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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: 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.)

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.

Background: Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF., Methods: Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms., Results: Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107-180] vs. 113 ml [IQR 89-147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002-1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004-1.026]; p = 0.009)., Conclusion: Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists., (© 2024. The Author(s).)

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.)

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 ).

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.)

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.

Background: Age- and gender-adjusted percentiles of coronary artery calcium (CAC) score are commonly reported to compare a patient's coronary atherosclerosis burden to that of others of the same age and gender. The number of calcified plaques (numCP) detected on CAC scanning, a measure of plaque diffusivity, is associated with increased cardiovascular risk and, in the intermediate CAC range, adds to the CAC score in predicting mortality. This study aims to develop adjusted percentiles for numCP to provide a better context for understanding CAC scan findings., Methods and Results: Using nonparametric modeling techniques, the distribution of numCP was analyzed in 70,320 consecutive, asymptomatic patients without prior clinically-diagnosed cardiovascular disease who were part of the Coronary Artery Calcium Consortium and supplemented by additional patients referred for clinical CAC scanning in a single center between 1998 and 2016. Nomograms for age-adjusted numCP percentiles for each gender were generated using quantile regression. The prevalence and average number of calcified coronary plaque were found to be higher in men than women. Distribution of numCP in women was found to closely mirror that of men approximately a decade younger. NumCP increased consistently across age groups in both men and women for each quantile category., Conclusions: A nomogram for age and gender-adjusted percentiles for the numCP on CAC scans has been developed in a large population of asymptomatic patients studied across multiple centers. This numCP nomogram may provide an additional tool for refining physician recommendations regarding treatment and expressing to patients how their CAC findings relate to others of similar age and gender. The numCP percentiles may also provide a meaningful way to evaluate and report the rate of progression of CAC on serial studies., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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.)

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.)

Aims: Non-invasive fractional flow reserve derived from coronary CT angiography (FFR CT ) has been shown to be predictive of lesion-specific ischemia as assessed by invasive fractional flow reserve (FFR). However, in practice, clinicians are often faced with an abnormal distal FFR CT in the absence of a discrete obstructive lesion. Using quantitative plaque analysis, we sought to determine the relationship between an abnormal whole vessel FFR CT (V-FFR CT ) and quantitative measures of whole vessel atherosclerosis in coronary arteries without obstructive stenosis., Methods: FFR CT was calculated in 155 consecutive patients undergoing coronary CTA with ≥25% but less than 70% stenosis in at least one major epicardial vessel. Semi-automated software was used to quantify plaque volumes (total plaque [TP], calcified plaque [CP], non-calcified plaque [NCP], low-density non-calcified plaque [LD-NCP]), remodeling index [RI], maximal contrast density difference [CDD] and percent diameter stenosis [%DS]. Abnormal V-FFR CT was defined as a minimum value of ≤0.75 across the vessel (at the most distal region where FFR CT was computed)., Results: Vessels with abnormal V-FFR CT had higher per-vessel TP (554 vs 331 mm 3 ), CP (59 vs 25 mm 3 ), NCP (429 vs 295 mm 3 ), LD-NCP (65 vs 35 mm 3 ) volume and maximum CDD (21 vs 14%) than those with normal V-FFR CT (median, p < 0.05 for all). Using a multivariate analysis to adjust for CDD and %DS, all measures of plaque volume were predictive of abnormal V-FFR CT (OR 2.09, 1.36, 1.95, 1.95 for TP, CP, NCP and LD-NCP volume, respectively; p < 0.05 for all)., Conclusion: Abnormal V-FFR CT in vessels without obstructive stenosis is associated with multiple markers of diffuse non-obstructive atherosclerosis, independent of stenosis severity. Whole vessel FFR CT may represent a novel measure of diffuse coronary plaque burden., (Copyright © 2018. Published by Elsevier Inc.)

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.)

Multiple coronary artery calcium (CAC) parameters have recently been proposed to improve risk prediction in patients with intermediate clinical risk based on CAC scoring, but outcome data that assess these variables are relatively sparse. We analyzed data from 11,633 consecutive asymptomatic patients undergoing CAC scanning that were followed for 8.8 ± 3.5 years for all-cause mortality (ACM). The patients who had coronary artery calcification were grouped by the number of calcified coronary plaques: 0, 1 to 5, 6 to 20, and >20 plaques. We examined the independent prognostic value of plaque number and its synergistic prognostic value when added to the CAC score. We observed a stepwise increase in ACM with increasing plaque number. In patients with a CAC score of 1 to 99, 6 plaques or more were associated with increased mortality. In patients with CAC scores of 100 to 399, there was a stepwise increase in ACM with increasing plaque number. For CAC >400, the risk of ACM was high regardless of plaque number. After risk adjustment, the number of plaques was a significant predictor of risk for ACM in the patients with an intermediate CAC score. In these patients, additional consideration of plaque number improved net reclassification improvement for predicting ACM by 29%. In conclusion, the number of calcified plaques adds to risk stratification beyond the CAC score in patients with intermediate CAC scores., (Copyright © 2017 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: 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.)

Purpose: The aim of this study was to evaluate the utility of automated plaque analysis in differentiating chronic total occlusion (CTO) from subtotal occlusion (SO) in patients with ambiguous coronary lesions on coronary computed tomography angiography (CTA)., Materials and Methods: A total of 63 patients with 63 ambiguous coronary lesions on CTA were included. The lesion length (LL), diameter stenosis, plaque volume and composition, remodeling index, and contrast density difference (CDD) (reflecting intraluminal contrast kinetics over the lesion) were assessed using an automatic software tool. All patients underwent invasive coronary angiography., Results: Coronary angiography confirmed 28 CTOs and 35 SOs. CTOs showed significantly longer LL (6.4±12.3 vs. 1.0±2.2 mm, P=0.03) and higher CDD (74%±31% vs. 55%±32%, P=0.02) compared with SO. The optimal thresholds for prediction of CTO for CDD and LL were ≥43% and ≥1 mm, respectively (max. sensitivity: 82% for CDD, max. specificity: 77% for LL). The guidewire manipulation time correlated with LL (r=0.529, P=0.004) and CDD (r=0.435, P=0.021) in lesions attempted by percutaneous coronary intervention., Conclusions: Automated computed tomography plaque analysis may be applied as a noninvasive tool to differentiate CTO from SO.

Introduction: Coronary computed tomographic angiography (CTA) can characterize coronary atherosclerotic plaque components as calcified and non-calcified. Quantitative measurements of coronary plaque burden by coronary CTA may play a role in serial studies to determine disease progression or response to medical therapies. The reproducibility from repeated assessment of such quantitative measurements from low-radiation dose coronary CTA has not been previously assessed., Purpose: To evaluate the interscan, interobserver and intraobserver reproducibility for coronary plaque volume assessment using semi-automatic plaque analyses algorithm in low radiation dose coronary CTA., Methods: In 50 consecutive patients undergoing two 128-slice dual source CT scans within 12 days with a mean radiation dose of 0.7 mSv per coronary CTA, the interscan, interobserver and intraobserver reproducibility of coronary plaque assessment using validated software (AutoPlaq) were evaluated., Results: Interscan, interobserver and intraobserver agreement for non-calcified and calcified plaque volumes were excellent (Spearman rho 0.87-0.99). Interscan mean percentage difference in non-calcified and calcified plaque volumes were 0.1% (p = 0.8) and 1.9% (p = 0.19) with limits of agreement of ±11% and ±48.5%; per inter- and intraobserver mean percentage differences were 0.1% (p = 0.25) and 0.3% (p = 0.001), and 0.3% (p = 0.33) and 0.4% (p = 0.59) with limits of agreement of ±7% and ±32.9%, and ±6.6% and ±32.1%, respectively., Conclusion: A semi-automatic plaque assessment algorithm in repeated low radiation dose coronary CTA allows for high reproducibility of coronary plaque characterization and quantification measures., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The prognostic implications of dyspnea and typical angina in patients referred for coronary CT angiography have not been examined. We examined features associated with incident mortality risk among individuals undergoing coronary computed tomographic angiography (CCTA) presenting with dyspnea, typical angina, and neither of these symptoms. 1147 consecutive individuals without known CAD (mean 61 years, 61.6 %men) undergoing CCTA comprised the study population 132 with dyspnea, 218 with typical angina, and 797 without dyspnea or typical angina (reference group). Mortality risk in relation to dyspnea or typical angina was evaluated with multivariable Cox proportional hazards models compared to reference. In addition, the prognosis associated with dyspnea or typical angina was assessed among age matched subgroups. Patients with dyspnea had a greater prevalence of C70 % stenosis (p\0.001) and coronary segments with plaque (p = 0.02) compared to the other two groups. During a follow-up of 3.1 years, 52 individuals died. By multivariable Cox models, compared to patients in reference group, dyspnea patients experienced higher mortality (HR 2.0, 95 % CI 1.0–4.0, p = 0.049) while typical angina patients did not (HR 1.1, 95 % CI 0.6–2.3, p = 0.76). In the matched group, the patients with dyspnea (HR 2.2, 95 % CI 1.1–4.3, p = 0.03) still had significantly reduced survival compared to the other two groups, while those with typical angina did not (HR 1.2, 95 % CI 0.6–2.6,p = 0.62). Dyspnea is associated with increased mortality ate compared to patients with typical angina and those with neither of these symptoms among patients undergoing CCTA.

Background: We investigated the relationship of quantitative plaque features from coronary computed tomography (CT) angiography and coronary vascular dysfunction by impaired myocardial flow reserve (MFR) by (13)N-Ammonia positron emission tomography (PET)., Methods and Results: Fifty-one patients (32 men, 62.4±9.5 years) underwent combined rest-stress (13)N-ammonia PET and CT angiography scans by hybrid PET/CT. Regional MFR was measured from PET. From CT angiography, 153 arteries were evaluated by semiautomated software, computing arterial noncalcified plaque (NCP), low-density NCP (NCP<30 HU), calcified and total plaque volumes, and corresponding plaque burden (plaque volumex100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum difference in luminal attenuation per unit area in the lesion), and plaque length. Quantitative stenosis, plaque burden, and myocardial mass were combined by boosted ensemble machine-learning algorithm into a composite risk score to predict impaired MFR (MFR≤2.0) by PET in each artery. Nineteen patients had impaired regional MFR in at least 1 territory (41/153 vessels). Patients with impaired regional MFR had higher arterial NCP (32.4% versus 17.2%), low-density NCP (7% versus 4%), and total plaque burden (37% versus 19.3%, P<0.02). In multivariable analysis with 10-fold cross-validation, NCP burden was the most significant predictor of impaired MFR (odds ratio, 1.35; P=0.021 for all). For prediction of impaired MFR with 10-fold cross-validation, receiver operating characteristics area under the curve for the composite score was 0.83 (95% confidence interval, 0.79-0.91) greater than for quantitative stenosis (0.66, 95% confidence interval, 0.57-0.76, P=0.005)., Conclusions: Compared with stenosis, arterial NCP burden and a composite score combining quantitative stenosis and plaque burden from CT angiography significantly improves identification of downstream regional vascular dysfunction., (© 2015 American Heart Association, Inc.)

Background: When coronary calcium scoring is performed in patients with suspected coronary artery disease, a separate noncontrast scan is acquired before contrast-enhanced coronary CT angiography (CTA)., Objective: Our aim was to develop and validate an automated method for calculating the coronary calcium score (CCS) from coronary CTA., Methods: We analyzed coronary CTA and noncontrast CT data sets of 84 patients (Agatston score >0). The CCS on noncontrast CT was measured using commercial methods. Coronary calcium volume was measured on coronary CTA using an automated standardized method with scan-specific calcium thresholds. Data sets were split into derivation (n = 40) and validation groups (n = 44). To calculate the CCS on coronary CTA, a conversion factor between calcium scores measured in noncontrast CT and the calcium volume measured on coronary CTA was derived by linear regression., Results: In the validation group, the median calculated CCS derived from CTA was 277 and 244 on noncontrast images (P = .12). This CCS showed an excellent correlation with the CCS from noncontrast images (Pearson, r = 0.95). In the validation group, 39 of 44 patients (88.6%) were classified into the same standard category (1-10, 11-100, 101-400, or >400) with an excellent agreement (weighted κ of 0.87)., Conclusion: CCSs can be accurately measured from contrast-enhanced coronary CTA by using an automated, standardized method, obviating the need for a noncontrast scan., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the utility of multiple automated plaque measurements from coronary computed tomographic (CT) angiography in determining hemodynamic significance by using invasive fractional flow reserve (FFR) in patients with intermediate coronary stenosis., Materials and Methods: The study was approved by the institutional review board. All patients provided written informed consent. Fifty-six intermediate lesions (with 30%-69% diameter stenosis) in 56 consecutive patients (mean age, 62 years; range, 46-88 years), who subsequently underwent invasive coronary angiography with assessment of FFR (values ≤0.80 were considered hemodynamically significant) were analyzed at coronary CT angiography. Coronary CT angiography images were quantitatively analyzed with automated software to obtain the following measurements: volume and burden (plaque volume × 100 per vessel volume) of total, calcified, and noncalcified plaque; low-attenuation (<30 HU) noncalcified plaque; diameter stenosis; remodeling index; contrast attenuation difference (maximum percent difference in attenuation per unit area with respect to the proximal reference cross section); and lesion length. Logistic regression adjusted for potential confounding factors, receiver operating characteristics, and integrated discrimination improvement were used for statistical analysis., Results: FFR was 0.80 or less in 21 (38%) of the 56 lesions. Compared with nonischemic lesions, ischemic lesions had greater diameter stenosis (65% vs 52%, P = .02) and total (49% vs 37%, P = .0003), noncalcified (44% vs 33%, P = .0004), and low-attenuation noncalcified (9% vs 4%, P < .0001) plaque burden. Calcified plaque and remodeling index were not significantly different. In multivariable analysis, only total, noncalcified, and low-attenuation noncalcified plaque burden were significant predictors of ischemia (P < .015). For predicting ischemia, the area under the receiver operating characteristics curve was 0.83 for total plaque burden versus 0.68 for stenosis (P = .04)., Conclusion: Compared with stenosis grading, automatic quantification of total, noncalcified, and low-attenuation noncalcified plaque burden substantially improves determination of lesion-specific hemodynamic significance by FFR in patients with intermediate coronary lesions., (© RSNA, 2015.)

Background: Impaired myocardial flow reserve (MFR) is a marker of coronary vascular dysfunction with prognostic significance., Objectives: We aimed to investigate the relationship between epicardial fat volume (EFV) measured from noncontrast CT and impaired MFR derived from rest-stress Rb-82 positron emission tomography (PET)., Methods: We retrospectively studied 85 consecutive patients without known coronary artery disease who underwent rest-stress Rb-82 myocardial PET/CT and were subsequently referred for invasive coronary angiography. EFV was computed from noncontrast CT by validated software and indexed to body surface area (EFVi, cm3/m2). Global stress and rest MFR were automatically derived from PET. Patient age, sex, cardiovascular risk factors, coronary calcium score (CCS), and EFVi were combined by boosted ensemble machine learning algorithm into a novel composite risk score, using 10-fold cross-validation, to predict impaired global MFR (MFR ≤2.0) by PET., Results: Patients with impaired MFR (44 of 85; 52%) were older (71 vs. 65 years; P = .03) and had higher frequency of CCS (≥400; P = .02) with significantly higher EFVi (63.1 ± 20.4 vs. 51.3 ± 14.1 cm3/m2; P = .003). On multivariate logistic regression (with age, sex, number of risk factors, CCS, and EFVi), EFVi was the only independent predictor of impaired MFR (odds ratio, 7.39; P = .02). The machine learning composite risk score significantly improved risk reclassification of impaired MFR compared to CCS or EFVi alone (integrated discrimination improvement = 0.19; P = .007 and IDI = 0.22; P = .002, respectively)., Conclusions: Increased EFVi and composite risk score combining EFVi and CCS significantly improve identification of impaired global MFR by PET., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA)., Method and Results: Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001)., Conclusion: Any and obstructive CAD is present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Coronary CTA allows characterization of non-calcified and calcified plaque and identification of high-risk plaque features., Objective: We aimed to quantitatively characterize and compare coronary plaque burden from CTA in patients with a first acute coronary syndrome (ACS) and controls with stable coronary artery disease., Materials and Methods: We retrospectively analyzed consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina with a first ACS, who underwent CTA as part of their initial workup before invasive coronary angiography and age- and gender-matched controls with stable chest pain; controls also underwent CTA with subsequent invasive angiography (total n = 28). Culprit arteries were identified in ACS patients. Coronary arteries were analyzed by automated software to quantify calcified plaque (CP), noncalcified plaque (NCP), and low-density NCP (LD-NCP, attenuation <30 Hounsfield units) volumes, and corresponding burden (plaque volume × 100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum percent difference in attenuation/cross-sectional area from proximal cross-section), and plaque length., Results: ACS patients had fewer lesions (median, 1), with higher total NCP and LD-NCP burdens (NCP: 57.4% vs 41.5%; LD-NCP: 12.5% vs 8%; P ≤ .04), higher maximal stenoses (85.6% vs 53.0%; P = .003) and contrast density differences (46.1 vs 16.3%; P < .006). Per-patient CP burden was not different between ACS and controls. NCP and LD-NCP plaque burden was higher in culprit vs nonculprit arteries (NCP: 57.8% vs 9.5%; LD-NCP: 8.4% vs 0.6%; P ≤ .0003); CP was not significantly different. Culprit arteries had increased plaque lengths, remodeling indices, stenoses, and contrast density differences (46.1% vs 10.9%; P ≤ .001)., Conclusion: Noninvasive quantitative coronary artery analysis identified several differences for ACS, both on per-patient and per-vessel basis, including increased NCP, LD-NCP burden, and contrast density difference., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: Quantitative measurements of coronary plaque volume may play a role in serial studies to determine disease progression or regression. Our aim was to evaluate the interscan reproducibility of quantitative measurements of coronary plaque volumes using a standardized automated method., Methods: Coronary dual source computed tomography angiography (CTA) was performed twice in 20 consecutive patients with known coronary artery disease within a maximum time difference of 100 days. The total plaque volume (TP), the volume of non-calcified plaque (NCP) and calcified plaque (CP) as well as the maximal remodelling index (RI) were determined using automated software., Results: Mean TP volume was 382.3 ± 236.9 mm(3) for the first and 399.0 ± 247.3 mm(3) for the second examination (p = 0.47). There were also no significant differences for NCP volumes, CP volumes or RI. Interscan correlation of the plaque volumes was very good (Pearson's correlation coefficients: r = 0.92, r = 0.90 and r = 0.96 for TP, NCP and CP volumes, respectively)., Conclusions: Automated software is a time-saving method that allows accurate assessment of coronary atherosclerotic plaque volumes in coronary CTA with high reproducibility. With this approach, serial studies appear to be possible., Key Points: Reproducibility of coronary atherosclerotic plaque volume in coronary CTA is high. Using automated software facilitates quantitative measurements. Serial studies to determine progression or regression of coronary plaque are possible.

Rationale and Objectives: Blooming artifact from calcified plaques often renders measurement of stenosis impossible on coronary computed tomographic angiography (CTA). We sought to evaluate the impact of modifying window level on reducing blooming artifact, and its impact on stenosis quantification., Materials and Methods: We analyzed 125 calcified segments from 53 patients who underwent CTA and invasive coronary angiography (ICA). Segmental stenosis on CTA was measured using three window settings: width of 1000 Hounsfield units (HU) and level of 200 HU ("default"), 1500/200 HU ("widened"), and width and level based on the mean HU of the calcified plaque and pericoronary fat ("calcium-specific"). Segmental stenosis on ICA was quantified by a blinded experienced reader., Results: ICA found ≥50% stenosis in 30 segments. Displaying segments with widened and calcium-specific settings improved overall accuracy of detecting ≥50% stenosis (P's < 0.001) by increasing the rate of accurately quantifying <50% stenosis (P's < 0.001), and improved correlation of stenosis quantification to ICA (P's < 0.05). There was no difference in stenosis quantification accuracy between widened and calcium-specific window settings. Limits of agreement between CTA stenosis quantification and ICA narrowed with widened and calcium-specific settings., Conclusions: We showed for the first time that in calcified segments, widening display window width significantly improved CTA quantification of stenosis compared to ICA., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)