Smoking and obesity predict high-risk plaque by coronary CTA in low coronary artery calcium score (CACS)

BackgroundThe AHA recommends statins in patients with CACS>100 AU. However in patients with low CACS (1–99 AU), no clear statement is provided, leaving the clinician in a grey-zone. High-risk plaque (HRP) criteria by coronary CTA are novel imaging biomarkers indicating a higher a-priori cardiovascular (CV) risk, which could help for decision-making. Therefore the objective of our study was to identify which CV-risk factors predict HRP in patients with low CACS 1–99.Methods1003 symptomatic patients with low-to-intermediate risk, a clinical indication for coronary computed tomography angiography (CCTA) and who had a coronary artery calcium score (CACS) between 1 and 99 AU, were enrolled. CCTA analysis included: stenosis severity and HRP-criteria: low-attenuation plaque (LAP <30HU, <60HU and <90HU) napkin-ring-sign, spotty calcification and positive remodeling. Multivariate regression models were created for predicting HRP-criteria by the major 5 cardiovascular risk factors (CVRF) (smoking, arterial hypertension, positive family history, dyslipidemia, diabetes) and obesity (BMI>25 ​kg/m²).Results304 (33.5%) were smokers. 20.4% of smokers had HRP compared with only 14.9% of non-smokers (p ​= ​0.045). Male gender was associated with HRP (p ​< ​0.001).Smoking but not the other 5 CVRF had the most associations with HRP-criteria (LAP<60HU/≥2 criteria:OR 1.59; 95%CI:1.07–2.35), LAP<90HU (OR 1.57; 95%CI:1.01–2.43), Napkin-Ring-Sign (OR 1.78; 95%CI:1.02–3.1) and positive remodelling (OR 1.54; 95%CI:1.09–2.19). Smoking predicted fibrofatty LAP<90HU in males only. Obesity predicted LAP<60HU in both females and males.ConclusionsIn patients with low CACS 1-99AU, male gender, smoking and obesity, but not the other CVRF predict HRP. These patients would rather benefit from intensification of primary CV-prevention measures such as statins.     

基于CCTA对胸痛病人高危斑块成分及血流动力学特征的研究

目的 基于冠状动脉CT血管成像（CCTA）研究伴高危斑块的胸痛病人其斑块成分特征及血流动力学特征。方法 回顾性纳入行CCTA且于2个月内行有创冠状动脉造影检查的43例冠心病病人,男30例,女13例,平均年龄（60.8±8.7）岁。依据病人是否存在高危斑块及胸痛将病人分为2组,组1同时存在胸痛和至少1个高危斑块特征（23例）,组2仅有胸痛或高危斑块特征任意一项（20例）。测量斑块成分特征参数[斑块总体积、钙化斑块体积、纤维斑块体积、脂质斑块体积占比（脂质斑块%）、脂质斑块面积、最小管腔面积、偏心指数]和血流动力学特征参数[基于CCTA的血流储备分数（FFR_CT）,斑块近、远端FFR_CT差值（△FFR_CT）]。采用Mann-Whitney U检验或独立样本t检验比较2组间参数的差异。利用约登指数计算斑块成分特征及血流动力学特征判断高危斑块合并胸痛的临界值,采用受试者操作特征（ROC）曲线分析计算其临界值的敏感度、特异度以及曲线下面积（AUC）。结果 组1的脂质斑块%、脂质斑块面积均高于组2（均P<0.05）,FFR_CT值低于组2（P<0.05）,2组间其他斑块成分特征参数及△FFR_CT差异均无统计学意义（均P>0.05）。分析脂质斑块%、脂质斑块面积及FFR_CT 特征参数的诊断能力,FFR_CT的临界值为0.82时的敏感度最高（61%）、特异度最低（85%）,AUC最高（0.80）。结论 采用CCTA分析高危斑块中脂质斑块成分特征并进行FFR_CT测量,可作为评估高危斑块合并胸痛病人的有效辅助手段,为临床治疗决策提供依据。     

Value of semiquantitative assessment of high-risk plaque features on coronary CT angiography over stenosis in selection of studies for FFRct

IntroductionThe degree of stenosis on coronary CT angiography (CCTA) guides referral for CT-derived flow reserve (FFRct). We sought to assess whether semiquantitative assessment of high-risk plaque (HRP) features on CCTA improves selection of studies for FFRct over stenosis assessment alone.MethodsPer-vessel FFRct was computed in 1,395 vessels of 836 patients undergoing CCTA with 25–99% maximal stenosis. By consensus analysis, stenosis severity was graded as 25–49%, 50–69%, 70–89%, and 90–99%. HRPs including low attenuation plaque (LAP), positive remodeling (PR), and spotty calcification (SC) were assessed in lesions with maximal stenosis. Lesion FFRct was measured distal to the lesion with maximal stenosis, and FFRct<0.80 was defined as abnormal. Association of HRP and abnormal lesion FFRct was evaluated by univariable and multivariable logistic regression models.ResultsThe frequency of abnormal lesion FFRct increased with increase of stenosis severity across each stenosis category (25–49%:6%; 50–69%:30%; 70–89%:54%; 90–99%:91%, p ?< ?0.001). Univariable analysis demonstrated that stenosis severity, LAP, and PR were predictive of abnormal lesion FFRct, while SC was not. In multivariable analyses considering stenosis severity, presence of PR, LAP, and PR and/or LAP were independently associated with abnormal FFRct: Odds ratio 1.58, 1.68, and 1.53, respectively (p ?< ?0.02 for all). The presence of PR and/or LAP increased the frequency of abnormal FFRct with mild stenosis (p ?< ?0.05) with a similar trend with 70–89% stenosis. The combination of 2 HRP (LAP and PR) identified more lesions with FFR < 0.80 than only 1 HRP.ConclusionsSemiquantitative visual assessment of high-risk plaque features may improve the selection of studies for FFRct.     

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.     

Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography

BackgroundElevated levels of inflammatory biomarkers are associated with increased cardiovascular morbidity and mortality.ObjectiveWe sought to determine whether elevated concentrations of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) predict progression of coronary artery disease (CAD) as determined by coronary CT angiography (coronary CTA).MethodsPatients presenting to the emergency department with acute chest pain who initially showed no evidence of an acute coronary syndrome underwent baseline and follow-up coronary CTA (median follow-up, 23.9 months) using identical acquisition and reconstruction parameters. Coronary CTA data of each major coronary artery were co-registered. Cross-sections were assessed for the presence of calcified and noncalcified plaques. Progression of atherosclerotic plaque and change of plaque composition from noncalcified to calcified plaque was evaluated and correlated to levels of hs-TnT and hs-CRP at the time of the baseline CT.ResultsFifty-four patients (mean age, 54.1 years; 59% male) were included, and 6775 cross-sections were compared. CAD was detected in 12.2 ± 21.2 cross-sections per patient at baseline. Prevalence of calcified plaque increased by 1.5 ± 2.4 slices per patient (P < .0001) over the follow-up period. On average, 1.6 ± 3.6 slices with new noncalcified plaque were found per patient (P < .0001) and 0.7 ± 1.7 slices with pre-existing noncalcified plaque had progressed to calcified plaque (P < .0001). After multivariate adjustment, change of overall CAD burden was predicted by baseline hs-TnT and hs-CRP (r = 0.29; P = .039 and r = 0.40; P = .004). Change of plaque composition was associated with baseline hs-TnT (r = 0.29; P = .03).ConclusionConcentrations of hs-TnT and hs-CRP are weakly associated with a significant increase in CAD burden and change in plaque composition over 24 months independent of baseline risk factors.     

Machine-learning integration of CT histogram analysis to evaluate the composition of atherosclerotic plaques: Validation with IB-IVUS

BackgroundTo determine whether machine learning with histogram analysis of coronary CT angiography (CCTA) yields higher diagnostic performance for coronary plaque characterization than the conventional cut-off method using the median CT number.MethodsWe included 78 patients with 78 coronary plaques who had undergone CCTA and integrated backscatter intravascular ultrasound (IB-IVUS) studies. IB-IVUS diagnosed 32 as fibrous- and 46 as fatty or fibro-fatty plaques. We recorded the coronary CT number and 7 histogram parameters (minimum and mean value, standard deviation (SD), maximum value, skewness, kurtosis, and entropy) of the plaque CT number. We also evaluated the importance of each feature using the Gini index which rates the importance of individual features. For calculations we used XGBoost. Using 5-fold cross validation of the plaque CT number, the area under the receiver operating characteristic curve of the machine learning- (extreme gradient boosting) and the conventional cut-off method was compared.ResultsThe median CT number was 56.38 Hounsfield units (HU, 8.00–95.90) for fibrous- and 1.15 HU (−35.8–113.30) for fatty- or fibro-fatty plaques. The calculated optimal threshold for the plaque CT number was 36.1 ± 2.8 HU. The highest Gini index was the coronary CT number (0.19) followed by the minimum value (0.17), kurtosis (0.17), entropy (0.14), skewness (0.11), the mean value (0.11), the standard deviation (0.06), and the maximum value (0.05), and energy (0.00). By validation analysis, the machine learning-yielded a significantly higher area under the curve than the conventional method (area under the curve 0.92 and 95%, confidence interval 0.86–0.92 vs 0.83 and 0.75–0.92, p = 0.001).ConclusionThe machine learning-was superior the conventional cut-off method for coronary plaque characterization using the plaque CT number on CCTA images.     

A cross-sectional survey of coronary plaque composition in individuals on non-statin lipid lowering drug therapies and undergoing coronary computed tomography angiography

IntroductionNon-statin therapy (NST) is used as second-line treatment when statin monotherapy is inadequate or poorly tolerated.ObjectiveTo determine the association of NST with plaque composition, alone or in combination with statins, in patients undergoing coronary computed tomography angiography (coronary CTA).MethodsFrom the multicenter CONFIRM registry, we analyzed individuals who underwent coronary CTA with known lipid-lowering therapy status and without prior coronary artery disease at baseline. We created a propensity score for being on NST, followed by stepwise multivariate linear regression, adjusting for the propensity score as well as risk factors, to determine the association between NST and the number of coronary artery segments with each plaque type (non-calcified (NCP), partially calcified (PCP) or calcified (CP)) and segment stenosis score (SSS).ResultsOf the 27,125 subjects in CONFIRM, 4,945 met the inclusion criteria; 371 (7.5%) took NST. At baseline, patients on NST had more prevalent risk factors and were more likely to be on concomitant cardiac medications. After multivariate and propensity score adjustment, NST was not associated with plaque composition: NCP (0.07 increase, 95% CI: −0.05, 0.20; p = 0.26), PCP (0.10 increase, 95% CI: −0.10, 0.31; p = 0.33), CP (0.18 increase, 95% CI: −0.10, 0.46; p = 0.21) or SSS (0.45 increase, 95% CI: −0.02,0.93; p = 0.06). The absence of an effect of NST on plaque type was not modified by statin use (p for interaction > 0.05 for all).ConclusionIn this cross-sectional study, non-statin therapy was not associated with differences in plaque composition as assessed by coronary CTA.     

CT ​Evaluation ​by ​Artificial ​Intelligence ​for ​Atherosclerosis,Stenosis and Vascular ​Morphology ​(CLARIFY): ​A ​Multi-center,international study

BackgroundAtherosclerosis evaluation by coronary computed tomography angiography (CCTA) is promising for coronary artery disease (CAD) risk stratification, but time consuming and requires high expertise. Artificial Intelligence (AI) applied to CCTA for comprehensive CAD assessment may overcome these limitations. We hypothesized AI aided analysis allows for rapid, accurate evaluation of vessel morphology and stenosis.MethodsThis was a multi-site study of 232 patients undergoing CCTA. Studies were analyzed by FDA-cleared software service that performs AI-driven coronary artery segmentation and labeling, lumen and vessel wall determination, plaque quantification and characterization with comparison to ground truth of consensus by three L3 readers. CCTAs were analyzed for: % maximal diameter stenosis, plaque volume and composition, presence of high-risk plaque and Coronary Artery Disease Reporting & Data System (CAD-RADS) category.ResultsAI performance was excellent for accuracy, sensitivity, specificity, positive predictive value and negative predictive value as follows: >70% stenosis: 99.7%, 90.9%, 99.8%, 93.3%, 99.9%, respectively; >50% stenosis: 94.8%, 80.0%, 97.0, 80.0%, 97.0%, respectively. Bland-Altman plots depict agreement between expert reader and AI determined maximal diameter stenosis for per-vessel (mean difference −0.8%; 95% CI 13.8% to −15.3%) and per-patient (mean difference −2.3%; 95% CI 15.8% to −20.4%). L3 and AI agreed within one CAD-RADS category in 228/232 (98.3%) exams per-patient and 923/924 (99.9%) vessels on a per-vessel basis. There was a wide range of atherosclerosis in the coronary artery territories assessed by AI when stratified by CAD-RADS distribution.ConclusionsAI-aided approach to CCTA interpretation determines coronary stenosis and CAD-RADS category in close agreement with consensus of L3 expert readers. There was a wide range of atherosclerosis identified through AI.     

Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy

BackgroundThe association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).MethodsFrom a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.ResultsWith a 3.3-years’ median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm³/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm³/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.ConclusionsThe rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.     

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)     

Coronary plaque characteristics in computed tomography and 2-year outcomes: The PREDICT study

BackgroundCoronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques).ObjectiveWe sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD).MethodsOf 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome.ResultsDuring the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (n = 515, no mural lesions), calcium (n = 654, calcified lesion alone), and plaque groups (n = 1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (P = 0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09–3.60; P = 0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome.ConclusionsPlaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD.     

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.     

Non-invasive assessment of coronary artery geometry using coronary CTA

AimTo assess the association of coronary artery geometry with the severity of coronary artery disease (CAD).Methods73 asymptomatic individuals at increased risk of CAD due to peripheral vascular disease (18 women, mean age 63.5 ± 8.2 years) underwent coronary computed tomography angiography (coronary CTA) using first generation dual-source CT. Curvature and tortuosity of the coronary arteries were quantified using semi-automatically generated centerlines. Measurements were performed for individual segments and for the entire artery. Coronary segments were labeled according to the presence of significant stenosis, defined as >70% luminal narrowing, and the presence of plaque. Comparisons were made by segment and by artery, using linear mixed models.ResultsOverall, median curvature and tortuosity were, respectively, 0.094 [0.071; 0.120] and 1.080 [1.040; 1.120] on a per-segment level, and 0.096 [0.078; 0.118] and 1.175 [1.090; 1.420] on a per-artery level. Curvature was associated with significant stenosis at a per-segment (p < 0.001) and per-artery level (p = 0.002). Curvature was 16.7% higher for segments with stenosis, and 13.8% higher for arteries with stenosis. Tortuosity was associated with significant stenosis only at the per-segment level (p = 0.002). Curvature was related to the presence of plaque at the per-segment (p < 0.001) and per-artery level (p < 0.001), tortuosity was only related to plaque at the per-segment level (p < 0.001).ConclusionCoronary artery geometry as derived from coronary CTA is related to the presence of plaque and significant stenosis.     

Quantification of coronary low-attenuation plaque volume for long-term prediction of cardiac events and reclassification of patients

BackgroundTo investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets.MethodsQuantification of LAPV was performed using dedicated software equipped with an adaptive plaque tissue algorithm in 1577 patients with suspected CAD. A combination of death and acute coronary syndrome was defined as primary endpoint. To assess the incremental prognostic value of LAPV, parameters were added to a baseline model including clinical risk and obstructive coronary artery disease (CAD), a baseline model including clinical risk and calcium scoring (CACS) and a baseline model including clinical risk and segment involvement score (SIS).ResultsPatients were followed for 5.5 years either by telephone contact, mail or clinical visits. The primary endpoint occurred in 30 patients. Quantified LAPV provided incremental prognostic information beyond clinical risk and obstructive CAD (c-index 0.701 vs. 0.767, p < .001), clinical risk and CACS (c-index 0.722 vs. 0.771, p < .01) and clinical risk and SIS (c-index 0.735 vs. 0.771, p < .01. A combined approach using quantified LAPV and clinical risk significantly improved the stratification of patients into different risk categories compared to clinical risk alone (categorical net reclassification index 0.69 with 95% CI 0.27 and 0.96, p < .001). The combined approach classified 846 (53.6%) patients as low risk (annual event rate 0.04%), 439 (27.8%) patients as intermediate risk (annual event rate 0.5%) and 292 (18.5%) patients as high risk (annual event rate 0.99%).ConclusionQuantification of LAPV provides incremental prognostic information beyond established CT risk patterns and permits improved stratification of patients into different risk categories.     

Chronic inflammatory diseases and coronary heart disease: Insights from cardiovascular CT

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states.     

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.     

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.     

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.     

Peri-coronary inflammation is associated with findings on coronary computed tomography angiography and fractional flow reserve

PurposePeri-coronary adipose tissue attenuation expressed by fat attenuation index (FAI) on coronary CT angiography (CCTA) reflects peri-coronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between FAI and whole vessel and lesion plaque quantification on CCTA in stable patients with intermediate epicardial stenosis evaluated by fractional flow reserve (FFR).MethodsA total of 187 left anterior descending arteries (LAD) with intermediate stenosis who underwent FFR measurement and CCTA were studied. FAI was assessed by the crude analysis of the mean CT attenuation value of LAD on CCTA. Determinants of FAI and FFR were explored. Furthermore, the impact of combined baseline data, CCTA-derived lesion plaque assessment, whole vessel quantification, cardiac mass and FAI on discrimination efficacy for ischemia was evaluated as FFR used for a reference standard.ResultsThe mean FAI and the median FFR values were −73.0 and 0.77, respectively. Multivariate analysis revealed that male, CCTA-derived positive remodeling, lower minimum lumen area, higher target vessel total cardiac mass, and lower FFR were independent predictors of FAI. CCTA-derived two-dimensional and three-dimensional analysis and FAI were independently and significantly associated with FFR values. Net reclassification index and integrated discrimination improvement index were both significantly improved when FAI was added to the baseline model for lesions with FFR <0.75, but not for FFR≤0.80.ConclusionsFAI was associated with FFR, CCTA-derived two-dimensional and three-dimensional lumen and plaque quantification and cardiac mass in patients with intermediate lesions in LAD, indicating that comprehensive CTA assessment may provide risk-stratification.