute CHest pain) trial was to investigate the long-term clinical impact of a coronary computed tomographic angiography (CTA)-guided treatment strategy in patients with recent acute-onset chest pain compared to standard care., Background: The prognostic implications of a coronary CTA-guided treatment strategy have not been compared in a randomized fashion to standard care in patients referred for acute-onset chest pain., Methods: Patients with acute chest pain but normal electrocardiograms and troponin values were randomized to treatment guided by either coronary CTA or standard care (bicycle exercise electrocardiogram or myocardial perfusion imaging). In the coronary CTA-guided group, a functional test was included in cases of nondiagnostic coronary CTA images or coronary stenoses of borderline severity. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), hospitalization for unstable angina pectoris (UAP), late symptom-driven revascularizations, and readmission for chest pain., Results: We randomized 299 patients to coronary CTA-guided strategy and 301 to standard care. After inclusion, 24 patients withdrew their consent. The median (interquartile range) follow-up duration was 18.7 (range 16.8 to 20.1) months. In the coronary CTA-guided group, 30 patients (11%) had a primary endpoint versus 47 patients (16%) in the standard care group (p = 0.04; hazard ratio [HR]: 0.62 [95% confidence interval: 0.40 to 0.98]). A major adverse cardiac event (cardiac death, MI, hospitalization for UAP, and late symptom-driven revascularization) was observed in 5 patients (2 MIs, 3 UAPs) in the coronary CTA-guided group versus 14 patients (1 cardiac death, 7 MIs, 5 UAPs, 1 late symptom-driven revascularization) in the standard care group (p = 0.04; HR: 0.36 [95% CI: 0.16 to 0.95]). Differences in cardiac death and MI (8 vs. 2) were insignificant (p = 0.06)., Conclusions: A coronary CTA-guided treatment strategy appears to improve clinical outcome in patients with recent acute-onset chest pain and normal electrocardiograms and troponin values compared to standard care with a functional test. (Cardiac-CT in the Treatment of Acute Chest Pain [CATCH]; NCT01534000)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The reader confidence and diagnostic accuracy of coronary CT angiography (CCTA) can be compromised by the presence of calcified plaques and stents causing blooming artifacts. Compared to conventional invasive coronary angiography (ICA), this may cause an overestimation of stenosis severity leading to false-positive results. In a pilot study, we tested the feasibility of a new coronary calcium image subtraction algorithm in relation to reader confidence and diagnostic accuracy., Methods: Forty-three patients underwent clinically indicated ICA and CCTA using a 320-detector row CT. Median Agatston score was 510. Two data sets were reconstructed: a conventional CCTA (CCTAconv) and a subtracted CCTA (CCTAsub), where calcifications detected on noncontrast images were subtracted from the CCTA. Reader confidence and concordance with ICA for identification of >50% stenosis were recorded. We defined target segments on CCTAconv as motion-free coronary segments with calcification or stent and low reader confidence. The effect of CCTAsub was assessed. No approval from the ethics committee was required according to Danish law., Results: A total of 76 target segments were identified. The use of coronary calcium image subtraction improved the reader confidence in 66% of these segments. In target segments, specificity (86% vs 65%; P < .01) and positive predictive value (71% vs 51%, P = .03) were improved using CCTAsub compared to CCTAconv without loss in negative predictive value., Conclusions: Our initial experience with coronary calcium image subtraction suggests that it is feasible and could lead to an improvement in reader confidence and diagnostic accuracy for identification of significant coronary artery disease., (Copyright © 2015 Society of Cardiovascular Computed Tomography. All rights reserved.)

The challenge for therapies targeting perfusion abnormalities is to identify and evaluate the region of interest. The aim of this study was to compare rest and stress myocardial perfusion measured by cardiac multi-detector computed tomography (MDCT) and cardiac magnetic resonance (CMR) imaging in patients with invasive coronary angiography demonstrated occluded vessels. Twenty-four patients with refractory angina due to occluded coronary arteries underwent perfusion imaging obtained by 320-MDCT scanner and 1.5 T MR scanner. Rest and adenosine stress images were obtained and interpreted using the modified 17-segment American Heart Association model. For the qualitative analysis, each segment was graded according to the following scoring system: 0 = no defect, 1 = hypoperfusion transmural extent <1/3, 2 = 1/3-1/2, 3 = >1/2, and 4 = infarct stigmata. In the semiquantitative analysis the perfusion was either scored 0 (normal) or 1 (abnormal). The summed rest and stress scores were calculated. MDCT and CMR had a high probability to identify perfusion defects. An excellent correlation between MDCT and CMR summed rest (r = 0.916) and stress scores (r = 0.915) was found. The interobserver reproducibility was high for MDCT and CMR images. The qualitative and semiquantitative MDCT against CMR analysis of rest and stress images showed high concordance to detect perfusion defects per vascular territory and on a per myocardial segment basis. 320-MDCT and CMR perfusion imaging can be used clinically to identify myocardial perfusion defects and potentially evaluate the effect of therapy targeting perfusion abnormalities.

Recent studies have suggested that pericardial adipose tissue (PAT) located in close vicinity to the epicardial coronary arteries may play a role in the development of coronary artery disease. PAT has primarily been measured with cardiac magnetic resonance imaging (CMRI) or with non-contrast cardiac multidetector computered tomography (MDCT) images. The aim of this study was to validate contrast MDCT derived measures of total PAT volume by a comparison to CMRI. In 52 patients, aged 60 years (34-81 years), Body Mass Index 28 kg/m(2) (18-39), and with stable ischemic heart disease, paired MDCT and CMRI scans were performed. The optimal fit for measuring PAT using contrast MDCT was developed and validated by the corresponding measures on CMRI. The median for PAT volume in patients was 175 ml (SD 68) and 153 ml (SD 60) measured by MDCT and CMRI respectively. Four different attenuation values were tested, and the smallest difference in PAT was noted when -30 to -190 HU were used in MDCT measures. The median difference between MDCT and CMRI for the assessment of PAT was 9 ml (SD 50) suggesting a reasonable robust method for the assessment of PAT in a large-scale study. Pericardial adipose tissue can be measured on standard coronary CT angiography images with a reasonable degree of accuracy when compared to CMRI.

Background: Image noise and multiple sources of artifact may affect the accurate interpretation of myocardial CT perfusion (CTP) studies. Although artifact within the image is often time dependent, tissue characteristics remain unchanged irrespective of cardiac phase., Objective: We assessed a new technique of 4-dimensional, spatiotemporal analysis, using redundant time domain information within additional phase acquisitions to reduce CTP image noise., Methods: Four-dimensional analysis was assessed in a static phantom and in 10 CTP studies with invasive fractional flow reserve (FFR) correlation. For each voxel within the CTP study the distribution of local Hounsfield values was measured in both time and space with the use of a customized program within MATLAB software. These values were filtered to eliminate those likely to represent noise or rapidly changing beam hardening artifact. All CTP images were acquired within a single heartbeat with 320 detector-row CT. Image noise was quantified as the SD of voxel values within myocardial segments. Contrast was measured between normal and abnormal vascular territories as assessed by FFR., Results: The mean image noise within the unprocessed CTP images was 30 HU (range, 23-42 HU). After 4-dimensional filtering the mean image noise was 22 HU (range, 15-29 HU). The mean reduction in image noise was 28% (P < 0.001). The mean contrast between normally perfused and ischemic segments was not significantly changed. The mean increase in contrast-to-noise ratio between ischemic territories and the myocardial average was 52% (P < 0.001)., Conclusion: Four-dimensional analysis of CTP significantly reduces image noise and may assist in the assessment of myocardial perfusion studies., (Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

To determine via meta-analysis the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTA) for assessment of significant obstructive coronary artery stenosis at different coronary artery calcium score (CACS) levels. Data of 12,053 versus 5,890 segments, 906 versus 758 arteries and 1,120 versus 514 patients in low versus high CACS subgroups from 19 eligible studies were compared. The per-patient prevalence of coronary artery disease was 48% versus 68%, respectively. Subgroups were stratified by different CACS thresholds ranging from 100 to 400. Meta-analyses of per-patient data comparing overall low versus high CACS subgroups resulted in a sensitivity of 97.5 (95.5-99)% versus 97 (94.5-98.5)%, specificity of 85 (82-88)% versus 66.5 (58-74.5)%, diagnostic odds ratio of 153 (81-290) versus 40 (20-83), positive predictive value of 85 (82-87)% versus 86 (84-88)%, negative predictive value of 97.5 (95-99)% versus 91 (88-94)% and overall accuracy of 91% versus 89% with 95% confidence interval, respectively. The drop in specificity was significant (P = 0.035), while the sensitivity and overall accuracy were insignificantly changed (P > 0.05). Meta-analyses of independent subgroups at CACS levels ≤10 and ≤100 demonstrated high specificities of 90 (94-100)% and 88.5 (81-91.5)%, whereas at CACS levels ≥400 the specificity declined significantly to 42 (28-56)% but with consistently retained high sensitivity of 97.5 (94-99)%. The specificity of CTA decreases with increasing CACS, while the sensitivity remains high independent of that. The suggested CACS thresholds are arbitrary and do not necessarily warrant cancelling angiography. Diagnostic studies are needed to explore whether a specific CACS threshold may serve as a pre-angiographic gatekeeper to prevent likely equivocal angiographies.

Multidetector coronary computed tomography angiography (CTA) is a promising modality for widespread clinical application because of its noninvasive nature and high diagnostic accuracy as found in previous studies using 64 to 320 simultaneous detector rows. It is, however, limited in its ability to detect myocardial ischemia. In this article, we describe the design of the CORE320 study ("Combined coronary atherosclerosis and myocardial perfusion evaluation using 320 detector row computed tomography"). This prospective, multicenter, multinational study is unique in that it is designed to assess the diagnostic performance of combined 320-row CTA and myocardial CT perfusion imaging (CTP) in comparison with the combination of invasive coronary angiography and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The trial is being performed at 16 medical centers located in 8 countries worldwide. CT has the potential to assess both anatomy and physiology in a single imaging session. The co-primary aim of the CORE320 study is to define the per-patient diagnostic accuracy of the combination of coronary CTA and myocardial CTP to detect physiologically significant coronary artery disease compared with (1) the combination of conventional coronary angiography and SPECT-MPI and (2) conventional coronary angiography alone. If successful, the technology could revolutionize the management of patients with symptomatic CAD., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to test the hypothesis that measures of left atrial (LA) function are independent predictors of mortality in patients with acute myocardial infarction., Background: Left atrial maximal volume (LAmax) is known to predict mortality in patients with acute myocardial infarction. In a previous pilot study, however, we found that LA function in terms of fractional change and left atrial ejection fraction (LAEF) assessed by multidetector computed tomography (MDCT) is more closely related to clinical heart failure than LAmax., Methods: We prospectively included 384 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent retrospectively gated, 64-slice MDCT coronary angiography and subsequent measurements of LA size and function. All patients were treated according to the current guidelines based on invasive coronary angiography. Patients were followed for a minimum of 2 years. The study endpoint was all-cause mortality., Results: The median follow-up time was 36 months (range 10 to 1,551 days). During follow-up, 35 (9%) patients died. Overall, 1- and 2-year survival in the study cohort was 97% and 94%. LA size and mechanical function was obtained in all patients: mean LAmax was 55 ± 11 ml/m(2), LA minimal volume 31 ± 11 ml/m(2), fractional change 45 ± 9%, and LAEF 32 ± 9%. Using a Cox proportional hazards model with adjustments for age, number of diseased coronary vessels, left ventricular ejection fraction (LVEF), and Killip class, both fractional change (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.94) and LAEF (HR: 0.63; 95% CI: 0.44 to 0.91) remained independent predictors of mortality. In contrast to this, LAmax was not significantly associated with an increased risk of mortality in this population., Conclusions: In a low-risk group of patients with NSTEMI, reduced LA function is an independent predictor of mortality and provides prognostic value incremental to that of LAmax., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to determine whether the amount of noncalcified plaque (NCP) in nonobstructive coronary lesions as detected by multidetector computed tomography (MDCT) was a predictor of future coronary events., Background: Patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) frequently have multiple coronary plaques, which may be detected with MDCT., Methods: We included 312 consecutive patients presenting with NSTEMI, who underwent 64-slice MDCT coronary angiography and coronary artery calcium scoring before invasive coronary angiography. All patients were treated according to current guidelines based on an invasive treatment approach. Quantitative measurements of plaque composition and volume were performed by MDCT in all nonobstructive coronary lesions. The endpoint was cardiac death, acute coronary syndrome, or symptom-driven revascularization., Results: After a median follow-up of 16 months, 23 patients had suffered a cardiac event. Age, male sex, and diabetes mellitus were all associated with an increasing amount of NCP. In a multivariate regression analysis for events, the total amount of NCP in nonobstructive lesions was independently associated with an increased hazard ratio (1.18/100-mm(3) plaque volume increase, p = 0.01). Contrary to this, neither Agatston score nor the amount of calcium in nonobstructive lesions was associated with an increased risk., Conclusions: Multidetector computed tomography plaque imaging identified patients at increased risk of recurrent coronary events after NSTEMI by measuring the total amount of NCP in nonobstructive lesions. The amount of calcified plaque was not associated with an increased risk., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. Methods and results A total of 82 healthy individuals (46 women) aged 45–78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. Conclusion MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP. [ABSTRACT FROM AUTHOR]

Background: The ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated.Methods: This is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48-72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure.Results: Of 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357).Conclusion: In patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA <12 hours of diagnosis did not significantly improve long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

A correction to the article "Computed Tomography Versus Invasive Coronary Angiography in Patients With Diabetes and Suspected Coronary Artery Disease" in the Diabetes Care (date) issue is presented which includes the addition of the clinical trial number.

Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type.Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Trial Registration: Clinicaltrials.gov, NCT02400229. [ABSTRACT FROM AUTHOR]

Aims To compare the diagnostic performance of a reduced-order computed tomography-derived fractional flow reserve (CT-FFR) technique derived from luminal deformation and static CT stress myocardial perfusion (CTP). Methods and results Forty-six patients (84 vessels) with suspected coronary artery disease from a single institution planned for elective coronary angiography prospectively underwent research indicated invasive fractional flow reserve (FFR) and 320-detector CT coronary angiography (CTA) and static CTP. Analyses were performed in separate blinded core laboratories for CT-FFR and CTP. CT-FFR was derived using a reduced-order model with dedicated software on a standard desktop computer. CTP was assessed visually and quantitatively by transmural perfusion ratio (TPR). Invasive FFR was significant in 33% (28/84) of vessels. Overall per-vessel sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for CT-FFR were 81%, 84%, 71%, 90%, and 83%, respectively, those of visual CTP were 54%, 92%, 79%, 77%, and 78%, respectively, and TPR were 64%, 48%, 42%, 70%, and 54%, respectively. Per-vessel receiver operator curve analysis demonstrated a significantly larger area under the curve (AUC) for CT-FFR (0.89) with that for visual CTP (0.72; P  = 0.016), TPR (0.55; P  < 0.0001), and CTA (0.76; P  = 0.04). The addition of CT-FFR to CTA provided superior improvement in performance (AUC 0.93; P  < 0.0001) compared with CTA alone, a combination of CTA with visual CTP (AUC 0.82; P  = 0.007) and CTA with TPR (AUC 0.78; P  = 0.0006). Conclusion Based on this selected cohort of patients, a reduced-order CT-FFR technique is superior to visual and quantitatively assessed static CTP in detecting haemodynamically significant coronary stenosis as assessed by invasive FFR. [ABSTRACT FROM AUTHOR]

Background: Women with previous preeclampsia have an increased risk of coronary artery disease later in life.Objectives: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.Methods: Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA.Results: A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity.Conclusions: Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829). [ABSTRACT FROM AUTHOR]