Management of Acute Myocardial Infarction During the COVID-19 Pandemic.

The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with COVID-19. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating a ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option

Inflammation and In-Stent Restenosis: The Role of Serum Markers and Stent Characteristics in Carotid Artery Stenting

BACKGROUND: Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography. METHODS: We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up. RESULTS: Over a median of 33.4 months follow-up (IQR: 14.9-53.7) of 210 procedures (mean age of 67.9±9.7 years, 71.9% male, 71.0% symptomatic) an ISR of ≥70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4-17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02-1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05-1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09-0.84, p = 0.010). CONCLUSIONS: The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR

Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation

Dedifferentiation, migration, and proliferation of resident vascular smooth muscle cells (SMCs) are key components of neointima formation after vascular injury. Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in this process, but the complex regulation of STAT3-dependent genes and the functional significance of inhibiting this pathway during the development of vascular proliferative diseases remain elusive. In this study, we demonstrate that STAT3 was activated in neointimal lesions following wire-induced injury in mice. Phosphorylation of STAT3 induced trans-activation of cyclin D1 and survivin in SMCs in vitro and in neointimal cells in vivo, thus promoting proliferation and migration of SMCs as well as reducing apoptotic cell death. WP1066, a highly potent inhibitor of STAT3 signaling, abrogated phosphorylation of STAT3 and dose-dependently inhibited the functional effects of activated STAT3 in stimulated SMCs. The local application of WP1066 via a thermosensitive pluronic F-127 gel around the dilated arteries significantly inhibited proliferation of neointimal cells and decreased the neointimal lesion size at 3 weeks after injury. Even though WP1066 application attenuated the injury-induced up-regulation of the chemokine RANTES at 6 h after injury, there was no significant effect on the accumulation of circulating cells at 1 week after injury. In conclusion, these data identify STAT3 as a key molecule for the proliferative response of SMC and neointima formation. Moreover, inhibition of STAT3 by the potent and specific compound WP1066 might represent a novel and attractive approach for the local treatment of vascular proliferative diseases

Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms. Methods and Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-$\alpha$ and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs. Conclusions: Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes

EGb761, a Ginkgo Biloba Extract, Is Effective Against Atherosclerosis In Vitro, and in a Rat Model of Type 2 Diabetes

BACKGROUND: EGb761, a standardized Ginkgo biloba extract, has antioxidant and antiplatelet aggregation and thus might protect against atherosclerosis. However, molecular and functional properties of EGb761 and its major subcomponents have not been well characterized. We investigated the effect of EGb761 and its major subcomponents (bilobalide, kaemferol, and quercetin) on preventing atherosclerosis in vitro, and in a rat model of type 2 diabetes. METHODS AND RESULTS: EGb761 (100 and 200 mg/kg) or normal saline (control) were administered to Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, for 6 weeks (from 3 weeks before to 3 weeks after carotid artery injury). Immunohistochemical staining was performed to investigate cell proliferation and apoptosis in the injured arteries. Cell migration, caspase-3 activity and DNA fragmentation, monocyte adhesion, and ICAM-1/VCAM-1 levels were explored in vitro. Treatment with EGb761 dose-dependently reduced intima-media ratio, proliferation of vascular smooth muscle cells (VSMCs) and induced greater apoptosis than the controls. Proliferation and migration of VSMCs in vitro were also decreased by the treatment of EGb761. Glucose homeostasis and circulating adiponectin levels were improved, and plasma hsCRP concentrations were decreased in the treatment groups. Caspase-3 activity and DNA fragmentation increased while monocyte adhesion and ICAM-1/VCAM-1 levels decreased significantly. Among subcomponents of EGb761, kaemferol and quercetin reduced VSMC migration and increased caspase activity. CONCLUSIONS: EGb761 has a protective role in the development of atherosclerosis and is a potential therapeutic agent for preventing atherosclerosis

An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel

Purpose: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. Methods: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. Results: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. Conclusion: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel crosssection and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options. © 2014 Curtin, Zhou