233 Prognostic implications of the automated detection of lipid core burden index at optical coherence tomography: post hoc analysis of the CLIMA study

Aims Plaque vulnerability features are associated with major coronary events and poor outcomes. However, routinary and reproducible manual assessment of plaque vulnerability features at optical coherence tomography (OCT) is still challenging. We recently developed and validated an OCT-derived automated approach that can identify the intra-plaque lipid core burden index (LCBI). Our aim was to investigate the association between the automated detection of OCT-derived LCBI and clinical events. Methods and results We conducted a post hoc analysis of the CLIMA study, a large prospective observational, multicentre registry recruiting all consecutive patients undergoing assessment of the proximal left anterior descending artery (LAD) segment by OCT in the context of clinically indicated coronary angiography. The automated detection of maximum LCBI was carried out in 4 mm of intervention-naïve proximal LAD segment (maxLCBI4mm) by using the validated software. The mean and median value of LCBI in all study population (n = 1003) was 407.6 and 411.1, respectively. Patients with higher LCBI (≥400) were more frequently male (P = 0.016) and affected by insulin-dependent diabetes mellitus (0.046). Furthermore, they showed more frequently at OCT analysis the vulnerable plaque characteristics investigated in the CLIMA study (Table 1). At Cox regression analysis, a maxLCBI4mm ≥400 predicted at 1 year both a hard endpoint of cardiac death and target-vessel myocardial infarction [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.2–5.3, P 0.011], as well as a composite endpoint of cardiac death, any myocardial infarction and target vessel revascularization (HR: 1.87, 95% CI: 1.1–3.1, P = 0.011). Conclusions In our study, the automated detection of LCBI at OCT was feasible and related to poorer clinical outcome at 1-year follow-up.

Cryo-electron microscopy revealed TACAN is extensively and specifically associated with membrane lipids

TACAN is not a mechanosensitive ion channel but significantly linked to the mechanical hyperalgesia. In this study, we show that the human TACAN is a homodimer with each monomer consisting of a body, a spring and a blade domains. The body domain contains six transmembrane helices that forms an independent channel. The spring domain adapts a loop-helix-loop configuration with the helix running within and parallel to the membrane. The blade domain is composed of two cytoplasmic helices. In addition, we found that all the helices of the body and the spring domains are specifically associated with membrane lipids. Particularly, a lipid core, residing within a cavity formed by the two body and spring domains, contacts with the helices from the body and spring domains and extends to reach two symmetrically arranged lipid clusters. These results extremely imply that the membrane lipids coordinate with the membrane-embedded protein to sense and transduce the mechanic signal.

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

Background Near infrared spectroscopy – intravascular ultrasound (NIRS-IVUS) imaging can provide a fully automated estimation of lipid burden, providing a two-dimensional spread-out plot, the Lipid Core Burden Index (LCBI), which has been associated with higher incidence of cardiac events. Optical coherence tomography (OCT) can identify lipid component with high accuracy and it is therefore potentially capable of measuring its longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Purpose The present study has been designed to validate a novel automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot plus other features of plaque vulnerability. Methods We compared the results obtained with a novel automated OCT alghorithm, developed utilising a convolutional neural network, with those obtained with conventional (manual) OCT and with NIRS-IVUS in a consecutive series of 40 patients with coronary artery disease. We tested and validated our new OCT algorithm to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. In each coronary plaque, the following measurements were obtained with NIRS-IVUS: 1) minimum lumen area (MLA), 2) vessel area at MLA site, 3) plaque burden (%) at MLA site, 4) NIRS-defined lipid pool arch and 5) maximum LCBI measurement within a 4 mm length. The following OCT features were obtained: 1) the MLA cross section, 2) the minimum fibrous cap thickness (FCT) in presence of lipid components and measured as the average of three measurements obtained in the same cross-section and 3) maximum LCBI within a 4 mm length. Results Three lesions groups were identified according to the studied lesions: 1) culprit lesions in patients with acute coronary syndrome (ACS, n=16), 2) non-culprit lesions in patients with ACS (n=12) and 3) lesions in patients with stable angina (n=12). OCT conventional assessment showed for the culprit ACS plaques a trend for a larger lipid arc and a significant thinner FCT (p=0.028). Consistently, NIRS-IVUS showed for culprit ACS plaques a more complex anatomy. A strong trend for increased maximum LPBI in 4mm segments was found in the culprit ACS group, regardless of the adopted imaging modality, either NIRS-IVUS or automated OCT (p=0.184 and p=0.066, respectively, figure 1). 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, applying a validated 400 cut off were 90.5 and 84.2 respectively. Conclusions We developed an automated approach, comparable to NIRS, to assess OCT images 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. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): CLI - Centro Lotta all'Infarto Spread-out plot by IVUS-NIRS and OCT

Accumulation of Plasma-Derived Lipids in the Lipid Core and Necrotic Core of Human Atheroma: Imaging Mass Spectrometry and Histopathological Analyses

Objective: To clarify the pathogenesis of human atheroma, the origin of deposited lipids, the developmental mechanism of liponecrotic tissue, and the significance of the oxidation of phospholipids were investigated using mass spectrometry-aided imaging and immunohistochemistry. Approach and Results: Atherosclerotic lesions in human coronary arteries were divided into 3 groups: pathological intimal thickening with lipid pool, atheroma with lipid core, and atheroma with necrotic core. The lipid pool and lipid core were characterized by the deposition of extracellular lipids. The necrotic core comprised extracellular lipids and liponecrotic tissue. The proportion of cholesteryl linoleate in cholesteryl linoleate+cholesteryl oleate fraction in the extracellular lipid and liponecrotic regions differed significantly from that of the macrophage foam cell–dominant region, and the plasma-derived components (apoB and fibrinogen) were localized in the regions. The liponecrotic region was devoid of elastic and collagen fibers and accompanied by macrophage infiltration in the surrounding tissue. Non–oxidized phospholipid (Non-OxPL), OxPL, and Mox macrophages were detected in the three lesions. In the atheroma with lipid core and atheroma with necrotic core, non-OxPL tended to localize in the superficial layer, whereas OxPL was distributed evenly. Mox macrophages were colocalized with OxPL epitopes. Conclusions: In human atherosclerosis, plasma-derived lipids accumulate to form the lipid pool of pathological intimal thickening, lipid core of atheroma with lipid core, and necrotic core of atheroma with necrotic core. The liponecrotic tissue in the necrotic core appears to be developed by the loss of elastic and collagen fibers. Non-OxPL in the accumulated lipids is oxidized to form OxPL, which may contribute to the lesion development through Mox macrophages.