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Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings ( r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm 3 [95% LoA: -0.27 cm 3 , 0.19 cm 3 ] and 0.02 cm 3 [95% LoA: -0.14 cm 3 , 0.19 cm 3 ], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Aims: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients., Methods and Results: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14-23.7) and OR 10.26 (3.36-31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05-6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67-4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08-4.86)]., Conclusion: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group., Competing Interests: Conflict of interest: P.P., and D.L. are supported by grants from Amgen and Philips. A.L. is a consultant for and on the advisory board of Medtronic, Abbott, Boston Scientific, and Philips. R.B. has received consulting honoraria from Caristo, Novartis, Silence Therapeutic and grant/research support from Amgen and is a member of the board of directors for the American Society of Nuclear Cardiology and the Society of Cardiovascular Computed Tomography. M.J.B. has received grants from the National Institutes of Health, U.S. Food and Drug Administration, AHA, Amgen, Novo Nordisk, and Bayer and is on the advisory boards for Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, 89Bio, Kaleido, Roche, Inozyme, emocha, VoxelCloud, and Kowa. D.S.B. and D.D. received software royalties from Cedars-Sinai Medical Center and hold a patent (US8885905B2 in the USA and World Intellectual Property Organization patent WO2011069120A1, ‘Method and System for Plaque Characterization’). S.S.V. has received honorarium from the American College of Cardiology (Associate Editor for Innovations, acc.org) and grant funding from the U.S. Department of Veterans Affairs, National Institutes of Health, World Heart Federation, and Tahir and Jooma Family. L.S. has received consulting honoraria from Amgen, Regeneron and Philips and research grants from Amgen and Philips. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: Recent studies suggest that the application of exercise activity questionnaires, including the use of a single-item exercise question, can be additive to the prognostic efficacy of imaging findings. This study aims to evaluate the prognostic efficacy of exercise activity in patients undergoing coronary computed tomography angiography (CCTA)., Methods and Results: We assessed 9772 patients who underwent CCTA at a single center between 2007 and 2020. Patients were divided into 4 groups of physical activity as no exercise (n ​= ​1643, 17%), mild exercise (n ​= ​3156, 32%), moderate exercise (n ​= ​3542, 36%), and high exercise (n ​= ​1431,15%), based on a single-item self-reported questionnaire. Coronary stenosis was categorized as no (0%), non-obstructive (1-49%), borderline (50-69%), and obstructive (≥70%). During a median follow-up of 4.64 (IQR 1.53-7.89) years, 490 (7.6%) died. There was a stepwise inverse relationship between exercise activity and mortality (p ​< ​0.001). Compared with the high activity group, the no activity group had a 3-fold higher mortality risk (HR: 3.3, 95%CI (1.94-5.63), p ​< ​0.001) after adjustment for age, clinical risk factors, symptoms, and statin use. For any level of CCTA stenosis, mortality rates were inversely associated with the degree of patients' exercise activity. The risk of all-cause mortality was similar among the patients with obstructive stenosis with high exercise versus those with no coronary stenosis but no exercise activity (p ​= ​0.912)., Conclusion: Physical activity as assessed by a single-item self-reported questionnaire is a strong stepwise inverse predictor of mortality risk among patients undergoing CCTA., Competing Interests: Declaration of competing interest All authors declare no conflict of interests, (Copyright © 2024. Published by Elsevier Inc.)

Background: Computed tomography attenuation correction (CTAC) improves perfusion quantification of hybrid myocardial perfusion imaging by correcting for attenuation artifacts. Artificial intelligence (AI) can automatically measure coronary artery calcium (CAC) from CTAC to improve risk prediction but could potentially derive additional anatomic features., Objectives: The authors evaluated AI-based derivation of cardiac anatomy from CTAC and assessed its added prognostic utility., Methods: The authors considered consecutive patients without known coronary artery disease who underwent single-photon emission computed tomography/computed tomography (CT) myocardial perfusion imaging at 3 separate centers. Previously validated AI models were used to segment CAC and cardiac structures (left atrium, left ventricle, right atrium, right ventricular volume, and left ventricular [LV] mass) from CTAC. They evaluated associations with major adverse cardiovascular events (MACEs), which included death, myocardial infarction, unstable angina, or revascularization., Results: In total, 7,613 patients were included with a median age of 64 years. During a median follow-up of 2.4 years (IQR: 1.3-3.4 years), MACEs occurred in 1,045 (13.7%) patients. Fully automated AI processing took an average of 6.2 ± 0.2 seconds for CAC and 15.8 ± 3.2 seconds for cardiac volumes and LV mass. Patients in the highest quartile of LV mass and left atrium, LV, right atrium, and right ventricular volume were at significantly increased risk of MACEs compared to patients in the lowest quartile, with HR ranging from 1.46 to 3.31. The addition of all CT-based volumes and CT-based LV mass improved the continuous net reclassification index by 23.1%., Conclusions: AI can automatically derive LV mass and cardiac chamber volumes from CT attenuation imaging, significantly improving cardiovascular risk assessment for hybrid perfusion imaging., Competing Interests: Funding Support and Author Disclosures This research was supported in part by the National Heart, Lung, and Blood Institute at the National Institutes of Health grant R35HL161195 (Principal Investigator: Dr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr Kavanagh has received software royalties for QPS software at Cedars-Sinai Medical Center. Dr Miller has received consulting fees and research support from Pfizer; and has served as a consultant for GE Healthcare. Dr Newby is supported by the British Heart Foundation; is a recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and has received honoraria for consultancy and lectures from AstraZeneca. Dr Berman has received software royalties for QPS software at Cedars-Sinai Medical Center; and has served as a consultant for GE Healthcare. Dr Slomka has received software royalties for QPS software at Cedars-Sina Medical Center, research grant support from Siemens Medical Systems, and consulting fees from Synektik., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Positive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA)., Methods: A total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling., Results: In the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26-3.48], P ​= ​0.004)., Conclusion: Greater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: To assess pericoronary adipose tissue (PCAT) density on coronary computed tomography angiography (CCTA) as a marker of inflammatory disease activity in coronary allograft vasculopathy (CAV)., Methods and Results: PCAT density, lesion volumes, and total vessel volume-to-myocardial mass ratio (V/M) were retrospectively measured in 126 CCTAs from 94 heart transplant patients [mean age 49 (SD 14.5) years, 40% female] who underwent imaging between 2010 and 2021; age- and sex-matched controls; and patients with atherosclerosis. PCAT density was higher in transplant patients with CAV [n = 40; -73.0 HU (SD 9.3)] than without CAV [n = 86; -77.9 HU (SD 8.2)], and controls [n = 12; -86.2 HU (SD 5.4)], P < 0.01 for both. Unlike patients with atherosclerotic coronary artery disease (n = 32), CAV lesions were predominantly non-calcified and comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without [32.4 mm3/g (SD 9.7) vs. 41.4 mm3/g (SD 12.3), P < 0.0001]. PCAT density and V/M improved the ability to predict CAV from area under the receiver operating characteristic curve (AUC) 0.75-0.85 when added to donor age and donor hypertension status (P < 0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality {odds ratio [OR] 18.0 [95% confidence interval (CI) 3.25-99.6], P < 0.01} and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularization [OR 7.47 (95% CI 1.8-31.6), P = 0.01] over 5.3 (SD 2.1) years., Conclusion: Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Increased PCAT density is associated with adverse clinical outcomes. These CCTA metrics could be useful for the diagnosis and monitoring of CAV severity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease., Methods and Results: A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P <0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P =0.017)., Conclusions: The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

Coronary computed tomography angiography (CCTA) has emerged as a pivotal tool for diagnosing and risk-stratifying patients with suspected coronary artery disease (CAD). Recent advancements in image analysis and artificial intelligence (AI) techniques have enabled the comprehensive quantitative analysis of coronary atherosclerosis. Fully quantitative assessments of coronary stenosis and lumen attenuation have improved the accuracy of assessing stenosis severity and predicting hemodynamically significant lesions. In addition to stenosis evaluation, quantitative plaque analysis plays a crucial role in predicting and monitoring CAD progression. Studies have demonstrated that the quantitative assessment of plaque subtypes based on CT attenuation provides a nuanced understanding of plaque characteristics and their association with cardiovascular events. Quantitative analysis of serial CCTA scans offers a unique perspective on the impact of medical therapies on plaque modification. However, challenges such as time-intensive analyses and variability in software platforms still need to be addressed for broader clinical implementation. The paradigm of CCTA has shifted towards comprehensive quantitative plaque analysis facilitated by technological advancements. As these methods continue to evolve, their integration into routine clinical practice has the potential to enhance risk assessment and guide individualized patient management. This article reviews the evolving landscape of quantitative plaque analysis in CCTA and explores its applications and limitations., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Background: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes., Methods and Results: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P <0.001), low attenuation plaque (63.1% versus 33.7%, P <0.001), napkin-ring sign (32.4% versus 11.0%, P <0.001), and spotty calcification (55.0% versus 34.9%, P <0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm 3 , P <0.001) and remodeling index (1.30 versus 1.20, P =0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%., Conclusions: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes., Registration Information: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

To evaluate if Indigenous Australians have higher coronary inflammation demonstrated non-invasively using pericoronary adipose tissue attenuation on coronary computed tomography angiography (CCTA). We retrospectively obtained a cohort 54 Indigenous patients age- and sex-matched to 54 non-Indigenous controls (age: 46.5 ± 13.1 years; male: n = 66) undergoing CCTA at the Royal Darwin Hospital and Monash Medical Centre. Patient groups were defined to investigate the interaction of ethnicity and sex: Indigenous + male, Indigenous + female, control + male, control + female. Semi-automated software was used to assess pericoronary adipose tissue attenuation (PCAT-a) and volume (PCAT-v). Males had significantly higher PCAT-a (- 86.7 ± 7.8 HU vs. - 91.3 ± 7.1 HU, p = 0.003) than females. Indigenous patients had significantly higher PCAT-v (1.5 ± 0.5cm 3 vs. 1.3 ± 0.4cm 3 , p = 0.032), but only numerically higher PCAT-a (p = 0.133) than controls. There was a significant difference in PCAT-a and PCAT-v across groups defined by Indigenous status and sex (p = 0.010 and p = 0.030, respectively). Among patients with matching CCTA contrast density, multivariable linear regression analysis showed an independent association between Indigenous status and PCAT-a. Indigenous men have increased PCAT-a in an age- and sex-matched cohort. Male sex is strongly associated with increased PCAT-a. Coronary inflammation may contribute to adverse cardiovascular outcomes in Indigenous Australians, but larger studies are required to validate these findings., (© 2023. Springer Nature Limited.)

Background: Coronary 18 F-sodium-fluoride ( 18 F-NaF) positron emission tomography (PET) showed promise in imaging coronary artery disease activity. Currently image processing remains subjective due to the need for manual registration of PET and computed tomography (CT) angiography data. We aimed to develop a novel fully automated method to register coronary 18 F-NaF PET to CT angiography using pseudo-CT generated by generative adversarial networks (GAN)., Methods: A total of 169 patients, 139 in the training and 30 in the testing sets were considered for generation of pseudo-CT from non-attenuation corrected (NAC) PET using GAN. Non-rigid registration was used to register pseudo-CT to CT angiography and the resulting transformation was used to align PET with CT angiography. We compared translations, maximal standard uptake value (SUV max ) and target to background ratio (TBR max ) at the location of plaques, obtained after observer and automated alignment., Results: Automatic end-to-end registration was performed for 30 patients with 88 coronary vessels and took 27.5 seconds per patient. Difference in displacement motion vectors between GAN-based and observer-based registration in the x-, y-, and z-directions was 0.8 ± 3.0, 0.7 ± 3.0, and 1.7 ± 3.9 mm, respectively. TBR max had a coefficient of repeatability (CR) of 0.31, mean bias of 0.03 and narrow limits of agreement (LOA) (95% LOA: - 0.29 to 0.33). SUV max had CR of 0.26, mean bias of 0 and narrow LOA (95% LOA: - 0.26 to 0.26)., Conclusion: Pseudo-CT generated by GAN are perfectly registered to PET can be used to facilitate quick and fully automated registration of PET and CT angiography., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Coronary 18 F-sodium fluoride ( 18 F-NaF) PET and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18 F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and 18 F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40-59) months of follow-up. On univariable receiver-operator-curve analysis, only 18 F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18 F-NaF PET), we achieved a substantial improvement ( P = 0.008 versus 18 F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18 F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background A new imaging metric using coronary computed tomography angiography (CCTA), addressing the peri-coronary adipose tissue (PCAT) computed tomography (CT) attenuation, has been clinically validated. This method provides information regarding coronary inflammation. It is unclear how coronary inflammation affects microvascular function. The non-invasive evaluation of coronary flow velocity reserve is widely used in clinical practice using Doppler measurement on the left anterior descending coronary artery (CFVR-lad) during stress-echocardiography (SE). We hypothesize that coronary inflammation affects CFVR-lad and, in the absence of overt CAD, they are significantly correlated. Methods We evaluated the relationship between coronary inflammation (by PCAT CT attenuation) and coronary microvascular function (by CFVR-lad) in subjects with no or non-obstructive (diameter stenosis <70%) coronary artery disease (CAD). Results Two-hundred and two subjects were enrolled in the study. The relationship between PCAT CT attenuation and CFVR-lad show a significant inverse relationship in the entire group of subjects enrolled in the study (r = -0.32, p < 0.001). Correlation between PCAT CT attenuation and CFVR-lad was significant in subjects with no or mild CAD-lad, while this was not the case in subjects with intermediate CAD-lad. The R and R 2 were respectively -0.40, -0.16 in subjects without CAD (p < 0.001) and - 0.35 and - 0.12 in subjects with mild CAD-lad (p = 0.001). Conclusions The main finding of the current study is the independent relationship between coronary microvascular function, by Doppler CFVR-lad during SE, in subjects without severely obstructive CAD in the left anterior descending coronary artery, and the level of local coronary inflammation, by PCAT attenuation measurement on CCTA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Studies have observed higher incidence of cardiovascular mortality in South Asians (SA), and lower prevalence in East Asians (EA), compared with Caucasians. These observations are not entirely explained by ethnic differences in cardiovascular risk factors and mechanistic factors such as variations in cardiac anatomy and physiology may play a role. This study compared ethnic differences in CT-assessed left ventricular (LV) mass, coronary anatomy and non-invasive fractional flow reserve (FFR CT )., Methods: Three-hundred symptomatic patients (age 59 ± 7.9, male 51%) underwent clinically-mandated CT-coronary-angiography (CTA) were matched for age, gender, BMI and diabetes (100 each ethnicity). Assessment of coronary stenosis, luminal dimensions and vessel dominance was performed by independent observers. LV mass, coronary luminal volume and FFR CT were quantified by blinded core-laboratory. A sub-analysis was performed on patients (n = 187) with normal/minimal disease (0-25% stenosis)., Results: Stenosis severity was comparable across ethnic groups. EA demonstrated less left-dominant circulation (2%) compared with SA (8.2%) and Caucasians (10.1%). SA compared with EA and Caucasians demonstrated smallest indexed LV mass, coronary luminal volumes and dimensions. EA compared with Caucasians had comparable indexed LV mass, coronary luminal dimensions and highest luminal volumes. The latter was driven by higher prevalence of right-dominance including larger and longer right posterior left ventricular artery. FFR CT in the left anterior descending artery (LAD) was lowest in SA (0.87) compared with EA (0.89; P = 0.009) and Caucasians (0.89; P < 0.001), with no difference in other vessels. All observed differences were consistent in patients with minimal disease., Conclusion: This single-centre study identified significant ethnic differences in CT-assessed LV mass, coronary anatomy and LAD FFR CT . These hypotheses generating results may provide a mechanistic explanation for ethnic differences in cardiovascular outcomes and require validation in larger cohorts., Competing Interests: Declaration of competing interest Dr Ihdayhid has received honorarium from Boston Scientific and Canon Medical. Associate Professor Ko has received honorarium and speaker fees from Medtronic, Canon Medical, St Jude, Novartis, Pfizer, Bristol-Myers Squibb and Lilly. Associate Professor Seneviratne has received honorarium from Canon Medical. Professor Achenbach has received research grants from Siemens Healthcare and Bayer. Dr Leipsic is a consultant for Edwards Lifesciences, Circl CVI, Heartflow Inc and has stock options in Circl CVI and HeartFlow Inc., (Copyright © 2020. Published by Elsevier Inc.)

Modern coronary computed tomography angiography (CTA) is the gold standard to visualize the epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT). The EAT is a metabolic active fat depot enclosed by the visceral pericardium and surrounds the coronary arteries. In disease states with increased EAT volume and dysfunctional adipocytes, EAT secretes an increased amount of adipocytokines and the resulting imbalance of proinflammatory and anti-inflammatory mediators potentially causes atherogenic effects on the coronary vessel wall in a paracrine way ("outside-to-inside" signaling). These EAT-induced atherogenic effects are reported to increase the risk for the development of coronary artery disease, myocardial ischemia, high-risk plaque features, and future major adverse cardiac events. Coronary inflammation plays a key role in the development and progression of coronary artery disease; however, its noninvasive detection remains challenging. In future, this clinical dilemma might be changed by the CTA-derived analysis of the PCAT. On the basis of the concept of an "inside-to-outside" signaling between the inflamed coronary vessel wall and the surrounding PCAT recent evidence demonstrates that PCAT computed tomography attenuation especially around the right coronary artery derived from routine CTA is a promising imaging biomarker and "sensor" to noninvasively detect coronary inflammation. This review summarizes the biological and technical principles of CTA-derived PCAT analysis and highlights its clinical implications to improve modern cardiovascular prevention strategies., Competing Interests: D.D. received software royalties from Cedars-Sinai Medical Center and has a patent. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Coronary computed tomographic angiography (CCTA) provides a wealth of clinically meaningful information beyond anatomic stenosis alone, including the presence or absence of nonobstructive atherosclerosis and high-risk plaque features as precursors for incident coronary events. There is, however, no uniform agreement on how to identify and quantify these features or their use in evidence-based clinical decision-making. This statement from the Society of Cardiovascular Computed Tomography and North American Society of Cardiovascular Imaging addresses this gap and provides a comprehensive review of the available evidence on imaging of coronary atherosclerosis. In this statement, we provide standardized definitions for high-risk plaque (HRP) features and distill the evidence on the effectiveness of risk stratification into usable practice points. This statement outlines how this information should be communicated to referring physicians and patients by identifying critical elements to include in a structured CCTA report - the presence and severity of atherosclerotic plaque (descriptive statements, CAD-RADS™ categories), the segment involvement score, HRP features (e.g., low attenuation plaque, positive remodeling), and the coronary artery calcium score (when performed). Rigorous documentation of atherosclerosis on CCTA provides a vital opportunity to make recommendations for preventive care and to initiate and guide an effective care strategy for at-risk patients., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: To assess the incremental value of quantitative plaque features measured from computed tomography angiography (CTA) for predicting side branch (SB) occlusion in coronary bifurcation intervention., Methods: We included 340 patients with 377 bifurcation lesions in the post hoc analysis of the CT-PRECISION registry. Each bifurcation was divided into three segments: the proximal main vessel (MV), the distal MV, and the SB. Segments with evidence of coronary plaque were analyzed using semi-automated software allowing for quantitative analysis of coronary plaque morphology and stenosis. Coronary plaque measurements included calcified and noncalcified plaque volumes, and corresponding burdens (respective plaque volumes × 100%/vessel volume), remodeling index, and stenosis., Results: SB occlusion occurred in 28 of 377 bifurcation lesions (7.5%). The presence of visually identified plaque in the SB segment, but not in the proximal and distal MV segments, was the only qualitative parameter that predicted SB occlusion with an area under the curve (AUC) of 0.792. Among quantitative plaque parameters calculated for the SB segment, the addition of noncalcified plaque burden (AUC 0.840, p = 0.003) and low-density plaque burden (AUC 0.836, p = 0.012) yielded significant improvements in predicting SB occlusion. Using receiver operating characteristic curve analysis, optimal cut-offs for noncalcified plaque burden and low-density plaque burden were > 33.6% (86% sensitivity and 78% specificity) and > 0.9% (89% sensitivity and 73% specificity), respectively., Conclusions: CTA-derived noncalcified plaque burden, when added to the visually identified SB plaque, significantly improves the prediction of SB occlusion in coronary bifurcation intervention., Trial Registration: ClinicalTrials.gov Identifier: NCT03709836 registered on October 17, 2018.

Background: High pericoronary adipose tissue (PCAT) attenuation and non-calcified plaque burden (NCP) measured from coronary CT angiography (CTA) have been implicated in future cardiac events. We aimed to evaluate the interobserver and intraobserver repeatability of PCAT attenuation and NCP burden measurement from CTA, in a sub-study of the prospective SCOT-HEART trial., Methods: Fifty consecutive CTAs from participants of the CT arm of the prospective SCOT-HEART trial were included. Two experienced observers independently measured PCAT attenuation and plaque characteristics throughout the whole coronary tree from CTA using semi-automatic quantitative software., Results: We analyzed proximal segments in 157 vessels. Intraobserver mean differences in PCAT attenuation and NCP plaque burden were -0.05HU and 0.92% with limits of agreement (LOA) of ±1.54 and ± 5.97%. Intraobserver intraclass correlation coefficients (ICC) for PCAT attenuation and NCP burden were excellent (0.999 and 0.978). Interobserver mean differences in PCAT attenuation and NCP plaque burden were 0.13HU [LOA ±1.67HU] and -0.23% (LOA ±9.61%). Interobserver ICC values for PCAT attenuation and NCP burden were excellent (0.998 and 0.944)., Conclusion: PCAT attenuation and NCP burden on CTA has high intraobserver and interobserver repeatability, suggesting they represent a repeatable and robust method of quantifying cardiovascular risk., Competing Interests: Declaration of competing interest Outside the current study, D.D., S.C., D.S., P.S. received software royalties from Cedars-Sinai Medical Center; D.D., D.S. P.S. hold a patent., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0-92] in TS vs. 0 [0-81]mm 3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.ClinicalTrial.gov Identifier: NCT01678261 ( https://clinicaltrials.gov/ct2/show/NCT01678261 ).

Background and Aims: Higher pericoronary adipose tissue (PCAT) attenuation, a novel marker of inflammation in coronary CT angiography (CTA), has been shown to indicate increased cardiac mortality. Supplementation of eicosapentaenoic acid (EPA) has been shown to decrease cardiovascular death. Whether blood levels of n-3 fatty acids are associated with differences in PCAT attenuation is unknown., Methods: This is a cross-sectional analysis including 64 symptomatic patients who underwent coronary CTA. PCAT attenuation was measured in Hounsfield Units (HU) around the proximal 40 mm of the right coronary artery using semi-automated software. Erythrocyte membrane fatty acid composition was analyzed using gas chromatography. Individual fatty acids were expressed as a percentage of total identified fatty acids., Results: The patient cohort was divided into two groups using the median PCAT attenuation of -78.1 HU (each n = 32). No differences were seen in age, sex, BMI or traditional cardiovascular risk factors (CVRF) between groups (all p > 0.05). In univariable analysis, significantly higher values of EPA (1.00% [0.78; 1.26] vs. 0.78% [0.63; 0.99]; p = 0.02) were seen in patients with lower PCAT attenuation. All other fatty acids showed no differences (all p > 0.05). Moreover, a significant negative correlation was seen between PCAT attenuation and EPA (CC: 0.38; p = 0.002). In multivariable analysis, an inverse association of EPA with PCAT attenuation existed (ß = -0.31, p = 0.017), independent of age, gender, BMI and number of CVRF (all p > 0.1)., Conclusions: High levels of EPA are associated with lower PCAT attenuation on coronary CTA. This may indicate a different composition of pericoronary adipose tissue, potentially caused by a lower degree of coronary inflammation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Our aim was to evaluate the performance of machine learning (ML), integrating clinical parameters with coronary artery calcium (CAC), and automated epicardial adipose tissue (EAT) quantification, for the prediction of long-term risk of myocardial infarction (MI) and cardiac death in asymptomatic subjects., Methods and Results: Our study included 1912 asymptomatic subjects [1117 (58.4%) male, age: 55.8 ± 9.1 years] from the prospective EISNER trial with long-term follow-up after CAC scoring. EAT volume and density were quantified using a fully automated deep learning method. ML extreme gradient boosting was trained using clinical co-variates, plasma lipid panel measurements, risk factors, CAC, aortic calcium, and automated EAT measures, and validated using repeated 10-fold cross validation. During mean follow-up of 14.5 ± 2 years, 76 events of MI and/or cardiac death occurred. ML obtained a significantly higher AUC than atherosclerotic cardiovascular disease (ASCVD) risk and CAC score for predicting events (ML: 0.82; ASCVD: 0.77; CAC: 0.77, P < 0.05 for all). Subjects with a higher ML score (by Youden's index) had high hazard of suffering events (HR: 10.38, P < 0.001); the relationships persisted in multivariable analysis including ASCVD-risk and CAC measures (HR: 2.94, P = 0.005). Age, ASCVD-risk, and CAC were prognostically important for both genders. Systolic blood pressure was more important than cholesterol in women, and the opposite in men., Conclusions: In this prospective study, machine learning used to integrate clinical and quantitative imaging-based variables significantly improves prediction of MI and cardiac death compared with standard clinical risk assessment. Following further validation, such a personalized paradigm could potentially be used to improve cardiovascular risk assessment., (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: Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation., Methods: Thin slice pre- and post-contrast studies obtained at 120 kVp, heart rate <60, with no plaque or artifact in the right coronary artery (RCA) were selected. Analysis was limited to pixels -30 Hounsfield units (HU) to -190 HU and from 10 mm to 50 mm distal to the RCA origin at a radial distance equal to the vessel diameter. A subgroup with no plaque across all coronaries was also analyzed., Results: Of 119 study pairs, the average RCA diameter was highly correlated at 3.85 mm (postcontrast) and 3.84 mm (precontrast), r = 0.97, p < 0.0001. The mean attenuation of pre- and postcontrast images was also highly correlated at -87.02 ± 7.15 HU and -82.74 ± 6.54 HU, respectively (r = 0.65, p < 0.0001). Pericoronary fat volume in the -190 to -30 HU range was 396 mm³ lower in the post contrast versus pre-contrast, consistent with higher attenuation (less negative) voxels postcontrast (p < 0.0001). Inter- and intra-reader agreement ranged 95-100% and 90% for precontrast and 85-90% for postcontrast studies, respectively. Subgroup analysis revealed precontrast attenuation -85.59 ± 7.53 HU and postcontrast -82.21 ± 7.15 HU were highly correlated r = 0.67, p < 0.0001., Conclusion: Pericoronary fat enhances with iodinated contrast, potentially explaining some of its risk-predictive capabilities. Fat attenuation and volume can be reliably measured from precontrast calcium scans, with volume quantification showing particularly strong correlation. Excellent inter- and intra-reader agreement is also demonstrated., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the occurrence of physiological significant coronary artery disease (CAD) by coronary CT angiography (CTA) derived fractional flow reserve (FFR CT ) in asymptomatic patients with a new diagnosis (<1 year) of type-2 diabetes mellitus (T2DM)., Methods: FFR CT -analysis was performed from standard acquired coronary CTA data sets. The per-patient minimum distal FFR CT -value (d-FFR CT ) in coronary vessels (diameter ⩾1.8 mm) was registered. The threshold for categorizing FFR CT -analysis as abnormal was a d-FFR CT ⩽0.75. Total plaque volume and volumes of calcified plaque, non-calcified plaque, and low-density non-calcified plaque (LD-NCP) were assessed by quantitative plaque analysis., Results: Overall, 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49(65), were studied. A total of 57% of patients had plaques. The d-FFR CT was ⩽0.75 in 12 (16%) patients. The d-FFR CT , median (IQR), was 0.84 (0.79-0.87). Median (range) d-FFR CT in patients with d-FFR CT ⩽0.75 was 0.70 (0.6-0.74). Patients with d-FFR CT ⩽0.75 versus d-FFR CT >0.75 had numerically higher plaque volumes for all plaques components, although only significant for the LD-NCP component., Conclusion: Every sixth asymptomatic patient with a new diagnosis of T2DM has hemodynamic significant CAD as evaluated by FFR CT. Flow impairment by FFR CT was associated with coronary plaque characteristics.

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction., Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses., Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0-5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score ( r =0.34; P <0.001), strongly with coronary artery calcium score ( r =0.62; P <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r =0.83; P <0.001). Low-attenuation plaque burden (7.5% [4.8-9.2] versus 4.1% [0-6.8]; P <0.001), coronary artery calcium score (336 [62-1064] versus 19 [0-217] Agatston units; P <0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P <0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10-2.34) per doubling; P =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06-10.5; P <0.001)., Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01149590.

Epicardial adipose tissue (EAT) is associated with cardiovascular risk. The longitudinal change in EAT volume (EATv) and density (EATd), and potential modulators of these parameters, has not been described. We prospectively recruited 90 patients with non-obstructive coronary atherosclerosis on baseline computed tomography coronary angiography (CTCA) performed for suspected coronary artery disease to undergo a repeat research CTCA. EATv in millilitres (mL) and EATd in Hounsfield units (HU) were analysed and multivariable regression analysis controlling for traditional cardiovascular risk factors (CVRF) performed to assess for any predictors of change. Secondary analysis was performed based on statin therapy. The median duration between CTCA was 4.3years. Mean EATv increased at follow-up (72 ± 33 mL to 89 ± 43 mL, p < 0.001) and mean EATd decreased (baseline -76 ± 6 HU vs. -86 ± 5 HU, p < 0.001). There were no associations between baseline variables of body mass index, age, sex, hypertension, hyperlipidaemia, diabetes or smoking on change in EATv or EATd. No difference in baseline, follow-up or delta EATv or EATd was seen in patients with (60%) or without baseline statin therapy. In this select group of patients, EATv consistently increased and EATd consistently decreased at long-term follow-up and these changes were independent of CVRF, age and statin use. Together with the knowledge of strong associations between EAT and cardiac disease, these findings may suggest that EAT is an independent parameter rather than a surrogate for cardiovascular risk.

Purpose: South Asian (SA) have been observed to have higher cardiovascular mortality rates compared to East Asians (EA) and Caucasians. Pericoronary adipose tissue (PCAT) attenuation around the right coronary artery (RCA) from coronary CT angiography (CTA) has been associated with coronary inflammation and cardiac death. We aimed to investigate i) the relationship between plaque characteristics and PCAT attenuation and ii) to assess gender and ethnic differences in PCAT attenuation using a matched cohort of SA, EA and Caucasians., Method: Three-hundred symptomatic patients who underwent CTA were matched for age, gender, BMI and diabetes (100 in each ethnic group). Semi-automated software was used to quantify the total volumes and burden of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP) and calcified plaque (CP) in blinded core-lab analysis. PCAT CT attenuation was measured around the RCA (10-50 mm from RCA ostium), the most standardized model for PCAT analysis., Results: The total volumes and burden of NCP, LD-NCP and CP were comparable in the ethnic groups (each p > 0.05). PCAT attenuation was higher in patients with coronary plaque. PCAT attenuation correlated with the total volumes and burden of NCP, LD-NCP and CP (r>0.17; p < 0.003). Within the RCA this correlation persisted only for NCP features (r>0.39;p < 0.001). Males showed higher PCAT attenuation (p < 0.001). PCAT attenuation was similar between Caucasian, EA and SA (p = 0.32)., Conclusions: PCAT CT attenuation correlated most with its surrounded NCP features further highlighting its role as surrogate measure of coronary inflammation. As coronary plaque burden and RCA PCAT attenuation did not differ between ethnic groups, causes of increased cardiac mortality in South Asians needs further investigations., (Copyright © 2020. Published by Elsevier B.V.)

Purpose of Review: Perivascular adipose tissue (PVAT) has a complex, bidirectional relationship with the vascular wall. In disease states, PVAT secretes pro-inflammatory adipocytokines which may contribute to atherosclerosis. Recent evidence demonstrates that pericoronary adipose tissue (PCAT) may also function as a sensor of coronary inflammation. This review details PVAT biology and its clinical translation to current imaging phenotyping., Recent Findings: PCAT attenuation derived from routine coronary computed tomography (CT) angiography is a novel noninvasive imaging biomarker of coronary inflammation. Pro-inflammatory cytokines released from the arterial wall diffuse directly into the surrounding PCAT and inhibit adipocyte lipid accumulation in a paracrine manner. This can be detected as an increased PCAT CT attenuation, a metric which associates with high-risk plaque features and independently predicts cardiac mortality. There is also evidence that PCAT attenuation relates to coronary plaque progression and is modified by systemic anti-inflammatory therapies. Due to its proximity to the coronary arteries, PCAT has emerged as an important fat depot in cardiovascular research. PCAT CT attenuation has the potential to improve cardiovascular risk stratification, and future clinical studies should examine its role in guiding targeted medical therapy.

Objectives: We sought to evaluate the accuracy of standardized total plaque volume (TPV) measurement and low-density non-calcified plaque (LDNCP) assessment from coronary CT angiography (CTA) in comparison with intravascular ultrasound (IVUS)., Methods: We analyzed 118 plaques without extensive calcifications from 77 consecutive patients who underwent CTA prior to IVUS. CTA TPV was measured with semi-automated software comparing both scan-specific (automatically derived from scan) and fixed attenuation thresholds. From CTA, %LDNCP was calculated voxels below multiple LDNCP thresholds (30, 45, 60, 75, and 90 Hounsfield units [HU]) within the plaque. On IVUS, the lipid-rich component was identified by echo attenuation, and its size was measured using attenuation score (summed score ∕ analysis length) based on attenuation arc (1 = < 90°; 2 = 90-180°; 3 = 180-270°; 4 = 270-360°) every 1 mm., Results: TPV was highly correlated between CTA using scan-specific thresholds and IVUS (r = 0.943, p < 0.001), with no significant difference (2.6 mm 3 , p = 0.270). These relationships persisted for calcification patterns (maximal IVUS calcium arc of 0°, < 90°, or ≥ 90°). The fixed thresholds underestimated TPV (- 22.0 mm 3 , p < 0.001) and had an inferior correlation with IVUS (p < 0.001) compared with scan-specific thresholds. A 45-HU cutoff yielded the best diagnostic performance for identification of lipid-rich component, with an area under the curve of 0.878 vs. 0.840 for < 30 HU (p = 0.023), and corresponding %LDNCP resulted in the strongest correlation with the lipid-rich component size (r = 0.691, p < 0.001)., Conclusions: Standardized noninvasive plaque quantification from CTA using scan-specific thresholds correlates highly with IVUS. Use of a < 45-HU threshold for LDNCP quantification improves lipid-rich plaque assessment from CTA., Key Points: • Standardized scan-specific threshold-based plaque quantification from coronary CT angiography provides an accurate total plaque volume measurement compared with intravascular ultrasound. • Attenuation histogram-based low-density non-calcified plaque quantification can improve lipid-rich plaque assessment from coronary CT angiography.

Objectives: To describe carotid plaque composition by computed tomography angiography (CTA) in asymptomatic subjects and to compare this to carotid plaque assessment by ultrasound, coronary plaques by coronary CTA, and inflammatory biomarkers in plasma., Methods: Middle-aged asymptomatic men, n = 43, without known cardiovascular disease and diabetes were included. Plaques in coronary and carotid arteries were evaluated using CTA. Total plaque volumes and plaque composition were assessed by a validated plaque analysis software. The 60% centile cut point was used to divide the population into low or high carotid total plaque volumes. The occurrence of carotid plaques and intima-media thickness (IMT) was estimated by ultrasound., Results: Carotid plaque by ultrasound was undiagnosed in 13 of 28 participants (46%) compared to CTA. Participants having carotid plaques by ultrasound had significantly higher absolute volumes of all CTA-defined carotid plaque subtypes and a higher fraction of calcified plaque. A high carotid total plaque volume was independently associated with age (adjusted odds ratio (OR) 1.41 [95% confidence interval (CI) 1.14-1.74], p = 0.001), IMT (adjusted OR 2.26 [95% CI 1.10-4.65], p = 0.03), and D-dimer (adjusted OR 8.86 [95% CI 1.26-62.37], p = 0.03). All coronary plaque features were significantly higher in participants with a high carotid total plaque volume., Conclusion: The occurrence of carotid plaques in asymptomatic individuals is underestimated by ultrasound compared to plaque assessment by CTA. Carotid plaque composition by CTA is different in individuals with and without carotid plaques by ultrasound., Key Points: • The occurrence of carotid plaques by ultrasound was underestimated in 46% of participants who had plaques by carotid CTA. • Participants with carotid plaques by ultrasound had higher volumes of all plaque subtypes and a higher calcified plaque component as determined by carotid CTA compared to participants without carotid plaques by ultrasound. • A high carotid total plaque volume was independently associated with age, intima-media thickness, and D-dimer.

Background: It has been shown that CT attenuation of noncalcified plaques depends on luminal contrast attenuation (LCA). Although tube potential (kilovolt [kV]) has been shown to exert influence on plaque attenuation through LCA as well as its direct effects, in-vivo studies have not investigated plaque attenuation at lower tube potentials less than 120 kV. We sought to evaluate the effect of kV and LCA on thresholds for lipid-rich and fibrous plaques as defined by intravascular ultrasound (IVUS)., Methods: CT attenuation of IVUS-defined plaque components (lipid-rich, fibrous, and calcified plaques) were quantified in 52 consecutive patients with unstable angina, who had coronary CT angiography performed at 100 kV (n = 25) or 120 kV (n = 27) using kV-adjusted contrast protocol prior to IVUS. CT attenuation of plaque components was compared between the two groups., Results: LCA was similar in the 100-kV and 120-kV groups (417.6 ± 83.7 Hounsfield Units [HU] vs 421.3 ± 54.9 HU, p = 0.77). LCA correlated with CT attenuation of lipid-rich (r = 0.49, p = 0.001) and fibrous plaques (r = 0.32, p < 0.05), but not with that of calcified plaques (r = 0.04, p = 0.81). When plaque attenuation was normalized to LCA, lipid-rich (0.087 ± 0.036, range -0.012-0.147) and fibrous plaque attenuation (0.234 ± 0.056, range 0.153-0.394) were distinct (p < 0.001) with no overlap for both kV groups. CT attenuation was not significantly different between 100-kV and 120-kV groups for lipid-rich (34.0 ± 21.5 vs 39.3 ± 12.9, p = 0.33) or fibrous plaques (95.4 ± 19.1 vs 97.6 ± 22.0, p = 0.75)., Conclusion: Plaque attenuation thresholds for non-calcified plaque components should be adjusted based on LCA. Further adjustment may not be required for different tube potentials., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background and Aims: LDL-C reduction has been associated with a decrease in noncalcified plaque (NCP) by serial quantitative coronary CT angiography (CTA). We evaluated the effect of LDL-C reduction on specific components of noncalcified plaque (NCP)., Methods: We analyzed 154 patients undergoing serial CTAs (118 men, 60 ± 10 years, interval 4 ± 2 years) with baseline LDL-C≥70 mg/dl. Semi-automated software was used for quantifying plaque components based on CT attenuation in Hounsfield units (HU): 30-75, low attenuation plaque (LAP); 76-130, medium-low attenuation plaque (MLAP); 131-350, medium attenuation plaque (MAP); >350, calcified plaque (CP). Decrease in LDL-C was defined as a reduction >10% of baseline LDL-C. Plaque volume changes were compared between patients with (n = 85) and without (n = 69) LDL-C decrease., Results: There was interval reduction in total plaque, LAP, MLAP, and MAP volumes in patients with LDL-C decrease vs. patients without LDL-C decrease before and after adjusting for differences between the two groups (all p ≤ 0.001). An increase in CP volume occurred in both groups (p = 0.42)., Conclusions: Decrease in LDL-C was associated with reduction in all components of NCP measured by quantitative CTA. Change in total NCP volume may be the optimal measurement for assessing changes over time of coronary plaque on CTA., (Copyright © 2019. Published by Elsevier B.V.)

Aims: Increased attenuation of pericoronary adipose tissue (PCAT) around the proximal right coronary artery (RCA) from coronary computed tomography angiography (CTA) has been shown to be associated with coronary inflammation and improved prediction of cardiac death over plaque features. Our aim was to investigate whether PCAT CT attenuation is related to progression of coronary plaque burden., Methods and Results: We analysed CTA studies of 111 stable patients (age 59.2 ± 9.8 years, 77% male) who underwent sequential CTA (3.4 ± 1.6 years between scans) with identical acquisition protocols. Total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density non-calcified plaque (LD-NCP) volumes and corresponding burden (plaque volume × 100%/vessel volume) were quantified using semi-automated software. PCAT CT attenuation (HU) was measured around the proximal RCA, the most standardized method for PCAT analysis. Patients with an increase in NCP burden (n = 51) showed an increase in PCAT attenuation, whereas patients with a decrease in NCP burden (n = 60) showed a decrease {4.4 [95% confidence interval (CI) 2.6-6.2] vs. -2.78 (95% CI -4.6 to -1.0) HU, P < 0.0001}. Changes in PCAT attenuation correlated with changes in the burden of NCP (r = 0.55, P < 0.001) and LD-NCP (r = 0.24, P = 0.01); but not CP burden (P = 0.3). Increased baseline PCAT attenuation ≥-75 HU was independently associated with increase in NCP (odds ratio 3.07, 95% CI 1.4-7.0; P < 0.008) and TP burden on follow-up CTA., Conclusion: PCAT attenuation measured from routine CTA is related to the progression of NCP and TP burden. This imaging biomarker may help to identify patients at increased risk of high-risk plaque progression and allow monitoring of beneficial changes from medical therapy., (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: We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative evaluation of 18 F-NaF PET coronary uptake., Methods and Results: Forty-five patients (age 67.1±6.9 years; 76% males) underwent CTA (CTA1) and combined 18 F-NaF PET/CTA (CTA2) imaging within 14 [10, 21] days. We fused CTA1 from visit 1 with 18 F-NaF PET (PET) from visit 2 and compared visual pattern of activity, maximal standard uptake (SUVmax) values, and target to background ratio (TBR) measurements on (PET/CTA1) fused versus hybrid (PET/CTA2). On PET/CTA2, 226 coronary plaques were identified. Fifty-eight coronary segments from 28 (62%) patients had high 18 F-NaF uptake (TBR >1.25), whereas 168 segments had lesions with 18 F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on coregistered PET/CTA1. There was no significant difference in 18 F-NaF uptake values between PET/CTA1 and PET/CTA2 (SUVmax, 1.16±0.40 versus 1.15±0.39; P=0.53; TBR, 1.10±0.45 versus 1.09±0.46; P=0.55). The intraclass correlation coefficient for SUVmax and TBR was 0.987 (95% CI, 0.983-0.991) and 0.986 (95% CI, 0.981-0.992). There was no fixed or proportional bias between PET/CTA1 and PET/CTA2 for SUVmax and TBR. Cardiac motion correction of PET scans improved reproducibility with tighter 95% limits of agreement (±0.14 for SUVmax and ±0.15 for TBR versus ±0.20 and ±0.20 on diastolic imaging; P<0.001)., Conclusions: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18 F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.

This expert consensus statement from the Society of Cardiovascular Computed Tomography (SCCT) provides an evidence synthesis on the use of computed tomography (CT) imaging for diagnosis and risk stratification of coronary artery disease in women. From large patient and population cohorts of asymptomatic women, detection of any coronary artery calcium that identifies females with a 10-year atherosclerotic cardiovascular disease risk of >7.5% may more effectively triage women who may benefit from pharmacologic therapy. In addition to accurate detection of obstructive coronary artery disease (CAD), CT angiography (CTA) identifies nonobstructive atherosclerotic plaque extent and composition which is otherwise not detected by alternative stress testing modalities. Moreover, CTA has superior risk stratification when compared to stress testing in symptomatic women with stable chest pain (or equivalent) symptoms. For the evaluation of symptomatic women both in the emergency department and the outpatient setting, there is abundant evidence from large observational registries and multi-center randomized trials, that CT imaging is an effective procedure. Although radiation doses are far less for CT when compared to nuclear imaging, radiation dose reduction strategies should be applied in all women undergoing CT imaging. Effective and appropriate use of CT imaging can provide the means for improved detection of at-risk women and thereby focus preventive management resulting in long-term risk reduction and improved clinical outcomes., (Copyright © 2018 Society of Cardiovascular Computed Tomography. All rights reserved.)

Aim: To determine differences in coronary plaque composition and inflammatory biomarkers between men and women with newly diagnosed Type 2 diabetes without known cardiovascular disease., Methods: A total of 88 people with newly diagnosed (<1 year) Type 2 diabetes underwent contrast-enhanced coronary computed tomography angiography. Advanced coronary plaque analysis was performed using semi-automated software. Plasma concentrations of inflammatory biomarkers were determined., Results: There were no significant differences between men (n=60) and women (n=28) regarding age or cardiovascular risk factors (all P>0.05). The median (quartiles) serum levels of fibrinogen [10.9 (9.8-12.6) μmol/l vs 9.7 (8.8-10.9) μmol/l], fibrin d-dimer [0.3 (0.2-0.4) mg/l vs 0.27 (0.2-0.4) mg/l] and C-reactive protein [3.1 (1.1-5.2) mg/l vs (0.8-2.6) 1.6 mg/l] were significantly higher in women (all P<0.05). Overall, men more often had multi-vessel involvement [28 men (47%) vs 4 women (14%)], and higher total plaque burden [median (quartiles) 11.6 (2.3-36.0)% vs 2.0 (0.4-5.4)%; both P<0.05]. The median (quartiles) total plaque volume [269.9 (62.6-641.9) mm 3 vs 61.1 (7.6-239.9) mm 3 ] and absolute calcified plaque volume [33.5 (8.3-148.3) mm 3 vs 4.7 (0.9-17.3) mm 3 ] were higher in men (both P<0.05). Women had a lower relative proportion of the calcified plaque component [median (quartiles) 7.8 (4.7-15.4)% vs 23.7 (8.4-31.1)%] and a higher relative proportion (median [quartiles]) of the non-low-density non-calfied plaque component [77.6 (66.0-86.0)% vs 63.6 (54.0-72.9)%; both P<0.05]., Conclusions: In people with newly diagnosed Type 2 diabetes, women had lower absolute coronary plaque volumes but a more unfavourable plaque composition and enhanced systemic inflammation compared with men., (© 2018 Diabetes UK.)

Background: Computed tomography coronary angiography (CTA) can be used for assessment of plaque characteristics; however, quantitative assessment of changes in plaque composition in response to LDL lowering has not been performed with CTA. We sought to assess the association between LDL reduction and changes in plaque composition with quantitative CTA., Methods: Quantification of total, calcified, non-calcified and low-density non-calcified plaque volumes (TPV, CPV, NCPV and LD-NCPV) was performed using semi-automated software in 234 vessels from 116 consecutive patients (89 men, 60 ± 10 years) with baseline LDL>70 mg/dl. Significant reduction in LDL was defined as a decrease by >10% of baseline LDL. Changes (Δ) in plaque volumes between the second and baseline study were compared between patients with LDL reduction (n = 63) and those with no decrease in LDL (n = 53)., Results: Median LDL at baseline was 98 mg/dl [interquartile range (IQR) 83-119 mg/dl] and median ΔLDL was -14 mg/dl (IQR -38 to 3 mg/dl). Mean interval between sequential CTA was 3.5 ± 1.6 years. TPV, NCPV, and LD-NCPV decreased in patients with a reduction in LDL compared to baseline; whereas, patients without reduction in LDL experienced an increase in TPV, NCPV and LD-NCPV. After adjusting for age, statin use, diabetes, baseline LDL and baseline TPV, reduction in LDL was associated with a decrease in TPV (P = 0.005), NCPV (P = 0.002) and LD-NCPV (P = 0.011) compared to patients without a reduction in LDL., Conclusion: Reduction in LDL was associated with beneficial changes in the amount and composition of noncalcified plaque as measured using semi-automated quantitative software by CTA., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary stenosis and plaque evaluation by coronary computed tomography angiography (CTA) may contribute to identify hemodynamically relevant lesions. We evaluated the most stenotic lesion including plaques proximal to it versus a total vessel analyses combined with stenosis for ischemia., Methods: Patients scheduled for clinically indicated invasive coronary angiography (ICA) for suspected coronary artery disease underwent coronary CTA and ICA including fractional flow reserve (FFR) as part of the NXT trial (clinicaltrials.govNCT01757678). Stenoses were visually graded ≤50%, 51-70%, and >70% on coronary CTA. Semi-automated plaque analyses were performed using a proximal to the FFR pressure sensor location (including the most severe lesion to the coronary ostium) versus a total vessel (vessel diameter ≥2 mm) approach. Coronary stenosis and plaque parameters were evaluated for discrimination of ischemia by logistic regressions and combined models analyzed using receiver operating characteristics (ROC) with invasive FFR≤ 0.80 as reference standard., Results: In 254 patients, mean (±SD) age 64 (±10) years, 64% male, a coronary CTA stenosis >50% was present in 239 (49%) vessels. Invasive FFR was ≤0.80 in 100 (21%) vessels. Coronary stenosis severity and low-density non-calcified plaque (LD-NCP) volume were independent predictors of ischemia in the "proximal" and "total-vessel" analyses. Stenosis severity + total vessel LD-NCP assessment performed better than stenosis severity + proximal LD-NCP evaluation (Area under curve [AUC] (95%CI): 0.83 (0.78-0.87) vs 0.81 (0.76-0.86), p-value = 0.009), whereas stenosis severity + proximal LD-NCP performed better than stenosis alone (AUC (95%CI): 0.81 (0.76-0.86) vs 0.78 (0.73-0.83), p-value = 0.019)., Conclusion: Adding total vessel high-risk plaque volume to stenosis severity improves discrimination of ischemia in coronary CTA performed in patients with stable angina pectoris., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR., Background: In patients with stable ischemic heart disease, FFR-guided revascularization, as compared with medical therapy alone, is reported to improve outcomes. Because morphological characteristics are the basis of plaque rupture and acute coronary events, a relationship between FFR and lesion characteristics may exist., Methods: This is a subanalysis of NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography), a prospective, multicenter study of 254 patients (age 64 ± 10 years, 64% male) with suspected stable ischemic heart disease; coronary computed tomography angiography including plaque morphology assessment, invasive angiography, and FFR were obtained for 383 lesions. Ischemia was defined by invasive FFR ≤0.80. Computed tomography angiography-defined morphological characteristics of plaques and their vascular location were used in univariate and multivariate analyses to examine their predictive value for invasive FFR. The distribution of various combinations of plaque morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR were examined., Results: The percentage of luminal stenosis, low-attenuation plaque (LAP) or necrotic core volume, left anterior descending coronary artery territory, and the presence of multiple lesions per vessel were the predictors of FFR. When grouped on the basis of degree of luminal stenosis, FFR-negative lesions had consistently smaller LAP volumes compared with FFR-positive lesions. The distribution of plaque characteristics in lesions with normal and abnormal FFR demonstrated that whereas FFR-negative lesions excluded likelihood of stenotic plaques with moderate to high LAP volumes, only one-third of FFR-positive lesions demonstrated obstructive plaques with moderate to high LAP volumes., Conclusions: In addition to the severity of luminal stenosis, necrotic core volume is an independent predictor of FFR. The distribution of plaque characteristics among lesions with varying luminal stenosis and normal and abnormal FFR may explain the outcomes associated with FFR-guided therapy., (Copyright © 2018. Published by Elsevier Inc.)

Background: We evaluated the diagnostic accuracy of a novel prototype for on-site determination of CT-based FFR (cFFR) on a standard personal computer (PC) compared to invasively measured FFR in patients with suspected coronary artery disease., Methods: A total of 91 vessels in 71 patients (mean age 65 ± 9 years) in whom coronary CT angiography had been performed due to suspicion of coronary artery disease, and who subsequently underwent invasive coronary angiography with FFR measurement were analyzed. For both cFFR and FFR, a threshold of ≤0.80 was used to indicate a hemodynamically relevant stenosis. The mean time needed to calculate cFFR was 12.4 ± 3.4 min. A very close correlation between cFFR and FFR could be shown (r = 0.85; p < 0.0001) with Bland-Altman analysis showing moderate agreement between FFR and cFFR with mild systematic overestimation of FFR values in CT (mean difference 0.0049, 95% limits of agreement ±2SD -0.007 to 0.008). Compared to FFR, the sensitivity of cFFR to detect hemodynamically significant lesions was 91% (19/21, 95% CI: 70%-99%), specificity was 96% (67/70, 95% CI: 88%-99%), positive predictive value 86% (95% CI: 65%-97%) and negative predictive value was 97% (95% CI: 90%-100%) with an accuracy of 93%., Conclusion: cFFR obtained using an on-site algorithm implemented on a standard PC shows high diagnostic accuracy to detect lesions causing ischemia as compared to FFR. Importantly, the time needed for analysis is short which may be useful for improving clinical workflow., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: We investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects., Methods: EAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE., Results: EAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm 3 , p < 0.001] [-76.9 vs -75.7 HU,p = 0.024]. EAT volume was lowest in individuals with no coronary calcium and was significant higher in subjects with early atherosclerosis (CCS 1-99) [74 vs 87 cm 3 ,p = 0.016] and in subjects with more advanced atherosclerosis (CCS≥100) [89 cm 3 ,p = 0.002]). EAT volume was independently related to serum levels of PAI-1, and MCP-1 and inversely related to adiponectin and HDL-cholesterol (p < 0.05). EAT density was inversely related to PAI-1 and LDL-cholesterol and positively associated to adiponectin, sICAM-1 and HDL-cholesterol (p < 0.05). EAT density was more significantly associated with MACE [(HR 0.8, 95%CI:0.7-0.98), p = 0.029] than EAT volume or CCS., Conclusion: EAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: Adverse plaque characteristics determined by coronary computed tomography angiography (CTA) have been associated with future cardiac events. Our aim was to investigate whether quantitative global per-patient plaque characteristics from coronary CTA can predict subsequent cardiac death during long-term follow-up., Methods and Results: Out of 2748 patients without prior history of coronary artery disease undergoing CTA with dual-source CT, 32 patients suffered cardiac death (mean follow-up of 5 ± 2 years). These patients were matched to 32 controls by age, gender, risk factors, and symptoms (total 64 patients, 59% male, age 69 ± 10 years). Coronary CTA data sets were analysed by semi-automated software to quantify plaque characteristics over the entire coronary tree, including total plaque volume, volumes of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP, attenuation <30 Hounsfield units), calcified plaque (CP), and corresponding burden (plaque volume × 100%/vessel volume), as well as stenosis and contrast density difference (CDD, maximum percent difference in luminal attenuation/cross-sectional area compared to proximal cross-section). In patients who died from cardiac cause, NCP, LD-NCP, CP and total plaque volumes, quantitative stenosis, and CDD were significantly increased compared to controls (P < 0.025 for all). NCP > 146 mm³ [hazards ratio (HR) 2.24; 1.09-4.58; P = 0.027], LD-NCP > 10.6 mm³ (HR 2.26; 1.11-4.63; P = 0.025), total plaque volume > 179 mm³ (HR 2.30; 1.12-4.71; P = 0.022), and CDD > 35% in any vessel (HR 2.85;1.4-5.9; P = 0.005) were associated with increased risk of future cardiac death, when adjusted for segment involvement score., Conclusion: Among quantitative global plaque characteristics, total, non-calcified, and low-density plaque volumes as well as CDD predict cardiac death in long-term follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: We hypothesize that in patients with suspected coronary artery disease (CAD), lower values of the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) result in lower fractional flow reserve (FFR)., Methods: V/M was computed in 238 patients from the NXT trial who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography (QCA) and FFR measurement in 438 vessels. Nitroglycerin was administered prior to CT, QCA and FFR acquisition. The V/M ratio was quantified on a patient-level from CT image data by segmenting the epicardial coronary arterial lumen volume (V) and the left ventricular myocardial mass (M). Calcified and noncalcified plaque volumes were quantified using semi-automated software., Results: The median value of V/M (18.57 mm 3 /g) was used to define equal groups of low and high V/M patients. Patients with low V/M had greater diameter stenosis by QCA, more plaque and lower FFR (0.80 ± 0.12 vs. 0.87 ± 0.08; P < 0.0001) than those with high V/M. A total of 365 vessels in 202 patients had QCA stenosis ≤50% and measured FFR. In these patients, those with low V/M had higher percent diameter stenosis by QCA, greater total plaque volume and lower FFR (0.81 ± 0.12 vs. 0.88 ± 0.07; P < 0.0001) than those with high V/M. In multivariate logistic regression analysis, V/M was an independent predictor of FFR ≤0.80 (all p-values < 0.001)., Conclusions: Patients with a low V/M ratio have lower FFR overall and in non-obstructive CAD, independent of plaque measures., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purposes of this study were to compare the presence, extent and composition of coronary plaques in asymptomatic patients with newly diagnosed type 2 diabetes to age- and sex-matched controls., Methods: Patients with newly diagnosed (<1 year) type 2 diabetes ( n = 44) and controls ( n = 44) underwent contrast-enhanced coronary computed tomography angiography. Advanced plaque analysis including total plaque volume and volumes of plaque components (calcified plaque and non-calcified plaque, including low-attenuation [low-density non-calcified plaque]) was performed using validated semi-automated software., Results: Coronary artery calcification was more often seen in patients with type 2 diabetes (66%) versus controls (48%), p < 0.05. Both the absolute volume (median; interquartile range) of low-density non-calcified plaque (7.9 mm 3 ; 0-50.5 mm 3 vs 0; 0-34.3 mm 3 , p < 0.05) and the increase in low-density non-calcified plaque ratio in relation to total plaque volume ( τ = 0.5, p < 0.001) were significantly higher in patients with type 2 diabetes. More patients with type 2 diabetes had spotty calcification (31% vs 0%, p < 0.05). By multivariate analysis, the presence of any low-density non-calcified plaque was higher in males (odds ratio: 4.06, p < 0.05), who also demonstrated a larger low-density non-calcified plaque volume ( p < 0.001). The presence and extent of low-density non-calcified plaque increased with age, smoking, hypertension and hyperglycaemia, all p < 0.05., Conclusion: Asymptomatic patients with newly diagnosed type 2 diabetes had plaque features associated with increased vulnerability as compared with age- and sex-matched controls.

Objectives: This study characterized and quantified subclinical atherosclerosis by coronary computed tomography angiography (CTA) in first-degree relatives of patients with early onset coronary artery disease (CAD)., Background: A strong family history of CAD is an important risk factor for adverse cardiovascular events. Whether predisposed individuals suffer an increased burden of coronary atherosclerosis and adverse plaque features is not known., Methods: We included 88 healthy middle-aged first-degree relatives from 59 families with early onset CAD. Participants were matched by age and sex with 88 control patients with atypical angina or nonanginal chest pain and no family history of CAD, referred for coronary CTA. A blinded analysis of plaque burden and composition was performed using semiautomated plaque quantification software. The relative differences between the median volumes or the odds ratios (OR) were compared between groups, using a mixed model., Results: First-degree relatives had significantly more affected coronary segments than controls (0 segments: 30% vs. 49%, respectively; 1 to 2 segments: 27% vs. 32%, respectively; 3 to 4 segments: 18% vs. 6%, respectively; and ≥5 segments: 25% vs. 14%, respectively; p = 0.001). In a multivariate model, the relative differences of total plaque, total calcified plaque (CP), total noncalcified plaque (NCP), and total low-density NCP (LD-NCP) were 5.8 (95% confidence interval [CI]: 2.8 to 11.9), 2.6 (95% CI: 1.5 to 4.5), 5.8 (95% CI: 2.9 to 12.0), and 3.6 (95% CI: 2.1 to 6.1), respectively. The adjusted OR of any positive remodeling plaque or any LD-NCP plaque was 4.2 (95% CI: 1.2 to 14) and 4.2 (95% CI: 1.9 to 9.5), respectively., Conclusions: Healthy first-degree relatives of patients with early onset CAD have an increased coronary plaque burden compared with symptomatic patients. The plaques display characteristics associated with myocardial ischemia and adverse coronary events., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: South Asian (SA) patients are known to have an increased incidence of acute cardiovascular events compared with Caucasians. The aim of this observational study was to compare the prevalence of coronary stenoses, the amount and composition of coronary atherosclerosis in a cohort of Caucasian and SA patients with stable chest pain, in non-acute settings., Methods and Results: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. In 963 consecutive Caucasian and SA patients undergoing coronary computed tomography angiography, atherosclerotic plaques were quantified using a semi-automated algorithm. The vessel per cent diameter and area stenosis were measured. Plaque composition was examined from the measurement of calcified, non-calcified, and total plaque burden. There were 420 Caucasian (238 males) and 543 SA (297 males) patients. Caucasian patients were older than SA patients (54.39 ± 11.65 vs. 49.83 ± 11.03 years) and had lower prevalence of diabetes (13.13 vs. 32.41%) and hyperlipidaemia (56.90 vs. 68.51%) (all P-values <0.001). After adjusting for differences in cardiovascular risk factors, there were no differences in per cent diameter and area stenosis, and no difference in the proportions of patients with one-, two-, or three-vessel disease. There was no difference in total plaque burden; however, the per cent non-calcified plaque composition was lower in Caucasians compared with SA (80.95 vs. 90.42%; P-value <0.001)., Conclusion: This study conducted in non-acute settings showed an ethnic difference in composition of coronary atherosclerotic plaque with lower non-calcified composition in Caucasian patients compared with SA patients, which was independent of age, diabetes, hyperlipidaemia, and the other available cardiovascular risk factors., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: We aimed to investigate whether quantitative plaque features measured from coronary CT angiography (CCTA) predict ischemia by myocardial perfusion SPECT imaging (MPI)., Methods and Results: Hundred and eighty-four consecutive patients (63% males) with suspected-coronary artery disease, undergoing hybrid CCTA, and attenuation corrected solid state 99mTc stress/rest MPI and single vessel ischemia were considered. Quantitative analysis of CCTA derived non-calcified plaque (NCP), low-density NCP [< 30 Hounsfield Units (HU)] (LDNCP), calcified and total plaque burdens (%, normalized to vessel volume), maximum diameter stenosis and contrast density difference (CD, maximum difference in HU/lumen area within lesion). Normal thresholds for plaque features were defined as 95th percentile thresholds, from 40% of vessels with non-ischemic MPI regions. These vessels were excluded from further analysis. Regional ischemia (≥ 2%) was quantified from MPI. All plaque features were higher in arteries corresponding to ischemia (P < 0.003 for all). In multi-variable analysis, abnormal NCP burden [odds ratio (OR) 2.6], LDNCP burden (OR 3.9), and CD (OR 2.7) were significantly associated with ischemia, whereas stenosis ≥ 50% was not (P = 0.14). In a subset of vessels with ≥ 50% stenosis, LDNCP burden (OR 4.3, P = 0.008) and CD (OR 3.7, P = 0.029) were associated with ischemia. In subsets of vessels with stenosis 30-69% and ≥ 70%, abnormal LDNCP burden (OR 6.4, P = 0.006) and CD (OR 7.3, P = 0.02) were associated with ischemia., Conclusions: Quantitative plaque features obtained from CCTA, LDNCP, and CD, are associated with ischemia by MPI independent of stenosis. LDNCP burden and CD are associated with ischemia in stenosis 30-69% and ≥ 70%, respectively., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)