Calcified Plaque Volume Research Articles

Diagnostic Performance of CT FFR With a New Parameter Optimized Computational Fluid Dynamics Algorithm From the CT-FFR-CHINA Trial: Characteristic Analysis of Gray Zone Lesions and Misdiagnosed Lesions.

To assess the diagnostic performance of fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (CT-FFR) obtained by a new computational fluid dynamics (CFD) algorithm to detect ischemia, using FFR as a reference, and analyze the characteristics of “gray zone” and misdiagnosed lesions. This prospective multicenter clinical trial (NCT03692936, https://clinicaltrials.gov/) analyzed 317 patients with coronary stenosis between 30 and 90% in 366 vessels from five centers undergoing CTA and FFR between November 2018 and March 2020. CT-FFR were obtained from a CFD algorithm (Heartcentury Co., Ltd., Beijing, China). Diagnostic performance of CT-FFR and CTA in detecting ischemia was assessed. Coronary atherosclerosis characteristics of gray zone and misdiagnosed lesions were analyzed. Per-vessel sensitivity, specificity and accuracy for CT-FFR and CTA were 89.9, 87.8, 88.8% and 89.3, 35.5, 60.4%, respectively. Accuracy of CT-FFR was 80.0% in gray zone lesions. In gray zone lesions, lumen area and diameter were significantly larger than lesions with FFR < 0.76 (both p < 0.001), lesion length, non-calcified and calcified plaque volume were all significantly higher than non-ischemic lesions (all p < 0.05). In gray zone lesions, Agatston score (OR = 1.009, p = 0.044) was the risk factor of false negative results of CT-FFR. In non-ischemia lesions, coronary stenosis >50% (OR = 2.684, p = 0.03) was the risk factor of false positive results. Lumen area (OR = 0.567, p = 0.02) and diameter (OR = 0.296, p = 0.03) had a significant negative effect on the risk of false positive results of CT-FFR. In conclusion, CT-FFR based on the new parameter-optimized CFD model provides better diagnostic performance for lesion-specific ischemia than CTA. For gray zone lesions, stenosis degree was less than those with FFR < 0.76, and plaque load was heavier than non-ischemic lesions.

Diagnostic efficacy of CCTA and CT-FFR based on risk factors for myocardial ischemia

BackgroundCoronary artery coronary computed tomography angiography (CCTA) can observe the degree of coronary artery stenosis and fractional flow reserve (FFR) can diagnose hemodynamic abnormalities caused by coronary artery stenosis. However, noninvasive imaging examination that can both observe the above two methods at the same time has not yet been elucidated.ObjectiveTo investigate the diagnostic efficacy of CCTA and computed tomography-derived fractional flow reserve (CT-FFR) based on different risk factors for myocardial ischemia.MethodsPatients undergoing CCTA in our hospital from August 18, 2020 to April 28, 2021 were randomly selected, and the data were subjected to CT-FFR analysis. Vascular characteristics were measured, including total plaque volume, calcified plaque volume, non-calcified plaque volume, plaque length, and lumen stenosis, and the patients were categorized into a non-ischemia group (FFR > 0.8) and an ischemia group (FFR ≤ 0.8). Plaque characteristics were compared between the two groups, and logistic regression analysis was employed to explore the correlations between plaque characteristics and ischemic lesions.ResultsFrom a total of 122 patients enrolled in the study, there were 218 vascular branches with FFR > 0.8 and 174 vascular branches with FFR ≤ 0.8. There were significant group differences in total plaque volume, calcified plaque volume, plaque length, and lumen stenosis > 50% (n). The obtained data were as follows: non-ischemic group 10.57 (4.80, 259.65), ischemic group 14.87 (3.39, 424.45), Z = 9.772, p = 0.002, non-ischemic group 10.57 (0, 168.77), ischemic group 14.87 (0, 191.00), Z = 2.503, p ≤ 0.001), non-ischemic group 8.17 (37.05, 40.53), ischemic group 8.38 (56.66, 86.47), Z = 5.923, p = 0.016, and lumen stenosis > 50%, non-ischemic group 46, ischemic group 90, x2 = 14.77, p ≤ 0.001. The regression analysis results indicated that total plaque volume, calcified plaque volume, plaque length and lumen stenosis > 50% were risk factors for myocardial ischemia, with ORs and p values of (2.311, p = 0.002), (1.021, p = 0.004), (2.159, p < 0.001), and (0.181, p < 0.001), respectively.ConclusionTotal plaque volume, calcified plaque volume, plaque length and lumen stenosis > 50% are predictors for myocardial ischemia. Coronary artery CCTA combined with CT-FFR could simultaneously observe the anatomical stenosis and evaluate myocardial blood supply at the functional level. Thus, myocardial ischemia could be better diagnosed.

Effect of long-term intensive cholesterol control on the plaque progression in elderly based on CTA cohort study.

To investigate the long-term effects of intensive LDL cholesterol-lowering treatments on lumen stenosis severity, plaque calcification, spotty calcifications, percent calcified plaque volume (PCPV), and Agatston coronary artery calcium score (CACS) based on coronary computed tomography angiography (CCTA) in elderly patients. A total of 240 patients over 60 years old (comprising 754 lesions) who underwent serial CCTA were retrospectively enrolled in this 5-year cohort study. Patients were divided into three groups: an intensive lipid-lowering group, a lipid-lowering group, and a control group. The stenosis severity, plaque volume (PV), plaque composition, PCPV, and high-risk plaque (HRP) presence were quantitatively analyzed. The CACS was calculated at baseline and follow-up. All patients were male with an average age of 66.8 ± 5.8 years old. Over time, increases in the percentages of obstructive coronary lesions (p < 0.001) were observed. Compared with those at baseline, the percentage of obstructive lesions remained unchanged (p = 0.077), and the percentage of spotty calcifications significantly decreased (p < 0.05) at the follow-up CCTA scan in the intensive lipid-lowering group. Patients in the intensive lipid-lowering group demonstrated a higher progression in calcified PV, CACS, and PCPV (all p < 0.05), and a significantly greater attenuation in fibrous-fatty and lipid-rich PV (all p < 0.05) than patients in other groups. The PV and contents increased gradually with time in all groups. Intensive LDL-C lowering was associated with slower progression of stenosis severity and reduction of high-risk plaque features, with increased plaque calcification and higher progression in PCPV. Comprehensive serial plaque evaluations by CCTAs may contribute to further refinement of risk stratification and reasonable lipid-lowering treatment in elderly patients. • Intensive LDL-C lowering increased coronary calcification and percent calcified plaque volume progression. • Comprehensive serial plaque evaluations by serial CCTAs may help to refine risk stratification.

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

Background:Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.Methods:In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use.Results:We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%–67%], unique environment, 37% [95% CI, 33%–44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%–66%]; unique environmental, 42% [95% CI, 34%–50%] and additive genetic, 78% [95% CI, 73%–80%]; unique environmental, 22% [95% CI, 20%–27%]), respectively.Conclusions:Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01738828.

Abstract WMP69: Features Of Calcified Carotid Atherosclerosis Are Associated With Stroke In Patients With Embolic Stroke Of Undetermined Source

Introduction: We examined qualitative features of calcified plaque in patients with embolic stroke of undetermined source (ESUS). Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA neck and meeting criteria for ESUS was identified. A segmentation software measured carotid bifurcation calcified plaque volumes. A neuroradiologist manually measured maximum carotid wall and calcified wall thickness (WT), maximum craniocaudal calcified plaque length, degree of circumferential involvement (none, punctate, 90°, 180°, 270°, 360°) and assessed for intimal, transmural, and adventitial calcifications. Descriptive statistics included medians and interquartile ranges. Differences between ipsilateral (carotid ipsi ) and contralateral (carotid contra ) carotid arteries to stroke side were tested using Wilcoxon Signed-Rank, McNemar, and marginal homogeneity tests. Results: Ninety-four subjects met criteria for ESUS. Mean age was 65 years and 55% were women. Carotid ipsi had a significantly higher volume of calcified plaque [Vol ipsi =39.1 (12.4, 86.7) vs Vol contra =25.9 (4.9, 71.7), p=0.05] and maximum calcified WT [CalcWT ipsi= 1.4 (0, 2.6) vs CalcWT contra =0 (0, 2.1), p=0.03] than carotid contra . There were no significant differences in the maximum craniocaudal calcified plaque length (p=0.09) or degree of circumferential calcified plaque involvement (p=0.35) between carotid ipsi and carotid contra . Intimal (p=0.03) but not transmural (p=0.14) or adventitial (p=0.12) calcifications were significantly more frequent in carotid ipsi than carotid contra . A subgroup analysis (n=48) including either carotid artery measuring ≥3mm in maximum WT showed intimal calcifications remained significantly associated with stroke side (p=0.02; Figure). Conclusion: Higher calcified plaque volumes, calcified wall thickness and intimal calcifications may be associated with ischemic stroke in patients with ESUS.

Effect of Calcification Based on Computer-Aided System on CT-Fractional Flow Reserve in Diagnosis of Coronary Artery Lesion.

This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group (FFR ≤ 0.8) and nonischemic group (FFR > 0.8). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group (P < 0.05). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference (P > 0.05). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group (P < 0.05). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups (P > 0.05). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.

Calcified versus non-calcified plaque volume fraction in patients with coronary artery disease and their association with outcome

Abstract Background The amount of coronary artery calcification is a general marker of coronary atherosclerosis and has been associated with increased risk of adverse cardiac events. On the other hand, calcification of coronary artery plaques has also been considered as a marker of plaque stabilization. Purpose We hypothesized that the fraction of the non-calcified volume of the total plaque volume in patients with coronary artery disease (CAD) is associated with abnormal myocardial perfusion and increased risk of future cardiac events. Methods Consecutive patients with suspected CAD undergoing sequential coronary computed tomography angiography (CCTA) with selective positron emission tomography (PET) perfusion imaging between 2007 and 2011 were selected. The total, calcified and non-calcified plaque volume (PV) were defined at patient-level. The non-calcified plaque volume fraction was calculated by dividing the non-calcified PV by the total PV, and expressed as percentage. Patients were divided into three groups: patients with 1) non-obstructive CAD (&amp;lt;50% diameter stenosis), 2) suspected coronary stenosis but normal PET perfusion and 3) suspected stenosis and abnormal regional PET perfusion. Difference between high vs. low PV was based on the median value. Clinical outcomes including all-cause mortality and myocardial infarction were recorded for 6.1 [SD 5.3–7.5] years. Results In total, 494 patients (age 63±9 years, 55% male) with documented atherosclerosis on CCTA were included. Total PV, calcified PV and non-calcified PV were all significantly larger in patients with abnormal myocardial perfusion compared to patients with non-obstructive CAD (370 [197–739] mm3 vs. 108 [59–177] mm3, 84 [23–220] mm3 vs. 9 [1–34] mm3 and 274 [157–500] mm3 vs. 94 [53–140] mm3, respectively, p&amp;lt;0.001 for all). However, the non-calcified fraction was smaller in patients with reduced myocardial perfusion (75 [63–86]% vs. 89 [76–98]%, p&amp;lt;0.001, Figure 1). During follow-up 35 events occurred. Patients with higher total PV, calcified PV and non-calcified PV showed worse outcome compared to patients with lower PV (log-rank p&amp;lt;0.001, Figure 2). In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome (log-rank χ2=5.54; p=0.019) even after adjusting for statin therapy or revascularization. Conclusion We observed that higher volumes of any plaque component in general are associated with abnormal perfusion and increased risk of future cardiac events. In contrast, patients with a lower non-calcified plaque volume fraction showed poorer outcome. Funding Acknowledgement Type of funding sources: None. Non-calcified plaque volume fractionKaplan-Meier survival analysis

Effects of left ventricular mass index on computed tomography derived fractional flow reserve in significant obstructive coronary artery disease

Abstract Background In significant obstructive coronary artery disease (SOCAD), a mismatched assessment of the severity of coronary artery stenosis may occur between invasive coronary angiography and computed tomography (CT) derived fractional flow reserve (FFRCT). The exact mechanisms of unexpected underestimation of FFRCT remain unknown. Purpose The aims of this study are (1) to clarify the mechanisms of underestimation on FFRCT; and (2) to identify the predictive factors of FFRCT underestimation above the value of 0.80 in SOCAD vessels. Methods A total of 1160 outpatients who underwent CT angiography (CTA) with FFRCT analysis for suspected coronary artery disease (CAD) between January 2017 and June 2020 were evaluated. Among them, 141 consecutive patients who had both CTA coupled to FFRCT analysis and invasive angiogram showing &amp;gt;75% coronary stenosis were included for analysis. Vessels were divided into two groups according to FFRCT at the distal vessel: FFRCT &amp;gt;0.80 (n=12) and FFRCT ≤0.80 (n=153). Vessel-related parameters, including vessel morphology (vessel length and lumen volume) and plaque components (non-calcified plaque volume and calcified plaque volume) and left ventricular (LV) myocardial-related parameters, including LV wall thickness at each site of the myocardium, and LV mass were evaluated semi-automatically. Results Vessel morphology and plaque components did not differ between FFRCT &amp;gt;0.80 and ≤0.80, whereas LV wall thickness (average; 10.7±2.7 vs. 8.4±1.6 mm, and maximal; 13.5±3.0 vs. 10.6±1.8 mm, all p value &amp;lt;0.001), LV mass (136.4±38.4 vs. 98.8±26.8 g, p&amp;lt;0.001), and LV mass index (73.8±22.6 vs. 51.8±12.2 g/m2, p&amp;lt;0.001) were significantly higher in FFRCT &amp;gt;0.80. Next, we investigated the parameters that correlated with FFRCT. Of all, vessel morphology and plaque components were not related to FFRCT, whereas maximal LV wall thickness, r=0.24, p=0.01; LV mass, r=0.19. p=0.04; and LV mass index, r=0.30, p=0.001) correlated with FFRCT. In the vessels showing FFRCT &amp;gt;0.80, only LV mass (r=0.84, p=0.005) and LV mass index (r=0.67, p=0.047) correlated with FFRCT. (Figure 1). LV mass index was the strongest predictor of a distal FFRCT of &amp;gt;0.80 with the area under curve (AUC) 0.81, 95% CI 0.62 – 1.00, P&amp;lt;0.0001 and an optimal cut-off value of 66.5 g/m2 sensitivity 77.8%, specificity 89.6% (Figure 2). Conclusions FFRCT is affected not by vessel-related parameters but LV myocardial-related parameters in SOCAD. The presence of an excessive LV mass is a major predictor of underestimation of FFRCT in SOCAD vessels. LV myocardial-related parameters should be considered when interpreting numerical values of FFRCT to avoid the possibility of overlooked SOCAD. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Impact of vascular morphology and plaque characteristics on computed tomography derived fractional flow reserve in early stage coronary artery disease

BackgroundComputed-tomography (CT) derived fractional-flow-reserve (FFRCT) gradually may decrease from proximal to distal vessels even without apparent coronary artery disease (CAD). It may be unclear whether the decrease in FFRCT at the distal coronal artery is physiological or due to stenosis. We decided to study predictive factors of an FFRCT decline below the pathological value of 0.80 in no-apparent CAD. MethodsA total of 150 consecutive patients who had both CT angiography coupled to FFRCT analysis and invasive angiogram showing < 20% coronary stenosis were included. Vessels were divided into two groups according to FFRCT at the distal vessel: FFRCT > 0.80 (n = 317) and FFRCT ≤ 0.80 (n = 114). ΔFFRCT was defined as the change in FFRCT from proximal to distal vessel. Vessel morphology (vessel length and lumen volume) and plaque characteristics [low-attenuation plaque volume, intermediate-attenuation (IAP) plaque volume, and calcified plaque volume] were evaluated. ResultsFFRCT decreased from proximal to distal for the three major vessels in both FFRCT > 0.80 and FFRCT ≤ 0.80. Compared to FFRCT > 0.80, IAP volume was significantly higher in all three major vessels in FFRCT ≤ 0.80. ΔFFRCT was correlated with vessel length and lumen volume in FFRCT > 0.80, whereas ΔFFRCT was correlated with IAP volume in FFRCT ≤ 0.80. IAP volume above 44.8 mm3 was the strongest predictor of distal FFRCT of ≤ 0.80. ConclusionsThe presence of IAP is a major predictor of gradual decrease of FFRCT below 0.80 in no-apparent CAD vessels. Vessel morphology and plaque characteristics should be considered when interpreting FFRCT.

Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data

Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm3), with necrotic core and fibro-fatty PV regression (− 5.7 mm3 and − 5.6 mm3, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (− 2.4 mm3). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm3). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm3), predominantly increasing in calcified PV (+ 35.9 mm3). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.

Association of Tube Voltage With Plaque Composition on Coronary CT Angiography: Results From PARADIGM Registry

ObjectivesThis study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA). BackgroundThe impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain. MethodsA total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta. ResultsWith increasing luminal HU (<350, 350-500, and >500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P < 0.001), and fibrofatty plaque (26%, 13%, and 4%; P < 0.001) and necrotic core (1.6%, 0.3%, and 0.0%; P < 0.001) were decreased. Higher tube voltage scanning (80, 100, and 120 kV) resulted in decreasing luminal attenuation (689 ± 135, 497 ± 89, and 391 ± 73 HU; P < 0.001) and calcified plaque volume (59%, 34%, and 23%; P < 0.001) and increased fibrofatty plaque (3%, 9%, and 18%; P < 0.001) and necrotic core (0.2%, 0.1%, and 0.6%; P < 0.001). Mediation analysis showed that the impact of 100 kV on plaque composition, compared with 120 kV, was primarily caused by an indirect effect through blood pool attenuation. Tube voltage scanning of 80 kV maintained a direct effect on fibrofatty plaque and necrotic core in addition to an indirect effect through the luminal attenuation. ConclusionsLow tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)

Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition

The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques. To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression. This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries. The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020. In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (β, -0.02; 95% CI, -0.03 to -0.01; P = .001) and fibro-fatty plaque (β, -0.03; 95% CI, -0.04 to -0.02; P < .001) and greater progression of high-density calcium plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (β, -0.03; 95% CI, -0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression. The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.

Relationship of Endothelial Shear Stress with Plaque Features with Coronary CT Angiography and Vasodilating Capability with PET.

Background Advances in three-dimensional reconstruction techniques and computational fluid dynamics of coronary CT angiography (CCTA) data sets make feasible evaluation of endothelial shear stress (ESS) in the vessel wall. Purpose To investigate the relationship between CCTA-derived computational fluid dynamics metrics, anatomic and morphologic characteristics of coronary lesions, and their comparative performance in predicting impaired coronary vasodilating capability assessed by using PET myocardial perfusion imaging (MPI). Materials and Methods In this retrospective study, conducted between October 2019 and September 2020, coronary vessels in patients with stable chest pain and with intermediate probability of coronary artery disease who underwent both CCTA and PET MPI with oxygen 15-labeled water or nitrogen 13 ammonia and quantification of myocardial blood flow were analyzed. CCTA images were used in assessing stenosis severity, lesion-specific total plaque volume (PV), noncalcified PV, calcified PV, and plaque phenotype. PET MPI was used in assessing significant coronary stenosis. The predictive performance of the CCTA-derived parameters was evaluated by using area under the receiver operating characteristic curve (AUC) analysis. Results There were 92 coronary vessels evaluated in 53 patients (mean age, 65 years ± 7; 31 men). ESS was higher in lesions with greater than 50% stenosis versus those without significant stenosis (mean, 15.1 Pa ± 30 vs 4.6 Pa ± 4 vs 3.3 Pa ± 3; P = .004). ESS was higher in functionally significant versus nonsignificant lesions (median, 7 Pa [interquartile range, 5-23 Pa] vs 2.6 Pa [interquartile range, 1.8-5 Pa], respectively; P ≤ .001). Adding ESS to stenosis severity improved prediction (change in AUC, 0.10; 95% CI: 0.04, 0.17; P = .002) for functionally significant lesions. Conclusion The combination of endothelial shear stress with coronary CT angiography (CCTA) stenosis severity improved prediction of an abnormal PET myocardial perfusion imaging result versus CCTA stenosis severity alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kusmirek and Wieben in this issue.

Prevalence and Characterization of Subclinical Coronary Atherosclerotic Plaque with CT among Individuals with HIV: Results from the Canadian HIV and Aging Cohort Study

Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography (n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors. Results There were 181 PLWH (mean age, 56 years ± 7; 167 men) and 84 healthy volunteers (mean age, 57 years ± 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively; P = .45), as were CAC score (odds ratio [OR], 1.06; 95% CI: 0.58, 1.94; P = .85) and overall plaque prevalence (prevalence ratio, 1.07; 95% CI: 0.86, 1.32; P = .55) after adjustment for cardiovascular risk. Noncalcified plaque prevalence (prevalence ratio, 2.5; 95% CI: 1.07, 5.67; P = .03) and volume (OR, 2.8; 95% CI: 1.05, 7.40; P = .04) were higher in PLWH. Calcified plaque frequency was reduced in PLWH (OR, 0.6; 95% CI: 0.40, 0.91; P = .02). Treatment with protease inhibitors was associated with higher volume of overall (OR, 1.8; 95% CI: 1.09, 2.85; P = .02) and mixed plaque (OR, 1.6; 95% CI: 1.04, 2.45; P = .03). Conclusion Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in asymptomatic people living with HIV without known cardiovascular disease compared with healthy volunteers without HIV. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lai in this issue.

Relationships between peripheral reactive hyperemia index with coronary plaque burden and prognosis in patients with unstable angina pectoris complicated with type 2 diabetes mellitus.

BackgroundCoronary plaque burden (CPB) is an important prognostic factor in patients with unstable angina pectoris (UAP). Our current study aims to investigate the relationships between peripheral reactive hyperemia index (RHI) with CPB and prognosis in patients with UAP complicated with type 2 diabetes mellitus (T2DM).MethodsThe clinical data of 187 UAP-T2DM patients who were treated in our center from June 2017 to January 2019 were retrospectively collected. RHI, CPB, and other clinical features were measured. The patients were followed up for 18 months and then divided into an adverse cardiovascular event (ACE) group (n=71, with ACEs) and a control group (n=116, without ACEs). The differences in RHI, CPB, and other clinical features between these two groups were compared, and the potential correlation between RHI and CPB was analyzed.ResultsCompared with the control group, the ACE group had significantly lower RHI (1.21±0.32 vs. 1.59±0.35, P=0.000) and left ventricular ejection fraction (LVEF) (42.92%±7.78% vs. 48.90%±6.76%, P=0.000) and a significantly higher left ventricular myocardial mass index (2.67±0.87 vs. 2.27±0.49 mg/g, P=0.000), carotid intima-media thickness (1.65±0.34 vs. 1.51±0.32 mm, P=0.000), number of coronary plaques (3.98±0.53 vs. 3.32±0.38, P=0.000), non-calcified plaque volume (32.89±12.56 vs. 22.58±9.97 mm3, P=0.000), calcified plaque volume (4.89±1.29 vs. 3.88±1.05 mm3, P=0.000), non-calcified plaque burden (5.70%±1.60% vs. 3.18%±1.08%, P=0.000), and calcified plaque burden (0.90%±0.22% vs. 0.65%±0.19%, P=0.000). Pearson linear correlation analysis showed that peripheral RHI was negatively correlated with plaque number, non-calcified plaque volume, calcified plaque volume, non-calcified plaque burden, and calcified plaque burden in patients with UAP complicated with T2DM (all P<0.05).ConclusionsDecreased peripheral RHI is associated with ACEs and CPB in patients with UAP complicated with T2DM.

Cardiovascular risk factors and illicit drug use may have a more profound effect on coronary atherosclerosis progression in people living with HIV.

To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm3/year vs. 4.9 [IQR: 1.5-18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm3/year vs. 0.2 [IQR: 0.0-0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm3/year vs. 0.1 [IQR: 0.0-3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm3, CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm3, CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm3, CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Abstract P372: Sex-Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source

Introduction: Non-stenotic carotid plaque may be the cause of ischemic stroke in some patients with embolic stroke of undetermined source (ESUS). We examined sex-differences in carotid plaque composition in patients with ESUS. Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA head/neck and meeting criteria for ESUS was identified. Carotid artery bifurcations (4cm segment) ipsilateral to the stroke were evaluated using a semi-automated segmentation software to measure total plaque volume and plaque subcomponents (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core [LRNC]). Sex-differences in baseline vascular risk factors and plaque subcomponent volumes were tested by Mann-Whitney U tests or students t-tests for continuous variables and Fisher’s exact test for categorical variables. Associations of each plaque subcomponent were tested by multivariate linear regressions. Results: Of 94 patients, 55% were women. Mean age of the cohort was 65 years. Women had higher body mass indices than men (29.2 vs 26.3; p=0.02). There were no other significant differences in age or vascular risk factors between men and women. Overall plaque volume (p=0.001) was significantly greater in men as was the volume of calcification (p&lt;0.001) and IPH (p=0.008) in carotid arteries ipsilateral to the stroke (Figure). No significant difference was detected in LRNC volume by sex (p=0.84). In multivariate analysis, male sex (β=45.9, 95% CI 18.0-73.7, p=0.002) and older age (β=1.85, 95% CI 0.73-3.0, p=0.001) were significantly associated with calcified plaque volume, and male sex (β= 6.7, 95% CI 2.6-10.8, p=0.002) with IPH. Neither age nor sex was significantly associated with LRNC. Conclusions: Sex-differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of non-stenotic carotid plaque to stroke mechanism in men versus women.

CCTA-derived functional and morphological features and their comparative performance in predicting impaired coronary vasodilatation by PET-myocardial perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 onbehalf EVINCI-SMARTOOL Background/Objectives: The relationship between biomechanical characteristics of a coronary lesion with myocardial blood flow has not been studied. We investigated the relationship between local endothelial shear stress (ESS) and computed tomography coronary angiography (CTCA)-derived anatomical and plaque characteristics data with impaired vasodilating capability assessed by positron emission tomography myocardial perfusion imaging (PET-MPI). Methods A total of 92 coronary vessels of 53 patients who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia were analysed. PET was considered abnormal when &amp;gt; 1 contiguous segments showed both stress Myocardial Blood Flow (MBF) ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or &amp;lt;1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. CTCA images were used to assess stenosis severity, lesion specific total plaque volume (PV), non-calcified PV and calcified PV as well as plaque phenotype. ESS was calculated for the full length of a lesion (total), as well as in the proximal, minimum lumen area and distal lesion segments. Results ESS was weakly correlated with total PV (rho = 0.273, p = 0.008), non-calcified PV (rho = 0.247, p = 0.017) and the volume of necrotic core (rho = 0.242, p = 0.02). ESS increased progressively with stenosis severity (p ≤ 0.001). ΕSS was also higher in functionally significant vs. non-significant lesions (10.4 [8.04-54.4] Pa vs. 3.9 [2.32-7.29] Pa, p ≤0.001). Addition of ESS to stenosis severity improved prediction (Δ[AUC]:0.113, 95% CI: 0.055 to 0.171, p = 0.0001) of functionally significant lesions. Conclusion There is a weak positive association between lesion-specific ESS and plaque volume. ESS increases progressively with stenosis severity and is higher in functionally significant lesions by PET-MPI. The addition of ESS to CTCA-anatomical information improves prediction of an abnormal PET-MPI result.

Effect of Low Calorie, High Anti-oxidant Diet on Progression of Coronary Artery Disease: A Single Case Experimental Study

Introduction: A large amount of scientific evidence supporting the hypothesis that nutritional modification might prevent cardiovascular disease (CVD) deaths, could even reverse the remodelling and risk factors of CVD. However, studies on the interplay between diet and CVD are scarce especially in low- and middle-income countries. The current single patient observational study attempted to evaluate the relationship between controlled diet along with standard medication and coronary artery disease (CAD) outcomes. Methods and results: A 69-year-old male, with a known history of diabetes and occasional postprandial angina, diagnosed with ischemic heart disease and triple vessel disease with 80-90% narrowing in all three epicardial branches of the coronary artery was enrolled in this study. The patient was put on the interventional phase (reverse diet) for 12 weeks after completion of the baseline phase. The reverse diet contained pre-portion ready to cook food products to fulfil daily requirements of breakfast, lunch, dinner, soup, and early morning diet. He was suggested for daily walk and exercise (less aerobic). At the end of the intervention, the patient's overall calcified and non-calcified plaque volume, lumen volume, atheroma plaque volume was found reduced as confirmed by computed tomography angiography (CTA). Additionally, the patient’s standard medications were also reduced after the intervention by approximately 50%. Conclusion: This single patient evidence suggested that the low calorie and anti-oxidant rich reverse diet intervention is capable to reduce the odds of CAD.

Reproducibility of quantitative plaque measurement in advanced coronary artery disease

BackgroundThe ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease. MethodsTwenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility. ResultsOverall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin’s coefficient 0.95 to 1.0). There were no substantial interscan differences (P ​> ​0.05 for all) for total (2063 ​± ​1246 ​mm3, mean of differences −35.6 ​mm3), non-calcified (1795 ​± ​910 ​mm3, mean of differences −4.3 ​mm3), calcified (298 ​± ​425 ​mm3, mean of differences −31.3 ​mm3) and low-attenuation (13 ​± ​13 ​mm3, mean of differences −2.6 ​mm3) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (−236.6 to 174 ​mm3 and -15.8 to 10.5 ​mm3 respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes. ConclusionIn the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease.