Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P = 0.62 and P = 0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.).

Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo.

AIMS: The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leukocyte activation but impair endothelialization, delaying effective device integration into arterial walls. Previously, we have shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leukocyte homeostasis and arterial healing. Furthermore, we have shown that a soluble synthetic peptide (known as P8RI) acts like a CD31 agonist. The aim of this study was to evaluate the effect of CD31-mimetic metal stent coating on the in vitro adherence of endothelial cells (ECs) and blood elements and the in vivo strut coverage and neointimal growth. METHODS AND RESULTS: We produced Cobalt Chromium discs and stents coated with a CD31-mimetic peptide through two procedures, plasma amination or dip-coating, both yielding comparable results. We found that CD31-mimetic discs significantly reduced the extent of primary human coronary artery EC and blood platelet/leukocyte activation in vitro. In vivo, CD31-mimetic stent properties were compared with those of DES and BMS by coronarography and microscopy at 7 and 28 days post-implantation in pig coronary arteries (n = 9 stents/group/timepoint). Seven days post-implantation, only CD31-mimetic struts were fully endothelialized with no activated platelets/leukocytes. At day 28, neointima development over CD31-mimetic stents was significantly reduced compared to BMS, appearing as a normal arterial media with the absence of thrombosis contrary to DES. CONCLUSION: CD31-mimetic coating favours vascular homeostasis and arterial wall healing, preventing in-stent stenosis and thrombosis. Hence, such coatings seem to improve the metal stent biocompatibility.

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis: A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).

BACKGROUND: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. METHODS: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. RESULTS: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. CONCLUSIONS: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.

Bioreactivity of stent material: Activation of platelets, coagulation, leukocytes and endothelial cell dysfunction in vitro.

Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants. Platelet adhesion was quantified in static and flow conditions. Thrombin generation was performed using the calibrated automated thrombogram. Neutrophil adhesion and formation of extracellular traps were visualized by scanning electron microscopy and by immunofluorescence. The phenotype of endothelial cells grown on CoCr was analyzed using specific antibodies, whereas the procoagulant potential was analyzed by measuring thrombin generation and protein C activation. Our results show that human blood platelets adhere to and are activated on CoCr in static and flow conditions. Overall, CoCr significantly induced thrombin generation in the presence or absence of platelets by 1.5- and 4.8-fold, respectively, involving activation of the contact pathway and activation of platelets. CoCr triggered leukocyte adhesion and behaved as a scaffold for the formation of neutrophil extracellular traps in the presence of platelets. Endothelial cells adhered and formed a monolayer covering CoCr. However, they switched from an anticoagulant phenotype to a procoagulant one with a significant 2.2-fold increase in thrombin generation due to a combined 30% reduced capacity to trigger protein C activation and 30% increased expression of tissue factor. Moreover, endothelial cells grown on CoCr acquired an inflammatory phenotype as indicated by the increased expression of ICAM-1 and VCAM-1. These data show that bare CoCr is prothrombotic and proinflammatory due to its capacity to activate platelets and coagulation and to induce leukocyte adhesion and activation. More importantly, even if endothelialization is achievable, the switch in endothelial phenotype prevents effective healing. Furthermore, we propose our methodology for future preclinical in vitro evaluation of the thrombogenicity of stent materials.

Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.

BACKGROUND: Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. METHODS: Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin-eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. RESULTS: Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm(2) vs. late: 2485 ± 1778 per mm(2); P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm(2) vs. late: 1428 ± 1023 per mm(2); P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. CONCLUSION: In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.

Impact of diabetes mellitus and metabolic syndrome on acute and chronic on-clopidogrel platelet reactivity in patients with stable coronary artery disease undergoing drug-eluting stent placement.

BACKGROUND: Previous studies, which compared the prevalence of high on-clopidogrel platelet reactivity (HCPR) in type 2 diabetes mellitus (T2DM) versus non-T2DM and obese versus nonobese patients provided conflicting results. METHODS: We compared the prevalence of HCPR in patients with T2DM, metabolic syndrome (MS), or neither T2DM nor MS undergoing drug-eluting stent implantation for stable coronary artery disease. Platelet functions were measured after a 600-mg clopidogrel loading dose and after 4 months on clopidogrel 75 mg/d. RESULTS: The prevalence of HCPR was significantly higher in 63 T2DM and 50 MS patients than in 43 patients with neither T2DM nor MS (46.0% and 52.0% vs 20.9%) after clopidogrel loading dose, whereas, at 4 months, only T2DM patients had a significantly higher prevalence of HCPR (50.8% and 31.3% vs 23.8%). By multivariable analysis, T2DM (odds ratio [OR] 3.62, 95% CI, 1.34-9.80, P = .011), MS (OR 4.00, 95% CI 1.39-11.46, P = .010), and previous chronic treatment with clopidogrel (OR 0.22, 95% CI 0.09-0.49; P < .001) were the main independent predictors of HCPR after clopidogrel loading dose, whereas only T2DM (OR 2.98, 95% CI 1.20-7.41, P = .017) was an important independent predictor of HCPR at 4 months. CONCLUSIONS: Both MS and T2DM were independent predictors of HCPR after clopidogrel loading dose. On clopidogrel maintenance therapy, only T2DM remained an independent predictor. This observation may be clinically relevant in the current era of antiplatelet therapy.

Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography.

Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.

Coronary artery disease and risk of major vascular events after cerebral infarction.

BACKGROUND AND PURPOSE: The impact of asymptomatic coronary artery disease on the risk of major vascular events in patients with cerebral infarction is unknown. METHODS: Four hundred five patients with acute cerebral infarction underwent carotid, femoral artery, thoracic, and abdominal aorta ultrasound examination. Of 342 patients with no known coronary heart disease, 315 underwent coronary angiography. We evaluated the 2-year risk of major vascular events (myocardial infarction, resuscitation after cardiac arrest, hospitalization for unstable angina or heart failure, stroke, or major peripheral arterial disease events) in patients with known coronary heart disease (n=63), and in the no known coronary heart disease group (n=315) as a function of coronary angiographic status (n=315). RESULTS: At 2 years, the estimated risk of major vascular events was 11.0% (95% confidence interval, 8.2-14.7). According to baseline coronary angiography, estimated risk was 3.4% in patients with no coronary artery disease (n=120), 8.0% with asymptomatic coronary artery stenosis <50% (n=113), 16.2% with asymptomatic coronary artery stenosis ≥ 50% (n=81), and 24.1% with known coronary heart disease (P<0.0001). Using no coronary artery disease as the reference, the age- and sex-adjusted hazard ratio (95% confidence interval) of vascular events was 2.10 (0.63-6.96) for asymptomatic coronary stenosis <50%, 4.36 (1.35-14.12) for asymptomatic coronary stenosis ≥ 50%, and 6.86 (2.15-21.31) for known coronary artery disease. CONCLUSIONS: In patients with nonfatal cerebral infarction, presence and extent of asymptomatic stenoses on coronary angiography are strong predictors of major vascular events within 2 years.

Platelet glycoprotein VI dimerization, an active process inducing receptor competence, is an indicator of platelet reactivity.

OBJECTIVE: The immune receptor homologue glycoprotein VI (GPVI)/FcR receptor γ chain complex is primarily responsible for platelet activation by collagen. There is growing evidence that optimal binding of GPVI to collagen depends on the assembly of GPVI dimers. The valence of GPVI on resting platelets needs to be clearly established because platelet avidity for collagen would be greater if GPVI is constitutively expressed as a dimer than as a monomer. METHODS AND RESULTS: Using a monoclonal antibody (9E18) that preferentially binds to GPVI dimers, we found that GPVI was maintained in a monomeric form on human resting platelets under the control of intraplatelet cAMP concentration. Activation by soluble agonists or von Willebrand factor induced a shift toward GPVI dimerization related to increased platelet adhesion to collagen. A correlation between platelet binding of 9E18 and P-selectin exposure was observed in patients experiencing coronary artery disease, and antagonists of the ADP receptor P2Y12 limited ADP-induced GPVI dimerization. CONCLUSION: The rapid assembly of highly competent dimers of GPVI at sites of vascular lesion represents an important step in the sequence of events leading to platelet activation by collagen. GPVI dimers could represent a new marker to analyze platelet reactivity.

In vitro and in vivo evidence for the role of elastase shedding of CD163 in human atherothrombosis.

AIMS: CD163 is a macrophage receptor for haemoglobin-haptoglobin (Hb-Hp) complexes, responsible for the clearance of haemoglobin. We hypothesized that production of soluble CD163 (sCD163) may be due to proleolytic shedding of membrane CD163 by neutrophil elastase, reported to be increased in culprit atherosclerotic plaques. We analysed the relationship between CD163 solubilization and elastase in vitro, in macrophage culture, ex vivo in human atherosclerotic plaque samples, and in vivo, in plasma of patients with coronary artery disease. METHODS AND RESULTS: Neutrophil elastase was shown to enhance CD163 shedding and to decrease the uptake of Hb-Hp complexes by cultured macrophages. In addition, cultured carotid endarterectomy samples showing features of intraplaque haemorrhage released more sCD163 and elastase/α1-antitrypsin (α1-AT) complexes than non-haemorrhagic plaques (n= 44). Plasma levels of sCD163 and neutrophil elastase (complexed with α1-AT) were measured in patients with an acute coronary syndrome (ACS, n= 42), stable angina pectoris (SAP, n= 28), or normal coronary angiograms without subclinical atherosclerosis (n= 21). Acute coronary syndrome patients had higher sCD163 and elastase/α1-AT complexes plasma concentrations than subjects without coronary atherosclerosis. Circulating sCD163 and elastase/α1-AT complexes were positively correlated in patients with ACS (r = 0.56, P< 0.0002) and SAP (r = 0.62, P< 0.0005). CONCLUSION: Our results suggest that neutrophil elastase promotes CD163 shedding, resulting in a decreased clearance of Hb by macrophages, which may favour plaque destabilization. This may be reflected by increased plasma levels of sCD163 and elastase/α1-AT complexes which are positively correlated in patients with coronary artery disease.

Clinical Significance of Culprit Vessel Occlusion in Patients With Non-ST-Elevation Myocardial Infarction Who Underwent Percutaneous Coronary Intervention.

In patients with non-ST-elevation myocardial infarction (NSTEMI), total occlusion of the culprit coronary artery (OCA) is not uncommon. We sought to determine the frequency and clinical impact of OCA at presentation in a large population of patients presenting with NSTEMI and who underwent systematic early invasive management. We performed a post hoc analysis of the TAO (Treatment of Acute Coronary Syndrome with Otamixaban) randomized trial, which included patients with NSTEMI with systematic coronary angiography within 72 hours. We compared the baseline characteristics and outcomes of patients according to whether the culprit vessel was occluded (thrombolysis in myocardial infarction flow grade [TFG] 0 to 1) or patent (TFG 2 to 3) at presentation. A total of 7,473 patients with NSTEMI with only 1 culprit lesion identified were enrolled, of whom 1,702 patients had OCA (22.8%). In the OCA group, coronary angiography was performed earlier (18 ± 15 vs 20 ± 16 hours, p <0.01), the culprit lesion was less likely to be the left anterior descending artery (26.5% vs 41.4%, p <0.001) but with more frequent angiographic thrombus (49.9% vs 22.7%, p <0.01). Culprit artery percutaneous coronary intervention during the index procedure was also more frequent (88.5% vs 78.1%, p <0.001) but with a lower rate of TFG grade 3 after the procedure and higher subsequent peak troponin I levels (8.3 ± 13.6 µg/L vs 5.6 ± 11.9 µg/L, p <0.001). At day 7, patients with OCA had higher mortality, and this persisted after adjustment on gender, Grace risk score, cardiovascular risk factors, and culprit vessel location (0.9% vs 0.4%, p = 0.02; adjusted odds ratio [OR] = 2.55, 95% confidence interval [CI] 1.23 to 5.29, p = 0.01). The absolute difference of mortality was maintained through 30 days: 1.2% versus 0.8%, p = 0.13; OR: 1.72, 95% CI 0.97 to 3.05, but mortality rates were similar by 180 days: 1.5% versus 1.6%, p = 0.8, adjusted OR = 1.11, 95% CI 0.69 to 1.80, p = 0.66. In conclusion, a significant proportion of patients with NSTEMI have a totally occluded culprit vessel at presentation. These patients are at higher risk of early mortality but not at 6 months.

Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases.

AIMS: P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations. METHODS AND RESULTS: Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at 'baseline' with P947-enhanced MRI. Atherosclerotic rabbits were divided into three groups: five rabbits were sacrificed ('baseline' group); five rabbits continued to be fed a lipid-supplemented diet ('high-fat' group); and five rabbits were switched from atherogenic to a purified chow diet ('low-fat' group). Four months later, a second P947-enhanced MRI was acquired in the 10 remaining rabbits. A significantly lower signal was detected in the aortic wall of rabbits from the 'low-fat' group as compared with rabbits from the 'high-fat' group (21 ± 6 vs. 46 ± 3%, respectively; P = 0.04). Such differences were not detected with the contrast agent P1135, which lacks the MMP-specific peptide sequence. In addition, the intensity of aortic wall enhancement detected with MRI after injection of P947 strongly correlated with actual MMP-2 gelatinolytic activity measured in corresponding aortic segments using zymography (r = 0.87). CONCLUSION: P947-enhanced MRI can distinguish dietary-induced variations in MMP-related enzymatic activity within plaques in an experimental atherosclerotic model, supporting its utility as a clinical imaging tool for in vivo detection of arterial wall remodelling.

[Clinical characteristics, management and prognostic evolution of patients admitted within six hours of symptom onset with st-segment elevation acute myocardial infarction complicated by cardiogenic shock : twenty year monocentric study]. / Évolution des caractéristiques cliniques, de la prise en charge et du pronostic des patients admis en choc cardiogénique au cours des six premières heures d'un infarctus du myocarde. Vingt ans d'expérience monocentrique.

BACKGROUND: Cardiogenic shock is one of the most serious complications of the acute myocardial infarction. Advances in interventional cardiology and early reperfusion strategy improved its management. AIM: Analysis of the clinical characteristics, management and prognostic evolution of patients admitted within 6 hours onset with ST-segment elevation acute myocardial infarction complicated by cardiogenic shock. METHODS: Follow-up study based on 2200 consecutive patients admitted with STEMI within 6 hours of symptom onset from 1988 to 2008. Among them 114 matched the criteria of cardiogenic shock. These were divided in two groups, according to the period: group 1 (N=57, among the first 1100 STEMI from 1988 to 1998) and group 2 (N=57, among the following 1100 STEMI from 1999 to 2008). RESULTS: This trial shows a similar rate of cardiogenic shock in STEMI (5%) in both 1100 patients groups. There is no overall change in patient's clinical characteristics, but improvements in earlier management, prehospital fibrinolysis and ventricular fibrillation treatment have been detected. Primary percutaneous coronary intervention was the most common revascularisation strategy. The proportion of patients achieving acute TIMI-3 flow in the infarct related artery increased (61% vs 80%, p= 0.11) but the mortality was still high (74% vs 63%, p= 0.22). CONCLUSION: The clinical characteristics of cardiogenic shock remain unchanged; its management is more successful with more often early reperfusion. The decline of mortality is unfortunately not significant. More aggressive treatment should probably be considered to improve outcomes.

Complete Revascularization vs Culprit Lesion-Only Percutaneous Coronary Intervention for Angina-Related Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction: Results From the COMPLETE Randomized Clinical Trial.

Importance: In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown. Objective: To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD. Design, Setting, and Participants: This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021. Interventions: Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization. Main Outcomes and Measures: Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end. Results: Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02). Conclusions and Relevance: In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.

Prevalence of coronary atherosclerosis in patients with cerebral infarction.

BACKGROUND AND PURPOSE: there is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease. METHODS: we consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6-11) after stroke onset. RESULTS: coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5-67.3) and coronary stenoses ≥ 50% were found in 25.7% (95% CI, 20.9-30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%. CONCLUSIONS: there is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.

Use of risk scores to identify lower and higher risk subsets among COMPASS-eligible patients with chronic coronary syndromes. Insights from the CLARIFY registry.

BACKGROUND: The COMPASS trial showed a reduction of ischemic events with low-dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding. HYPOTHESIS: The CHA2 DS2 VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade-off between ischemic and bleeding events, among COMPASS-eligible patients. METHODS: We identified the COMPASS-eligible population within the CLARIFY registry (>30.000 patients with CCS). High-bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0-1) or high (≥ 2) CHA2 DS2 VaSc; low (0-12) or intermediate (13-19) REACH RIS, and low (0-6) or intermediate (7-10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion). RESULTS: The COMPASS-eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1-2.5) and 0.5 (0.4-0.6) per 100 patient-years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6-3.4]) with similar bleeding risk (0.5 [0.4-0.7]) as the overall population. Patients with low CHA2 DS2 VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3-1.3]) with similar bleeding risk (0.5 [0.2-1.1]). CONCLUSIONS: Intermediate REACH RIS identified potential optimal candidates for adjunction of low-dose rivaroxaban while patients with low CHA2 DS2 VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.

Leukotriene receptor antagonism and the prevention of extracellular matrix degradation during atherosclerosis and in-stent stenosis.

OBJECTIVE: The lipid-derived inflammatory mediators leukotrienes (LTs) are produced during vascular injury. The aim of the present study was to determine the role of LT receptor signaling in the pathophysiology of in-stent stenosis. METHODS AND RESULTS: New Zealand White rabbits were fed 0.3% cholesterol and subjected to angioplasty with balloon dilatation and stent implantation in the right carotid artery. Rabbits treated for 2 weeks with the BLT receptor antagonist BIIL284 (3 mg/kg once daily by oral gavage) displayed a significantly reduced in-stent intimal hyperplasia in carotid arteries compared with vehicle-treated rabbits. In addition, BIIL284 treatment significantly reduced the extracellular matrix metalloproteinase (MMP)-2 and MMP-9 activities in stented arteries. The inhibited MMP-9 activity was correlated with decreased macrophage content in the lesions. The LTB(4)-induced migration of vascular smooth muscle cells was significantly inhibited by transfection with siRNA against MMP-2. Finally, human arteries subjected to ex vivo angioplasty and stent implantation displayed an increased in-stent intimal hyperplasia and higher MMP-2 and -9 activities in the presence of LTB(4). CONCLUSIONS: These results suggest a key role of LT signaling in the extracellular matrix degradation associated with hyperlipidemia and in-stent stenosis. In conclusion, targeting LT receptors may represent a therapeutic strategy in atherosclerosis and interventional cardiology.

Case report of anterior ST-elevation myocardial infarction in a patient with coronavirus disease-2019.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is an infectious disease appeared in China in December 2019 and, since then, has spread worldwide at a rapid pace. CASE SUMMARY: A patient with COVID-19 was hospitalized in our institution for a diabetic foot ulcer and presented afterwards a pulmonary oedema and concomitant anterior ST-segment elevation myocardial infarction. We report here on the initial presentation, coronary care and intervention, and clinical course of this patient. DISCUSSION: Emergent percutaneous coronary intervention is feasible and safe in COVID-19 patients but requires a multidisciplinary effort involving caregivers from infectious disease, intensive care, and cardiology teams.

Nonculprit Lesion Severity and Outcome of Revascularization in Patients With STEMI and Multivessel Coronary Disease.

BACKGROUND: In the COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial, angiography-guided percutaneous coronary intervention (PCI) of nonculprit lesions with the aim of complete revascularization reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (MI) and multivessel coronary artery disease. OBJECTIVES: The purpose of this study was to determine the effect of nonculprit-lesion stenosis severity measured by quantitative coronary angiography (QCA) on the benefit of complete revascularization. METHODS: Among 4,041 patients randomized in the COMPLETE trial, nonculprit lesion stenosis severity was measured using QCA in the angiographic core laboratory in 3,851 patients with 5,355 nonculprit lesions. In pre-specified analyses, the treatment effect in patients with QCA stenosis ≥60% versus <60% on the first coprimary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization was determined. RESULTS: The first coprimary outcome was reduced with complete revascularization in the 2,479 patients with QCA stenosis ≥60% (2.5%/year vs. 4.2%/year; hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47 to 0.79), but not in the 1,372 patients with QCA stenosis <60% (3.0%/year vs. 2.9%/year; HR: 1.04; 95% CI: 0.72 to 1.50; interaction p = 0.02). The second coprimary outcome was reduced in patients with QCA stenosis ≥60% (2.9%/year vs. 6.9%/year; HR: 0.43; 95% CI: 0.34 to 0.54) to a greater extent than patients with QCA stenosis <60% (3.3%/year vs. 5.2%/year; HR: 0.65; 95% CI: 0.47 to 0.89; interaction p = 0.04). CONCLUSIONS: Among patients with ST-segment elevation MI and multivessel coronary artery disease, complete revascularization reduced major CV outcomes to a greater extent in patients with stenosis severity of ≥60% compared with <60%, as determined by quantitative coronary angiography.