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Backgrounds: Coronary computed tomography angiography (CTA) allows for the assessment of atherosclerotic plaque burden across the entire coronary vasculature. No studies have examined the relationship between the underlying pathology of the culprit lesion and total plaque burden in patients with acute coronary syndromes. The aim of this study was to compare the total plaque burden between patients with plaque rupture versus plaque erosion., Methods: A total of 232 patients who presented with their first non-ST-segment elevation acute coronary syndrome and underwent both CTA and optical coherence tomography imaging before intervention were selected. Quantitative analysis was performed using semi-automated software (Autoplaque version 3.0, Cedars-Sinai Medical Center). An attenuation of <30 Hounsfield units defined low-density non-calcified plaque (LDNCP). All 3 vessels were assessed using the modified 17-segment American Heart Association model for coronary segment classification., Results: Among 232 patients, 125 (53.9%) had plaque rupture and 107 (46.1%) had plaque erosion. Total plaque burden (48.2 [39.8-54.9] % vs. 44.1 [38.6-50.0] %, P ​= ​0.006), total non-calcified plaque (NCP) burden (46.6 [39.1-53.3] % vs. 43.0 [37.6-49.2] %, P ​= ​0.013), total LDNCP burden (2.3 [1.4-3.0] % vs. 1.7 [1.2-2.6] %, P ​= ​0.016), and total calcified plaque (CP) burden (0.8 [0.1-1.6] % vs. 0.4 [0.0-1.4] %, P ​= ​0.047) were significantly greater in patients with culprit plaque rupture than in those with culprit plaque erosion., Conclusion: Patients with plaque rupture, compared with those with plaque erosion, had a greater total plaque burden, NCP burden, LDNCP burden, and CP burden., Clinical Trial Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04523194., Competing Interests: Declaration of competing interest Disclosures: Dr. Niida received a grant from the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad. Outside the present study, Dr. Dey has received software royalties from Cedars-Sinai Medical Center and has a patent. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid and stock options from Elucid. Dr. Jang has received educational grants from Abbott Vascular and a consulting fee from Svelte Medical Systems. The remaining authors have nothing to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between plaque burden and microscopic characterization of plaque features as it pertains to clinical presentation has not been fully investigated. The aim of this study was to compare the relationship between plaque burden and plaque vulnerability in patients with acute coronary syndromes (ACS) versus chronic coronary syndrome (CCS)., Methods: Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) before coronary intervention were enrolled. All plaques were detected in culprit vessels using CTA, and total plaque volume (TPV) and OCT features were assessed at the corresponding sites. All plaques were divided into three groups according to the tertile levels of TPV (low TPV: <96.5 ​mm 3 , moderate TPV: 96.5-164.7 ​mm 3 , high TPV: ≥164.8 ​mm 3 )., Results: A total of 990 plaques were imaged by OCT in 419 patients: 445 plaques in 190 (45.3%) patients with ACS and 545 in 229 (54.7%) with CCS. Macrophage was more prevalent in plaques with greater TPV in patients who presented with ACS but not in those who presented with CCS (low vs. moderate vs. high TPV group: macrophage 57.4% vs. 71.8% vs. 82.4% in ACS; 63.4% vs. 67.8% vs. 66.7% in CCS; interaction P ​= ​0.004). Lipid arc increased as TPV increased, especially in patients who presented with ACS. Conversely, the layer index increased as TPV increased in patients with CCS., Conclusion: Greater plaque burden was closely related to higher levels of plaque vulnerability in ACS and greater volume of layered plaque in CCS., Trial Registration: clinicaltrials.gov Identifier: NCT04523194., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, Elucid, and Biomarin, stock options from Elucid, and is on the advisory board of Cleerly. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated., Objectives: This study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability., Methods: Patients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography-derived vulnerable features among the 4 groups., Results: Among 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB., Conclusions: Greater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)., Competing Interests: Funding Support and Author Disclosures Dr Fujimoto was supported by fellowship grants from the Uehara Memorial Foundation (Tokyo, Japan) and the Fukuda Foundation for Medical Technology (Tokyo, Japan). Dr Ferencik has received consulting fees from Siemens Healthineers, Elucid, Heartflow, and BioMarin; served on the advisory board for Cleerly; and has stock options for Elucid. Dr Jang has received educational grants from Abbott Vascular; his research has been supported by Mrs Gillian Gray through the Allan Gray Fellowship Fund in Cardiology and by Mukesh and Priti Chatter through the Chatter Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This paper develops a computationally efficient model for automatic patient-specific seizure prediction using a two-layer LSTM from multichannel intracranial electroencephalogram time-series data. We decrease the number of parameters by employing a smaller input size and fewer electrodes, thereby making the model a viable option for wearable and implantable devices. We test the proposed prediction model on 26 patients from the European iEEG dataset, which is the largest epileptic seizure dataset. We also apply an automatic preprocessing technique based on a common average reference to remove artifacts from this dataset. The simulation results show that the model with its simple structure in conjunction with the mean post-processing procedure performed the best, with an average AUC of 0.885. This study is the first that utilizes the European database for epilepsy prediction application and the first that analyzes the effect of the seizure type on the system performance and demonstrates that the seizure type has a considerable impact.

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8% vs. 66.7%, P < 0.001), thin-cap fibroatheroma (26.1% vs. 17.5%, P = 0.026), microvessels (61.8% vs. 34.6%, P < 0.001), and cholesterol crystals (38.6% vs. 25.6%, P = 0.003). Layered plaque was associated with a higher level of vascular inflammation and a higher prevalence of plaque vulnerability, which might play an important role in rapid plaque progression.Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT04523194 ., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Positive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA)., Methods: A total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling., Results: In the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26-3.48], P ​= ​0.004)., Conclusion: Greater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease., Methods and Results: A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P <0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P =0.017)., Conclusions: The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

Background: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes., Methods and Results: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P <0.001), low attenuation plaque (63.1% versus 33.7%, P <0.001), napkin-ring sign (32.4% versus 11.0%, P <0.001), and spotty calcification (55.0% versus 34.9%, P <0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm 3 , P <0.001) and remodeling index (1.30 versus 1.20, P =0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%., Conclusions: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes., Registration Information: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Background: Although patients with high-risk plaque (HRP) on coronary computed tomography angiography (CTA) are reportedly at increased risk for future cardiovascular events, individual HRP features have not been systematically validated against high-resolution intravascular imaging., Objectives: The aim of this study was to correlate HRP features on CTA with plaque characteristics on optical coherence tomography (OCT)., Methods: Patients who underwent both CTA and OCT before coronary intervention were enrolled. Plaques in culprit vessels identified by CTA were evaluated with the use of OCT at the corresponding sites. HRP was defined as a plaque with at least 2 of the following 4 features: positive remodeling (PR), low-attenuation plaque (LAP), napkin-ring sign (NRS), and spotty calcification (SC). Patients were followed for up to 3 years., Results: The study included 448 patients, with a median age of 67 years and of whom 357 (79.7%) were male, and 203 (45.3%) presented with acute coronary syndromes. A total of 1,075 lesions were analyzed. All 4 HRP features were associated with thin-cap fibroatheroma. PR was associated with all OCT features of plaque vulnerability, LAP was associated with lipid-rich plaque, macrophage, and cholesterol crystals, NRS was associated with cholesterol crystals, and SC was associated with microvessels. The cumulative incidence of the composite endpoint (target vessel nontarget lesion revascularization and cardiac death) was significantly higher in patients with HRP than in those without HRP (4.7% vs 0.5%; P = 0.010)., Conclusions: All 4 HRP features on CTA were associated with features of vulnerability on OCT. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)., Competing Interests: Funding Support and Author Disclosures Dr Jang’s research has been supported by Mrs. Gillian Gray through the Allan Gray Fellowship Fund in Cardiology and by Mukesh and Priti Chatter through the Chatter Foundation; and Dr Jang has received educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems. Dr Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit. In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17 C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased. These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is not known whether there is a sex difference in the association between perivascular inflammation and plaque vulnerability. The aim of this study was to investigate the sex-specific association between perivascular inflammation and plaque vulnerability., Methods: Patients who underwent coronary computed tomography angiography and optical coherence tomography were enrolled. All images were analyzed at a core laboratory. The level of perivascular inflammation was assessed by pericoronary adipose tissue attenuation on computed tomography angiography and the level of plaque vulnerability by optical coherence tomography. Patients were classified into 3 groups according to tertile levels of culprit vessel pericoronary adipose tissue attenuation (low inflammation, ≤-73.1 Hounsfield units; moderate inflammation, -73.0 to -67.0 Hounsfield units; or high inflammation, ≥-66.9 Hounsfield units)., Results: A total of 968 lesions in 409 patients were included: 184 lesions in 82 women (2.2 plaques per patient) and 784 lesions in 327 men (2.4 plaques per patient). Women were older (median age, 71 versus 65 years; P <0.001) and had less severe coronary artery disease with a lower plaque burden than men. In women, it was found that perivascular inflammation was significantly associated with plaque vulnerability, with a higher prevalence of thin-cap fibroatheroma and greater macrophage grades in the high inflammation group compared with the low inflammation group (low versus moderate versus high inflammation in women: 18.5% versus 31.8% versus 46.9%, P =0.002 for low versus high inflammation; 3 versus 4 versus 12, P <0.001 for low versus high inflammation, respectively). However, no significant differences were observed among the 3 groups in men., Conclusions: Perivascular inflammation was associated with a higher prevalence of thin-cap fibroatheroma and more significant macrophage accumulation in women but not in men., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194., Competing Interests: Disclosures Dr Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems Inc. Dr Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. The other authors report no conflicts.

Background: Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated., Methods and Results: A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin-cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P <0.001), lipid-rich plaque (165 [88.7%] versus 346 [80.7%], P =0.014), macrophages (147 [79.0%] versus 294 [68.5%], P =0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P =0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P <0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P <0.001; 8 [4.3%] versus 1 [0.2%], P <0.001; 5 [2.7%] versus 3 [0.7%], P =0.030; and 5 [2.7%] versus 2 [0.5%], P =0.013, respectively)., Conclusions: The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

Background: Recently, it was reported that noncalcified plaque (NCP) volume was an independent predictor for cardiac events. Pericoronary adipose tissue (PCAT) attenuation is a marker of vascular inflammation and has been associated with increased cardiac mortality. The aim of this study was to evaluate the relationships between NCP volume, plaque vulnerability, and PCAT attenuation., Methods: Patients who underwent preintervention coronary computed tomography angiography and optical coherence tomography were enrolled. Plaque volume was measured by computed tomography angiography, plaque vulnerability by optical coherence tomography, and the level of coronary inflammation by PCAT attenuation. The plaques were divided into 2 groups of high or low NCP volume based on the median NCP volume., Results: Among 704 plaques in 454 patients, the group with high NCP volume had a higher prevalence of lipid-rich plaque (87.2% versus 75.9%; P <0.001), thin-cap fibroatheroma (38.1% versus 20.7%; P <0.001), macrophage (77.8% versus 63.4%; P <0.001), microvessel (58.2% versus 42.9%; P <0.001), and cholesterol crystal (42.0% versus 26.7%; P <0.001) than the group with low NCP plaque volume. The group with high NCP volume also had higher PCAT attenuation than the group with low NCP volume (-69.6±10.0 versus -73.5±10.6 Hounsfield unit; P <0.001). In multivariable analysis, NCP volume was significantly associated with thin-cap fibroatheroma and high PCAT attenuation. In the analysis of the combination of PCAT attenuation and NCP volume, the prevalence of thin-cap fibroatheroma was the highest in the high PCAT attenuation and high NCP volume group and the lowest in the low PCAT attenuation and low NCP volume group., Conclusions: Higher NCP volume was associated with higher plaque vulnerability and vascular inflammation. The combination of PCAT attenuation and NCP volume may help identify plaque vulnerability noninvasively., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194., Competing Interests: Disclosures Dr Jang received educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Outside the current study, Dr Dey received software royalties from the Cedars-Sinai Medical Center and has a patent. The other authors report no conflicts.

Patients with acute coronary syndromes caused by plaque erosion might be managed conservatively without stenting. Currently, the diagnosis of plaque erosion requires an invasive imaging procedure. We sought to develop a deep learning (DL) model that enables an accurate diagnosis of plaque erosion using coronary computed tomography angiography (CTA). A total of 532 CTA scans from 395 patients were used to develop a DL model: 426 CTA scans from 316 patients for training and internal validation, and 106 separate scans from 79 patients for validation. Momentum Distillation-enhanced Composite Transformer Attention (MD-CTA), a novel DL model that can effectively process the entire set of CTA scans to diagnose plaque erosion, was developed. The novel DL model, compared to the convolution neural network, showed significantly improved AUC (0.899 [0.841-0.957] vs. 0.724 [0.622-0.826]), sensitivity (87.1 [70.2-96.4] vs. 71.0 [52.0-85.8]), and specificity (85.3 [75.3-92.4] vs. 68.0 [56.2-78.3]), respectively, for the patient-level prediction. Similar results were obtained at the slice-level prediction AUC (0.897 [0.890-0.904] vs. 0.757 [0.744-0.770]), sensitivity (82.2 [79.8-84.3] vs. 68.9 [66.2-71.6]), and specificity (80.1 [79.1-81.0] vs. 67.3 [66.3-68.4]), respectively. This newly developed DL model enables an accurate CT diagnosis of plaque erosion, which might enable cardiologists to provide tailored therapy without invasive procedures.Clinical Trial Registration: http://www.clinicaltrials.gov , NCT04523194., (© 2023. The Author(s).)

Background: High cardiovascular mortality has been reported in young patients with diabetes. However, the underlying pathology in different age groups of patients with diabetes has not been studied., Methods and Results: The aim of this study was to investigate the plaque characteristics and underlying pathology of acute coronary syndrome in different age groups of patients with or without diabetes in a large cohort. Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging were included. Culprit plaque was classified as plaque rupture, plaque erosion, or calcified plaque and stratified into 5 age groups. Plaque characteristics including features of vulnerability were examined by optical coherence tomography. Among 1394 patients, 482 (34.6%) had diabetes. Patients with diabetes, compared with patients without diabetes, had a higher prevalence of lipid-rich plaque (71.2% versus 64.8%, P =0.016), macrophage (72.0% versus 62.6%, P <0.001), and cholesterol crystal (27.6% versus 19.7%, P <0.001). Both diabetes and nondiabetes groups showed a decreasing trend in plaque erosion with age (patients with diabetes, P =0.020; patients without diabetes, P <0.001). Patients without diabetes showed an increasing trend with age in plaque rupture ( P =0.004) and lipid-rich plaque ( P =0.018), whereas patients with diabetes had a high prevalence of these vulnerable features at an early age that remained high across age groups., Conclusions: Patients without diabetes showed an increasing trend with age in plaque rupture and lipid-rich plaque, whereas patients with diabetes had a high prevalence of these vulnerable features at an early age. These results suggest that atherosclerotic vascular changes with increased vulnerability start at a younger age in patients with diabetes., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04523194, NCT03479723. URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041692.

Outcomes after myocardial infarction in women remain poor. The number of cardiovascular risk factors in women increase with age, however the relation between risk factors and culprit plaque characteristics in this population is poorly understood. The aim of the study was to investigate the relation between risk factors and culprit plaque characteristics in women with acute coronary syndrome (ACS). A total of 382 women who presented with ACS and underwent pre-intervention optical coherence tomography imaging of the culprit lesion were included in this analysis. The culprit plaques were categorized as plaque rupture, plaque erosion or calcified plaque, and then stratified by age and risk factors. The predominant pathology of ACS was plaque erosion in young patients (<60 years), which decreased with age (p <0.001). Current smokers had a high prevalence of plaque rupture (60%) and lipid plaque (79%). Women with diabetes tended to have more lipid plaque (70%) even at a young age. In women with hyperlipidemia, the prevalence of lipid plaques was modest in younger ages, but rose gradually with age (p <0.001). An increasing age trend for lipid plaque was also observed in women with hypertension (p = 0.03) and current smokers (p = 0.01). In conclusion, early treatment of risk factors such as diabetes in young women might be important before accelerated progression of atherosclerosis begins as age advances. Clinical trial registration: http://www.clinicaltrials.gov, NCT01110538, NCT03479723 and NCT02041650., Competing Interests: Declaration of Competing Interest Dr. Jang received educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Coronary artery disease reporting and data system (CAD-RADS) predicts future cardiovascular events in patients with coronary artery disease (CAD). However, information on vascular inflammation and vulnerability remains scarce., Methods: Patients who underwent coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) prior to coronary intervention were enrolled. All three coronary arteries were evaluated for CAD-RADS score and pericoronary adipose tissue (PCAT) attenuation, while the culprit vessel was analyzed for plaque vulnerability by OCT., Results: A total of 385 patients with 915 lesions were divided into two groups based on CAD-RADS score: 103 (26.8%) were categorized as CAD-RADS 4b/5 and 282 (73.2%) as CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had a higher level of PCAT attenuation (mean of 3 coronary arteries) than those with CAD-RADS ≤4a (-68.4 ​± ​6.7 HU vs. -70.1 ​± ​6.5, P ​= ​0.022). The prevalence of macrophage was higher, and lipid index was greater in patients with CAD-RADS 4b/5 than CAD-RADS ≤4a (94.2% vs. 83.0%, P ​= ​0.004, 1845 vs. 1477; P ​= ​0.003). These associations were significant in the culprit vessels of patients with chronic coronary syndrome but not in those with acute coronary syndromes., Conclusions: Higher CAD-RADS score was associated with higher levels of vascular inflammation and plaque vulnerability., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Layered plaque, a signature of previous plaque disruption, is a known predictor of rapid plaque progression. Layered plaque can be identified in vivo by optical coherence tomography. Studies have reported differences in plaque burden between women and men, but sex differences in the pattern of layered plaque are unknown., Methods: Preintervention optical coherence tomography images of 533 patients with chronic coronary syndromes were analyzed. Detailed plaque characteristics of layered and nonlayered plaques of the target lesion were compared between men and women., Results: The prevalence of layered plaque was similar between men (N=418) and women (N=115; 55% versus 54%; P =0.832). In men, more features of plaque vulnerability were identified in layered plaque than in nonlayered plaque: lipid plaque (87% versus 69%; P <0.001), macrophages (69% versus 56%; P =0.007), microvessels (72% versus 39%; P <0.001), and cholesterol crystals (49% versus 30%; P <0.001). No difference in plaque vulnerability between layered and nonlayered plaques was observed in women. Layered plaque in men had more features consistent with previous plaque rupture than in women: interrupted pattern (74% versus 52%; P <0.001) and a greater layer index (1198 [781-1835] versus 943 [624-1477]; P <0.001)., Conclusions: In men, layered plaques exhibit more features of vascular inflammation and vulnerability as well as evidence of previous plaque rupture, compared with nonlayered plaques, whereas in women, no difference was observed between layered and nonlayered plaques. Vascular inflammation (plaque rupture) may be the predominant mechanism of layered plaque in men, whereas a less inflammatory mechanism may play a key role in women., Registration: URL: http://www., Clinicaltrials: gov; Unique Identifier: NCT01110538, NCT04523194., Competing Interests: Disclosures Dr Jang’s research has been supported by Mrs Gillian Gray through the Allan Gray Fellowship Fund in Cardiology and by Mukesh and Priti Chatter through the Chatter Foundation. Dr Jang received educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems Inc. All other authors have no relationships relevant to the contents of this paper to disclose.

Compared with plaque rupture, plaque erosion has distinct features, which can be diagnosed only by intravascular optical coherence tomography. Computed tomography angiography (CTA) features of plaque erosion have not been reported. The aim of the present study was to identify the CTA features specific for plaque erosion in patients with non-ST-segment elevation acute coronary syndromes to enable a diagnosis of erosion without invasive procedures. Patients with non-ST-segment elevation acute coronary syndromes who underwent preintervention CTA and optical coherence tomography imaging of culprit lesions were enrolled. Plaque volume and high-risk plaque (HRP) features were assessed by CTA. Among 191 patients, plaque erosion was the underlying mechanism in 89 patients (46.6%) and plaque rupture in 102 patients (53.4%). The total plaque volume (TPV) was lower in plaque erosion than in plaque rupture (133.6 vs 168.8 mm 3 , p = 0.001). Plaque erosion had a lower prevalence of positive remodeling than plaque rupture (75.3% vs 87.3%, p = 0.033). As the number of HRP features decreased, plaque erosion became more prevalent (p = 0.014). In the multivariable logistic regression analysis, lower TPV and less prevalent HRP features were associated with a higher prevalence of plaque erosion. The addition of TPV ≤116 mm 3 and HRP features ≤1 to the known predictors significantly increased the area under the curve of the plaque erosion prediction receiver operator characteristics. Plaque erosion, compared with plaque rupture, had a lower plaque volume and less prevalent HRP features. CTA may be helpful for identifying the underlying pathology of acute coronary syndromes., Competing Interests: Disclosures Dr. Jang has received educational grant support from Abbott Vascular and a consulting fee from Svelte Medical Systems. Outside the present study, Dr. Dey has received software royalties from Cedars-Sinai Medical Center and has a patent. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated., Methods: Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS., Results: Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm 3 [114.2 mm 3 to 275.0 mm 3 ] vs. 119.3 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7-60.1%] vs. 53.7%[46.8-60.6%], p = 0.001), and plaque burden (86.5%[81.7-85.7%] vs. 82.6%[77.9-85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8-67.8%] vs. 57.5%[48.9-60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014)., Conclusion: Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS., Clinical Trial Registration: http://www., Clinicaltrials: gov , NCT01110538, NCT03479723, UMIN000041692., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vascular inflammation plays a key role in atherogenesis and in the development of acute coronary syndromes. Coronary inflammation can be measured by peri-coronary adipose tissue (PCAT) attenuation on computed tomography angiography. We examined the relationships between the level of coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics by optical coherence tomography., Methods: A total of 474 patients (198 acute coronary syndromes and 276 stable angina pectoris) who underwent preintervention coronary computed tomography angiography and optical coherence tomography were included. To compare the relationships between the level of coronary artery inflammation and detailed plaque characteristics, we divided the subjects into high (n=244) and low (n=230) PCAT attenuation groups using a threshold value of -70.1 Hounsfield units., Results: The high PCAT attenuation group, compared with the low PCAT attenuation group, had more males (90.6% versus 69.6%; P <0.001), more non-ST-segment elevation myocardial infarction (38.5% versus 25.7%; P =0.003), and less stable angina pectoris (51.6% versus 65.2%; P =0.003). Aspirin, dual antiplatelet, and statins were less frequently used in the high PCAT attenuation group compared to the low PCAT attenuation group. Patients with high PCAT attenuation, compared with those with low PCAT attenuation, had lower ejection fraction (median 64% versus 65%; P =0.014) and lower levels of high-density lipoprotein cholesterol (median 45 versus 48 mg/dL; P =0.027). Optical coherence tomography features of plaque vulnerability were significantly more common in patients with high PCAT attenuation, compared to those with low PCAT attenuation, including lipid-rich plaque (87.3% versus 77.8%; P =0.006), macrophage (76.2% versus 67.8%; P =0.041), microchannels (61.9% versus 48.3%; P =0.003), plaque rupture (38.1% versus 23.9%; P <0.001), and layered plaque (60.2% versus 50.0%; P =0.025)., Conclusions: Optical coherence tomography features of plaque vulnerability were significantly more common in patients with high PCAT attenuation, compared with those with low PCAT attenuation. Vascular inflammation and plaque vulnerability are intimately related in patients with coronary artery disease., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04523194.

Background: Vascular inflammation has been recognized as one of the key factors in the pathogenesis of acute coronary syndromes (ACS). Pericoronary adipose tissue (PCAT) attenuation by computed tomography angiography has emerged as a marker specific for coronary artery inflammation. We examined the relationship between clinical presentation and coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics., Methods: Patients with ACS or stable angina pectoris (SAP) who underwent preintervention coronary computed tomography angiography and optical coherence tomography were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries. PCAT attenuation and optical coherence tomography findings were compared between patients with ACS versus SAP., Results: Among 471 patients (ACS: 198, SAP: 273), PCAT attenuation was higher in ACS patients than in SAP patients both at the culprit plaque level (-67.5±9.6 Hounsfield unit [HU] versus -71.5±11.0 HU, P< 0.001) and at the culprit vessel level (-68.3±7.7 HU versus -71.1±7.9 HU, P< 0.001). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in ACS patients than in SAP patients (-68.8±6.3 HU versus -70.5±7.1 HU, P =0.007). After adjusting patient characteristics, not only thin-cap fibroatheroma (OR: 3.41; 95% CI: 1.89-6.17) and macrophages (OR: 3.32; 95% CI: 1.76-6.26) but also PCAT attenuation around the culprit plaque (OR: 1.03; 95% CI: 1.00-1.05) was associated with the clinical presentation of ACS., Conclusions: PCAT attenuation at culprit plaque, culprit vessel, and pan-coronary levels was higher in ACS patients than in SAP patients. Vascular inflammation appears to play a crucial role in the development of ACS., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04523194.

Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p < 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application., (© 2022. Springer Nature Limited.)

Background The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut microbiota and coronary plaque characteristics in patients with coronary artery disease. Methods and Results Patients who underwent both optical coherence tomography and intravascular ultrasound imaging and provided stool and blood specimens were included. The composition of gut microbiota was evaluated using 16S rRNA sequencing. A total of 55 patients were included. At the genus level, 2 bacteria were associated with the presence of thin-cap fibroatheroma, and 9 bacteria were associated with smaller fibrous cap thickness. Among them, some bacteria had significant associations with inflammatory/prothrombotic biomarkers. Dysgonomonas had a positive correlation with interleukin-6, Paraprevotella had a positive correlation with fibrinogen and negative correlation with high-density lipoprotein cholesterol, Succinatimonas had positive correlations with fibrinogen and homocysteine, and Bacillus had positive correlations with fibrinogen and high-sensitivity C-reactive protein. In addition, Paraprevotella , Succinatimonas , and Bacillus were also associated with greater plaque volume. Ten bacteria were associated with larger fibrous cap thickness. Some were associated with protective biomarker changes; Anaerostipes had negative correlations with trimethylamine N-oxide, tumor necrosis factor α, and interleukin-6, and Dielma had negative correlations with trimethylamine N-oxide, white blood cells, plasminogen activator inhibitor-1, and homocysteine, and a positive correlation with high-density lipoprotein cholesterol. Conclusions Bacteria that were associated with vulnerable coronary plaque phenotype and greater plaque burden were identified. These bacteria were also associated with elevated inflammatory or prothrombotic biomarkers. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000041692.

Background: Despite the significant decline in cardiovascular mortality in women over the past several decades, sex differences in the underlying pathology of acute coronary syndromes remain poorly understood. Previous postmortem studies have demonstrated sex differences in coronary plaque morphology with a higher prevalence of plaque erosion in young women and more plaque rupture in older women after menopause, whereas men showed no increase in prevalence of plaque rupture with age. However, in vivo data are limited., Methods: This study included patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging of the culprit lesion. The culprit plaque was categorized as plaque rupture, plaque erosion or culprit plaque with calcification, and stratified by age. Features of plaque vulnerability at culprit lesion were also analyzed., Results: In 1368 patients (women=286), women and men had a similar distribution of culprit plaque morphology (plaque rupture versus plaque erosion). However, significant sex differences were found in the underlying mechanisms of acute coronary syndrome among different age groups: women showed a significant ascending trend with age in plaque rupture ( P <0.001) and the features of plaque vulnerability such as lipid plaque ( P <0.001), thin-cap fibroatheroma ( P =0.005), and microstructures including macrophages, cholesterol crystals, and calcification ( P =0.026). No trend was observed in men., Conclusions: Age related sex differences in culprit plaque morphology and vulnerability were identified in patients with acute coronary syndrome: prevalence of plaque rupture and vulnerability increased with age in women but not in men., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01110538 and NCT03479723.

Objectives: The aim of this study was to compare the level of coronary inflammation between plaque rupture and plaque erosion using pericoronary adipose tissue (PCAT) attenuation., Background: Vascular inflammation plays a key role in plaque rupture, while the role of inflammation in plaque erosion remains less well defined. PCAT attenuation determined using computed tomography has emerged as a marker specific for coronary artery inflammation., Methods: Patients with non-ST-segment elevation acute coronary syndromes who underwent preintervention coronary computed tomographic angiography and optical coherence tomographic culprit lesion imaging were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries., Results: Among 198 patients, plaque rupture was the underlying mechanism in 107 (54.0%) and plaque erosion in 91 (46.0%). Plaque rupture had higher PCAT attenuation than plaque erosion both at the culprit plaque level (-65.8 ± 7.5 HU vs -69.5 ± 11.4 HU; P = 0.010) and at the culprit vessel level (-67.1 ± 7.1 HU vs -69.6 ± 8.2 HU; P = 0.024). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in patients with plaque rupture than in plaque erosion, indicating a higher level of inflammation (-67.9 ± 5.7 HU vs -69.9 ± 6.8 HU; P = 0.030). In multivariable analysis, plaque rupture was significantly associated with high PCAT attenuation., Conclusions: PCAT attenuation in culprit plaque, culprit vessel, and all 3 coronary arteries was higher in plaque rupture than in plaque erosion. The results suggest that pancoronary inflammation plays a more significant role in plaque rupture than in plaque erosion. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)., Competing Interests: Funding Support and Author Disclosures Dr Jang’s research was supported by Mr and Mrs Allan and Gill Gray and by Mr and Mrs Michael and Kathryn Park. Dr Dey is supported by National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). The funders had no role in the design or conduct of this research. Dr Jang has received educational grant support from Abbott Vascular; and consulting fees from Svelte Medical Systems and Mitobridge. Outside the present study, Dr Dey has received software royalties from Cedars-Sinai Medical Center; and has a patent. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Recently, layered plaque, an optical coherence tomography equivalent of healed plaque, has been gaining attention. However, detailed layered plaque characteristics including the burden of plaque layer have not been investigated. Patients with acute coronary syndromes who underwent preintervention optical coherence tomography imaging of culprit lesion were included. Layer index, a product of the mean layer arc and layer length, was correlated with the pattern of layer and culprit pathology. In addition, layer index was compared between culprit and nonculprit plaques. Finally, predictors for greater layer index were identified using general linear modeling. In 349 patients, 99 culprit plaques had layered phenotype (28.4%), whereas among 465 nonculprit plaques, 165 had layered pattern (35.5%). Layer index was greater in multilayer pattern versus single-layer pattern (1,688.5 vs 996.6, p <0.001), interrupted layer phenotype versus intact layer phenotype (1,276.5 vs 646.8, p <0.001), rupture versus erosion at culprit lesion (1,191.0 vs 861.8, p <0.001), and culprit versus nonculprit plaque (1,475.6 vs 983.4, p <0.001). The general linear modeling revealed that multilayer pattern (regression coefficient b [B] 7.332, p <0.001), interrupted layer phenotype (B 4.624, p <0.001), culprit lesion (B 2.792, p = 0.001), lipid-rich plaque (B 1.953, p = 0.032), and culprit plaque rupture (B: 1.943, p = 0.008) were the significant predictors for greater layer index. In conclusion, layer index (burden of layered plaque) was greater in multilayer pattern, interrupted layer phenotype, at culprit plaque, lipid-rich plaque, and in cases with culprit plaque rupture., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: South Asians, and Indians in particular, are known to have a higher incidence of premature atherosclerosis and acute coronary syndromes (ACS) with worse clinical outcomes, compared to populations with different ethnic backgrounds. However, the underlying pathobiology accounting for these differences has not been fully elucidated., Methods: ACS patients who had culprit lesion optical coherence tomography (OCT) imaging were enrolled. Culprit plaque characteristics were evaluated using OCT., Results: Among 1315 patients, 100 were South Asian, 1009 were East Asian, and 206 were White. South Asian patients were younger (South Asians vs. East Asians vs. Whites: 51.6 ± 13.4 vs. 65.4 ± 11.9 vs. 62.7 ± 11.7; p < 0.001) and more frequently presented with ST-segment elevation myocardial infarction (STEMI) (77.0% vs. 56.4% vs. 35.4%; p < 0.001). On OCT analysis after propensity group matching, plaque erosion was more frequent (57.0% vs. 38.0% vs. 50.0%; p = 0.003), the lipid index was significantly greater (2281.6 [1570.8-3160.6] vs. 1624.3 [940.9-2352.4] vs. 1303.8 [1090.0-1757.7]; p < 0.001), and the prevalence of layered plaque was significantly higher in the South Asian group than in the other two groups (52.0% vs. 30.0% vs. 34.0%; p = 0.003)., Conclusions: Compared to East Asians and Whites, South Asians with ACS were younger and more frequently presented with STEMI. Plaque erosion was the predominant pathology for ACS in South Asians and their culprit lesions had more features of plaque vulnerability., Clinical Trial Registration: http://www.clinicaltrials.gov, NCT03479723., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background A recent study reported that the outcome of patients with plaque erosion treated with stenting is poor when the underlying plaque is lipid rich. However, the detailed phenotype of patients with plaque erosion, particularly as related to different age groups, has not been systematically studied. Methods and Results Patients with acute coronary syndromes caused by plaque erosion were selected from 2 data sets. Demographic, clinical, angiographic, and optical coherence tomography findings of the culprit lesion were compared between 5 age groups. Among 579 erosion patients, male sex and current smoking were less frequent, and hypertension, diabetes, and chronic kidney disease were more frequent in older patients. ST-segment-elevation myocardial infarction was more frequent in younger patients. Percentage of diameter stenosis on angiogram was greater in older patients. The prevalence of lipid-rich plaque (27.3% in age <45 years and 49.4% in age ≥75 years, P <0.001), cholesterol crystal (3.9% in age <45 years and 21.8% in age ≥75 years, P =0.027), and calcification (5.5% in age <45 years and 54.0% in age ≥75 years, P <0.001) increased with age. After adjusting risk factors, younger patients were associated with the presence of thrombus, and older patients were associated with greater percentage of diameter stenosis and the presence of lipid-rich plaque and calcification. Conclusions The demographic, clinical, angiographic, and plaque phenotypes of patients with plaque erosion distinctly vary depending on age. This may affect the clinical outcome in these patients. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03479723, NCT02041650.

Objectives: This study sought to identify morphological predictors of rapid plaque progression., Background: Two patterns of plaque progression have been described: slow linear progression and rapid step-wise progression. The former pattern will cause stable angina when the narrowing reaches a critical threshold, whereas the latter pattern may lead to acute coronary syndromes or sudden cardiac death., Methods: Patients who underwent optical coherence tomography (OCT) imaging during the index procedure and follow-up angiography with a minimum interval of 6 months were selected. Nonculprit lesions with a diameter stenosis of ≥30% on index angiography were assessed. Lesion progression was defined as a decrease of angiographic minimum lumen diameter ≥0.4 mm at follow-up (mean, 7.1 months). Baseline morphological characteristics of plaques with rapid progression were evaluated by OCT. In a subgroup with follow-up OCT imaging for plaques with rapid progression, morphological changes from baseline to follow-up were assessed., Results: Among 517 lesions in 248 patients, 50 lesions showed rapid progression. These lesions had a significantly higher prevalence of lipid-rich plaque (76.0% vs. 50.5%, respectively), thin-cap fibroatheroma (TCFA) (20.0% vs. 5.8%, respectively), layered plaque (60.0% vs. 34.0%, respectively), macrophage accumulation (62.0% vs. 42.4%, respectively), microvessel (46.0% vs. 29.1%, respectively), plaque rupture (12.0% vs. 4.7%, respectively), and thrombus (6.0% vs. 1.1%, respectively) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.02 to 4.62; p = 0.045]), TCFA (OR: 5.85; 95% CI: 2.01 to 17.03; p = 0.001), and layered plaque (OR: 2.19; 95% CI: 1.03 to 4.17; p = 0.040) as predictors of subsequent rapid lesion progression. In a subgroup analysis for plaques with rapid progression, a new layer was detected in 25 of 41 plaques (61.0%) at follow-up., Conclusions: Lipid-rich plaques, TCFA, and layered plaques were predictors of subsequent rapid plaque progression. A new layer, a signature of previous plaque disruption and healing, was detected in more than half of the lesions with rapid progression at follow-up. (Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538)., Competing Interests: Funding Support and Author Disclosures Dr. Jang has received educational grants from Abbott Vascular; and research was supported by Mr. and Mrs. Michael and Kathryn Park and by Mrs. and Mr. Gill and Allan Gray, who had no role in the design or conduct of this research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.

Background The role of coronary calcification in cardiovascular events and plaque stabilization is still being debated, and factors involved in the progression of coronary calcification are not fully understood. This study aimed to identify the predictors for rapid progression of coronary calcification. Methods and Results Patients with serial optical coherence tomography imaging at baseline and at 6 months were selected. Changes in the calcification index and predictors for progression of calcification were studied. Calcification index was defined as the product of the mean calcification arc and calcification length. Rapid progression of calcification was defined as an increase in the calcification index above the median value. Among 187 patients who had serial optical coherence tomography imaging, 235 calcified plaques were identified in 105 patients (56.1%) at baseline. After 6 months, the calcification index increased in 95.3% of calcified plaques from 132.0 to 178.2 ( P <0.001). In multivariable analysis, diabetes mellitus (odds ratio [OR], 3.911; P <0.001), chronic kidney disease (OR, 2.432; P =0.037), lipid-rich plaque (OR, 2.698; P =0.034), and macrophages (OR, 6.782; P <0.001) were found to be independent predictors for rapid progression of coronary calcification. Interestingly, rapid progression of calcification was associated with a significant reduction of inflammatory features (thin-cap fibroatheroma; from 21.2% to 11.9%, P =0.003; macrophages; from 74.6% to 61.0%, P =0.001). Conclusions Diabetes mellitus, chronic kidney disease, lipid-rich plaque, and macrophages were independent predictors for rapid progression of coronary calcification. Baseline vascular inflammation and subsequent stabilization may be related to rapid progression of calcification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.

Background Specific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy. Methods and Results Patients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin-cap area (defined as an area with fibrous cap thickness <200 μm) was measured using a 3-dimensional computer-aided algorithm, and changes in the thin-cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin-cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. In multivariable analysis, baseline thin-cap area (odds ratio [OR] 1.442; 95% CI, 1.024-2.031, P =0.036), macrophage index (OR, 1.031; 95% CI, 1.002-1.061, P =0.036), and layered plaque (OR, 2.767; 95% CI, 1.024-7.479, P =0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index. Conclusions Three optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin-cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.