Culprit Plaque Research Articles

Differential culprit plaque morphology in acute coronary syndrome: a comparison between very young patients (≤35 years) and older counterparts using optical coherence tomography.

Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT. This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young 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 older than very young 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 very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P < 0.001) groups. Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.

Age-related Pancoronary Characteristics in Patients with ST-segment Elevation Myocardial Infarction

Background: Age-related vulnerable characteristics of pancoronary plaques in patients with ST-segment elevation myocardial infarction (STEMI) have not been systemically evaluated by optical coherence tomography (OCT). Therefore, we sought to explore the discrepancies in pancoronary characteristics between younger and older patients with STEMI through OCT. Methods: This retrospective single-center study included 588 patients who had STEMI and underwent three-vessel OCT through emergency percutaneous coronary intervention between October 2016 and September 2018. With a median age of 56 years as a cutoff, the patients were divided into a younger group (≤56 years, n = 298) and an older group (&gt;56 years, n = 290). Results: A total of 795 non-culprit plaques were found in 298 of the younger patients, whereas 858 non-culprit plaques were identified in 290 of the older patients. Fewer high-risk OCT plaques (15.8% vs. 23.1%; P = 0.025), as well as other structures (cholesterol crystals, P = 0.001; microchannels, P = 0.032; calcifications, P &lt; 0.001; spotty calcifications, P &lt; 0.001; large calcifications, P &lt; 0.001; and thrombi, P = 0.001) were identified in younger patients than older patients, at the patient level. In addition, pancoronary vulnerability in younger patients was independently predicted by culprit plaque rupture {CLIMA-defined high-risk plaques (odds ratio [OR]: 3.179; 95% CI: 1.501 to 6.733; P = 0.003), non-culprit rupture (OR: 3.802; 95% CI: 1.604 to 9.014; P = 0.002), non-culprit thin-cap fibroatheroma (OR: 3.536; 95% CI: 2.051 to 6.094; P &lt; 0.001)}, hypertension (OR: 1.920; 95% CI: 1.099 to 3.355; P = 0.022), and total cholesterol (OR: 1.094; 95% CI: 1.002 to 1.195; P = 0.045). In older patients with STEMI, the predictor was male sex (OR: 3.031; 95% CI: 1.352 to 6.795; P = 0.007). Conclusions: Among patients with STEMI, younger patients had limited vulnerable plaque characteristics, and pancoronary vulnerability was associated with culprit plaque rupture, hypertension, and total cholesterol. In contrast, older patients had greater pancoronary vulnerability with the single predictor of male sex, thus suggesting that traditional risk factors have limited applicability in predicting pancoronary vulnerability in older patients.

Coronary artery calcification and plaque stability： an optical coherence tomography study

BackgroundCoronary artery calcification (CAC), a surrogate of atherosclerosis, is related to stent underexpansion and adverse cardiac events. However, the effect of CAC on plaque stability is still controversial and the morphological significance of CAC has yet to be elucidated. MethodsA retrospective series of 419 patients with acute coronary syndrome (ACS) who underwent optical coherence tomography (OCT) were enrolled. Patients were classified into three groups based on the calcification size in culprit plaques and the features of the culprit and non-culprit plaques among these groups were compared. Logistic regression was used to analyze independent risk factors for culprit plaque rupture and the nonlinear relationship between calcification parameters and culprit plaque rupture. Furthermore, we compared the detailed calcification parameters of different kinds of plaques. ResultsA total of 419 culprit plaques and 364 non-culprit plaques were identified. The incidence of calcification was 53.9 % in culprit plaques and 50.3 % in non-culprit plaques. Compared with culprit plaques without calcification, plaque rupture, macrophages and cholesterol crystals were more frequently observed in the spotty calcification group, and the lipid length was longer; the incidence of macrophages and cholesterol crystals was higher in the macrocalcification group. Calcification tended to be smaller in ruptured plaques than in non-ruptured plaques. Moreover, the arc and length of calcification were greater in culprit plaques than in non-culprit plaques. ConclusionsVulnerable features were more frequently observed in culprit plaques with spotty calcification, whereas the presence of macrocalcification calcifications did not significantly increase plaque vulnerability. Calcification tends to be larger in culprit plaques than in non-culprit plaques.

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction.

As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI). A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features. The median RvD1 level was 129.7 (56.6-297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20-3.66, P = 0.010), healed plaques (≥246.4 pg/mL, OR: 2.17, 95% CI: 1.11-4.24, P = 0.023), and calcification (≥293.38 pg/mL, OR: 2.10, 95% CI: 1.21-3.66, P = 0.008) at culprit lesions. Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.

Tau Protein in the Retina

AbstractBackgroundCurrently there is no definite cure for Alzheimer’s therefore early detection is critical. Undetected Alzheimer’s Disease (AD) can lead to severe accidents, neglecting to take essential medications, injury to oneself or others, and/or financial problems. Currently, biomarkers are the most promising way to detect Alzheimer’s early on. Biomarkers such as beta‐amyloid and tau levels taken through invasive mehods or brain scans that involve radiation are among them.As the retina is an extension of the brain and the brain structure, it is possible to detect misfolded proteins via retinal examination non‐invasively. The aim of this study was to discover the binding property of curcumin to both Tau and AB in the retina as a potential biomarker for AD.MethodIn this study, 20 patients were invited with mild AD who had undergone retinal examination within the past 2 years. All the patients had retinal imaging with curcumin which revealed misfolded proteins during the examination and then they were advised to take daily curcumin. The mean age of the patients was 71, and the patients were instructed to take Curcumin Meriva in 500 mg supplements once daily after their prior examinations. All patients had tests repeated with FAF and Heidelberg Spectralis OCT device. The regions with abnormal lesions on FAF were detected and the layer of the defect was scanned by OCT plus compared with the previous imaging of the patients. The images were examined in a masked fashion by 2 specialists.ResultThe images disclosed hyperfluorescent lesions on FAF and OCT revealed accumulations in the inner layers of the retina. Some accumulations had dot shapes and others had fibril‐tangle shapes. Some lesions were present in prior exams, but they were more pronounced and shinier after curcumin use. Their size and shape were in concordance with misfolded proteins in the brain (Figure).ConclusionRetinal examination with curcumin revealed AB plaques in the retina in prior studies. Our study is the first that may demonstrate an easy way to detect the culprit plaque Tau inside the retina of live patients.

CAD-RADS score, vascular inflammation, and plaque vulnerability

Abstract Background Coronary artery disease reporting and data system (CAD-RADS), which is widely used to report the severity of coronary artery disease on coronary computed tomography angiography (CTA), predicts the risk of future cardiovascular events. However, the relationship between the CAD-RADS score and vascular inflammation and plaque vulnerability has not been investigated. Objective The aim of this study was to correlate the CAD-RADS score with vascular inflammation and plaque vulnerability. Methods This is an observational, single-center cohort study with prospective clinical follow-up. Patients who underwent both coronary CTA and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. Patients were categorized into two groups according to the CAD-RADS score (≤4a or 4b/5). All coronary arteries were analyzed for high-risk plaque features (positive remodeling, low-attenuation plaque, napkin-ring sign, and spotty calcification) and peri-coronary adipose tissue (PCAT) attenuation. PCAT attenuation was measured around the culprit lesion and in the proximal segment of all 3 coronary arteries. OCT features of plaque vulnerability were evaluated in culprit vessels. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as composite endpoints of unplanned target vessel revascularization, unplanned non-target vessel revascularization, nonfatal acute coronary syndrome, stroke, and cardiac death. Results Among 369 patients with 902 lesions, 104 (28.2%) were categorized in CAD-RADS 4b/5 and 265 (61.8%) in CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had higher PCAT attenuation than those with CAD-RADS ≤4a at all three levels (mean of 3 coronary vessels: -67.9 ± 6.9 HU vs. -70.2 ± 6.5, P=0.004; culprit vessel: -67.4 ± 7.9 vs. -70.2 ± 7.6, P=0.004; culprit plaque: -67.0 ± 9.3 vs. -69.9 ± 10.5, P=0.009; respectively) (Figure 1 A). Lipid-rich plaque and macrophage, as detected by OCT, were more prevalent in the culprit vessel in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (89.0% vs. 78.5%, P=0.001; 76.6% vs. 64.9%, P=0.001; respectively) (Figure 1B). All HRP features, as detected by CTA, were more frequently observed in patients with CAD-RADS 4b/5 than those with CAD-RADS ≤4a (P for all &amp;lt;0.001) (Figure 2). The cumulative incidence of MACCE was higher in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (15.0% vs. 5.8%, P=0.045). Conclusions Higher CAD-RADS score was associated with a higher level of pan-coronary vascular inflammation and plaque vulnerability.Figure 1Figure 2

Comparison of plaque characteristics among different age groups in patients with acute coronary syndromes with or without diabetes

Abstract Background It has been reported that young patients with diabetes mellitus (DM) had a higher mortality rate after myocardial infarction. However, plaque characteristics among different age groups in patients with acute coronary syndromes (ACS) with or without DM are unknown. Purpose The aim of this study was to investigate the plaque characteristics among different age groups in ACS patients with or without DM in a large population. Methods Patients who presented with ACS and underwent preintervention OCT imaging were included. The culprit plaque was categorized as plaque rupture (PR), plaque erosion (PE) or calcified plaque (CP), and stratified by 5 age groups. Features of plaque vulnerability were also analyzed. Results Among 1394 patients, 482 (34.6%) had DM. DM patients had a higher prevalence of lipid-rich plaque (71.2% vs. 64.8%, p=0.016), macrophage (72.0% vs. 62.6%, p&amp;lt;0.001), and cholesterol crystal (27.6% vs. 19.7%, p&amp;lt;0.001) than non-DM patients. Non-DM patients showed a significant ascending trend with age in PR (p=0.004), lipid-rich plaque (p=0.018), whereas DM patients had a high prevalence of these vulnerable features at early age, which plateaued across the different age groups. Both DM and non-DM groups showed a significant decreasing trend in PE with age (non-DM patients, p&amp;lt;0.001; DM patients, p=0.020). Conclusions DM patients had a high prevalence of lipid-rich plaque and a high incidence of plaque rupture at early age. This pattern persisted across the different age groups.

Predictors of residual lipid content detected by near-infrared spectroscopy after elective stenting in patients with chronic coronary syndrome

Abstract Backgrounds Residual lipid-rich plaque (LRP) in stented segments assessed by near-infrared spectroscopy (NIRS) immediately after percutaneous coronary intervention (PCI) is reportedly associated with target lesion failure. However, morphological determinants of residual LRP after elective PCI remains unknown. Purpose This single-center observational study aimed to explore morphological and procedural predictors of residual LRP after electing PCI. Methods We investigated 340 consecutive patients who underwent elective NIRS-intravascular ultrasound-guided PCI for de novo coronary lesions. Lesions requiring balloon dilatation or debulking before NIRS imaging, requiring ≥2 remote stent deployment in the vessel, being treated with drug-coated balloon, and having insufficient NIRS imaging were excluded. Maximum lipid core burden index in 4mm (maxLCBI4mm) in culprit segment both before and after PCI was assessed by NIRS. Residual LRP was defined as post-PCI maxLCBI4mm in stented lesions &amp;gt;200. Baseline clinical and morphological findings were compared between lesions with versus without residual LRP. Multivariable logistic regression analysis was performed to determine predictors of residual LRP. Results A total of 236 de novo lesions in 223 patients were included in the final dataset. After PCI, residual LRP was observed in 69 (29%) lesions. Patients with residual LRP tended to be older than those without residual LRP. Pre-PCI maxLCBI4mm in culprit lesions, plaque burden, and remodeling index were greater in lesions with residual LRP. Post-PCI minimum stent area and expansion index tended to be smaller in lesions with residual LRP. In a multivariable analysis, pre-PCI maxLCBI4mm (per 10, adjusted odds ratio [OR]:1.04; 95% confidence interval [CI]: 1.02 to 1.05; p&amp;lt;0.01) and stent expansion index (per 10%, adjusted OR: 0.80; 95%CI: 0.64 to 0.99; p=0.047) were independently predictive of residual LRP. Conclusions In patients undergoing elective PCI, greater pre-PCI maxLCBI4mm and smaller stent expansion were associated with post-PCI residual LRP.

Simultaneous, free-breathing, non-contrast 3D whole-heart coronary magnetic resonance angiography and vulnerable plaque imaging in patients with suspected acute coronary syndrome

Abstract Background Coronary artery high-risk plaque identified on cardiovascular magnetic resonance (CMR) is associated with future coronary events, independent of coronary artery luminal stenosis. We have recently developed a 3-dimensional whole-heart free-breathing non-contrast CMR sequence that allows for simultaneous high-resolution visualisation of the coronary arteries and vulnerable plaque on co-registered bright and black blood images (iT2prep-BOOST) with 100% respiratory scan efficiency. Objectives To validate iT2prep-BOOST in patients with non-ST-segment elevation myocardial infarction (NSTEMI) against the reference standard imaging modalities of invasive X-ray coronary angiography and intravascular imaging [optical coherence tomography (OCT)/intravascular ultrasound (IVUS)]. Methods 41 consecutive patients with suspected NSTEMI, based upon clinical history, electrocardiographic changes and positive high-sensitivity troponin assays, were recruited into the study. Invasive coronary angiography ± intravascular imaging was used to classify coronary segments into the following categories: normal, non-culprit and culprit segments; stenosed segments as well as segments with vulnerable plaque features (lipid, calcium, fibroatheroma, thin cap fibroatheroma (TCFA), plaque rupture and thrombus). The highest plaque/myocardial signal intensity ratio (PMR) in each coronary segment was analysed on iT2prep-BOOST. Results The mean iT2prep-BOOST acquisition time was 10.8 ± 1.3 minutes. The mean ± standard error of mean (SEM) PMR of culprit segments was significantly higher than non-culprit segments, which was significantly higher than normal segments (1.01 ± 0.05 vs. 0.67 ± 0.01 vs. 0.35 ± 0.01, P&amp;lt;0.001). Coronary segments with lipid, calcium and fibroatheroma had a significantly higher PMR compared to normal coronary segments (P&amp;lt;0.001) but lower than segments with TCFA, plaque rupture and thrombus (P&amp;lt;0.001). There was a progressive increase in PMR with increasing degree of coronary stenosis (P&amp;lt;0.001). Patients with type 2 diabetes, hypertension, hyperlipidaemia and family history of coronary artery disease had a significantly higher PMR on iT2prep-BOOST (P&amp;lt;0.001, P=0.02, P=0.04 and P=0.02 respectively). Finally, PMR was positively correlated with HbA1c, total cholesterol, non-HDL cholesterol, LDL cholesterol and triglyceride levels (P&amp;lt;0.001, P=0.02, P=0.02, P=0.05 and P=0.05 respectively). Conclusions In summary, the proposed iT2prep-BOOST framework has the potential to simultaneously acquire coronary artery angiography and to differentiate normal segments from non-culprit and culprit plaque segments. Furthermore, PMR is associated with both biochemical and patient related risk factors for coronary artery disease (CAD). The long-term prognostic value of PMR needs to be investigated in a longitudinal multi-centre study of patients with suspected CAD.Figure 1Figures 2 and 3

Non-flow limiting non-culprit plaque characteristics in patients presenting with STEMI versus NSTEMI

Abstract Background Non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) are often considered distinct clinical entities. Although differences in culprit plaque characteristics have been described extensively, less is known about differences in non-culprit (NC) plaque characteristics. Purpose To compare plaque characteristics of fractional flow reserve (FFR)-negative NC lesions as assessed by optical coherence tomography (OCT) in STEMI and NSTEMI patients. Methods PECTUS-obs is a prospective, observational study in which 438 patients presenting with STEMI or NSTEMI underwent OCT of any intermediate FFR-negative NC lesion (defined as a FFR &amp;gt;0.80) after treatment of the infarct related artery. Quantitative and qualitative OCT analyses were performed by an independent core laboratory. A high risk plaque (HRP) was defined as the presence of ≥2 of the following prespecified criteria: 1) a lipid arc ≥90°, 2) a minimal fibrous cap thickness &amp;lt;65 µm, or 3) either cap rupture or thrombus presence. In the present sub-analysis, lesion-level plaque characteristics were compared between patients presenting with STEMI versus NSTEMI while accounting for within-patient clustering and correcting for prespecified clinical variables (age, history of myocardial infarction, diabetes, and estimated glomerular filtration rate (eGFR)). Results Among 420 patients with at least one analyzable OCT, 217 (51.7%) presented with STEMI and 203 (48.3%) with NSTEMI. Patients with STEMI were younger (mean age 62±10 vs 65±11 years, p=0.004) and less frequently had diabetes (11.1% vs 18.2%, p=0.037) and hypercholesterolemia (31.8% vs 41.6%, p=0.038). Baseline mean eGFR (84±19 vs 75±19 ml/min, p&amp;lt;0.001) and low density lipoprotein-cholesterol levels (3.2±1.2 vs 2.9±1.2, p=0.010) were higher in STEMI patients with fewer of these patients using lipid lowering therapy (18.9% vs 33.0%, p&amp;lt;0.001) before enrollment. A total of 494 NC lesions were analyzed, which were equally distributed in number and location between groups. The mean fractional flow reserve was 0.89±0.05 and was comparable between groups (p=0.26). Patients with STEMI had a smaller minimal lumen area (2.56±1.48 vs 2.84±1.58 mm2, p=0.031) and minimal lumen diameter (1.47±0.44 vs 1.55±0.45 mm, p=0.026) with a subsequent larger percentage area stenosis (64±15 vs 61±17%, p=0.022). Lipid plaques were more common in STEMI patients (81.7% vs 70.7%, p=0.006) and the maximal lipid arc more frequently was ≥90º (79.0% vs 69.0%, p=0.018). There was no difference in the presence of plaque ruptures (8.3% vs 11.2%, p=0.31) or HRP (32.9% vs 29.3%, p=0.40), whereas macrophage accumulation was more prevalent in STEMI patients (27.8% vs 18.2%, p=0.040). Conclusions FFR-negative NC lesions in patients with STEMI have smaller luminal dimensions, and more frequently harbor lipid plaques and macrophage accumulation. No difference was observed in the prevalence of HRP or plaque rupture.

Biological profiling in the spectrum of acute coronary syndrome: characterizing patients from MINOCA to NSTEMI with different features of the culprit plaque

Abstract Background In the last two decades, the development of procedures and tools such as coronary angiography and optical coherence tomography (OCT) have made it possible to highlight several aspects of acute coronary syndromes (ACS), identifying multiple subgroups such as patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) and ruptured fibrous cap (RFC) or intact fibrous cap (IFC) culprit lesions. The aim of the study is to better characterize the ACS spectrum by evaluating the biological profile of non-characterized NTSEMI, RFC-NSTEMI, IFC-NSTEMI, and MINOCA patients. Methods We enrolled 56 consecutive patients presenting with ACS, specifically 16 patients with non-characterized NSTEMI, 12 patients with RFC-NSTEMI, 8 patients with IFC-NSTEMI, and 20 patients with MINOCA. Biological samples were collected and stored. We performed gene expression analysis through qRT-PCR technique for 21 genes. Results Our data displayed several differences in gene expression levels involved in inflammation, cellular adhesion, extracellular matrix turnover, and oxidative stress between the groups under examination. We observed no significant difference between non-characterized NSTEMI and MINOCA for all the studied genes. Alongside, MINOCA displayed significantly lower levels of the following genes than RFC and IFC patients: CD44, GPX1, ICAM1, PLA2G7, SOD1, and VEGFA. Furthermore, when compared with IFC patients, MINOCA showed lower levels of EDN1, LGALS8, MMP1, and TNF, and non-characterized NSTEMI showed a lower gene expression of CD31, ICAM1, and PI16. Finally, CD44, EDN1, GPX1, LGALS8, NOS3, SOD1, TFRC, and VEGFA were more expressed in RFC and IFC compared to non-characterized NSTEMI patients. Conclusions Our preliminary data, besides exploring new pathways in MINOCA patients, reflects the need for characterization and patients’ stratifications in the clinical management of ACS, since no differences were observed between non-characterized NSTEMI and MINOCA. This result may indicate that a one size fits all approach is not the most suitable since a plaque could be an innocent bystander and should be treated accordingly. A precision medicine approach that recognizes the presence of obstructive plaque and defines the type of culprit plaque (i.e., RFC or IFC) could identify better treatment, for a tailored therapy, allowing better prognosis and quality of life.Figure

Abstract 045: A Radiomics Based Pipeline for Paired Risk‐Stratification of Intracranial Atherosclerotic Plaques

Introduction High resolution vessel wall imaging (HR‐VWI) enables accurate visualization of intracranial atherosclerotic plaques. Radiomics can be utilized as an objective quantification method of plaque appearance and shape. We aimed to analyze the radiomics features (RFs) obtained from 7T‐HR‐VWI to differentiate between culprit and non‐culprit plaques in patients with intracranial atherosclerotic disease (ICAD). Methods Patients with ICAD as stroke etiology undergoing HR‐VWI were included in the study. Culprit plaques in the vascular territory of the stroke were identified. The degree of stenosis, area degree of stenosis and plaque burden were calculated. Three‐dimensional segmentation of the plaque was performed, and RFs were extracted. We then evaluated multiple machine learning models to predict and identify culprit plaques using significantly different RFs. The dataset was then randomly divided into training and testing datasets, and the trained model was evaluated on the independent testing dataset. Results The study included 33 patients with ICAD as the cause of stroke. Univariate analysis revealed 38 significantly different RFs between culprit and non‐culprit plaques in pre‐contrast MRI, 39 in post‐contrast MRI and 25 RFs that were different between pre and post contrast MRIs. Additionally, seven shape‐based RFs exhibited significant distinctions between the two plaque types. The random forest model achieved an accuracy rate of 81% (88% sensitivity and 75% specificity) in identifying culprit plaques in the independent testing dataset. This model successfully identified the culprit plaque in 7 out of 8 cases during the testing phase. Conclusion In this study symptomatic culprit plaques had a different signature RFs compared to other plaque within the same subject. A machine learning model built with RFs successfully identified the symptomatic atherosclerotic plaques in most cases. Radiomics is a promising tool for stratification of plaques in patients with ICAD.

Morphological Characteristics of Culprit Plaques in Acute Myocardial Infarction Patients With Different Scores of Type A Personality - An Intravascular Optical Coherence Tomography Study.

Previous studies have suggested a relationship between type A personality and the occurrence of coronary artery disease, so we used intravascular optical coherence tomography (OCT) to investigate the morphological characteristics of culprit plaques in acute myocardial infarction (AMI) patients with different scores of type A personality. A total of 221 AMI patients who underwent preintervention imaging of culprit lesions and an assessment of type A behavior pattern were included. According to the scores for the behavior questionnaire, these patients were divided into 3 groups: non-type A personality (n=91), intermediate personality (n=73), and type A personality (n=57). Patients with type A personality were younger (P=0.003) and had a higher level of total cholesterol (P=0.029) and more severe luminal stenosis (P=0.046). In addition, the prevalence of microchannels (P<0.001), macrophage accumulation (P<0.001), and plaque rupture (P=0.010) with greater number (P<0.001), cavity angle (P<0.001), and length (P<0.001) was highest in the type A personality group. The culprit lesions of AMI patients with increased scores for type A personality had more severe coronary luminal stenosis, and the proportion of vulnerable features was increased.

A Non-Linear Role of Hyperlipidemia on Progression of Intracranial Atherosclerotic Plaques and Acute Downstream Ischemic Events.

Intracranial atherosclerotic stenosis (ICAS) is the leading cause of ischemic stroke worldwide. Hyperlipidemia is a major contributor to atherosclerosis. However, the effect of hyperlipidemia on the evolution of intracranial atherosclerotic plaques and downstream ischemic episodes remains unclear. In this study, we aimed to assess the radiological features of ICAS plaques and to explore the relationship between hyperlipidemia and plaque progression. We included people with ICAS (≥50% stenosis) undergoing high-resolution magnetic resonance imaging. The culprit plaque was defined as the sole, or in case of multiple stenosis, the narrowest plaque on the intracranial artery responsible for acute ischemic stroke. Demographic, clinical data, plaque features on MRI, and lipid parameters were compared between culprit and non-culprit plaques. Plaque enhancement was graded as Grade 0, 1 and 2 by comparing to the adjacent normal vessel wall and pituitary funnel after contrast enhancement on T1-weighted sequences. 162 patients were included (mean age 57.7±12.1 years, male 61.6%), 110 of whom were identified as culprit plaque with an ipsilateral acute stroke. High-grade enhancement was the most prominent MRI feature of the culpable plaque (Grade-2: OR 6.539, 95%CI 1.706-23.707, p=0.006). LDL cholesterol was significantly associated with overall acute ischemic stroke caused by culprit plaque. After stratification by enhancement grading LDL was independently associated with ischemic events in Grade-1 enhancement plaques (OR 6.778, 95%CI 2.122-21.649, p=0.001). In patients with Grade-2 enhancement plaques, however, LDL was not associated with ischemic event; in contrast, Neutrophil/Lymphocyte ratio was independently associated with ischemic events caused by Grade-2 enhancement plaques (OR 2.188, 95%CI 1.209-3.961, p=0.010). LDL was related with ischemia events in intermediate stage of intracranial atherosclerotic plaque progression, an excellent period for intensive lipid-lowering treatment. In advanced stage, inflammatory agents maybe the main contributor to ischemic events.

Association of culprit plaque enhancement ratio, hypoperfusion and HbA1c with recurrent ischemic stroke in patients with atherosclerotic stenosis of the middle cerebral artery

PurposeTo investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. MethodEighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. ResultsHigher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). ConclusionsCulprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.

Cardiovascular Risk Factors and Culprit Plaque Characteristics in Women With Acute Coronary Syndromes

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 (<60years), 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.

Spotty calcium deposits within acute coronary syndrome (ACS)-causing culprit lesions impact inflammatory vessel-wall interactions and are associated with higher cardiovascular event rates at one year follow-up: Results from the prospective translational OPTICO-ACS study program

Background and aimsSpotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients. MethodsCL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed. ResultsSCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05). ConclusionsThis study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS.

Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study.

Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. Registration of the study at clinicalTrials.gov (NCT03129503).

Associations of Culprit Vessel Size and Plaque Characteristics in Patients with ST-Segment Elevation Myocardial Infarction.

Small vessel disease (SVD) widely exists in patients with acute coronary syndrome. However, the plaque characteristic of SVD has not been investigated. Optical coherence tomography (OCT) of culprit lesion was examined in 576 patients with ST-segment elevation myocardial infarction (STEMI) and finally 404 patients with qualified images were analysed of plaque phenotypes and microstructure. The cohort was divided into three groups according to vessel diameters of culprit lesion which were measured by OCT. Major adverse cardiac events (MACEs) were recorded of each patient and compared among patients with different vessel diameters and plaque phenotypes. Gender, age and body mass index (BMI) were significantly different among patients with different diameters of culprit vessels (98.4% vs. 85.7% vs.71.4%, p 0.001; 40.0 7.0 vs. 54.9 6.6 vs. 68.9 5.8, p 0.001; 28.4 4.0 vs. 25.8 2.9 vs. 25.2 3.0, p 0.001, respectively). Moreover, patients with diameters of culprit lesion 3 mm presented with more incidence of plaque rupture and macrophage (57.7% vs. 42.1% vs. 46.2%, p = 0.015, 55.1% vs. 41.0% vs. 36.9%, p = 0.010). Total MACE did not differ among groups of different vessel diameters and plaque phenotypes. Vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes. NCT03593928.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1β. Circulating plasma levels of interleukin-1β decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.