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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance. [ABSTRACT FROM AUTHOR]

We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case's home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and C o levels were positively and significantly correlated with serum levels of C-reactive protein. We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings. [Display omitted] [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%-8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients. [ABSTRACT FROM AUTHOR]

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). As the vascular endothelium is profoundly affected by the haemodynamic environment to which it is exposed, we employed computational fluid dynamic (CFD) analysis of the luminal geometry from 17 patients with optical coherence tomography (OCT)-defined plaque erosion, to determine the flow environment permissive for plaque erosion. Our results demonstrate that 15 of the 17 cases analysed occurred on stenotic plaques with median 31% diameter stenosis (interquartile range 28–52%), where all but one of the adherent thrombi located proximal to, or within the region of maximum stenosis. Consequently, all flow metrics related to elevated flow were significantly increased (time averaged wall shear stress, maximum wall shear stress, time averaged wall shear stress gradient) with a reduction in relative residence time, compared to a non-diseased reference segment. We also identified two cases that did not exhibit an elevation of flow, but occurred in a region exposed to elevated oscillatory flow. Our study demonstrates that the majority of OCT-defined erosions occur where the endothelium is exposed to elevated flow, a haemodynamic environment known to evoke a distinctive phenotypic response in endothelial cells. [ABSTRACT FROM AUTHOR]

Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology. Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation. • Monocyte-derived macrophages to study macrophages infiltrating coronary plaques. • Optical Coherence Tomography to identify the mechanism of plaque destabilization. • Pro-thrombotic, oxidative macrophages are prevalent in ruptures with inflammation. [ABSTRACT FROM AUTHOR]

Aims  Layered plaques represent signs of previous plaque destabilization. A recent study showed that acute coronary syndrome (ACS) patients with layered culprit plaque have more vulnerability at the culprit lesion and systemic inflammation. We aimed to compare the characteristics of non-culprit plaques between patients with or without layered plaque at the culprit lesion. We also evaluated the characteristics of layered non-culprit plaques, irrespective of culprit plaque phenotype. Methods and results We studied ACS patients who had undergone pre-intervention optical coherence tomography (OCT) imaging. The number of non-culprit lesions was evaluated on coronary angiogram and morphological characteristics of plaques were studied by OCT. In 349 patients, 99 (28.4%) had layered culprit plaque. The number of non-culprit plaques in patients with or without layered culprit plaque was similar (3.2 ± 0.8 and 2.8 ± 0.8, P  = 0.23). Among 465 non-culprit plaques, 145 from patients with layered culprit plaque showed a higher prevalence of macrophage infiltration (71.0% vs. 60.9%, P  = 0.050). When analysed irrespective of culprit plaque phenotype, layered non-culprit plaques showed higher prevalence of lipid (93.3% vs. 86.0%, P  = 0.028), thin cap fibroatheroma (29.7% vs. 13.7%, P  < 0.001), and macrophage infiltration (82.4% vs. 54.0%, P  < 0.001) than non-layered plaques. Plaques with layered phenotype at both culprit and non-culprit lesions had the highest vulnerability. Conclusion  In ACS patients, those with layered phenotype at the culprit lesion demonstrated greater macrophage infiltration at the non-culprit sites. Layered plaque at the non-culprit lesions was associated with more features of plaque vulnerability, particularly when the culprit lesion also had a layered pattern. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease, a condition associated with an increased incidence of recurrent ischaemic events and higher mortality. Based on recent evidences, a strategy of staged percutaneous coronary intervention (PCI) of obstructive non-culprit lesions should be considered the gold standard for the management of these patients. However, several issues remain still unresolved. Indeed, what is the optimal timing of staged PCI is not completely defined. Moreover, assessment of intermediate non-culprit lesions represent still a clinical conundrum, as pressure-wire indexes do not seem able to correctly identify those patients in whom deferral is safe. Intracoronary imaging may help to identify untreated non-culprit lesions containing vulnerable plaques that may portend a higher risk of future cardiovascular events. However, there are hitherto no studies demonstrating that preventive PCI of vulnerable plaques or more intensive pharmacological treatment is associated with an improved clinical outcome. In this review, we discuss the recent evolving concepts about management of non-culprit plaques in STEMI patients, proposing a diagnostic and therapeutic algorithm to guide physicians in clinical practice. We also underscore the several knowledge gaps to address in future studies. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Aims The CLIMA study, on the relationship between c oronary p l aque morphology of the left anter i or descending artery and twelve m onths clinic a l outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint. Methods and results From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicaltrial.gov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA <3.5 mm2 [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1–4.0], FCT <75 µm (HR 4.7, 95% CI 2.4–9.0), lipid arc circumferential extension >180° (HR 2.4, 95% CI 1.2–4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2–6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1–18.6). Conclusion The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Patients with acute coronary syndrome (ACS) associated to high C-reactive protein (CRP) levels exhibit a higher risk of future acute ischemic events. Yet, the positive predictive value of CRP is too low to guide a specific treatment. Our study aims to identify a high-risk patient subset who might mostly benefit from anti-inflammatory treatment on the basis of the combination of optical coherence tomography (OCT) assessment of the culprit vessel and CRP serum levels. Patients admitted for ACS and undergoing pre-interventional OCT assessment of the culprit vessel were selected from "Agostino Gemelli" Hospital OCT Registry. The primary end-point was recurrent ACS (re-ACS). CRP levels ≥2 mg/L were considered abnormal. The overall study population consisted of 178 patients. Among these, 156 patients were included in the primary end-point analysis. The re-ACS rate was 23% at 3-year follow-up. High CRP (2.587, 95% CI:1.345–10.325, p = 0.031), plaque rupture (3.985, 95% CI:1.698–8.754, p = 0.009), macrophage infiltration (3.145, 95% CI:1.458–9.587, p = 0.012) and multifocal atherosclerosis (2.734, 95% CI:1.748–11.875, p = 0.042) were independent predictors of re-ACS. All patients (14/14) with high CRP and with all OCT high-risk features had re-ACS. At the other extreme, only 4 of the 82 patients with low CRP levels and lack of high-risk features at OCT examination exhibited re-ACS at follow-up. The combination of systemic evidence of inflammation and OCT findings in the culprit plaque identifies very high-risk ACS. Future studies are warranted to confirm these findings and to test an anti-inflammatory treatment in this patient subset. • High CRP and OCT features of the culprit vessel predict recurrent coronary events. • Patients with high-risk OCT features and high CRP experienced a recurrent ACS. • Our findings may contribute to individualize the secondary prevention of ACS. [ABSTRACT FROM AUTHOR]

Aims Plaque rupture (PR) represents the most common substrate of coronary thrombosis, in at least 50% of cases. Chronic low grade inflammation is a common background for atherosclerosis development; however, increased plaque inflammation may predispose by itself to PR. In the last decade, studies performed by optical coherence tomography (OCT) have allowed to establish the severity of plaque inflammation by assessing macrophage infiltration (MØI). Our retrospective study aimed at assessing the role of plaque inflammation in PR among patients with acute coronary syndrome (ACS) using OCT. Methods and results We enrolled 56 patients with ACS exhibiting PR at the site of the culprit stenosis identified by OCT. Patients were divided into two cohorts according to the presence of MØI at OCT analysis, defined as signal-rich, distinct, or con fluent punctate regions that exceed the intensity of background speckle noise. Serum high-sensitivity C-reactive protein (CRP) was measured on admission by latex-enhanced immunophelometric assay. Thirty-seven (66%) patients had MØI at the site of PR, whereas 19 (34%) patients had no evidence of MØI. Patients with MØI showed a higher rate of CRP values >3 mg/dL as compared with those without MØI (92% vs. 47%, P = 0.004). In contrast, patients without MØI had a higher prevalence of hypertension compared with those with MØI (89% vs. 59%, P = 0.021). Furthermore, the group with MØI exhibited a significantly higher rate of lipid-rich plaques (86% vs. 50%, P = 0.008), a higher rate of multifocal disease (59% vs. 10%, P < 0.001), and an MØI in both culprit and remote lesions (97% vs. 0%, P < 0.001) compared with those without MØI. At multivariate analysis, CRP value >3 mg/dL was the only independent predictor of MØI in the culprit plaque (OR 8.72, 95% CI 1.78-41.67, P = 0.007). Conclusions In conclusion, PR can be caused by predominant inflammatory or non-inflammatory mechanisms, over a common low-grade chronic inflammatory background well known from pathology observations. [ABSTRACT FROM AUTHOR]

Patients with an acute coronary syndrome (ACS) due to plaque rupture had a worse prognosis when compared with those without plaque rupture with a higher rate of target vessel revascularization and readmission for unstable angina, suggesting that both stent failure and disease progression occur more frequently. However, it is not known whether recurrent episodes of coronary instability in the same patient are caused by the same pathogenetic mechanism. Thus, we sought to investigate the mechanisms of coronary instability imaged by optical coherence tomography in patients with recurrent ACS events. The present case series, with 4 patients having recurrent ACS, shows that the same mechanism of coronary instability is present during both first and recurrent instability. This hypothesis-generating finding may support further studies targeted at assessing the mechanisms of coronary instability recurrence and how to tailor preventive measures to the underlying mechanism of instability. [ABSTRACT FROM AUTHOR]

Objectives: To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). Methods: In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. Results: Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). Conclusions: CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age. [ABSTRACT FROM AUTHOR]

Aims The prevalence of plaque rupture at the culprit lesion identified by optical coherence tomography (OCT) in different clinical subset of patients undergoing coronary angiography and its clinical predictors remain to be defined. Methods All studies including patients with OCT evaluation of the culprit coronary plaque were included. The prevalence of culprit plaque rupture (CPR) and thin-cap fibro-atheroma (TCFA) were the primary endpoints. The factors associated with these findings were studied in a subset of patients with different clinical presentations [ST-elevation myocardial (STEMI) vs. nonST-elevation myocardial infarction (NSTEMI) vs. unstable angina (UA) vs. stable angina pectoris (SAP)]. Results One hundred and fifty citations were initially appraised at the abstract level and 23 full-text studies were assessed. The mean prevalence of CPR and TCFA was 48.1% (40.5-55.8) and 48.7% (37.4-60.1), respectively. The prevalence of CPR and TCFA were higher in STEMI (70.4 and 76.6%) than in NSTEMI (55.6 and 56.3%) and UA (39.1 and 52.9%) or SAP (6.2 and 22.8%). In the overall population at meta-regression analysis, TCFA and current smoking were the only predictors of CPR (B 3.6:2.0-5.1, P < 0.001 and 0.06:0.02-0.1, P = 0.002, respectively). The factors associated with CPR were different depending on clinical presentation. Hypertension was the only clinical predictor for STEMI (B 3.3: 1.2.-5.3 P = 0.001), while advanced age (B 0.12: 0.02-0.22, P = 0.021), diabetes mellitus (B 0.04: 0.01-0.08, P = 0.012), and hyperlipidaemia (B 0.07:0.02-0.11, P = 0.005) were the predictors in NSTEMI and UA. No clinical predictor was found in SA. Conclusions Our analysis showed high rates of CPR and TCFA detected by OCT in CAD patients, especially in those with ACS, although their prevalence is not negligible in stable patients. TCFA seems to be a strong predictor of CPR in all the ACS scenarios. [ABSTRACT FROM AUTHOR]

Background Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. Aim We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. Methods This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 ± 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 ± 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. Results In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (≥30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 ± 114 vs 59 ± 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). Conclusions Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

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Aims Bifurcations represent challenging lesions which may benefit from improved understanding of stent-related vessel complications. Since optical coherence tomography (OCT) allows us to detect post-stenting vessel injuries, we sought to assess the geographic pattern of stent-related complications occurring during provisional stenting of bifurcated lesions. Methods and results Fifty-one patients with bifurcated lesions treated by provisional stenting and undergoing intra-procedural OCT assessment were enrolled. OCT images were acquired with the aim of guiding the percutaneous coronary intervention but were re-analysed off-line for the present study. The stented bifurcation was divided into four segments [three in the main vessel (MV) and one in the side branch (SB)]. The following acute post-stenting vessel injuries/complications at the different bifurcation segments were evaluated: (i) stent under-expansion, (ii) stent malapposition, (iii) stent edge dissection, (iv) side-branch ostium dissection, (v) tissue prolapse, (vi) intracoronary thrombus, and (vii) in-stent dissection. A total of 55 bifurcation lesions undergoing provisional stenting were analysed. At least one OCT complication was detectable in all cases. Across different bifurcation sites, significant differences in the occurrence of stent complications were observed. In particular, stent malapposition was more common at the proximal MV segment (P < 0.001), while tissue prolapse was more common at the distal MV segment (P < 0.001). Conclusion In bifurcated interventions, OCT often detects vessel injuries/stent complications, which tend to have a specific geographical distribution. In particular, stent malapposition is more common at the proximal MV and tissue prolapse at the distal MV segment. [ABSTRACT FROM PUBLISHER]

Background The management of patients with angiographically intermediate coronary lesions is a major clinical issue. Fractional flow reserve provides validated functional insights while optical coherence tomography provides high resolution anatomic imaging. Both techniques may be applied to guide management in case of angiographically intermediate coronary lesions. Moreover, these techniques may be used to optimize the result of percutaneous coronary intervention. We aim to compare the clinical and economic impact of fractional flow reserve versus optical coherence tomography guidance in patients with angiographically intermediate coronary lesions. Methods/Design Patients with at least one angiographically intermediate coronary lesion will be randomized (ratio 1:1) to fractional flow reserve or optical coherence tomography guidance. In the fractional flow reserve arm, percutaneous coronary intervention will be performed if fractional flow reserve value is ⩽0.80, and will be conducted with the aim of achieving a post-percutaneous coronary intervention fractional flow reserve target value of ⩾0.90. In the optical coherence tomography arm, percutaneous coronary intervention will be performed if percentage of area stenosis (AS%) is ⩾75% or 50 to 75% with minimal lumen area <2.5 mm2, or if a major plaque ulceration is detected. In case of percutaneous coronary intervention, optical coherence tomography will guide the procedure in order to minimize underexpansion, malapposition, and edge dissections. Cost load and clinical outcome will be prospectively assessed at one and thirteen months. The assessed clinical outcome measures will be: major cardiovascular events and occurrence of significant angina defined as a Seattle Angina Questionnaire score <90 in the angina frequency scale. Discussion The FORZA trial will provide useful guidance for the management of patients with coronary artery disease by prospectively assessing the use of two techniques representing the gold standard for functional and anatomical definition of coronary plaques. Trial registration Clinicaltrials.gov NCT01824030 [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages' infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation. [ABSTRACT FROM AUTHOR]

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque. [ABSTRACT FROM AUTHOR]

Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM 2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM 2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM 2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 μg/m3), CI95 % (1.087–3.364), p = 0.025]. Patients with PR presented a steady increase in PM 2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability. [Display omitted] • Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). • Acute PM 2.5 exposure, especially on the same day of ACS, is associated with an increased risk of plaque rupture as mechanism of coronary plaque instability. • Mitigation strategies are crucial to reduce the burden of ischemic heart disease, especially in patients with a higher risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS), and inflammation plays a key role in plaque instability. We assessed the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target-vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p = 0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression, PE with MØI was an independent predictor of MACEs [HR = 2.95, 95% CI (1.09–8.02), p = 0.034]. Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. Image 1 • Presence of macrophage infiltrates (MØI) at erosion sites is associated with vulnerable coronary plaque features. • Presence of plaque erosion (PE) with MØI is associated with a worse prognosis at long-term follow-up. • Worse prognosis in patients with MØI was mainly driven by a higher risk of cardiac death and target-vessel revascularization (TVR). • Progression of non-culprit lesions may be involved in determining prognosis in patients with MØI. [ABSTRACT FROM AUTHOR]

Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden. Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area × thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm3 [1.45–11.26] vs. 1.69 mm3 [0.09–5.02], p = 0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p = 0.012), and heavy calcification (29.2% vs. 3.7%, p = 0.013). Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS. Unlabelled Image • Dual quantitative coronary angiography (QCA) has been tested for the assessment of thrombus volume in experimental models. • In this in vivo study, dual QCA-thrombus volume was correlated with optical coherence tomography indices of thrombus burden. • A combination of angiographic features may enable the discrimination of patients with plaque rupture and intact fibrous cap. • Dual QCA may be useful to guide thrombus removal and aid prognostic stratification in patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background: Optical-coherence-tomography (OCT) is an emerging invasive coronary imaging with still undefined clinical value. Recent data have underlined daily impact of such technique in several clinical settings such as acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) guidance. We aimed at assessing the trends and outcomes of OCT use in a high-volume percutaneous coronary interventions (PCI)-center.Methods: Over 6 years, 1025 coronary artery segments in 877 patients underwent OCT evaluation. Clinical and procedural characteristics were prospectively collected. Clinical setting for OCT was: "Diagnostic OCT" (OCT for lesion evaluation after coronary angiography without further PCI); "PCI-guidance OCT" (OCT as a guidance for complex PCI, both by intention or after diagnostic OCT). Primary study end-point was the occurrence of target-vessel-failure (TVF) during the follow-up.Results: Overall, OCT was successful in 99.1% of attempted lesions. Only one complication (coronary dissection requiring urgent PCI) occurred during OCT. After a follow-up of 695 ± 562 days, TVF occurred in 8.2% of cases. Despite similar baseline characteristics, TVF-free survival curves were different in the two populations (5.4% after diagnostic OCT and 9.9% after PCI-guidance OCT). Minimal-lumen-area (MLA) of target lesion was independently associated with TVF (HR 0.7, 95% CI 0.6-0.8). This was mainly driven by a significant impact of MLA in patients not revascularized (HR 0.6, 95% CI 0.4-0.9). TVF did not change according to the study period despite the selection of patients with increasing complexity.Conclusions: OCT has a good safety profile across a broad spectrum of patients encountered in daily practice. The easy-to-assess MLA parameter may help stratify prognosis of patients undergoing OCT. These data call for further evaluations of OCT clinical impact.Summary: OCT is a light-based imaging tool which had subvert the quite ordinary world of coronary imaging and the present study evaluates OCT use in a high-volume center. Our results suggest that application of OCT in "real world" patients presenting higher risk has a good safety profile. Several factors could predict a worse long-term outcome in patients undergoing OCT evaluation, mostly related to more complex clinical conditions. These findings could encourage even low-to intermediate volume centers to improve their OCT use in daily practice. [ABSTRACT FROM AUTHOR]

Abstract Background A sizeable proportion of patients with Acute Coronary Syndromes (ACS) shows a unique adaptive immune system profile, associated to a worse outcome, characterized by higher CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/Treg ratio and plaque phenotype as assessed by Optical Coherence Tomography (OCT). Methods Peripheral blood mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact Fibrous Cap (NSTEMI-IFC, n = 18). Stable Angina patients (SA, n = 18) were used as controls. We examined the frequency of CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry. Results CD4+CD28null frequency (median, range) was significantly higher in NSTEMI-RFC patients (17.3%, 12.5–33.8) as compared with NSTEMI-IFC (3.8%, 0.3–14.1) and SA (3%, 0.6–17.7) (P < 0.001 for all comparisons). We also found a higher CD4+CD28null/Treg ratio in NSTEMI-RFC patients (6.6%, 3.7–13.9) than in NSTEMI-IFC (1.6%, 0.3–5.2) and SA (1.2%, 0.3–8.7) (P < 0.001 for all comparisons). Finally, there was an inverse correlation between CD4+CD28null/Treg ratio and cap-thickness (R = −0.44; P = 0.002). Conclusion Patients with NSTEMI presenting with RFC as culprit lesion at OCT evaluation have a specific perturbation of adaptive immunity, mostly involving CD4+CD28null T- cells and Tregs, as compared with patients with IFC and SA. This specific imbalance of T-cells might play a key role in fibrous cap thinning, predisposing atherosclerotic plaque to rupture. Highlights • Plaque rupture at OCT evaluation is associated to a specific adaptive immune system signature. • A deeper perturbation of adaptive immunity might be involved in fibrous cap thinning. • Molecular and morphological plaque phenotyping might be a new frontier for personalized medicine. [ABSTRACT FROM AUTHOR]

Background The decision-making process of patients with angiographically-intermediate coronary lesions (ICL) is clinically challenging and may benefit from adjunctive invasive techniques. Fractional-flow-reserve (FFR) represents the gold standard to evaluate ICL but frequency-domain optical-coherence-tomography (OCT) is a novel, promising, high resolution coronary imaging technique, which allows physiopathologic assessment of coronary plaque. We investigated the possible relation between OCT and FFR in selected ICL patients. Methods Stable or unstable patients with ICL who underwent both FFR and OCT assessment at two large tertiary centers were retrospectively enrolled. FFR was performed according to standard methodology. OCT images were (on blind to clinical and FFR results) analyzed to assess minimal lumen area (MLA), percentage area stenosis (AS), thrombus and plaque ulceration. Results Forty patients were identified (62 ± 10 years, 93% symptomatic, 35% acute presentation, 93% left-anterior-descending artery ICL). Percentage diameter stenosis at quantitative coronary angiography was 40 ± 12% and FFR was 0.85 ± 0.07. MLA ( p = 0.009), AS ( p < 0.001) and plaque ulceration ( p = 0.02) were significantly associated with FFR values. An integrated assessment of AS (≥ or < 70%), MLA (≥ or < 2.5 mm 2 ) and presence or absence of thrombus and plaque ulceration was found to have the potential to accurately (sensitivity 91%, specificity 93%) predict FFR results. Conclusion In patients with ICL, a combination of different OCT parameters may help predict FFR results. These findings suggest that only a comprehensive assessment of lesion features by OCT can allow an accurate prediction of lesion severity assessed by FFR. [ABSTRACT FROM AUTHOR]

Background Left main (LM) atherosclerotic lesions affect clinical outcomes. Frequency domain-optical coherence tomography (FD-OCT) allows detailed characterization of non-ostial coronary atherosclerotic lesions. The clinical impact of FD-OCT assessment of LM bifurcation disease on the revascularization decision is unknown. Methods Patients who underwent FD-OCT assessment to guide management of angiographically intermediate distal LM stenosis were retrospectively selected. The FD-OCT LM criteria for percutaneous or surgical revascularization were: – LM area stenosis (AS) ≥ 75% – LM AS > 50% < 75% with minimum lumen area < 4 mm 2 or plaque ulceration – critical FD-OCT ostial stenosis on the left anterior descending or circumflex arteries. Clinical follow-up was obtained to evaluate the occurrence of target vessel failure (TVF) defined as cardiac death and/or acute myocardial infarction (AMI) not related to other vessel and/or target vessel revascularization. Results Out of 131 patients underwent FD-OCT assessment of LM, 122 patients (93%) entered the study. Based on FD-OCT features, 58 (48%) patients were conservatively managed, while the remaining 64 (52%) were revascularized by stenting (n = 48) or surgery (n = 16). After a mean follow-up of 18 months, TVF-free survival was not different between patients undergoing conservative management vs. revascularization (HR 0.40, CI 95% 0.10–1.61, P = 0.20). Of note, two patients only in the conservative management group had TVF (elective LM stenting, no death or myocardial infarction). Conclusions This preliminary experience suggests that a FD-OCT based management for patients with angiographically-intermediate LM bifurcation stenosis may help identify patients in whom revascularization could be deferred. Such observation calls for further evaluations by appropriately designed trials. [ABSTRACT FROM AUTHOR]

Aim To compare in patients with ACS (acute coronary syndromes) a PCI (percutaneous coronary intervention) approach based on FFR (fractional flow reserve) vs. one based on OCT (optical coherence tomography). Methods and results Consecutive patients admitted for ACS and treated with a PCI approach based on OCT or on FFR (recruited in two different studies) were compared and matched with propensity score analysis. Target Lesion revascularization (TLR) was the primary end point, while major adverse cardiovascular events [MACEs defined as the composite of death from cardiac causes, non-fatal MI, clinically driven target vessel revascularization (TVR), or re-hospitalization due to unstable angina] were the secondary ones. Sub-group analysis was performed for patients with FFR/OCT performed on culprit lesions and not. 285 patients were enrolled in the OCT-guided group and 335 in the FFR-guided group, 197 for each being selected after propensity score. After 25 months (range: 7–39 months), OCT-guided group were exposed to lower incidence of TLR (4.1% vs. 14.2% p < 0.01) compared with FFR-guided group without impact on MACEs (14.2% vs. 14.2%, p = 1) or all-cause death (3.6% vs. 1.1%, p = 0.34). At Kaplan-Maier curve analysis for MACEs OCT-guided and FFR-guided groups showed similar outcomes (HR 1.19, CI 0.65–2.2, p = 0.54). Subgroup analysis on culprit and not culprit vessel demonstrated consistent results. Conclusions An OCT based approach in ACS patients offers a reduction in TLR when compared to a PCI-FFR driven. These findings should be confirmed in randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background Endothelialisation is a crucial event after percutaneous coronary intervention (PCI). Endothelial progenitor cells (EPCs) are bone marrow derived elements with reparative properties. We aimed to assess the relationship between circulating EPC levels and stent neointimal hyperplasia (NIH) using frequency domain optical coherence tomography (FD-OCT). Methods Patients undergoing elective PCI to native vessels and randomised to bare metal stent (BMS) alone versus BMS plus drug coated balloon (DCB) were included. At six months, angiographic follow-up and FD-OCT were performed to measure percentage neointimal hyperplasia volume obstruction (%NIHV), and percentage of uncovered stent struts (%US). Venous blood samples were obtained before the procedure and at six months to detect CD34+CD45dimKDR + EPC levels. Results Twenty patients were enrolled. A significant relationship was observed between baseline EPC levels and %NIHV (R: 0.63, p: 0.03) and %US (R: − 0.56, p: 0.01) at follow-up. Both EPC levels and DCB use were independently related to %NIHV (β: 0.55; p < 0.001 and β: − 0.51; p: 0.001, respectively), while only EPC levels were independently associated to %US (β: − 0.52; p: 0.01). Higher %NIHV (p: 0.004) and lower %US (p: 0.005) were observed in patients with stable or increasing EPC level. Conclusion Our study shows a relationship between EPC levels and stent strut coverage, supporting a dual role for these cells in favouring stent endothelialisation but also NIH growth. [ABSTRACT FROM AUTHOR]

Abstract: Stent thrombosis (ST) is the most dramatic complication of coronary stenting. Mechanisms of ST are multiple, including procedural and patient-related factors. A considerable burden of metal inside the coronary has been associated with ST as suggested by the higher rate of ST in case of multiple overlapping or complex two stents procedure in bifurcation lesions. However, occasional stent loss and failure to retrieve it may be a substrate of ST, especially if multiple layers of stent struts are incompletely crushed. Here, we describe a case of very late ST on a partially crushed stent previously lost inside the coronary circulation, using optical coherence tomography (OCT) for guidance during the procedure. [Copyright &y& Elsevier]