Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Abstract-The plasminogen activator (PA) system, which controls the formation and activity of plasmin, plays a key role in modulating hemostasis, thrombosis, and several other biological processes. While a great deal is known about the function of the PA system, it remains a focus of intensive investigation, and the list of biological pathways and human diseases that are modulated by normal and pathologic function of its components continues to lengthen. Because of remarkable advances in molecular genetics, the laboratory mouse has become the most useful animal system to study the normal and pathologic functions of the PA system. The purpose of this review is to summarize studies that have used genetically modified mice to examine the functions of the PA system in hemostasis and thrombosis, intimal hyperplasia after vascular injury, and atherosclerosis. Particular emphasis is placed on the vascular functions of PA inhibitor-1, a key regulator of the PA system, and the multiple variables that appear to account for the complex role of PA inhibitor-1 in regulating vascular remodeling. Lastly, the strengths and limitations of using mice to model human vascular disease processes are discussed. (Arterioscler Thromb Vasc Biol.

With the expanded legalization of marijuana, its medical and recreational use have sharply increased over the past decade. A wide array of new forms of cannabis is available on the market today, and the potencies are ten times those of forms previously tested, meaning that the true impact of marijuana on the cardiovascular system remains unclear. Cannabis mainly exerts its effects via the sympathetic and parasympathetic nervous systems, with different doses affecting different cannabinoids receptors. Studies have shown that marijuana plays a role in thrombosis, inflammation, and atherosclerosis. Case reports have linked marijuana use to myocardial infarction, cardiac arrythmias, cardiomyopathies, stroke, and arteritis. Most patients are young, healthy men with no cardiovascular risk factors; however, the patient population is expected to change to include older individuals in the future. The widespread public perception of safety accompanying marijuana use has contributed to its increased use among the elderly, who are the most at risk population for acute cardiovascular events. In this review, we aim to provide a basic understanding of the physiological effects of marijuana on the cardiovascular system and to review the current literature regarding cardiovascular diseases linked to marijuana use in adults.

BackgroundControversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). Coronary artery bypass grafting (CABG) has been compared with percutaneous coronary intervention (PCI) using drug‐eluting stents (DES) in recent randomized controlled trials (RCTs).Methods and ResultsRCTs comparing PCI with DES versus CABG in diabetic patients with MVD who met inclusion criteria were analyzed (protocol registration No. CRD42013003693). Primary end point (major adverse cardiac events) was a composite of death, myocardial infarction, and stroke at a mean follow‐up of 4 years. Analyses were performed for each outcome by using risk ratio (RR) by fixed‐ and random‐effects models. Four RCTS with 3052 patients met inclusion criteria (1539 PCI versus 1513 CABG). Incidence of major adverse cardiac events was 22.5% for PCI and 16.8% for CABG (RR 1.34, 95% CI 1.16 to 1.54, P<0.0001). Similar results were obtained for death (14% versus 9.7%, RR 1.51, 95% CI 1.09 to 2.10, P=0.01), and MI (10.3% versus 5.9%, RR 1.44, 95% CI 0.79 to 2.6, P=0.23). Stroke risk was significantly lower with DES (2.3% versus 3.8%, RR 0.59, 95% CI 0.39 to 0.90, P=0.01) and subsequent revascularization was several‐fold higher (17.4% versus 8.0%, RR 1.85, 95% CI 1.0 to 3.40, P=0.05).ConclusionsThese data demonstrate that CABG in diabetic patients with MVD at low to intermediate surgical risk (defined as EUROSCORE <5) is superior to MVD PCI with DES. CABG decreased overall death, nonfatal myocardial infarction, and repeat revascularization at the expense of an increase in stroke risk.

Summary. Background: Vascular smooth muscle cell (VSMC) migration is a critical process in arterial remodeling. Purified plasminogen activator inhibitor-1 (PAI-1) is reported to both promote and inhibit VSMC migration on two-dimensional (D) surfaces. Objective: To determine the effects of PAI-1 and vitronectin (VN) expressed by VSMC themselves on migration through physiological collagen matrices. Methods: We studied migration of wild-type (WT), PAI-1-deficient, VN-deficient, PAI-1/VN doubly-deficient (DKO) and PAI-1-transgenic (Tg) VSMC through three-D collagen gels. Results: WT VSMC migrated significantly slower than PAI-1-and VN-deficient VSMC, but significantly faster than DKO VSMC. Experiments with recombinant PAI-1 suggested that basal VSMC PAI-1 expression inhibits migration by binding VN, which is secreted by VSMC and binds collagen. However, PAI-1-over-expressing Tg VSMC migrated faster than WT VSMC. Reconstitution experiments with recombinant PAI-1 mutants suggested that the pro-migratory effect of PAI-1 over-expression required its anti-plasminogen activator (PA) and LDL receptor-related protein (LRP) binding functions, but not VN binding. While promoting VSMC migration in the absence of PAI-1, VN inhibited the pro-migratory effect of active PAI-1. Conclusions: In isolation, VN and PAI-1 are each pro-migratory. However, via formation of a high-affinity, non-motogenic complex, PAI-1 and VN each buffers the otherÕs pro-migratory effect. The level of PAI-1 expression by VSMC and the concentration of VN in extracellular matrix are critical determinants of whether PAI-1 and VN promote or inhibit migration. These findings help to rectify previously conflicting reports and suggest that PAI-1/ VN stoichiometry plays an important role in VSMC migration and vascular remodeling.Keywords: collagen, PAI-1, vascular smooth muscle cell, vitronectin.Intimal hyperplasia is a central process in acquired vascular diseases, such as atherosclerosis and restenosis after balloon angioplasty. A key step in intimal hyperplasia is the migration of vascular smooth muscle cells (VSMC) from the media, through the extracellular matrix (ECM) composed of collagen, elastin and multiple other components, into the intima. The plasminogen activation (PA) system plays a major role in the regulation of cell migration and the development of intimal hyperplasia [1,2]. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of tissue-and urinary-type plasminogen activators (t-PA and u-PA, respectively) and a major regulator of fibrinolysis [3]. PAI-1 is present in plasma, platelets, endothelial cells, VSMC and the ECM. PAI-1 expression in the vascular wall is increased in several human vascular diseases characterized by neointima formation, suggesting that PAI-1 may regulate the development of intimal hyperplasia [4,5]. PAI-1 binds vitronectin (VN), an adhesive glycoprotein present in ECM that plays key roles in cell adhesion and migration [6,7]. Binding of PAI-1 inhibits VNÕs interactions with its receptors on VSMC, ...

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Viral myocarditis is inflammation of the myocardium secondary to viral infection. The clinical presentation of viral myocarditis is very heterogeneous and can range from nonspecific symptoms of malaise and fatigue in subclinical disease to a more florid presentation, such as acute cardiogenic shock and sudden cardiac death in severe cases. The accurate and prompt diagnosis of viral myocarditis is very challenging. Endomyocardial biopsy is considered to be the gold standard test to confirm viral myocarditis; however, it is an invasive procedure, and the sensitivity is low when myocardial involvement is focal. Cardiac imaging hence plays an essential role in the noninvasive evaluation of viral myocarditis. The current coronavirus disease 2019 (COVID-19) pandemic has generated considerable interest in the use of imaging in the early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related myocarditis. This article reviews the role of various cardiac imaging modalities used in the diagnosis and assessment of viral myocarditis, including COVID-19-related myocarditis.