Fibrous Cap Thickness Research Articles

Relationship between hemoglobin A1C and characteristics of plaque vulnerability in stable coronary disease: an optical coherence tomography study.

Patients with diabetes mellitus are at increased risk of cardiovascular events. We aimed to analyze the impact of serum HbA1c levels on coronary plaque characteristics in stable coronary disease. Two hundred sixty-one patients who underwent optical coherence tomography (OCT) examination before elective percutaneous coronary intervention for a de novo obstructive lesions were included in this single-center retrospective analysis. Patients were divided into tertiles according to HbA1c level (tertile 1: HbA1c < 6.3%, tertile 2: 6.3 ≤ HbA1c < 7.8%, tertile 3: HbA1c ≥ 7.8%) and OCT findings were compared. Fibrous cap thickness (FCT) was significantly thinner in tertile 3 compared to tertile 1 and tertile 2 (103.9 ± 48.2µm [tertile 1] vs. 107.5 ± 60.6µm [tertile 2] vs. 86.2 ± 35.8µm [tertile 3], p = 0.03). Higher prevalence of thin-cap fibroatheroma (TCFA) was observed in tertile 3 vs tertile 1 and tertile 2 (19.5% [tertile 1] vs. 19.5% [tertile 2] vs. 33.3% [tertile 3], p = 0.04). HbA1c inversely correlated with FCT (beta coefficient - 4.89, 95% confidence interval - 8.40 to - 1.39, p < 0.01). The logistic regression model revealed that the probability of having TCFA was positively associated with HbA1c with a small change in the range of low and medium HbA1c and a big change in the range of high HbA1c. Furthermore, minimal lumen area and reference lumen area were smaller in tertile 3. In patients with stable coronary disease, high serum HbA1c levels are associated with higher plaque burden and thinner FCT on OCT, while low and medium HbA1c levels result in similar plaque vulnerability.

Effects of TCFA on stent neointimal coverage at 9months after EXCEL drug-eluting stent implantation assessed by OCT.

The aim of this study was to investigate the effects of thin-cap fibroatheromas (TCFAs) on stent neointimal coverage at the 9‑month follow-up after EXCEL stent implantation assessed by optical coherence tomography (OCT). Atotal of 93 patients with non-ST elevation acute coronary syndrome (NSTEACS) who underwent EXCEL stent implantation were prospectively enrolled in the study and divided into aTCFA group (n = 47) and anon-TCFA group (n = 46) according to whether EXCEL stents covered the TCFAs. ATCFA was defined as aplaque with lipid content in more than one quadrant and fibrous cap thickness measuring less than 65 μm. The effect of TCFAs on stent neointimal coverage at the 9‑month follow-up after stent implantation was evaluated by OCT. The primary study endpoints were the incidence of neointimal uncoverage and stent malapposition. At the 9‑month follow-up, the minimal lumen diameter of the TCFA group tended to be smaller (2.8 ± 0.8 vs. 2.1 ± 0.8, p = 0.08) and the diameter of stenosis in the TCFA group tended to be larger (15.1 ± 10.3% vs. 26.3 ± 15.1%, p = 0.08) than those in the non-TCFA group. The mean intimal thickness of the TCFA group was significantly lower than that of the non-TCFA group (67.2 ± 35.5 vs. 145.1 ± 48.7, p < 0.001). The uncovered struts (10.1 ± 9.7 vs. 4.8 ± 4.3, p = 0.05) and malapposed struts (2.1 ± 4.7 vs. 0.3 ± 0.5, p = 0.003) in the TCFA group were more significant than those in the non-TCFA group. Multivariate analysis showed that TCFAs and lesion types were independent predictors of incomplete neointimal coverage (p < 0.05), and lesion types were independent predictors of stent malapposition (p < 0.05). In patients with NSTEACS, TCFAs delayed endothelium coverage at 9months after stent implantation, and TCFAs were independent predictors of incomplete neointimal coverage of the stent.

Transcoronary stem cell transfer and evolution of infarct-related artery atherosclerosis: evaluation with conventional and novel imaging techniques including Quantitative Virtual Histology (qVH).

It has been suggested that infarct-related artery (IRA) atherosclerosis progression after stem cell transcoronary administration might represent a stem-cell mediated adverse effect. To evaluate, using conventional (quantitative coronary angiography, QCA, intravascular ultrasound - IVUS) and novel (quantitative virtual histology - qVH) tools, evolution of IRA atherosclerosis following transcoronary stem cell transfer. QCA, IVUS, VH-IVUS and qVH were performed in 22 consecutive patients (4 women) aged 59 years (data provided as median) undergoing a distal-to-stent infusion of 2.21 × 106 CD34+CXCR4+ autologous bone marrow cells via a cell delivery-dedicated perfusion catheter at anterior AMI day 7. Imaging was repeated at 12 months. This was a substudy of Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial (NCT00316381). 18.2% subjects showed absence of distal-to-stent angiographic/IVUS atherosclerotic lesion(s) at baseline and no new lesion(s) at 12-months. In the remaining cohort, there were 28 lesions by QCA (32 by IVUS) at baseline and no new lesion(s) at follow-up. Three fibroatheromas evolved (2 to calcified fibroatheroma and 1 to a fibrocalcific lesion); other plaques maintained their stable (low-risk) phenotypes. Diameter stenosis of QCA-identified lesions was 29.5 vs. 26.5% (p = 0.012, baseline vs. 12-months). Gray-scale IVUS showed reduction in area stenosis (33.8 vs. 31.0%, p = 0.004) and plaque burden (66.27 vs. 64.56%, p = 0.009) at 12-months. Peak fibrotic plaque content increased from 70.41% to 75.0% (p = 0.004). qVH peak confluent necrotic core area and minimal fibrous cap thickness remained stable (0.64 vs. 0.59 mm2, p = 0.290, and 0.15 vs. 0.16 mm, p = 0.646). This study, using a range of classic and novel imaging techniques, indicates lack of any stimulatory effect of transcoronary stem cell transfer on coronary atherosclerosis. Whether, and to what extent, a moderate reduction in plaque burden and stenosis severity at 12-months results from optimized pharmacotherapy and/or stem cell transfer requires further elucidation.

Numerical simulation study of fracture mechanics of the atherosclerotic plaque

Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.

Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis.Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (<30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax).Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708–1,286 mm3, p = 0.03), patients who qualified with stroke (1,856–1,440 mm3, p = 0.05), and non-statin users (1,325–1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (rs = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (rs = −0.4, p = 0.02) and calcium volume (rs = −0.4, p = 0.03).Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.

A novel animal model for vulnerable atherosclerotic plaque: dehydrated ethanol lavage in the carotid artery of rabbits fed a Western diet.

The study of unstable atherosclerotic plaques is limited by the absence of ideal animal models to reproduce the plaque instability observed in humans. In this study, we attempted to develop a novel animal model for vulnerable atherosclerotic plaques using dehydrated ethanol lavage in rabbits fed a Western diet (WD). A total of 30 New Zealand White (NZW) rabbits were randomized to 5 groups, including a control group with or without WD, a balloon injury with WD group, and an ethanol injury with or without WD group. Operations were conducted using the right common carotid artery as the target vessel. All animals were followed up for 3 months unless a vascular event occurred. Blood samples and carotid artery specimens were ultimately collected for analysis of atherogenesis. Compared to rabbits in which lesions were induced by balloon injury, those subjected to an ethanol lavage with high cholesterol diet showed progressive atherosclerotic lesions in all carotid artery segments, which were characterized by greater plaque burden, smaller minimum lumen area (MLA), and increased vulnerability as indicated by abundant macrophages, scattered smooth muscle cell (SMC) composition, higher matrix metalloproteinase-9 (MMP-9) expression in plaques, thinner fibrous cap thickness, and higher possibility of stroke event (50% vs. 0%). Meanwhile, the serum interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) levels in the ethanol injury group with a high-cholesterol diet were significantly higher than those in the balloon injury group after 3 months (all P<0.01). We successfully established a novel animal model for vulnerable atherosclerosis by ethanol exposure of the carotid segment that has a higher predictive value for the probability of ischemic events than the balloon injury model. Therefore, it may represent a promising animal model for investigating new therapeutic approaches, novel imaging modalities, and underlying mechanisms for vulnerable atherosclerotic plaque.

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

BackgroundHigh mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). MethodsPlasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. ResultsMannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 μm (odds ratio = 1.32 per each 10 μmol/L mannose change [95% confidence interval, 1.05–1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 μmol/L: 4.0(95%CI, 1.4–11.3), p = 0.006). ConclusionThe current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.

Relationship betweeen the amount and location of macrophages and clinical outcome: subanalysis of the CLIMA-study

BackgroundThe ability of optical coherence tomography (OCT) to recognize intraplaque macrophage infiltration is now well acknowledged. This post-hoc analysis of the CLIMA study aimed to address the clinical impact of the circumferential extension of OCT-defined macrophages and their location at one year follow-up. MethodsThe multicentre CLIMA study enrolled 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending (LAD) coronary artery. Measurements of circumferential extension of macrophages and measurements of the distance from intima-lumen contour to macrophages string were performed at the plaque cross-section judged as containing the greatest amount of macrophages. The main study endpoint was a composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). ResultsPatients with large macrophage arc (p = 0.001) and superficial macrophage arc (p < 0.001) showed a higher one-year incidence of the main one-year composite endpoint. Consistently hypertension (p = 0.018), family history of CAD (p = 0.046), diabetes mellitus (p = 0.036), lower ejection fraction (p = 0.009) and chronic kidney disease (p = 0.019) were more frequently found in patients experiencing the main composite endpoint. At multivariate Cox regression analysis, fibrous cap thickness < 75 μm (HR 2.51, 95% 1.46–4.32), presence of large (HR 1.97, 95%CI 1.16–3.35, p = 0.012) and superficial (HR 1.72, 95%CI 1.02–2.90; p = 0.040) macrophage arc remained independent predictors of the main composite endpoint. Large macrophage arc was associated with target LAD related MI. ConclusionThe present post-hoc analysis of the CLIMA showed that the circumferential extension of macrophages and their location are related to a composite endpoint of cardiac death, MI and/or TVR.

Abstract 9935: Culprit Plaque Morphology in Young versus Elder Acute Coronary Syndrome Patients: An Optical Coherence Tomography Study

Objective: Culprit plaque morphology in young acute coronary syndrome (ACS) patients differs from that of elder patients. The underlying mechanisms responsible for ACS in younger compared to elder patients are yet to be explored with optical coherence tomography. Methods: This was a prospective, single-center, investigational study. Patients were divided into groups according to age, ≤35 (N=43) and &gt;35 years (N=50) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). Results: A total of 93 patients were included in this analysis. Thin-cap fibroatheroma (TCFA) was significantly higher among elder than younger patients for both PR (80.0% vs. 31.8%, p=0.002) and PE (66.7% vs. 6.3%, p&lt;0.001) groups. Microchannels were also significantly more prevalent among elder than younger patients for both PR (65.0% vs. 18.2%, p=0.004) and PE groups (55.6% vs.12.5%, p=0.013). Macrophages were significantly higher in elder than younger patients for both PR (25.0% vs. 0%, p=0.018) and PE (44.4% vs. 0%, p=0.003) groups. In contrast, fibrous cap thickness was greater in younger than elder patients for both PR (105.71±48.02 μm vs. 58.00±15.76 μm, p&lt;0.001) and PE (126.67±48.22 μm vs. 54.38±24.21 μm, p&lt;0.001) groups. Intimal thickness was greater in elder than younger patients for both PR (728.00±313.92 mm 2 vs. 342.27±142.02 mm 2 , p&lt;0.001) and PE (672.78±334.57 mm 2 vs. 295.00±99.60 mm 2 , p&lt;0.001) groups. Plaque type, thrombus formation, and minimal luminal diameter did not differ significantly according to age. Conclusion: We conclude that the high resolution of OCT is able to define the detailed microstructure of the culprit lesion and allows a greater understanding of the mechanisms of coronary artery disease. The frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in elder ACS patients compared to younger patients. However, fibrous cap thickness was significantly greater in younger ACS patients compared to elder patients.

Abstract 9862: Correlation of Lipoprotein(a) and Plaque Morphology in Very Young Acute Coronary Syndrome Patients Using Optical Coherence Tomography

Background: Levels of lipoprotein (Lp) (a) are a useful marker for risk stratification of cardiovascular diseases. This genetic biomarker is suggestive of patient predisposition to an acute coronary event. Its correlation with the plaque morphology is yet to be explored with optical coherence tomography (OCT). Aim: To study the correlation of Lp(a) levels and plaque morphology in very young (&lt;35 years) patients presenting with acute coronary syndrome(ACS). Methods: A prospective, single-centre, observational study was conducted at a tertiary-care centre. Very young patients with acute coronary syndrome and fit for OCT guided invasive coronary angiography were included. Lp(a) levels were compared between healthy controls and these very young ACS patients. Correlation of Lp(a) levels and plaque characteristics in very young ACS patients was done using OCT imaging. Results: A total of 80 subjects were enrolled in the study. Out of these 40 were very young ACS and 40 were age matched healthy controls. Mean levels of Lp(a) were 28.10±13.96 nmol/l and 61.20±55.88 nmol/l in healthy controls and very young patients with ACS respectively (p=0.022). In very young patients, plaque rupture and erosion were the mechanism of acute coronary syndrome in 67.5% and 32.5% patients, respectively. Among very young ACS patients, those with Lp(a) levels &lt;75 nmol/l had a mean thin cap fibroatheroma thickness of 96.89±65.52 μm and those with Lp(a) levels ≥75 nmol/l had a mean thin cap fibroatheroma thickness of 67.85±53.80 μm (p=0.158). Conclusion: It was revealed that patients with higher Lp(a) levels had lesser thickness of fibrous cap on OCT imaging compared with lower levels of Lp(a). Lp(a) levels were independently associated with ACS in very young (&lt;35 years) patients, with plaque rupture being the commonest mechanism. Hence, we conclude that higher Lp(a) levels predispose to ACS at a very young age associated with lowering of fibrous cap thickness.

Abstract 13099: Correlation of Lipoprotein(a) Levels With Coronary Plaque Morphological Features and Vulnerability: An Optical Coherence Tomography Study

Introduction: High lipoprotein(a) level is a potential independent risk factor for coronary artery disease (CAD). However, the relationship between the Lp(a) value and the morphological characteristics of plaque defined by optical coherence tomography (OCT) has not been completely clarified so far. Meanwhile, no evidence has been raised for a clear cut-off value of Lp(a) for preventing the process of CAD. Hypothesis: Based on the biological properties of Lp(a), We assessed the hypothesis that the Lp(a) levels may relate to the vulnerable features of lipid plaque defined by OCT. Methods: 420 CAD patients who had undergone OCT scan to at least 1 main coronary vessel during 2013-2018 were enrolled. Patients were first stratified into 3 levels according to the values of Lp(a) at admission: Lp(a)&lt;30 mg/dl (Group A), 30-60 mg/dl(Group B), and &gt;60 mg/dl(Group C). After enrolled the cases with Lp(a) &gt;60mg/dl, we chose cases of the other 2 groups matching according to traditional risk factors of CAD to our current analysis. OCT pullbacks of the target vessels were collected and analyzed at every 0.4 mm by 2 independent observers blinded to the clinical data and angiographies with QIVUS software. Results: A total of 90 cases were enrolled into the current study, with 30 cases in each group. Lipid plaque in Group B and Group C had a thinner minimum fibrous cap thickness, wider maximum lipid arc, longer lipid length, and greater lipid index than Group A. The Lp(a) levels significantly correlated with lipid length (r=0.283), the maximum arc of lipid(r=0.293), lipid index(r=0.357), and inversely correlated with minimum fibrous cap thickness (r =-0.403). Multivariate analysis demonstrated that the Lp(a) level was independently associated with TCFA (odds ratio 1.035, 95% confidence interval 1.014-1.057). In addition, the ROC curve analysis results (AUC =0.694, p &lt; 0.001) indicated the Lp(a) is a good diagnostic indicator for detecting TCFA, and the optimal cut-off was 33.65 mg/dl. Conclusions: Our current study indicates that CAD patients with higher Lp(a) level(&gt;30 mg/dl) exhibited a higher prevalence of TCFA and had more other typical vulnerable characteristics defined by OCT. New Lp(a) lowering therapy could aim at a level of &lt; 33.65mg/dl for stabilizing coronary plaque.

Abstract 9162: Increased Ratio of B2/B1-like Lymphocytes in the Perivascular Adipose Tissue Could Contribute to Plaque Destabilization in Human Coronary Arteries: Preliminary Results

Introduction: B-lymphocyte density in the pericoronary adipose tissue (PvAT) was correlated with plaque size in human coronary arteries. However, the subtypes of B cells in the PvAT and atherosclerotic plaque composition have not investigated yet. Hypothesis: We hypothesized that B2 and the ratio of B2/B1-like lymphocytes in the PvAT will correlate with an increase in components related to plaque destabilization and a decrease in components related to plaque stabilization. B1-like lymphocytes will correlate with an increase of components related to plaque stabilization. Methods: Coronary arteries were freshly dissected with adjacent PvAT. The most important atherosclerotic plaque was selected from each main coronary artery. From 107 artery segments, we calculated the percentage of arterial obstruction, intima-media thickness, the minimum fibrous cap thickness, and the percentage of collagen, smooth muscle cells, fibrous cap, calcification, lipid, necrosis, and intraplaque hemorrhage. We considered B2-lymphocytes as CD20 + CD43 - and B1-like lymphocytes as CD20 + CD43 + using the immunohistochemistry double staining technique. The densities of B2, B1-like, and the ratio of B2/B1-like lymphocytes were correlated with plaque composition using linear, negative binomial, or Poisson regressions models with clustering for multiple measures in the same individual and adjusted for age, sex, hypertension, diabetes, body mass index, sedentary lifestyle, smoking, and alcohol consumption. Results: B2 and B1-like lymphocyte density in the PvAT were not correlated with plaque components. However, the increase of the ratio of B2/B1-like lymphocytes was associated with a decrease in intraplaque collagen (β= -0.19, 95%CI= -0.35; -0.03, p=0.01), calcification (β= -0.15, 95%CI= -0.28; -0.02, p=0.01), hemorrhage (β= -0.08, 95%CI= -0.15; -0.02, p=0.009), minimum fibrous cap thickness (β= -0.03, 95%CI= -0.04; -0.01, p&lt;0.001), and an increase in the number of vasa vasorum in adventitia layer (β= 0.006, 95%CI=0.001; 0.01, p=0.006). Conclusions: An increase in the ratio of B2/B1-like lymphocytes in the PvAT could contribute to plaque destabilization by the decrease of atherosclerotic plaque components related to plaque stabilization.

Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment.

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p < 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p < 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.

Gender-based in vivo comparison of culprit plaque characteristics and plaque microstructures using optical coherence tomography in acute coronary syndrome.

Introduction: Women perform worse after acute coronary syndrome (ACS) than men. The reason for these differences is unclear. The aim was to ascertain gender differences in the culprit plaque characteristics in ACS. Methods: Patients with ACS undergoing percutaneous coronary intervention for the culprit vessel underwent optical coherence tomography (OCT) imaging. Culprit plaque was identified as lipid rich,fibrous, and calcific plaque. Mechanisms underlying ACS are classified as plaque rupture, erosion,or calcified nodule. A lipid rich plaque along with thin-cap fibroatheroma (TCFA) was a vulnerable plaque. Plaque microstructures including cholesterol crystals, macrophages, and microvessels were noted. Results: A total of 52 patients were enrolled (men=29 and women=23). Baseline demographic features were similar in both the groups except men largely were current smokers (P <0.001). Plaque morphology,men vs. women: lipid rich 88.0% vs. 90.5%; fibrous 4% vs 0%; calcific 8.0% vs. 9.5% (P = 0.64). Of the ACS mechanisms in males versus females; plaque rupture (76.9 % vs. 50 %), plaque erosion (15.4 % vs.40 %) and calcified nodule (7.7 % vs. 10 %) was noted (P = 0.139). Fibrous cap thickness was (50.19 ±11.17 vs. 49.00 ± 10.71 mm, P = 0.71) and thin-cap fibroatheroma (96.2% vs. 95.0%, P = 1.0) in men and women respectively. Likewise no significant difference in presence of macrophages (42.3 % vs. 30%, P = 0.76), microvessels (73.1% vs. 60 %, P = 0.52) and cholesterol crystals (92.3% vs. 80%, P = 0.38). Conclusion: No significant gender-based in-vivo differences could be discerned in ACS patients’ culprit plaques morphology, characteristics, and underlying mechanisms.

Frequency and predictors of thin-cap fibroatheroma progression: a comprehensive and dynamic in-vivo OCT study

Abstract Purpose To assess the evolution of thin-cap fibroatheroma (TCFA) and to explore predictors for its progression by using optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods We enrolled ACS patients with non-culprit TCFA at baseline and corresponding OCT images at follow-up of 9 to 15 months. Clinical, angiographic and OCT data were collected and analyzed according to established methods. TCFA was defined as a lipid plaque with maximum lipid arc &amp;gt;90° and fibrous cap thickness &amp;lt;65μm. Considering the resolution of OCT, the regression of TCFA was defined as an increase of fibrous cap thickness &amp;gt;10μm. Inversely, TCFA progression was defined as a decrease, constant or ≤10μm increase of fibrous cap thickness. Results 41 patients with 55 non-culprit TCFAs were taken into final analysis. 17 patients (41.5%) had patient-level progression and 22 TCFAs (40.0%) progressed at plaque-level with a median follow-up duration of 371 days. 11 (20.0%) of the 55 TCFAs happened subclinical rupture at follow-up, including 10 with the formation a new layer and 1 without the detection of the new layer. Besides, another patient suffered re-myocardial infarction because of the rupture of TCFA induced acute thrombosis and lumen occlusion during follow-up. The baseline clinical and angiographic characteristics were similar between the two cohorts. The progression group had a significantly higher prevalence of macrophage infiltration and vasa vasorum at baseline than the non-progression group (Figure 1). Multivariate analysis identified macrophage infiltration (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 1.01 to 27.91; p=0.049]) as the independent predictor of TCFA progression. When it came to the evolution of lesion morphology and lipid components, the progression cohort had a higher percent change of lumen stenosis and lipid length (Figure 2). Conclusions About 40% of non-culprit TCFAs in ACS patients progressed in fibrous cap thickness at a median interval of 1 year. Macrophage infiltration was the independent predictor of non-culprit TCFA progression. The progression of fibrous cap thickness was usually accompanied with an aggressive evolution of other lesion characteristics. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the National Key R&amp;D Program of China Baseline OCT characteristicsPercent change of lesion morphology

Optical coherence tomography-defined vulnerable plaque characteristics in relation to functional severity of coronary stenoses stratified by quantitative flow ratio

Abstract Background The functional severity and morphological features of epicardial lesions are both related to plaque vulnerability and adverse coronary events. However, their relationship remains controversial, especially in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Purpose This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with optical coherence tomography (OCT)-defined vulnerable plaques such as thin-cap fibroatheromas (TCFAs) in a board spectrum of population, including patients presenting stable angina and NSTE-ACS. Methods We identified patients who underwent OCT examinations from 2 prospective cohorts and then assessed interrogated vessels with QFR. Lesions were divided into tertiles: QFR-T1 (QFR &amp;lt;0.85)&amp;lt;qfr),&amp;gt;, QFR-T2 (0.85 to 0.93) and QFR-T3 (QFR &amp;gt;0.93). Results This post-hoc analysis included 83 lesions from 79 patients (mean age: 61.5±9.8 years, males: 58%). Patients with NSTE-ACS accounted for the majority of the population (67%). The median % diameter stenosis and median QFR value were 42% (36 to 49%) and 0.88 (0.83 to 0.95), respectively. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) (p=0.003 and 0.018, respectively). Overall significant differences were observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness (FCT), and minimal lumen area (MLA) (p=0.017, 0.040, and &amp;lt;0.001, respectively). The Spearman's correlation analysis showed that QFR was significantly related to MLA (ρ = 0.537, p&amp;lt;0.001), % area stenosis (ρ = –0.512, p&amp;lt;0.001), maximum lipid arc (ρ = –0.360, p=0.002), lipid length (ρ = –0.242, p=0.038), lipid index (ρ = –0.333, p=0.004), and thinnest FCT (ρ = 0.315, p=0.006). In the multivariable analysis, QFR ≤0.80 remained as a significant determinant of TCFAs regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted odds ratio = 4.387, 95% confidence interval: 1.297 to 14.839, p=0.017). In addition, QFR demonstrated moderate predictive ability for OCT-TCFA (area under the curve = 0.72, 95% confidence interval: 0.58 to 0.86, p=0.003) with the best cutoff of ≤0.86 (sensitivity: 65%; specificity: 73%; negative predictive value: 85%; accuracy: 71%). Conclusions Lower QFR was related to OCT-TCFA and other vulnerable plaque characteristics in angiographically mild-to-intermediate stable lesions and culprit lesions from NSTE-ACS. The QFR might be a useful tool for ruling out high-risk, rupture-prone plaques without using any pressure wires or vasodilators. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Jiangsu Provincial Key Research and Development Program Flow diagram of patient selectionOCT findings according to QFR tertiles

Adoption of a new automated optical coherence tomography software to obtain a lipid plaque spread-out plot

Abstract Background Near infrared spectroscopy – intravascular ultrasound (NIRS-IVUS) imaging can provide a fully automated estimation of lipid burden, providing a two-dimensional spread-out plot, the Lipid Core Burden Index (LCBI), which has been associated with higher incidence of cardiac events. Optical coherence tomography (OCT) can identify lipid component with high accuracy and it is therefore potentially capable of measuring its longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Purpose The present study has been designed to validate a novel automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot plus other features of plaque vulnerability. Methods We compared the results obtained with a novel automated OCT alghorithm, developed utilising a convolutional neural network, with those obtained with conventional (manual) OCT and with NIRS-IVUS in a consecutive series of 40 patients with coronary artery disease. We tested and validated our new OCT algorithm to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. In each coronary plaque, the following measurements were obtained with NIRS-IVUS: 1) minimum lumen area (MLA), 2) vessel area at MLA site, 3) plaque burden (%) at MLA site, 4) NIRS-defined lipid pool arch and 5) maximum LCBI measurement within a 4 mm length. The following OCT features were obtained: 1) the MLA cross section, 2) the minimum fibrous cap thickness (FCT) in presence of lipid components and measured as the average of three measurements obtained in the same cross-section and 3) maximum LCBI within a 4 mm length. Results Three lesions groups were identified according to the studied lesions: 1) culprit lesions in patients with acute coronary syndrome (ACS, n=16), 2) non-culprit lesions in patients with ACS (n=12) and 3) lesions in patients with stable angina (n=12). OCT conventional assessment showed for the culprit ACS plaques a trend for a larger lipid arc and a significant thinner FCT (p=0.028). Consistently, NIRS-IVUS showed for culprit ACS plaques a more complex anatomy. A strong trend for increased maximum LPBI in 4mm segments was found in the culprit ACS group, regardless of the adopted imaging modality, either NIRS-IVUS or automated OCT (p=0.184 and p=0.066, respectively, figure 1). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r=0.75). The sensitivity and specificity of automated OCT to detect significant LCBI, applying a validated 400 cut off were 90.5 and 84.2 respectively. Conclusions We developed an automated approach, comparable to NIRS, to assess OCT images that can provide a dedicated lipid plaque spread-out plot to address plaque vulnerability. The automated OCT software can promote and improve OCT clinical applications for the identification of patients at risk of hard events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): CLI - Centro Lotta all'Infarto Spread-out plot by IVUS-NIRS and OCT

TH1 lymphocytes in the perivascular adipose tissue correlate with plaque composition and increase the risk of intraplaque haemorrhages in coronary arteries: an autopsy study

Abstract Background Inflammation in the perivascular adipose tissue (PvAT) might play a role in coronary artery disease. The T helper 1 (Th1) lymphocytes are the most popular T helper (Th) lymphocytes in atherosclerotic plaques and are proatherogenic. However, the association between the Th1 and Th lymphocytes in the PvAT with coronary atherosclerosis composition was not previously investigated in humans. Purpose We investigated the correlation between Th CD4+ and Th1 CD4+CXCR3+ lymphocytes in the PvAT with atherosclerotic plaque composition. Methods Human coronary arteries were freshly dissected with adjacent PvAT. The most important atherosclerotic plaque was selected of the main coronary arteries and was stained with hematoxylin-eosin, Masson's trichrome, and Verhöeff. We calculated the percentage of arterial obstruction, intima-media thickness, the minimum fibrous cap thickness, and the percentual of collagen, smooth muscle cells (SMC), fibrous cap, calcification, lipid, necrosis, and intraplaque hemorrhage. The atherosclerotic plaques were classified in stable and unstable plaques (hemorrhages and thrombus). The density of Th lymphocytes (CD4+), Th1 (CD4+CXCR3+), and the ratio of Th1/Th were detected using the immunohistochemistry double staining technique. The densities and the ratio Th1/Th were correlated with plaque composition using linear, negative binomial, or Poisson regressions models with clustering for multiple measures in the same individual and adjusted for age, sex, hypertension, diabetes, body mass index, sedentary lifestyle, smoking, and alcohol consumption. Results We evaluated a sample of 126 coronary arteries from 58 subjects. The individuals were older (70.4±14.3 years old), sex was equally distributed, 74% had hypertension, and 40% diabetes. In multivariate analysis, the Th lymphocytes were negatively correlated with calcification content (β=−0.21, 95% CI: −0.41; −0.006, p=0.043). The Th1 lymphocytes were not correlated with plaque composition; however, the increase of Th1 density in relation to Th lymphocytes was negatively correlated with SMC (β=−35.6, 95% CI: −68.5; −2.83, p=0.03) and the fibrous cap content (β=−11.6, 95% CI: −19.1; −4.05, p=0.003). Additionally, the higher proportion of Th1/Th lymphocytes increased the risk of intraplaque haemorrhages compared to stable coronary plaques (OR=15.5, 95% CI: 1.23; 196.4, p=0.03). Conclusions The increase of pro-inflammatory Th1 lymphocytes in the PvAT was correlated to the decrease of components in atherosclerotic plaques related to plaque stabilization, such as SMC and fibrous cap content. Additionally, the increase in the proportion of pro-inflammatory Th1 lymphocytes in the PvAT also increases the risk of intraplaque haemorrhages in coronary arteries. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): São Paulo Research Foundation (FAPESP) Figure 1Figure 2

Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: an intravascular optical coherence tomography study

BackgroundApolipoprotein (Apo) A1 and Apo B are strongly associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the relationship between the Apo B/A1 ratio and the morphology of coronary vulnerable plaques has not been fully elucidated in patients with ASCVD.MethodsA total of 320 patients with ASCVD undergoing percutaneous coronary intervention were enrolled and assigned into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) group. The morphology of culprit plaque was analyzed by intravascular optical coherence tomography. Association between the Apo B/A1 ratio and coronary vulnerable plaques were evaluated using logistic regression models and receiver operator characteristic (ROC) curve analyses.ResultsThe Apo B/A1 ratio was higher in ACS patients than CCS patients (0.77 ± 0.28 vs. 0.64 ± 0.22, P < 0.001) and it was also higher in patients with plaque rupture, erosion or thrombus than those without culprit plaques. The high Apo B/A1 ratio was associated with high percent of vulnerable plaques compared with low ratio group. The Apo B/A1 ratio was negatively related to fibrous cap thickness in lipid-rich plaque (r = − 0.228, P = 0.043). Univariate and multivariate logistic regression analyses revealed that the Apo B/A1 ratio was an independent factor of plaque rupture, erosion, and thrombus. The area under the ROC curve of the Apo B/A1 ratio for plaque rupture, erosion, and thrombus were 0.632, 0.624, and 0.670 respectively (P < 0.001 for all), which were higher than that of low-density lipoprotein cholesterol.ConclusionsThe Apo B/A1 ratio is an independent predictor for plaque rupture, erosion, and thrombus in patients with ASCVD.

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

BackgroundProprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited.MethodsIn this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up.ResultsLDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8–29.2] μm vs 13.2 [7.4–18.6] μm; P = 0.029), greater increases in minimum lumen area (0.20[0.10–0.33] mm2 vs 0.13 [0.12–0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8–24.5] vs. 8.4̊ [2.0–10.5]; P = 0.008).ConclusionsThe addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype.Trial registrationClinicalTrials.gov Identifier: NCT04851769. Registered 2 Mar 2019.