High-risk Plaque Features Research Articles

Imaging residual inflammatory cardiovascular risk.

Targeting residual cardiovascular risk in primary and secondary prevention, would allow deployment of novel therapeutic agents, facilitating precision medicine. For example, lowering vascular inflammation is a promising strategy to reduce the residual inflammatory cardiovascular risk in patients already receiving optimal medical therapy, but prescribing novel anti-inflammatory treatments will be problematic due to the lack of specific companion diagnostic tests, to guide their targeted use in clinical practice. Currently available tests for the detection of coronary inflammation are either non-specific for the cardiovascular system (e.g. plasma biomarkers) or expensive and not readily available (e.g. hybrid positron emission tomography imaging). Recent technological advancements in coronary computed tomography angiography (CCTA) allow non-invasive detection of high-risk plaque features (positive remodelling, spotty calcification, low attenuation plaque, and napkin-ring sign) and help identify the vulnerable patient, but they provide only indirectly information about coronary inflammation. Perivascular fat attenuation index (FAI), a novel method for assessing coronary inflammation by analysing routine CCTA, captures changes in the perivascular adipose tissue composition driven by inflammatory signals coming from the inflamed coronary artery, by analysing the three-dimensional gradients of perivascular attenuation, followed by adjustments for technical, anatomical, and biological factors. By detecting vascular inflammation, perivascular FAI enhances cardiovascular risk discrimination which could aid more cost-effective deployment of novel therapeutic agents. In this article, we present the existing non-invasive modalities for the detection of coronary inflammation and provide a practical guide for their use in clinical practice.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound

To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Nuclear Imaging: Focus on Vascular Probes

Noninvasive imaging technologies offer to identify several anatomic and molecular features of high-risk plaques. For the noninvasive molecular imaging of atherosclerotic plaques, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 18F-fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical for molecular imaging of atherosclerotic plaques with positron emission tomography. The intensity of FDG uptake in the vascular wall correlates closely with the degree of macrophage infiltration in atherosclerotic plaques. FDG positron emission tomographic imaging has become a powerful tool to identify and monitor noninvasively inflammatory activities in atherosclerotic plaques over time. This review examines how FDG positron emission tomographic imaging has given us deeper insight into the role of inflammation in atherosclerotic plaque progression and discusses perspectives for alternative radiopharmaceuticals to FDG that could provide a more specific and simple identification of high-risk lesions and help improve risk stratification of atherosclerotic patients. Visual Overview- An online visual overview is available for this article.

Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease

BackgroundAlthough the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)–defined HRPC. ObjectivesThe current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease. MethodsA total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm2, plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories. ResultsThe proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group. ConclusionsPhysiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438)

The best predictor of ischemic coronary stenosis: subtended myocardial volume, machine learning-based FFRCT, or high-risk plaque features?

The present study aimed to compare the diagnostic performance of a machine learning (ML)-based FFRCT algorithm, quantified subtended myocardial volume, and high-risk plaque features for predicting if a coronary stenosis is hemodynamically significant, with reference to FFRICA. Patients who underwent both CCTA and FFRICA measurement within 2weeks were retrospectively included. ML-based FFRCT, volume of subtended myocardium (Vsub), percentage of subtended myocardium volume versus total myocardium volume (Vratio), high-risk plaque features, minimal lumen diameter (MLD), and minimal lumen area (MLA) along with other parameters were recorded. Lesions with FFRICA ≤ 0.8 were considered to be functionally significant. One hundred eighty patients with 208 lesions were included. The lesion length (LL), diameter stenosis, area stenosis, plaque burden, Vsub, Vratio, Vratio/MLD, Vratio/MLA, and LL/MLD4 were all significantly longer or larger in the group of FFRICA ≤ 0.8 while smaller minimal lumen area, MLD, and FFRCT value were noted. The AUC of FFRCT + Vratio/MLD was significantly better than that of FFRCT alone (0.935 versus 0.873, p < 0.001). High-risk plaque features failed to show difference between functionally significant and insignificant groups. Vratio/MLD-complemented ML-based FFRCT for "gray zone" lesions with FFRCT value ranged from 0.7 to 0.8 and the combined use of these two parameters yielded the best diagnostic performance (86.5%, 180/208). ML-based FFRCT simulation and Vratio/MLD both provide incremental value over CCTA-derived diameter stenosis and high-risk plaque features for predicting hemodynamically significant lesions. Vratio/MLD is more accurate than ML-based FFRCT for lesions with simulated FFRCT value from 0.7 to 0.8. • Machine learning-based FFR CT and subtended myocardium volume both performed well for predicting hemodynamically significant coronary stenosis. • Subtended myocardium volume was more accurate than machine learning-based FFR CT for "gray zone" lesions with simulated FFR value from 0.7 to 0.8. • CT-derived high-risk plaque features failed to correctly identify hemodynamically significant stenosis.

Quantitative assessment of carotid plaque morphology (geometry and tissue composition) using computed tomography angiography

ObjectiveQuantification of carotid plaque morphology (geometry and tissue composition) may help stratify risk for future stroke and assess plaque progression or regression in response to medical risk factor modification. We assessed the feasibility and reliability of morphologic measurements of carotid plaques using computed tomography angiography (CTA) and determined the minimum detectable change in plaque features by this approach. MethodsCTA images of both carotid arteries in 50 patients were analyzed by two observers using a semiautomatic image analysis program, yielding 93 observations per user (seven arteries were excluded because of prior stenting). One observer repeated the analyses 4 weeks later. Measurements included total plaque volume; percentage stenosis (by diameter and area); and tissue composition for calcium, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). Reliability of measurements was assessed by intraclass and interclass correlation and Bland-Altman plots. Dice similarity coefficient (DSC) and modified Hausdorff distance (MHD) assessed reliability of geometric shape measurements. We additionally computed the minimum amount of change in these features detectable by our approach. ResultsThe cohort was 51% male (mean age, 70.1 years), and 56% had a prior stroke. The mean (± standard deviation) plaque volume was 837.3 ± 431.3 mm3, stenosis diameter was 44.5% ± 25.6%, and stenosis area was 58.1% ± 29.0%. These measurements showed high reliability. Intraclass correlation coefficients for plaque volume, percentage stenosis by diameter, and percentage stenosis by area were 0.96, 0.87, and 0.83, respectively; interclass correlation coefficients were 0.88, 0.84, and 0.78. Intraclass correlations for tissue composition were 0.99, 0.96, and 0.86 (calcium, LRNC, and IPH, respectively), and interclass correlations were 0.99, 0.92, and 0.92. Shape measurements showed high intraobserver (DSC, 0.95 ± 0.04; MHD, 0.16 ± 0.10 mm) and interobserver (DSC, 0.94 ± 0.05; MHD, 0.19 ± 0.12 mm) luminal agreement. This approach can detect a change of at least 3.9% in total plaque volume, 1.2 mm3 in calcium, 4.3 mm3 in LRNC, and 8.6 mm3 in IPH with the same observer repeating measurements and 9.9% in plaque volume, 1.9 mm3 in calcium, 7.9 mm3 in LRNC, and 6.8 mm3 in IPH for two different observers. ConclusionsCarotid plaque geometry (total volume, diameter stenosis, and area stenosis) and tissue composition (calcium, LRNC, and IPH) are measured reliably from clinical CTA images using a semiautomatic image analysis program. The minimum change in plaque volume detectable is ∼4% if the same observer makes both measurements and ∼10% for different observers. Small changes in plaque composition can also be detected reliably. This approach can facilitate longitudinal studies for identifying high-risk plaque features and for quantifying plaque progression or regression after treatment.

Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability using radiomic analysis of coronary computed tomography angiography.

AimsIdentification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability.Methods and resultsWe prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65–0.78 vs. 0.59, CI: 0.57–0.62; P < 0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72–0.88 vs. 0.66, CI: 0.58–0.73; P < 0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82–0.91 vs. 0.65, CI: 0.64–0.66; P < 0.001).ConclusionCoronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.

RELATIONSHIP BETWEEN LIPID BURDEN DETECTED BY NEAR-INFRARED SPECTROSCOPY AND VULNERABLE PLAQUE FEATURES BY MULTIDETECTOR COMPUTED TOMOGRAPHY

Multidetector computed tomography (MDCT)-derived high-risk plaque features have been reported to be low attenuation plaque, spotty calcification, positive remodeling, and napkin ring sign. This study sought to elucidate the relationship between these MDCT-derived high-risk plaque features and lipid

Plaque Assessment on Serial Coronary CTA

This review addresses the role of serial coronary computed tomography angiography (CTA) on the evaluation of atherosclerosis progression, risk stratification, and targeting individual pharmacotherapy. The presence, extent, and severity of coronary artery disease (CAD) detected by coronary CTA are associated with an adverse prognosis. Similarly, the presence of high-risk plaque features such as positive remodeling, low-attenuation plaque, spotty calcifications, and napkin-ring sign are associated with major adverse cardiac events. More recently, examinations using serial coronary CTA have also shown that these static CTA plaque features are associated with a more rapid progression of atherosclerosis on follow-up imaging and may identify a subset of patients at increased risk for plaque rupture. While the impact of serial CTA findings on management and hard outcomes remains a topic of ongoing investigation, available data supports the ability of statin therapy to reduce CTA-identified plaque burden and modify plaque composition. Coronary CTA identifies various plaque features associated with an increased risk of plaque progression and adverse cardiac events. Available data support the use of CTA to individualize statin therapy and utilize serial CTA imaging to study the impact of pharmacotherapy on plaque burden and outcomes.

Sex differences in coronary artery plaque composition detected by coronary computed tomography: quantitative and qualitative analysis.

BackgroundSex differences in the calculation of coronary heart disease risk have been analysed extensively. However, data on coronary plaque morphology diverge. We analysed plaque characteristics in patients with suspected coronary artery disease (CAD) and defined prognostic factors using coronary computed tomography angiography (CCTA).MethodsA total of 6,050 consecutive patients underwent CCTA and were enrolled in the registry. Patients with known CAD were excluded. The patients were propensity score matched (1:1 male:female) for age and known coronary risk factors. Coronary arteries were evaluated for stenosis, plaque types (non-calcified, mixed and calcified) and high-risk plaque features (napkin-ring sign, low-attenuation plaque, spotty calcifications, positive remodelling). Clinical follow-up was performed.ResultsA total of 1,050 patients (525 female, 525 male) in matched cohorts were selected for analysis. CCTA showed significantly higher calcium scores for males (mean 180.5 vs 67.8 AU, p < 0.0001) and a higher rate of CAD (66.0% vs 34.1%, p < 0.0001). In a total of 16,800 segments, males had significantly more plaques (861 vs 752, p < 0.0001) with a significantly larger proportion of calcified plaques, while females had more mixed and non-calcified plaques (33.5% vs 24.4%, p = 0.006 and 24.1% vs 13.6%, p = 0.22, respectively). After a mean follow-up of 5.6 years, major adverse cardiac event (MACE) rate was 5.3% in male and 1.9% in female patients (p < 0.05). The relative odds ratio for high-risk plaque features to predict MACE was higher in females.ConclusionBased on a higher relative risk for women with high-risk plaque features, the findings of our study support the increased importance of a differentiated qualitative plaque analysis to improve the risk stratification for both sexes.

Abstract TMP96: Carotid Plaque Characteristics Correlated to Baseline Vascular Risk Factors in a Large Randomized Trial: Results from CREST-2

Objectives: Assessment of carotid disease is most commonly performed with duplex ultrasonography (DUS). Measures of plaque area and tissue composition from DUS images may identify patients at risk for future neurologic events, and may assess the effects of vascular risk-factor modification (by measuring change in plaque area and/or tissue constituents). We quantified plaque area and tissue constituents from DUS images of CREST-2 participants at baseline and correlated them with their baseline vascular risk factors. Methods: CREST-2 consists of two multicenter, randomized trials in patients with asymptomatic ≥70% carotid stenosis comparing intensive medical management (IMM) plus endarterectomy or stenting vs IMM alone. Baseline B-mode DUS images from 500 patients underwent manual plaque outlining and automatic pixel brightness assessment. Plaque area, grayscale median (GSM), Gray-Weale score for heterogeneity, and areas for intraplaque hemorrhage and lipid were the output parameters. We computed the parameter estimates (95% confidence intervals) for baseline patient characteristics (age, sex, race, diabetes, smoking, BMI, blood pressure and LDL levels) versus plaque characteristics. Results: High-risk plaque features (larger plaque area, lower GSM , lower Gray-Weale scores, or larger areas of hemorrhage and lipid) were present in older patients, males, and those with elevated diastolic blood pressure and LDL levels (Table). Conclusions: In a randomized trial of asymptomatic patients with high-grade carotid stenosis, DUS-based computation of plaque geometry and tissue composition is feasible. Elevated diastolic blood pressure and LDL levels at baseline are associated with high-risk plaque characteristics. These novel findings identify potentially modifiable targets for aggressive treatment to reduce stroke-risk in patients with carotid stenosis.

Personalized Assessment of the Coronary Atherosclerotic Arteries by Intravascular Ultrasound Imaging: Hunting the Vulnerable Plaque.

The term “vulnerable plaque” is commonly used to refer to an atherosclerotic plaque that is prone to rupture and the formation of thrombosis, which can lead to several cardiovascular and cerebrovascular events. Coronary artery atherosclerosis has a wide variety of different phenotypes among patients who may have a substantially variable risk for plaque rupture and cardiovascular events. Mounting evidence has proposed three distinctive histopathological mechanisms: plaque rupture, plaque erosion and calcified nodules. Studies have demonstrated the characteristics of plaques with high vulnerability such as the presence of a thin fibrous cap, a necrotic lipid-rich core, abundant infiltrating macrophages and neovascularization. However, traditional coronary angiographic imaging fails to determine plaque vulnerability features, and its ability to individualize treatment strategies is limited. In recent decades, catheter-based intravascular ultrasound imaging (IVUS) modalities have been developed to identify vulnerable plaques and ultimately vulnerable patients. The aim is to individualize prediction, prevention and treatment of acute coronary events based on the identification of specific features of high-risk atherosclerotic plaques, and to identify the most appropriate interventional procedures for their treatment. In this context, the aim of this review is to discuss how personalized assessment of coronary atherosclerotic arteries can be achieved by intravascular ultrasound imaging focusing on vulnerable plaque detection.

Non obstructive high-risk plaque but not calcified by coronary CTA, and the G-score predict ischemia

BackgroundThe association of plaque morphology with ischemia in non-obstructive lesions has not been fully eludicated: Calcium density and high-risk plaque features have not been explored.Objectives: to assess whether high-risk plaque or calcified, and global mixed including non-calcified plaque burden (G-score) by coronary CTA predict ischemia in non-obstructive lesions using non-invasive fractional flow reserve (FFRCT). MethodsIn 106 patients with low-to-intermediate pre-test probability referred to coronary 128-slice dual source CTA, lesion-based and distal FFRCT were computated.The 4 high-risk-plaque criteria: Low-attenuation-plaque, Napkin Ring Sign, positive remodelling and spotty calcification were recorded. Plaque density (HU) and stenosis (MLA,MLD,%area,%diameter stenosis) were quantified. Plaque composition was classified as type 1–4:1 = calcified, 2 = mixed (calcified > non-calcified), 3 = mixed (non-calcified > calcified), 4 = non-calcified, and expressed by the G-score: Z = Sum of type 1–4 per segment. The total plaque segment involvement score (SIS) and the Coronary Calcium Score (Agatston) were calculated. Results89 non–obstructive lesions were included. Both lesion-based and distal FFRCT were lower in high-risk-plaque as compared to calcified (0.85 vs 0.93, p < 0.001 and 0.79 vs 0.86, p = 0.002). The prevalence of lesion-based ischemia (FFRCT<0.8) was higher in high-risk-plaque as compared to calcified (25% vs. 2.5%, p = 0.007). Similarly, the rate of distal ischemia (40% vs 17.5%) was higher, respectively.Lower plaque density (HU) indicating higher lipid plaque component (p = 0.024) predicted lesion based FFRCT in low attenuation plaque. For all lesions (n = 89) including calcified (p = 0.003), the correlation enhanced.Positive remodelling and an increasing non-calcified plaque burden (G-score) in relation to calcified were associated with lower FFRCT distal (p = 0.042), but not the SIS and calcium score. ConclusionHigh-risk-plaque but not calcified, an increasing lipid-necrotic-core component and non-calcified mixed plaque burden (G-score) predict ischemia in non-obstructive lesions (INOCA), while an increasing calcium compactness acts contrary.

Computed Tomography Coronary Angiography Derived High Risk Plaques Predict Physiological Significance of Coronary Artery Stenoses as Assessed with Invasive Fractional Flow Reserve

Background: High-risk plaque (HRP) characteristics such as low attenuation plaque (LAP), positive remodelling and spotty calcification are feasibly identified on computed tomography coronary angiography (CTCA). The presence of ≥2HRP are considered very high-risk with a strong independent association with prognosis. Fractional Flow Reserve (FFR) however, remains the reference standard for lesion-level coronary intervention in stable patients. Purpose: We investigated the relationship between qualitative HRP (non-invasive anatomical assessment) and FFR (invasive functional assessment). Methods: Consecutive stable coronary artery disease patients who underwent CTCA and invasive FFR at MonashHeart between 2009–2017 were reviewed. Patients with significant FFR (<0.8) were propensity-matched for age, sex and cardiovascular risk factors to patients with non-significant FFR resulting in 55 patients per group. Logistic regression analysis was applied to define predictors of FFR significance. Odds ratios (OR) with respective 95% confidence intervals are reported. Results: The presence of a single HRP feature in a lesion was similar between FFR significant vs non-significant (78% vs 72%, p = 0.66). The presence of ≥2 HRP features in a lesion was greater in FFR significant vessels (51% vs 25%, p = 0.01). Univariable predictors of FFR-significance included increasing total plaque burden (p = 0.002), increasing minimal luminal area (p = 0.002), ≥2HRP features (p = 0.007), and presence of LAP (p = 0.05). On multivariable assessment, total plaque burden (Odds Ratio (OR 1.06 (1.01–1.11), p = 0.01), decreasing minimal luminal area (OR 0.54 (0.41–0.81), p = 0.001), and ≥2HRP (OR 3.91 (1.43–10.71), p = 0.008) remained independent predictors of significant invasive FFR. Conclusions: The presence of ≥2 HRP features within a coronary lesion non-invasively identified on CTCA independently predict FFR significance.

Association between 18F-Sodium Fluoride Positron Emission Tomography Uptake and High-Risk Plaque Features on Optical Coherence Tomography in Patients with Acute Coronary Syndrome

Association between 18F-Sodium Fluoride Positron Emission Tomography Uptake and High-Risk Plaque Features on Optical Coherence Tomography in Patients with Acute Coronary Syndrome

Quantitative but not Qualitative Computed Tomography Coronary Angiography High Risk Plaque Characteristics are Associated with Major Adverse Cardiovascular Events in Patients with Non-Significant Invasive Fractional Flow Reserve

Background: Functionally non-significant coronary stenoses by fractional flow reserve assessment (FFR >0.8) are not routinely intervened upon. These patients may still remain at risk of major adverse cardiovascular events (MACE). Computed tomography coronary angiography (CTCA) allows non-invasive assessment of qualitative and quantitative high-risk plaque (HRP) morphology which are associated with future MACE. We seek to determine if HRP was associated with MACE in patients with functionally non-significant FFR. Methods: Consecutive patients with stable chest pain who underwent CTCA and FFR within a 3-month interval, between 2009–2017, at MonashHeart were examined. Qualitative HRP were low attenuation plaque (LAP, <30 Hounsfield units), positive remodelling and spotty calcification. Quantitative HRP was regarded as LAP volume normalised to vessel length analysed (distal plaque to ostium). MACE was defined as cardiovascular death, myocardial infarction (MI) or unstable angina. Results: 54 patients (age 63 ± 11, 70% males) were evaluated. There were 39 vessels in 39 patients (72%) with qualitative HRP. Seven patients (13%) experienced MACE over 5.4-year median follow-up with 5 demonstrating qualitative HRP. The mean interval between CTCA and MACE was 576 days. Qualitative HRP features were not associated with MACE, LAP (p = 0.2), positive remodelling (p = 0.99), spotty calcification (p = 0.69). Normalised LAP volume was predictive of MACE (Hazard Ratio 1.10, 95% confidence interval 1.01–1.10, p = 0.02). Traditional anatomic predictors of MACE, including total plaque burden (p = 0.91), minimal luminal area <4 mm (p = 0.99) and total plaque volume (p = 0.4) were not significant predictors. Conclusions: In patients with functionally non-significant FFR, there remains a risk of MACE and quantitative but not qualitative HRP characteristics appear to associate with prognosis.

Coronary CT Angiography with Knowledge-Based Iterative Model Reconstruction for Assessing Coronary Arteries and Non-Calcified Predominant Plaques.

ObjectiveTo assess the effects of iterative model reconstruction (IMR) on image quality for demonstrating non-calcific high-risk plaque characteristics of coronary arteries.Materials and MethodsThis study included 66 patients (53 men and 13 women; aged 39–76 years; mean age, 55 ± 13 years) having single-vessel disease with predominantly non-calcified plaques evaluated using prospective electrocardiogram-gated 256-slice CT angiography. Paired image sets were created using two types of reconstruction: hybrid iterative reconstruction (HIR) and IMR. Plaque characteristics were compared using the two algorithms. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images and the CNR between the plaque and adjacent adipose tissue were also compared between the two reformatted methods.ResultsSeventy-seven predominantly non-calcified plaques were detected. Forty plaques showed napkin-ring sign with the IMR reformatted method, while nineteen plaques demonstrated napkin-ring sign with HIR. There was no statistically significant difference in the presentation of positive remodeling, low attenuation plaque, and spotty calcification between the HIR and IMR reconstructed methods (all p > 0.5); however, there was a statistically significant difference in the ability to discern the napkin-ring sign between the two algorithms (χ2 = 12.12, p < 0.001). The image noise of IMR was lower than that of HIR (10 ± 2 HU versus 12 ± 2 HU; p < 0.01), and the SNR and CNR of the images and the CNR between plaques and surrounding adipose tissues on IMR were better than those on HIR (p < 0.01).ConclusionIMR can significantly improve image quality compared with HIR for the demonstration of coronary artery and atherosclerotic plaques using a 256-slice CT.

Abstract 17414: Increased Activity of Brain Region Governing Stress Perception is Associated With Plaque Vulnerability and Vascular Inflammation in Acute Myocardial Infarction Population; Retrospective and Prospective Study Evaluated by 18 FDG-PET/CT and OCT

Backgrounds: Chronic mental stress is a major risk factor of coronary artery disease, but there is a lack of direct mechanistic evidence between brain amygdala activity, a neural stress center, versus plaque vulnerability in acute coronary syndrome. In this study, we aimed to evaluate whether brain amygdala activity in AMI patients assessed by 18 F-FDG PET/CT could be associated with vascular inflammation in carotid beds and high-risk coronary plaque features evaluated by OCT. Methods and Results: In retrospective analysis, the patients who underwent 18 F-FDG PET/CT and CAG at Korea University Guro Hospital (Seoul, Korea). Among 1802 patients underwent 18 F-FDG PET/CT from October 1 2009 to 31 December 31 2015, 230 patients received CAG. After excluding 36 patients who had active cancer or brain disease, 198 were stratified according to degree of coronary severity by syntax score [none (n=159); mild to moderate (n=26); severe (n=13)]. Brain amygdalar activity on PET was quantified as target-to-background ratio (TBR) of standardized uptake value (amygdalar SUV max /temporal SUV mean ). The amygdalar TBR was significantly higher in patients with severe coronary disease rather than those without coronary stenosis or mild to moderate stenosis assessed by syntax score (P=0.03). Intriguingly, among 13 patients with severe CAD, the amygdalar TBR significantly increased in the 6 patients presented as AMI compared to non-MI patients (P=0.03). In following prospective study, we performed 18 F-FDG PET/CT in AMI patients underwent percutaneous coronary intervention within index admission period, and in patients with chronic stable angina (CSA) as control. The plaque morphology in non-culprit segment of infarct-related artery (IRA) was estimated by OCT in AMI patients. Brain amygdalar TBR was significantly higher in AMI patients compared to CSA patients (p&lt;0.05). In AMI patients, amygdalar activity was significantly associated with vascular inflammation quantified as carotid TBR (p&lt;0.05). The increased amygdalar activity was associated with high-risk plaque characteristics of non-culprit segments of IRA. Conclusions: The amygdalar activity assessed by 18 F-FDG PET/CT was significantly higher in patients with AMI than CSA. This amygdalar activity was related to vulnerable plaque characteristics of IRA. Our results suggest that brain emotional activity in ACS could contribute to plaque instability in pan-vascular beds.

Prognostic Value of Intravascular Ultrasound in Patients With Coronary Artery Disease

BackgroundIt has been shown that intravascular ultrasound (IVUS) and radiofrequency (RF-)IVUS can detect high-risk coronary plaque characteristics. ObjectivesThe authors studied the long-term prognostic value of (RF-)IVUS-derived plaque characteristics in patients with coronary artery disease (CAD) undergoing coronary angiography. MethodsFrom 2008 to 2011, (RF-)IVUS was performed in 1 nonstenotic segment of a nonculprit coronary artery in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. The pre-defined primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, nonfatal ACS, or unplanned revascularization. Hazard ratios (HRs) were adjusted for age, sex, and clinical risk factors. ResultsDuring a median follow-up of 4.7 years, 152 patients (26.2%) had MACE. The presence of a lesion with a minimal luminal area ≤4.0 mm2 was independently associated with MACE (HR: 1.49; 95% CI: 1.07 to 2.08; p = 0.020), whereas the presence of a thin-cap fibroatheroma lesion or a lesion with a plaque burden ≥70% on its own were not. Results were comparable when the composite endpoint included cardiac death instead of all-cause death. The presence of a lesion with a plaque burden of ≥70% was independently associated with the composite endpoint of cardiac death, nonfatal ACS, or unplanned revascularization after exclusion of culprit lesion-related events (HR: 1.66; 95% CI: 1.06 to 2.58; p = 0.026). Likewise, each 10-U increase in segmental plaque burden was independently associated with a 26% increase in risk of this composite endpoint (HR: 1.26 per 10-U increase; 95% CI: 1.03 to 1.52; p = 0.022). ConclusionsIVUS-derived small luminal area and large plaque burden, and not RF-IVUS–derived compositional plaque features on their own, predict adverse cardiovascular outcome during long-term follow-up in patients with CAD. (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis–Intravascular Ultrasound Study [AtheroRemoIVUS]; NCT01789411)

Current and Emerging Preclinical Approaches for Imaging-Based Characterization of Atherosclerosis.

Atherosclerotic plaques can remain quiescent for years, but become life threatening upon rupture or disruption, initiating clot formation in the vessel lumen and causing acute myocardial infarction and ischemic stroke. Whether and how a plaque ruptures is determined by its macroscopic structure and microscopic composition. Rupture-prone plaques usually consist of a thin fibrous cap with few smooth muscle cells, a large lipid core, a dense infiltrate of inflammatory cells, and neovessels. Such lesions, termed high-risk plaques, can remain asymptomatic until the thrombotic event. Various imaging technologies currently allow visualization of morphological and biological characteristics of high-risk atherosclerotic plaques. Conventional protocols are often complex and lack specificity for high-risk plaque. Conversely, new imaging approaches are emerging which may overcome these limitations. Validation of these novel imaging techniques in preclinical models of atherosclerosis is essential for effective translational to clinical practice. Imaging the vessel wall, as well as its biological milieu in small animal models, is challenging because the vessel wall is a small structure that undergoes continuous movements imposed by the cardiac cycle as it is adjacent to circulating blood. The focus of this paper is to provide a state-of-the-art review on techniques currently available for preclinical imaging of atherosclerosis in small animal models and to discuss the advantages and limitations of each approach.