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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]

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]

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]

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]

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]

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]

Background: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. Methods: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. Results: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). Conclusions: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

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]

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]

The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS ( n = 10), pre-DEB ( n = 10), post-DEB ( n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm ( p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % ( p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting). Clinical Trial Registration Information: . Identifier: NCT01057563. [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]

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]

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]

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]