Plaque Healing Research Articles

Abstract 4136597: Atherosclerotic plaque healing as a marker of plaque vulnerability: Insight from intracoronary polarization-sensitive optical frequency domain imaging

Background: Collagen is the major extracellular matrix that imparts mechanical strength to fibrous caps covering fibroatheromas. Intracoronary polarimetry with polarization-sensitive (PS) optical frequency domain imaging (OFDI) measures polarization properties, such as birefringence and depolarization (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, while depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose: This study aimed to investigate polarimetric signatures of coronary lesions with healed coronary plaques (HCP) in patients with ACS and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions. Methods: We conducted a single center prospective registry of intracoronary PS-OFDI imaging in patients with coronary artery disease (n = 50). A total of 862 OFDI frames selected from culprit or target lesions were analyzed. Coronary plaque phenotypes were assessed using conventional OFDI imaging. HCP was defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components on intensity images. Birefringence and depolarization of the newer intima was measured in cross-sectional images. Birefringence and depolarization of ACS- and CCS-lesions were compared using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate the diagnostic performance of polarimetric signatures for identifying ACS-lesions. Results: Compared to CCS-lesions, ACS-lesions featured significantly higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025). Conclusions: Intracoronary polarimetry provides quantitative assessment of plaque composition in patients. Further research is warranted to investigate whether birefringence can serve as a marker of healing failure following plaque rupture and erosion.

Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation.

Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47-73 years) was significantly lower than in young ones (24-27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies.

The association of cholesterol crystals and non-culprit plaque characteristics in AMI patients: an OCT study

Objective: To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment. Methods: This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups. Results: A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque (OR=1.583, 95%CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture (OR=1.632, 95%CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions: Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

Layered plaque is associated with high levels of vascular inflammation and vulnerability in patients with stable angina pectoris.

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8% vs. 66.7%, P < 0.001), thin-cap fibroatheroma (26.1% vs. 17.5%, P = 0.026), microvessels (61.8% vs. 34.6%, P < 0.001), and cholesterol crystals (38.6% vs. 25.6%, P = 0.003). Layered plaque was associated with a higher level of vascular inflammation and a higher prevalence of plaque vulnerability, which might play an important role in rapid plaque progression.Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT04523194 .

Abstract 15654: Layered Plaques and Plaque Vulnerability in Patients With Stable Angina Pectoris

Backgrounds: Layered plaque, a signature of previous plaque destabilization and healing, is one of the predictors for rapid plaque progression, the mechanism of which is unknown. Aims: To investigate the level of vascular inflammation and plaque vulnerability in layered plaques to elucidate possible mechanisms of rapid plaque progression. Methods: Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Pericoronary adipose tissue (PCAT) attenuation was measured at the plaque level on CTA. OCT features of plaque vulnerability were assessed at the corresponding site. Results: A total of 475 plaques from 195 patients presented with stable angina pectoris were included. Layered plaques (n=241), compared to non-layered plaques (n=234), had a higher level of vascular inflammation (-70.94 [-77.86, -64.66] HU vs. -73.52 [-80.83, -67.66] HU, P=0.014, Figure 1). Layered plaques also had a higher prevalence of the features of plaque vulnerability (Figure 2), including lipid-rich plaque (83.8% vs. 66.7%, P&lt;0.001), thin-cap fibroatheroma (TCFA) (26.1% vs. 17.5%, P=0.026), microchannel (61.8% vs. 34.6%, P&lt;0.001), and cholesterol crystal (38.6% vs. 25.6%, P=0.003). Conclusions: Layered plaque was associated with higher levels of vascular inflammation and plaque vulnerability, which might play an important role in plaque progression.

Air pollution and plaque healing in acute coronary syndromes.

Plaque healing plays a key role in coronary atherosclerosis1 and represents ‘the second hit’ required to cause an acute coronary syndrome (ACS) after plaque destabilization, this latter being the ‘first hit’.1–3 Moreover, an impaired plaque healing has been found in patients with recurrent ACS, suggesting its importance in preventing repeated symptomatic coronary thrombosis.3 Nonetheless, mechanisms modulating plaque healing are unknown. Air pollution is an important yet overlooked cardiovascular risk factor.4–6 We recently demonstrated that increased long-term particulate matter 2.5 (PM2.5) exposure was associated with coronary plaque inflammation, vulnerability and rupture at optical coherence tomography (OCT) analysis in ACS patients.4 However, the relationship between plaque healing and air pollution has not been yet determined. We investigated the association between air pollution and healed plaques in patients with ACS, stratified by first or recurrent ACS, and whether the previous observation that PM2.5 exposure is associated with coronary plaque vulnerability is valid also in patients with recurrent ACS.5

Layered plaque and plaque volume in patients with acute coronary syndromes.

Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated. Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS. Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm3[114.2 mm3 to 275.0 mm3] vs. 119.3 mm3[68.9 mm3 to 185.5 mm3], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7-60.1%] vs. 53.7%[46.8-60.6%], p = 0.001), and plaque burden (86.5%[81.7-85.7%] vs. 82.6%[77.9-85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8-67.8%] vs. 57.5%[48.9-60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014). Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS. http://www. gov , NCT01110538, NCT03479723, UMIN000041692.

Diagnosis of coronary layered plaque by deep learning

Healed coronary plaques, morphologically characterized by a layered phenotype, are signs of previous plaque destabilization and healing. Recent optical coherence tomography (OCT) studies demonstrated that layered plaque is associated with higher levels of local and systemic inflammation and rapid plaque progression. However, the diagnosis of layered plaque needs expertise in OCT image analysis and is susceptible to inter-observer variability. We developed a deep learning (DL) model for an accurate diagnosis of layered plaque. A Visual Transformer (ViT)-based DL model that integrates information from adjacent frames emulating the cardiologists who review consecutive OCT frames to make a diagnosis was developed and compared with the standard convolutional neural network (CNN) model. A total of 237,021 cross-sectional OCT images from 581 patients collected from 8 sites were used for training and internal validation, and 65,394 images from 292 patients collected from another site were used for external validation. In the five-fold cross-validation, the ViT-based model provided better performance (area under the curve [AUC]: 0.860; 95% confidence interval [CI]: 0.855–0.866) than the standard CNN-based model (AUC: 0.799; 95% CI: 0.792–0.805). The ViT-based model (AUC: 0.845; 95% CI: 0.837–0.853) also surpassed the standard CNN-based model (AUC: 0.791; 95% CI: 0.782–0.800) in the external validation. The ViT-based DL model can accurately diagnose a layered plaque, which could help risk stratification for cardiac events.

1150 SEX-BASED DIFFERENCES IN CORONARY PLAQUE PHENOTYPE AND HEALING AT OPTICAL COHERENCE TOMOGRAPHY (OCT) ANALYSIS

Abstract Introduction Atherosclerotic plaque healing is a dynamic process that promotes plaque repair after destabilization. Previous studies showed that healed plaques are more common in patients with chronic coronary syndrome than in those with acute coronary syndrome, suggesting that they might be a marker of clinical stability. The mechanisms underlying plaque healing are not completely understood. The aim of the present study was to evaluate sex-based differences in plaque phenotype and healing of non-culprit coronary lesions by optical coherence tomography. Methods In this observational, single-center cohort study, we enrolled patients from the OCT Registry of the Fondazione Policlinico A Gemelli IRCCS. A total of 205 patients with both acute coronary syndromes or chronic coronary syndromes undergoing coronary angiography and intravascular OCT imaging of non-culprit vessels were included in the analysis and divided into two groups according to gender. Results Of 205 patients, 153 were male (75%) and 52 (25%) female. Compared with male patients, female patients had lower prevalence of lipid-rich plaque (40.4% vs. 57.7%; p=0.030), plaque rupture (7.7% vs. 21.2%; p=0.028) and cholesterol crystal (13.5% vs. 29.5%; p=0.022). Mean lipid arc and calcium depht were significantly lower in female patients than in male ones (118.0° ± 79.9° vs. 135.5° ± 77.9°; p=0.011; and 52.7 µm ± 79.2 µm vs. 72.3 µm ± 93.5 µm; p=0.007) while fibrous cap tended to be thicker (108.2 µm ± 70.4 µm vs. 96.2 µm ± 72.9 µm; p=0.055). Healed plaques were significantly more frequent in female patients than in male patients (51.9% vs 34.6%; p = 0.027). The prevalence of fibrous plaque, thrombi, neovascularization, diffuse calcifications and spotty calcification was not different between the two groups. Conclusion Females have a distinct atherosclerotic phenotype and healing capacity compared with male patients, including lower prevalence of lipid-rich plaque, cholesterol crystals and plaque ruptures and higher prevalence of healed plaques in non-culprit coronary lesions.

Abstract 10602: The Relationship Between Layered Plaque and Plaque Volume in Patients With Acute Coronary Syndromes

Introduction: Layered plaque is a signature of previous subclinical plaque destabilization and healing, which can be identified by optical coherence tomography (OCT). Silent plaque rupture or erosion with formation of a layer might contribute to rapid step-wise progression of plaque. We examined the relationship between layered plaques detected by OCT and plaque burden detected by intravascular ultrasound (IVUS) in patients with acute coronary syndromes (ACS). Methods: Patients presented with ACS who underwent preintervention OCT and IVUS were included in the analysis. Layered plaque was identified by OCT, and plaque burden was measured by IVUS around the culprit lesion. IVUS findings were compared between patients with layered plaque versus those without layered plaque. Results: Among 150 patients, total atheroma volume (TAV) (183.27 mm 3 [114.2 mm 3 to 275.0 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.004), percent atheroma volume (PAV) (60.06 % [54.7 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %], p=0.001), and plaque burden (PB) (86.51 % [81.7 % to 85.7 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.001) were significantly higher in patients with layered plaques than non-layered plaques (Figure). When multi, single, and non-layered plaques were compared, TAV (188.69 mm 3 [122.1 mm 3 to 293.6 mm 3 ] vs. 137.85 mm 3 [100.1 mm 3 to 208.4 mm 3 ] vs. 119.27 mm 3 [68.9 mm 3 to 185.5 mm 3 ], p=0.021), PAV (62.12 % [56.8 % to 67.8 %] vs. 57.52 % [48.9 % to 60.1 %] vs. 53.69 % [46.8 % to 60.6 %] p&lt;0.001), and PB (87.44 % [81.8 % to 89.3 %] vs. 84.7 % [77.9 % to 88.0 %] vs. 82.58 % [77.9 % to 85.4 %], p=0.018) were significantly greater in multi-layered plaques than others. Conclusions: This study demonstrates that layered plaques, compared to non-layered plaques, have significantly greater plaque burden in patients with ACS, indicating plaque disruption and healing process, rather than gradual smooth muscle proliferation, significantly contributes to plaque progression at the culprit lesion in patients with ACS.

Diagnosis of coronary layered plaque by deep learning

Abstract Background/Introduction Healed coronary plaques, morphologically characterized by a layered pattern, are signatures of previous plaque disruption and healing. Recent optical coherence tomography (OCT) studies showed that layered plaque is associated with vascular vulnerability and rapid plaque progression. However, the diagnosis of layered plaque requires expertise in OCT image interpretation and is susceptible to interobserver variability. Purpose We aimed to develop a deep learning (DL) model for an accurate diagnosis of layered plaque. Methods We developed a Visual Transformer (ViT)-based DL model emulating the cardiologists who review consecutive OCT frames to make a diagnosis (Figure 1), and compared it to the standard convolutional neural network (CNN) model. We used 302,415 cross-sectional OCT images from 873 patients collected from 9 sites: 237,021 images from 581 patients for training and internal validation from 8 sites, and 65394 images from 292 patients collected from another site for external validation. Results Model performances were evaluated using the area under the receiver operating characteristics (AUC). In the five-fold cross validation, the ViT-based model showed better performance than the standard CNN-based model with AUC of 0.886 (95% confidence interval [CI], 0.882–0.891) compared with 0.797 (95% CI, 0.790–0.804). The ViT-based model also outperformed the standard CNN-based model in the external validation, with an AUC of 0.857 (95% CI, 0.849–0.864) compared to 0.806 (95% CI, 0.797–0.815) (Figure 2). Conclusion(s) The ViT-based DL model will help cardiologists to make an accurate diagnosis of layered plaque, which might help to stratify the risk of future adverse cardiac events. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Mrs. Gillian Gray through the Allan Gray Fellowship Fund in Cardiology

Optical coherence tomography in coronary atherosclerosis assessment and intervention.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

734 Have I lost my large rupture cavity? The fingerprint of atherosclerotic plaque healing detected by serial optical coherence tomography imaging

Abstract A 64-year-old man, prior smoker, with a history of paroxysmal atrial fibrillation was referred to our hospital due to worsening dyspnoea, progressively worsening angina, and a positive stress EKG testing. Coronary angiography (CAG) showed an angiographically intermediate stenosis of the mid left anterior descending (LAD) artery and a focal, complex lesion of the distal right coronary artery (RCA) (Figure 1A and B, red arrow). Treatment of the LAD stenosis was deferred based on a negative fractional flow reserve value (i.e. 0.85). Optical coherence tomography (OCT) imaging (ILUMIEN OPTIS, Abbott Vascular, Santa Clara, CA) was performed to better characterize the RCA lesion, which disclosed a ruptured thin-cap fibroatheroma (TCFA) with a large ‘empty’ cavity (Figure 1C–G, red arrows) and overlying ‘layered’ tissue (Figure 1H, white arrowheads). Based on these OCT findings, suggestive of initial plaque healing, and on a large residual lumen dimension (i.e. minimum lumen area, MLA, at the rupture site: 7.7 mm2), this lesion was not treated with percutaneous coronary intervention. The patient was discharged on aspirin, edoxaban, metoprolol, rosuvastatin, and ezetimibe, and remained clinically stable for more than 1 year. Due to angina recurrence, a new CAG was performed 18 months after the first admission, revealing a progression of the mid LAD stenosis that was treated with a 2.5/28 mm drug-eluting stent, and an improvement of the RCA lesion angiographic appearance (smooth contour) (Figure 1A′–B′). RCA OCT imaging was repeated demonstrating a complete healing of the large rupture cavity with all the hallmarks of the reparative process (Figure 1C′–H′): (1) re-established fibrous cap integrity and smooth vessel lumen profile; (2) thickening of the fibrous cap and reduction of lipid burden (i.e., transformation of TCFA into thick-cap fibroatheroma, ThCFA); (3) replacement of the ‘empty’ cavity with new ‘granulation tissue’; (4) initial calcification of the plaque; (5) heterogeneous signal-rich layers with distinct optical-signal intensity (layered, ‘onion-like’ pattern); and (6) mild lumen narrowing (MLA at the rupture site: 6.9 mm2).

713 Culprit plaque morphology and healing capacity in patients with and without preinfarction angina: an optical coherence tomography imaging study

Abstract Aims The relationship between culprit plaque morphology, healed culprit plaques prevalence and clinical presentation of acute myocardial infarction (AMI) remains largely unexplored. We hypothesized that angina preceding the occurrence of AMI (pre-infarction angina, PIA) may reflect a distinct morphologic phenotype of culprit plaques and potentially different healing capacity. Methods and results We conducted a retrospective observational study in patients with AMI who underwent intracoronary optical coherence tomography (OCT) imaging of the culprit lesion before PCI at the Fondazione Policlinico A. Gemelli–Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome. Based on the clinical history, patients were classified into two groups: (i) PIA group, defined as either intermittent chest pain within 6 h preceding the final episode of chest pain, or unstable angina (or both) in the week preceding AMI or (ii) no-PIA group, defined as a single episode of chest pain without prodromal symptoms in the preceding week. Culprit plaques were classified as plaque rupture (PR) or intact fibrous cap (IFC), and presence of layered appearance (healed plaque, HP) was assessed. Thrombus burden (TB) was estimated, and prevalence of diffuse calcification, neovascularization, and OCT-defined macrophage accumulation were evaluated. A total of 102 patients with AMI were included (50 PIA, 52 no-PIA). Patients with PIA showed a higher prevalence of IFC than PR (58% vs. 42%, P = 0.030). PR in patients with PIA were more frequently associated with macrophage accumulation (71.4% vs. 28.6% P = 0.001), and TB tended to be lower [22.0 (15.8–30.3) vs. 38.5 (12.8–67.5), P = 0.145]. Diffuse calcifications were significantly less frequent in patients with PIA (22.0% vs. 40.4%, P = 0.045), while neovascularization tended to be more frequent (58.0% vs. 42.3%, P = 0.113). HPs prevalence was significantly higher in the PIA than in the no-PIA group (66.0% vs. 25.0%, P &amp;lt; 0.001). Conclusions Patients with PIA have a distinct culprit plaque phenotype, more frequently characterized by IFC and a relatively lower TB, with a significantly higher prevalence of plaque healing.

103 Coronary plaque healing and diabetes: insights from optical coherence tomography imaging

Abstract Aims Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. Methods and results In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P &amp;lt; 0.001). At segment-based analysis, normal vessel structure, pathological intimal thickening (PIT), and spotty calcifications were significantly less prevalent in diabetic patients (2.1% vs. 5.1%, P = 0.001; 7.2% vs. 9.5%, P = 0.05; 9.9% vs. 13.6%, P = 0.02, respectively), whereas neovascularization was significantly higher (19.2% vs. 15.6%, P = 0.035). Conclusions Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.

Abstract 12824: Culprit Plaque Morphology and Healing Capacity in Patients With and Without Pre-Infarction Angina: An Optical Coherence Tomography Imaging Study

Introduction: The relationship between culprit plaque morphology, healed culprit plaques prevalence and clinical presentation of acute myocardial infarction (AMI) remains largely unexplored. Hypothesis: We hypothesized that pre-infarction angina (PIA) may reflect a distinct morphologic phenotype of culprit plaques and a different healing capacity. Methods: We conducted a retrospective observational study in patients with AMI who underwent intracoronary optical coherence tomography (OCT) imaging of the culprit lesion before PCI at the Fondazione Policlinico Gemelli-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome. Based on the clinical history, patients were classified into 2 groups: i) PIA group, defined as either intermittent chest pain within 6 hours preceding the final episode of chest pain, or unstable angina (or both) in the week preceding AMI; or ii) no-PIA group, defined as a single episode of chest pain without prodromal symptoms in the preceding week. Culprit plaques were classified as plaque rupture (PR) or intact fibrous cap (IFC), and presence of layered appearance (healed plaque, HP) was assessed. Thrombus burden (TB) was estimated, and prevalence of diffuse calcification, neovascularization, and OCT-defined macrophage accumulation were evaluated. Results: A total of 102 patients with AMI were included (50 PIA, 52 no-PIA). Patients with PIA showed a higher prevalence of IFC than PR (58% vs 42%, p=0.030). PR in patients with PIA were more frequently associated with macrophage accumulation (71.4% vs 28.6% p=0.001), and TB tended to be lower [22.0 (15.8-30.3) vs. 38.5 (12.8-67.5), p=0.145]. Diffuse calcifications were significantly less frequent in patients with PIA (22.0% vs. 40.4%, p=0.045), while neovascularization tended to be more frequent (58.0% vs. 42.3%, p=0.113). HPs prevalence was significantly higher in the PIA than in the no-PIA group (66.0% vs 25.0%, p&lt;0.001). Conclusions: Patients with PIA have a distinct culprit plaque phenotype, more frequently characterized by IFC and a relatively lower TB, with a significantly higher prevalence of plaque healing.

In vivo evidence of atherosclerotic plaque erosion and healing in patients with acute coronary syndrome using serial optical coherence tomography imaging

The EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) allowed us to observe the healing process of coronary plaque erosion in vivo. The present study aimed to investigate the incidence of newly formed healed plaque and different baseline characteristics of acute coronary syndrome (ACS) patients caused by plaque erosion with or without newly formed healed plaque using optical coherence tomography (OCT). A total of 137 ACS patients with culprit plaque erosion who underwent pre-intervention OCT imaging and received no stent implantation were enrolled. Patients were stratified according to the presence or absence of newly formed healed phenotype at 1-month (137 patients) or 1-year OCT follow-up (52 patients). Patient's baseline clinical, angiographic, OCT characteristics and outcomes were compared. There were 55.5% (76/137) of patients developed healed plaque at 1 month, and 69.2% (36/52) of patients developed healed plaque at 1 year. Patients with newly formed healed plaque had larger thrombus burden, and lower degree of area stenosis (AS%) at baseline than those without, and thrombus burden and AS% were predictors of plaque healing. The healing process was accompanied by the significant increase of AS% and incidence of microchannels, and greater inflammatory response. The outcomes appeared to be similar between the two groups. Newly formed healed plaque was found in more than half of ACS patients with plaque erosion without stenting. Patients with newly formed healed plaque had lower luminal stenosis and larger thrombus burden. During healing process, luminal stenosis increased gradually.

Inflammation during the life cycle of the atherosclerotic plaque.

Inflammation orchestrates each stage of the life cycle of atherosclerotic plaques. Indeed, inflammatory mediators likely link many traditional and emerging risk factors with atherogenesis. Atheroma initiation involves endothelial activation with recruitment of leucocytes to the arterial intima, where they interact with lipoproteins or their derivatives that have accumulated in this layer. The prolonged and usually clinically silent progression of atherosclerosis involves periods of smouldering inflammation, punctuated by episodes of acute activation that may arise from inflammatory mediators released from sites of extravascular injury or infection or from subclinical disruptions of the plaque. Smooth muscle cells and infiltrating leucocytes can proliferate but also undergo various forms of cell death that typically lead to formation of a lipid-rich 'necrotic' core within the evolving intimal lesion. Extracellular matrix synthesized by smooth muscle cells can form a fibrous cap that overlies the lesion's core. Thus, during progression of atheroma, cells not only procreate but perish. Inflammatory mediators participate in both processes. The ultimate clinical complication of atherosclerotic plaques involves disruption that provokes thrombosis, either by fracture of the plaque's fibrous cap or superficial erosion. The consequent clots can cause acute ischaemic syndromes if they embarrass perfusion. Incorporation of the thrombi can promote plaque healing and progressive intimal thickening that can aggravate stenosis and further limit downstream blood flow. Inflammatory mediators regulate many aspects of both plaque disruption and healing process. Thus, inflammatory processes contribute to all phases of the life cycle of atherosclerotic plaques, and represent ripe targets for mitigating the disease.

Ultrasound patterns of localized cutaneous leishmaniasis and clinical correlations.

A single-center retrospective study reviewed the following sonographic features of 18 confirmed cases of localized cutaneous leishmaniasis to identify shared presentation patterns: echotexture, lesion borders, hypodermal involvement, soft-tissue changes, and vascular pattern. A second objective was to correlate these patterns with clinical characteristics, including sex, age, anatomical location, nodule vs. plaque presentation, raised borders, granulation tissue, swelling, hyperkeratotic crusting, disease onset, and healing time. Two main patterns were identified with high-frequency ultrasonography. The first pattern was characterized by a high level of inflammation and deep hypodermal involvement, while the second variant showed involvement limited to the dermis, with minimal inflammation. The "inflammatory pattern" showed ill-defined borders, mixed echotexture, prominent vascularity with central distribution, and was correlated with clinical signs of ulceration, granulation tissue, raised borders, and longer healing time (p < 0.05). The "pauci-inflammatory pattern" presented a well-defined structure with decreased echogenicity, reduced or absent vascularity with minimal soft-tissue changes, and was associated with a shorter healing time (p < 0.05).

Non-culprit ruptured vulnerable plaque healing and stabilization by an aggressive lipid-lowering therapy

Non-culprit ruptured vulnerable plaque healing and stabilization by an aggressive lipid-lowering therapy