The Relationship Between Obstructive Sleep Apnea and Coronary Plaque: A Coronary Computed Tomographic Angiography Study.

BACKGROUND: Coronary artery disease continues to be the most important cause of morbidity and mortality. Obstructive sleep apnea (OSA) is independently associated with subclinical atherosclerosis. In this study, we aimed to assess the relationship between the presence of coronary plaques and OSA and between coronary plaque burden and the severity of OSA according to plaque type. METHODS: In this cross-sectional study, we enrolled 214 consecutive patients who were divided into four groups of 43 patients (age: 52.3 ± 6.4 years) without OSA, 51 patients (age: 53.9 ± 6.7 years) with mild OSA, 40 patients (age: 55.2 ± 5.9 years) with moderate OSA, and 80 patients (age: 54.9 ± 7.2 years) with severe OSA according to the apnea-hypopnea index (AHI). We performed coronary computed tomographic angiography (CCTA) and evaluated plaque positivity, the presence of non-calcified/mixed plaques, and total stenosis score for each group. RESULTS: The prevalence of non-calcified/mixed plaques was three times higher in the severe OSA (41.3%) group and two times higher in the moderate OSA (30.0%) group compared to the patients without OSA (14.0%). When the four groups were examined in terms of plaque burden, the total stenosis score was found to increase with the presence and severity of OSA (0.27 ± 0.85, 1.07 ± 2.44, 1.75 ± 2.85, and 2.55 ± 3.96 respectively, p = 0.001). In addition, AHI and age were independent predictors of the presence of non-calcified/mixed plaques (p < 0.001 and p = 0.007, respectively). CONCLUSIONS: The presence of coronary artery plaques, especially non-calcified/mixed plaques, and coronary artery stenosis as measured by CCTA was significantly associated with the severity of sleep-disordered breathing in symptomatic patients at low to intermediate risk of coronary artery disease. Prospective studies are needed to establish the relationship between plaque burden and OSA.

Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis.

AIMS: Cholesterol efflux capacity (CEC) was recently shown to predict future cardiovascular (CV) events. Psoriasis both increases CV risk and impairs CEC. However, whether having poor CEC is associated with coronary plaque burden is currently unknown. We aimed to assess the cross-sectional relationship between coronary plaque burden assessed by quantitative coronary computed tomography angiography (CCTA) with CEC in a well-phenotyped psoriasis cohort. METHODS AND RESULTS: Total burden and non-calcified burden (NCB) plaque indices were assessed in 101 consecutive psoriasis patients using quantitative software. Cholesterol efflux capacity was quantified using a cell-based ex vivo assay measuring the ability of apoB-depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Cholesterol efflux capacity was inversely correlated with NCB (unadjusted ß-coefficient -0.33; P < 0.001), and this relationship persisted after adjustment for CV risk factors (ß -0.24; P < 0.001), HDL-C levels (ß -0.22; P < 0.001), and apoA1 levels (ß -0.19; P < 0.001). Finally, we observed a significant gender interaction (P < 0.001) whereby women with low CEC had higher NCB compared to men with low CEC. CONCLUSIONS: We show that CEC is inversely associated with prevalent coronary plaque burden measured by quantitative CCTA. Low CEC may therefore be an important biomarker for subclinical coronary atherosclerosis in psoriasis. CLINICALTRIALSGOV: NCT01778569.

Pericardial fat volume and coronary risk factors as predictors of non-calcified coronary plaque presence among patients with coronary calcium score = 0.

INTRODUCTION: There is scarce data linking pericardial fat volume (PFV) and classical coronary risk factors with non-calcified plaque presence among patients with CAC = 0 in the literature. MATERIAL AND METHOD: A total of 811 patients with chest pain suggestive of angina underwent CT coronary angiography for the assessment of coronary artery disease were collected. Of these, 417 with CAC = 0 were included in the analysis. RESULT: Patients with non-calcified plaque were older (54 ± 9 versus 50 ± 10, P = 0.01) and had a higher prevalence of diabetes mellitus (31% versus 17%, P = 0.02), high BMI (29.9 versus 28.3, P = 0.04), and increased PFV (123 cm3 versus 99 cm3, P < 0.01) compared to patients without plaque. In multivariate regression analysis, high BMI[OR(CI) = 1.1(1-1.3), P = 0.02] was an independent predictor of non-calcified coronary plaque presence among patients with CAC = 0 after adjustment to variables with P < 0.05 in the univariate analysis. CONCLUSION: In patients with a CAC score of 0, advanced age, diabetes mellitus, increased PFV, and high BMI were all associated with the presence of non-calcified plaque. After multivariate adjustment, increased BMI remained a significant independent predictor for non-calcified plaque presence.

Non-calcified plaque in asymptomatic patients with zero coronary artery calcium score: A systematic review and meta-analysis.

BACKGROUND: There is growing interest in understanding the coronary atherosclerotic burden in asymptomatic patients with zero coronary artery calcium score (CACS). In this population, we aimed to investigate the prevalence and severity of non-calcified coronary plaques (NCP) as detected by coronary CT angiography (CCTA), and to analyze the associated clinical predictors. METHODS: This was a systematic review with meta-analysis of studies indexed in PubMed/Medline and Web of Science from inception of the database to March 31st, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I2 statistics whilst Funnel plots and Egger's test were used to assess for publication bias. RESULTS: From a total of 14 studies comprising 37808 patients, we approximated the pooled summary estimates for the overall prevalence of NCP to be 10% (95%CI: 6%-13%). Similarly, the pooled prevalence of obstructive NCP was estimated at 1.1% (95%CI: 0.7%-1.5%) from a total of 10 studies involving 21531 patients. Hypertension [OR: 1.46 (95%CI:1.31-1.62)] and diabetes mellitus [OR: 1.69 (95%CI: 1.41-1.97)] were significantly associated with developing any NCP, with male gender being the strongest predictor [OR: 3.22 (95%CI: 2.17-4.27)]. CONCLUSION: There is a low burden of NCP among asymptomatic subjects with zero CACS. In a subset of this population who have clinical predictors of NCP, the addition of CCTA has a potential to provide a better insight about occult coronary atherosclerosis, however, a risk-benefit approach must be factored in prior to CCTA use given the low prevalence of NCP.

Non-calcified plaque-based coronary stenosis grading in contrast enhanced CT.

BACKGROUND: The high mortality rate associated with coronary heart disease has led to state-of-the-art non-invasive methods for cardiac diagnosis including computed tomography and magnetic resonance imaging. However, stenosis computation and clinical assessment of non-calcified plaques has been very challenging due to their ambiguous intensity response in CT i.e. a significant overlap with surrounding muscle tissues and blood. Accordingly, this research presents an approach for computation of coronary stenosis by investigating cross-sectional lumen behaviour along the length of 3D coronary segments. METHODS: Non-calcified plaques are characterized by comparatively lower-intensity values with respect to the surrounding. Accordingly, segment-wise orthogonal volume was reconstructed in 3D space using the segmented coronary tree. Subsequently, the cross sectional volumetric data was investigated using proposed CNN-based plaque quantification model and subsequent stenosis grading in clinical context was performed. In the last step, plaque-affected orthogonal volume was further investigated by comparing vessel-wall thickness and lumen area obstruction w.r.t. expert-based annotations to validate the stenosis grading performance of model. RESULTS: The experimental data consists of clinical CT images obtained from the Rotterdam CT repository leading to 600 coronary segments and subsequent 15786 cross-sectional images. According to the results, the proposed method quantified coronary vessel stenosis i.e. severity of the non-calcified plaque with an overall accuracy of 83%. Moreover, for individual grading, the proposed model show promising results with accuracy equal to 86%, 90% and 79% respectively for severe, moderate and mild stenosis. The stenosis grading performance of the proposed model was further validated by performing lumen-area versus wall-thickness analysis as per annotations of manual experts. The statistical results for lumen area analysis precisely correlates with the quantification performance of the model with a mean deviation of 5% only. CONCLUSION: The overall results demonstrates capability of the proposed model to grade the vessel stenosis with reasonable accuracy and precision equivalent to human experts.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

AIMS: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. CONCLUSION: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

Special Report on the Consensus QIBA Profile for Objective Analytical Validation of Non-calcified and High-risk Plaque and Other Biomarkers using Computed Tomography Angiography.

RATIONALE AND OBJECTIVES: Evidence is building in support of the clinical utility of atherosclerotic plaque imaging by computed tomography angiography (CTA). There is increasing organized activity to embrace non-calcified plaque (NCP) as a formally defined biomarker for clinical trials, and high-risk plaque (HRP) for clinical care, as the most relevant measures for the field to advance and worthy of community efforts to validate. Yet the ability to assess the quantitative performance of any given specific solution to make these measurements or classifications is not available. Vendors use differing definitions, assessment metrics, and validation data sets to describe their offerings without clinician users having the capability to make objective assessments of accuracy and precision and how this affects diagnostic confidence. MATERIALS AND METHODS: The QIBA Profile for Atherosclerosis Biomarkers by CTA was created by the Quantitative Imaging Biomarkers Alliance (QIBA) to improve objectivity and decrease the variability of noninvasive plaque phenotyping. The Profile provides claims on the accuracy and precision of plaque measures individually and when combined. RESULTS: Individual plaque morphology measurements are evaluated in terms of bias (accuracy), slope (consistency of the bias across the measurement range, needed for measurements of change), and variability. The multiparametric plaque stability phenotype is evaluated in terms of agreement with expert pathologists. The Profile is intended for a broad audience, including those engaged in discovery science, clinical trials, and patient care. CONCLUSION: This report provides a rationale and overview of the Profile claims and how to comply with the Profile in research and clinical practice. SUMMARY STATEMENT: This article summarizes objective means to validate the analytical performance of non-calcified plaque (NCP), other emerging plaque morphology measurements, and multiparametric histology-defined high-risk plaque (HRP), as outlined in the QIBA Profile for Atherosclerosis Biomarkers by CTA.

Testosterone therapy and the risk of cardiovascular disease in older, hypogonadal men.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study.

AIM: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). METHODS: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. RESULTS: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001). CONCLUSION: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. GERMAN CLINICAL TRIALS REGISTER: DRKS00031954.

Case report: Strong low-density-cholesterol reduction accompanied by shrinkage of low-attenuation coronary plaque during lipid-lowering treatment with bempedoic acid-serial evaluation by coronary computed tomography angiography.

Here, we present a patient with coronary artery disease and prior percutaneous coronary interventions. This patient had to discontinue taking multiple statins and ezetimibe due to intolerance with musculoskeletal complaints and nausea. Monotherapy with bempedoic acid was well tolerated and was exceptionally effective at lipid lowering, enabling patients to achieve the low-density lipoprotein target of <55 mg/dl, as recommended by current guidelines. In addition, serial coronary computed tomography angiography performed upon clinical indications, during 20 months of lipid-lowering treatment with bempedoic acid, demonstrated signs of favorable plaque component modification, with shrinkage of the low-attenuation plaque component compared to baseline findings.

Predictors of non-calcified plaque presence and future adverse cardiovascular events in symptomatic rural Appalachian patients with a zero coronary artery calcium score.

BACKGROUND: Coronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment. METHODS: A retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years. RESULTS: Based on logistic regression, age (OR 1.039, 95% CI [1.020-1.058], p â€‹< â€‹0.001), diabetes mellitus (OR 2.192, 95% CI [1.307-3.676], p â€‹< â€‹0.003), tobacco use (OR 1.748, 95% CI [1.157-2.643], p â€‹< â€‹0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003-1.015], p â€‹< â€‹0.002), and hypertension (OR 1.613, 95% CI [1.024-2.540], p â€‹< â€‹0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p â€‹< â€‹0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26-128.26], p â€‹< â€‹0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025-4.627], p â€‹< â€‹0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. CONCLUSION: NCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Clinical feasibility of using effective atomic number maps derived from non-contrast spectral computed tomography to identify non-calcified atherosclerotic plaques: a preliminary study.

Background: To assess the clinical feasibility of using effective atomic number (Zeff) maps derived from non-contrast-enhanced computed tomography (NCECT) scans obtained by dual-layer spectral computed tomography (DLCT) to identify non-calcified atherosclerotic plaques. Methods: A total of 37 patients with 86 non-calcified atherosclerotic plaques confirmed by contrast-enhanced CT (CECT) were enrolled in this retrospective study. Both spectral-based-images (SBI) and conventional images (CI) were reconstructed from NCECT and CECT scans. The presence of plaques on NCECT Zeff maps and CIs were independently assessed by 2 radiologists. In CECT scans, plaques and regions of interest (ROIs) in vessel lumens were assessed with CT attenuation and Zeff values, and the proportion of plaques was determined as Area (plaque)/Area (vessel). The CT and Zeff values for plaques and blood were recorded from both CECT and NCECT scans. Contrast-to-noise ratios (CNRs) of the plaques were calculated and compared using CT attenuation and Zeff values. Finally, interobserver agreement was evaluated. Results: A total of 47 of the 86 (54.7%) plaques were identified on Zeff map images derived from the NCECT scans while only 7 (8.1%) plaques were identified on the CI. There was no significant difference between the mean vessel ROI area measured on CIs and that measured on Zeff map images (502.19 vs. 498.14 mm2; P=0.28), while the mean plaque ROI area was larger (81.45 vs. 75.46 mm2). The observer consensus of vessel and plaque ROI area measurements using both methods was excellent, with interclass correlation coefficients (ICCs) of 0.99 and 0.94, respectively. For the 7 plaques detected both by NCECT CI and Zeff mapping, the CT attenuation and Zeff blood values were both larger than the plaque values [42.00 vs. 25.67 Hounsfield unit (HU); 7.33 vs. 7.19 HU; both P<0.05]; the plaque ROI area measurement on the NCE Zeff map was smaller than that on the CE CI (48.73 vs. 77.76 mm2), but was much larger than that on the NCE CI (18.39 mm2). For all 47 plaques detected by NCE Zeff mapping, the CT attenuation and Zeff values of blood and plaques on the NCECT images showed no significant differences (42.53 vs. 35.14 HU; P=0.18; 7.32 vs. 7.31, P=0.71); however, the CNR of Zeff was significantly higher than the CT attenuation value (1.69 vs. 1.12; P<0.05) derived from the NCECT scans. Inter-reviewer agreement was good (ICC =0.78). Conclusions: Zeff map images derived from NCECT SBI with DLCT provide a potentially feasible approach for identifying non-calcified atherosclerotic plaques, which might be clinically useful for the screening of asymptomatic at-risk patients.

Non-contrast CT-based radiomic signature of pericoronary adipose tissue for screening non-calcified plaque.

Objective.To develop two combined clinical-radiomics models of pericoronary adipose tissue (PCAT) for the presence and characterization of non-calcified plaques on non-contrast CT scan.Approach.Altogether, 431 patients undergoing Coronary Computed Tomography Angiography from March 2019 to June 2021 who had complete data were enrolled, including 173 patients with non-calcified plaques of the right coronary artery(RCA) and 258 with no abnormality. PCAT was segmented around the proximal RCA on non-contrast CT scan (calcium score acquisition). Two best models were established by screening features and classifiers respectively using FeAture Explorer software. Model 1 distinguished normal coronary arteries from those with non-calcified plaques, and model 2 distinguished vulnerable plaques in non-calcified plaques. Performance was assessed by the area under the receiver operating characteristic curve (AUC-ROC).Main results.4 and 9 features were selected for the establishment of the radiomics model respectively through Model 1 and 2. In the test group, the AUC values, sensitivity, specificity and accuracy were 0.833%, 78.3%, 80.8%, 76.6% and 0.7467%, 75.0%, 77.8%, 73.5%, respectively. The combined model including radiomics features and independent clinical factors yielded an AUC, sensitivity, specificity and accuracy of 0.896%, 81.4%, 86.5%, 77.9% for model 1 and 0.752%, 75.0%, 77.8%, 73.5% for model 2.Significance.The combined clinical-radiomics models based on non-contrast CT images of PCAT had good diagnostic efficacy for non-calcified and vulnerable plaques.

Synergistic value of fractional flow reserve and low­density non­calcified plaque based on coronary computed tomography angiography for the identification of lesion­specific ischemia.

Increasing evidence has suggested that plaque characteristics are closely associated with ischemia, and coronary computed tomography (CT) angiography-derived fractional flow reserve (FFRCT) based on deep machine learning algorithms has also been used to identify lesion-specific ischemia. Therefore, the aim of the present study was to explore the predictive ability of plaque characteristics in combination with deep learning-based FFRCT for lesion-specific ischemia. To meet this end, invasive FFR was used as a reference standard, with the joint aims of the early prediction of ischemic lesions and guiding clinical treatment. In the present study, the plaque characteristics, including non-calcified plaque (NCP), low-density NCP (LD-NCP), plaque length, total plaque volume (TPV), remodeling index, calcified plaque, fibrous plaque and plaque burden, were obtained using a semi-automated program. The FFRCT values were derived based on a deep machine learning algorithm. On the basis of the data obtained, differences among the values between the atopic ischemia and the non-significant lesions groups were analyzed to further determine the predictive value of independent predictors for atopic ischemia. Of the plaque features, FFRCT, LD-NCP, NCP, TPV and plaque length differed significantly when comparing between the lesion-specific ischemia and no hemodynamic abnormality groups, and LD-NCP and FFRCT were both independent predictors for ischemia. Additionally, FFRCT combined with LD-NCP showed a greater ability at discriminating ischemia compared with FFRCT or LD-NCP alone. Taken together, the findings of the present study suggest that the combination of FFRCT and LD-NCP has a synergistic effect in terms of predicting ischemia, thereby facilitating the identification of specific ischemia in patients with coronary artery disease.

The association of coronary non-calcified plaque loading based on coronary computed tomography angiogram and adverse cardiovascular events in patients with unstable coronary heart disease-a retrospective cohort study.

Background: Coronary computed tomography angiogram (CCTA) has the characteristics of non-invasive, high resolution, and can accurately determine the characteristics of tubular wall plaques. The non-calcified plaque loading of the coronary arteries is unstable and prone to shedding, leading to adverse cardiovascular events. However, few studies focused on the predictive value of non-calcified plaque loading for adverse cardiovascular events in patients with unstable coronary heart disease (CHD). The present study was conducted to investigate the association of coronary non-calcified plaque loading based on CCTA and adverse cardiovascular events in patients with unstable CHD. Methods: A total of 206 patients with unstable CHD were collected and followed up for 1 year. The patients were divided into an observation group (n=56) and a control group (n=150) according to whether adverse cardiovascular events occurred or not. We analyzed the predictive value of coronary artery non-calcified plaque loading for adverse cardiovascular events in unstable CHD using receiver operating characteristic and multivariate logistics regression analysis. Results: Compared with the control group, the non-calcified plaque volume in the observation group was increased (160.10±44.02 vs. 128.06±42.22 mm3, P=0.000); non-calcified plaque loading increased (26.93%±7.98% vs. 21.46%±7.62%, P=0.000); carotid intima-media thickness increased (1.49±0.17 vs. 1.40%±0.18 mm, P=0.001); and left ventricular ejection fraction (LVEF) was significantly reduced (53.28%±7.39% vs. 58.02%±7.91%, P=0.000). Non-calcified plaque volume and non-calcified plaque loading have certain diagnostic value for recurrence of adverse cardiovascular events within 1 year (P<0.05). A non-calcified plaque volume >145.58 mm3 is a risk factor for recurrence of adverse cardiovascular events (P<0.05). Conclusions: Increased non-calcified plaque volume in patients with unstable CHD is associated with the development of adverse cardiovascular events in patients with unstable CHD.

Repeatability of quantitative pericoronary adipose tissue attenuation and coronary plaque burden from coronary CT angiography.

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.

A three-dimensional quantification of calcified and non-calcified plaques in coronary arteries based on computed tomography coronary angiography images: Comparison with expert's annotations and virtual histology intravascular ultrasound.

The detection, quantification and characterization of coronary atherosclerotic plaques has a major effect on the diagnosis and treatment of coronary artery disease (CAD). Different studies have reported and evaluated the noninvasive ability of Computed Tomography Coronary Angiography (CTCA) to identify coronary plaque features. The identification of calcified plaques (CP) and non-calcified plaques (NCP) using CTCA has been extensively studied in cardiovascular research. However, NCP detection remains a challenging problem in CTCA imaging, due to the similar intensity values of NCP compared to the perivascular tissue, which surrounds the vasculature. In this work, we present a novel methodology for the identification of the plaque burden of the coronary artery and the volumetric quantification of CP and NCP utilizing CTCA images and we compare the findings with virtual histology intravascular ultrasound (VH-IVUS) and manual expert's annotations. Bland-Altman analyses were employed to assess the agreement between the presented methodology and VH-IVUS. The assessment of the plaque volume, the lesion length and the plaque area in 18 coronary lesions indicated excellent correlation with VH-IVUS. More specifically, for the CP lesions the correlation of plaque volume, lesion length and plaque area was 0.93, 0.84 and 0.85, respectively, whereas the correlation of plaque volume, lesion length and plaque area for the NCP lesions was 0.92, 0.95 and 0.81, respectively. In addition to this, the segmentation of the lumen, CP and NCP in 1350 CTCA slices indicated that the mean value of DICE coefficient is 0.72, 0.7 and 0.62, whereas the mean HD value is 1.95, 1.74 and 1.95, for the lumen, CP and NCP, respectively.

Sex-related differences in the association between plasma fibrinogen and non-calcified or mixed coronary atherosclerotic plaques.

BACKGROUND: Plasma fibrinogen (FIB) has been demonstrated to be a risk factor for cardiovascular disease. Patients with non-calcified plaque (NCP) or mix plaque (MP) have a higher risk of poor outcomes. However, the association between FIB and the presence of NCP or MP (NCP/MP) remains unclear, and if present, whether sex has any impact on this association remains unknown. The aim of this study was to investigate the role of FIB in predicting the presence of NCP/MP and evaluate whether sex has any impact on this association. METHODS: A total of 329 subjects were recruited, and the clinical and laboratory data were collected. Plasma FIB was detected by enzyme-linked immunosorbent assay. According to whether they had coronary atherosclerotic plaques and the characteristics of the most stenotic plaque, we divided them into three groups: no plaque (NP), calcified plaque (CP), and NCP/MP. RESULTS: Patients with NCP/MP had significantly higher FIB level in females, but not in males. Multiple logistic regression analysis showed that FIB was an independent risk factor for the presence of NCP/MP (odds ratio [OR] = 3.677, 95% CI 1.539-8.785, P = 0.003) in females. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value FIB for predicting the presence of NCP/MP was 3.41 g/L (area under curve [AUC] = 0.73, 95% CI 0.63-0.82, P <  0.001) in females. CONCLUSIONS: FIB is independently associated with the presence of NCP/MP in females, but not in males. These results suggest that the potential significance of FIB-lowering regimens in females with NCP/MP.

The effect of heart rate on coronary plaque measurements in 320-row coronary CT angiography.

Repeatability of quantitative assessment of atherosclerotic plaques is important for the accurate detection of high-risk plaques in coronary CT angiography (CTA). We assessed the effect of heart rate (HR) on plaque CT number using a coronary artery model and a cardiac phantom capable of simulating cardiac motion. The coronary artery model with luminal stenosis on a cardiac phantom was imaged with a simulated HR of 0, 50, 60, and 70 beats per minute using a 320-row CT scanner. We reconstructed CT images for cardiac diastolic phases (for 75% R-R interval) using filtered back projection (FBP), hybrid iterative reconstruction (AIDR3D), and model-based iterative reconstruction (FIRST). Two observers measured plaque attenuation in the lesion with 75% stenosis. The coefficient of determination (R2) was obtained to evaluate interobserver agreement. At HR 70, FIRST improved the correlation between two observers compared with FBP and AIDR3D (FIRST: R2 = 0.68, p < 0.05; FBP: R2 = 0.29, p = 0.31; AIDR3D: R2 = 0.22, p = 0.18). These R2 at HR 70 were lower compared with at HR 50 (FIRST: R2 = 0.92, p < 0.05; FBP: R2 = 0.83, p < 0.05; AIDR3D: R2 = 0.87, p < 0.05) and HR 0 (FIRST: R2 = 0.97, p < 0.05; FBP: R2 = 0.89, p < 0.05; AIDR3D: R2 = 0.95, p < 0.05). Higher HR affected plaque measurement repeatability in coronary CTA. FIRST may improve plaque measurement repeatability at the higher HR compared with FBP and AIDR3D.