Coronary Artery Plaque Phenotype and 5-Year Clinical Outcomes in Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography.

In this review, we summarise new insights into diagnostic approaches and treatment strategies for coronary artery disease (CAD) in patients with diabetes mellitus (DM). Despite the improvements in therapy, the clinical management of DM patients remains challenging as they develop more extensive CAD at a younger age and consistently have worse clinical outcomes than non-DM patients. Current diagnostic modalities as well as revascularisation treatments mainly focus on ischemic lesions. However, the impact of plaque morphology and composition are emerging as strong predictors of adverse cardiac events even in the absence of identified ischemia. In particular, the presence of vulnerable plaques such as thin-cap fibroatheroma (TCFA) lesions has been identified as a very strong predictor of future adverse events. This emphasises the need for an approach combining both functional and morphological methods in the assessment of lesions. In particular, optical coherence tomography (OCT) has proven to be a valuable asset by truly identifying TCFAs. New treatment strategies should consist of individualised and advanced medical regimens and may evolve towards plaque sealing through percutaneous treatment.

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

BACKGROUND: The aim of this study was to investigate the effects of thin-cap fibroatheromas (TCFAs) on stent neointimal coverage at the 9­month follow-up after EXCEL stent implantation assessed by optical coherence tomography (OCT). METHODS: A total 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 a TCFA group (n = 47) and a non-TCFA group (n = 46) according to whether EXCEL stents covered the TCFAs. A TCFA was defined as a plaque 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 9­month follow-up after stent implantation was evaluated by OCT. The primary study endpoints were the incidence of neointimal uncoverage and stent malapposition. RESULTS: At the 9­month 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). CONCLUSION: In patients with NSTEACS, TCFAs delayed endothelium coverage at 9 months after stent implantation, and TCFAs were independent predictors of incomplete neointimal coverage of the stent.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Using Optical Coherence Tomography to Identify Lipid and Its Impact on Interventions and Clinical Events　- A Scoping Review.

BACKGROUND: Optical coherence tomographic (OCT) imaging has enabled identification of lipid, with increasing interest in how it may affect coronary interventions and clinical outcomes. This review summarizes the available evidence around OCT identification of lipid and its effect on interventions, clinical events, and the natural history of coronary disease.Methods and Results:We conducted a scoping review using the Medline, HealthStar, and Embase databases for articles published between 1996 and 2021. We screened 1,194 articles and identified 51 for inclusion in this study, summarizing the key findings. The literature supports a common OCT definition of lipid as low-signal regions with diffuse borders, validated against histology and other imaging modalities with acceptable intra- and inter-rater reliability. There is evidence that OCT-identified lipid at the site of stent implantation increases the risk of edge dissection, incomplete stent apposition, in-stent tissue protrusion, decreased coronary flow after stenting, side branch occlusion, and post-procedural cardiac biomarker increases. In mostly retrospective studies, lipid indices measured at non-stented sites are associated with plaque progression and the development of recurrent ischemic events. CONCLUSIONS: There is extensive literature supporting the ability of OCT to identify lipid and demonstrating a substantial impact of lipid on percutaneous coronary intervention outcomes. Future work to prospectively evaluate the effect of the characteristics of lipid-rich plaques on long-term clinical outcomes is needed.

Prognostic value of characteristics of plaque combined with residual syntax score among patients with STEMI undergoing primary PCI: an intravascular optical coherence tomography study.

AIM: The present study aimed to explore these characteristics, particularly thin-cap fibroatheroma (TCFA), in relation to residual syntax score (rSS) in patients who presented with acute MI. METHODS AND OUTCOMES: A total of 434 consecutive patients with MI aged ≥18 years who had STEMI underwent primary PCI. Notably, compared with other subgroups, the presence of TCFA in culprit lesions and a higher level of rSS, were significantly associated with MACE. When rSS was divided into three groups, high rSS levels were associated with a higher incidence of MACE, in the subgroups of without TCFA (P = 0.005), plaque erosion (P = 0.045), macrophage infiltration (P = 0.026), and calcification (P = 0.002). AUC of ROC curve was 0.794 and 0.816, whereas the AUC of the survival ROC was 0.798 and 0.846. CONCLUSION: The results of this study could be used in clinical practice to support risk stratification. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT03593928 .

Vulnerable plaques and patients: state-of-the-art.

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients.

Age- and Gender-Related Differences in Coronary Lesion Plaque Composition on Optical Coherence Tomography.

BACKGROUND: The pathophysiology and chronological course of atherosclerosis seems to be different between men and women due to biological differences, and age and gender differences in plaque composition of coronary lesions remain to be elucidated.Methods and Results:A total of 860 consecutive patients with a median age of 69 years (IQR, 60-78 years) who underwent optical coherence tomography (OCT) of culprit lesions was included. The composition of culprit plaque on OCT was compared between female (n=171) and male (n=689) subjects in younger (<70 years old) and elderly (≥70 years old) patients. In elderly patients, the prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in women than in men (30.6 vs. 15.2%, P<0.001). In younger patients, the prevalence of large calcification was significantly higher in women than in men (60.0 vs. 32.8%, P<0.001). The prevalence of other vulnerable plaque characteristics (i.e., macrophages, microchannels, and spotty calcification), was similar between women and men. Elderly women had a significantly higher prevalence of TCFA (OR, 2.13; 95% CI: 1.33-3.44, P=0.002) than other patients. CONCLUSIONS: Women had a higher prevalence of TCFA and of large calcification than men in patients ≥70 and <70 years old, respectively. This may facilitate the understanding of gender differences in the pathogenesis of coronary atherosclerosis, and the tailoring of therapy and of prevention according to age and gender.

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.

[Predictors of acute coronary syndrome in patients with ischaemic heart disease]. / Prediktory ostrogo koronarnogo sindroma u patsientov s ishemicheskoi bolezn'iu serdtsa.

Acute coronary syndrome has for a long time been giving no way of decreasing mortality related to ischaemic heart disease. The primary cause of acute coronary syndrome in the majority of cases is rupture of an unstable atherosclerotic plaque in the coronary artery followed by thrombosis thereof. The main missions of modern cardiology include: assessment of the risk of acute coronary syndrome, identification of predictors of adverse events, and working-out of measures aimed at prevention and optimal management of patients with ischaemic heart disease. This article deals with clinical and morphological factors associated with destabilization of coronary plaques, their rupture, and the development of an acute coronary event.

Postprandial Hyperchylomicronemia and Thin-Cap Fibroatheroma in Nonculprit Lesions.

Objective- Although postprandial hypertriglyceridemia can be a risk factor for coronary artery disease, the extent of its significance remains unknown. This study aimed to investigate the correlation between the postprandial lipid profiles rigorously estimated with the meal tolerance test and the presence of lipid-rich plaque, such as thin-cap fibroatheroma (TCFA), in the nonculprit lesion. Approach and Results- A total of 30 patients with stable coronary artery disease who underwent a multivessel examination using optical coherence tomography during catheter intervention for the culprit lesion were enrolled. Patients were divided into 2 groups: patients with TCFA (fibrous cap thickness ≤65 µm) in the nonculprit lesion and those without TCFA. Serum remnant-like particle-cholesterol and ApoB-48 (apolipoprotein B-48) levels were measured during the meal tolerance test. The value of remnant-like particle-cholesterol was significantly greater in the TCFA group than in the non-TCFA group ( P=0.045). Although the baseline ApoB-48 level was similar, the increase in the ApoB-48 level was significantly higher in the TCFA group than in the non-TCFA group ( P=0.028). In addition, the baseline apolipoprotein C-III levels was significantly greater in the TCFA group ( P=0.003). These indexes were independent predictors of the presence of TCFA (ΔApoB-48: odds ratio, 1.608; 95% confidence interval, 1.040-2.486; P=0.032; apolipoprotein C-III: odds ratio, 2.581; 95% confidence interval, 1.177-5.661; P=0.018). Conclusions- Postprandial hyperchylomicronemia correlates with the presence of TCFA in the nonculprit lesion and may be a residual risk factor for coronary artery disease.

Three-Dimensional Fibrous Cap Structure of Coronary Lipid Plaque　- ST-Elevation Myocardial Infarction vs. Stable Angina.

BACKGROUND: Fibrous cap thickness (FCT) is one of the key features of coronary vulnerable plaque. FCT is measured at an arbitrary point, determined on visual assessment of 2-D cross-sectional imaging. This method has poor reproducibility. The aim of this study was to compare the 3-D structure of FC in non-culprit lipid plaques between patients with ST-elevation myocardial infarction (STEMI) and with stable angina (SA) on optical coherence tomography. Methods and Results: A total of 54 non-culprit plaques from 23 STEMI and 23 SA patients were evaluated. Thin cap fibroatheroma (TCFA), defined as lipid plaque with FCT <80 µm, was identified using a novel algorithm. The number of TCFA, surface area of each TCFA, and the sum total area of TCFA in the target vessel were measured. Patients with STEMI had a greater median number of TCFA (9, IQR 1-17 vs. 2, IQR 0-5; P=0.002), the largest median single TCFA area (0.40, IQR 0.14-0.69 vs. 0.08, IQR 0.04-0.16 mm2; P<0.001) and median sum total area of TCFA (1.04, IQR 0.41-1.95 vs. 0.24, IQR 0.08-0.48 mm2, P<0.004). CONCLUSIONS: Patients with STEMI, as compared with those with SA, have greater vulnerability to non-culprit plaque.

Mean platelet volume and coronary plaque vulnerability: an optical coherence tomography study in patients with non-ST-elevation acute coronary syndrome.

BACKGROUND: The association between mean platelet volume (MPV) and coronary plaque vulnerability in patients with non-ST-elevation ACS (NSTE-ACS) has not been investigated. We performed a retrospective study to evaluate the association between MPV and plaque vulnerability using optical coherence tomography (OCT). METHODS: Consecutive NSTE-ACS patients who underwent pre-intervention OCT examination in our center were included in this study. Features of coronary plaques in the culprit arteries were classified as rupture, nonrupture with thin-cap fibroatheroma (TCFA), and nonrupture and non-TCFA. ROC analyses were used to determine the predictive efficacy of MPV for plaque rupture, and multivariate logistic regression analysis was performed to evaluate the potential independent predictors of plaque vulnerability. RESULTS: Overall, 94 patients were included in this study. We identified 17 patients with plaque rupture, 10 with nonrupture with TCFA, and 67 with nonrupture and non-TCFA. ROC analyses showed that MPV ≥ 10.5 fL was predictive of plaque rupture in NSTE-ACS patients. Univariate analyses indicated that patients with higher MPV (≥ 10.5 fL) had higher body mass index and poorer lipid profiles compared to those with lower MPV. Moreover, those with higher MPV had higher incidences of plaque rupture and thrombosis (both P < 0.05). Results of multivariate analyses showed that diabetes and higher platelet distribution width (PDW) were independent risk factors of TCFA (P = 0.032 and 0.046, respectively), while diabetes, higher BMI, higher PDW, and higher MPV were independent determinants of plaque rupture in our cohorts (P all < 0.05). CONCLUSIONS: Higher MPV is independently associated with higher risk of plaque rupture as evidenced by OCT in our cohort of NSTE-ACS patients.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study.

BACKGROUND: Previously, we have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear. This study sought to investigate the impact of CD14++CD16+ monocytes on plaque vulnerability, as assessed by virtual histology intravascular ultrasound (VH-IVUS), as well as their relationship to fluctuating glucose levels in patients with asymptomatic coronary artery disease (CAD). METHODS: Fifty-one patients with asymptomatic CAD, who were undergoing lipid-lowering therapy and underwent VH-IVUS evaluation for angiographically mild to moderate lesions, were enrolled in the study. Standard VH-IVUS parameters, including the percentage volume of the necrotic core (%NC) within the plaque and the presence of a virtual histology thin-cap fibroatheroma (VH-TCFA), were then evaluated. Additionally, monocyte subsets were assessed by flow cytometry, and daily glucose fluctuations were analyzed by measuring the mean amplitude of glycemic excursion (MAGE). RESULTS: Among 82 plaques from 22 diabetes mellitus (DM) patients and 29 non-DM patients, 15 VH-TCFAs were identified. CD14++CD16+ monocyte counts significantly correlated with both  %NC and the presence of VH-TCFA (%NC: r = 0.339, p = 0.002; VH-TCFA: p = 0.003). Multivariate logistic regression analysis revealed that CD14++CD16+ monocyte counts were independently associated with VH-TCFA (odds ratio = 1.029, p = 0.004). Furthermore, CD14++CD16+ monocyte counts were significantly correlated with the MAGE score in the non-DM patients (r = 0.544, p = 0.005). CONCLUSIONS: CD14++CD16+ monocyte levels are associated with coronary plaque vulnerability and can serve as a biomarker for VH-TCFA in patients with CAD undergoing lipid-lowering therapy. In patients without DM, glucose fluctuations may alter the balance of monocyte subsets. Trial registration UMIN Registry number: UMIN000021228.

Prevalence of Thin-Cap Fibroatheroma in Relation to the Severity of Anatomical and Physiological Stenosis.

BACKGROUND: The relationship between the features of morphologically unstable plaque and physiological lesion severity remains elusive. We aimed to investigate this relationship using optical coherence tomography (OCT)-derived high-risk plaque characteristics and fractional flow reserve (FFR) as the degree of anatomical and physiological stenosis severity.Methods and Results:We investigated 286 de novo intermediate and severe coronary lesions in 248 patients who underwent OCT and FFR examinations. Lesions were divided into tertiles based on either FFR or quantitative coronary angiographic diameter stenosis (QCA-%DS). The OCT findings were compared among the tertiles of FFR and QCA-%DS. FFR and QCA tertiles were defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74≤FFR≤0.81), and FFR-T3 (FFR >0.81); and QCA-T1 (%DS ≥61%), QCA-T2 (51%≤%DS<61%), and QCA-T3 (%DS <51%). The prevalence of thin-cap fibroatheroma (TCFA) was significantly greater in FFR-T1 (20.0%) than in FFR-T2 and FFR-T3 (7.0%, P=0.03 and 7.7%, P=0.04, respectively), although no significant differences were observed among the QCA tertiles. CONCLUSIONS: Physiological severity of coronary stenosis evaluated by FFR correlated with plaque instability in terms of TCFA. Preferable clinical outcomes for lesions with negative FFR based on the existing clinical evidence might be attributable to less likelihood of TCFA.

Differences determined by optical coherence tomography volumetric analysis in non-culprit lesion morphology and inflammation in ST-segment elevation myocardial infarction and stable angina pectoris patients.

BACKGROUND: While the current methodology for determining fibrous cap (FC) thickness of lipid plaques is based on manual measurements of arbitrary points, which could lead to high variability and decreased accuracy, it ignores the three-dimensional (3-D) morphology of coronary artery disease. OBJECTIVE: To compare, utilizing optical coherence tomography (OCT) assessments, volumetric quantification of FC, and macrophage detection using both visual assessment and automated image processing algorithms in non-culprit lesions of STEMI and stable angina pectoris (SAP) patients. METHODS: Lipid plaques were selected from 67 consecutive patients (1 artery/patient). FC was manually delineated by a computer-aided method and automatically classified into three thickness categories: FC < 65 µm (i.e., thin-cap fibroatheroma [TCFA]), 65-150 µm, and >150 µm. Minimum thickness, absolute categorical surface area, and fractional luminal area of FC were analyzed. Automated detection and quantification of macrophage was performed within the segmented FC. RESULTS: A total of 5,503 cross-sections were analyzed. STEMI patients when compared with SAP patients had more absolute categorical surface area for TCFA (0.43 ± 0.45 mm(2) vs. 0.15 ± 0.25 mm(2) ; P = 0.011), thinner minimum FC thickness (31.63 ± 17.09 µm vs. 47.27 ± 26.56 µm, P = 0.012), greater fractional luminal area for TCFA (1.65 ± 1.56% vs. 0.74 ± 1.2%, P = 0.046), and greater macrophage index (0.0217 ± 0.0081% vs. 0.0153 ± 0.0045%, respectively, P < 0.01). CONCLUSION: The novel OCT-based 3-D quantification of the FC and macrophage demonstrated thinner FC thickness and larger areas of TCFA coupled with more inflammation in non-culprit sites of STEMI compared with SAP.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study.

AIMS: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. METHODS AND RESULTS: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). CONCLUSION: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes.

BACKGROUND: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. METHODS AND RESULTS: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin-ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. CONCLUSIONS: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Thin-cap fibroatheroma in acute coronary syndrome: Implication for intravascular imaging assessment.

Acute coronary syndrome (ACS), a significant cardiovascular disease threat, has garnered increased focus concerning its etiological mechanisms. Thin-cap fibroatheroma (TCFA) are central to ACS pathogenesis, characterized by lipid-rich plaques, profuse foam cells, cholesterol crystals, and fragile fibrous caps predisposed to rupture. While TCFAs may be latent and asymptomatic, their pivotal role in ACS risk is undeniable. High-resolution imaging techniques like Optical coherence tomography (OCT) and Intravascular ultrasound (IVUS) are instrumental for effective TCFA detection. Therapeutic strategies encompass pharmacological and interventional measures, including antiplatelet agents, statins, and Percutaneous Coronary Intervention (PCI), aiding in plaque stabilization, inflammation reduction, and rupture risk mitigation. Despite the strong correlation between TCFAs and adverse prognoses in ACS patients, early detection and rigorous treatment significantly enhance patient prognosis and diminish cardiovascular events. This review aims to encapsulate recent advancements in TCFA research within ACS, covering formation mechanisms, clinical manifestations, and prognostic implications.