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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.

Background: High-intensity plaque (HIP) on magnetic resonance imaging (MRI) has been documented as a powerful predictor of periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI). Despite the recent proposal of three-dimensional HIP quantification to enhance the predictive capability, the conventional pulse sequence, which necessitates the separate acquisition of anatomical reference images, hinders accurate three-dimensional segmentation along the coronary vasculature. Coronary atherosclerosis T 1 -weighted characterization (CATCH) enables the simultaneous acquisition of inherently coregistered dark-blood plaque and bright-blood coronary artery images. We aimed to develop a novel HIP quantification approach using CATCH and to ascertain its superior predictive performance compared to the conventional two-dimensional assessment based on plaque-to-myocardium signal intensity ratio (PMR)., Methods: In this prospective study, CATCH MRI was conducted before elective stent implantation in 137 lesions from 125 patients. On CATCH images, dedicated software automatically generated tubular three-dimensional volumes of interest on the dark-blood plaque images along the coronary vasculature, based on the precisely matched bright-blood coronary artery images, and subsequently computed PMR and HIP volume (HIP vol ). Specifically, HIP vol was calculated as the volume of voxels with signal intensity exceeding that of the myocardium, weighted by their respective signal intensities. PMI was defined as post-PCI cardiac troponin-T > 5 × the upper reference limit., Results: The entire analysis process was completed within 3 min per lesion. PMI occurred in 44 lesions. Based on the receiver operating characteristic curve analysis, HIP vol outperformed PMR for predicting PMI (C-statistics, 0.870 [95% CI, 0.805-0.936] vs. 0.787 [95% CI, 0.706-0.868]; p = 0.001). This result was primarily driven by the higher sensitivity HIP vol offered: 0.886 (95% CI, 0.754-0.962) vs. 0.750 for PMR (95% CI, 0.597-0.868; p = 0.034). Multivariable analysis identified HIP vol as an independent predictor of PMI (odds ratio, 1.15 per 10-μL increase; 95% CI, 1.01-1.30, p = 0.035)., Conclusions: Our semi-automated method of analyzing coronary plaque using CATCH MRI provided rapid HIP quantification. Three-dimensional assessment using this approach had a better ability to predict PMI than conventional two-dimensional assessment., Competing Interests: Declaration of Competing Interest Yoshiaki Komori is an employee of Siemens Japan KK. Other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

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 Positron emission tomography (PET) using 18 F-sodium fluoride ( 18 F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between 18 F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent 18 F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased 18 F-fluoride uptake in at least one vessel. Individuals with increased 18 F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; P <0.0001). Indeed, the calcium score only increased in coronary segments with 18 F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; P <0.001) and remained unchanged in segments without 18 F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; P =0.329). Baseline coronary 18 F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; P <0.0001 for all). At the segmental level, baseline 18 F-fluoride activity was an independent predictor of calcium score at 12 months ( P <0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score ( P =0.50). Conclusions Coronary 18 F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.

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: 18 F-sodium fluoride ( 18 F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18 F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA])., Methods: Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18 F-NaF PET and coronary CT angiography. We assessed the association between coronary 18 F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume., Results: In 50 patients (64% males, 63 ± 7 years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18 F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001)., Conclusions: Automated assessment of disease activity across the entire coronary vasculature is feasible using 18 F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Background: Epicardial adipose tissue (EAT) volume (cm 3 ) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography., Methods: Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction., Results: At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P <0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P =0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm 3 and coronary artery calcium ≥100 AU and was highest in subjects with both ( P <0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers., Conclusions: Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.

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.

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.)

Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18 F-sodium fluoride ( 18 F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA)., Background: Coronary 18 F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18 F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized., Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm 3 ). Patients with HRPs were recruited to undergo 18 F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion-corrected 18 F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured., Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18 F-NaF activity. Lesions with 18 F-NaF uptake had higher surrounding PCAT density than those without 18 F-NaF uptake (-73 HU; interquartile range -79 to -68 HU vs. -86 HU; interquartile range -94 to -80 HU; p < 0.001). 18 F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18 F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP)., Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18 F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18 F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features., (Copyright © 2019 American College of Cardiology Foundation. 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.)

Coronary 18 F-sodium fluoride ( 18 F-NaF) PET identifies ruptured plaques in patients with recent myocardial infarction and localizes to atherosclerotic lesions with active calcification. Most studies to date have performed the PET acquisition 1 h after injection. Although qualitative and semiquantitative analysis is feasible with 1-h images, residual blood-pool activity often makes it difficult to discriminate plaques with 18 F-NaF uptake from noise. We aimed to assess whether delayed PET performed 3 h after injection improves image quality and uptake measurements. Methods: Twenty patients (67 ± 7 y old, 55% male) with stable coronary artery disease underwent coronary CT angiography (CTA) and PET/CT both 1 h and 3 h after the injection of 266.2 ± 13.3 MBq of 18 F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, SUV max , corrected SUV max (cSUV max ), and target-to-background (TBR) ratio in lesions defined by CTA on 1-h versus 3-h 18 F-NaF PET. Results: On 1-h PET, 26 CTA lesions with 18 F-NaF PET uptake were identified in 12 (60%) patients. On 3-h PET, we detected 18 F-NaF PET uptake in 7 lesions that were not identified on 1-h PET. The median cSUV max and TBRs of these lesions were 0.48 (interquartile range [IQR], 0.44-0.51) and 1.45 (IQR, 1.39-1.52), respectively, compared with -0.01 (IQR, -0.03-0.001) and 0.95 (IQR, 0.90-0.98), respectively, on 1-h PET (both P < 0.001). Across the entire cohort, 3-h PET SUV max was similar to 1-h PET measurements (1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], P = 0.30), and the background activity was lower (0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], P < 0.001). On 3-h PET, TBR, cSUV max , and noise were significantly higher (respectively: 2.30 [IQR, 1.70-2.68] vs. 1.28 [IQR, 0.98-1.56], P < 0.001; 0.38 [IQR, 0.27-0.70] vs. 0.90 [IQR, 0.64-1.17], P < 0.001; and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). Median cSUV max and TBR increased by 92% (range, 33%-225%) and 80% (range, 20%-177%), respectively. Conclusion: Blood-pool activity decreases on delayed imaging, facilitating the assessment of 18 F-NaF uptake in coronary plaques. Median TBR increases by 80%, leading to the detection of more plaques with significant uptake than are detected using the standard 1-h protocol. A greater than 1-h delay may improve the detection of 18 F-NaF uptake in coronary artery plaques., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Aims: Certain novel biomarkers may predict atherosclerotic cardiovascular disease (ASCVD) events; however, data on their relationship to coronary atherosclerosis and its progression as measured by coronary artery calcium (CAC) scanning is lacking. We evaluated the association between novel biomarkers and presence or progression of CAC., Methods: The EISNER study was a prospective trial of patients without known ASCVD. Data on CAC and several biomarkers (hs-CRP, LTβR, osteopontin [OPN], RAGE, TNFR1α and TROY) were available at baseline and 4-year follow-up. Biomarkers were standardized and summed for a composite score. CAC progression was defined by the square-root (CAC SQRT ) method and rapid (top decile) progression. Adjusted regression models created a final prediction model for baseline CAC and CAC progression., Results: 1207 subjects (mean age 58.4 ± 8 years, 53% male) were evaluated; 621 had a baseline CAC >0, in whom 323 progressed by CAC SQRT , and 121 rapidly progressed. Baseline CAC was associated only with OPN (p = 0.03), TROY (p = 0.0058) and TNFR1α (p = 0.0039) in unadjusted analyses. In adjusted analyses, only OPN was independently related to CAC progression using CAC SQRT (p = 0.04)., Conclusions: OPN identifies progression of atherosclerosis in persons free of ASCVD at baseline and may be a useful predictive tool to guide ASCVD prevention management., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.)

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.)

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.)

Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed.

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.)

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.)

Objectives: Coronary computed tomography angiography (CTA) allows the detection of obstructive coronary artery disease. However, its ability to predict the hemodynamic significance of stenoses is limited. We assessed differences in plaque characteristics and contrast density difference between hemodynamically significant and non-significant stenoses, as defined by invasive fractional flow reserve (FFR)., Methods: Lesion characteristics of 59 consecutive patients (72 lesions) in whom invasive FFR was performed in at least one coronary artery with moderate to high-grade stenoses in coronary CTA were evaluated by two experienced readers. Coronary CTA data sets were acquired on a second-generation dual-source CT scanner using retrospectively ECG-gated spiral acquisition or prospectively ECG-triggered axial acquisition mode. Plaque volume and composition (non-calcified, calcified), remodeling index as well as contrast density difference (defined as the percentage decline in luminal CT attenuation/cross-sectional area over the lesion) were assessed using a semi-automatic software tool (Autoplaq). Additionally, the transluminal attenuation gradient (defined as the linear regression coefficient between intraluminal CT attenuation and length from the ostium) was determined. Differences in lesion characteristics between hemodynamically significant (invasively measured FFR ≤0.80) and non-significant lesions (FFR >0.80) were determined., Results: Mean patient age was 64±11 years with 44 males (75%). 21 out of 72 coronary artery lesions (29%) were hemodynamically significant according to invasive FFR. Mean invasive FFR was 0.66±0.12 vs. 0.91±0.05 for hemodynamically significant versus non-significant lesions. Hemodynamically significant lesions showed a significantly greater percentage of non-calcified plaque compared to non-hemodynamically relevant lesions (51.3±15.3% vs. 43.6±16.5%, p=0.021). Contrast density difference was significantly increased in hemodynamically relevant lesions (26.0±20.2% vs. 16.6±10.9% for non-significant lesions; p=0.013). At a threshold of ≥24%, the contrast density difference predicted hemodynamically significant lesions with a specificity of 75%, sensitivity of 33%, PPV of 35% and NPV of 73%. The transluminal attenuation gradient showed no significant difference between hemodynamically significant and non-significant lesions (-1.4±1.4HU/mm vs. -1.1±1.3HU/mm, p=n.s.)., Conclusions: Quantitative contrast density difference across coronary lesions in coronary CTA data sets may be applied as a non-invasive tool to identify hemodynamically significant stenoses., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Rationale: Patients with chronic obstructive pulmonary disease (COPD) suffer from significantly more cardiovascular comorbidity and mortality than would be anticipated from conventional risk factors. The aim of this study was to determine whether COPD patients have a higher coronary artery calcium score (CACS) and epicardial fat burden, compared to control subjects, and their association with cardiovascular events., Methods: From a registry of 1906 patients 81 patients with clinically diagnosed COPD were one-to-one matched to 81 non-COPD control subjects with a smoking history, according to their age, sex, and the number of classic cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, family history of premature coronary artery disease). CACS, epicardial fat, and subsequent major adverse cardiovascular events (MACE) during follow-up were compared between groups., Results: Patients with COPD (Global Initiative for Chronic Obstructive Lung Disease-classification I: 5%, II: 23%, III: 16% and IV: 56%) showed no difference in CACS (median difference 68 Agatston Units [95% confidence interval -176.5 to 192.5], p=0.899) or epicardial fat volume (mean difference -0.5 cm3 [95% confidence interval -20.9 to 21.9], p=0.961) compared with controls. After a median follow-up of 42.6 months a higher incidence of MACE was observed in COPD patients (RR=2.80, p=0.016) compared with controls. Cox proportional hazard regression identified cardiac ischemias and CACS as independent predictors for MACE., Conclusion: COPD patients experienced a higher MACE incidence compared to controls despite no baseline differences in coronary calcification and epicardial fat burden. Other mechanisms such as undersupply of medication seem to account for an excess cardiovascular comorbidity in COPD patients.

Unlabelled: Whether (18)F-FDG PET can detect inflammation in the coronary arteries remains controversial. We examined (18)F-FDG uptake at the culprit sites of acute myocardial infarction (AMI) after percutaneous coronary stenting (PCS) by coregistering PET and coronary CT angiography (CTA)., Methods: Twenty nondiabetic patients with AMI (median age, 62 y; 16 men and 4 women) and 7 nondiabetic patients with stable coronary artery disease (CAD; median age, 67 y; 4 men and 3 women) underwent (18)F-FDG PET and coronary CTA 1-6 d after PCS of culprit stenoses. After a low-carbohydrate dietary preparation and more than 12 h of fasting, 480 MBq of (18)F-FDG were injected, and PET images were acquired 3 h later. Helical CTA was performed on a dual-source scanner. Stent position on attenuation-correction noncontrast CT and CTA was used to fuse PET and CTA. Two experienced readers masked to patient data independently quantified maximum target-to-background ratio (maxTBR) at each PCS site. A maxTBR greater than 2.0 was the criterion for significant uptake., Results: Compared with stable CAD patients, more AMI patients exhibited a PCS site maxTBR greater than 2.0 (12/20 vs. 1/7, P = 0.04). More AMI patients were active smokers (9/20 vs. 0/7 in stable CAD, P = 0.03). After adjusting for baseline demographic differences, stent-myocardium distance, and myocardial (18)F-FDG uptake, presentation of AMI was positively associated with a PCS site maxTBR greater than 2.0 (odds ratio, 31.6; P = 0.044). Prevalence of excess myocardial (18)F-FDG uptake was similar in both populations (8/20 AMI vs. 3/7 stable CAD, P = 0.89)., Conclusion: Systematic fusion of (18)F-FDG PET and coronary CTA demonstrated increased culprit site (18)F-FDG uptake more commonly in patients with AMI than in patients with stable CAD. However, this approach failed to detect increased signal at the culprit site in nearly half of AMI patients, highlighting the challenging nature of in vivo coronary artery plaque metabolic imaging. Nonetheless, our findings suggest that imaging of coronary artery inflammation is feasible, and further work evaluating (18)F-FDG uptake in high-risk coronary plaques prior to rupture would be of great interest.

Objective: Epicardial fat volume (EFV) is related to calcified coronary plaques. However, it is unknown whether baseline EFV or changes in EFV affect the progression of coronary artery calcification over time., Methods: We identified 375 consecutive asymptomatic subjects with an intermediate risk of developing coronary artery disease, who underwent serial non-contrast CT at least 3-5 years apart. Subjects were divided into tertiles of CCS progression (% increase) between the 2 scans. Subjects from the upper tertile (High Progressors) were matched by age and gender to 81 subjects from the lower tertile (Low Progressors). All subjects underwent serial measurements of CCS and EFV. Relationships between EFV and CCS progression, and change in plaque number were examined., Results: At baseline, there was no difference in EFV, and EFV indexed to body surface area (EFVi) between the groups. At follow-up, EFV, EFVi and percent increase in EFVi-change were higher in High Progressors than Low Progressors (EFV, 102 ± 38 cm(3) vs. 90 ± 35 cm(3), p=0.03; EFVi, 50 ± 16cm(3)/m(2) vs. 46 ± 15 cm(3)/m(2), p=0.03; percent increase in EFVi-change, 15 ± 22% vs. 7 ± 20%, p=0.02). On multivariate analysis, after adjusting for conventional risk factors, EFVi increase ≥15% [odds ratio (OR) 2.3, p<0.05], log (baseline CCS) [OR 0.3, p<0.0001] and scan interval time [p=0.003, OR 1.0] were predictive of being a High Progressor. EFVi increase ≥ 15% (β=3.0, p=0.02) and hypertension (β=3.1, p=0.01) were independent predictors of number of new calcified plaques on follow-up., Conclusion: Increase in EFV is associated with greater progression of coronary artery calcification in intermediate-risk subjects., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Introduction: Pericardial fat is emerging as an important parameter for cardiovascular risk stratification. We extended previously developed quantitation of thoracic fat volume (TFV) from non-contrast coronary calcium (CC) CT scans to also quantify pericardial fat volume (PFV) and investigated the associations of PFV and TFV with CC and the Metabolic Syndrome (METS)., Methods: TFV is quantified automatically from user-defined range of CT slices covering the heart. Pericardial fat contours are generated by spline interpolation between 5-7 control points, placed manually on the pericardium within this cardiac range. Contiguous fat voxels within the pericardium are identified as pericardial fat. PFV and TFV were measured from non-contrast CT for 201 patients. In 105 patients, abdominal visceral fat area (VFA) was measured from an additional single-slice CT. In 26 patients, images were quantified by two readers to establish inter-observer variability. TFV and PFV were examined in relation to Body Mass Index (BMI), waist circumference and VFA, standard coronary risk factors (RF), CC (Agatston score >0) and METS., Results: PFV and TFV showed excellent correlation with VFA (R=0.79, R=0.89, p<0.0001), and moderate correlation with BMI (R=0.49, R=0.48, p<0.0001). In 26 scans, the inter-observer variability was greater for PFV (8.0+/-5.3%) than for TFV (4.4+/-3.9%, p=0.001). PFV and TFV, but not RF, were associated with CC [PFV: p=0.04, Odds Ratio 3.1; TFV: p<0.001, OR 7.9]. PFV and TFV were also associated with METS [PFV: p<0.001, OR 6.1; TFV p<0.001, OR 5.7], unlike CC [OR=1.0 p=NS] or RF. PFV correlated with low-HDL and high-glucose; TFV correlated with low-HDL, low-adiponectin, and high glucose and triglyceride levels., Conclusions: PFV and TFV can be obtained easily and reproducibly from routine CC scoring scans, and may be important for risk stratification and monitoring.

To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.