Imaging coronary atherosclerotic precursors of acute myocardial infarction from baseline coronary computed tomography angiography to follow-up optical coherence tomography.

Purpose To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume. Materials and Methods This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years ± 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess interreader, intrareader, and interstudy reproducibility. Results Baseline and repeat coronary CT angiography scans were acquired within 19 days ± 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs ≥ 0.96) without bias. Scanner variability was ±18.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to ±29.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an α error of .05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up. Conclusion State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scan-rescan reproducibility. © RSNA, 2016 Online supplemental material is available for this article.

ObjectivesThis study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography–based plaque characteristics. BackgroundCoronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known. MethodsUtilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography–adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion. ResultsCL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs. ConclusionsIn a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA.

How early can atherosclerosis be detected by coronary CT angiography? Insights from quantitative CT analysis of serial scans in the PARADIGM trial

Prediction of plaque progression using different machine learning models of pericoronary adipose tissue radiomics based on coronary computed tomography angiography.

Plaque Morphology as Predictor of Late Plaque Events in Patients With Asymptomatic Type 2 Diabetes: A Long-Term Observational Study

Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Association between calcium density and future ACS risk. A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Funding Acknowledgements Type of funding sources: None. Background Currently, no recommendations are endorsed by the different scientific societies on the clinical use of repeated coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). Purpose The aim of this study was to develop and validate a practical and simple CCTA risk score to predict medium-term disease progression in symptomatic patients at low-to-intermediate probability of CAD. Methods Six hundred forty-six [430 (derivation cohort) and 216 (validation cohort)] symptomatic patients with two repeated, clinically indicated CCTA scans, non-obstructive stenosis, and absence of high-risk plaque at baseline CCTA were included. Disease progression was defined as the new occurrence of obstructive CAD (stenosis≥50%) and/or high-risk plaque features at follow-up CCTA. Results In the derivation cohort a total of 167 (27%) patients experienced disease progression. Hazard ratios for disease progression derived from multivariable Cox proportional hazard model were as follows: 1.8 (95% confidence interval: 1.1–2.8) for active smoking, 1.2 (1.1–1.3) for segment involvement score, 0.45 (0.29–0.69) for calcified plaque (vs. non-calcified plaque), 2.7 (1.8–4.0) for stenosis 25–49% (vs. stenosis &amp;lt;25%), and 1.6 (1.1–2.4) for left main or proximal left anterior descending coronary artery location. The C-statistic of the derived score was 0.69 (0.63–0.74) and 0.62 (0.54–0.71) in the derivation and validation cohorts, respectively. Figure shows 2 explicative cases. Conclusions The new CCTA-based risk score is a simple and practical tool which can predict mid-term CAD progression in symptomatic patients with non-obstructive CAD.

No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. We analyzed diagnostic performance of dual-acquisition CCTA for the detection of vasospastic angina. The patients were categorized into three groups according to their provocation test result (negative, n = 36; probable positive, n = 18; positive, n = 31). The diagnostic accuracy in terms of CCTA per patient had a sensitivity of 55% (95% CI, 40-69), specificity of 89% (95% CI, 74-97), positive predictive value (PPV) of 87% (95% CI, 72-95), and negative predictive value (NPV) of 59% (95% CI, 51-67). Dual-acquisition CCTA can support the non-invasive detection of vasospastic angina with relatively good specificity and PPV. CCTA was helpful for non-invasive screening of variant angina.

We evaluate the feasibility and safety of coronary computed tomography angiography (CCTA) as the first-line investigation in heart transplant patients and the rate of coronary allograft vasculopathy detected using CCTA. From September 2003 to June 2009, we prospectively included 65 heart transplant recipients, retaining 62 who underwent yearly CCTA for coronary allograft vasculopathy detection (261 CCTAs). We used 16-slice, 64-slice, and 2×64-slice CT machines. Patients with coronary artery stenosis by CCTA had a confirmation and a further follow-up exclusively by conventional coronary angiography (CCA). No major coronary events occurred during the study. Of the 62 baseline CCTAs, 37 (60%) were normal, 18 (29%) showed wall thickening, and 7 (11%) known significant stenosis, confirmed by CCA. The mean follow-up duration was 5 years. At the last follow-up, 26 (70%) patients with normal baseline findings remained normal, 9 (24%) had wall thickening, and 2 (6%) significant stenoses. Time to stenosis was consistently greater than 3 years. Of the 18 patients with initially wall thickening, 14 (78%) had wall thickening and 4 (22%) significant stenosis at last follow-up. The mean interval without any coronary lesion was 9.46±3.98 years. The mean interval without de novo significant stenosis was 10.31±4 years. CCTA seems to be a safe noninvasive tool for monitoring heart transplant patients, and thus obviating the need for CCA. In patients with normal baseline CCTA, a 2-year interval between CCTAs may be safe.

BackgroundWhether statin treatment can improve hemodynamic status of coronary atherosclerotic plaque remains unknown. It is of clinical interest to explore the hemodynamic change of coronary lesions after statin treatment.Methods and ResultsConsecutive patients with intermediate pre‐test probability of coronary artery disease were prospectively enrolled and underwent baseline coronary computed tomography angiography (CCTA) as well as follow‐up CCTA. The primary end point was to determine the lesion‐specific change of △computed tomography‐derived fractional flow reserve (△CT‐FFR, defined as the change of CT‐FFR value across each lesion) after rosuvastatin treatment. The secondary end point was to compare the change of other plaque characteristics according to serial CCTA findings. 152 patients (mean age: 67.1±9.7 years, 100 men, mean follow‐up duration of 13.9±2.5 months) were finally included. In non‐calcified plaque subgroup, △CT‐FFR was significantly lower at follow‐up compared with baseline (0.051±0.010 versus 0.035±0.012, P=0.013). All other parameters were not found to be significantly different between baseline and follow‐up CCTA measurements. In calcified plaque and mixed plaque subgroups, all parameters showed no significant differences between baseline and follow‐up CCTA groups (P>0.05 for all). According to multivariate regression analysis, non‐calcified plaque was >2 times more likely than calcified plaque to observe the decrease of △CT‐FFR (adjusted hazard ratio: 2.05 [1.03–4.09], P=0.042).ConclusionsIn patients with mild to intermediate coronary stenosis, rosuvastatin treatment resulted in a reduction in lesion‐specific △CT‐FFR at mid‐term follow‐up. This hemodynamic improvement was mainly observed for non‐calcified lesions.

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 (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm 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 TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) 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 TAVnorm (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 TAVnorm and may be the preferred method to report coronary atherosclerotic burden.

The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and composition of coronary atherosclerosis between patients experiencing an early (≤90 days) versus late ACS (>90 days) after baseline coronary computed tomography angiography (CCTA). From a multicenter study, we enrolled patients who underwent a clinically indicated baseline CCTA and experienced ACS during follow-up. Separate core laboratories performed blinded adjudication of ACS events and quantification of CCTA including compositional plaque volumes by Hounsfield units (HU): calcified plaque >350 HU, fibrous plaque 131-350 HU, fibrofatty plaque 31-130 HU and necrotic core <30 HU. In 234 patients (mean age 62 ± 12 years, 36% women), early and late ACS occurred in 129 and 105 patients after a mean of 395 ± 622 days, respectively. Patients with early ACS had a greater maximal diameter stenosis and maximal cross-sectional plaque burden as compared to patients with late ACS (P < 0.05). Larger total, fibrous, fibrofatty, and necrotic core volumes were observed in the early ACS group (P < 0.05). Findings for total, fibrous, fibrofatty, and necrotic core volumes were reproduced in an external validation cohort (P < 0.05). Volumetric differences in composition of coronary atherosclerosis exist between ACS patients according to their timing antecedent to the acute event. These data support that a large burden of non-calcified plaque on CCTA is strongly associated with near-term plaque instability and ACS risk.

Objective: To investigate the impact of the deep-learning-based CT fractional flow reserve (CT-FFR) on clinical decision-making and long-term prognosis in patients with obstructive coronary heart disease. Methods: In this single-center retrospective cohort study, consecutive patients with obstructive coronary heart disease (with at least one stenosis≥50%) on their first coronary computed tomography angiography (CCTA) in Beijing Anzhen Hospital from February 2017 to July 2018 were included. Baseline clinical and CT characteristics were collected. Deep-learning-based CT-FFR and Leiden CCTA risk score were calculated. All patients enrolled were followed up for at least 5 years. The study endpoint was major adverse cardiovascular events (MACE), defined as the composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization. Receiver operating characteristic (ROC) curves were drawn to define the optimal cut-off point of the Leiden score in predicting the 5-year MACE, and survival analysis and Cox regression were performed to explore the related factors of MACE. Results: A total of 622 patients, aged 61 (54, 66) years, with 407 (65.4%) males were included. Diagnostic coronary angiography was performed in 78 patients after their baseline CCTA, with 34 (43.6%) patients had CT-FFR>0.80. During a follow-up time of 2 181 (2 093, 2 355) days, 155 patients (24.9%) suffered from MACE. ROC derived optimal cut-off point of Leiden score for predicting MACE was 15.48. Survival analysis found that male patients, Leiden risk score>15 and CT-FFR≤0.80 had worse prognosis. Multivariate Cox regression analysis identified CT-FFR≤0.80 as an robust and independent predictor of MACE (HR=4.98, 95%CI 3.15-7.86, P<0.001). Conclusion: Deep-learning-based CT-FFR aids in clinical decision-making and the evaluation of long-term prognosis in patients with obstructive coronary heart disease.

Randomized Comparison of Progression of Atherosclerotic Plaques and Calcification of Coronary Artery in Atrial Fibrillation Patients Treated With Edoxaban Versus Warfarin (The REPRESENT-AF trial)