Search

Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition affecting 5% to 8% of patients presenting with acute myocardial infarction. Initially it was considered a favorable clinical diagnosis, nowadays it is known that MINOCA can significantly affect patient quality of life and portends a guarded prognosis. Therefore, it is of utmost importance to identify the specific pathophysiological mechanism underlying this clinical condition in order to set up a targeted pharmacological and non-pharmacological therapy. Coronary angiography is still a mandatory diagnostic test to rule out obstructive coronary artery disease but has limited capability to identify other potential functional and structural etiologies of MINOCA. The purpose of this review is to provide an overview of the invasive diagnostic work-up of patients with MINOCA, highlighting the diagnostic tools warranted beyond coronary angiography inside the cath lab (intracoronary provocation tests, intracoronary imaging and indexes for the assessment of coronary microvascular dysfunction), and the remaining essential knowledge gaps in this field.

Background: 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., Methods: 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., Results: Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm 3 [114.2 mm 3 to 275.0 mm 3 ] vs. 119.3 mm 3 [68.9 mm 3 to 185.5 mm 3 ], 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)., Conclusion: 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., Clinical Trial Registration: http://www., Clinicaltrials: gov , NCT01110538, NCT03479723, UMIN000041692., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Nature Limited.)

Background: Plaque rupture (PR) is the main cause of coronary thrombosis in non-ST segment elevation myocardial infarction (NSTEMI), but can be found in stable coronary artery disease (CAD). Our study compared the morphology and local inflammatory activity of ruptured plaques between stable CAD and NSTEMI patients using frequency-domain optical coherence tomography (FD-OCT)., Methods: We retrospectively evaluated 70 plaques with PR at the FD-OCT (25 in stable CAD patients and 45 in NSTEMI patients). Main clinical, angiographic, and morphological features were compared., Results: Besides an overall equivalence in clinical and angiographic features (except for more smokers among NSTEMI patients), some important FD-OCT differences in plaque morphology emerged: PR in NSTEMI was characterized by more macrophage infiltrates (78% in NSTEMI patients vs 20% in stable CAD patients; P<.001) and intraluminal thrombosis (84% in NSTEMI patients vs 48% in stable CAD patients; P<.01). Quantitative analysis showed a higher density of macrophages in NSTEMI than in stable CAD patients: median max normalized standard deviation (NSD) was 0.0934 (IQR, 0.0796-0.1022) vs 0.0689 (IQR, 0.0598-0.0787); P<.01 and mean NSD was 0.062 (IQR, 0.060-0.065) vs 0.053 (IQR, 0.051-0.060); P<.001. Other morphological features did not differ between stable CAD and NSTEMI patients. Main FD-OCT quantitative parameters like minimal lumen area and plaque length were also equivalent between the 2 groups., Conclusions: Differences in morphological features of PR between stable CAD and NSTEMI patients suggest that local inflammation contributes to the unstable fate of the atherosclerotic plaque.

Aims: Layered plaques represent signs of previous plaque destabilization. A recent study showed that acute coronary syndrome (ACS) patients with layered culprit plaque have more vulnerability at the culprit lesion and systemic inflammation. We aimed to compare the characteristics of non-culprit plaques between patients with or without layered plaque at the culprit lesion. We also evaluated the characteristics of layered non-culprit plaques, irrespective of culprit plaque phenotype., Methods and Results: We studied ACS patients who had undergone pre-intervention optical coherence tomography (OCT) imaging. The number of non-culprit lesions was evaluated on coronary angiogram and morphological characteristics of plaques were studied by OCT. In 349 patients, 99 (28.4%) had layered culprit plaque. The number of non-culprit plaques in patients with or without layered culprit plaque was similar (3.2 ± 0.8 and 2.8 ± 0.8, P = 0.23). Among 465 non-culprit plaques, 145 from patients with layered culprit plaque showed a higher prevalence of macrophage infiltration (71.0% vs. 60.9%, P = 0.050). When analysed irrespective of culprit plaque phenotype, layered non-culprit plaques showed higher prevalence of lipid (93.3% vs. 86.0%, P = 0.028), thin cap fibroatheroma (29.7% vs. 13.7%, P < 0.001), and macrophage infiltration (82.4% vs. 54.0%, P < 0.001) than non-layered plaques. Plaques with layered phenotype at both culprit and non-culprit lesions had the highest vulnerability., Conclusion: In ACS patients, those with layered phenotype at the culprit lesion demonstrated greater macrophage infiltration at the non-culprit sites. Layered plaque at the non-culprit lesions was associated with more features of plaque vulnerability, particularly when the culprit lesion also had a layered pattern., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background Seasonal variations in acute coronary syndromes (ACS) have been reported, with incidence and mortality peaking in the winter. However, the underlying pathophysiology for these variations remain speculative. Methods and Results Patients with ACS who underwent optical coherence tomography were recruited from 6 countries. The prevalence of the 3 most common pathologies (plaque rupture, plaque erosion, and calcified plaque) were compared between the 4 seasons. In 1113 patients with ACS (885 male; mean age, 65.8±11.6 years), the rates of plaque rupture, plaque erosion, and calcified plaque were 50%, 39%, and 11% in spring; 44%, 43%, and 13% in summer; 49%, 39%, and 12% in autumn; and 57%, 30%, and 13% in winter ( P =0.039). After adjusting for age, sex, and other coronary risk factors, winter was significantly associated with increased risk of plaque rupture (odds ratio [OR], 1.652; 95% CI, 1.157-2.359; P =0.006) and decreased risk of plaque erosion (OR, 0.623; 95% CI, 0.429-0.905; P =0.013), compared with summer as a reference. Among patients with rupture, the prevalence of hypertension was significantly higher in winter ( P =0.010), whereas no significant difference was observed in the other 2 groups. Conclusions Seasonal variations in the incidence of ACS reflect differences in the underlying pathobiology. The proportion of plaque rupture is highest in winter, whereas that of plaque erosion is highest in summer. A different approach may be needed for the prevention and treatment of ACS depending on the season of its occurrence. Registration URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03479723.

The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. Macrophages from coronary plaques are not available, and monocyte-derived macrophages (MDMs) are usually considered as a surrogate. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). At morphological analysis, MDMs of CAD patients had a higher prevalence of round than spindle cells, whereas in healthy subjects the prevalence of the two morphotypes was similar. Compared to healthy subjects, MDMs of CAD patients had reduced efferocytosis, lower transglutaminase-2, CD206 and CD163 receptor levels, and higher tissue factor (TF) levels. At OCT, patients with a higher prevalence of round MDMs showed more frequently a lipid-rich plaque, a thin-cap fibroatheroma, a greater intra-plaque macrophage accumulation, and a ruptured plaque. The MDM efferocytosis correlated with minimal lumen area, and TF levels in MDMs correlated with the presence of ruptured plaque. MDMs obtained from CAD patients are characterized by a morpho-phenotypic heterogeneity with a prevalence of round cells, showing pro-inflammatory and pro-thrombotic properties. The MDM profile allows identifying CAD patients at high risk.

Diabetes mellitus (DM) increases cardiovascular morbidity and mortality. A statin is routinely prescribed to patients with DM. However, whether a statin therapy is equally effective in plaque stabilization in DM patients compared with non-DM patients is unknown. A total of 117 lipid-rich plaques were imaged in 90 patients (54 plaques in 41 DM patients and 63 plaques in 49 non-DM patients) with coronary artery disease, those who were treated with a statin and underwent serial optical coherence tomography imaging were included in this study (mean follow-up period, 362 ± 38 days). The changes in minimum fibrous cap thickness (FCT) and lipid index between baseline and 1-year follow-up were compared between the 2 groups. Minimum FCT increased and lipid index decreased with statin therapy in both groups. No significant differences were observed in percent changes of minimum FCT (p = 0.796) and lipid index (p = 0.336) between DM and non-DM patients. Statin therapy induced a significant increase in FCT and a significant decrease in lipid index in both groups. Vascular response to statin therapy was similar between the 2 groups irrespective of DM status., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study conducted detailed analysis of calcified culprit plaques in patients with acute coronary syndromes (ACS)., Background: Calcified plaques as an underlying pathology in patients with ACS have not been systematically studied., Methods: From 1,241 patients presenting with ACS who had undergone pre-intervention optical coherence tomography imaging, 157 (12.7%) patients were found to have a calcified plaque at the culprit lesion. Calcified plaque was defined as a plaque with superficial calcification at the culprit site without evidence of ruptured lipid plaque., Results: Three distinct types were identified: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion (prevalence of 25.5%, 67.4%, and 7.1%, respectively). Eruptive calcified nodules were frequently located in the right coronary arteries (44.4%), whereas superficial calcific sheet was most frequently found in the left anterior descending coronary arteries (68.4%) (p = 0.012). Calcification index (mean calcification arc × calcification length) was greatest in eruptive calcified nodules, followed by superficial calcific sheet, and smallest in calcified protrusion (median 3,284.9 [interquartile range (IQR): 2,113.3 to 5,385.3] vs. 1,644.3 [IQR: 1,012.4 to 3,058.7] vs. 472.5 [IQR: 176.7 to 865.2]; p < 0.001). The superficial calcific sheet group had the highest peak post-intervention creatine kinase values among the groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 241 [IQR: 116 to 612] IU/l vs. 834 [IQR: 141 to 3,394] IU/l vs. 745 [IQR: 69 to 1,984] IU/l; p = 0.032)., Conclusions: Three distinct types of calcified culprit plaques are identified in patients with ACS. Superficial calcific sheet, which is frequently located in the left anterior descending coronary artery, is the most prevalent type and is also associated with greatest post-intervention myocardial damage. (Identification of Predictors for Coronary Plaque Erosion in Patients With Acute Coronary Syndrome; NCT03479723)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies suggest that conservative management with antithrombotic therapy without stenting may be an option in selected patients with acute coronary syndrome (ACS). We evaluated whether a glycoprotein IIb/IIIa inhibitor, tirofiban, would offer additional benefit in patients with plaque erosion presenting with ACS who were treated with antiplatelet therapy without stenting., Patients and Methods: Forty-nine patients who completed 1-year follow-up optical coherence tomography imaging in the EROSION study were divided into two groups: tirofiban (n=32) versus no tirofiban (n=17). Thrombus volume, thrombus burden, and the incidence of major adverse cardiovascular events were evaluated., Results: At baseline, the tirofiban group had similar thrombus volume [3.73 (1.27-12.49) vs. 3.51 (1.70-8.65) mm, P=0.983] and marginally greater thrombus burden [17.9 (10.1-26.1) vs. 10.6 (6.8-19.0)%, P=0.097]. At 1 month, the tirofiban group had smaller residual thrombus volume [0.00 (0.00-1.78) vs. 0.94 (0.07-4.20) mm, P=0.054], thrombus burden [0.0 (0.0-6.4) vs. 7.0 (1.8-14.8)%, P=0.024], and greater reduction of thrombus volume (85.4±24.6 vs. 67.1±27.1%, P=0.021). These differences were maintained up to 1 year. Complete resolution of thrombus at 1 month was more frequent in the tirofiban group (53.1 vs. 17.6%, P=0.031). None of the patients experienced major bleeding during the initial hospitalization. The 1-year major adverse cardiovascular events rate was not different (5.6 vs. 15.0%, P=0.336)., Conclusion: In patients with ACS caused by plaque erosion who were managed conservatively without stenting, tirofiban provided additional benefit in reducing residual thrombus without an increased risk for bleeding.

Background: Perilipin 2 (PLIN2) is a protein that potentially facilitates atherogenesis in native coronary arteries or arteries with an implanted drug-eluting stent (DES). The aim of the study was to determine PLIN2 protein levels in peripheral monocytes of enrolled subjects and compare them between patients with native coronary artery disease (CAD) and those with an in-stent restenosis (ISR) due to neoatherosclerosis occurring >1 year after DES implantation., Methods: Forty-two patients were prospectively enrolled in the study in 3:1 fashion and underwent coronary catheterization. Both groups were angiographically matched for CAD burden with respect to the number of diseased vessels. Neoatherosclerosis was determined by intracoronary optical coherence tomography (OCT) among patients with ISR., Results: Patients with ISR due to neoatherosclerosis had significantly higher PLIN2 protein levels in peripheral blood monocytes compared to patients with native CAD (342.47 ± 75.63[SE] versus 119.51 ± 20.95, p < 0.001). PLIN2 protein levels did not significantly differ between unstable and stable disease phenotype (125.59 ± 131.02 vs. 146.14 ± 111.87, p = 0.109)., Conclusions: In this explorative study, PLIN2 protein levels are significantly increased in patients with neoatherosclerosis, irrespective of clinical presentation, implicating that it might play a pathogenetic role in accelerated atherosclerosis after DES implantation. Further larger clinical studies are warranted to confirm these initial findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded., Methods and Results: We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients [mean age 63.0 ± 10.7 years, 40 (50%) male]. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0-60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause [12 (32.4%) vs. 2 (4.7%); P = 0.002], cardiac death [7 (18.9%) vs. 0 (0.0%); P = 0.005], and readmission for ACS [10 (27.0%) vs. 3 (7.0%); P = 0.015] as well as a worse angina status as assessed by SAQ [Seattle score: 88.0 (33.0-100.0) vs. 100.0 (44.0-100.0); P = 0.001] when compared with patients with a negative test., Conclusions: We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Plaque rupture (PR) represents the most common substrate of coronary thrombosis, in at least 50% of cases. Chronic low grade inflammation is a common background for atherosclerosis development; however, increased plaque inflammation may predispose by itself to PR. In the last decade, studies performed by optical coherence tomography (OCT) have allowed to establish the severity of plaque inflammation by assessing macrophage infiltration (MØI). Our retrospective study aimed at assessing the role of plaque inflammation in PR among patients with acute coronary syndrome (ACS) using OCT., Methods and Results: We enrolled 56 patients with ACS exhibiting PR at the site of the culprit stenosis identified by OCT. Patients were divided into two cohorts according to the presence of MØI at OCT analysis, defined as signal-rich, distinct, or confluent punctate regions that exceed the intensity of background speckle noise. Serum high-sensitivity C-reactive protein (CRP) was measured on admission by latex-enhanced immunophelometric assay. Thirty-seven (66%) patients had MØI at the site of PR, whereas 19 (34%) patients had no evidence of MØI. Patients with MØI showed a higher rate of CRP values >3 mg/dL as compared with those without MØI (92% vs. 47%, P = 0.004). In contrast, patients without MØI had a higher prevalence of hypertension compared with those with MØI (89% vs. 59%, P = 0.021). Furthermore, the group with MØI exhibited a significantly higher rate of lipid-rich plaques (86% vs. 50%, P = 0.008), a higher rate of multifocal disease (59% vs. 10%, P < 0.001), and an MØI in both culprit and remote lesions (97% vs. 0%, P < 0.001) compared with those without MØI. At multivariate analysis, CRP value >3 mg/dL was the only independent predictor of MØI in the culprit plaque (OR 8.72, 95% CI 1.78-41.67, P= 0.007)., Conclusions: In conclusion, PR can be caused by predominant inflammatory or non-inflammatory mechanisms, over a common low-grade chronic inflammatory background well known from pathology observations., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Background: Natriuretic peptides are diagnostic/prognostic biomarkers in major cardiovascular diseases. We aimed at assessing the predictive role of N-terminal pro-A-type (NT-proANP) and pro-B-type (NT-proBNP) natriuretic peptides levels toward cardiovascular outcome in both stable and unstable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in a non-primary PCI setting., Methods: A total of 395 patients undergoing PCI with stent implantation for either stable angina (SA) or non ST-elevation acute coronary syndrome (NSTE-ACS) were enrolled. Pre-procedural NT-proANP and NT-proBNP levels were measured. Occurrence of major adverse cardiac events (MACEs), composite of cardiac death, non-fatal myocardial infarction, and clinically driven target lesion revascularization (c-TLR), was the endpoint of the study. Follow up mean time was 48.53±14.69months., Results: MACEs occurred in forty-four patients (11%) during follow up. Both NT-proANP levels [3170 (2210-4630) vs 2283 (1314-3913) fmol/mL, p=0.004] and NT-proBNP levels [729 (356-1353) vs 511 (267-1006) fmol/mL, p=0.04] were significantly higher in patients with MACEs compared to patients without MACEs. Similar results were found when considering hard MACEs (myocardial infarction and cardiac death). NT-proANP levels were significantly higher in patients with c-TLR compared with patients without c-TLR [3705 (2766-5184) vs 2343 (1340-3960) fmol/mL, p=0.021]. At multivariate analysis, NT-proANP levels were a significant predictor of MACEs (HR 1.09, 95% CI 1.03-1.18, p=0.04). Kaplan-Meyer curves revealed that patients with elevated NT-proANP levels (>2.100fmol/mL) had a lower MACE free survival (p=0.003)., Conclusions: Both NT-proANP and NT-proBNP levels were higher in CAD patients experiencing MACEs following PCI in a non-primary setting. Notably, only NT-proANP levels significantly affected prognosis after PCI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Progression of coronary atherosclerosis (ATS) has clinical implications. Serum levels of γ-glutamyltransferase (GGT), a marker of oxidative stress, predict the risk of cardiovascular events. However, the role of GGT levels in the progression of coronary ATS has never been established., Materials and Methods: Consecutive patients undergoing two coronary angiographies (CAs) separated by at least 6 months were prospectively enrolled between May 2008 and June 2010. All patients were discharged on statins after the first CA. The severity and extent of coronary ATS were graded according to Bogaty's score, and the variation (Δ) in stenosis score and extent index between follow-up (S2 and E2) and basal values (S1 and E1) were calculated. Predictors of ΔS2-1 and ΔE2-1 were assessed among clinical and laboratory data, including GGT levels, analyzed as Δ between follow-up and basal values (ΔGGT2-1)., Results: We enrolled 100 consecutive patients (age 64±11 years, 68% men). Compliance with statin therapy was 100%. At multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔS2-1 (B=0.18, SE=0.07, P=0.05), with Δlow-density lipoprotein-cholesterol2-1 levels being of borderline statistical significance (P=0.07). On multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔE2-1 (B=0.32; SE=0.11; P=0.04), with active smoking habit and Δfibrinogen2-1 levels being of borderline statistical significance (P=0.08 and 0.06, respectively)., Conclusion: ΔGGT2-1 is associated with angiographic coronary ATS progression in patients with ischemic heart disease on statin treatment, suggesting that oxidative stress may be another therapeutic target for preventing ATS progression beyond that of lipid-lowering therapies.

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]

Introduction: Healed plaques, morphologically characterized by a layered phenotype, are frequently found in subjects with sudden cardiac death. However, in vivo data are lacking. Aim: To determine the prevalence, morphologic characteristics, and clinical significance of healed culprit plaques of patients with acute coronary syndrome (ACS) by using optical coherence tomography (OCT). Methods: A total of 376 ACS patients (252 ST-elevation MI and 124 non ST elevation ACS) who had undergone pre-intervention OCT imaging of the culprit lesion were enrolled. Patients were stratified according to the presence of layered phenotype, defined as layers of different optical density at OCT. Clinical, laboratory, OCT characteristics, and 1-year outcome were compared between the two groups. Results: Among 376 patients, 108 (28.7%) healed plaques were identified. Hyperlipidemia, diabetes, and history of myocardial infarction (MI) were more frequent in patients with healed plaques (44.4% vs 33.2%, p=0.041; 35.2% vs 23.5%, p=0.021; 15.7% vs 6.3%, p=0.009). High sensitive C-reactive protein was significantly higher in patients with healed plaques (4.98 [1.00-11.32] mg/L vs 3.00 [0.30-10.15] mg/L, p=0.029). Plaque rupture (64.8% vs 53.0%, p=0.039), TCFA (56.5% vs 42.5%, p=0.016) and macrophage accumulation (81.1% vs 63.4%, p=0.001) were common in the layered group. OCT also revealed greater area stenosis in plaques with layered phenotype [79.2±9.5% vs 74.3±14.3%, p=0.001]. The incidence of major adverse cardiovascular events was similar between the two groups, except that all cause rehospitalization rate was higher in the healed plaque group (32.7% vs. 16.5%, p=0.013). Conclusions: Healed plaques, a signature of prior plaque destabilization, were found at the culprit site in more than one quarter of ACS patients. Such patients were more frequently diabetic, hyperlipidemic, or had a history of MI. Healed plaques frequently showed OCT features of vulnerability with evidence of local and systemic inflammation. The combination of plaque vulnerability, local inflammation, and greater plaque burden in addition to systemic inflammation may outweigh the protective mechanism of plaque healing and predispose those plaques to develop occlusive thrombus. [ABSTRACT FROM AUTHOR]