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Introduction: After ST-segment elevation myocardial infarction (STEMI), follow-up imaging is currently recommended only in patients with left ventricular ejection fraction (LVEF) <40%. Left ventricular global longitudinal strain (LVGLS) was shown to improve risk stratification over LVEF in these patients but has not been thoroughly studied during follow-up. The aim of this study was to explore the changes in LVGLS after STEMI and their potential prognostic value., Materials and Methods: Data were analyzed from an ongoing STEMI registry. Echocardiography was performed during the index hospitalization and 1 year after STEMI; LVGLS was expressed as an absolute value and the relative LVGLS change (ΔGLS) was calculated. The study end point was all-cause mortality., Results: A total of 1,409 STEMI patients (age 60 ± 11 years; 75% men) who survived at least 1 year after STEMI and underwent echocardiography at follow-up were included. At 1-year follow-up, LVEF improved from 50% ± 8% to 53% ± 8% (P < .001) and LVGLS from 14% ± 4% to 16% ± 3% (P < .001). Median ΔGLS was 14% (interquartile range, 0.5%-32%) relative improvement. Starting 1 year after STEMI, a total of 87 patients died after a median follow-up of 69 (interquartile range, 38-103) months. The optimal ΔGLS threshold associated with the end point (derived by spline curve analysis) was a relative decrease >7%. Cumulative 10-year survival was 91% in patients with ΔGLS improvement or a nonsignificant decrease, versus 85% in patients with ΔGLS decrease of >7% (P = .001). On multivariate Cox regression analysis, ΔGLS decrease >7% remained independently associated with the end point (hazard ratio, 2.5 [95% CI, 1.5-4.1]; P < .001) after adjustment for clinical and echocardiographic parameters., Conclusions: A significant decrease in LVGLS 1 year after STEMI was independently associated with long-term all-cause mortality and might help further risk stratification and management of these patients during follow-up., Competing Interests: Conflicts of Interest This study is supported by a Novartis AG research grant. J.J.B. has received speaker fees from Abbott Vascular, Edwards Lifesciences, and Omron. N.A.M. has received speaker fees from Philips Ultrasound, Abbott Vascular, Omron, and GE Healthcare. K.T. has received speaker fees from Astra Zeneca, Bayer, Berlin Menarini, Boehringer-Ingelheim, Biotronik, Novo-Nordisk, and Servier. The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Alnylam, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Medis, Pfizer, Pie Medical, and Medtronic. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET)., Methods and Results: From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [15O]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021)., Conclusion: The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone., Competing Interests: Conflict of interest: Dr Wang is supported by a research grant from the University of Turku. Dr Saraste received speaker or consultancy fees from Amgen, Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. Dr Knuuti received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer Ingelheim, Pfizer, and Merck, outside of the submitted work. Dr Bax received speaker fees from Abbot Vascular and Edwards Lifesciences. The Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Bayer, Abbott Vascular, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. The remaining authors have no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The various plaque components have been associated with ischemia and outcomes in patients with coronary artery disease (CAD). The main goal of this analysis was to test the hypothesis that, at patient level, the fraction of non-calcified plaque volume (PV) of total PV is associated with ischemia and outcomes in patients with CAD. This ratio could be a simple and clinically useful parameter, if predicting outcomes., Methods: Consecutive patients with suspected CAD undergoing coronary computed tomography angiography with selective positron emission tomography perfusion imaging were selected. Plaque components were quantitatively analyzed at patient level. The fraction of various plaque components were expressed as percentage of total PV and examined among patients with non-obstructive CAD, suspected stenosis with normal perfusion, and those with reduced myocardial perfusion. Clinical outcomes included all-cause mortality and myocardial infarction., Results: In total, 494 patients (age 63 ​± ​9 years, 55% male) were included. Total PV and all plaque components were significantly larger in patients with reduced myocardial perfusion compared to patients with normal perfusion and those with non-obstructive CAD. During follow-up 35 events occurred. Patients with any plaque component ​≥ ​median showed worse outcomes (log-rank p ​< ​0.001 for all). In addition, low-attenuation plaque ​≥ ​median was associated with worse outcomes independent of total PV (adjusted HR: 2.754, 95% CI: 1.022-7.0419, p ​= ​0.045). The fractions of the various plaque components were not associated with outcomes., Conclusion: Larger total PV or any plaque component at patient level are associated with abnormal myocardial perfusion and adverse events. The various plaque components as fraction of total PV lack additional prognostic value., Competing Interests: Declaration of competing interest The department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands has received unrestricted research grants from Bayer, Abbott Vascular, Medtronic, Biotronik, Boston Scientific, GE Healthcare and Edwards Lifesciences. Dr. Knuuti received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer and Merck, outside of the submitted work. Dr. Saraste received consultancy fees from Amgen, Astra Zeneca, Boehringer Ingelheim, and Pfizer, and speaker fees from Abbott, Astra Zeneca, and Bayer. Dr. Jukema received research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Commission Seventh Framework Programme, and research support from Amgen, Astellas, AstraZeneca, Daiichi- Sankyo, Lilly, Merck-Schering-Plough, Pfizer, Roche, and Sanofi. Dr. Bax received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments. Factors potentially affecting ESS values were examined, including sex, lumen diameter and distance from the ostium. Segments were categorized according to lumen diameter tertiles into small (< 2.6 mm), intermediate (2.6-3.2 mm) or large (≥ 3.2 mm) segments. A total of 349 normal vessels from 168 patients (mean age 59 ± 9 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex artery and right coronary artery (minimal ESS 2.3 Pa vs. 1.9 Pa vs. 1.6 Pa, p < 0.001 and maximal ESS 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa, p < 0.001). Men had lower ESS values than women, also after adjusting for lumen diameter (p < 0.001). ESS values were highest in small segments compared to intermediate or large segments (minimal ESS 3.8 Pa vs. 1.7 Pa vs. 1.2 Pa, p < 0.001 and maximal ESS 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa, p < 0.001). A weak to strong correlation was found between ESS and distance from the ostium (ρ = 0.22-0.62, p < 0.001). CCTA-based ESS values increase rapidly and become widely scattered with decreasing lumen diameter. This needs to be taken into account when assessing the added value of ESS beyond lumen diameter in highly stenotic lesions., (© 2022. The Author(s).)

Background: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD., Methods and Results: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [ 15 O]H 2 O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001)., Conclusions: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD., (© 2022. The Author(s).)

Pericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and women without atherosclerosis on CCTA are lacking. The aim of the current study was to assess the mean PCAT attenuation in individuals without coronary artery atherosclerosis on CCTA. Data on PCAT attenuation in men and women without coronary artery atherosclerosis on CCTA were included in this retrospective analysis. The PCAT attenuation was analyzed from the proximal part of the right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCx). For patient level analyses the mean PCAT attenuation was defined as the mean of the three coronary arteries. In 109 individuals (mean age 45 ± 13 years; 44% men), 320 coronary arteries were analyzed. The mean PCAT attenuation of the overall population was - 64.4 ± 8.0 HU. The mean PCAT attenuation was significantly lower in the LAD compared with the LCx and RCA (- 67.8 ± 7.8 HU vs - 62.6 ± 6.8 HU vs - 63.6 ± 7.9 HU, respectively, p < 0.001). In addition, the mean PCAT attenuation was significantly higher in men vs. women in all three coronary arteries (LAD: - 65.7 ± 7.6 HU vs - 69.4 ± 7.6 HU, p = 0.014; LCx: - 60.6 ± 7.4 HU vs - 64.3 ± 5.9 HU, p = 0.008; RCA: -61.7 ± 7.9 HU vs - 65.0 ± 7.7 HU, p = 0.029, respectively). The current study provides mean PCAT attenuation values, derived from individuals without CAD. Moreover, the mean PCAT attenuation is lower in women vs. men. Furthermore, the mean PCAT attenuation is significantly lower in the LAD vs LCx and RCA., (© 2022. The Author(s).)

Aims: Evolving evidence suggests that endothelial wall shear stress (ESS) plays a crucial role in the rupture and progression of coronary plaques by triggering biological signalling pathways. We aimed to investigate the patterns of ESS across coronary lesions from non-invasive imaging with coronary computed tomography angiography (CCTA), and to define plaque-associated ESS values in patients with coronary artery disease (CAD)., Methods and Results: Symptomatic patients with CAD who underwent a clinically indicated CCTA scan were identified. Separate core laboratories performed blinded analysis of CCTA for anatomical and ESS features of coronary atherosclerosis. ESS was assessed using dedicated software, providing minimal and maximal ESS values for each 3 mm segment. Each coronary lesion was divided into upstream, start, minimal luminal area (MLA), end and downstream segments. Also, ESS ratios were calculated using the upstream segment as a reference. From 122 patients (mean age 64 ± 7 years, 57% men), a total of 237 lesions were analyzed. Minimal and maximal ESS values varied across the lesions with the highest values at the MLA segment [minimal ESS 3.97 Pa (IQR 1.93-8.92 Pa) and maximal ESS 5.64 Pa (IQR 3.13-11.21 Pa), respectively]. Furthermore, minimal and maximal ESS values were positively associated with stenosis severity (P < 0.001), percent atheroma volume (P < 0.001), and lesion length (P ≤ 0.023) at the MLA segment. Using ESS ratios, similar associations were observed for stenosis severity and lesion length., Conclusions: Detailed behaviour of ESS across coronary lesions can be derived from routine non-invasive CCTA imaging. This may further improve risk stratification., Competing Interests: Conflict of interest: Dr Saraste received consultancy fees from Amgen, Astra Zeneca, Boehringer Ingelheim, and Pfizer and speaker fees from Abbott, Astra Zeneca, and Bayer. Dr Bax received speaker fees from Abbot Vascular and Edwards Lifesciences. Dr Knuuti received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, and Merck, outside of the submitted work. The Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Bayer, Abbott Vascular, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. The remaining authors have no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We examined age differences in whole-heart volumes of non-calcified and calcified atherosclerosis by coronary computed tomography angiography (CCTA) of patients with future ACS., Methods: A total of 234 patients with core-lab adjudicated ACS after baseline CCTA were enrolled. Atherosclerotic plaque was quantified and characterized from the main epicardial vessels and side branches on a 0.5 ​mm cross-sectional basis. Calcified plaque and non-calcified plaque were defined by above or below 350 Hounsfield units. Patients were categorized according to their age by deciles. Also, coronary artery calcium scores (CACS) were evaluated when available., Results: Patients were on average 62.2 ​± ​11.5 years old. On the pre-ACS CCTA, patients showed diffuse, multi-site, predominantly non-obstructive atherosclerosis across all age categories, with plaque being detected in 93.5% of all ACS cases. The proportion calcified plaque from the total plaque burden increased significantly with older presentation (10% calcification in those <50 years, and 50% calcification in those >80 years old). Patients with ACS <50 years had remarkably lower atherosclerotic burden compared with older patients, but a high proportion of high risk markers such as low-attenuation plaque. CACS was >0 in 85% of the patients older than 50 years, and in 57% of patients younger than 50 years., Conclusion: The proportion of calcified plaque varied depending on patient age at the time of ACS. Only a small proportion of plaque was calcified when ACS occurred at <50 years old, while this increased gradually with older age. Purely non-calcified atherosclerotic plaque was not uncommon in patients <50 years., Competing Interests: Declaration of competing interest Dr. Chinnaiyan is a non-compensated medical advisory board member of Heartflow Inc. Dr. Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research, receives support from CV Diagnostix and Ausculsciences, receives educational support from TeraRecon Inc., and has equity interest in General Electric. Dr. Min is an employee of Cleerly, 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. Shaw is on the scientific advisory board for Covanos, Inc. The remaining authors have no relevant conflicts to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Aims: Atherosclerosis develops progressively and worsens over time, yet event risk patterns vary in the left circumflex (LCx), right coronary artery (RCA) and left anterior descending (LAD). The aim of this analysis was to examine varying progressive disease alterations between the three major coronary arteries., Methods and Results: Patients were included from a prospective, international registry of consecutive patients who underwent serial CCTA at a median interval of 3.3 years. Annual progression of quantitative total and compositional plaque volume were compared between the three coronary arteries (LCx, LAD, and RCA). Other analyses compared stenosis ≥50% and new high-risk plaque (HRP; ≥2 of the following: spotty calcification, positive remodelling, napkin-ring sign, and low-attenuation plaque) on follow-up. Generalized estimating equations and marginal Cox regression models were used to compare progression, with covariate adjustment by the baseline atherosclerotic cardiovascular disease risk score, statin use, and plaque burden. Quantitative plaque measurements were calculated in 1344 patients (age 60 ± 9 years, 57% men). Plaque progression occurred less often in the LCx (41.0%) as compared to the RCA (52.7%) and LAD (77.4%, P &lt; 0.001). Odds for annual plaque burden increase ≥population mean were 1.98- and 1.43-fold as high in the LAD (P &lt; 0.001) and RCA (P &lt; 0.001) as compared to the LCx. Similarly, the LAD was associated with a 2.45 higher risk of progression to obstructive CAD (P &lt; 0.001), as compared to the LCx; with no differences between the RCA and LCx (P = 0.13). New HRP lesions formed least often in the LCx (3.4%), followed by the RCA (8.1%) and most often in the LAD (10.1%; P &lt; 0.001)., Conclusions: Our findings reveal novel insights into varied patterns of atherosclerotic plaque progression within the LCx as compared to the other epicardial coronary arteries. These varied patterns reflect differing stages in the disease process or differing pathogenic milieu across the coronary arteries., Competing Interests: Conflict of interest: K.C. is a non-compensated medical advisor for Heartflow Inc. L.J.S. is on the scientific advisory board for Covanos Inc. J.A.L. is a consultant to and hold stock options in Circle CVI and HeartFlow and receives research support from GE Healthcare and serves on the speakers’ bureau for Philips and GE Healthcare. G.S. has received speaker or other honoraria from Cook, Terumo, QOOL Therapeutics, and Orchestra Biomed; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Aims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and composition of coronary atherosclerosis between patients experiencing an early (≤90 days) versus late ACS (>90 days) after baseline coronary computed tomography angiography (CCTA)., Methods and Results: From a multicenter study, we enrolled patients who underwent a clinically indicated baseline CCTA and experienced ACS during follow-up. Separate core laboratories performed blinded adjudication of ACS events and quantification of CCTA including compositional plaque volumes by Hounsfield units (HU): calcified plaque >350 HU, fibrous plaque 131-350 HU, fibrofatty plaque 31-130 HU and necrotic core <30 HU. In 234 patients (mean age 62 ± 12 years, 36% women), early and late ACS occurred in 129 and 105 patients after a mean of 395 ± 622 days, respectively. Patients with early ACS had a greater maximal diameter stenosis and maximal cross-sectional plaque burden as compared to patients with late ACS (P < 0.05). Larger total, fibrous, fibrofatty, and necrotic core volumes were observed in the early ACS group (P < 0.05). Findings for total, fibrous, fibrofatty, and necrotic core volumes were reproduced in an external validation cohort (P < 0.05)., Conclusions: Volumetric differences in composition of coronary atherosclerosis exist between ACS patients according to their timing antecedent to the acute event. These data support that a large burden of non-calcified plaque on CCTA is strongly associated with near-term plaque instability and ACS risk., Competing Interests: Conflict of interest: Dr Chow receives support from CV Diagnostix and Ausculsciences, educational support from TeraRecon Inc., and has equity interest in General Electric. Dr Leipsic is a consultant and has stock options in Circle CVI and HeartFlow and receives research support from GE Healthcare. Dr Min is an employee of Cleerly, Inc. Dr Shaw serves on the scientific advisory board for Covanos, 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. The remaining authors have no relevant conflicts to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA)., Methods and Results: From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281)., Conclusions: Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis., Competing Interests: Conflict of interest: J.K.M. has an equity interest in Cleerly. K.C. is a non-compensated medical advisory board member of Heartflow Inc. H.S. 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. L.J.S. serves on the scientific advisory board for Covanos, Inc. The remaining authors have no relevant disclosures., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes., Methods: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes., Results: Of the 3053 patients (age 66 ​± ​10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 ​± ​940 ​mm 3 vs. 3040 ​± ​970 ​mm 3 , p ​< ​0.0001), whereas the myocardial mass was comparable between the 2 groups (122 ​± ​33 ​g vs. 122 ​± ​32 ​g, p ​= ​0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 ​± ​6.8 ​mm 3 /g vs. 25.7 ​± ​7.5 ​mm 3 /g, p ​< ​0.0001). Among subjects with obstructive CAD (n ​= ​2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 ​± ​6.7 ​mm 3 /g vs. 25.0 ​± ​7.3 ​mm 3 /g, p ​< ​0.0001 and 25.6 ​± ​6.9 ​mm 3 /g vs. 27.3 ​± ​7.6 ​mm 3 /g, respectively, p ​= ​0.006)., Conclusion: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation., Competing Interests: Declaration of competing interest The department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Medtronic, Biotronik, Boston Scientific, and Edwards Lifesciences. Dr. Patel has received research grants from HeartFlow, Bayer, Janssen, and the National Heart, Lung, and Blood Institute; and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Fairbairn has served on the Speakers Bureau for HeartFlow. Dr. Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Hurwitz Koweek has received research support and speaking fees from HeartFlow and Siemens. Dr. Pontone has received institutional research grant and/or honorarium as consultant/speaker from GE Healthcare, Boehringer, Bracco, Medtronic, Bayer, and HeartFlow. Dr. Sonck has received research grant support from the Cardiopath PhD program. Dr. Rabbat has served as a consultant for HeartFlow. Dr. De Bruyne has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE Healthcare, Bayer, Philips, HeartFlow, Edwards Lifesciences, and Sanofi. Dr. Rogers is employee of and owns equity in HeartFlow. Dr. Leipsic has received research grants from GE Healthcare and Edwards Lifesciences; and has served as a consultant for and holds stock options in Circle Cardiovascular Imaging and HeartFlow Inc. Dr. Bax has received speaker fees from Abbot Vascular. Dr. Knuuti has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim and Merck, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with diabetes mellitus (DM) may show diffuse coronary artery atherosclerosis on coronary computed tomography angiography (CTA). The present study aimed at quantification of atherosclerotic plaque with CTA and its association with myocardial ischemia on positron emission tomography (PET) in DM patients. Of 922 symptomatic outpatients without previously known coronary artery disease who underwent CTA, 115 with DM (mean age 65 ± 8 years, 58% male) who had coronary atherosclerosis and underwent both quantified CTA (QCTA) and PET were included in the study. QCTA analysis was performed on a per-vessel basis and the most stenotic lesion of each vessel was considered. Myocardial ischemia on PET was based on absolute myocardial blood flow at stress ≤ 2.4 ml/g/min. Of the 345 vessels included in the analysis, 135 (39%) had flow-limiting stenosis and were characterized by having longer lesions, higher plaque volume, more extensive plaque burden and higher percentage of dense calcium (37 ± 22% vs 28 ± 22%, p = 0.001). On univariable analysis, QCTA parameters indicating the degree of stenosis, the plaque extent and composition were associated with presence of ischemia. The addition of the QCTA degree of stenosis parameters (x 2 36.45 vs 88.18, p < 0.001) and the QCTA plaque extent parameters (x 2 88.18 vs 97.44, p = 0.01) to a baseline model increased the association with ischemia. In DM patients, QCTA variables of vessel stenosis, plaque extent and composition are associated with ischemia on PET and characterize the hemodynamic significant atherosclerotic lesion., (© 2022. The Author(s).)

Background: Among symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque., Objectives: Among patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume., Methods: A total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up)., Results: Across baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm 3 (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm 3 increase in calcified plaque, there was a 5.5 mm 3 increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001)., Conclusions: CAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk., Competing Interests: Funding Support and Author Disclosures Partial funding was provided by a gift from the Dalio Foundation (New York, New York) and supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation funded by the Ministry of Science and Information and Communications Technology of Korea (Grant number 2012027176). Dr Chinnaiyan is a medical advisor (unpaid) for Heartflow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.)

Importance: The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques., Objective: To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression., Design, Setting, and Participants: This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries., Main Outcomes and Measures: The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020., Results: In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (β, -0.02; 95% CI, -0.03 to -0.01; P = .001) and fibro-fatty plaque (β, -0.03; 95% CI, -0.04 to -0.02; P < .001) and greater progression of high-density calcium plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (β, -0.03; 95% CI, -0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression., Conclusions and Relevance: The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.

Background: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE)., Methods: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted., Results: The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​< ​0.001., Conclusions: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. Dr. Habib Samady serves on the medical advisory board of Philips and has equity holding in Covanos. The remaining authors have no relevant disclosures., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Women exhibit less burden of anatomic obstructive coronary atherosclerotic disease as compared with men of the same age, but contradictorily show similar or higher cardiovascular mortality rates. The higher prevalence of nonexertional cardiac symptoms and nonobstructive coronary atherosclerotic disease in women may lead to lack of recognition and appropriate management, resulting in undertesting and undertreatment. Leaders in women's health from the American College of Cardiology's Cardiovascular Disease in Women Committee present novel imaging cases that may provoke thought regarding the broad clinical spectrum of myocardial infarction and ischemia with nonobstructive coronary arteries in women. These unique imaging approaches are based on the concept of targeting sex-specific differences in acute and stable ischemic heart disease., Competing Interests: Funding Support and Author Disclosures The 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: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries., Methods and Results: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001)., Conclusion: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Importance: Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement., Objective: To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR., Design, Setting, and Participants: Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018., Interventions: Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve., Main Outcomes and Measures: The primary end point was invasive FFR of 0.80 or less., Results: Of the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (≥2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001)., Conclusions and Relevance: A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion., Trial Registration: ClinicalTrials.gov Identifier: NCT02173275.

Background and Aims: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex., Methods: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm 3 , (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAV norm ) in mm 3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAV norm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed., Results: The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAV norm , but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAV norm ) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAV norm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex., Conclusions: PAV was less affected by patient's body surface area then PV and TAV norm and may be the preferred method to report coronary atherosclerotic burden., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. Dr. Habib Samady serves on the scientific advisory board of Philips, has equity interest in Covanos Inc., and has a research grant from Medtronic. Dr. Kavitha Chinnaiyan is a non-compensated medical advisory board member of Heartflow Inc. The remaining authors have no relevant disclosures., (Copyright © 2020. Published by Elsevier Inc.)

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.)

Sudden death is the most abrupt clinical presentation of acute coronary syndrome. The presence of acute luminal thrombosis is the histopathological hallmark of sudden coronary death. There are 3 main etiologies that can give rise to an acute luminal thrombus: plaque rupture, plaque erosion and, less frequently, eruptive calcified nodules. Coronary computed tomography angiography (CCTA) has the ability to identify high-risk plaque features of coronary artery disease that are associated with future adverse cardiac events. In this report, we illustrate 2 cases of suspected sudden coronary death with a thorough description of how CCTA can be employed to detect high-risk plaque features using histopathology as a gold standard., Competing Interests: Declaration of competing interest All authors have no relevant conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Aims: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders., Methods: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability., Results: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265)., Conclusion: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. The Department of Cardiology of the Leiden University Medical Center received research grants from Biotronik, Medtronic, Boston Scientific and Edwards Lifesciences. Arthur J.H.A. Scholte received consulting fees from GE Healthcare and Canon., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known., Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS., Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019., Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque)., Main Outcomes and Measures: Association between calcium density and future ACS risk., Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases., Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

The purpose of this review is to summarize the work published by the Journal of Cardiovascular Computed Tomography (JCCT) for the year 2019, highlighting original research and new guidelines., Competing Interests: Declaration of competing interest CNC receives research support from and has received speaker fees from Siemens Healthineers. JAL serves as a consultant and holds stock options with Circle CVI and HeartFlow and receives research support from GE Healthcare. JKM receives funding from the Dalio Foundation, NIH, and GE Healthcare. JKM also serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Coronary computed tomography angiography (CCTA) is the optimal non-invasive test to rule out coronary artery disease (CAD). Decisions to perform coronary revascularization have traditionally been based upon ischemia testing. This review summarizes the latest observations and trials evaluating the suitability of CCTA to select patients for invasive coronary angiography (ICA) and subsequent revascularization., Recent Findings: Recent data shows that beyond stenosis, whole-heart quantification and characterization of coronary atherosclerotic plaque improves the estimation of myocardial ischemia. This comprehensive evaluation of the coronary artery tree has greater diagnostic accuracy for invasive fractional flow reserve (FFR) than conventional stress tests. Further, clinical trials have demonstrated that the performance of CCTA in patients with a clinical indication for ICA results in more effective patient care and significantly lower costs., Summary: Besides the excellent ability to rule out CAD, recent data shows that quantification and characterization of the coronary artery tree results in high accuracy for ischemia and that CCTA-guided care to select patients for ICA and revascularization is effective. Trials evaluating revascularization based on CCTA findings may be needed., Competing Interests: Conflict of Interest Inge J. van den Hoogen declares no conflict of interest. Alexander R. van Rosendael declares no conflict of interest. Fay Y. Lin declares no conflict of interest. Jeroen J. Bax declares no conflict of interest. Leslee J. Shaw declares no conflict of interest.

Background: Coronary-computed tomography angiography (CTA) has limited accuracy to predict myocardial ischemia. Besides luminal area stenosis, other coronary plaque morphology and composition parameters may help to assess ischemia. With the integration of coronary CTA and adenosine stress CT myocardial perfusion (CTP), reliable information regarding coronary anatomy and function can be derived in one procedure. This analysis aimed to investigate the association between coronary stenosis severity, plaque composition and morphology and the presence of ischemia measured with adenosine stress myocardial CTP., Methods and Results: 84 patients (age, 62 ± 10 years; 48% men) who underwent sequential coronary CTA and adenosine stress myocardial CT perfusion were analyzed. Automated quantification was performed in all coronary lesions (quantitative CTA). Downstream myocardial ischemia was assessed by visual analysis of the rest and stress CTP images and defined as a summed difference score of ≥1. One or more coronary plaques were present in 146 coronary arteries of which 31 (21%) were ischemia-related. Of the lesions with a stenosis percentage <50%, 50%-70%, and >70%, respectively, 9% (6/67), 18% (9/51), and 57% (16/28) demonstrated downstream ischemia. Furthermore, mean plaque burden, plaque volume, lesion length, maximal plaque thickness, and dense calcium volume were significantly higher in ischemia-related lesions, but only stenosis severity (%) (OR 1.06; 95% CI 1.02-1.10; P = .006) and lesion length (mm) (OR 1.26; 95% CI 1.02-1.55; P = .029) were independent correlates., Conclusions: Increasing stenosis percentage by quantitative CTA is positively correlated to myocardial ischemia measured with adenosine stress myocardial CTP. However, stenosis percentage remains a moderate determinant. Lumen area stenosis and lesion length were independently associated with ischemia, adjusted for coronary plaque volume, mean plaque burden, maximal lesion thickness, and dense calcium volume.

Aims: The interpretation of adenosine stress myocardial computed tomography perfusion (CTP) is often hampered by image artefacts caused by cardiac motion, beam hardening, and cone beam. The aim of the present analysis was to assess the influence of the heart-rate response during adenosine infusion, patient characteristics, and medication use on the interpretability of stress myocardial CTP examinations., Methods and Results: Interpretability of stress myocardial CTP examinations was evaluated in 120 patients who underwent sequentially coronary CTA and adenosine stress myocardial CTP (320-row CT scanner, temporal resolution 175 ms) and scored as follows: excellent = absence of any artefact (n = 27, 22%); good = presence of artefacts that do not interfere with the study interpretability (n = 56, 47%); fair = artefacts that do interfere with interpretability (n = 35, 29%); poor = uninterpretable study due to artefacts (n = 2, 2%). 'Fair' and 'poor' were merged into 'reduced' for comparisons. Increasing heart rate during stress myocardial CTP acquisition was related to worse interpretability (excellent: 61.7 ± 13.4 bpm vs. good: 69.8 ± 13.5 bpm vs. reduced: 78.1 ± 17.0 bpm, P < 0.001). Thirteen (11%) of all examinations were considered non-diagnostic. In patients with a heart rate exceeding 85 bpm, 76% of the studies were 'reduced' interpretable. In multivariate analysis, no use of beta blocker (baseline or additional use prior to coronary CTA) (OR: 0.2, P = 0.012), increasing heart rate during coronary CTA (OR: 1.09, P = 0.032), younger age (OR: 0.92, P = 0.021), and the use of calcium antagonist (OR: 6.48, P = 0.017) were independently associated with a heart rate ≥85 bpm during stress myocardial CTP., Conclusion: Higher heart rate during the acquisition of stress myocardial CTP was related to worse interpretability. Furthermore, increasing heart rate during and no beta blocker use prior to the previously performed coronary CTA, younger age, and the use of calcium antagonist were independently associated with a heart rate ≥85 bpm during stress myocardial CTP acquisition., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aspirin use for primary prevention in patients at high risk with diabetes mellitus (DM) is often recommended under the assumption that most patients with DM have coronary artery disease (CAD). However, not all patients may have CAD. The present study evaluated, in 425 patients at high risk with DM (without chest pain syndrome or a history of cardiac disease), the prevalence of CAD on coronary computed tomography angiography (CTA). Moreover, the association between the presence and number of traditional cardiovascular (CV) risk factors and CAD (on coronary CTA) was evaluated. The median coronary artery calcium score was 29 (interquartile range 0 to 298). On coronary CTA, 116 patients (27%) had no CAD (defined as <30% stenosis). Of the 309 patients (73%) with any CAD (≥30% stenosis), 35% had obstructive CAD (≥50% stenosis). The number of traditional CV risk factors was not associated with the presence of any CAD (≥30% stenosis; p = 0.18) or obstructive CAD (≥50% stenosis; p = 0.13). Hypertension was the only traditional CV risk factor associated with a higher frequency of any CAD (≥30% stenosis; odds ratio = 2.21, 95% CI 1.43 to 3.41, p <0.001) and obstructive CAD (≥50% stenosis; odds ratio 2.03, 95% CI 1.33 to 3.11, p = 0.001). In conclusion, in patients at high risk with DM without chest pain syndrome, any CAD was ruled out by coronary CTA in 27%, whereas 65% of the patients did not have obstructive CAD. The number of CV risk factors was not associated with the presence of CAD. Hypertension was the only traditional CV risk factor that was associated with a higher frequency of CAD. These observations support potential use of coronary CTA to tailor aspirin therapy in patients at high risk with DM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Diabetic patients with coronary artery disease (CAD) are often free of chest pain syndrome. A useful modality for non-invasive assessment of CAD is coronary computed tomography angiography (CTA). However, the prognostic value of CAD on coronary CTA in diabetic patients without chest pain syndrome is relatively unknown. Therefore, the aim was to investigate the long-term prognostic value of coronary CTA in a large population diabetic patients without chest pain syndrome., Methods: Between 2005 and 2013, 525 diabetic patients without chest pain syndrome were prospectively included to undergo coronary artery calcium (CAC)-scoring followed by coronary CTA. During follow-up, the composite endpoint of all-cause mortality, non-fatal myocardial infarction (MI), and late revascularization (>90 days) was registered., Results: In total, CAC-scoring was performed in 410 patients and coronary CTA in 444 patients (431 interpretable). After median follow-up of 5.0 (IQR 2.7-6.5) years, the composite endpoint occurred in 65 (14%) patients. Coronary CTA demonstrated a high prevalence of CAD (85%), mostly non-obstructive CAD (51%). Furthermore, patients with a normal CTA had an excellent prognosis (event-rate 3%). An incremental increase in event-rate was observed with increasing CAC-risk category or coronary stenosis severity. Finally, obstructive (50-70%) or severe CAD (>70%) was independently predictive of events (HR 11.10 [2.52;48.79] (P = .001), HR 15.16 [3.01;76.36] (P = .001)). Obstructive (50-70%) or severe CAD (>70%) provided increased value over baseline risk factors., Conclusion: Coronary CTA provided prognostic value in diabetic patients without chest pain syndrome. Most importantly, the prognosis of patients with a normal CTA was excellent.