Non-calcified Plaque Research Articles

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

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). 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. 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.

Impact of visceral fat on coronary artery disease as defined by quantitative computed tomography angiography.

Obesity is associated with all-cause mortality and cardiovascular disease (CVD). Visceral fat (VF) is an important CVD risk metric given its independent correlation with myocardial infarction and stroke. This study aims to clarify the relationship between the presence and severity of VF with the presence and severity of coronary artery plaque. In 145 consecutive asymptomatic patients, atherosclerosis imaging-quantitative computed tomography was performed for total plaque volume (TPV) and percentage atheroma volume, as well as the volume of noncalcified plaque (NCP), calcified plaque, and low-density NCP (LD-NCP), diameter stenosis, and vascular remodeling. This study also included VF analysis and subcutaneous fat analysis, recording of outer waist circumference, and percentage body fat analysis. The mean age of the patients was 56.1 [SD 8.5] years, and 84.0% were male. Measures of visceral adiposity (mean [SD, Q1-Q3 thresholds]) included estimated body fat, 28.7% (9.0%, 24.1%-33.0%); VF, 169.8 cm2 (92.3, 102.0-219.0 cm2 ); and subcutaneous fat, 223.6 mm2 (114.2, 142.5-288.0 mm2 ). The Spearman correlation coefficients of VF and plaque volume included TPV 0.22 (p = 0.0074), calcified plaque 0.12 (p = 0.62), NCP 0.25 (p = 0.0023), and LD-NCP 0.37 (p < 0.0001). There was a progression of the median coronary plaque volume for each quartile of VF including TPV (Q1: 19.8, Q2: 48.1, Q3: 86.4, and Q4: 136.6 mm3 [p = 0.0098]), NCP (Q1: 15.7, Q2: 35.4, Q3: 86.4, and Q4: 136.6 mm3 [p = 0.0032]), and LD-NCP (Q1: 0.6, Q2: 0.81, Q3: 2.0, and Q4: 5.0 mm3 [p < 0.0001]). These findings demonstrate progression with regard to VF and TPV, NCP volume, and LD-NCP volume. Notably, there was a progression of VF and amount of LD-NCP, which is known to be high risk for future cardiovascular events. A consistent progression may indicate the future utility of VF in CVD risk stratification.

Relation of Gender to Atherosclerotic Plaque Characteristics by Differing Angiographic Stenosis Severity

It is unknown whether gender influences the atherosclerotic plaque characteristics (APCs) of lesions of varying angiographic stenosis severity. This study evaluated the imaging data of 303 symptomatic patients from the derivation arm of the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial, all of whom underwent coronary computed tomographic angiography and clinically indicated nonemergent invasive coronary angiography upon study enrollment. Index tests were interpreted by 2 blinded core laboratories, one of which performed quantitative coronary computed tomographic angiography using an artificial intelligence application to characterize and quantify APCs, including percent atheroma volume (PAV), low-density noncalcified plaque (LD-NCP), noncalcified plaque (NCP), calcified plaque (CP), lesion length, positive arterial remodeling, and high-risk plaque (a combination of LD-NCP and positive remodeling ≥1.10); the other classified lesions as obstructive (≥50% diameter stenosis) or nonobstructive (<50% diameter stenosis) based on quantitative invasive coronary angiography. The relation between APCs and angiographic stenosis was further examined by gender. The mean age of the study cohort was 64.4±10.2years (29.0% female). In patients with obstructive disease, men had more LD-NCP PAV (0.5±0.4 vs 0.3±0.8, p=0.03) and women had more CP PAV (11.7±1.6 vs 8.0±0.8, p=0.04). Obstructive lesions had more NCP PAV compared with their nonobstructive lesions in both genders, however, obstructive lesions in women also demonstrated greater LD-NCP PAV (0.4±0.5 vs 1.0±1.8, p=0.03), and CP PAV (17.4±16.5 vs 25.9±18.7, p=0.03) than nonobstructive lesions. Comparing the composition of obstructive lesions by gender, women had more CP PAV (26.3±3.4 vs 15.8±1.5, p=0.005) whereas men had more NCP PAV (33.0±1.6 vs 26.7±2.5, p=0.04). Men had more LD-NCP PAV in nonobstructive lesions compared with women (1.2±0.2 vs 0.6±0.2, p=0.02). In conclusion, there are gender-specific differences in plaque composition based on stenosis severity.

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

BackgroundCoronary 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. MethodsA 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. ResultsBased on logistic regression, age (OR 1.039, 95% CI [1.020–1.058], p ​< ​0.001), diabetes mellitus (OR 2.192, 95% CI [1.307–3.676], p ​< ​0.003), tobacco use (OR 1.748, 95% CI [1.157–2.643], p ​< ​0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003–1.015], p ​< ​0.002), and hypertension (OR 1.613, 95% CI [1.024–2.540], p ​< ​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 ​< ​0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26–128.26], p ​< ​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 ​< ​0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. ConclusionNCP 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.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial

BackgroundPositron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). MethodsThis post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. ResultsIn 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = − 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). ConclusionIn patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Interplay Between Zero CAC, Quantitative Plaque Analysis, and Adverse Events in a Diverse Patient Cohort.

Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis. We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death. A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median age of those without CAC was 52 years (interquartile range, 44-59) and 60 years (interquartile range, 53-68) in those with CAC. Most patients were Hispanic (58%), and the rest were non-Hispanic Black (28%), non-Hispanic White (10%), and non-Hispanic Asian (5%). The majority had CAC=0 (55%). The negative predictive value of CAC=0 was 92.8%, 99.9%, and 99.9% for any plaque, obstructive coronary artery stenosis, and the composite outcome of all-cause death, myocardial infarction, or coronary revascularization, respectively. Among patients without CAC (n=1237), 89 patients (7%) had evidence of plaque on their coronary computed tomography angiography with a median low-attenuation noncalcified plaque burden of 4% (2-7). There were no significant differences in the negative predictive value for CAC=0 by sex, race, or ethnicity. Patients with ≥2 risk factors had higher odds of having plaque with zero CAC. In summary, no sex, race, or ethnicity differences were demonstrated in the negative predictive value of a zero CAC; however, patients with ≥2 risk factors had a higher prevalence of plaque. A small percentage (7%) of symptomatic patients undergoing coronary computed tomography angiography with zero CAC had noncalcified coronary plaque, with the implication that caution is needed for downscaling of preventive treatment in patients with zero CAC, chest pain, and multiple risk factors.

Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥ 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07–1.24), coronary diameter stenosis ≥ 50% (OR 1.27, 95% CI 1.09–1.47), ≥ 4 segments involved (OR 1.13, 95% CI 1.01–1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05–1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02–1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

Impact of virtual monoenergetic levels on coronary plaque volume components using photon-counting computed tomography

ObjectivesVirtual monoenergetic images (VMIs) from photon-counting CT (PCCT) may change quantitative coronary plaque volumes. We aimed to assess how plaque component volumes change with respect to VMIs.MethodsCoronary CT angiography (CTA) images were acquired using a dual-source PCCT and VMIs were reconstructed between 40 and 180 keV in 10-keV increments. Polychromatic images at 120 kVp (T3D) were used as reference. Quantitative plaque analysis was performed on T3D images and segmentation masks were copied to VMI reconstructions. Calcified plaque (CP; > 350 Hounsfield units, HU), non-calcified plaque (NCP; 30 to 350 HU), and low-attenuation NCP (LAP; − 100 to 30 HU) volumes were calculated using fixed thresholds.ResultsWe analyzed 51 plaques from 51 patients (67% male, mean age 65 ± 12 years). Average attenuation and contrast-to-noise ratio (CNR) decreased significantly with increasing keV levels, with similar values observed between T3D and 70 keV images (299 ± 209 vs. 303 ± 225 HU, p = 0.15 for mean HU; 15.5 ± 3.7 vs. 15.8 ± 3.5, p = 0.32 for CNR). Mean NCP volume was comparable between T3D and 100–180-keV reconstructions. There was a monotonic decrease in mean CP volume, with a significant difference between all VMIs and T3D (p < 0.05). LAP volume increased with increasing keV levels and all VMIs showed a significant difference compared to T3D, except for 50 keV (28.0 ± 30.8 mm3 and 28.6 ± 30.1 mm3, respectively, p = 0.63).ConclusionsEstimated coronary plaque volumes significantly differ between VMIs. Normalization protocols are needed to have comparable results between future studies, especially for LAP volume which is currently defined using a fixed HU threshold.Clinical relevance statementDifferent virtual monoenergetic images from photon-counting CT alter attenuation values and therefore corresponding plaque component volumes. New clinical standards and protocols are required to determine the optimal thresholds to derive plaque volumes from photon-counting CT.Key Points• Utilizing different VMI energy levels from photon-counting CT for the analysis of coronary artery plaques leads to substantial changes in attenuation values and corresponding plaque component volumes.• Low-energy images (40–70 keV) improved contrast-to-noise ratio, however also increased image noise.• Normalization protocols are needed to have comparable results between future studies, especially for low-attenuation plaque volume which is currently defined using a fixed HU threshold.

Accuracy and limitation of plaque detection by coronary CTA: a section-to-section comparison with optical coherence tomography

Plaques identified by Coronary CT angiography (CCTA) are important in clinical diagnosis and primary prevention. High-risk plaque features by CCTA have been extensively validated using optical coherence tomography (OCT). However, since their general diagnostic performance and limitations have not been fully investigated, we sought to compare CCTA with OCT among consecutive vessel sections. We retrospectively compared 188 consecutive plaques and 84 normal sections in 41 vessels from 40 consecutive patients referred for chest pain evaluation who had both CCTA and OCT with a median time lapse of 1 day. The distance to reference points were used to co-register between the modalities and the diagnostic performance of CCTA was evaluated against OCT. Plaque categories evaluated by CT were calcified, non-calcified and mixed. The diagnostic performance of CCTA was excellent for detecting any plaque identified by OCT with the sensitivity, specificity, negative and positive predictive values and accuracy of 92%, 98%, 99%, 84% and 93%, respectively. The lower than expected negative predictive value was due to failure of detecting sub-millimeter calcified (≤ 0.25 mm2) (N = 12) and non-calcified plaques (N = 4). Misclassification of plaque type accounted for majority of false negative findings (25/41, 61%) which was most prevalent among the mixed plaque (19/41, 46%). There was calcification within mixed plaques (N = 5) seen by CCTA but missed by OCT. Our findings suggest that CCTA is excellent at identifying coronary plaques except those sub-millimeter in size which likely represent very early atherosclerosis, although the clinical implication of very mild atherosclerosis is yet to be determined.

One-step integrated coronary–carotid–cerebral computed tomography angiography to evaluate cardiovascular and cerebrovascular atherosclerosis

PurposeThis study aims to develop a low-radiation dose, one-step integrated coronary–carotid–cerebral computed tomography angiography (ICCC-CTA) technique to analyze the relationship between cardiovascular and cerebrovascular atherosclerosis and evaluate the risk factors of plaque to provide an early-stage treatment to patients and reduce vascular events.MethodsA total of 300 consecutive asymptomatic patients with cardiovascular risk factors who underwent ICCC-CTA were enrolled in this prospective study. The association between coronary and carotid-cerebrovascular atherosclerosis was assessed. The primary cardiovascular risk factors for various plaque types in cardiovascular or cerebrovascular disease were evaluated using multivariate analysis.ResultsAmong 300 patients, 189 (63%) had plaques in their coronary and cerebral arteries. The presence of calcified and mixed plaques in the carotid-cerebral and coronary arteries was strongly correlated (χ2 = 20.71, P = 0.001; χ2 = 8.96, P = 0.003, respectively). Multivariate logistic regression analysis revealed that abnormal blood glucose [OR = 1.44, 95% CI 0.12–0.62, P = 0.01] and abnormal total cholesterol [OR = 1.28, 95% CI 0.07–0.46, P = 0.01] are risk factors in all the models in the coronary artery, non-calcified plaque group. Abnormal blood glucose [OR = 1.43, 95% CI 0.11–0.61, P = 0.01] and abnormal systolic blood pressure [OR = 1.02, 95% CI 0.01–0.04, P = 0.02] are risk factors in all the models in the coronary artery calcified plaque group. Abnormal blood glucose level [OR = 1.44, 95% CI = 0.12–0.62, P = 0.01] was only a risk factor in the non-calcified plaque carotid–cerebral artery group.ConclusionsWe confirm that elevated blood glucose and total cholesterol levels are associated with coronary and carotid-cerebrovascular plaques using the novel one-step low dose cerebral-carotid-cardiac CTA technique. These findings will provide insights for further studies focusing on developing low-radiation dose one-step ICCC-CTA to screen cardiovascular/cerebrovascular plaques in general population with cardiovascular risk factors.Advances in knowledgeWe developed a low–radiation dose, one-step ICCC-CTA technique to detect cardiovascular and cerebrovascular atherosclerosis. We evaluated the risk factors for plaque burden for the early treatment and reduction of vascular events. These findings supported the development of low–radiation dose one-step ICCC-CTA to screen for cardiovascular/cerebrovascular disease in general population with cardiovascular risk factors.

AI-Guided Quantitative Plaque Staging Predicts Long-Term Cardiovascular Outcomes in Patients at Risk for Atherosclerotic CVD

BackgroundThe recent development of artificial intelligence–guided quantitative coronary computed tomography angiography analysis (AI-QCT) has enabled rapid analysis of atherosclerotic plaque burden and characteristics. ObjectivesThis study set out to investigate the 10-year prognostic value of atherosclerotic burden derived from AI-QCT and to compare the spectrum of plaque to manually assessed coronary computed tomography angiography (CCTA), coronary artery calcium scoring (CACS), and clinical risk characteristics. MethodsThis was a long-term follow-up study of 536 patients referred for suspected coronary artery disease. CCTA scans were analyzed with AI-QCT and plaque burden was classified with a plaque staging system (stage 0: 0% percentage atheroma volume [PAV]; stage 1: >0%-5% PAV; stage 2: >5%-15% PAV; stage 3: >15% PAV). The primary major adverse cardiac event (MACE) outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and all-cause mortality. ResultsThe mean age at baseline was 58.6 years and 297 patients (55%) were male. During a median follow-up of 10.3 years (IQR: 8.6-11.5 years), 114 patients (21%) experienced the primary outcome. Compared to stages 0 and 1, patients with stage 3 PAV and percentage of noncalcified plaque volume of >7.5% had a more than 3-fold (adjusted HR: 3.57; 95% CI 2.12-6.00; P < 0.001) and 4-fold (adjusted HR: 4.37; 95% CI: 2.51-7.62; P < 0.001) increased risk of MACE, respectively. Addition of AI-QCT improved a model with clinical risk factors and CACS at different time points during follow-up (10-year AUC: 0.82 [95% CI: 0.78-0.87] vs 0.73 [95% CI: 0.68-0.79]; P < 0.001; net reclassification improvement: 0.21 [95% CI: 0.09-0.38]). Furthermore, AI-QCT achieved an improved area under the curve compared to Coronary Artery Disease Reporting and Data System 2.0 (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.023) and manual QCT (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.040), although net reclassification improvement was modest (0.09 [95% CI: −0.02 to 0.29] and 0.04 [95% CI: −0.05 to 0.27], respectively). ConclusionsThrough 10-year follow-up, AI-QCT plaque staging showed important prognostic value for MACE and showed additional discriminatory value over clinical risk factors, CACS, and manual guideline-recommended CCTA assessment.

Predicting coronary plaque progression with conventional plaque parameters and radiomics features derived from coronary CT angiography.

To determine the value of combining conventional plaque parameters and radiomics features derived from coronary computed tomography angiography (CCTA) for predicting coronary plaque progression. Clinical data and CCTA images of 400 patients who underwent at least two CCTA examinations between January 2009 and August 2020 were analyzed retrospectively. Diameter stenosis, total plaque volume and burden, calcified plaque volume and burden, noncalcified plaque volume and burden (NCPB), pericoronary fat attenuation index (FAI), and other conventional plaque parameters were recorded. The patients were assigned to a training cohort (n = 280) and a validation cohort (n = 120) in a 7:3 ratio using a stratified random splitting method. The area under the receiver operating characteristics curve (AUC) was used to evaluate the predictive abilities of conventional parameters (model 1), radiomics features (model 2), and their combination (model 3). FAI and NCPB were identified as independent risk factors for coronary plaque progression in the training cohort. Both model 2 (training cohort AUC: 0.814, p < 0.001; validation cohort AUC: 0.729, p = 0.288) and model 3 (training cohort AUC: 0.824, p < 0.001; validation cohort AUC: 0.758, p = 0.042) had better diagnostic performances in predicting plaque progression than model 1 (training cohort AUC: 0.646; validation cohort AUC: 0.654). Moreover, model 3 was slightly higher than model 2, although not statistically significant. The combination of conventional coronary plaque parameters and CCTA-derived radiomics features had a better ability to predict plaque progression than conventional parameters alone. The conventional coronary plaque characteristics such as noncalcified plaque burden, pericoronary fat attenuation index, and radiomics features derived from CCTA can identify plaques prone to progression, which is helpful for further clinical decision-making of coronary artery disease. • FAI and NCPB were identified as independent risk factors for predicting plaque progression. • Coronary plaque radiomics features were more advantageous than conventional parameters in predicting plaque progression. • The combination of conventional coronary plaque parameters and radiomics features could significantly improve the predictive ability of plaque progression over conventional parameters alone.

Pericoronary Adipose Tissue Density, Inflammation, and Subclinical Coronary Artery Disease Among People With HIV in the REPRIEVE Cohort.

Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population. In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates. Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001). Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.

Epicardial adipose tissue volume, plaque vulnerability and myocardial ischemia in non-obstructive coronary artery disease

BackgroundEpicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Whether increased EAT volume is associated with coronary plaque vulnerability and demand myocardial ischemia in patients with non-obstructive coronary artery disease (CAD) is less explored. MethodsIn 125 patients (median age 63[58, 69] years and 58% women) with chest pain and non-obstructive CAD, EAT volume was quantified on non-contrast cardiac CT images. EAT volume in the highest tertile (>125 ml) was defined as high EAT volume. Total coronary plaque volume and plaque vulnerability were quantified by coronary CT angiography (CCTA). Demand myocardial ischemia was detected by contrast dobutamine stress echocardiography. ResultsHigh EAT volume was more common in men and associated with higher BMI, hypertension, increased left ventricular mass index (LVMi), C-reactive protein (CRP) and positive remodelling (all p < 0.05). There was no difference in age, coronary calcium score, total and non-calcified plaque volume or presence of demand myocardial ischemia between groups (all p ≥ 0.34). In a multivariable model, obesity (p = 0.006), hypertension (p = 0.007) and LVMi (p = 0.016) were independently associated with high EAT volume. Including plaque vulnerability in an alternative model, positive remodelling (p = 0.038) was independently associated with high EAT volume. ConclusionIn non-obstructive CAD, high EAT volume was associated with cardiometabolic risk factors, inflammation and plaque vulnerability, while there was no association with demand myocardial ischemia or coronary plaque volume. Following our results, the role of EAT volume as a biomarker in non-obstructive CAD remains unclear.

Early Development of Atherosclerotic Plaques in the Coronary Arteries after Radiotherapy for Breast Cancer (BACCARAT Study).

Background-Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods-The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results-At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion-Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512.

Improving image quality with super-resolution deep-learning-based reconstruction in coronary CT angiography.

To evaluate the effect of super-resolution deep-learning-based reconstruction (SR-DLR) on the image quality of coronary CT angiography (CCTA). Forty-one patients who underwent CCTA using a 320-row scanner were retrospectively included. Images were reconstructed with hybrid (HIR), model-based iterative reconstruction (MBIR), normal-resolution deep-learning-based reconstruction (NR-DLR), and SR-DLR algorithms. For each image series, image noise, and contrast-to-noise ratio (CNR) at the left main trunk, right coronary artery, left anterior descending artery, and left circumflex artery were quantified. Blooming artifacts from calcified plaques were measured. Image sharpness, noise magnitude, noise texture, edge smoothness, overall quality, and delineation of the coronary wall, calcified and noncalcified plaques, cardiac muscle, and valves were subjectively ranked on a 4-point scale (1, worst; 4, best). The quantitative parameters and subjective scores were compared among the four reconstructions. Task-based image quality was assessed with a physical evaluation phantom. The detectability index for the objects simulating the coronary lumen, calcified plaques, and noncalcified plaques was calculated from the noise power spectrum (NPS) and task-based transfer function (TTF). SR-DLR yielded significantly lower image noise and blooming artifacts with higher CNR than HIR, MBIR, and NR-DLR (all p < 0.001). The best subjective scores for all the evaluation criteria were attained with SR-DLR, with significant differences from all other reconstructions (p < 0.001). In the phantom study, SR-DLR provided the highest NPS average frequency, TTF50%, and detectability for all task objects. SR-DLR considerably improved the subjective and objective image qualities and object detectability of CCTA relative to HIR, MBIR, and NR-DLR algorithms. The novel SR-DLR algorithm has the potential to facilitate accurate assessment of coronary artery disease on CCTA by providing excellent image quality in terms of spatial resolution, noise characteristics, and object detectability. • SR-DLR designed for CCTA improved image sharpness, noise property, and delineation of cardiac structures with reduced blooming artifacts from calcified plaques relative to HIR, MBIR, and NR-DLR. • In the task-based image-quality assessments, SR-DLR yielded better spatial resolution, noise property, and detectability for objects simulating the coronary lumen, coronary calcifications, and noncalcified plaques than other reconstruction techniques. • The image reconstruction times of SR-DLR were shorter than those of MBIR, potentially serving as a novel standard-of-care reconstruction technique for CCTA performed on a 320-row CT scanner.

Statins influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

ObjectivesCholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-β HDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA). MethodsEvaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol. ResultsABCA1-CEC negatively correlated with ABCG1-CEC (r = −0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20–3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65–1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61–0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23–0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18–3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and < 0.001 respectively). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20–7.86]) only in patients not exposed to statins during follow-up (p-for-interaction = 0.009). ConclusionIn patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.

Age- and Sex-Specific Nomographic CT Quantitative Plaque Data From a Large International Cohort

BackgroundWith growing adoption of coronary computed tomographic angiography (CTA), there is increasing evidence for and interest in the prognostic importance of atherosclerotic plaque volume. Manual tools for plaque segmentation are cumbersome, and their routine implementation in clinical practice is limited. ObjectivesThe aim of this study was to develop nomographic quantitative plaque values from a large consecutive multicenter cohort using coronary CTA. MethodsQuantitative assessment of total atherosclerotic plaque and plaque subtype volumes was performed in patients undergoing clinically indicated coronary CTA, using an Artificial Intelligence–Enabled Quantitative Coronary Plaque Analysis tool. ResultsA total of 11,808 patients were included in the analysis; their mean age was 62.7 ± 12.2 years, and 5,423 (45.9%) were women. The median total plaque volume was 223 mm3 (IQR: 29-614 mm3) and was significantly higher in male participants (360 mm3; IQR: 78-805 mm3) compared with female participants (108 mm3; IQR: 10-388 mm3) (P < 0.0001). Total plaque increased with age in both male and female patients. Younger patients exhibited a higher prevalence of noncalcified plaque. The distribution of total plaque volume and its components was reported in every decile by age group and sex. ConclusionsThe authors developed pragmatic age- and sex-stratified percentile nomograms for atherosclerotic plaque measures using findings from coronary CTA. The impact of age and sex on total plaque and its components should be considered in the risk-benefit analysis when treating patients. Artificial Intelligence–Enabled Quantitative Coronary Plaque Analysis work flows could provide context to better interpret coronary computed tomographic angiographic measures and could be integrated into clinical decision making.

Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer

BackgroundPatients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune...

Plaque Progression Differences Between Apixaban and Rivaroxaban in Patients With Atrial Fibrillation Measured With Cardiac Computed Tomography and Plaque Quantification.

Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.