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

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

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: High-risk plaques (HRP) detected on coronary computed tomography angiography (CTA) confer an increased risk of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel biomarker of coronary inflammation. This study aimed to evaluate the association of PCAT with HRP and subsequent ACS development in patients with stable coronary artery disease (CAD)., Methods: Patients with stable CAD who underwent coronary CTA from 2011 to 2016 and had available outcome data were included. We studied 41 patients with HRP propensity matched to 41 controls without HRP (60 ± 10 years, 67% males). PCAT was assessed using semi-automated software on a per-patient basis in the proximal right coronary artery (PCAT RCA ) and a per-lesion basis (PCAT Lesion ) around HRP in cases and the highest-grade stenosis lesions in controls., Results: PCAT RCA and PCAT Lesion were higher in HRP patients than controls (PCAT RCA : -80.7 ± 6.50 HU vs. -84.2 ± 8.09 HU, p = 0.03; PCAT Lesion : -79.6 ± 7.86 HU vs. -84.2 ± 10.3 HU, p = 0.04), and were also higher in men (PCAT RCA : -80.5 ± 7.03 HU vs. -86.1 ± 7.08 HU, p < 0.001; PCAT Lesion : -79.6 ± 9.06 HU vs. -85.2 ± 7.96 HU, p = 0.02). Median time to ACS was 1.9 years, within a median follow-up of 5.3 years. PCAT RCA alone was higher in HRP patients who subsequently presented with ACS (-76.8 ± 5.69 HU vs. -82.0 ± 6.32 HU, p = 0.03). In time-dependent analysis, ACS was associated with HRP and PCAT RCA ., Conclusions: PCAT attenuation is increased in stable CAD patients with HRP and is associated with subsequent ACS development. Further investigation is required to determine the clinical implications of these findings.

Aim: We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus disease 2019 (COVID-19)., Methods: We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ± 16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death., Results: In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (β = 10.6, p = 0.005) and EAT attenuation (β = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1-13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 [95% CI 1.8-14.1] per doubling p = 0.011) and EAT attenuation (OR 3.4 [95% CI 1.5-7.5] per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4-4.6, p = 0.002), chronic lung disease (OR 1.3 [95% CI 1.1-1.7], p = 0.011), and history of heart failure (OR 3.5 [95% 1.1-8.2], p = 0.037)., Conclusions: EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals., Methods: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm 3 ) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU., Results: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm 3 vs. 73.7 cm 3 ), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score)., Conclusions: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification. Trial registration NCT00927693.

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.)

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.)

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.)

Epicardial adipose tissue (EAT) is associated with the development of atrial fibrillation (AF). EAT thickness identified on transthoracic echocardiography (TTE). The relationship between EAT volume and left atrial appendage (LAA) function is not well-known. We aimed to investigate the associations between EAT thickness and LAA emptying flow velocity and LAA orifice area. This single-center retrospective study enrolled 202 patients who underwent both TTE and transesophageal echocardiography (TEE). EAT thickness was measured on TTE in parasternal long-axis view. We measured LAA orifice areas in 41 patients with 3-dimensional TEE data. Spearman's correlation coefficient was used to determine the relationships between EAT thickness and LAA emptying flow velocity and LAA orifice area. We created a receiver operating characteristic curve for low LAA emptying flow velocity (< 20 cm/s) and determined the best cutoff for EAT thickness according to the maximum Youden index. There was a significant negative correlation between EAT thickness and LAA emptying flow velocity (ρ = - 0.56, P < 0.001) and a significant positive correlation between EAT thickness and LAA orifice area (ρ = 0.38, P = 0.014). The best EAT thickness cutoff value for low LAA emptying flow velocity was > 5.1 mm (c-statistics, 75.7%). A thickened EATT was associated with low LAA emptying flow velocity, which increases the risk of thromboembolic phenomena in the presence of AF.

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.

Background: Cardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software., Methods: We used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type., Results: The intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm 3 ) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm 3 ) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p < 0.0001 for correlation) for both epicardial and intra-thoracic fat. By Bland-Altman analysis for epicardial fat measurements, mean difference of intra-observer was 0.90 cm 3 with 95% confidence intervals (0.22,1.7) and -1.8 cm 3 for inter-observer, with 95% CI (-2.9, -0.69). Bland-Altman plots for intra-thoracic fat measurements were similarly impressive for both inter- and intra-observer reads., Conclusions: Our data showed that measuring epicardial and intra-thoracic fat volumes by CT using a semi-automated software has excellent intra-observer and inter-observer reliability. Cardiac fat volumes can be obtained easily and reproducibly from routine calcium scoring scans and may help in assessing cardiovascular risk., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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: 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.)

Objectives: Coronary atherosclerosis in patients with type 2 diabetes mellitus may be promoted by regional fat distribution. We investigated the association between anthropometric measures of obesity, truncal fat mass, epicardial adipose tissue and coronary atherosclerosis in asymptomatic patients and matched controls., Methods: We examined 44 patients and 59 controls [mean (standard deviation) age 64.4 ± 9.9 vs 61.8 ± 9.7, male 50% vs 47%, diabetes duration mean (standard deviation) 7.7 ± 1.5] with coronary computed tomography angiography. Coronary plaques were quantified as total, calcified, non-calcified and low-density non-calcified plaque volumes (mm 3 ). Regional fat distribution was assessed by dual-energy X-ray absorptiometry, body mass index (kg/m 2 ), waist circumference (cm) and epicardial fat volume (mm 3 ). Endothelial function and systemic inflammation were evaluated by peripheral arterial tonometry (log transformed Reactive Hyperemia Index) and C-reactive protein (mg/L)., Results: Body mass index and waist circumference ( p  < 0.02) were associated with coronary plaque volumes. Body mass index was associated with low-density non-calcified plaque volume after adjustment for age, sex and diabetes status ( p  < 0.01). Truncal fat mass ( p  > 0.51), waist circumference ( p  > 0.06) and epicardial adipose tissue ( p  > 0.17) were not associated with coronary plaque volumes in adjusted analyses., Conclusion: Body mass index is associated with coronary plaque volumes in diabetic as well as non-diabetic individuals.

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.)

Importance: Pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation measured from coronary CT angiography (CTA) may be a promising metric in identifying high-risk plaques., Objective: To determine whether high-risk plaque characteristics from coronary CTA are associated with PCAT CT attenuation in patients with a first acute coronary syndrome (ACS) and matched controls with stable coronary artery disease (CAD)., Design, Setting, and Participants: This retrospective, single-center case-control study (data were acquired at the University of Erlangen from 2009-2010) analyzed the CTA data sets of 19 patients who presented with ACS and 16 controls with stable CAD who were matched based on sex, age, and risk factors. Study observers were blinded to patients' clinical data. Semiautomated software was used to quantify and characterize plaques. The CT attenuation (Hounsfield unit [HU]) of PCAT was automatically measured around all lesions., Main Outcomes and Measures: To investigate the association between high-risk plaque characteristics from CTA and PCAT CT attenuation as a novel surrogate measure of coronary inflammation., Results: A total of 35 patients (mean [SD] age, 59.5 [11.3] years; 30 men [86%] and 5 women [14%]) were included in the analysis. Low- and intermediate-attenuation noncalcified plaque (NCP) burden were increased in culprit lesions (n = 19) compared with both nonculprit lesions (n = 55) in patients with ACS (12.6% vs 3.6%; P < .001; 38.4% vs 19.4%; P < .001) and the control group's highest-grade stenosis lesions (n = 16) (12.6% vs 5.6%; P = .002; 38.4% vs 22.1%; P < .001). Pericoronary adipose tissue attenuation was increased around culprit lesions (n = 19) compared with nonculprit lesions (n = 55) in patients with ACS (-69.1 HU vs -74.8 HU; P = .01) and highest-grade stenosis lesions in control patients (n = 16) (-69.1 HU vs -76.4 HU; P = .01). Pericoronary adipose tissue CT attenuation of all lesions in patients with ACS (n = 74) correlated more strongly with intermediate-attenuation (r = 0.393; P = .001) over low-attenuation (r = 0.221; P = .06) and high-attenuation NCP burden (r = -0.103; P = .38). In a multivariable analysis, low- and intermediate-attenuation NCP burden and PCAT CT attenuation were independently associated with the presence of culprit lesions (P < .05)., Conclusions and Relevance: Pericoronary CT attenuation was increased around culprit lesions compared with nonculprit lesions of patients with ACS and the lesions of matched controls. Combined quantitative high-risk plaque features and PCAT CT attenuation may allow for a more reliable identification of vulnerable plaques.

Epicardial adipose tissue (EAT) is a visceral fat deposit related to coronary artery disease. Fully automated quantification of EAT volume in clinical routine could be a timesaving and reliable tool for cardiovascular risk assessment. We propose a new fully automated deep learning framework for EAT and thoracic adipose tissue (TAT) quantification from non-contrast coronary artery calcium computed tomography (CT) scans. The first multi-task convolutional neural network (ConvNet) is used to determine heart limits and perform segmentation of heart and adipose tissues. The second ConvNet, combined with a statistical shape model, allows for pericardium detection. EAT and TAT segmentations are then obtained from outputs of both ConvNets. We evaluate the performance of the method on CT data sets from 250 asymptomatic individuals. Strong agreement between automatic and expert manual quantification is obtained for both EAT and TAT with median Dice score coefficients of 0.823 (inter-quartile range (IQR): 0.779-0.860) and 0.905 (IQR: 0.862-0.928), respectively; with excellent correlations of 0.924 and 0.945 for EAT and TAT volumes. Computations are performed in <6 s on a standard personal computer for one CT scan. Therefore, the proposed method represents a tool for rapid fully automated quantification of adipose tissue and may improve cardiovascular risk stratification in patients referred for routine CT calcium scans.

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

Aims: To compare the predictive value of epicardial and intrathoracic fat volume (EFV, IFV), coronary artery calcium (CAC) score, and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for major adverse cardiac events (MACE)., Methods and Results: Follow-up was obtained in 275 patients with known or suspected coronary artery disease (CAD), who underwent SPECT-MPI including non-contrast cardiac computed tomography (CT) for attenuation correction to evaluate ischaemic heart disease and in whom EFV, IFV, and CAC score were calculated from non-contrast CT. Associations between fat volume, traditional cardiovascular risk factors, CAC score, and SPECT-MPI results were assessed and MACE predictors identified by Cox proportional hazard regression and global χ(2) statistics. After a median follow-up of 2.9 years, MACE were recorded in 38 patients. In univariate Cox regression analysis, EFV and IFV were predictors of MACE (P = 0.013 and P = 0.004, respectively). In multivariate analysis, EFV and IFV provided incremental predictive value beyond traditional cardiovascular risk factors (P < 0.05 and P < 0.01). However, after adjustment for CAC score and SPECT-MPI results, EFV and IFV fell short of statistical significance as independent outcome predictors., Conclusion: Quantification of EFV and IFV is associated with MACE and may improve risk stratification beyond traditional cardiovascular risk factors. However, once CAC score and/or SPECT-MPI results are known, EFV and IFV do not provide any added clinically relevant prognostic value. Further studies may identify the subpopulation with the largest relative merit of EFV and IFV as an adjunct to SPECT-MPI and CAC score., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Epicardial adipose tissue (EAT) volume is associated with plaque formation and cardiovascular event risk, its density may reflect tissue composition and metabolic activity., Objectives: Global and regional associations between EAT volume and density, ischemia and coronary calcium were investigated using a novel automatic quantitative measurement software., Methods: 71 patients with an intermediate pre-test probability for coronary artery disease and inducible ischemia by SPECT were matched to two same-gender controls (total of 213 patients, 90% male, age 60 ± 10 years). Non-contrast CT for assessment of EAT volume, density (in Hounsfield Unit [HU]) and coronary calcium score (CCS) was performed., Results: Global EAT volume was significantly increased in ischemic patients compared to controls (96 ± 49 vs. 82 ± 36 cm(3), p = 0.04), density showed no significant difference (-75.6 ± 4.3 vs. -75.1 ± 4.1HU, p = 0.63). EAT volume and density differed significantly between coronary territories (LAD: 37 ± 18 cm(3), -77.8 ± 4.5HU; LCx: 16 ± 9 cm(3), -73.9 ± 4.1HU; RCA: 36 ± 17 cm(3), -71.7 ± 4.8HU, p < 0.001). For regional ischemia, only LCx territory showed a significantly higher EAT volume (18 ± 8 vs. 16 ± 9 cm(3), p = 0.048). Multivariable logistic regression revealed a significant association with ischemia for EAT volume (OR 2.09 (1.0; 4.3), p = 0.049) and CCS (OR 1.43 (1.1; 1.9), p = 0.006). EAT volume significantly improved discrimination of ischemia over CCS (Integrated Discrimination Improvement: 3.5%, 95%CI: 1.1-6.1%, p = 0.004). Hypertension was the only risk factor significantly influencing EAT volume and density (98 ± 48 vs. 78 ± 31 cm(3), p = 0.002, -76.0 ± 4.1 vs. -74.5 ± 4.1 HU, p = 0.01)., Conclusions: EAT volume is associated with myocardial ischemia and improves the discriminative power for independent ischemia prediction over CCS. In hypertensive patients, EAT is characterized by lower density and higher volumes., (Copyright © 2016 Society of Cardiovascular Computed Tomography. All rights reserved.)

Background: The aim of the current study was to examine whether the use of highly active antiretroviral therapy (HAART) in patients with HIV is associated with changes in pericardial fat and myocardial lipid content measured by cardiovascular magnetic resonance (CMR)., Methods: In this prospective case-control study, we compared 27 HIV seropositive (+) male subjects receiving HAART to 22 control male subjects without HIV matched for age, ethnicity and body mass index. All participants underwent CMR imaging for determination of pericardial fat [as volume at the level of the origin of the left main coronary artery (LM) and at the right ventricular free wall] and magnetic resonance spectroscopy (MRS) for evaluation of intramyocardial lipid content (% of fat to water in a single voxel at the interventricular septum). All measurements were made by two experienced readers blinded to the clinical history of the study participants. Two-sample t-test, Spearman's correlation coefficient or Pearson's correlation coefficient and multivariable logistic regression were used for statistical analysis., Results: Pericardial fat volume at the level of LM origin was higher in HIV (+) subjects (33.4 cm(3) vs. 27.4 cm(3), p = 0.03). On multivariable analysis adjusted for age, Framingham risk score (FRS) and waist/hip ratio, pericardial fat remained significantly associated to HIV-status (OR 1.09, p = 0.047). For both HIV (+) and HIV (-) subjects, pericardial fat volume showed strong correlation with intramyocardial lipid content (r = 0.58, p < 0.0001) and FRS (r = 0.53, p = 0.0002). Among HIV (+) subjects, pericardial fat was significantly higher in patients with lipo-accumulation (37 cm(3) vs. 27.1 cm(3), p = 0.03) and showed significant correlation with duration of both HIV infection (r = 0.5, p = 0.01) and HAART (r = 0.46, p = 0.02)., Conclusions: Pericardial fat content is increased in HIV (+) subjects on chronic HAART (>5 years), who demonstrate HAART-related lipo-accumulation and prolonged HIV duration of infection. Further investigation is warranted to determine whether increased pericardial fat is associated with higher cardiovascular risk leading to premature cardiovascular events in this patient population.

Purpose: The authors aimed to develop and validate an automated algorithm for epicardial fat volume (EFV) quantification from noncontrast CT., Methods: The authors developed a hybrid algorithm based on initial segmentation with a multiple-patient CT atlas, followed by automated pericardium delineation using geodesic active contours. A coregistered segmented CT atlas was created from manually segmented CT data and stored offline. The heart and pericardium in test CT data are first initialized by image registration to the CT atlas. The pericardium is then detected by a knowledge-based algorithm, which extracts only the membrane representing the pericardium. From its initial atlas position, the pericardium is modeled by geodesic active contours, which iteratively deform and lock onto the detected pericardium. EFV is automatically computed using standard fat attenuation range., Results: The authors applied their algorithm on 50 patients undergoing routine coronary calcium assessment by CT. Measurement time was 60 s per-patient. EFV quantified by the algorithm (83.60 ± 32.89 cm(3)) and expert readers (81.85 ± 34.28 cm(3)) showed excellent correlation (r = 0.97, p < 0.0001), with no significant differences by comparison of individual data points (p = 0.15). Voxel overlap by Dice coefficient between the algorithm and expert readers was 0.92 (range 0.88-0.95). The mean surface distance and Hausdorff distance in millimeter between manually drawn contours and the automatically obtained contours were 0.6 ± 0.9 mm and 3.9 ± 1.7 mm, respectively. Mean difference between the algorithm and experts was 9.7% ± 7.4%, similar to interobserver variability between 2 readers (8.0% ± 5.3%, p = 0.3)., Conclusions: The authors' novel automated method based on atlas-initialized active contours accurately and rapidly quantifies EFV from noncontrast CT.

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.)

Purpose: The purpose of our study is to present a surgical technique of primary porous orbital ball implantation with overlying mucus membrane graft (MMG) for reconstruction of severely contracted socket and to evaluate prosthesis retention and motility in comparison to dermis fat graft (DFG)., Study Design: Prospective comparative study., Materials and Methods: A total of 24 patients of severe socket contracture (Grade 2-4 Krishna's classification) were subdivided into two groups, 12 patients in each group. In Group I, DFG have been used for reconstruction. In Group II, porous polyethylene implant with MMG has been used as a primary procedure for socket reconstruction. In Group I DFG was carried out in usual procedure. In case of Group II, vascularized scar tissues were separated 360° and were fashioned into four strips. A scleral capped porous polyethylene implant was placed in the intraconal space and four strips of scar tissue were secured to the scleral cap and extended part overlapped the implant to make a twofold barrier between the implant and MMG. Patients were followed-up as per prefixed proforma. Prosthesis motility and retention between the two groups were measured., Results: In Group I, four patients had recurrence of contracture with fall out of prosthesis. In Group II stable reconstruction was achieved in all the patients. In terms of prosthesis motility, maximum in Group I was 39.2% and Group II, was 59.3%. The difference in prosthesis retention (P = 0.001) and motility (P = 0.004) between the two groups was significant., Conclusion: Primary socket reconstruction with porous orbital implant and MMG for severe socket contracture is an effective method in terms of prosthesis motility and prosthesis retention.

Objective: Epicardial fat volume (EFV) is linked to cardiovascular event risk. The aim of this study was to evaluate whether EFV is independently related to concurrent presence of both myocardial ischemia and obstructive coronary stenosis., Methods: We studied 92 consecutive patients without known coronary artery disease (CAD) who underwent Rb-82 PET, coronary calcium scoring (CCS) and invasive coronary angiography (ICA) within 6 months. EFV was computed from non-contrast CT by validated software and indexed to body surface-area (EFVi, cm(3)/m(2)). Ischemia was defined by ≥ 5% difference of total perfusion deficit (quantified by validated software) between stress and rest. Obstructive stenosis was defined ≥ 50% luminal diameter stenosis., Results: Fifty three patients had both ischemia and stenosis. Compared to those without, patients with both having ischemia and stenosis had significantly higher CCS (1125 ± 1230 vs. 626 ± 690, p = 0.02) and EFVi (64.6 ± 20.6 vs. 49.7 ± 14.2 cm(3)/m(2), p=0.0002). On multivariable analysis after adjusting age, gender, cardiovascular risk factors, chest pain, and CCS (≥ 400), only elevated EFVi (>68.1cm(3)/m(2)) significantly predicted concurrent presence of both ischemia and stenosis (odds ratio 6.18, 95% confidence interval 1.73-22.01, p = 0.005). Area under the receiver-operator-characteristic analysis demonstrated a trend towards improved incremental prediction of concurrent myocardial ischemia and obstructive stenosis over age, gender, chest pain, and high CCS (0.73 vs. 0.65, p = 0.09)., Conclusions: Our study suggests that elevated EFVi measured using non-contrast CT may be related to concurrent presence of both ischemia and stenosis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of coronary artery disease (CAD) through possible paracrine interaction with the coronary arteries. We examined the association of EAT with metabolic syndrome and the prevalence and progression of coronary artery calcium (CAC) burden., Methods: CAC scan was performed in 333 asymptomatic diabetic patients without prior history of CAD (median age 54 years, 62% males), followed by a repeat scan after 2.7±0.3 years. CAC progression was defined as >2.5mm(3) increase in square root transformed volumetric CAC scores. EAT and intra-thoracic fat volumes were quantified using a dedicated software (QFAT), and were examined in relation to the metabolic syndrome, baseline CAC scores and CAC progression., Results: Both epicardial and intra-thoracic fat were associated with metabolic syndrome after adjustment for conventional cardiovascular risk factors, but the association was attenuated after additional adjustment for body mass index. EAT, but not intra-thoracic fat, showed significant association with baseline CAC scores (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.04-1.22, p=0.04) and CAC progression (OR 1.12, 95% CI 1.05-1.19, p<0.001) after adjustment for conventional measures of obesity and risk factors., Conclusion: EAT volume measured on non-contrast CT is an independent marker for the presence and severity of coronary calcium burden and also identifies individuals at increased risk of CAC progression. EAT quantification may thus add to the prognostic value of CAC imaging., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Epicardial fat volume (EFV) is linked to cardiovascular event risk. We aimed to investigate the relationships between EFV and weight change., Methods: From the EISNER (Early Identification of Subclinical Atherosclerosis using Non-invasive Imaging Research) Registry with baseline and follow-up coronary calcium scans (1248 subjects), we selected a cohort of 374 asymptomatic subjects matched using age decade, gender and coronary calcium score (CCS) as a measure of subclinical cardiovascular risk, who underwent 2 scans at an interval of 4.1±0.4 years. Using semi-automated validated software, pericardial contours were generated on all slices by spline interpolation from 5 to 10 control points. EFV was computed as fat volume within the pericardial contours. Weight gain/loss was defined as >5% change., Results: At baseline, EFV was moderately correlated to weight, body mass index (BMI) and waist circumference (r=0.51, 0.41 and 0.50, p<0.0001). EFV change was weakly correlated to change in weight (r=0.37, p<0.0001), BMI (r=0.39, p<0.0001) and waist circumference (r=0.21, p=0.002). On multivariable linear regression analysis, weight change [β=1.2, 95% confidence interval (CI) 0.9-1.5, p<0.001], BMI change (β=1.2, 95% CI 0.9-1.5, p<0.001), gender (β=-6.4, 95% CI -10.9 to -1.8, p=0.006) and hypertension (β=4.7, 95% CI 0.5-9.0, p=0.03) predicted EFV change. EFV decreased in 54 subjects with weight loss and increased in 71 subjects with weight gain (-2.3±21.1% vs. 23.3±24.4%, p<0.001)., Conclusions: EFV is related to body weight, BMI and waist circumference. Reduction in weight may stabilize or reduce EFV, while weight gain may promote EFV increase., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Epicardial fat volume (EFV) quantified on noncontrast cardiac computed tomography relates to cardiovascular prognosis. We sought to define the upper normal limit of body surface area (BSA)-indexed EFV (EFVi) in a healthy population and to validate it as a predictor of major adverse cardiovascular events (MACE). We analyzed noncontrast cardiac computed tomography scans of 226 healthy subjects with a low Framingham Risk Score (FRS; ≤6%) performed for coronary calcium scoring (CCS). EFV was quantified using validated software and indexed to BSA. We defined the 95th percentile as the upper normal limit. Subsequently, we reanalyzed a separate cohort of 232 participants from a previously published case-control study with 4-year follow-up and 58 cases of MACE to test the additive value of an abnormally high EFVi for predicting MACE. Of the 226 healthy participants 51% were men (mean age 52 ± 9 years). EFV correlated to BSA (r = 0.373, p <0.0001). Median, range, and 25th and 75th percentiles of the non-normally distributed EFVi were 33.3, 10.8 to 96.6, and 24.5 and 45.5 cm(3)/m(2). The 95th percentile definition of the upper normal limit of EFVi was 68.1 cm(3)/m(2). For prediction of MACE, EFVi values higher than the newly defined threshold emerged as a significant and independent predictor after controlling for confounders (odds ratio 2.8, 95% confidence interval 1.3 to 6.4, p = 0.012) and trended in its additive value to the combination of CCS ≥400 and FRS (area under the receiver operating characteristic curve 0.714 vs 0.675, p = 0.1277). In conclusion, in a healthy population we determined 68.1 cm(3)/m(2) as the 95th percentile threshold for abnormally high EFVi. EFVi exceeding this value independently predicted MACE and trended to add to CCS and FRS in this prediction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Epicardial fat volume (EFV) has been associated with prevalent but not incident coronary artery calcium. However, the relationship between EFV and development of incident coronary calcium (incCC) has not been reported., Objective: We evaluated the relationship between epicardial fat volume and the development of coronary artery calcium over 3-5 years., Methods: From 1248 subjects who underwent 2 serial noncontrast cardiac CT scans 3-5 years (median, 4 years) apart to measure coronary calcium score of 0 who subsequently developed incident coronary calcium (incCC(+)) were matched to 106 controls in whom coronary calcium score remained 0 (incCC(-)). EFV was calculated by determination of the pericardial contour, followed by identification of fat voxels with the use of validated software (QFAT). Baseline EFV and EFV indexed to body surface area (EFVi) and subsequent EFV and EFVi changes were compared between incCC(-) and incCC(+) populations. A significant EFV increase was defined as a ≥10% and ≥25% increase from the baseline value., Results: Baseline EFVi was similar between the 2 groups [EFVi, 40.9 ± 17.9 cm³ (median, 38.3 cm³) in incCC(-) vs 40.3 ± 16.3 cm³ (median, 37.0 cm³) in incCC(+); P = 0.96]. On the follow-up CT, EFVi increased in 74.5% of incCC(-) and in 76.4% of incCC(+) (P = 0.75). EFVi changes between the 2 groups were similar [4.9 ± 8.9 cm³ (median, 4.9 cm³) in incCC(-) vs 4.2 ± 8.0 cm³) (median, 3.5 cm³) in incCC(+); P = 0.67]. On multivariate analysis, after adjusting for cardiovascular risk factors, incCC was not related to an increase in EFVi at a 10% or 25% level., Conclusions: In very low-risk subjects with a coronary calcium score of 0, baseline EFVi and change in EFVi after 3-5 years were not related to the development of incidental coronary artery calcium., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Epicardial fat volume (EFV) measured from noncontrast CT is associated with coronary atherosclerosis and increased risk of major adverse cardiovascular events. Interscan reproducibility of EFV quantification from noncontrast CT has not been reported., Objective: We evaluated the interscan (intrascanner and interscanner) reproducibility of EFV and thoracic fat volume (TFV) measurements from noncontrast CT., Methods: We studied 25 consecutive patients who were scanned twice with 4-slice multidetector CT (MDCT), with 120 kVp, 2.5-mm slice thickness (intrascanner) and 23 consecutive patients who were scanned with MDCT and electron beam CT (EBCT) with 3-mm slice thickness (interscanner). For each scan, EFV and TFV were measured from user-defined range of CT slices covering the heart by experienced imaging cardiologists. Voxels within -30 to -190 HU within the epicardial contours was quantified as EFV. TFV was quantified within the heart range automatically. Repeatability coefficient (RC), defined as 1.96 × SD of the differences between pairs of repeated measures, was determined., Results: Correlations for interscan measurements of EFV and TFV were high for both intrascanner (MDCT-MDCT) and interscanner (EBCT-MDCT) data (correlation coefficient ≥0.98). RC values were lowest (4.3% for EFV and 5.4% for TFV) for intrascanner same-observer measurement. For intrascanner cross-observer measurement, RC values were 10.7% for EFV and 9.0% for TFV. For interscanner data, RC values ranged from 6.8% to 8.2%., Conclusion: Epicardial and thoracic fat measurements with the use of either MDCT or EBCT are highly reproducible., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: We evaluated the association between pericardial fat and myocardial ischemia for risk stratification., Background: Pericardial fat volume (PFV) and thoracic fat volume (TFV) measured from noncontrast computed tomography (CT) performed for calculating coronary calcium score (CCS) are associated with increased CCS and risk for major adverse cardiovascular events., Methods: From a cohort of 1,777 consecutive patients without previously known coronary artery disease (CAD) with noncontrast CT performed within 6 months of single photon emission computed tomography (SPECT), we compared 73 patients with ischemia by SPECT (cases) with 146 patients with normal SPECT (controls) matched by age, gender, CCS category, and symptoms and risk factors for CAD. TFV was automatically measured. Pericardial contours were manually defined within which fat voxels were automatically identified to compute PFV. Computer-assisted visual interpretation of SPECT was performed using standard 17-segment and 5-point score model; perfusion defect was quantified as summed stress score (SSS) and summed rest score (SRS). Ischemia was defined by: SSS - SRS ≥4. Independent relationships of PFV and TFV to ischemia were examined., Results: Cases had higher mean PFV (99.1 ± 42.9 cm(3) vs. 80.1 ± 31.8 cm(3), p = 0.0003) and TFV (196.1 ± 82.7 cm(3) vs. 160.8 ± 72.1 cm(3), p = 0.001) and higher frequencies of PFV >125 cm(3) (22% vs. 8%, p = 0.004) and TFV >200 cm(3) (40% vs. 19%, p = 0.001) than controls. After adjustment for CCS, PFV and TFV remained the strongest predictors of ischemia (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.53 to 5.52, p = 0.001 for each doubling of PFV; OR: 2.64, 95% CI: 1.48 to 4.72, p = 0.001 for TFV). Receiver operating characteristic analysis showed that prediction of ischemia, as indicated by receiver-operator characteristic area under the curve, improved significantly when PFV or TFV was added to CCS (0.75 vs. 0.68, p = 0.04 for both)., Conclusions: Pericardial fat was significantly associated with myocardial ischemia in patients without known CAD and may help improve risk assessment., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to evaluate whether pericardial fat has value in predicting the risk of future adverse cardiovascular outcomes., Background: Pericardial fat volume (PFV) and thoracic fat volume (TFV) can be routinely measured from noncontrast computed tomography (NCT) performed for calculating coronary calcium score (CCS) and may predict major adverse cardiac event (MACE) risk., Methods: From a registry of 2,751 asymptomatic patients without known cardiac artery disease and 4-year follow-up for MACE (cardiac death, myocardial infarction, stroke, late revascularization) after NCT, we compared 58 patients with MACE with 174 same-sex, event-free control subjects matched by a propensity score to account for age, risk factors, and CCS. The TFV was automatically calculated, and PFV was calculated with manual assistance in defining the pericardial contour, within which fat voxels were automatically identified. Independent relationships of PFV and TFV to MACE were evaluated using conditional multivariable logistic regression., Results: Patients experiencing MACE had higher mean PFV (101.8 +/- 49.2 cm(3) vs. 84.9 +/- 37.7 cm(3), p = 0.007) and TFV (204.7 +/- 90.3 cm(3) vs. 177 +/- 80.3 cm(3), p = 0.029) and higher frequencies of PFV >125 cm(3) (33% vs. 14%, p = 0.002) and TFV >250 cm(3) (31% vs. 17%, p = 0.025). After adjustment for Framingham risk score (FRS), CCS, and body mass index, PFV and TFV were significantly associated with MACE (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.03 to 2.95 for each doubling of PFV; OR: 1.78, 95% CI: 1.01 to 3.14 for TFV). The area under the curve from receiver-operator characteristic analyses showed a trend of improved MACE prediction when PFV was added to FRS and CCS (0.73 vs. 0.68, p = 0.058). Addition of PFV, but not TFV, to FRS and CCS improved estimated specificity (0.72 vs. 0.66, p = 0.008) and overall accuracy (0.70 vs. 0.65, p = 0.009) in predicting MACE., Conclusions: Asymptomatic patients who experience MACE exhibit greater PFV on pre-MACE NCT when they are compared with event-free control subjects with similar cardiovascular risk profiles. Our preliminary findings suggest that PFV may help improve prediction of MACE., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To develop a prediction equation for percent body fat (BF%) from skin fold thickness in a random sample of free-living 75-year-olds and to compare with published equations for the elderly., Setting: Goteborg part of the Nordic Research on Aging (NORA) study in 1991/92., Subjects & Methods: Anthropometric measurements were performed in 286 participants (125 males,161 females) and body composition was estimated by four compartment model (4C) from total body water (TBW) and total body potassium (TBK) in every alternative subjects. BF % predicted from skin fold thickness (BFSF) was validated against BF % estimated from 4C model (BF4C) and was compared with BFSF and BF % predicted from equations by Durnin and Womersley, 1974 (BFDW), Deurenberg et al.,1989 (BFPD) and, Visseretal.,1994(BFMV), respectively., Results: The BFSF correlated well with BF4C (r = 0.86, SEE = 4.05). Compared to BF4C, both BFPD and BFMV over estimated BF % by 3.26 and 3.63 in males and 9.56 and 9.23 in females, respectively. BFDW underestimated BF % in females by 1.06 and overestimated by 3.12 in males. BFSF showed best agreement with BF4C, where the 95 % of differences lie between +/- 7.4 in males and +/- 8.7 in females, respectively., Conclusion: BF % predicted from skin fold thickness correlated well with estimated BF % in 75-year-olds. Different prediction equations gave different values for BF % and population-specific prediction equations seem preferable in the elderly population.

Agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) are pharmacologically active antihyperglycemic agents that act by increasing peripheral tissue sensitivity to insulin. Many of these agonists have antihyperglycemic activity that is directly proportional to their ability to bind and activate PPAR gamma; however, recent data bring this relationship into question. In this report we describe a new PPAR gamma agonist, CLX-0921, that is derived from a natural product. This thiazolidinedione (TZD) has a spectrum of activity that differs from commercially available TZDs. It is a weak activator of PPAR gamma (EC(50) of 0.284 micromol/L) compared to rosiglitazone (EC(50) 0.009 micromol/L). Despite this difference, the drug maintains potent glucose uptake activity in vitro and glucose-lowering activity in vivo that is equipotent to that of rosiglitazone. Moreover, CLX-0921 showed a 10-fold reduction in in vitro adipogenic potential compared to rosiglitazone. CLX-0921 also increases glycogen synthesis, an activity not typically associated with rosiglitazone or pioglitazone. Thus CLX-0921 appears to have a distinct spectrum of activity relative to other TZDs.

Objective: To develop a bioelectrical impedance (BIA) prediction equation for fat-free mass (FFM(BIA)) and present reference values of FFM and body fat (BF) for healthy Swedish elderly from population-based representative samples., Subjects: This study is based on 823 (344 males, 479 females) participants from two systematic samples of birth cohorts in Göteborg aged 70 (cohort H70V, 201 males and 299 females) and 75 (cohort NORA75, 143 males and 180 females)., Methods: Body composition was measured with BIA (BIA-101, RJL system, Detroit) in both cohorts and was estimated by a four-compartment (4C) model from total body water (TBW) and total body potassium (TBK) in a sub-sample of the NORA75 cohort. The FFM(BIA) was validated against the FFM from the 4C model (FFM(4C))., Results: The FFM(BIA) correlated well with FFM(4C) (r=0.95, SEE=2.64 kg). The FFM(BIA) (kg) in 70-y-old males and females were 58.5+/-5.4 and 43.4+/-4.4, and for 75-y-old males and females were 56.1+/-4.7 and 42.5+/-4, respectively. The body fat in kg (FM) among 70-y-old males and females were 25.2+/-8.1 and 25.7+/-8.4, and for 75-y-old males and females were 21.7+/-7.1 and 22.8+7.2, respectively. The percent body fat (BF%) among 70-y-old males and females were 29.5+/-5.8 and 36.3+/-6.4, and for 75-y-old males and females were 27.3+/-6 and 34.1+/-6.1, respectively., Conclusion: The FFM, FM and BF% from this study might be used as reference values for Swedish elderly aged 70 and 75 y.