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Abstract Background Diabetes is an independent risk factor for cardiovascular disease. The purpose of this study was to identify the risk factors for vulnerable coronary plaques (VCPs), which are associated with adverse cardiovascular events, and to determine the value of coronary CT angiography (CCTA) in patients with type 2 diabetes mellitus (T2DM) and VCPs. Methods Ninety-eight T2DM patients who underwent CCTA and intravascular ultrasound (IVUS) were retrospectively included and analyzed. The patients were grouped and analyzed according to the presence or absence of VCPs. Results Among the patients with T2DM, time in range [TIR {the percentage of time blood glucose levels were in the target range}] (OR = 0.93, 95% CI = 0.89–0.96; P

The introduction into clinical practice of intravascular imaging, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and their derivatives, allowed for the in vivo assessment of coronary atherosclerosis in humans, including insights into plaque evolution and progression process. Intravascular ultrasound, the most commonly used intravascular modality in many countries, due to its low resolution cannot assess many features of vulnerable plaque such as lipid plaque or thin-cap fibroatheroma. Thus, novel methods were introduced to facilitate this problem including virtual histology intravascular ultrasound and later on near-infrared spectroscopy and OCT. Howbeit, none of the currently used modalities can assess all known characteristics of plaque vulnerability; hence, the idea of combining different intravascular imaging methods has emerged including NIRS-IVUS or OCT-IVUS imaging. All of those described methods may allow us to identify the most vulnerable plaques, which are prone to cause acute coronary syndrome, and thus they may allow us to introduce proper treatment before plaque destabilization. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of the present study is to evaluate whether advanced coronary atherosclerosis analysis by CCTA may improve prognostic stratification among diabetic patients at high cardiovascular risk (CV risk).Methods and Results: The study population consisted of 265 consecutive diabetic patients at high CV risk who underwent CCTA for suspected CAD between January 2011 and December 2016. For every patients both traditional and advanced, qualitative and quantitative coronary plaque analysis were performed. The occurrence of cardiac death, ACS, and non-urgent revascularization were recorded at follow-up. Among the 265 patients enrolled, 21 were lost to follow-up, whereas 244 (92%) had a complete follow-up (mean 45 ± 22 months) and were classified at high (n = 67) or very high cardiovascular risk (n = 177), according to ESC Guidelines. A total of 63 events were recorded (3 Cardiac Death, 3 NSTEMI, 8 unstable angina, 36 late non-urgent revascularization and 13 non-cardiac death) in 57 different patients. Elevated fibro-fatty plaque volume was the only predictor of events over age, gender and traditional risk factor when ACS and MACE were considered as end-points [HR (95% CI) 6.01 (1.65-21.87), p = 0.006 and 3.46 (2.00-5.97); p < 0.001].Conclusion: The present study confirms the prognostic role of advance coronary atherosclerosis evaluation beyond risk factors and stenosis severity, even in diabetics. Despite the very high cardiovascular risk of study population, a not negligible portion (23%) of patients exhibited totally normal coronaries. [ABSTRACT FROM AUTHOR]

This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis. The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization. Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events. The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662) [ABSTRACT FROM AUTHOR]

The aim of this study was to demonstrate that the transluminal contrast attenuation gradient (TAG), a new CT imaging-derived marker of functional significance of a coronary stenosis, is directly associated with the vulnerability degree of atheromatous coronary plaques. Material and methods: This is a prospective study on 21 patients with 30 atheromatous plaques in the coronary arteries, who underwent cardiac computed tomography angiography (CCTA) for assessment of coronary plaques. Results: Twelve plaques were classified as vulnerable (40%) and 18 plaques (60%) as non-vulnerable. Plaques associated with a TAG value above 10 HU exhibited in a significantly higher proportion CCTA markers of plaque vulnerability, as compared to plaques in which the attenuation gradient was below 10 HU. TAG values >10 HU were associated with a higher amount of plaque volume (107.4 ± 91.2 mm3 vs. 56.0 ± 37.5 mm3, p = 0.009), necrotic core (32.5 ± 36.9 mm3 vs. 3.1 ± 3.2 mm3, p = 0.0003), and fibro-fatty tissue (17.7 ± 16.3 mm3 vs. 4.0 ± 2.6 mm3, p = 0.0002), as compared to those lesions with TAG values below 10 HU. Linear regression analysis revealed a significant correlation between TAG values and CCTA features of plaque instability: necrotic core (r = −0.73, p

The aim of this preliminary study was to assess the effectiveness of transluminal contrast attenuation gradient (TAG) determined by computed tomographic angiography (CTA), for the evaluation of the functional significance of coronary artery stenoses in patients with acute coronary syndromes produced by vulnerable coronary plaques, and to demonstrate the correlation between this new parameter and the vulnerability markers of the culprit lesions.

Background Rapid plaque progression and positive remodeling are recognized as vulnerable coronary plaque characteristics. This study examined whether serial carotid ultrasonography might be of value for assessment of coronary plaque progression and positive remodeling, measured by serial intravascular ultrasound (IVUS), in survivors of acute myocardial infarction (AMI). Methods Thirty-nine patients with AMI had repeated examinations by IVUS of culprit coronary arteries and echolucency of the coronary artery on admission (1st test) and 6 months later (2nd test). Plaque volume and external elastic membrane area of the native segment (15 ± 9 mm in length) beginning 5 mm proximal to the stent edge in the culprit coronary artery were measured using volumetric IVUS. Echolucency of the carotid artery was assessed by integrated backscatter (IBS) analysis. Lower IBS reflects an echolucent and lipid-rich plaque. Results Increase in coronary plaque volume and positive remodeling over 6 months occurred in 17 and 12 patients, respectively. The % change in carotid IBS value over 6 months was correlated with the % change in the coronary plaque volume ( r = −0.69, p < 0.001). The aggravated change in the carotid IBS was significantly associated with increase in the coronary plaque volume and positive remodeling over 6 months (OR 0.94 and 0.95, respectively, 95% CI 0.90–0.99, both p < 0.05). Conclusions Serial measurements of echolucency of the carotid artery may be of value for assessment of short-term progression and positive remodeling of coronary plaques in AMI survivors. [ABSTRACT FROM AUTHOR]

Vascular calcification plays a prominent role in cardiovascular disease. Once considered to be a passive consequence of aging, this pathological process is now accepted to be dynamic and tightly regulated, its onset triggered by inflammation and necrosis and its progression bearing key similarities to osteogenesis. A major potential advance in our ability to understand the natural history and clinical implications of vascular calcification is the detection of its early and dynamic stages through the use of the positron-emitting radiotracer, (18)F-sodium fluoride. Alongside anatomical information gained from computed tomography, hybrid positron emission and computed tomography (PET/CT) imaging with (18)F-sodium fluoride has, for the first time, enabled the non-invasive detection of microcalcification within the aortic valve, great vessels, and vulnerable coronary plaque. This has raised promise that exploring this process may allow improved risk prediction, better application of current therapies and ultimately the development of novel treatments to target this widespread pathology. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. Background: A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. Methods: All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified [NCP], mixed [MP], calcified [CP]) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign [non-NRS], and heterogeneous with NRS). Results: No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval [CI]: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). Conclusions: The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions. [Copyright &y& Elsevier]

Background: The presence of ceramide in human coronary plaques is a risk factor for ischemic heart disease, but its visualization in the human vessel wall is currently beyond the scope of any available imaging techniques.Methods and Results:Deposition of ceramide was examined by fluorescent angioscopy (FA) and microscopy (FM) using golden fluorescence (Go) as a specific marker of ceramide in yellow plaques, which were obtained from 23 autopsy subjects and classified by conventional angioscopy and histology. Ceramide was observed by FM in 34 of the 41 yellow plaques with a necrotic core (NC) but rarely in the 28 without. Ceramide and macrophages/foam cells co-deposited mainly in the border zone of the NC and fibrous cap (FC). The Go of ceramide was seen when the fibrous cap thickness was ≤100 µm. FA was performed to detect coronary plaques exhibiting Go in patients with coronary artery disease. Ceramide was also detected by FA in 6 of 18 yellow plaques (33.3%) in 8 patients with stable angina and in 18 of 24 yellow plaques (75.0%, P<0.05 vs. stable angina) in 8 patients with old myocardial infarction., Conclusions: The Go of ceramide in human coronary plaques is detectable by FA and Go could be used as a marker of vulnerable plaque (i.e., thin FC with NC).

Myocardial infarction and sudden cardiac death are frequently the first manifestation of coronary artery disease. For this reason, screening of asymptomatic coronary atherosclerosis has become an attractive field of research in cardiovascular medicine. Necropsy studies have described histopathological changes associated with the development of acute coronary events. In this regard, thin-cap fibroatheroma has been identified as the main vulnerable coronary plaque feature. Hence, many imaging techniques, such as coronary computed tomography, cardiac magnetic resonance or positron emission tomography, have tried to detect noninvasively these histomorphological characteristics with different approaches. In this article, we review the role of these diagnostic tools in the detection of vulnerable coronary plaque with particular interest in their advantages and limitations as well as the clinical implications of the derived findings., Competing Interests: Conflict-of-interest statement: No conflict of interests needs to be declared by any of the authors who contributed to this manuscript.

Unlabelled: (18)F-FDG PET/CT can be used to detect arterial atherosclerotic plaque inflammation. However, avid myocardial glucose uptake may preclude its use for visualizing coronary plaques. Fatty acid loading or calcium channel blockers could decrease myocardial (18)F-FDG uptake, thus assisting coronary plaque inflammation identification. The present prospective randomized trial compared the efficacies of different interventions for suppressing myocardial (18)F-FDG uptake. We also investigated whether circulating free fatty acid (cFFA) levels predicted the magnitude of myocardial (18)F-FDG uptake., Methods: Thirty-six volunteers ate a high-fat low-carbohydrate meal, followed by a 12-h fasting period. They were then randomized to 1 of 4 intervention groups. Group 1 received no additional preparation and served as a reference. Groups 2 and 3, respectively, received a commercial high-fat solution containing 43.8 g of lipids or 50 mL of olive oil 1 h before (18)F-FDG injection to evaluate the impact of fatty acid loading on myocardial (18)F-FDG uptake. Group 4 received verapamil to evaluate the effect of calcium channel blockers. Cardiac PET/CT was performed after administration of 370 MBq of (18)F-FDG. Myocardial uptake suppression was assessed using a qualitative visual scale and by measuring the myocardial maximum standardized uptake value (SUV(max)). Insulin, glucose, and cFFA were serially measured., Results: The qualitative visual scale showed good myocardial (18)F-FDG uptake suppression in 8 of 9, 5 of 9, 4 of 9, and 8 of 9 subjects of groups 1, 2, 3, and 4, respectively (P = 0.09). SUV(max) did not significantly differ between groups (P = 0.17). Interestingly, cFFA levels were higher in volunteers with good suppression (0.80 ± 0.31 mmol/L) than in those with poor suppression (0.53 ± 0.15 mmol/L; P = 0.011). We found an inverse correlation between cFFA level (measured at (18)F-FDG injection) and the SUV(max) (R = 0.61). Receiver-operating-characteristic curve analysis identified 0.65 mmol/L cFFA as the best cutoff value to predict adequate (18)F-FDG uptake suppression (positive predictive value, 89%)., Conclusion: A high-fat low-carbohydrate meal followed by a 12-h fasting period effectively suppressed myocardial (18)F-FDG uptake in most subjects. Neither complementary fatty acid loading nor verapamil administered 1 h before (18)F-FDG injection conferred any additional benefit. Myocardial (18)F-FDG uptake was inversely correlated with cFFA level, representing an interesting way to predict myocardial (18)F-FDG uptake suppression., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)