Association Between Serum Uric Acid Levels and Neoatherosclerosis.

Neoatherosclerosis is a major cause of stent failure after percutaneous coronary intervention. Metabolism such as hyperuricemia is associated with in-stent restenosis (ISR). However, the association between serum uric acid (sUA) levels and in-stent neoatherosclerosis (ISNA) has never been validated.A total of 216 patients with 220 ISR lesions who had undergone optical coherence tomography (OCT) of culprit stents were included in this study. According to their sUA levels, eligible patients were divided into two groups [normal-sUA group: sUA < 7 mg/dL, n = 126, and high-sUA group: sUA ≥ 7 mg/dL, n = 90]. OCT findings were analyzed and compared between the normal- and high-sUA groups.The incidence of ISNA (63.0% versus 43.0%, P = 0.004) was significantly higher in the high-sUA group than in the normal-sUA group. Lipid plaques (66.3% versus 43.0%, P < 0.001) and thin-cap fibroatheroma (38.0% versus 18.0%, P = 0.001) were observed more frequently in the restenotic tissue structure in patients in the high-sUA group than in those in the normal-sUA group. Meanwhile, univariate (OR: 1.208, 95% CI: 1.037-1.407; P = 0.015) and multivariate (OR: 1.254, 95% CI: 1.048-1.501; P = 0.013) logistic regression analyses indicated that sUA levels were an independent risk factor for ISNA after adjusting for relevant risk factors.The high-sUA levels were an independent risk factor for the occurrence of neoatherosclerosis in patients with ISR via OCT.

Correlation Between Serum Uric Acid Levels and Coronary Plaque Characteristics on Optical Coherence Tomography.

Elevated serum uric acid (sUA) is associated with increasing risk of coronary heart disease (CHD). However, existing research is limited by potential confounders. Herein, our study aims to probe the association between sUA levels and the morphological characteristics of coronary plaque by a propensity score matching (PSM) analysis.All 420 patients with CHD who had undergone optical coherence tomography of culprit lesions were included. Eligible patients were assigned into 2 groups according to sUA level: high-sUA group (sUA ≥ 6.0 mg/dL) and low-sUA group (sUA < 6.0 mg/dL). PSM was applied to control the balance of baseline characteristics.After PSM, a total of 112 patients were included in our study (56 in each group). The high-sUA group showed a higher prevalence of TCFA (35.7% versus 16.1%, P = 0.03) and macrophage infiltration (33.9% versus 14.3%, P = 0.026) compared with the low-sUA group. Plaques in the high-sUA group had a wider maximum lipid arc (166.51° (115.77°, 224.14°) versus 142.29° (93.95°, 169.06°), P = 0.048), longer calcification length (6.77 (3.90, 20.55) mm versus 4.20 (1.95, 7.45) mm, P = 0.040), and thinner minimum fibrous cap thickness (43.81 (28.17, 62.26) µm versus 92.57 (46.25, 135.37) µm, P = 0.003). Correlation analysis indicated that the sUA value was inversely associated with the minimum fibrous cap thickness (r = -0.332, P = 0.015) and positively associated with the maximum lipid arc (r = 0.399, P = 0.003), average lipid arc (r = 0.347, P = 0.011), and calcification length (r = 0.386, P = 0.006).The relationship between high-sUA levels and typical vulnerable features of plaques persisted after balancing the traditional risk factors.

Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome.

INTRODUCTION: The progression and pattern of coronary atherosclerosis in diabetes mellitus (DM) is different from non-DM, leading to a higher rate of vascular complications in DM. OBJECTIVE: This study aims to assess and compare the high-risk plaque characteristics in the culprit artery of DM and non-DM patients with acute coronary syndrome (ACS) using virtual histology intravascular ultrasound (VH-IVUS). METHODS: A total of 158 ACS patients were included, 63 of whom were known to have DM. IVUS analysis was done in the de novo target vessel and culprit lesion for which percutaneous coronary intervention was planned. Culprit lesions with a visual-estimate angiographic stenosis of <70% were excluded. RESULTS: The mean age of patients was 52.4 ± 11.6 years. The study group comprised 82% men, 31% with hypertension, and 39.87% with DM. No significant difference was observed between the DM and non-DM groups in relation to quantitative IVUS parameters like lesion length, minimal lumen area, and plaque area. However, there was a significant difference in VH-IVUS parameters like higher necrotic core and dense calcium in the DM patients than in the non-DM patients (p < 0.01). The occurrence of VH-derived thin-cap fibroatheroma (VH-TCFA) in the culprit vessel was significantly higher in the DM group than in the non-DM group (25.3 vs. 5.2%; p < 0.01). Positive vessel-wall remodeling was noted in both groups without any significant difference (p = 0.74). CONCLUSION: The DM patients had high-risk plaque composition features like a higher necrotic core, which is a marker of plaque vulnerability. Thus, aggressive medical therapy targeting vascular inflammation using high-dose statins would help in the stabilization of unstable plaque morphology and the reduction of major cardiovascular events.

Relationships of coronary culprit-plaque characteristics with duration of diabetes mellitus in acute myocardial infarction: an intravascular optical coherence tomography study.

BACKGROUND: Diabetes mellitus (DM) or pre-diabetes status is closely associated with features of vulnerable coronary lesions in patients with stable coronary heart disease or acute coronary syndrome. However, the association between duration of diabetes and the morphologies and features of vulnerable plaques has not been fully investigated in patients with acute myocardial infarction (AMI). METHODS: We enrolled a total of 279 patients who presented with AMI between March 2017 and March 2019 and underwent pre-intervention optical coherence tomography imaging of culprit lesions. Patients with DM were divided into two subgroups: a Short-DM group with DM duration of < 10 years and a Long-DM group with DM duration of ≥ 10 years. Baseline clinical data and culprit-plaque characteristics were compared between patients without DM (the non-DM group), those in the Short-DM group, and those in the Long-DM group. RESULTS: Patients with DM represented 34.1% of the study population (95 patients). The Short- and Long-DM groups included 64 (67.4%) and 31 patients (32.6%), respectively. Glycated hemoglobin A1c (HbA1c) levels were significantly higher in the Long-DM group than the Non- or Short-DM groups (8.4% [Long-DM] versus 5.7% [Non-DM] and 7.6% [Short-DM], P < 0.001). In addition, the highest prevalence of lipid-rich plaques, thin-cap fibroatheroma (TCFA), and plaque ruptures of culprit lesions were observed in the Long-DM group (lipid-rich plaques: 80.6% [Long-DM] versus 52.2% [Non-DM] and 62.5% [Short-DM], P = 0.007; TCFA: 41.9% [Long-DM] versus 19.6% [Non-DM] and 31.3% [Short-DM], P = 0.012; plaque rupture: 74.2% [Long-DM] versus 46.7% [Non-DM] and 48.4% [Short-DM], P = 0.017). The frequency of calcification was significantly higher among patients with DM than among those without (62.1% versus 46.2%, P = 0.016); however, no significant differences were found between the DM subgroups (61.3% [Long-DM] versus 62.5% [Short-DM], P = 0.999). CONCLUSIONS: Increased duration of DM combined with higher HbA1c levels influences culprit-plaque characteristics in patients with DM who suffer AMI. These findings might account for the higher risks of cardiac death in DM patients with long disease duration. Trial registration This study is registered at clinicaltrials.gov as NCT03593928.

Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics.

AIMS: Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phenotypes. METHODS AND RESULTS: We assessed coronary atherosclerotic plaque burden and phenotype by optical coherence tomography in 52 patients and measured the levels of circulating miRs across the transcoronary gradient. The overall plaque load was significantly correlated with transcoronary concentration gradients of miR-126-3p (P = 0.04), miR-145-5p (P = 0.01), miR-155-5p (P < 0.01), and miR-29b-3p (P = 0.02), but not with other miRs such as miR-92a-3p. In patients with a high extent of vulnerable plaques as assessed by the presence of thin-cap fibroatheromas (TCFAs), significantly higher transcoronary gradients were observed, particularly for miR-126-3p, miR-126-5p, and miR-145-5p (all P < 0.02). Transcoronary gradients of miR-126-3p (P < 0.01), miR-126-5p (P < 0.01), miR-145-5p (P = 0.01), miR-29b-3p (P = 0.03), and miR-155-5p (P = 0.02) demonstrated a significant discriminatory power to predict the presence of TCFAs (AUC > 0.7 for all). Moreover, aortic and venous coronary sinus levels of miR-29b-3p were inversely correlated with plaque fibrosis, a finding that is consistent with the anti-fibrotic activity of miR-29b-3p. CONCLUSION: The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.

BMCS-Net: A Bi-directional multi-scale cascaded segmentation network based on transformer-guided feature Aggregation for medical images.

convolutional neural networks (CNNs) show great potential in medical image segmentation tasks, and can provide reliable basis for disease diagnosis and clinical research. However, CNNs exhibit general limitations on modeling explicit long-range relation, and existing cures, resorting to building deep encoders along with aggressive downsampling operations, leads to loss of localized details. Transformer has naturally excellent ability to model the global features and long-range correlations of the input information, which is strongly complementary to the inductive bias of CNNs. In this paper, a novel Bi-directional Multi-scale Cascaded Segmentation Network, BMCS-Net, is proposed to improve the performance of medical segmentation tasks by aggregating these features obtained from Transformers and CNNs branches. Specifically, a novel feature integration technique, termed as Two-stream Cascaded Feature Aggregation (TCFA) module, is designed to fuse features in two-stream branches, and solve the problem of gradual dilution of global information in the network. Besides, a Multi-Scale Expansion-Aware (MSEA) module based on the convolution of feature perception and expansion is introduced to capture context information, and further compensate for the loss of details. Extensive experiments demonstrated that BMCS-Net has an excellent performance on both skin and Polyp segmentation datasets.

Association of the monocytes to high-density lipoprotein cholesterol ratio with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

BACKGROUND: Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an independent predictor of atherosclerosis and in-stent restenosis (ISR). However, the association between MHR and the incidence of in-stent neoatherosclerosis (ISNA) remains to be validated. METHODS: This study included 216 patients with acute coronary syndrome who had 220 ISR lesions and had undergone optical coherence tomography (OCT). All eligible patients were divided into three groups according to their MHR tertile level. OCT characteristics were comparatively analyzed between groups of different MHR levels, and univariate and multivariate logistic regression analyses were constructed to assess correlations between MHR level and ISNA as well as in-stent thin-cap fibroatheroma (TCFA). A receiver operating characteristic curve was used to determine the optimal MHR thresholds for predicting ISNA and in-stent TCFA. RESULTS: The incidence of ISNA (70.3% vs. 61.1% vs. 20.3%, P < 0.001) and in-stent TCFA (40.5% vs. 31.9% vs. 6.8%, P < 0.001) was the highest in the third tertile, followed by the second and first tertiles, respectively. Multivariate analysis revealed that MHR was independently associated with ISNA (odds ratio [OR], 7.212; 95% confidence interval [CI], 1.287-40.416; P = 0.025) and in-stent TCFA (OR, 5.610; 95% CI, 1.743-18.051; P = 0.004) after adjusting for other clinical factors. The area under the curve was 0.745 (95% CI, 0.678-0.811; P < 0.001) for the prediction of ISNA and 0.718 (95% CI, 0.637-0.778; P < 0.001) for the prediction of in-stent TCFA. CONCLUSION: MHR levels are an independent risk factor for ISNA.

Predictors of Near-Infrared Spectroscopy-Detected Lipid-Rich Plaques by Optical Coherence Tomography-Defined Morphological Features in Patients With Acute Coronary Syndrome.

Background: Near-infrared spectroscopy (NIRS) provides the localization of lipid-rich components in coronary plaques. However, morphological features in NIRS-detected lipid-rich plaques (LRP) are unclear. Methods: A total of 140 de novo culprit lesions in 140 patients with the acute coronary syndrome (ACS) who underwent NIRS and optical coherence tomography (OCT) examinations for the culprit lesions at the time of percutaneous coronary interventions were investigated. We defined a NIRS-LRP as a lesion with a maximum lipid core burden index of 4 mm [LCBI4mm] > 500 in the culprit plaque. Clinical demographics, angiographic, and OCT findings were compared between the patients with NIRS-LRP (n = 54) vs. those without NIRS-LRP (n = 86). Uni- and multivariable logistic regression analyses were performed to examine the independent OCT morphological predictors for NIRS-LRP. Results: Clinical demographics showed no significant differences between the two groups. The angiographic minimum lumen diameter was smaller in the NIRS-LRP group than in the non- NIRS-LRP group. In OCT analysis, the minimum flow area was smaller; lipid angle, lipid length, the prevalence of thin-cap fibroatheroma, and cholesterol crystals were greater in the NIRS-LRP group than in the non-NIRS-LRP group. Plaque rupture and thrombi were more frequent in the NIRS-LRP group, albeit not significant. In a multivariable logistic regression analysis, presence of thin-cap fibroatheroma [odds ratio (OR): 2.56; 95% CI: 1.12 to 5.84; p = 0.03] and cholesterol crystals (OR: 2.90; 95% CI: 1.20 to 6.99; p = 0.02) were independently predictive of NIRS-LRP. Conclusions: In ACS culprit lesions, OCT-detected thin-cap fibroatheroma and cholesterol crystals rather than plaque rupture and thrombi were closely associated with a great lipid-core burden.

No-reflow phenomenon and in vivo cholesterol crystals combined with lipid core in acute myocardial infarction.

BACKGROUND: The release of lipid-laden plaque material subsequent to ST-segment elevation myocardial infarction (STEMI) may contribute to the no-reflow phenomenon. The aim of this study was to investigate the association between in vivo cholesterol crystals (CCs) detected by optical coherence tomography (OCT) and the no-reflow phenomenon after successful percutaneous coronary intervention (PCI) in patients with acute STEMI. METHODS: We investigated 182 patients with STEMI. Based on the thrombolysis in myocardial infarction (TIMI) flow grade after PCI, patients were divided into a no-reflow group (n = 31) and a reflow group (n = 151). On OCT, CCs were defined as thin, high-signal intensity regions within a plaque. A multivariable logistic regression analysis was performed to determine predictors for the no-reflow phenomenon. RESULTS: The prevalence of CCs was higher in the no-reflow group than the reflow group (no-reflow group, 77% vs. reflow group, 53%; p = 0.012). The multivariable logistic model showed that the CC number, lipid arc and ostial lesions were positive independent predictors of no-reflow. The combination of a lipid arc ≥ 139°and CC number ≥ 12 showed good predictive performance for the no-reflow phenomenon (sensitivity, 48%; specificity, 93%; and accuracy, 86%). CONCLUSION: In vivo CCs at the culprit plaque are associated with the no-reflow phenomenon after PCI in patients with STEMI. The combination of the number of CCs and lipid arc can predict the no-reflow phenomenon after PCI with a high accuracy of 86%.

Risk Stratification in Acute Coronary Syndrome by Comprehensive Morphofunctional Assessment With Optical Coherence Tomography.

Background: Artificial intelligence enables simultaneous evaluation of plaque morphology and computational physiology from optical coherence tomography (OCT). Objectives: This study sought to appraise the predictive value of major adverse cardiovascular events (MACE) by combined plaque morphology and computational physiology. Methods: A total of 604 patients with acute coronary syndrome who underwent OCT imaging in ≥1 nonculprit vessel during index coronary angiography were retrospectively enrolled. A novel morphologic index, named the lipid-to-cap ratio (LCR), and a functional parameter to evaluate the physiologic significance of coronary stenosis from OCT, namely, the optical flow ratio (OFR), were calculated from OCT, together with classical morphologic parameters, like thin-cap fibroatheroma (TCFA) and minimal lumen area. Results: The 2-year cumulative incidence of a composite of nonculprit vessel-related cardiac death, cardiac arrest, acute myocardial infarction, and ischemia-driven revascularization (NCV-MACE) at 2 years was 4.3%. Both LCR (area under the curve [AUC]: 0.826; 95% CI: 0.793-0.855) and OFR (AUC: 0.838; 95% CI: 0.806-0.866) were superior to minimal lumen area (AUC: 0.618; 95% CI: 0.578-0.657) in predicting NCV-MACE at 2 years. Patients with both an LCR of >0.33 and an OFR of ≤0.84 had significantly higher risk of NCV-MACE at 2 years than patients in whom at least 1 of these 2 parameters was normal (HR: 42.73; 95% CI: 12.80-142.60; P < 0.001). The combination of thin-cap fibroatheroma and OFR also identified patients at higher risk of future events (HR: 6.58; 95% CI: 2.83-15.33; P < 0.001). Conclusions: The combination of LCR with OFR permits the identification of a subgroup of patients with 43-fold higher risk of recurrent cardiovascular events in the nonculprit vessels after acute coronary syndrome.

In vivo correlation between morphological characteristics of coronary plaques and functional characteristics of carotid arteries in acute coronary syndrome.

BACKGROUND: Carotid artery temperature heterogeneity (ΔΤ) measured by microwave radiometry (MWR) has been associated with future cardiovascular events including acute coronary syndromes. The vulnerable plaques of the coronary arterial tree, that can be ideally depicted by intracoronary imaging such as optical coherence tomography (OCT) have anatomical characteristics such as the thin fibrous cap (TCFA), that make them vulnerable to rupture. The scope of the study was to assess the implication of the carotid artery temperature heterogeneity on the culprit coronary plaque morphology in patients presenting with acute myocardial infarction. METHODS: 34 patients presented with an acute myocardial infarction were enrolled in the study. All patients underwent percutaneous coronary intervention (PCI) and OCT for the evaluation of the anatomical characteristics of the culprit lesion. After the completion of the PCI all patients underwent carotid ultrasound and MWR of both carotid arteries and thermal heterogeneity of the carotid arteries was assessed. Blood samples were collected for high sensitivity C-reactive protein (CRP) analysis. RESULTS: Thirty four patients, 21 with STEMI (61.76%) and 13 (38.23%) with NSTEMI, were included in the study. Patients with ruptured plaques had significantly increased hsCRP compared to patients that did not have a ruptured plaque (14.41±4.02 vs 9.9±2.5, P<0.005). Thermal heterogeneity, was significantly increased in ruptured plaques compared to no ruptured ones (1.01±0.31 vs 0.51±0.14°C, P=0.001), and in plaques with TCFA compared to those without a TCFA (0.82±0.37 vs 0.60±0.05°C, P=0.001). Diabetes mellitus, ΔΤ and hsCRP, were entered in the multivariate analysis, from which DM (OR 4.12; 95% CI 0.77-22.07; P=0.07) and ΔΤ (OR for 0.1°C increase 1.43; 95% CI 1.03-1.98; P=0.03) remained in the final analysis, and only ΔΤ was independently associated with the presence of the TCFA. Regarding plaque rupture, STEMI, hsCRP, and ΔT were entered in the multivariate analysis from which hsCRP (OR 1.51; 95% CI 0.99-2.28; P=0.051) and ΔΤ (OR for 0.1°C increase 3.40; 95% CI 1.29-8.96; P=0.013) remained in the final analysis with the ΔT being the only variable.

Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study.

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).

Association between serum adipsin and plaque vulnerability determined by optical coherence tomography in patients with coronary artery disease.

BACKGROUND: Early identification of vulnerable plaques is important for patients with coronary artery disease (CAD) to reduce acute coronary events and improve their prognosis. We sought to examine the relationship between adipsin, an adipokine secreted from adipocytes, and plaque vulnerability in CAD patients. METHODS: A total of 103 plaques from 99 consecutive patients who underwent coronary angiography were assessed by optical coherence tomography. The serum level of adipsin was measured using enzyme-linked immunosorbent assay (ELISA). The accuracy of adipsin for detecting thin-cap fibroatheroma (TCFA) was determined by the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 99 patients, 49 were classified into the low adipsin group and 50 into the high adipsin group according to the median level of serum adipsin (2.43 µg/mL). The plaques from the high adipsin group exhibited a greater lipid index (2,700.0 vs. 1,975.9° × mm, P=0.015) and an increased proportion of TCFAs (41.2% vs. 21.2%, P=0.028) compared with the low adipsin group. Serum adipsin was found to be negatively correlated with fibrous cap thickness (ρ=-0.322, P=0.002), while it was positively correlated with average lipid arc (ρ=0.253, P=0.015), maximum lipid arc (ρ=0.211, P=0.044), lipid core length (ρ=0.241, P=0.021), lipid index (ρ=0.335, P=0.001), and vulnerability score (ρ=0.254, P=0.014). Furthermore, adipsin had a significant association with TCFAs (OR: 1.290, 95% CI: 1.048-1.589, P=0.016) in the multivariate analysis, while having a moderate diagnostic accuracy for TCFAs (AUC: 0.710, 95% CI: 0.602-0.817, P<0.001). CONCLUSIONS: Our findings suggest that serum adipsin is significantly and positively correlated with the incidence of TCFAs. The application of adipsin as a biomarker may offer improvement in the diagnosis of vulnerable plaques and clinical benefits for CAD patients.

Comprehensive Assessment of High-Risk Plaques by Dual-Modal Imaging Catheter in Coronary Artery.

Coronary plaque destabilization involves alterations in microstructure and biochemical composition; however, no imaging approach allows such comprehensive characterization. Herein, the authors demonstrated a simultaneous microstructural and biochemical assessment of high-risk plaques in the coronary arteries in a beating heart using a fully integrated optical coherence tomography and fluorescence lifetime imaging (FLIm). It was found that plaque components such as lipids, macrophages, lipids+macrophages, and fibrotic tissues had unique fluorescence lifetime signatures that were distinguishable using multispectral FLIm. Because FLIm yielded massive biochemical readouts, the authors incorporated machine learning framework into FLIm, and ultimately, their approach enabled an automated, quantitative imaging of multiple key components relevant for plaque destabilization.

In vivo morphologic comparison of saphenous vein grafts and native coronary arteries following non-ST elevation myocardial infarction.

OBJECTIVE: This study aimed to assess the pathophysiological differences between saphenous vein grafts (SVG) and native coronary arteries (NCA) following presentation with non-ST elevated myocardial infarction (NSTEMI). BACKGROUND: There is accelerated pathogenesis of de novo coronary disease in harvested SVG following coronary artery bypass (CABG) surgery, which contributes to both early and late graft failure, and is also causal in adverse outcomes following vein graft PCI. However in vivo assessment, with OCT imaging, comparing the differences between vein grafts and NCAs has not previously been performed. METHODS: We performed a retrospective, observational, analysis in patients who underwent PCI with adjunctive OCT imaging following presentation with NSTEMI, where the infarct-related artery (IRA) was either in an SVG or NCA. RESULTS: A total of 1550 OCT segments was analysed from thirty patients with a mean age of 66.3 (±9.0) years were included. The mean graft age of 13.9 (±5.6) years in the SVG group. OCT imaging showed that the SVG group had evidence of increased lipid pool burden (lipid pool quadrants, 2.1 vs 2.7; p = 0.021), with a reduced fibro-atheroma cap-thickness in the SVG group (45.0 µm vs 38.5 µm; p = 0.05) and increased burden of calcification (calcified lesion length = 0.4 mm vs 1.8 mm; p = 0.007; calcified quadrants = 0.2 vs 0.9; p = 0.001; arc of superficial calcium deposits = 11.6° vs 50.9°; p = 0.007) when compared to NCA. CONCLUSION: This OCT study has demonstrated that vein grafts have a uniquely atherogenic environment which leads to the development of calcified, lipogenic, thin-capped fibro-atheroma's, which may be pivotal in the increased, acute and chronic graft failure rate, and may underpin the increased adverse outcomes following vein graft PCI.

In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF2:Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting ß-particles during 18F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, n = 5) and controls (New Zealand White, n = 2). Rabbits were fasted for 6 h before 5.55 × 107 Bq (1.5 mCi) of 18F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Conclusion: Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease.

Wenyang Huoxue Jiedu formula inhibits thin-cap fibroatheroma plaque formation via the VEGF/VEGFR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: For many years, Guangzhou University of Chinese Medicine has been successfully using the empirical Wenyang Huoxue Jiedu formula (WHJF) to treat coronary heart disease. Modern theories of acute coronary syndrome mainly focus on rupture of thin-cap fibroatheromas (TCFAs), which is closely related to the release of vascular endothelial growth factor and its receptor (VEGF/VEGFR). AIM OF STUDY: We investigated the effects of WHJF on the formation of TCFA plaques and the potential mechanism (VEGF/VEGFR signaling pathway). MATERIALS AND METHODS: For the in vivo experiments, WHJF was administered to ApoE-/- mice, as a model of TCFA plaque formation. Aortic sections of the mice were obtained, and the vulnerability index and new vessel density of plaques were calculated by the Movat staining assay and immunohistochemistry kit, respectively. Protein and mRNA expression levels of VEGF/VEGFR in aortas were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. In vitro, WHJF serum was produced in rats on the fourth day 2 h after the first administration of different concentrations of WHJF. Proliferation, migration, and lumen formation ability of human umbilical vein endothelial cells (HUVECs) treated with sera from these rats were assayed by the CKK-8 kit, Transwell plates, and Matrigel assay, respectively. Protein and mRNA expression levels of signaling molecules in the VEGF/VEGFR pathways were also examined. RESULTS: In vivo, the vulnerability index and new vessel density of plaques in the WHJF group were lower than those values in the blank control group (P < 0.05). No differences were found between the groups in the expression levels of VEGF/VEGFR (P > 0.05). In vitro, the proliferation, migration, and tube formation of HUVECs in the high-dose WHJF group were reduced compared to the control group (P < 0.05). This finding was in agreement with the downregulation of VEGFR-2 and pERK (P < 0.05). The mRNA expression of signaling molecules showed no difference between the groups (P > 0.05). CONCLUSIONS: WHJF inhibits TCFA formation by influencing the VEGF/VEGFR signaling pathway.

Stabilization of high-risk plaques.

The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing globally and they have become the leading cause of death in most countries. Numerous experimental and clinical studies have been conducted to identify major risk factors and effective control strategies for ASCVDs. The development of imaging modalities with the ability to determine the plaque composition enables us to further identify high-risk plaque and evaluate the effectiveness of different treatment strategies. While intensive lipid-lowering by statins can stabilize or even regress plaque by various mechanisms, such as the reduction of lipid accumulation in a necrotic lipid core, the reduction of inflammation, and improvement of endothelial function, there are still considerable residual risks that need to be understood. We reviewed important findings regarding plaque vulnerability and some encouraging emerging approaches for plaque stabilization.

Current OCT Approaches Do Not Reliably Identify TCFAs.

It is now clearly established that Thin-Capped Fibroatheromas (TCFAs) lead to most Acute Coronary Syndromes (ACSs). The ability to selectively intervene on TCFAs predisposed to rupture and ACSs would dramatically alter the practice of cardiology. While the ability of OCT to identify thin walled plaques at micron scale resolutions has represented a major advance, it is a misconception that it can reliably identify TCFAs. One major reason is that the 'diffuse border' criteria currently used to determine 'lipid plaque' is almost undoubtedly from high scattering in the intima and not because of core composition (necrotic core). A second reason is that, rather than looking at lipid collections, studies need to be focused on identifying necrotic cores with OCT. Necrotic cores are characteristic of TCFAs and not lipid collections. Numerous other OCT approaches are available which can potentially accurately assess TCFAs, but these have not been aggressively pursed which we believe likely stems in part from the misconceptions over the efficacy of 'diffuse borders'.

Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.

OBJECTIVES: This study investigated coronary artery remodeling patterns associated with clinical outcomes. BACKGROUND: In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. METHODS: Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). RESULTS: Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. CONCLUSIONS: The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. ( PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466).