Pericoronary Adipose Tissue Attenuation Research Articles

Right coronary artery pericoronary fat attenuation index as a future predictor for acute coronary events in nonobstructive coronary artery disease - a prospective single centre study.

Evaluation of pericoronary adipose tissue changes induced by inflammation by non-invasive techniques is challenging. To find the association between pericoronary adipose tissue attenuation (FAI) changes and future acute coronary events in nonobstructive coronary artery disease. Ours was a single-centre, prospective observational study on patients with atypical chest pain who underwent coronary computed tomography angiography (CCTA). In patients with CADRADS 1 to 3 nonobstructive coronary artery disease (CAD), pericoronary FAI was measured around the proximal right coronary artery (RCA) and coronary artery segment with plaque using semi-automated postprocessing software. Patients were followed up for development of acute coronary events (ACE). Kaplan-Meier curves were used to see event-free survival rates. Of 120 patients with a mean follow-up period of 67 months, 21 patients developed acute coronary events. RCA-FAI and lesion FAI of patients with ACE were significantly higher as compared to patients without events. ROC curve analysis showed RCA-FAI as the best predictor of ACE at a cut-off point of>-77.3 Hounsfield unit (HU) (with an AUC of 0.915) with high sensitivity (95.24%), specificity (83.84%), and negative predictive value (98.80%). On multivariate analysis, RCA-FAI, diabetes mellitus, and stenosis ≥50% were independent risk factors of ACE with hazard ratios of 1.335 (1.173-1.518), 4.950 (1.716-14.278), and 7.446 (2.257-24.566), respectively. RCA FAI can predict ACE in nonobstructive coronary artery disease patients. Detection of high RCA FAI of>-77.3 HU on CCTA can help to identify high-risk patients who need regular follow-up and early initiation of interventions.

Response to 'Prognostic value of lesion-specific pericoronary adipose tissue attenuation? Importantly, but not yet!'

Response to 'Prognostic value of lesion-specific pericoronary adipose tissue attenuation? Importantly, but not yet!'

Estimating inflammatory risk in atherosclerotic cardiovascular disease: plaque over plasma?

Inflammation is an important driver of disease in the context of atherosclerosis, and several landmark trials have shown that targeting inflammatory pathways can reduce cardiovascular event rates. However, the high cost and potentially serious adverse effects of anti-inflammatory therapies necessitate more precise patient selection. Traditional biomarkers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), show an association with cardiovascular risk on a population level, but do not have specificity for local plaque inflammation. Nowadays, advancements in non-invasive imaging of the vasculature enable direct assessment of vascular inflammation. Positron emission tomography (PET) tracers such as 18F-fluorodeoxyglucose (18F-FDG) enable detection of metabolic activity of inflammatory cells but are limited by low specificity and myocardial spillover effects. 18F-sodium fluoride (18F-NaF) is a tracer that identifies active microcalcification in plaques, indicating vulnerable plaques. 68Ga-DOTATATE targets pro-inflammatory macrophages by binding to somatostatin receptors, which enhances specificity for plaque inflammation. Coronary computed tomography angiography (CCTA) provides high-resolution images of coronary arteries, identifying high-risk plaque features. Measuring pericoronary adipose tissue attenuation (PCATa) on CCTA represents a novel marker of vascular inflammation. This review examines both established and emerging methods for assessing atherosclerosis-related inflammation, emphasizing the role of advanced imaging in refining risk stratification and guiding personalized therapies. Integrating these imaging modalities with measurements of systemic and molecular biomarkers could shift atherosclerotic cardiovascular disease management toward a more personalized approach.

Patient-Level Pericoronary Adipose Tissue Mean Attenuation: Associations with Plaque Characteristics.

Pericoronary adipose tissue attenuation (PCATa), observed from coronary computed tomography angiography (CCTA), is emerging as an inflammation marker. This study evaluated the relationship between PCATa and plaque characteristics, including plaque type, burden, and coronary calcification. An observational study was conducted on 466 patients with suspected chronic coronary syndrome who underwent clinically indicated CCTA. PCATa was measured along the proximal 40 mm of the coronary arteries and averaged to represent the patient's level. Plaque type was assessed, compositional plaque volumes were measured, and plaque burdens were quantified. The coronary calcification scores (CCSs) were categorized into groups. Statistical methods included t-tests, ANOVA, and multivariate regression analysis. PCATa differed significantly between calcified (-81.7 Hounsfield units (HU)) and soft (-77.5 HU) plaques. PCATa was positively associated with total plaque burden (β = 3.6) and non-calcified plaque burden (β = 7.0), but negatively correlated with calcified plaque burden (β = -3.5), independent of clinical factors and tube voltage (p < 0.05). The effect of PCATa was stronger when plaques of a different composition were absent. No significant differences in PCATa were found among different CCS groups. PCATa increased for calcified compared to soft plaques. The non-calcified plaque burden was associated with a higher PCATa, while the calcified plaque burden was associated with a lower PCATa.

Effect of Vessel Attenuation, VMI Level, and Reconstruction Kernel on Pericoronary Adipose Tissue Attenuation for EID CT and PCD CT: An Ex Vivo Porcine Heart Study.

BACKGROUND. Pericoronary adipose tissue (PCAT) attenuation and the fat attenuation index (FAI) may serve as markers of inflammation and the risk of adverse cardiac events. However, standardization of relevant CT acquisition and reconstruction parameters is lacking. OBJECTIVE. The purpose of this study was to investigate the influence of vessel attenuation, the virtual monoenergetic image (VMI) level, and the reconstruction kernel on PCAT attenuation and FAI by use of energy-integrating detector (EID) and photon-counting detector (PCD) CT systems in an ex vivo porcine heart model. METHODS. The right coronary artery (RCA) of a porcine heart was injected with saline or varying contrast medium dilutions to achieve vessel attenuation ranging from 0 to 1000 HU. After each injection, the heart was sequentially scanned by EID CT at 120 kVp and PCD CT at 140 kVp at a constant CTDIvol of 10 mGy. For EID CT, polychromatic images were reconstructed with a Qr40 kernel. For PCD CT, VMIs (obtained at 40-80 keV in 10-keV increments) were reconstructed with Qr40, Bv40, and Bv56 kernels. ROIs were placed to measure RCA and PCAT attenuation. FAI was determined using software; histogram analysis was performed to assess voxel attenuation in the volumes of interest for FAI calculation. RESULTS. Correlations were observed between attenuation in the RCA and attenuation in the adjacent PCAT (r = 0.3-1.0) and between vessel attenuation and the FAI (r = -0.9 to 1.0). For PCAT attenuation and the FAI, these associations became progressively weaker when progressively sharper kernels were used. For increasing vessel attenuation on EID CT and for increasing VMI level on PCD CT, FAI histograms showed right shifts in peak attenuation values; the percentage of histogram voxels that met the threshold range for inclusion in FAI calculation was 9-38% for EID CT and 6-39% for PCD CT at VMI levels of 70-80 keV. For PCD CT, use of sharper kernels was associated with left shifts in peak attenuation values and greater percentages of voxels within the threshold range for inclusion in FAI calculation. CONCLUSION. PCAT attenuation and the FAI are influenced by vessel lumen attenuation, the VMI level, and the reconstruction kernel. A minority of pericoronary voxels contribute to FAI measurements for polychromatic EID CT and for PCD CT at high VMI levels. CLINICAL IMPACT. These findings may help standardize acquisition and reconstruction parameters for PCAT attenuation and FAI measurements.

Incremental prognostic value of pericoronary adipose tissue attenuation beyond conventional features in patients with nonobstructive coronary artery disease

Background and aimsIt remains uncertain whether pericoronary adipose tissue attenuation (PCATa) is associated with clinical outcome in patients with nonobstructive coronary artery disease (CAD). We aim to investigate the incremental prognostic value of PCATa beyond clinical and coronary computed tomographic angiography (CCTA) features in patients with nonobstructive CAD. MethodsConsecutive patients with chest pain suspected of CAD referred for CCTA from January 2017 to December 2018 were prospectively included. Multivariable Cox proportional hazard regression analysis was employed to identify the predictive factors for major adverse cardiovascular events (MACE), while the receiver operating characteristics (ROC) curve was utilized to assess the discriminatory capacity of PCATa. Kaplan-Meier curves were ultilized to visually represent event-free survival and were compared using Log-rank tests among groups stratified by high-risk plaque (HRP) and PCATa. ResultsOf the 1614 patients (mean age 59.0 years, 55.6% male) with nonobstructive CAD, 68 (4.2%) suffered MACE during a median follow-up of 28.6 months. After multivariable adjustment, PCATa was identified as an independent predictor (HR: 1.060, 95%CI: 1.025-1.096, p=0.001). The inclusion of PCATa significantly enhanced the discrimination capacity [AUC:0.72(0.66-0.78), p=0.041] and risk reclassification (NRI=1.99, P<0.001; IDI=0.93, p<0.001) beyond the influence of clinical and CCTA factors. In the presence of HRP, a higher PCATa was found to be associated with a relatively higher risk of MACE compared to a lower PCATa (HR: 2.45, 95%CI: 1.09-5.52, p=0.031). ConclusionsPCATa is positively correlated with adverse outcome in patients with nonobstructive CAD, and it offers incremental predictive value beyond clinical variables and CCTA characteristics.

Correlation of Sarcopenia with Coronary Artery Disease Severity and Pericoronary Adipose Tissue Attenuation: A Coronary CT Study.

To investigate the association between sarcopenia, as appraised with CT-derived muscle metrics, and cardiovascular status, as assessed via coronary CT angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS) and with pericoronary adipose tissue (pCAT) metrics. A retrospective observational study conducted on patients who underwent CCTA. The cross-sectional area (CSA) and attenuation values of the paravertebral muscles at the T8 level and the pectoralis major muscles at the T6 level were measured. The patient height was employed for the normalization of the skeletal muscle CSA. The pCAT attenuation around the coronary arteries was assessed, and the CAD severity was graded using the CAD-RADS reporting system. Regression analyses were performed to assess the impact of demographics, clinical factors, and CT variables on the CAD-RADS and pCAT. A total of 220 patients were included (132 males, median age 65 years). Regression analyses showed the associations of CAD with age and sex (p < 0.001). Familiarity with CAD was related to the left anterior descending artery pCAT (p = 0.002) and circumflex artery pCAT (p = 0.018), whereas age was related to the left anterior descending artery pCAT (p = 0.032). Weak positive correlations were found between the lower muscle density and lower pCAT attenuation (ρ = 0.144-0.240, p < 0.039). This study demonstrated weak associations between the sarcopenia indicators and the cardiovascular risk, as assessed by the CAD severity and pCAT inflammation. However, these correlations were not strong predictors of CAD severity, as age and traditional cardiovascular risk factors overshadowed the impact of sarcopenia in the cardiovascular risk assessment.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p&amp;lt;0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p&amp;lt;0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p&amp;lt;0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p&amp;gt;0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT &amp; plaque burden

Noninvasive predictors of residual coronary microvascular dysfunction after elective percutaneous coronary intervention

Abstract Backgrounds Coronary computed tomographic angiography (CCTA) provides noninvasive assessments of coronary plaque morphologies and perivascular inflammation. Morphological features associated with residual coronary microvascular dysfunction (CMD) after elective percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to examine prevalence and predictors of residual CMD and its phenotypes after elective PCI. Methods We investigated consecutive patients who were scheduled for elective fractional flow reserve (FFR)-guided PCI for de novo single lesions with pre-PCI CCTA data. Pre- and post-PCI comprehensive physiological assessments including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed by using pressure temperature sensor-tipped guidewire in all patients. Patients with periprocedural myocardial infarction were excluded. Residual CMD was defined as lesions with post-PCI coronary flow reserve (CFR) &amp;lt;2.0, which was further categorized as functional (IMR&amp;lt;25) or structural (IMR ≥25) CMD. Results A total of 198 de novo lesions in 198 patients were included in the final dataset. Pre- and post-PCI mean CFR were 1.79 [1.27, 2.53] and 2.72 [2.00, 4.04], respectively. Residual CMD was observed in 24.7% (49/198) of patients, categorized as functional (n=26) or structural (n=23). Patients with residual CMD showed older age, less frequent diabetes mellitus, current smoking and a culprit lesion in left anterior descending artery (LAD), and higher CCTA-defined calcium score in the culprit vessel compared with those in patients without residual CMD. Multivariable logistic regression analysis showed that age (adjusted odds ratio [OR]:1.04; 95% confidence interval [CI]: 1.00 to 1.08; p=0.04) and non-LAD (adjusted OR: 2.18; 95%CI: 1.03 to 4.63; p=0.04) were independently associated with residual CMD. In patients with residual CMD, patients with structural CMD tended to have more frequent diabetes mellitus (43.5% vs 19.2%, P=0.13) and atrial fibrillation (26.1% vs 7.7%) and showed significantly lower pericoronary adipose tissue attenuation (PCATA) in right coronary artery (RCA) by CCTA (-79.9 HU vs -74.6 HU, P=0.04) compared with patients with functional CMD. CCTA-detected epicardial fat volume and attenuation showed no significant differences between patients with residual functional CMD, those with residual structural CMD, and those without residual CMD. Multivariable analysis revealed that diabetes mellitus (adjusted OR: 5.18; 95%CI: 1.14 to 23.7; p=0.03) and PCATA in RCA (adjusted OR: 0.93; 95% CI: 0.85 to 1.00; p=0.05) were independently predictive of residual structural CMD. Conclusions Residual CMD was observed in approximately 25% of patients undergoing elective PCI. CCTA-defined calcium score and PCATA, along with clinical factors could be potential predictors of post-PCI residual CMD and its phenotypes.

Impact of ultra-high-resolution on cardiac CT assessment of coronary artery stenoses, plaque burden/composition, and pericoronary adipose tissue attenuation

Abstract Background Conventional coronary computed tomography angiography (CCTA) overestimates stenoses within stents and calcified arteries due to "blooming" artifacts. Ultra-high-resolution coronary CT (UHR-CT) may overcome this limitation because of higher spatial resolution. Purpose To investigate differences in coronary arterial lumen volume, stenosis severity, and plaque composition, between CCTA and UHRCT in patients with stents and/or high coronary calcium scores. Methods As part of a prospective pilot study, 14 patients referred for invasive coronary angiography for evaluation of obstructive CAD underwent UHRCT (Canon Precision, 160 x 0.25mm slices) prior to catheterization. Images of identical cardiac phases were reconstructed in two badges for comparison: 1) Ultra-high resolution using a 1,024 x 1,024 matrix, 0.25 mm, and 2) conventional resolution with a 524 x 524 matrix, 0.5 mm. All images were reconstructed using iterative reconstruction algorithm (AIDR 3D) and a sharp kernel (FC05). For the left main and three coronary arteries, an automated contour analysis using a dedicated software (QAngioCT RE 3.2, Medis, Netherlands) was performed to compare conventional CCTA vs. UHR-CT resolution images across common vascular and plaque metrics, including lumen and vessel volume, plaque burden/volume, plaque composition based upon predefined fixed intensity cut-off values of CT attenuation, minimal and maximal plaque thickness, pericoronary adipose tissue attenuation (PCAT), minimal lumen area and diameter, and diameter stenosis. All lumen and vessel contours were generated by the software, without manual editing. The segment model proposed by the SCCT was used as reference and the lesions classified as greater than 25% stenosis by visual assessment were recorded. The quality of the images was subjectively assessed using a 5-point Likert scale. Vessel segments with scores 1 (severe artifacts) and 2 (pronounced artifacts) were not included in the analysis. Results The mean patient age was 68.5 years (±6.8), 2 were female (14.3%), 6 patients had stents (11 stented segments) and the mean Agatston score was 947.6 (±449) among the 8 non-stented patients. A total of 56 vessels, 133 segments, and 57 lesions were analyzed. Eight segments (6%) were excluded from the analysis due to poor quality. Results on a per segment and per lesion basis were summarized in the table. The mean PCAT value was significantly lower for the UHRCT images compared to NR reconstruction in both segment (p&amp;lt;0.001) and lesion based (p=0.002) analyses. Plaque differentiation varied by UHRCT resulted in a lower fibrous plaque volumes but higher necrotic (low attenuation) plaque volumes. Conclusions Ultra-high-resolution CT image analysis results in significantly different coronary artery plaque volume and PCAT assessment vs. conventional resolution CCTA. These findings have implications for evaluating high-risk plaque features and perivascular inflammation in patients.Table 1

Association of vasospastic angina with myocardial bridging and pericoronary adipose tissue attenuation on computed tomography angiography

Abstract Background Recent studies have suggested that vasospastic angina (VSA) is associated with myocardial bridging (MB). The relationship between VSA and pericoronary adipose tissue (PCAT) inflammation has also been reported but still remains to be determined. Purpose We investigated clinical and coronary computed tomography angiographic (CCTA) features in patients with VSA diagnosed by spasm provocation test (SPT). Methods We retrospectively studied patients with clinically suspected VSA who underwent both SPT with intracoronary acetylcholine administration and CCTA within three months before SPT at Tsuchiura Kyodo General Hospital. PCAT inflammation was evaluated on CCTA images by fat attenuation index (FAI) which has been recently used as a novel biomarker of coronary inflammation. In FAI analysis, we measured FAI of the proximal segments not only for 4mm (FAI4mm) but also for the inner and thinner 2mm pericoronary adipose tissue layer from the vessel wall (FAI2mm), since FAI2mm has been reported to provide better discriminating efficacy for VSA diagnosis than FAI4mm. We also evaluated the presence or absence of MB and its features including length, depth and location on CCTA images. Results A total of 172 patients were studied and VSA was diagnosed in 39.0% (67/172) of patients by SPT according to the latest guideline. Male (74.6% vs 49.5%, P=0.001), smoking history (74.6% vs 48.6%, P=0.001) were more frequent, and prevalence of CCTA-defined MB (47.8% vs 34.3%, P=0.082) and RCA-FAI2mm (-68.73 HU vs -73.35 HU, P&amp;lt;0.001) were higher in patients with versus without VSA. In multivariable analysis, presence of CCTA-defined MB (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.26-5.19, P=0.0095), RCA-FAI2mm (OR 1.05, 95% CI 1.01-1.09, P=0.025), and smoking (OR 3.40, 95% CI 1.57-7.36, P=0.0019) were independently associated with VSA. A combination of high RCA-FAI2mm (≥-68.93HU, the best cut-off obtained by ROC analysis with AUC of 0.64, 95% CI 0.551 - 0.728), smoking history and existence of MB could predict VSA with 73.7% of probability, while an absence of all 3 covariates could exclude VSA with 85.3% of probability. Conclusion CCTA-defined MB, high RCA-FAI2mm and smoking were independently predictive of VSA.

The prognostic value of epicardial and pericoronary adipose tissue in heart failure with preserved ejection fraction using coronary computed tomography angiography.

To assess the prognostic significance of epicardial adipose tissue volume (EATv) and pericoronary adipose tissue attenuation (PCATa) in patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study was based on HFpEF and controls who underwent coronary CT angiography (CCTA) screening to rule out coronary disease. Comparisons of EATv and PCATa were made between HFpEF patients and a control group, using statistical analyses including Kaplan-Meier and Cox regression to assess prognostic significance. A total of 224 patients were retrospectively analysed. The EATv was 56.1 ± 11.9 cm3 and PCATa in the right coronary artery (PCATa-RCA) was -74.7 HU ± 3.82 in HFpEF patients, which increased significantly compared with controls. Among them, 112 HFpEF patients (mean age: 71.9 ± 8.5 years; 40% male) were followed up for a median of 27 ± 0.6 months (range 2-47 months). EATv and PCATa-RCA were predictive of outcome with an optimal threshold of 56.29 cm3 and -71.17 HU, respectively. In Kaplan-Meier analysis, the high EATv and PCATa-RCA attenuation had significantly higher rates of composite outcomes (log-rank test, all P < .01). EATv and PCATa-RCA were independently predictive of outcome following adjustment for confounding variables (EATv: hazard ratio [HR] 1.03; 95% CI (1.01-1.06); P < .01, PCTAa-RCA: HR 1.44; 95% CI 1.27-1.62; P < .001)). Increased EATv and PCATa-RCA are associated with worse clinical outcomes in HFpEF patients. This study highlights the potential of CCTA-derived adipose tissue metrics as novel, non-invasive biomarkers for risk stratification in HFpEF.

The pericoronary adipose tissue attenuation in CT strongly depends on kernels and iterative reconstructions.

To investigate the influence of kernels and iterative reconstructions on pericoronary adipose tissue (PCAT) attenuation in coronary CT angiography (CCTA). Twenty otherwise healthy subjects (16 females; median age 52 years) with atypical chest pain, low risk of coronary artery disease (CAD), and without CAD in photon-counting detector CCTA were included. Images were reconstructed with a quantitative smooth (Qr36) and three vascular kernels of increasing sharpness levels (Bv36, Bv44, Bv56). Quantum iterative reconstruction (QIR) was either switched-off (QIRoff) or was used with strength levels 2 and 4. The fat-attenuation-index (FAI) of the PCAT surrounding the right coronary artery was calculated in each dataset. Histograms of FAI measurements were created. Intra- and inter-reader agreements were determined. A CT edge phantom was used to determine the edge spread function (ESF) for the same datasets. Intra- and inter-reader agreement of FAI was excellent (intra-class correlation coefficient = 0.99 and 0.98, respectively). Significant differences in FAI were observed depending on the kernel and iterative reconstruction strength level (each, p < 0.001), with considerable inter-individual variation up to 34 HU and intra-individual variation up to 33 HU, depending on kernels and iterative reconstruction levels. The ESFs showed a reduced range of edge-smoothing with increasing kernel sharpness, causing an FAI decrease. Histogram analyses revealed a narrower peak of PCAT values with increasing iterative reconstruction levels, causing aFAI increase. PCAT attenuation determined with CCTA heavily depends on kernels and iterative reconstruction levels both within and across subjects. Standardization of CT reconstruction parameters is mandatory for FAI studies to enable meaningful interpretations. Question Do kernels and iterative reconstructions influence pericoronary adipose tissue (PCAT) attenuation in coronary CT angiography (CCTA)? Findings Significant differences in fat-attenuation-index (FAI) were observed depending on the kernel and iterative reconstruction strength level with considerable inter- and intra-individual variation. Clinical relevance PCAT attenuation heavily depends on kernels and iterative reconstructions requiring CT reconstruction parameter standardization to enable meaningful interpretations of fat-attenuation differences across subjects.

Clinical Applications and Advancements of Positron Emission Tomography/Computed Tomography in Cardio-Oncology: A Comprehensive Literature Review and Emerging Perspectives.

Recent advancements in molecular biology, biotechnology, chemistry/radiochemistry, artificial intelligence, and imaging techniques have significantly propelled the field of cardiovascular molecular imaging. This review aims to provide a comprehensive overview of the current state of cardiovascular positron emission tomography (PET) imaging and cardiac computed tomography (CT), exploring their roles in elucidating molecular and cellular processes, enabling early disease detection, and guiding novel therapeutic interventions for cardiovascular conditions. Cardiovascular PET imaging strives to uncover molecular and cellular events preceding visible anatomical manifestations or physiological changes. Meanwhile, cardiac CT has evolved into a multifaceted modality, offering insights into both anatomy and function. Utilizing advanced CT technologies allows for a thorough evaluation, encompassing fractional flow reserve, perfusion imaging, pericoronary adipose tissue attenuation, atherosclerotic plaque characterization, cardiomyopathies, structural cardiac abnormalities, and congenital heart anomalies. The emergence of hybrid imaging, combining PET and CT, presents innovative prospects in cardiology. This approach enables the simultaneous assessment of cardiac perfusion and coronary anatomy in a singular scan, providing complementary insights relevant to potential coronary artery disease. Despite the substantial potential impact, operational familiarity with this hybrid tool remains limited, and its integration into routine clinical practice warrants further exploration. In summary, the review underscores the transformative impact of recent technological advancements on cardiovascular molecular imaging. The integration of PET and CT, along with their individual capabilities, holds promise for early disease detection and informed clinical decision-making. While acknowledging the potential of hybrid imaging, it emphasizes the need for increased operational familiarity and continued exploration to facilitate its seamless integration into routine clinical practice. The insights gained from this review contribute to the ongoing dialogue in the field, offering a foundation for future research and advancements in cardiovascular imaging.

Relationship Between Calcified Plaque Burden, Vascular Inflammation, and Plaque Vulnerability in Patients With Coronary Atherosclerosis

BackgroundCoronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated. ObjectivesThis study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability. MethodsPatients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography–derived vulnerable features among the 4 groups. ResultsAmong 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB. ConclusionsGreater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)

Diagnosis of perimenopausal coronary heart disease patients using radiomics signature of pericoronary adipose tissue based on coronary computed tomography angiography

To assess whether the radiomics signature of pericoronary adipose tissue (PCAT) from coronary computed tomography angiography (CCTA) can distinguish between perimenopausal women with coronary heart disease (CHD) and those without coronary artery disease (CAD). This single-center retrospective case–control study comprised 140 perimenopausal women with CHD presenting with chest pain who underwent CCTA within 48 h of admission. They were matched with 140 control patients presenting with chest pain but without CAD, based on age, risk factors, radiation dose and CT tube voltage. For all participants, PCAT around the proximal right coronary artery was segmented, from which radiomics features and the fat attenuation index (FAI) were extracted and analyzed. Subsequently, corresponding models were developed and internally validated using Bootstrap methods. Model performance was assessed through measures of identification, calibration, and clinical utility. Using logistic regression analysis, an integrated model that combines clinical features, fat attenuation index and radiomics parameters demonstrated enhanced discrimination ability for perimenopausal CHD (area under the curve [AUC]: 0.80, 95% confidence interval [CI]:0.740–0.845). This model outperformed both the combination of clinical features and PCAT attenuation (AUC 0.67, 95% CI 0.602–0.727) and the use of clinical features alone (AUC 0.66, 95% CI 0.603–0.732). Calibration curves for the three predictive models indicated satisfactory fit (all p > 0.05). Moreover, decision curve analysis demonstrated that the integrated model offered greater clinical benefit compared to the other two models. The CCTA-based radiomics signature derived from the PCAT model outperforms the FAI model in differentiating perimenopausal CHD patients from non-CAD individuals. Integrating PCAT radiomics with the FAI could enhance the diagnostic accuracy for perimenopausal CHD.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Pericoronary adipose tissue for predicting long-term outcomes.

Pericoronary adipose tissue (PCAT) attenuation obtained by coronary computed tomography angiography (CCTA) has been associated with coronary inflammation and outcomes. Whether PCAT attenuation is predictive of major adverse cardiac events (MACE) during long-term follow-up is unknown. Symptomatic patients with coronary artery disease (CAD) who underwent CCTA were included, and clinical outcomes were evaluated. PCAT was measured at all lesions for all three major coronary arteries using semi-automated software. A comparison between patients with and without MACE was made on both a per-lesion and a per-patient level. The predictive value of PCAT attenuation for MACE was assessed in Cox regression models. In 483 patients (63.3 ± 8.5 years, 54.9% men), 1561 lesions were analysed over a median follow-up duration of 9.5 years. The mean PCAT attenuation was not significantly different between patients with and without MACE. At a per-patient level, the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE were 0.970 (95% CI: 0.933-1.008, P = 0.121) when the average of all lesions per patient was analysed, 0.992 (95% CI: 0.961-1.024, P = 0.622) when only the most obstructive lesion was evaluated, and 0.981 (95% CI: 0.946-1.016, P = 0.285) when only the lesion with the highest PCAT attenuation per individual was evaluated. Adjusted HRs for vessel-specific PCAT attenuation in the right coronary artery, left anterior descending artery, and left circumflex artery were 0.957 (95% CI: 0.830-1.104, P = 0.548), 0.989 (95% CI: 0.954-1.025, P = 0.550), and 0.739 (95% CI: 0.293-1.865, P = 0.522), respectively, in predicting long-term MACE. In patients referred to CCTA for clinically suspected CAD, PCAT attenuation did not predict MACE during long-term follow-up.

Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation

Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown. To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation. This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024. The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography). The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging. The 267 included patients had a mean age of 57.1 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% CI, 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right coronary artery and left anterior descending at baseline and follow-up. In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long term.

Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial—rationale and design

BackgroundCardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. MethodsEighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. ResultsAs of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1β, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. ConclusionEKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system. Trial registrationRegistry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www.clinicaltrials.gov/study/NCT06342609?term=EKSTROM&rank=1