Comparison between different approaches to evaluate fibrous cap thickness in sequential optical coherence tomography studies.

BACKGROUND: In this in-vivo human study we tested the reproducibility for optical coherence tomography (OCT) assessment of lumen area (LA) and plaque components measurements, such as lipid arc extension and fibrous cap thickness (FCt). METHODS: We tested the variability of LA, lipid arc and FCt assessments in two repeated OCT pullbacks from the same diseased coronary segment matched using fiduciary anatomical landmarks. In particular, for the reliability of minimal FCt measurement we compared four different approaches based on continuous (longitudinal) or segmental (spot) individuation of smaller thickness: 1) comparison of single minimal FCt individuated alongside all plaque extension in the two pullbacks (Longitudinal (L)-spot minimal FCt value); 2) comparison of the mean FCt values of the plaque in the two pullbacks (L-plot mean FCt value); 3) comparison between the single minimal FCt value obtained in the first pullback and the single FCt obtained in the matched CS of second pullback (L-spot CS matched FCt value); 4) comparison of measurements obtained by visual selection of CS with minimal FCt s in the two pullbacks (single-spot minimal FCt value). RESULTS: From the paired analyses of 20 non culprit lesions (accounting for a total of 387 matched CS), we found a suboptimal in-segment correlation for LA (Intra-Class Coefficient [ICC] 0.731), but a good in-segment correlation for lipid arc (ICC 0.963). Regarding FCt measurement, a high reproducibility was obtained applying continuous assessment; in particular, the best correlation was observed with L-spot minimal FCt value and the L-plot mean FCt (ICC 0.893 and 0.952, respectively) with small inter-pullback differences (confidence intervals less than 0.04 mm). CONCLUSIONS: In this methodological study we observed a good reproducibility for quantitative plaque measurements with OCT confirming its reliability for serial assessment. In particular, longitudinal measurement in multiple adjacent frames seems to be the more accurate and reproducible approach for sequential FCt assessment.

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events - Results from the CLIMA Registry.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.

Complete Transfemoral Endovascular Repair with Homemade Steerable Sheath of Intercostal Artery Patch Aneurysm after Open Repair of Thoracoabdominal Aortic Aneurysm.

The aim of this paper is to describe a case of complete transfemoral approach for endovascular treatment of a large intercostal patch aneurysm with custom-made stent-graft in a patient with Loeys-Dietz syndrome and previous multiple aortic operations. Three aortic components were used to exclude a 65-mm intercostal patch aneurysm. Because of the reimplantation site of supra-aortic trunks in a previous open arch repair, we used a complete transfemoral approach with a homemade steerable sheath to deliver all the renovisceral bridging stents through the downward side-branches. No major complications were registered. A 6-month follow-up resulted uneventfully, and an initial shrinkage of the aneurysmal lesion was found. The use of a homemade steerable sheath was safe and effective for catheterization and stenting of all the target vessels through the downward side branches.

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

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

Clinical outcomes of suboptimal stent deployment as assessed by optical coherence tomography: long-term results of the CLI-OPCI registry.

BACKGROUND: Intraprocedural optical coherence tomography (OCT) is a valuable tool for guidance of percutaneous coronary intervention, but long-term follow-up data are lacking. AIMS: The aim of this study was to address the long-term (7.5 years) clinical impact of quantitative OCT metrics of suboptimal stent implantation. METHODS: This retrospective study includes 391 patients with long-term follow-up (mean 2,737 days; interquartile range 1,301-3,143 days) from the multicentre Centro per la Lotta contro l'Infarto - Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) registry. OCT-assessed suboptimal stent deployment required the presence of at least one of the following pre-defined OCT findings: in-stent MLA <4.5 mm2, proximal or distal reference lumen narrowing with lumen area <4.5 mm2, significant proximal or distal edge dissection width ≥200 µm. RESULTS: One hundred and two patients (26.1%) with 138 stented lesions (27.7%) experienced a device-oriented cardiovascular event (DOCE). In-stent MLA <4.5 mm2 (38.1% vs 19.8%, p<0.001), in-stent lumen expansion <70% (29.5% vs 20.3%, p=0.032), proximal reference lumen narrowing <4.5 mm2 (6.5% vs 1.4%, p=0.004), and distal reference lumen narrowing <4.5 mm2 (12.9% vs 3.6%, p=0.001) were significantly more common in the DOCE vs non-DOCE group. OCT-assessed suboptimal stent deployment was an independent predictor of long-term DOCE (HR 2.17, p<0.001), together with bare metal stent implantation (HR 1.73, p=0.003) and prior revascularisation (HR 1.53, p=0.017). CONCLUSIONS: The presence of OCT-assessed suboptimal criteria for stent implantation was related to a worse clinical outcome at very long-term follow-up. This information further supports an OCT-guided strategy of stent deployment.

Myocardial infarction with non-obstructive coronary artery disease.

As a result of the increased use of coronary angiography in acute myocardial infarction in the last two decades, myocardial infarction with non-obstructive coronary arteries (MINOCA) has received growing attention in everyday clinical practice. At the same time, research interest in MINOCA has increased significantly. MINOCA is a heterogeneous disease entity seen in 5-10% of all patients with myocardial infarction, especially in women. Clinically, MINOCA may be difficult to distinguish from other non-ischaemic conditions that can cause similar symptoms and myocardial injury. There is still some confusion around the diagnosis, investigation and management of patients with MINOCA. The present review summarises the current knowledge of MINOCA regarding epidemiology, pathophysiology, investigation, and treatment, with a special focus on imaging modalities. In addition, remaining important knowledge gaps are highlighted.

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

PURPOSE: Near infrared spectroscopy-Intravascular ultrasound (NIRS-IVUS) provide a fully automated Lipid Core Burden Index (LCBI). Optical coherence tomography (OCT) is potentially capable of measuring lipid longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. The present study has been designed to validate an automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot. METHODS: We compared results obtained with conventional (manual) OCT, with those obtained with a novel automated OCT algorithm and with NIRS-IVUS in consecutive 40 patients. Our goal was to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Three groups were identified according to the studied lesions: (1) culprit lesions in ACS patients (n = 16), (2) non-culprit lesions in ACS patients (n = 12) and (3) lesions in stable patients (n = 12). OCT (either manual and automated) and NIRS-IVUS assessment showed for culprit ACS plaques a more complex anatomy. RESULTS: A strong trend for increased LCBI was found in the culprit ACS group, regardless of the adopted imaging modality (either NIRS-IVUS or automated OCT). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r = 0.75). The sensitivity and specificity of automated OCT to detect significant LCBI (> 400) were 90.5 and 84.2 respectively. CONCLUSION: We developed an OCT automated approach that can provide a dedicated lipid plaque spread-out plot to address plaque vulnerability. The automated OCT software can promote and improve OCT clinical applications for the identification of patients at risk of hard events.

Prevalence and quantitative assessment of macrophages in coronary plaques.

Although optical coherence tomography (OCT) proved to be able to identify macrophage clusters, there are no available data on the possibility to obtain reproducible measurements of their circumferential extension and location. The purpose of the present post-hoc analysis of the CLIMA study was to revise the clinical and demographic variables of patients having coronary plaques with macrophages and to investigate the reproducibility of their quantitative assessment. A total of 577 patients out of 1003 undergoing OCT showed macrophage accumulation. Three groups were identified; group 1 (426 patients) without macrophages, group 2 (296) patients with low macrophage content (less than median value [67°] of circumferential arc) and group 3 (281) with high macrophage content arc [> 67°]. Patients with macrophages (groups 2 and 3) showed a higher prevalence of family history for coronary artery disease and hypercholesterolemia and had a significantly larger body mass index. Furthermore, group 3 had more commonly triple vessel disease and higher value of LDL cholesterol levels compared to the two other groups. The inter-observer agreement for macrophage interpretation was good: R values were 0.97 for the circumferential arc extension, 0.95 for the minimum distance and 0.98 for the mean distance. A non-significant correlation between circumferential extension of macrophages and hsCRP values was found (R = 0.013). Quantitative assessment of macrophage accumulations can be obtained with high reproducibility by OCT. The presence and amount of macrophages are poorly correlated with hsCRP and identify patients with more advanced atherosclerosis and higher LDL cholesterol levels.

Coronary inflammation: why searching, how to identify and treat it.

Inflammation plays an important role in the development of atherosclerotic lesions. A variety of stimuli promote atherosclerosis, including increased LDL cholesterol in blood, exposure to tobacco, diabetes mellitus, hypertension, or rheological stress. Inflammatory cells have an established role in the growth of atherosclerotic lesions. Macrophages recognize and internalise ox-LDL to eventually become lipid-laden foam cells, the hallmark cellular component of atheroma. Infiltrating CD4-T cells have a role too, by interacting with ox-LDL and other antigens. Cytokines secreted by inflammatory cells stimulate smooth muscle cells migration whilst macrophages produce metalloprotease that lead to fibrous cap rupture. The necrotic debris of died macrophages and smooth muscle cells help to continue the inflammatory process. The inflammatory response can also directly activate platelets and promote thrombus formation at the surface of complicated coronary plaques. The CANTOS trial can be waived as an innovative study promoting a novel approach of personalized medicine. In patients with previous myocardial infarction, high-sensitivity C-reactive protein level of 2 mg and normal LDL level (<70 mg/dL), canakinumab a therapeutic monoclonal antibody targeting interleukin-1ß, at a dose of 150 mg every 3 months, led to a significant reduction of the primary efficacy end point: nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death at 48 months. Based on the CANTOS results, patients on statins and residual inflammatory risk as assessed by means of a high-sensitivity CRP >2 mg/l at baseline have a high risk of future cardiac events, comparable to that of statin-treated patients with suboptimal cholesterol LDL level. The inhibition of interleukin-1ß by means of canakinumab, which is only one of many potential anti-inflammatory pathways, open new perspectives, showing that a selective inhibition of the inflammatory pathway may be beneficial in reducing cardiovascular risk. In a process of personalized medicine, there is need to accurately identify patients at high risk of events, to be treated with potent statins or anti-inflammatory drugs. Perhaps in the near future a more specific assessment of coronary inflammations, possibly obtained with imaging modalities (either invasive or non-invasive), will better select patients at risk of events. In this scenario, in the setting of secondary prevention, OCT may serve the scope of identifying vulnerable plaques with local aggregates of inflammatory cells. Future studies are needed to understand the clinical effectiveness of strategies based on invasive coronary assessment.

Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study.

AIMS: The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical 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.

'Precision medicine' and ischaemic heart disease: the stage is set for the new antibody based therapies (lipid lowering and anti-inflammatory).

Improving cardiovascular risk assessment requires a 'personalized' approach. Appraisal of well-known cardiovascular risk factors should be integrated with markers of cardiovascular risk such as LDL cholesterol (C-LDL) and C-reactive protein (CRP). Results of the recent trials of PCSK9 inhibitor monoclonal antibodies open new interesting perspective. Data regarding the use of Evolocumab, in secondary prevention settings, in high-risk patients are very encouraging. In the same vein, the CANTOS study demonstrated, for the first time, that Canakinumbab, an antibody with anti-inflammatory action (with no effects on C-LDL levels), decreases significantly the risk of major cardiovascular events in a high-risk population with elevated CRP and optimal C-LDL. This trial, for the first time, suggested a strategy distinguishing the anti-inflammatory from the cholesterol lowering component, thus differentiating the treatment. In the ensuing years, we will probably witness the clinical application of this concept.

In vivo vulnerability grading system of plaques causing acute coronary syndromes: An intravascular imaging study.

BACKGROUND: Autopsy studies shed light on the interplay between fatal acute coronary syndromes (ACS) and features of plaque vulnerability. This is a prospective pilot study designed for generating a new in vivo imaging grading system of plaque vulnerability. METHODS: We studied 87 coronary vessels in 63 consecutive patients: 48 with Acute Coronary Syndrome (ACS) and 15 with stable coronary artery disease using IntraVascular-Ultrasound Near-Infrared-Spectroscopy (IVUS-NIRS) and Optical Coherence Tomography (OCT). We identified 99 lesions: 21 were the ACS culprit lesions (18 ulcerations and 3 with intact fibrous cap), 78 were non-culprit lesions including plaques located in the same ACS culprit vessel (N12), plaques located in a non-culprit vessel in patients with ACS (28) and target lesions of stable patients (N 38). A second analysis focused on lipid plaques, comparing the 18 ACS culprit ulcerated lesions and the 55 non-culprit lesions. RESULTS: The co-presence of the following three features of vulnerability [Minimal Luminal Area (MLA) <4 mm2, Fibrous Cap Thickness (FCT) < 75 µm and superficial macrophages] was by far more frequent in ACS culprit lesions than in controls (OR 40.6 for all lesions and OR 45.7 for ulcerated culprit lesions only). The triple-feature OCT grading identified vulnerable plaques with a much higher accuracy than that obtained applying each single feature of vulnerability. CONCLUSIONS: The co-presence of the 3 OCT features of vulnerability (MLA < 4 mm2, FCT < 75 µm and superficial macrophages) identifies culprit ACS lesions with a very high odd ratio. This finding could set the basis for a new OCT vulnerability grading system including superficial macrophages.

Role of optical coherence tomography in identifying sub-optimal stent positioning and predicting major adverse cardiac events in a comparative study with angiography: a CLIO-OPCI II sub-study.

BACKGROUND: Quantitative coronary angiography (QCA) is the gold standard for evaluating correct stenting, despite its limitation in recognizing features indicative of suboptimal deployment. This subanalysis of the CLI-OPCI II registry addressed the role of optical coherence tomography (OCT) to verify whether suboptimal OCT deployment occurs in the presence of an optimal angiographic result. PATIENTS AND METHODS: We retrospectively analyzed 125 lesions in the 105 patients with major adverse cardiac events of the CLI-OPCI II. Every lesion was evaluated with OCT and angiography, including visual and QCA assessment. Optimal angiographic result was defined as residual stenosis of less than 30% at QCA and absence of haziness at visual angiography. The following OCT features of suboptimal stenting were considered: edge dissection (linear rim of tissue with a width >200 µm), reference lumen narrowing (lumen area <4.5 mm in the presence of significant residual plaque adjacent to stent endings), and in-stent narrowing (minimum lumen area<4.5 mm). RESULTS: Among the 125 lesions, 105 showed an optimal angiographic result. At OCT, a suboptimal positioning was common (56%). In the group of optimal angiographic results, OCT showed a suboptimal deployment in 54% of cases. Minimum lumen area of less than 4.5 mm, distal and proximal reference narrowing, and distal edge dissections were found in 30, 25, 15, and 7% of cases, respectively. CONCLUSION: This substudy of the CLI-OPCI II showed that in patients with major adverse cardiac events, the presence of an optimal postintervention angiographic appearance with suboptimal OCT metrics is a frequent finding. Our data further support the effectiveness of OCT, which provide valuable information even in the presence of optimal poststenting angiographic results.

Limitations of OCT in identifying and quantifying lipid components: an in vivo comparison study with IVUS-NIRS.

AIMS: We aimed to assess the agreement between IVUS-NIRS and OCT to assess lipid plaques in patients with acute coronary syndromes or stable angina. In addition, the impact of both macrophages and calcifications was investigated. METHODS AND RESULTS: Forty-three patients undergoing both IVUS-NIRS and OCT assessment of the culprit and/or non-culprit coronary lesions were enrolled. Cross-sections from lipid plaques, calcified plaques and normal-appearing vessel tracts were identified and matched with the two imaging techniques. Lipid arc was measured by both IVUS-NIRS and OCT. Macrophage presence and calcifications were also investigated with OCT. OCT detected a lipid plaque in 90 cross-sections (48.9%), with a sensitivity of 85.5% and a specificity of 69.7% as compared with IVUS-NIRS. The percentage of OCT false positive was 20.1% and of false negative was 4.9% for lipid plaque detection. The Pearson correlation coefficient for lipid arc was 0.675, p=0.0001. Macrophages were detected in 73% of OCT false positive cross-sections. Conversely, calcifications were present in 66.7% of OCT false negative cross-sections. The variability of lipid arc was independently associated with macrophages (beta=0.295, p=0.013). CONCLUSIONS: Agreement between IVUS-NIRS and OCT for lipid plaque detection is suboptimal. The presence of macrophages and superficial calcifications on OCT negatively affects lipid detection.

Suboptimal stent deployment is associated with subacute stent thrombosis: optical coherence tomography insights from a multicenter matched study. From the CLI Foundation investigators: the CLI-THRO study.

BACKGROUND: Acute or subacute stent thrombosis (ST) is a well-described complication usually causing acute coronary syndromes and, in the worst case scenario, sudden cardiac death. In this study, we aimed at exploring the potential role of optical coherence tomography (OCT) in the understanding of the mechanism of ST. METHODS: Twenty-one consecutive patients, after acute coronary syndromes due to a definite subacute ST, were assessed with OCT and matched 1:2 with 42 patients undergoing OCT for scheduled follow-up. Optical coherence tomography assessment was focused on features indicative of nonoptimal stent deployment: underexpansion, malapposition, edge dissection, and reference lumen narrowing. RESULTS: Optical coherence tomography revealed a minimum stent area sensibly smaller in the ST group (5.6 ± 2.6 vs 6.8 ± 1.7 mm(2); P = .03) with a higher incidence of stent underexpansion when compared with the control group (42.8% vs 16.7%; P = .05). Dissection at stent edges was more commonly detected in ST group (52.4% vs 9.5%; P < .01). No significant differences between the 2 groups were observed for malapposition (52.4% vs 38.1%; P = .651) and reference lumen narrowing (19.0% vs 4.8%; P = .172). At least 1 OCT finding indicative of suboptimal stent deployment was detectable in 95.2% of patients experiencing ST versus 42.9% of the control group (P < .01). CONCLUSIONS: Optical coherence tomography assessment in patients experiencing subacute ST revealed nonoptimal stent deployment in almost all cases with higher incidence of stent underexpansion and edge dissection, potentially explaining the cause of this adverse event. The adoption of an OCT-guided percutaneous coronary intervention protocol could have a potential for the prevention of ST in complex cases.

Quantification of manual thrombus removal in patients with acute coronary syndromes: a study exploiting serial frequency domain-optical coherence tomography.

AIMS: Thrombus aspiration is useful in improving myocardial reperfusion in comparison to conventional percutaneous coronary intervention in patients with acute myocardial infarction. Nonetheless, assessment of thrombus aspiration efficacy is lacking. Aim of this study was to quantify by frequency domain optical coherence tomography (OCT) the amount of thrombus removal in patients with acute coronary syndromes undergoing manual thrombus aspiration, correlating it with the actual size of the retrieved material. METHODS: Twenty-five consecutive patients with acute coronary syndrome were enrolled. OCT assessment of thrombotic lesions was performed before and after thrombus aspiration and repeated after stent deployment. OCT thrombus assessment was based on an established scoring technique. The aspirated material was analyzed by histology, and its planimetry was correlated with OCT-derived thrombus removal. RESULTS: The percentage of thrombus removal [(prethrombus aspiration minus post-thrombus aspiration)/(prethrombus aspiration × 100)] was 48.9; the delta measurement of the removed thrombus calculated by OCT correlated well with the planimetry-measured aspirated material (r = 0.56, P < 0.01). CONCLUSION: The present study showed the following: the thrombus score derived by OCT measurements correlated reasonably well with the planimetry measure of surface area of the actual aspirated material; after thrombus aspiration a large amount of residual thrombus can be appreciated at the target lesion site; and tissue components such as cholesterol debris and inflammatory cells can often be retrieved during thrombus aspiration.