Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA,the PARADIGM study

Background and aimsDifferent methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex.MethodsThe PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm³, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAV_norm) in mm³ [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAV_norm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed.ResultsThe study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11–13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAV_norm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAV_norm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAV_norm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex.ConclusionsPAV was less affected by patient's body surface area then PV and TAV_norm and may be the preferred method to report coronary atherosclerotic burden.     

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography

PurposeInvestigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities.MethodsThree patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDI_vol at 6.7 mGy), 60% ASIR (CTDI_vol 4.3 mGy) and Veo (CTDI_vol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities.ResultsPlaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm³ and 337 mm³–252 mm³ for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm³–391 mm³ for lumen volume and vessel volume from 939 mm³ to 830 mm³. The intensities did not change overall between the different reconstructions for either lumen or plaque.ConclusionWe found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted.     

Comparison of coronary atherosclerotic plaque progression in East Asians and Caucasians by serial coronary computed tomographic angiography: A PARADIGM substudy

ObjectivesTo investigate potential differences in plaque progression (PP) between in East Asians and Caucasians as well as to determine clinical predictors of PP in East Asians.BackgroundStudies have demonstrated differences in cardiovascular risk factors as well as plaque burden and progression across different ethnic groups.MethodsThe study comprised 955 East Asians (age 60.4 ?± ?9.3 years, 50.9% males) and 279 Caucasians (age 60.4 ?± ?8.6 years, 74.5% males) who underwent two serial coronary computed tomography angiography (CCTA) studies over a period of at least 24 months. Patients were enrolled and analyzed from the PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging) registry. After propensity-score matching, plaque composition and progression were compared between East Asian and Caucasian patients. Within East Asians, the plaque progression group (defined as plaque volume at follow-up CCTA minus plaque volume at baseline CCTA> 0) was compared to the no PP group to determine clinical predictors for PP in East Asians.ResultsIn the matched cohort, baseline volumes of total plaque as well as all plaque subtypes were comparable. There was a trend towards increased annualized plaque progression among East Asians compared to Caucasians (18.3 ?± ?24.7 ?mm³/year vs 16.6 ?mm³/year, p ?= ?0.054). Among East Asians, 736 (77%) had PP. East Asians with PP had more clinical risk factors and higher plaque burden at baseline (normalized total plaque volume of144.9 ?± ?233.3 ?mm³ vs 36.6 ?± ?84.2 ?mm³ for PP and no PP, respectively, p ?< ?0.001). Multivariate logistic regression analysis showed that baseline normalized plaque volume (OR: 1.10, CI: 1.10–1.30, p ?< ?0.001), age (OR: 1.02, CI: 1.00–1.04, p ?= ?0.023) and body mass index (OR: 2.24, CI: 1.01–1.13, p ?= ?0.024) were all predictors of PP in East Asians. Clinical events, driven mainly by percutaneous coronary intervention, were higher among the PP group with a total of 124 (16.8%) events compared to 22 (10.0%) in the no PP group (p ?= ?0.014).ConclusionEast Asians and Caucasians had comparable plaque composition and progression. Among East Asians, the PP group had a higher baseline plaque burden which was associated with greater PP and increased clinical events.     

Endothelial shear stress computed from coronary computed tomography angiography: A direct comparison to intravascular ultrasound

IntroductionIntravascular ultrasound (IVUS) studies have shown that biomechanical variables, particularly endothelial shear stress (ESS), add synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with coronary computed tomography angiography (CCTA) would be helpful to enable broad population risk-screening.AimTo compare the accuracy of ESS computation of local ESS metrics by CCTA vs IVUS imaging.MethodsWe analyzed 59 patients from a registry of patients who underwent both IVUS and CCTA for suspected CAD. CCTA images were acquired using either a 64- or 256-slice scanner. Lumen, vessel, and plaque areas were segmented from both IVUS and CCTA (59 arteries, 686 3-mm segments). Images were co-registered and used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics (CFD) and reported in consecutive 3-mm segments.ResultsAnatomical plaque characteristics (vessel, lumen, plaque area and minimal luminal area [MLA] per artery) were correlated when measured with IVUS and CCTA: 12.7 ​± ​4.3 vs 10.7 ​± ​4.5 ​mm², r ​= ​0.63; 6.8 ​± ​2.7 vs 5.6 ​± ​2.7 ​mm², r ​= ​0.43; 5.9 ​± ​2.9 vs 5.1 ​± ​3.2 ​mm², r ​= ​0.52; 4.5 ​± ​1.3 vs 4.1 ​± ​1.5 ​mm², r ​= ​0.67 respectively. ESS metrics of local minimal, maximal, and average ESS were also moderately correlated when measured with IVUS and CCTA (2.0 ​± ​1.4 vs 2.5 ​± ​2.6 ​Pa^, r ​= ​0.28; 3.3 ​± ​1.6 vs 4.2 ​± ​3.6 ​Pa, r ​= ​0.42; 2.6 ​± ​1.5 vs 3.3 ​± ​3.0 ​Pa, r ​= ​0.35, respectively). CCTA-based computation accurately identified the spatial localization of local ESS heterogeneity compared to IVUS, with Bland-Altman analyses indicating that the absolute ESS differences between the two CCTA methods were pathobiologically minor.ConclusionLocal ESS evaluation by CCTA is possible and similar to IVUS; and is useful for identifying local flow patterns that are relevant to plaque development, progression, and destabilization.     

Longitudinal assessment of coronary plaque volume change related to glycemic status using serial coronary computed tomography angiography: A PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) substudy

BackgroundData on the impact of glycemic status on coronary plaque progression have been limited. This study evaluated the association between glycemic status and coronary plaque volume change (PVC) using coronary computed tomography angiography (CCTA).MethodsA total of 1296 subjects (61 ± 9, 56.9% male) who underwent serial CCTA with available glycemic status were enrolled and analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.6–4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were categorized into the following groups according to glycemic status: normal, pre-diabetes (pre-DM), and diabetes mellitus (DM).ResultsDuring the follow-up, significant differences in PVC (normal: 51.3 ± 83.3 mm³ vs. pre-DM: 51.0 ± 84.3 mm³ vs. DM: 72.6 ± 95.0 mm³; p < 0.001) and annualized PVC (normal: 14.9 ± 24.9 mm³ vs. pre-DM: 15.7 ± 23.8 mm³ vs. DM: 21.0 ± 27.7 mm³; p = 0.001) were observed among the 3 groups. Compared with normal individuals, individuals with pre-DM showed no significant differences in the adjusted odds ratio (OR) for plaque progression (PP) (1.338, 95% confidence interval [CI] 0.967–1.853; p = 0.079). However, the adjusted OR for PP was higher in DM individuals than in normal individuals (1.635, 95% CI 1.126–2.375; p = 0.010).ConclusionDM had an incremental impact on coronary PP, but pre-DM appeared to have no significant association with an increased risk of coronary PP after adjusting for confounding factors.Clinical trial registrationClinicalTrials.gov NCT02803411.     

Age related compositional plaque burden by CT in patients with future ACS

BackgroundWe examined age differences in whole-heart volumes of non-calcified and calcified atherosclerosis by coronary computed tomography angiography (CCTA) of patients with future ACS.MethodsA total of 234 patients with core-lab adjudicated ACS after baseline CCTA were enrolled. Atherosclerotic plaque was quantified and characterized from the main epicardial vessels and side branches on a 0.5 ?mm cross-sectional basis. Calcified plaque and non-calcified plaque were defined by above or below 350 Hounsfield units. Patients were categorized according to their age by deciles. Also, coronary artery calcium scores (CACS) were evaluated when available.ResultsPatients were on average 62.2 ?± ?11.5 years old. On the pre-ACS CCTA, patients showed diffuse, multi-site, predominantly non-obstructive atherosclerosis across all age categories, with plaque being detected in 93.5% of all ACS cases. The proportion calcified plaque from the total plaque burden increased significantly with older presentation (10% calcification in those <50 years, and 50% calcification in those >80 years old). Patients with ACS <50 years had remarkably lower atherosclerotic burden compared with older patients, but a high proportion of high risk markers such as low-attenuation plaque. CACS was >0 in 85% of the patients older than 50 years, and in 57% of patients younger than 50 years.ConclusionThe proportion of calcified plaque varied depending on patient age at the time of ACS. Only a small proportion of plaque was calcified when ACS occurred at <50 years old, while this increased gradually with older age. Purely non-calcified atherosclerotic plaque was not uncommon in patients <50 years.     

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.     

Implications of computed tomography reconstruction algorithms on coronary atheroma quantification: Comparison with intravascular ultrasound

BackgroundAdvances in coronary computed tomography angiography (CCTA) reconstruction algorithms are expected to enhance the accuracy of CCTA plaque quantification. We aim to evaluate different CCTA reconstruction approaches in assessing vessel characteristics in coronary atheroma using intravascular ultrasound (IVUS) as the reference standard.MethodsMatched cross-sections (n ?= ?7241) from 50 vessels in 15 participants with chronic coronary syndrome who prospectively underwent CCTA and 3-vessel near-infrared spectroscopy-IVUS were included. Twelve CCTA datasets per patient were reconstructed using two different kernels, two slice thicknesses (0.75 ?mm and 0.50 ?mm) and three different strengths of advanced model-based iterative reconstruction (IR) algorithms. Lumen and vessel wall borders were manually annotated in every IVUS and CCTA cross-section which were co-registered using dedicated software. Image quality was sub-optimal in the reconstructions with a sharper kernel, so these were excluded. Intraclass correlation coefficient (ICC) and repeatability coefficient (RC) were used to compare the estimations of the 6 CT reconstruction approaches with those derived by IVUS.ResultsSegment-level analysis showed good agreement between CCTA and IVUS for assessing atheroma volume with approach 0.50/5 (slice thickness 0.50 ?mm and highest strength 5 ADMIRE IR) being the best (total atheroma volume ICC: 0.91, RC: 0.67, p ?< ?0.001 and percentage atheroma volume ICC: 0.64, RC: 14.06, p ?< ?0.001). At lesion-level, there was no difference between the CCTA reconstructions for detecting plaques (accuracy range: 0.64–0.67; p ?= ?0.23); however, approach 0.50/5 was superior in assessing IVUS-derived lesion characteristics associated with plaque vulnerability (minimum lumen area ICC: 0.64, RC: 1.31, p ?< ?0.001 and plaque burden ICC: 0.45, RC: 32.0, p ?< ?0.001).ConclusionCCTA reconstruction with thinner slice thickness, smooth kernel and highest strength advanced IR enabled more accurate quantification of the lumen and plaque at a segment-, and lesion-level analysis in coronary atheroma when validated against intravascular ultrasound. Clinicaltrials.gov (NCT03556644)     

Progression of whole-heart Atherosclerosis by coronary CT and major adverse cardiovascular events

BackgroundThe current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE).MethodsThe multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted.ResultsThe study population comprised 1166 patients (age 60.5 ?± ?9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ?< ?0.001.ConclusionsWhole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.     

Diagnostic value of comprehensive on-site and off-site coronary CT angiography for identifying hemodynamically obstructive coronary artery disease

BackgroundThis study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V_sub) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR_CT) was assessed.MethodsProspectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V_sub. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR_CT, the incremental value of off-site FFR_CT was tested.ResultsIn 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V_sub were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V_sub/MLA² outperformed all these on-site CCTA parameters (AUC = 0.85) and V_sub was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR_CT and V_sub/MLA² was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR_CT was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02).ConclusionsIn comprehensive on-site CCTA assessment, V_sub/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V_sub was incremental to all evaluated CCTA indices. Additionally, adding FFR_CT only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR_CT.     

Cumulative exposure amount of PM2.5 in the ambient air is associated with coronary atherosclerosis - Serial coronary CT angiography study

BackgroundWe investigated the change of coronary atherosclerosis with long-term exposure to fine particulate matter of aerodynamic diameter <2.5 ?μm (PM_2.5) using coronary computed tomography angiography (CCTA).MethodsSubjects undergoing serial CCTAs between January 2007 and December 2017 (n ?= ?3,127) were analyzed. Each individual's cumulative amount of PM_2.5 exposure between the two CCTAs was evaluated by Kriging interpolation and zonal analysis, considering the time interval between the two CCTAs. The main outcome was progression of coronary artery calcium (CAC) with additional semiquantitative analysis on the changes in the severity and composition of atherosclerotic plaques.ResultsThe CAC scores increased by 30.8 Agatston units per-year under a median PM_2.5 concentration 24.9 ?μg/m³ and tended to increase with the cumulative amount of PM_2.5 exposure (r ?= ?0.321, p ?<0.001). The CAC progressed in 1,361 (43.5%) subjects during a median 53 months follow-up. The cumulative amount of PM_2.5 exposure was independently associated with CAC progression (adjusted OR 1.09, p ?<0.001). By random forest analysis, the relative impact of cumulative amount of PM_2.5 exposure on CAC progression was higher than that of traditional cardiovascular risk factors and the average concentration of PM_2.5. The extent of coronary atherosclerosis and newly developed calcified plaque on follow-up were also significantly associated with the cumulative amount of PM_2.5 exposure.ConclusionsCumulative exposure to air pollution is associated with the progression of diffuse coronary calcification, the importance of which may be more significant than other traditional cardiovascular risk factors. Further investigations into the causality between PM_2.5 and coronary atherosclerosis are warranted to improve global cardiovascular health.     

Coronary volume to left ventricular mass ratio in patients with diabetes mellitus

BackgroundDiabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes.MethodsPatients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes.ResultsOf the 3053 patients (age 66 ?± ?10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 ?± ?940 ?mm³ vs. 3040 ?± ?970 ?mm³, p ?< ?0.0001), whereas the myocardial mass was comparable between the 2 groups (122 ?± ?33 ?g vs. 122 ?± ?32 ?g, p ?= ?0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 ?± ?6.8 ?mm³/g vs. 25.7 ?± ?7.5 ?mm³/g, p ?< ?0.0001). Among subjects with obstructive CAD (n ?= ?2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 ?± ?6.7 ?mm³/g vs. 25.0 ?± ?7.3 ?mm³/g, p ?< ?0.0001 and 25.6 ?± ?6.9 ?mm³/g vs. 27.3 ?± ?7.6 ?mm³/g, respectively, p ?= ?0.006).ConclusionThe V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation.     

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.     

Predictive value of the coronary artery calcium score and advanced plaque characteristics: Post hoc analysis of the PREDICT registry

BackgroundWhether coronary plaque characteristics assessed in coronary computed tomography angiography (CCTA) in association with the coronary artery calcium score (CACS) have predictive value for coronary events is unclear. We aimed to examine the predictive value of the CACS and plaque characteristics for the occurrence of coronary events.MethodsAmong 2802 patients who were analyzed in the PREDICT registry, 2083 with suspected coronary artery disease (CAD) were studied using post hoc analysis. High-risk plaques were defined as having ≥2 adverse characteristics, such as low computed tomographic attenuation, positive remodeling, spotty calcification, and napkin-ring sign. An adjudicative composite of coronary events (cardiac death, nonfatal acute coronary syndrome, and coronary revascularization ≥3 months after indexed CCTA) were analyzed.ResultsSeventy-three (3.5%) patients had coronary events and 313 (15.0%) had high-risk plaques. Multivariate Cox proportional hazard analysis showed that high-risk plaques remained an independent predictor of coronary events (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.13–3.34, P ?= ?0.0154), as well as the log-transformed CACS (adjusted HR 1.24, 95% CI 1.11–1.39, P ?= ?0.0002) and the presence of obstructive stenosis (adjusted HR 5.63, 95% CI 3.22–10.12, P 0.0001). In subgroup analyses, high-risk plaques were independently predictive only in the low CACS class (<100).ConclusionThis study shows that assessment of adverse features by coronary plaque imaging independently predicts coronary events in patients with suspected CAD and a low CACS. Our findings suggest that the clinical value of high-risk plaques to CACS and stenosis assessment appears marginal.     

Epicardial adipose tissue density and volume are related to subclinical atherosclerosis,inflammation and major adverse cardiac events in asymptomatic subjects

BackgroundWe investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects.MethodsEAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE.ResultsEAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm³, p < 0.001] [-76.9 vs -75.7 HU,p = 0.024]. EAT volume was lowest in individuals with no coronary calcium and was significant higher in subjects with early atherosclerosis (CCS 1-99) [74 vs 87 cm³,p = 0.016] and in subjects with more advanced atherosclerosis (CCS≥100) [89 cm³,p = 0.002]). EAT volume was independently related to serum levels of PAI-1, and MCP-1 and inversely related to adiponectin and HDL-cholesterol (p < 0.05). EAT density was inversely related to PAI-1 and LDL-cholesterol and positively associated to adiponectin, sICAM-1 and HDL-cholesterol (p < 0.05). EAT density was more significantly associated with MACE [(HR 0.8, 95%CI:0.7–0.98), p = 0.029] than EAT volume or CCS.ConclusionEAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation.     

Sex differences in computed tomography angiography-derived coronary plaque burden in relation to invasive fractional flow reserve

BackgroundDistinct sex-related differences exist in coronary artery plaque burden and distribution. We aimed to explore sex differences in quantitative plaque burden by coronary CT angiography (CCTA) in relation to ischemia by invasive fractional flow reserve (FFR).MethodsThis post-hoc analysis of the PACIFIC trial included 581 vessels in 203 patients (mean age 58.1 ​± ​8.7 years, 63.5% male) who underwent CCTA and per-vessel invasive FFR. Quantitative assessment of total, calcified, non-calcified, and low-density non-calcified plaque burden were performed using semiautomated software. Significant ischemia was defined as invasive FFR ≤0.8.ResultsThe per-vessel frequency of ischemia was higher in men than women (33.5% vs. 7.5%, p ​< ​0.001). Women had a smaller burden of all plaque subtypes (all p ​< ​0.01). There was no sex difference on total, calcified, or non-calcified plaque burdens in vessels with ischemia; only low-density non-calcified plaque burden was significantly lower in women (beta: -0.183, p ​= ​0.035). The burdens of all plaque subtypes were independently associated with ischemia in both men and women (For total plaque burden (5% increase): Men, OR: 1.15, 95%CI: 1.06–1.24, p ​= ​0.001; Women, OR: 1.96, 95%CI: 1.11–3.46, p ​= ​0.02). No significant interaction existed between sex and total plaque burden for predicting ischemia (interaction p ​= ​0.108). The addition of quantitative plaque burdens to stenosis severity and adverse plaque characteristics improved the discrimination of ischemia in both men and women.ConclusionsIn symptomatic patients with suspected CAD, women have a lower CCTA-derived burden of all plaque subtypes compared to men. Quantitative plaque burden provides independent and incremental predictive value for ischemia, irrespective of sex.     

Sex- and age-specific differences in the long-term prognostic value of morphological plaque features detected by coronary computed tomography angiography

BackgroundAlthough sex- and age-specific differences in coronary plaque features detected by coronary computed tomography angiography (CCTA) are known, insufficient information regarding the long-term prognostic value of these findings exists.MethodsA total of 1615 patients with suspected but not previously diagnosed coronary artery disease (CAD) were examined by CCTA and coronary plaque features were assessed. The median follow-up period was 10.5 (IQR 9.2–11.4) years. Cox proportional-hazards analysis was used for the combined endpoint of cardiac death or nonfatal myocardial infarction.ResultsThe endpoint occurred more often in patients older than 65 years (5.66% vs. 2.05%; p = 0.00029) but similarly between female (3.34%) and male (3.07%) patients (p = 0.76). Both sexes displayed a similar prevalence for noncalcified (female vs. male: 0.77 ± 1.38 vs. 0.89 ± 1.41; p = 0.098) and low-attenuation (female vs. male: 2.6% vs. 4.37%; p = 0.096) plaques. As assessed by p for interaction CADRADS (p for interaction = 0.013), noncalcified plaques (p for interaction = 0.022) and low-attenuation plaques (p for interaction = 0.045) had a better primary endpoint association in women than in men. Concerning age, no difference in outcome association was apparent as evaluated by p for interaction.ConclusionCCTA demonstrates excellent long-term prognostic value irrespective of sex and age and independent from the higher prevalence of atherosclerotic plaques in men and patients older than 65 years. Although similarly prevalent in both sexes, noncalcified and low-attenuation plaques exhibit a better prognostic value in women.     

Consistency of quantitative analysis of coronary computed tomography angiography

BackgroundThe present study aimed to assess the reliability and reproducibility of coronary computed tomography angiography (CCTA) for the serial quantitative assessment of plaque volume.MethodsPatients who underwent repeated CCTA scans within 90 days were retrospectively screened and enrolled. Clinical data and CCTA imaging data were collected. Paired CCTA scans were analyzed using the quantitative method by separate observers blinded to the other paired CCTA scans. Results were compared between the index CCTA and follow-up CCTA.ResultsPaired CT scans of 95 patients (61 ± 13 years; 56.8% men) with same tube voltages (kVp) at both CCTAs and 24 patients (57 ± 19 years; 48.3% men) with different kVp at two CCTAs were analyzed. In patients with same kVp at both CCTAs, there were no difference in PV and PVs of each components in per-segment analysis and per-lesion analysis (all p > 0.05). In per-lesion analysis of CCTAs from patients who used different kVp between two CCTAs, lesion length, area and diameter stenosis, and PVs were not different between index and follow-up CCTAs (all p > 0.05). Segment length and PV were also showed no difference between two serial CCTAs in per-segment analysis.ConclusionWe showed the reproducibility and reliability of quantitative analysis of CCTA for assessment of coronary plaques. CCTA can be applied for the serial quantitative assessment of coronary artery disease progression, regardless of differences in the image acquisition protocol.     

Deep learning with convolutional neural network for estimation of the characterisation of coronary plaques: Validation using IB-IVUS

IntroductionDeep learning approaches have shown high diagnostic performance in image classifications, such as differentiation of malignant tumors and calcified coronary plaque. However, it is unknown whether deep learning is useful for characterizing coronary plaques without the presence of calcification using coronary computed tomography angiography (CCTA). The purpose of this study was to compare the diagnostic performance of deep learning with a convolutional neural network (CNN) with that of radiologists in the estimation of coronary plaques.MethodsWe retrospectively enrolled 178 patients (191 coronary plaques) who had undergone CCTA and integrated backscatter intravascular ultrasonography (IB-IVUS) studies. IB-IVUS diagnosed 81 fibrous and 110 fatty or fibro-fatty plaques. We manually captured vascular short-axis images of the coronary plaques as Portable Network Graphics (PNG) images (150 × 150 pixels). The display window level and width were 100 and 700 Hounsfield units (HU), respectively. The deep-learning system (CNN; GoogleNet Inception v3) was trained on 153 plaques; its performance was tested on 38 plaques. The area under the curve (AUC) obtained by receiver operating characteristic analysis of the deep learning system and by two board-certified radiologists was compared.ResultsWith the CNN, the AUC and the 95% confidence interval were 0.83 and 0.69–0.96, respectively; for radiologist 1 they were 0.61 and 0.42–0.80; for radiologist 2 they were 0.68 and 0.51–0.86, respectively. The AUC for CNN was significantly higher than for radiologists 1 (p = 0.04); for radiologist 2 it was not significantly different (p = 0.22).ConclusionDL-CNN performed comparably to radiologists for discrimination between fatty and fibro-fatty plaque on CCTA images.Implications for practiceThe diagnostic performance of the CNN and of two radiologists in the assessment of 191 ROIs on CT images of coronary plaques whose type corresponded with their IB-IVUS characterization was comparable.