Thrombotic Myocardial Infarction Research Articles

Characterization of myocardial injury phenotype by thermal liquid biopsy.

With the advent and implementation of high-sensitivity cardiac troponin assays, differentiation of patients with distinct types of myocardial injuries, including acute thrombotic myocardial infarction (TMI), acute non-thrombotic myocardial injury (nTMi), and chronic coronary atherosclerotic disease (cCAD), is of pressing clinical importance. Thermal liquid biopsy (TLB) emerges as a valuable diagnostic tool, relying on identifying thermally induced conformational changes of biomolecules in blood plasma. While TLB has proven useful in detecting and monitoring several cancers and autoimmune diseases, its application in cardiovascular diseases remains unexplored. In this proof-of-concept study, we sought to determine and characterize TLB profiles in patients with TMI, nTMi, and cCAD at multiple acute-phase time points (T 0 h, T 2 h, T 4 h, T 24 h, T 48 h) as well as a follow-up time point (Tfu) when the patient was in a stable state. TLB profiles were collected for 115 patients (60 with TMI, 35 with nTMi, and 20 with cCAD) who underwent coronary angiography at the event presentation and had subsequent follow-up. Medical history, physical, electrocardiographic, histological, biochemical, and angiographic data were gathered through medical records, standardized patient interviews, and core laboratory measurements. Distinctive signatures were noted in the median TLB profiles across the three patient types. TLB profiles for TMI and nTMi patients exhibited gradual changes from T0 to Tfu, with significant differences during the acute and quiescent phases. During the quiescent phase, all three patient types demonstrated similar TLB signatures. An unsupervised clustering analysis revealed a unique TLB signature for the patients with TMI. TLB metrics generated from specific features of TLB profiles were tested for differences between patient groups. The first moment temperature (TFM) metric distinguished all three groups at time of presentation (T0). In addition, 13 other TLB-derived metrics were shown to have distinct distributions between patients with TMI and those with cCAD. Our findings demonstrated the use of TLB as a sensitive and data-rich technique to be explored in cardiovascular diseases, thus providing valuable insight into acute myocardial injury events.

CMR Manifestations, Influencing Factors and Molecular Mechanism of Myocarditis Induced by COVID-19 Mrna Vaccine.

Although immunization with the 2019 coronavirus disease (COVID-19) mRNA vaccine is considered to be an effective measure to reduce the number of serious cases or deaths associated with COVID-19, rare cases of cardiac complications have been reported in the literature, encompassing acute myocardial injury, arrhythmia, vasculitis, endothelial dysfunction, thrombotic myocardial infarction and myocarditis. Interestingly, patients diagnosed with myocarditis after receiving the COVID-19 mRNA vaccine exhibit abnormal cardiac magnetic resonance (CMR) findings, suggesting CMR can be a valuable non-invasive diagnostic tool. In populations immunized with the COVID-19 mRNA vaccine, the risk in teenagers and young men is significantly higher. Myocardial injury in male patients is mainly myocarditis, while in female patients, myocarditis and pericardial effusion are predominantly found. Generally, the symptoms of myocarditis are relatively mild and complete recovery can be achieved. Moreover, the incidence rate associated with the second dose is significantly higher than with the first or third dose. This article brings together the latest evidence on CMR characteristics, influencing factors and pathogenesis of myocarditis caused by the COVID-19 mRNA vaccine. At the same time, we make recommendations for populations requiring immunization with the COVID-19 mRNA vaccine.

Acute ischemic stroke: a rare complication of hump-nosed pit viper (Hypnale spp.) bite: a case report

BackgroundHump-nosed pit viper is a medically important deadly venomous snake in Sri Lanka and is the commonest cause of venomous snakebites in the country. It frequently causes local effects and systemic manifestations such as acute kidney injury and coagulopathy that occur in less than 10% of all bites. This also includes some atypical presentations such as thrombotic microangiopathy and myocardial infarction. Currently, no antivenom is available for hump-nosed pit viper bites in Sri Lanka, and patients are managed with supportive treatment. This case illustrates an acute ischemic stroke following a hump-nosed viper bite, which is the second case in the literature.Case presentationA 71-year-old a Sinhalese male patient presented with left-sided hemiparesis with mouth deviation on day 2 of hump-nosed viper (Hypnale spp.) bite on the right foot. Non-contrast computed tomography of brain showed right ischemic stroke in internal capsule. He was given antiplatelets and statins and continued supportive treatment including limb physiotherapy and speech therapy. He recovered completely and was discharged on day 4 with clinic follow-up.ConclusionsPhysicians should be aware that ischemic cerebral infarcts may occur following hump-nosed pit viper bites.

Coronary Thrombosis after Rabbit-ATG in LTx Recipient

Introduction Rabbit anti-thymocyte globulin (rATG) is a polyclonal antibody that targets human T lymphocytes; it can be used as an induction agent at the time of lung transplant (LTx) or as treatment for steroid refractory allograft rejection. rATG-induced platelet activation and hypercoagulability has been reported. Herein, we report a case of acute thrombotic myocardial infarction (MI) after the first dose of rATG in an LTx recipient with steroid refractory rejection. Case Report The patient is a 60-year-old man with COPD who underwent a bilateral LTx in May 2018. He had an uneventful post-LTx course, but presented 18 months later with dyspnea and a 600-cc decline in FEV1. A CT scan of the chest showed diffuse bronchial thickening and a bronchoscopy with bronchoalveolar lavage and transbronchial biopsies showed rhinovirus, but no evidence of acute cellular rejection. Donor specific antibodies were absent. The patient was empirically treated with high-dose corticosteroids, but presented a month later with another 400-cc decline in FEV1, prompting admission and treatment with rATG for presumed steroid refractory rejection. During admission, his labs were remarkable for mild anemia and thrombocytosis (781 K/µL). Thirty minutes into his rATG infusion, the patient complained of shortness of breath, chest discomfort, diaphoresis, and right-arm numbness. The infusion was stopped. His labs revealed elevated troponin (0.382 ng/mL), and his EKG showed an ST elevation in leads II, III and aVF along with ST depression in leads I and aVL suggestive of inferior wall MI. Emergent cardiac catheterization and ventriculogram showed 100% occlusion of the mid-distal right coronary artery with heavy clot burden, inferior wall hypokinesis, and a mildly reduced ejection fraction. A drug-eluting stent was placed, which resulted in near resolution of ST elevation. Of note, his prior pre-LTx cardiac catheterization had no angiographic evidence of coronary artery disease (CAD). Summary rATG activates platelets and establishes a link between complement and coagulation cascades, which may explain the clinically observed phenomenon of rATG-induced hypercoagulability. To the best of our knowledge, this is the first report of rATG-induced coronary arterial thrombosis in an LTx recipient with no prior CAD, but with thrombocytosis at the time of rATG infusion.

Antiphospholipid syndrome and valvular heart disease, a complex scenario of thrombotic events, a case report

BackgroundAntiphospholipid syndrome (APS) is a rare coagulation disorder associated with thrombotic events, myocardial infarction, and valvular heart disease. During valvular replacement surgery, the high risk of thrombosis combined with the operative risks in these specific groups of patients poses a challenge to the medical team.Case presentationWe present a case of a female patient with APS and mixed aortic valve disease. During surgery, she suddenly developed complete cardiac arrest. Three months later, after she recovered, and while she was still on close follow up, a thrombotic event caused myocardial infarction. After prompt and precise treatment, the patient successfully recovered; one year after surgery patient is doing well.ConclusionAdequate surgical technique along with optimal anticoagulation strategies and long term follow up are of paramount importance to ensure an uneventful recovery. A multidisciplinary team is required to manage these complex scenarios and high-risk patients.

Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19.

AimsFollowing the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement.Methods and ResultsTwenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was <55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score –0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF <55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients.ConclusionsPancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.

Changes in characteristics and management among patients with ST-elevation myocardial infarction due to COVID-19 infection.

ObjectivesTo assess changes in characteristics and management among ST‐elevation myocardial infarction (STEMI) patients with coronavirus disease (COVID‐19) who underwent primary percutaneous coronary intervention.MethodsOur prospective, monocentric study enrolled all STEMI patients who underwent PPCI during the COVID‐19 outbreak (n = 83). This cohort was first compared with a previous cohort of STEMI patients (2008–2017, n = 1,552 patients) and was then dichotomized into a non‐COVID‐19 group (n = 72) and COVID‐19 group (n = 11).ResultsIn comparison with the pre‐outbreak period, patients during the outbreak period were older (59.6 ± 12.9 vs. 62.6 ± 12.2, p = .03) with a delayed seek to care (mean delay first symptoms‐balloon 3.8 ± 3 vs. .7.4 ± 7.7, p < .001) resulting in a two‐fold higher in‐hospital mortality (non COVID‐19 4.3% vs. COVID‐19 8.4%, p = .07). Among the 83 STEMI patients admitted during the outbreak period, 11 patients were infected by COVID‐19. Higher biological markers of inflammation (C‐reactive protein: 28 ± 39 vs. 98 ± 97 mg/L, p = .04), of fibrinolysis (D‐dimer: 804 ± 1,500 vs. 3,128 ± 2,458 μg/L, p = .02), and antiphospholipid antibodies in four cases were observed in the COVID‐19 group. In this group, angiographic data also differed: a thrombotic myocardial infarction nonatherosclerotic coronary occlusion (MINOCA) was observed in 11 cases (1.4% vs. 54.5%, p < .001) and associated with higher post‐procedure distal embolization (30.6% vs. 72.7%, p = .007). The in hospital mortality was significantly higher in the COVID‐19 group (5.6% vs. 27.3%, p = .016).ConclusionThe COVID‐19 outbreak implies deep changes in the etiopathogenesis and therapeutic management of STEMI patients with COVID‐19. The impact on early and long‐term outcomes of systemic inflammation and hypercoagulability in this specific population is warranted.

A novel experimental thrombotic myocardial infarction and primary angioplasty model in swine.

We sought to develop a reproducible animal model for acute myocardial infarction (AMI) in adult atherosclerosis-prone pigs. A coil was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolaemic pigs and left untreated until thrombotic occlusion. Then, we crossed the thrombotic occlusion with a guidewire, followed by predilatation, thrombus visualisation with optical coherence tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularisation, we calculated the index of microcirculatory resistance (IMR). After a feasibility phase (six animals), acute thrombotic occlusion was achieved in all 20 pigs. Eighteen animals were successfully revascularised and survived until sacrifice. Thrombus formation was confirmed by OCT, measurement of thrombin-antithrombin complexes and pathology examination. Myocardial necrosis was confirmed by troponin T elevation, myocardial staining and pathology examination. Distal thrombotic embolisation and microvascular obstruction were supported by increased IMR and pathology examination. A porcine model of thrombotic occlusion AMI in miniaturised adult spontaneously atherosclerosis-prone pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty completed this model which mirrors human pathological conditions with myocardial infarction, necrosis and distal embolisation.

A novel experimental thrombotic myocardial infarction and primary angioplasty model in atherosclerotic swine

We sought to develop a reproducible, percutaneous basic science and translational animal model for the generation of thrombotic occlusion acute myocardial infarction in adult atherosclerotic pigs. A vascular coil COOK TORNADO® 38 inches (3–3.5 × 20–50 mm) was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolemic pigs and left untreated until a thrombotic intracoronary occlusion was present. After the angiographic confirmation of total occlusion, we proceeded to crossing the newly formed thrombotic occlusion with a guidewire, followed by pre-dilatation with a semi compliant balloon, thrombus visualization with Optical Coherence Tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularization, we calculated the index of microcirculatory resistance (IMR) to estimate microvascular obstruction. AMI was confirmed by ECG, biochemical, histological, macroscopic examination and TTC imaging. After feasibility phase (6 animals), acute thrombotic occlusion was achieved in 20 pigs. In total, 18 were successful revascularized and survived until the previously selected time for sacrifice. Time to occlusion after coil placement was 69 ± 29 min, thrombus formation was confirmed by OCT, thrombin-antithrombin complexes (TAT) measurements and pathology examination. Myocardial necrosis by troponin I elevation, myocardial staining and pathology examination. Distal thrombotic embolization and microvascular obstruction were supported by increased IMR and pathology examination. Thrombotic occlusion AMI in miniaturized adult spontaneously atherosclerotic pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty mirrors human pathological conditions with myocardial infarction, necrosis and distal embolization. Our model closely simulates human presentation of AMI and can be used to evaluate antithrombotic agents and primary angioplasty techniques.

A novel porcine model of thrombotic myocardial infarction with cardiac dysfunction sensitive to dual antiplatelet therapy

Few effective porcine models of myocardial infarction (MI) related to platelet thrombus formation are available. In this study, we established a novel porcine MI model and examined the effect of dual antiplatelet therapy (DAPT) with aspirin and prasugrel, a P2Y12 antagonist, using this MI model. Thrombotic MI was photochemically induced using rose bengal. Male miniature pigs were divided into 3 treatment groups: Sham, MI, and DAPT. In the DAPT group, aspirin (10 mg/kg, p.o.) and prasugrel (1 mg/kg, p.o.) were administered 4 h before photo-irradiation. Platelet aggregation, MI volume, and cardiac function were evaluated 24 h after photo-irradiation. Inhibition of ADP-induced platelet aggregation in the DAPT group was about 45%, similar to the effects of DAPT in a clinical setting. No MI was observed in the Sham group, and MI volume was 12.9 ± 2.9% in the left ventricle (P = 0.0016) in the MI group. Additionally, an increase in end-systolic volume (P = 0.0006), and a decrease in stroke volume (P = 0.0001) and ejection fraction (P < 0.0001) were observed in the MI group compared to the Sham group without any changes in end-diastolic volume. DAPT significantly decreased MI volume (P = 0.0006) and ameliorated cardiac dysfunction compared to the MI group. In conclusion, a novel porcine model of thrombotic MI with cardiac dysfunction was established. In this model, DAPT decreased MI volume and ameliorated of cardiac dysfunction, suggesting that this porcine MI model could be useful for future research on MI and antithrombotic agents.

Wisdom of artificial crowds feature selection in untargeted metabolomics: An application to the development of a blood-based diagnostic test for thrombotic myocardial infarction

IntroductionHeart disease remains a leading cause of global mortality. While acute myocardial infarction (colloquially: heart attack), has multiple proximate causes, proximate etiology cannot be determined by a blood-based diagnostic test. We enrolled a suitable patient cohort and conducted a non-targeted quantification of plasma metabolites by mass spectrometry for developing a test that can differentiate between thrombotic MI, non-thrombotic MI, and stable disease. A significant challenge in developing such a diagnostic test is solving the NP-hard problem of feature selection for constructing an optimal statistical classifier. ObjectiveWe employed a Wisdom of Artificial Crowds (WoAC) strategy for solving the feature selection problem and evaluated the accuracy and parsimony of downstream classifiers in comparison with traditional feature selection techniques including the Lasso and selection using Random Forest variable importance criteria. Materials and methodsArtificial Crowd Wisdom was generated via aggregation of the best solutions from independent and diverse genetic algorithm populations that were initialized with bootstrapping and a random subspaces constraint. Results/ConclusionsStrong evidence was observed that a statistical classifier utilizing WoAC feature selection can discriminate between human subjects presenting with thrombotic MI, non-thrombotic MI, and stable Coronary Artery Disease given abundances of selected plasma metabolites. Utilizing the abundances of twenty selected metabolites, a leave-one-out cross-validation estimated misclassification rate of 2.6% was observed. However, the WoAC feature selection strategy did not perform better than the Lasso over the current study.

A Novel Porcine Model of Thrombotic Myocardial Infarction with Cardiac Dysfunction for the Evaluation of Antiplatelet Agents

A Novel Porcine Model of Thrombotic Myocardial Infarction with Cardiac Dysfunction for the Evaluation of Antiplatelet Agents

TCT-311 A novel experimental thrombotic myocardial infarction and primary angioplasty model in atherosclerotic swine

TCT-311 A novel experimental thrombotic myocardial infarction and primary angioplasty model in atherosclerotic swine

Circulating Prolidase Activity in Patients with Myocardial Infarction.

Collagen is a major determinant of atherosclerotic plaque stability. Thus, identification of differences in enzymes that regulate collagen integrity could be useful for predicting susceptibility to atherothrombosis or for diagnosing plaque rupture. In this study, we sought to determine whether prolidase, the rate-limiting enzyme of collagen turnover, differs in human subjects with acute myocardial infarction (MI) versus those with stable coronary artery disease (CAD). We measured serum prolidase activity in 15 patients with stable CAD and 49 patients with acute MI, of which a subset had clearly defined thrombotic MI (n = 22) or non-thrombotic MI (n = 12). Prolidase activity was compared across study time points (at cardiac catheterization, T0; 6 h after presentation, T6; and at a quiescent follow-up, Tf/u) in acute MI and stable CAD subjects. We performed subgroup analyses to evaluate prolidase activity in subjects presenting with acute thrombotic versus non-thrombotic MI. Although prolidase activity was lower at T0 and T6 versus the quiescent phase in acute MI and stable CAD subjects (p < 0.0001), it was not significantly different between acute MI and stable CAD subjects at any time point (T0, T6, and Tf/u) or between thrombotic and non-thrombotic MI groups. Preliminary data from stratified analyses of a small number of diabetic subjects (n = 8) suggested lower prolidase activity in diabetic acute MI subjects compared with non-diabetic acute MI subjects (p = 0.02). Circulating prolidase is not significantly different between patients with acute MI and stable CAD or between patients with thrombotic and non-thrombotic MI. Further studies are required to determine if diabetes significantly affects prolidase activity and how this might relate to the risk of MI.

Abstract 344: Comparative Metabolomic Profiling of Thrombotic Myocardial Infarction Reveals a Metabolic Signature Distinct From Non-Thrombotic Myocardial Infarction and Stable Coronary Artery Disease in Human Participants

Background: Current non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. Aim: The aim of this study is to identify change specific to plaque disruption and pathological thrombosis. Methods: We quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI and 15 stable CAD subjects at two acute phase [time of catheterization (T0), six hours (T6)] and one quiescent (&gt;3 months follow-up) time points. A statistical classifier was constructed utilizing (T0) abundances of a parsimonious set of metabolites that demonstrated a significant change between quiescent phase and the acute phase that was distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects. Results: Nineteen metabolites (Table 1) with an intra-subject fold change from time of acute thrombotic MI presentation to the quiescent state were distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate &lt;5%). Conclusions: We have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state and from acute non-thrombotic MI and stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.

Identification of a plasma metabolomic signature of thrombotic myocardial infarction that is distinct from non-thrombotic myocardial infarction and stable coronary artery disease.

AimsCurrent non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. The aim of this study was to identify changes specific to plaque disruption and pathological thrombosis that are distinct from acute myocardial necrosis.Methods and resultsWe quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing baseline (T0) abundances of a parsimonious set of 17 qualifying metabolites. Qualifying metabolites were those that demonstrated a significant change between the quiescent phase and the acute phase and that were distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at presentation.Nineteen metabolites demonstrated an intra-subject change from time of acute thrombotic MI presentation to the quiescent state that was distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate <5%).ConclusionsWe have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.

Systems characterization of differential plasma metabolome perturbations following thrombotic and non-thrombotic myocardial infarction

Myocardial infarction (MI) is an acute event characterized by myocardial necrosis. Thrombotic MI is caused by spontaneous atherosclerotic plaque disruption that results in a coronary thrombus; non-thrombotic MI occurs secondary to oxygen supply-demand mismatch. We sought to characterize the differential metabolic perturbations associated with these subtypes utilizing a systems approach. Subjects presenting with thrombotic MI, non-thrombotic MI and stable coronary artery disease (CAD) were included. Whole blood was collected at two acute time-points and at a time-point representing the quiescent stable disease state. Plasma metabolites were analyzed by untargeted UPLC-MS/MS and GC–MS. A weighted network was constructed, and modules were determined from the resulting topology. To determine perturbed modules, an enrichment analysis for metabolites that demonstrated between-group differences in temporal change across the disease state transition was then conducted. Biological significanceWe report evidence of metabolic perturbations of acute MI and determine perturbations specific to thrombotic MI. Specifically, a module characterized by elevated glucocorticoid steroid metabolites following acute MI showed greatest perturbation following thrombotic MI. Modules characterized by elevated pregnenolone metabolites, monoacylglycerols, and acylcarnitines were perturbed following acute MI. A module characterized by a decrease in plasma amino acids following thrombotic MI was differentially perturbed between MI subtypes.

Acute coronary syndrome in acute stroke

Elevated troponin levels are commonly found in patients with acute stroke and approximately 60 % of stroke patients suffer from an accompanying coronary artery disease. Troponin release can be caused either by an acute thrombotic myocardial infarction or by insufficient coronary perfusion due to neurocardiogenic causes like blood pressure or heart rate variability without thrombotic coronary occlusion. Due to the often unclear pathological cause of troponin release and the risk of secondary hemorrhage during dual antiplatelet therapy, the determination of the best time point for coronary diagnostics and therapy in stroke patients is a common challenge in clinical daily routine. Based on the current literature, we describe a potential diagnostic and therapeutic approach in stroke patients with increased troponin levels. First, the probability of an acute thrombotic myocardial infarction should be evaluated based on clinical, laboratory, and electrocardiographic parameters. In case of suspected myocardial infarction, a diagnostic coronary angiography/CT angiography should be performed and dual antiplatelet therapy should be given depending on the intracranial bleeding risk. In patients with high risk of intracranial bleeding, thrombus aspiration and balloon dilatation should be considered. In patients with acute stroke and elevated troponin levels, a thorough diagnostic workup is necessary to estimate the probability for a thrombotic myocardial infarction and to prevent cardiac and neurologic complications.

Thrombotic myocardial infarction with aspiration of large thrombi

Thrombotic myocardial infarction with aspiration of large thrombi

Hormonal contraceptives with ethinyl estradiol were associated with increased thrombotic stroke and MI

QUESTION Are hormonal contraceptives associated with increased risk for thrombotic stroke or myocardial infarction (MI)? METHODS DESIGN Population-based cohort study with linkage of 4 national registries between 1995 and 2009. SETTING Denmark. PARTICIPANTS 1 626 158 women 15 to 49 years of age. Exclusion criteria included past venous or arterial thrombotic event; past gynecologic breast lung abdominal or hematologic cancer; or past hysterectomy sterilization bilateral oophorectomy or 2 unilateral oophorectomies. Data were censored during pregnancies. RISK FACTORS Filled prescriptions for hormonal contraceptives. Analyses were adjusted for age; education (level and duration); calendar year; and use of medications for hypertension heart disease diabetes and hyperlipidemia. OUTCOMES Thrombotic stroke and MI identified through diagnostic codes in the National Registry of Patients and the Register of Causes of Death. MAIN RESULTS 3311 (0.2%) women had a thrombotic stroke and 1725 (0.1%) had an MI during 14 251 063 woman-years of follow-up. Thrombotic stroke. Incidence in nonusers was 24 per 100 000 woman-years (2260 events). Levonorgestrel intrauterine devices (IUDs) were associated with reduced risk (adjusted relative risk [aRR] 0.73 95% CI 0.54 to 0.98); progestin-only pills or implants were not associated with increased risk (aRR range 0.44 to 1.4). Two of three 20-microg ethinyl estradiol formulations six of seven 30- to 40-microg formulations and one of two 50-microg formulations were associated with increased risk (aRR range 1.5 to 2.3) (Table). The vaginal ring was associated with increased risk (aRR 2.5 CI 1.4 to 4.4). MI. Incidence in nonusers was 13 per 100 000 woman-years (1228 events). Progestin-only interventions were not associated with increased risk (aRR range 0 to 2.1). One 20-microg ethinyl estradiol formulation five 30- to 40-microg formulations and both 50-microg formulations were associated with increased risk (aRR range 1.6 to 4.3) (Table). The vaginal ring was not associated with increased risk. Data were insufficient to evaluate hormonal contraceptives given in a patch. CONCLUSION Oral hormonal contraceptives containing ethinyl estradiol were associated with increased risk for thrombotic stroke and myocardial infarction.Association between prescription for hormonal contraceptives and thrombotic stroke or MI*OutcomesHormonal contraceptivesRRdagger (95% CI)Thrombotic strokeEthinyl estradiol 20 microg plus progestindouble dagger1.6 (1.4 to 1.9)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.8 (1.6 to 1.9)Ethinyl estradiol 50 microg plus progestin||2.0 (1.5 to 2.7)MIEthinyl estradiol 20 microg plus progestindouble dagger1.4 (1.1 to 1.8)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.9 (1.7 to 2.1)Ethinyl estradiol 50 microg plus progestin||3.7 (2.8 to 5.0)*MI = myocardial infarction; RR = risk ratio; CI defined in Glossary.daggerAdjusted for progestin type age and calendar year. Risk > 1.0 indicates increased risk associated with hormonal contraceptive use. P = 0.24 for dose trend in thrombotic stroke; P < 0.001 for dose trend in MI.double daggerProgestin = desogestrel gestodene or drospirenone. section signProgestin = norethindrone levonorgestrel norgestimate desogestrel gestodene drospirenone or cyproterone acetate.||Progestin = norethindrone or levonorgestrel.