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Objectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. Methods Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. Results The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (

Aims: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes., Methods and Results: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004)., Conclusion: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse., Objectives: This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins., Methods: The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque., Results: The authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively)., Conclusions: In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction., Competing Interests: Funding Support and Author Disclosures This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (grant no. 2012027176). The study was also funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging (New York, New York, USA) and the Michael Wolk Foundation (New York, New York, USA). Dr Min is an employee of Cleerly Inc. Dr Leipsic is a consultant to and holds stock options in Circle CVI and HeartFlow; and has received modest speaking fees from Philips and GE Healthcare. Dr Chinnaiyan is a noncompensated medical advisory board member of Heartflow Inc. Dr Samady serves on the scientific advisory board of Philips; has equity interest in Covanos Inc; and has a research grant from Medtronic, Abbott Vascular, and Philips. Dr Virmani is a consultant of Abbott Vascular, Boston Scientific, Celonova, OrbusNeich Medical, Terumo Corporation, W.L. Gore, Edwards Lifesciences, Cook Medical, CSI, ReCor Medical, SinoMedical Sciences Technology, Surmodics, and Bard BD; and is a scientific Advisory Board Member of Medtronic and Xeltis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Purpose: In this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis., Materials and Methods: In this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty., Results: A total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD ( n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD ( n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque., Conclusion: In participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque. Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue., Competing Interests: Disclosures of conflicts of interest: P.I. No relevant relationships. C.N. No relevant relationships. S.B.Z. No relevant relationships. H.G. No relevant relationships. P.B. Consulting fees from Edwards Lifesciences, Neovasc, and Boston Scientific. S.S. No relevant relationships. S.A. No relevant relationships. M.H.A. Grant/contract from Siemens; consulting fees from Philips. D.A. No relevant relationships. D.S.B. Software royalties from Cedars-Sinai Medical Center. M.J.B. No relevant relationships. F.C. No relevant relationships. T.Q.C. No relevant relationships. H.J.C. No relevant relationships. K.C. Executive Committee and Board of Directors, Society for Cardiovascular Computed Tomography (SCCT), unpaid. B.J.W.C. Saul and Edna Goldfarb Chair in Cardiac Imaging; research grants from TD Bank, AusculSciences, Artrya, and CV Diagnostix; board member of SCCT (ended in 2021); stock in GE (equity sold in 2021). R.C.C. Consults for Covera Health, GE Healthcare, and Cleerly (not related to the topic of this article). A.D. No relevant relationships. G.F. No relevant relationships. M.H. No relevant relationships. J.H. Grant/contract from Edwards Lifesciences, payment or honoraria from Abbott Vascular and Edwards Lifesciences, support for meetings and travel from Abbott Vascular and Edwards Lifesciences. P.A.K. University Hospital Zurich holds a research grant with GE Healthcare (unrelated to the present study), Advisory Board for GE Healthcare on the myocardial perfusion tracer Flurpiridaz (unrelated to present study), Vice Chair of the Swiss Society of Nuclear Medicine (unpaid). Y.J.K. No relevant relationships. E.M. No relevant relationships. H.M. No relevant relationships. P.d.A.G. No relevant relationships. G.P. No relevant relationships. G.L.R. No relevant relationships. R.R. Board member of SCCT. T.C.V. No relevant relationships. F.Y.L. Research grant from GE. L.J.S. No relevant relationships. J.N. No relevant relationships. J.J.B. The department of cardiology, Leiden University Medical Center has received unrestricted research grants from Abbott, Edwards Lifesciences, Bayer, Novartis, Boston Scientific, Medtronic, Biotronik, GE Healthcare; payment or honoraria from Speaker Bureau Abbott and Edwards Lifesciences. J.A.L. Unrestricted research grant from GE Healthcare, stock options and consulting fees from HeartFlow and Circle CVI, payment or honoraria from Philips, board of directors of SCCT, deputy editor for Radiology: Cardiothoracic Imaging., (© 2022 by the Radiological Society of North America, Inc.)

Aims: The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea., Methods and Results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD., Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA)., Background: Coronary CTA can noninvasively assess coronary plaques quantitatively., Methods: Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome., Results: Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm 3 [interquartile range (IQR): 0.0 to 39.6 mm 3 ]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm 3 [IQR: 0.0 to 127.4 mm 3 ]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm 3 [IQR: 96.7 to 306.4 mm 3 ]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features., Conclusions: The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)., Competing Interests: Funding Support And Author Disclosures This work was supported by a grant from Seoul National University Hospital research fund (Grant No. 0320200430), the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176) (to Dr. Chang), and the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2017R1E1A1A03070779, 2018R1A2A3075511, 2019R1A2C2084099, and 2020R1A2C1A01011543). The study was also funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Koo has received institutional research grant support from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr. Samady has served on the scientific advisory board of Philips; has an equity interest in Covanos Inc.; and has received research grant support from Medtronic. Dr. Min has received funding from the Dalio Foundation, the National Institutes of Health, and GE Healthcare; has served on the scientific advisory board of Arineta and GE Healthcare; and has an equity interest in Cleerly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS)., Methods and Results: Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. ≥ 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 ± 163.7 vs. 63.8 ± 94.2 mm3, P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 ± 44.1 vs. 75.3 ± 98.6 mm3, P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed., Conclusion: Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics., Background: Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known., Methods: Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion., Results: CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs., Conclusions: In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions., Methods and Results: Within the ICONIC study, a nested case-control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (≥50%) and non-obstructive (<50%) diameter stenosis, with HRP defined as ≥2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5-525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P < 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26-2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61-3.25, P = 0.42)., Conclusions: While HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA)., Methods: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm 3 ) at follow-up minus PV at index > 0. Annual change of PV (mm 3 /year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year., Results: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors., Conclusion: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Objectives: This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP)., Background: It is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP., Methods: Patients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. HRP was defined as lesions with ≥2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions., Results: A total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 ± 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05)., Conclusions: The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation., Background: Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images., Methods: Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split., Results: The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups., Conclusions: An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level., Competing Interests: James K. Min received funding from the Dalio Foundation. Dr. Pontone receives institutional research grant support and is a speaker for Heartflow, Medtronic, GE Healthcare, Bracco Diagnostics, and Bayer Life Sciences. Dr. Jonathon Leipsic is a consultant and has reported stock options with Circle CVI and HeartFlow. Gabriel Maliakal previously worked at Weill Cornell Medicine but is now an employee at Cleerly Health. The work done in this study was during Gabriel Maliakal’s full-time employment at Weill Cornell Medicine. Dr. Min previously worked at Weill Cornell Medicine but is now an employee and has an equity interest in Cleerly Health. The work done in this study was during Dr.Min’s full-time employment at Weill Cornell Medicine. Dr. Shaw has an equity interest in Cleerly Health. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Aims: In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent., Methods and Results: Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004)., Conclusion: Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men., Methods and Results: A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55-65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41-0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD)., Conclusion: Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01443637., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P <0.001; statistical model, 0.81 [0.75-0.87], P =0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP.

Objectives: This study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography-derived fractional flow reserve (FFR CT ) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)-based triage program., Background: FFR CT is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied., Methods: ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFR CT were studied. FFR CT  ≤0.80 was considered positive for hemodynamically significant stenosis., Results: Among 555 patients, 297 underwent coronary CTA and FFR CT (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFR CT was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFR CT groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFR CT results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFR CT when revascularization was deferred. Negative FFR CT was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFR CT (8.0%) and coronary CTA (22.9%) (p < 0.001). There was no difference in overall costs between the coronary CTA and FFR CT groups ($8,582 vs. $8,048; p = 0.550)., Conclusions: In ACP, FFR CT is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFR CT , which is associated with higher nonobstructive disease on invasive angiography., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA)., Methods and Results: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features., Conclusion: A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFR CT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFR CT ) with downstream care and clinical outcomes., Background: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes., Methods: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFR CT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured., Results: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFR CT  ≤0.80 and in 89 (5.60%) with an FFR CT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFR CT  ≤0.80 and 12 occurred in those with an FFR CT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFR CT  ≤0.80 compared with 10 (0.60%) patients with an FFR CT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFR CT  ≤0.80 compared with patients with an FFR CT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01)., Conclusions: The 1-year outcomes from the ADVANCE FFR CT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFR CT compared with patients with abnormal FFR CT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The long-term prognostic value of coronary computed tomography angiography (CCTA)-identified coronary artery disease (CAD) has not been evaluated in elderly patients (≥70 years). We compared the ability of coronary CCTA to predict 5-year mortality in older vs. younger populations., Methods and Results: From the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age <70 years (n = 7198) vs. ≥70 years (n = 1786). The severity of CAD was classified according to: (i) maximal stenosis degree per vessel: none, non-obstructive (1-49%), or obstructive (>50%); (ii) segment involvement score (SIS): number of segments with plaque. Cox-proportional hazard models assessed the relationship between CCTA findings and time to mortality. At a mean 5.6 ± 1.1 year follow-up, CCTA-identified CAD predicted increased mortality compared with patients with a normal CCTA in both <70 years [non-obstructive hazard ratio (HR) confidence interval (CI): 1.70 (1.19-2.41); one-vessel: 1.65 (1.03-2.67); two-vessel: 2.24 (1.21-4.15); three-vessel/left main: 4.12 (2.27-7.46), P < 0.001] and ≥70 years [non-obstructive: 1.84 (1.15-2.95); one-vessel: HR (CI): 2.28 (1.37-3.81); two-vessel: 2.36 (1.33-4.19); three-vessel/left main: 2.41 (1.33-4.36), P = 0.014]. Similarly, SIS was predictive of mortality in both <70 years [SIS 1-3: 1.57 (1.10-2.24); SIS ≥4: 2.42 (1.65-3.57), P < 0.001] and ≥70 years [SIS 1-3: 1.73 (1.07-2.79); SIS ≥4: 2.45 (1.52-3.93), P < 0.001]. CCTA findings similarly predicted long-term major adverse cardiovascular outcomes (MACE) (all-cause mortality, myocardial infarction, and late revascularization) in both groups compared with patients with no CAD., Conclusion: The presence and extent of CAD is a meaningful stratifier of long-term mortality and MACE in patients aged <70 years and ≥70 years old. The presence of obstructive and non-obstructive disease and the burden of atherosclerosis determined by SIS remain important predictors of prognosis in older populations., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFR CT ) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFR CT in Japan are scarce, so we assessed the clinical impact of using FFR CT in a Japanese population.Methods and Results:The ADVANCE registry is an international prospective FFR CT registry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFR CT , treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFR CT occurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFR CT ≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFR CT >0.80) (20.5% vs. 46.1%, P=0.0001). After FFR CT , 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFR CT were medically treated. MACE occurred in 5 patients with positive FFR CT , but none occurred in patients with negative FFR CT within 90 days., Conclusions: In this Japanese population, FFR CT modified the treatment strategy in more than half of the patients. FFR CT showed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Background: The extent to which the presence and extent of subclinical atherosclerosis by coronary computed tomography angiography influences a potential mortality benefit of statin is unknown. We evaluated the relationship between statin therapy, mortality, and subclinical atherosclerosis., Methods: In the CONFIRM study, patients with normal or non-obstructive plaque (<50% diameter stenosis) for whom data on baseline statin use was available were included. Coronary artery calcium (CAC) was quantified using the Agatston score. The extent of non-obstructive coronary atherosclerosis was quantified using the segment involvement score (SIS). 8,016 patients were followed for a median of 2.5 years with analysis of all-cause mortality and major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, unstable angina, target vessel revascularization, and coronary artery disease-related hospitalization., Results: 1.2% of patients experienced all-cause mortality. Patients not on baseline statin therapy had a stepwise increased risk of all-cause mortality by CAC (relative to CAC = 0; CAC 1-99: hazard ratio [HR] 1.65, CAC 100-299: HR 2.19, and CAC≥300: HR 2.98) or SIS (relative to SIS = 0; SIS 1: HR 1.62, SIS 2-3: 2.48 and SIS≥4: 2.95). Conversely, in patients on baseline statin therapy, there was no significant increase in mortality risk with increasing CAC (p value for interaction = 0.049) or SIS (p value for interaction = 0.007). The incidence of MACE was 2.1%. Similar to the all-cause mortality, the risk of MACE was increased with CAC or SIS strata in patient not on baseline statin therapy. However, this relation was not observed in patient on baseline statin therapy., Conclusion: In individuals with non-obstructive coronary artery disease, increased risk of adverse events occurs with increasing CAC or SIS who are not on baseline statin therapy. Statin therapy is associated with a mitigation of risk of cardiac events in the presence of increasing atherosclerosis, with no particular threshold of disease burden., Competing Interests: Dr. James K. Min receives research support from the Dalio Institute of Cardiovascular Imaging. This study was also funded, in part, by a generous gift from the Dalio Institute of Cardiovascular Imaging (New York, NY) and the Michael Wolk Foundation (New York, NY). Dr. Min has a research agreement with GE Healthcare, serves on the scientific advisory board of Arineta, and has ownership in MDDX. Dr. Nam received research grant support from Pfizer, Medtronic and Biosensors, and served as a consultant to Saint Jude Medical. Dr. Achenbach received grant support from Siemens and Bayer Schering Pharma and has served as a consultant for Servier. Dr. Al-Mallah received support from the American Heart Association, BCBS Foundation of Michigan, and Astellas. Dr. Cademartiri received grant support from GE Healthcare and has served on the Speakers’ Bureau of Bracco and as a consultant for Servier. Dr. Maffei received grant support from GE Healthcare. Dr. Chow receives educational and research support from TeraRecon and research support from CV Diagnostix. Dr Leipsic is a consultant and has stock options in both Heartflow and Circl CVI and has received speaking fees from GE Healthcare. Dr. Hausleiter is a speaker honoraria from Abbott Vascular and Edwards LifeSciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden., Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS., Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA-evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs)., Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm 3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm 3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP., Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden., (Published by Elsevier Inc.)

Over 8 million patients seek emergency department care for acute chest pain annually in the United States alone, and <5% have an acute coronary syndrome. In the absence of overt electrocardiographic or biomarker evidence, expensive and time-consuming diagnostic strategies are frequently required. Beginning in 2000, radionuclide myocardial perfusion, stress echocardiography, cardiac magnetic resonance imaging, and coronary computed tomographic angiography have become increasingly common in evaluating these patients. This review paper focuses on randomized clinical trials that provide the evidence base for these diagnostic strategies. Novel imaging modalities combining high-sensitivity troponin with imaging or combined anatomic-physiological evaluation using fractional flow reserve by computed tomography are also discussed., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the diagnostic yield of triple rule out (TRO) versus coronary computed tomography angiography (CTA) scanning in patients with acute chest pain enrolled in a large statewide registry., Background: Although TRO scans provide simultaneous evaluation of coronary artery disease (CAD), pulmonary embolism (PE), and aortic disease (AD), their use is not well defined., Methods: Patients undergoing TRO or coronary CTA at 53 Michigan institutions for acute chest pain (in the emergency department or inpatient setting) in the ACIC (Advanced Cardiovascular Imaging Consortium) were included. Demographic characteristics, scan findings, and image quality parameters were compared between coronary CTA and TRO scans. The primary outcome was diagnostic yield, defined as obstructive CAD (>50% stenosis), PE, or AD; secondary outcomes were radiation dose, contrast volume, and image quality., Results: From July 2007 to September 2013, 12,834 patients underwent computed tomography scanning (TRO, n = 1,555; coronary CTA, n = 11,279). The TRO group had more women (57.1% vs. 47.8%, p < 0.001). Diagnostic yield was similar (TRO, 17.4% vs. coronary CTA, 18.3%; p = 0.37), driven by CAD (15.5% vs. 17.2%, p = 0.093); PE and AD were 1.1% and 0.4% (p = 0.004) and 1.7% and 1.1% (p = 0.046). TRO had higher median radiation (9.1 mSv vs. 6.2 mSv; p < 0.0001) and mean contrast (113 ± 6 ml vs. 89 ± 17 ml; p < 0.0001) doses. Nondiagnostic images were frequent in TRO (9.4% vs. 6.5%; p < 0.0001). In emergency department patients, PE and AD were more often detected on TRO. Among inpatients, there were no differences in overall yield or in that of PE, AD, or CAD., Conclusions: TRO was associated with slightly higher yield of PE and AD, specifically in the emergency department. This benefit comes with higher nondiagnostic image quality, radiation, and contrast doses. Although TRO may be of value in selected patients, its indiscriminate use is not warranted. The appropriate use of TRO needs to be further defined. (Advanced Cardiovascular Imaging Consortium [ACIC]; NCT00640068)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality., Approach and Results: Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque., Conclusions: The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD., Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier NCT01443637., (© 2015 American Heart Association, Inc.)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥ 64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n = 690) were matched 1:1:1 to those with 1 component (n = 690) and 2 components (n = 690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p < 0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p > 0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p = 0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p = 0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A best-practice intervention previously demonstrated significant dose reduction over a period of one year. We sought to evaluate whether this reduction would be incremental and sustained by promoting new scanner technology in the context of an ongoing quality improvement program during a 3-year period in a statewide registry of coronary computed tomography angiography., Methods and Results: In this prospective, controlled, nonrandomized study involving 11 901 patients at 15 Michigan centers participating in the Advanced Cardiovascular Imaging Consortium, radiation doses and image quality were compared between the following periods: control (May to June 2008) versus follow-up I (July 2008 to June 2009) and follow-up I versus follow-up II (July 2009 to April 2011). Intervention during these study periods included continuous education, feedback, and mandatory participation in this initiative. The median radiation dose remained unchanged from control to follow-up I: dose-length product of 697 (interquartile range, 407-1163) to 675 (interquartile range, 418-1146) mGy·cm (P=0.93). With the introduction of newer technology in follow-up I period, there was incremental 31% decrease during follow-up II to median dose-length product of 468 (interquartile range, 292-811) mGy·cm (P<0.0001). No significant change was noted in the percentage of diagnostic quality scans from follow-up I (92%) to follow-up II (92.7%)., Conclusions: Although ongoing application of a best-practice algorithm was associated with sustaining previously achieved targets, the use of newer scanner technology resulted in incremental radiation dose reduction in a statewide coronary computed tomography angiography registry without image quality degradation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00640068.

Objectives: This study was designed to assess the effects on resource utilization of routine coronary computed tomographic angiography (CCTA) in triaging chest pain patients in the emergency department (ED)., Background: The routine use of CCTA for ED evaluation of chest pain is feasible and safe., Methods: We conducted a retrospective multivariate analysis of data from two risk-matched cohorts of 894 ED patients presenting with chest pain to assess the impact of CCTA versus standard evaluation on admissions rate, length of stay, major adverse cardiovascular event rates, recidivism rates, and downstream resource utilization., Results: The overall admission rate was lower with CCTA (14% vs. 40%; p < 0.001). Standard evaluation was associated with a 5.5-fold greater risk for admission (odds ratio [OR]: 5.53; p < 0.001). Expected ED length of stay with standard evaluation was about 1.6 times longer (OR: 1.55; p < 0.001). There were no differences in the rates of death and acute myocardial infarction within 30 days of the index visit between the two groups. The likelihood of returning to the ED within 30 days for recurrent chest pain was 5 times greater with standard evaluation (OR: 5.06; p = 0.022). Standard evaluation was associated with a 7-fold greater likelihood of invasive coronary angiography without revascularization (OR: 7.17; p < 0.001), while neither group was significantly more likely to receive revascularization (OR: 2.06; p = 0.193). The median radiation dose with CCTA was 5.88 mSv (n = 1039; confidence interval: 5.2 to 6.4)., Conclusions: The routine use of CCTA in ED evaluation of chest pain reduces healthcare resource utilization., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Assessment of chest pain patients remains a clinical challenge in the emergency department (ED). Several randomized controlled trials (RCTs) have shown the additive value of coronary computed tomographic angiography (CCTA) compared with standard care. Not all of them, however, had enough power to detect differences in clinical outcomes like revascularization. Therefore, we performed a meta-analysis to test the safety and efficacy of this non-invasive diagnostic approach in low- and intermediate-risk chest pain patients., Methods: MEDLINE/PubMed was systematically screened for RCTs comparing CCTA and non-CCTA approaches for ED patients presenting with chest pain. Baseline features, diagnostic strategies, and outcome data were appraised and pooled with random-effect methods computing summary estimates [95% confidence intervals (CIs)]., Results: A total of four RCT studies including 2567 patients were identified, with similar inclusion and exclusion criteria. Patients in the CCTA group were more likely to undergo percutaneous or surgical revascularization during their index visit, with an odd ratio of 1.88 (1.21-2.92). Time to diagnosis was reduced with CCTA (-7.68 h;-12.70 to 2.66) along with costs of care in the ED (-$680; -1.060 to -270: all CI 95%)., Conclusion: The present meta-analysis shows that a strategy with CCTA used as first imaging test for low- and intermediate-risk patients presenting to the ED with chest pain appears safe and seems not to increase subsequent invasive coronary angiographies. The approach is cost-effective although limited data and incomplete cost analyses have been performed. CCTA increases coronary revascularizations, with still an unknown effect on prognosis, especially in the long term.

Objectives: This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA)., Background: CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-CCTA patterns of follow-up ICA and REV are incompletely defined., Methods: We examined 15,207 intermediate likelihood patients from 8 sites in 6 countries; these patients were without known CAD, underwent CCTA, and were followed up for 2.3 ± 1.2 years for all-cause mortality. Coronary artery stenosis was judged as obstructive when ≥50% stenosis was present. A multivariable logistic regression was used to estimate ICA use. A Cox proportional hazards model was used to estimate all-cause mortality., Results: During follow-up, ICA rates for patients with no CAD to mild CAD according to CCTA were low (2.5% and 8.3%), with similarly low rates of REV (0.3% and 2.5%). Most ICA procedures (79%) occurred ≤3 months of CCTA. Obstructive CAD was associated with higher rates of ICA and REV for 1-vessel (44.3% and 28.0%), 2-vessel (53.3% and 43.6%), and 3-vessel (69.4% and 66.8%) CAD, respectively. For patients with <50% stenosis, early ICA rates were elevated; over the entirety of follow-up, predictors of ICA were mild left main, mild proximal CAD, respectively, or higher coronary calcium scores. In patients with <50% stenosis, the relative hazard for death was 2.2 (p = 0.011) for ICA versus no ICA. Conversely, for patients with CAD, the relative hazard for death was 0.61 for ICA versus no ICA (p = 0.047)., Conclusions: These findings support the concept that CCTA may be used effectively as a gatekeeper to ICA., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The predictive value of coronary computed tomographic angiography (cCTA) in subjects without chest pain syndrome (CPS) has not been established. We investigated the prognostic value of coronary artery disease detection by cCTA and determined the incremental risk stratification benefit of cCTA findings compared with clinical risk factor scoring and coronary artery calcium scoring (CACS) for individuals without CPS., Methods and Results: An open-label, 12-center, 6-country observational registry of 27 125 consecutive patients undergoing cCTA and CACS was queried, and 7590 individuals without CPS or history of coronary artery disease met the inclusion criteria. All-cause mortality and the composite of all-cause mortality and nonfatal myocardial infarction were measured. During a median follow-up of 24 months (interquartile range, 18-35 months), all-cause mortality occurred in 136 individuals. After risk adjustment, compared with individuals without evidence of coronary artery disease by cCTA, individuals with obstructive 2- and 3-vessel disease or left main coronary artery disease experienced higher rates of death and composite outcome (P<0.05 for both). Both CACS and cCTA significantly improved the performance of standard risk factor prediction models for all-cause mortality and the composite outcome (likelihood ratio P<0.05 for all), but the incremental discriminatory value associated with their inclusion was more pronounced for the composite outcome and for CACS (C statistic for model with risk factors only was 0.71; for risk factors plus CACS, 0.75; for risk factors plus CACS plus cCTA, 0.77). The net reclassification improvement resulting from the addition of cCTA to a model based on standard risk factors and CACS was negligible., Conclusions: Although the prognosis for individuals without CPS is stratified by cCTA, the additional risk-predictive advantage by cCTA is not clinically meaningful compared with a risk model based on CACS. Therefore, at present, the application of cCTA for risk assessment of individuals without CPS should not be justified.

Objectives: This study was conducted to evaluate the correlation between stress test results and coronary computed tomography angiography (CCTA) findings and comparative diagnostic performance of the 2 modalities in patients undergoing invasive coronary angiography (ICA)., Background: Recent data suggest that only a third of patients undergoing ICA have obstructive coronary artery disease (CAD); accurate pre-ICA risk stratification is needed., Methods: At 47 centers participating in the ACIC (Advanced Cardiovascular Imaging Consortium) in Michigan, patients without known CAD who were undergoing CCTA within 3 months of a stress test were studied. Demographics, risk factors, symptoms, and stress test results were correlated with obstructive CAD (>50% stenosis) on CCTA and ICA., Results: Among 6,198 patients (age 56 ± 12 years, 48% men), >50% stenosis was seen in 1,158 (18.7%) on CCTA. Independent predictors included male sex (odds ratio [OR]: 2.37, 95% confidence interval [CI]: 1.83 to 3.06), current smoking (OR: 2.23, 95% CI: 1.57 to 3.17), older age (OR per 10-year increment: 2.14, 95% CI: 1.89 to 2.41), hypertension (OR: 1.8, 95% CI: 1.37 to 2.34), and typical angina (OR: 1.48, 95% CI: 1.03 to 2.12). Stress test results were not predictive. Among patients undergoing ICA (n = 621), there was a strong correlation of ICA with CCTA findings (OR: 9.09, 95% CI: 5.57 to 14.8, p < 0.001), but not stress results (OR: 0.79, 95% CI: 0.56 to 1.11, p = 0.17)., Conclusions: Stress test findings did not predict obstructive CAD on CCTA, observed in <20% of patients in this large study group. The strong association of CCTA with ICA suggests that it may serve as an effective "gatekeeper" to invasive testing in patients needing adjudication of stress test results. (Advanced Cardiovascular Imaging Consortium: A Collaborative Quality Improvement Project [ACIC]; NCT00640068)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA)., Background: The frequency and clinical relevance of CAD in patients without CAC are unclear., Methods: We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed., Results: Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84)., Conclusions: In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pretest probabilities of angiographically significant CAD derived from invasive coronary angiography (guideline probabilities). Reliability of guideline probabilities has not been investigated in patients referred to noninvasive CAD testing., Methods and Results: We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography. Angina typicality was recorded with the use of accepted criteria. Pretest likelihoods of CAD with ≥ 50 diameter stenosis (CAD50) and ≥ 70 diameter stenosis (CAD70) were calculated from guideline probabilities. Computed tomographic angiography images were evaluated by ≥ 1 expert reader to determine the presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40 in men, 19 in women) and CAD70 (27 men, 11 women) compared with other symptom categories (P<0.001 for all). Observed CAD50 and CAD70 prevalences were substantially lower than those predicted by guideline probabilities in the overall population (18 versus 51 for CAD50, 10 versus 42 for CAD70; P<0.001), driven by pronounced differences in patients with atypical angina (15 versus 47 for CAD50, 7 versus 37 for CAD70) and typical angina (29 versus 86 for CAD50, 19 versus 71 for CAD70). Marked overestimation of disease prevalence by guideline probabilities was found at all participating centers and across all sex and age subgroups., Conclusion: In this multinational study of patients referred for coronary computed tomographic angiography, determination of pretest likelihood of angiographically significant CAD by the invasive angiography-based guideline probabilities greatly overestimates the actual prevalence of disease.

Objectives: The purpose of this study was to compare the efficiency, cost, and safety of a diagnostic strategy employing early coronary computed tomographic angiography (CCTA) to a strategy employing rest-stress myocardial perfusion imaging (MPI) in the evaluation of acute low-risk chest pain., Background: In the United States, >8 million patients require emergency department evaluation for acute chest pain annually at an estimated diagnostic cost of >$10 billion., Methods: This multicenter, randomized clinical trial in 16 emergency departments ran between June 2007 and November 2008. Patients were randomly allocated to CCTA (n = 361) or MPI (n = 338) as the index noninvasive test. The primary outcome was time to diagnosis; the secondary outcomes were emergency department costs of care and safety, defined as freedom from major adverse cardiac events in patients with normal index tests, including 6-month follow-up., Results: The CCTA resulted in a 54% reduction in time to diagnosis compared with MPI (median 2.9 h [25th to 75th percentile: 2.1 to 4.0 h] vs. 6.3 h [25th to 75th percentile: 4.2 to 19.0 h], p < 0.0001). Costs of care were 38% lower compared with standard (median $2,137 [25th to 75th percentile: $1,660 to $3,077] vs. $3,458 [25th to 75th percentile: $2,900 to $4,297], p < 0.0001). The diagnostic strategies had no difference in major adverse cardiac events after normal index testing (0.8% in the CCTA arm vs. 0.4% in the MPI arm, p = 0.29)., Conclusions: In emergency department acute, low-risk chest pain patients, the use of CCTA results in more rapid and cost-efficient safe diagnosis than rest-stress MPI. Further studies comparing CCTA to other diagnostic strategies are needed to optimize evaluation of specific patient subsets. (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment [CT-STAT]; NCT00468325)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Large multicenter studies validating the prognostic value of coronary computed tomographic angiography (CCTA) and left ventricular ejection fraction (LVEF) are lacking. We sought to confirm the independent and incremental prognostic value of coronary artery disease (CAD) severity measured using 64-slice CCTA over LVEF and clinical variables., Methods and Results: A large international multicenter registry (CONFIRM Registry) was queried, and CCTA patients with LVEF data on CCTA were screened. Patients with a history of myocardial infarction, coronary revascularization, or cardiac transplantation were excluded. The National Cholesterol Education Program-Adult Treatment Panel III risk was calculated for each patient, and CCTA was evaluated for CAD severity (normal, nonobstructive, non-high-risk, or high-risk CAD) and LVEF <50%. Patients were followed for an end point of all-cause mortality; 27 125 patients underwent CCTA at 12 participating centers, with a total of 14 064 patients meeting the analysis criteria. Follow-up was available for 13 966 (99.3%) patients (mean follow-up of 22.5 months; 95% confidence interval, 22.3 to 22.7 months). All-cause mortality (271 deaths) occurred in 0.65% of patients without coronary atherosclerosis, 1.99% of patients with nonobstructive CAD, 2.90% of patients with non-high-risk CAD, and 4.95% for patients with high-risk CAD. Multivariable analysis confirmed that LVEF <50% (hazard ratio, 2.74; 95% confidence interval, 2.12 to 3.51) and CAD severity (hazard ratio,1.58; 95% confidence interval, 1.42 to 1.76) were predictors of all-cause mortality, and CAD severity had incremental value over LVEF and clinical variables., Conclusions: Our results demonstrate that CCTA measures of CAD severity and LVEF have independent prognostic value. Incorporation of CAD severity provides incremental value for predicting all-cause death over routine clinical predictors and LVEF in patients with suspected obstructive CAD.

Rapid technological advances have facilitated high-resolution noninvasive coronary angiography using multislice computed tomography. Appropriateness guidelines recently have been published in the Journal of the American College of Cardiology and endorsed by several imaging specialty societies. Clinical studies are now available supporting the use of this method in selected diagnostic situations, particularly when the exclusion of coronary artery disease is of paramount clinical concern.

Objectives: This study sought to compare the safety, diagnostic efficacy, and efficiency of multi-slice computed tomography (MSCT) with standard diagnostic evaluation of low-risk acute chest pain patients., Background: Over 1 million patients have emergency center evaluations for acute chest pain annually, at an estimated diagnostic cost of over $10 billion. Multi-slice computed tomography has a high negative predictive value for exclusion of coronary artery stenoses., Methods: We randomized patients to MSCT (n = 99) versus SOC (n = 98) protocols. The MSCT patients with minimal disease were discharged; those with stenosis >70% underwent catheterization, whereas cases with intermediate lesions or non-diagnostic scans underwent stress testing. Outcomes included: safety (freedom from major adverse events over 6 months), diagnostic efficacy (clinically correct and definitive diagnosis), as well as time and cost of care., Results: Both approaches were completely (100%) safe. The MSCT alone immediately excluded or identified coronary disease as the source of chest pain in 75% of patients, including 67 with normal coronary arteries and 8 with severe disease referred for invasive evaluation. The remaining 25% of patients required stress testing, owing to intermediate severity lesions or non-diagnostic scans. During the index visit, MSCT evaluation reduced diagnostic time compared with SOC (3.4 h vs. 15.0 h, p < 0.001) and lowered costs (1,586 dollars vs. 1,872 dollars, p < 0.001). Importantly, MSCT patients required fewer repeat evaluations for recurrent chest pain (MSCT, 2 of 99 (2.0%) patients vs. SOC, 7 of 99 (7%) patients; p = 0.10)., Conclusions: Multi-slice computed tomographic coronary angiography can definitively establish or exclude coronary disease as the cause of chest pain. However, inability to determine the physiological significance of intermediate severity coronary lesions and cases with inadequate image quality are present limitations. (Study of Coronary Artery Computed Tomography to Diagnose Emergency Chest Pain CR; http://clinicaltrials.gov/ct/show/NCT00273832?order=1; NCT00273832).

Objectives: The aim of our study was to evaluate the diagnostic accuracy of multislice computed tomography (MSCT) coronary angiography using a new 64-slice scanner., Background: The new 64-slice MSCT scanner has improved spatial resolution of 0.4 mm and a faster rotation time (330 ms) compared to prior MSCT scanners., Methods: We studied 70 consecutive patients undergoing elective invasive coronary angiography. Patients were excluded for atrial fibrillation, but not for high heart rate, coronary calcification, or obesity. All vessels were analyzed, including those <1.5 mm in diameter; MSCT lesions were analyzed quantitatively as well as by a qualitative scale and compared to quantitative coronary angiography (QCA). Results were also analyzed for significant coronary stenoses (over 50% luminal narrowing) by segment, by artery, and by patient., Results: All scans showed diagnostic image quality. Of 1,065 segments, 935 (88%) could be evaluated, and 773 of 935 (83%) could be assessed quantitatively by both MSCT and QCA. The Spearman correlation coefficient between MSCT and QCA was 0.76 (p < 0.0001). Bland-Altman analysis demonstrated a mean difference in percent stenosis of 1.3 +/- 14.2%. A total of 26% of patients had calcium scores above 400 Agatston U, 25% had heart rates >70 beats/min, and 50% were obese. Specificity, sensitivity, and positive and negative predictive values for the presence of significant stenoses were: by segment (n = 935), 86%, 95%, 66%, and 98%, respectively; by artery (n = 279), 91%, 92%, 80%, and 97%, respectively; by patient (n = 70), 95%, 90%, 93%, and 93%, respectively., Conclusions: Our results indicate high quantitative and qualitative diagnostic accuracy of 64-slice MSCT in comparison to QCA in a broad spectrum of patients.

No approach to describing the heart's dynamic geometry has been widely adopted, probably because all require questionable assumptions of chamber shape, symmetry, or placement of the measuring devices. In other words, these approaches require assumptions about shape to reach conclusions about shape. We present an analysis that avoids such assumptions and provides an objective description of how the left ventricle deforms and rotates during the cardiac cycle. We only assume that the deformation of the left ventricular cavity is homogeneous, and explicitly validate this assumption. Our analysis yields the following new information about the contracting left ventricle: three principal directions of deformation and the relative length change alone these directions: the axis and angle of rotation, and relative volume. All these changes are referenced to the ventricle's configuration at end-diastole. We instrumented 13 dogs with tantalum screws without opening their chests. During systole, the three principal directions of deformation essentially are aligned along apex-base, anterior-posterior, and septum-free wall directions. There is little length change in the apex-base direction. The anterior and septal principal directions do not remain fixed with respect to the heart's anatomy during systole. During isovolumic relaxation and early filling, systolic shape changes are reversed. During slow filling, only small shape changes occur. Opening the pleura or performing a sternotomy and pericardiectomy makes the heart change orientation within the chest, but does not alter the magnitude of shortening, relative to the left ventricle's end-diastolic configuration.