Thrombosis within the left anterior descending coronary artery and left ventricle after high-dose nitrous oxide use.

We present a man in his 30s with acute anterior myocardial infarction due to thrombotic occlusion of the left anterior descending artery and subsequent left ventricular thrombus formation after high-dose recreational use of nitrous oxide (N2O). Initial questioning for use of illicit substances was negative, but low vitamin B12 levels and severely elevated homocysteine levels prompted us to interrogate for the use of laughing gas. On questioning, the patient admitted to have used this substance, which he presumed to be innocent. Neither percutaneous coronary intervention with balloon dilatation nor intravenous glycoprotein IIb/IIIa receptor antagonist, nor continuous use of anticoagulation and double antiplatelet therapy resulted in thrombus resolution. Due to a severely reduced left ventricular function, despite 3 months on heart failure therapy, the patient is being counselled for intracardiac defibrillator implantation. We conclude that N2O, notably when consumed in conjunction with other proatherogenic substances, is associated with thrombosis: a relation possibly mediated by severe hyperhomocysteinaemia.

New Insights into Mechanisms of Action for Omega-3 Fatty Acids in Atherothrombotic Cardiovascular Disease.

PURPOSE OF REVIEW: Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates. The purpose of this review is to evaluate mechanisms related to the potential benefits of omega-3 fatty acids in atherothrombotic disease. RECENT FINDINGS: Large randomized clinical trials are currently under way to test the cardiovascular benefits of omega-3 fatty acids at a pharmacologic dosage (4 g/day). A large randomized trial with a prescription EPA-only formulation was shown to reduce a composite of cardiovascular events by 25% in statin-treated patients with established cardiovascular disease or diabetes and other CV risk factors. EPA and DHA have distinct tissue distributions as well as disparate effects on membrane structure and lipid dynamics, rates of lipid oxidation, and signal transduction pathways. Compared to other TG-lowering therapies, EPA has been found to inhibit cholesterol crystal formation, inflammation, and oxidative modification of atherogenic lipoprotein particles. The anti-inflammatory and endothelial benefits of EPA are enhanced in combination with a statin. Omega-3 fatty acids like EPA only at a pharmacologic dose reduce fasting TG and interfere with mechanisms of atherosclerosis that results in reduced cardiovascular events. Additional mechanistic trials will provide further insights into their role in reducing cardiovascular risk in subjects with well-managed LDL-C but elevated TG levels.

Efficacy of Direct Acting Oral Anticoagulant Drugs in Treatment of Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation.

Direct acting oral anticoagulants (DOACs) are increasingly used for thromboembolic prophylaxis in patients with atrial fibrillation (AF). However, there is limited data to evaluate the use of DOACs for the treatment of pre-existing left atrial appendage thrombus. We aimed to determine the efficacy of DOACs in treatment of left atrial appendage (LAA) thrombus utilizing transesophageal echocardiographic (TEE) and clinical outcomes. In this single-center study, we identified 33 patients that were treated for LAA thrombus with DOAC. Eighteen were treated with apixaban, 10 with dabigatran, and 5 with rivaroxaban. The primary endpoint was defined as resolution of LAA thrombus (in patients undergoing TEE), or death, major bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke, or peripheral embolization. In this study, 15 of the 16 patients treated with DOACs who underwent follow-up TEE had resolution of LAA thrombus, with a mean duration of 112 days. Of the 15 patients who achieved resolution of the LAA thrombus, 14 had resolution by their first follow-up TEE. In the 17 patients without a follow-up TEE, 1 died of a retroperitoneal bleed (28 days after DOAC initiation), and 1 suffered an ischemic stroke (484 days after DOAC initiation). In general, patients without a follow-up TEE were older and had more co-morbidities. Although these results are descriptive and limited in number of patients, we believe this is ample evidence that DOACs are relatively safe and efficacious in treatment of patients with AF and concomitant LAA thrombus.

[Coronary thrombosis: Physiopathology and treatment in the era of tailored medicine]. / Thrombose coronaire : physiopathologie et traitement à l'ère de la médecine personnalisée.

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.

Aspiration thrombectomy and intracoronary tirofiban via GuideLiner® catheter for a thrombosed aneurysmal vessel.

A 52-year-old Asian male with no traditional risk factors for coronary artery disease presented with acute coronary syndrome. Coronary angiography showed complete thrombotic occlusion of the left circumflex with a large thrombus burden in the setting of diffuse aneurysmal enlargement of the coronary arteries consistent with antecedent Kawasaki disease. Manual thrombectomy with adjunctive intracoronary tirofiban was performed utilizing the GuideLiner catheter® (Vascular Solutions, Inc., MN, USA). Stent implantation was deferred. Follow-up imaging 48 h later showed preserved coronary flow and decreased thrombus burden. The GuideLiner catheter, a monorail guiding device, served a novel role in thrombus aspiration and intracoronary medication delivery.

[Rivaroxaban-resistant right ventricular thrombus, successfully treated with vitamin K antagonist in a patient with dilated cardiomyopathy]. / Oporna na rywaroksaban skrzeplina w prawej komorze, skutecznie leczona antagonista witaminy K u chorego z kardiomiopatia rozstrzeniowa.

Rivaroxaban, a selective inhibitor of active factor X belongs to the group of direct-acting oral anticoagulants (DOAC), more and more often replacing vitamin K antagonists (VKA) in venous thromboembolic disease and nonvalvular atrial fibrillation. Attempts are also being made to use DOAC to treat locally formed intracardiac thrombi, mainly in the left atrium and its appendage, in atrial fibrillation and in heart failure. Rarely diagnosed local right ventricular thrombus (RVT) may be a complication of dilated cardiomyopathy (DCM). CASE REPORT: The authors present a case of a 40-year-old male with DCM and RVT located in the apex, which was imaged in echocardiography, magnetic resonance and multislice computed tomography. During treatment with rivaroksaban (2x15 mg: 4 weeks; 1x20 mg: 4 months) diminishing of RVT was not observed. After 2 months of VKA use complete resolution of RVT was noted. The case presented is probably the first described RVT treated with rivaroxaban. The authors conclude that in some cases, anticoagulation with VKA may be more effective than DOAC in intracardiac thrombi therapy, especially when it is meticulously monitored. Overlapping effect on RVT due to anticoagulants use with a different mechanism of action cannot be excluded.

Effect of Qi-regulating,Phlegm-resolving,and Blood-promoting Prescription on Rat Coronary Microvascular Thrombosis and Coronary Microvascular Occlusion.

Objective To explore the effect of qi-regulating,phlegm-resolving,and blood-promoting prescription on coronary microvascular thrombosis and coronary microvascular occlusion in rat models. Methods Totally 125 healthy clean-grade male SD rats weighing (300±25) g were sequentially numbered and then randomly divided into treatment group (n=60),control group (n=60) and blank group (n=5).Rats in the treatment group and control group received apical left ventricular injection of sodium laurate to establish rat models of coronary microvascular thrombosis. Then,rats in the control group were given distilled water by gavage one day before operation and after surgery. In contrast,rats in the treatment group were given qi-regulating,phlegm-resolving,and blood-promoting prescription by gavage one day before operation and after surgery. Five rats from both treatment group and control group were killed at each of six time points (1 hour,24th hour,7th day,14th day,21th day,and 28th day),and the myocardium specimens were harvested. The 5 rats in the blank group did not receive any special treatment and were given normal feeding;in the 28th day,they were sacrificed to obtain the myocardial specimens. Pathological sections of rat myocardial tissues were made to observe and compare the degrees of coronary microvascular thrombosis and coronary microvascular obstruction.Results In the treatment group and the control group,coronary microvascular thrombosis occurred 1 hour after apical sodium laurate injection and reached the peak at the 24th hour. Compared with the blank group,the treatment group and the control group showed different degree of coronary microvascular obstruction. Comparison between the treatment group and the control group at each time point showed that the coronary microvascular thrombosis in the treatment group was significantly lower than that in the control group (P<0.05 or P<0.01).The severity of coronary microvascular occlusion was significantly milder in the treatment group than in the control group (P<0.05 or P<0.01).Conclusions Apical left ventricular injection of sodium laurate successfully established rat models of coronary microvascular thrombosis. Qi-regulating,phlegm-resolving,and blood-promoting prescription can reduce coronary microvascular thrombosis and improve coronary microvascular obstruction.

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization.

AIM: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME). METHODS: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses. RESULTS: Pretreatment with the combination of ligustrazine (27 mg·kg(-1)·d(-1)) and berberine (90 mg·kg(-1)·d(-1)) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1ß, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg(-1)·d(-1)). CONCLUSION: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.

Rivaroxaban therapy resulting in the resolution of right atrial thrombosis resistant to ordinary control with warfarin in a patient with atrial fibrillation.

A 72-year-old man with non-valvular atrial fibrillation and metastatic liver and lung cancer after surgery for colon cancer developed thrombosis in the right atrium one month after decreasing the dose of warfarin due to the introduction of double anti-platelet therapy for coronary stent implantation. Restoring the warfarin dose with ordinary control for two months did not result in any changes in the size of the thrombus; however, the subsequent substitution of rivaroxaban (oral treatment with a direct Factor Xa inhibitor) for warfarin ultimately resolved the thrombosis.

A cautionary tale on the use of antiplatelet treatment following TURP.

A pleasant 74-year-old man was discharged home following a complication-free transurethral resection of his prostate (TURP) and successful trial without catheter. Unfortunately, on postoperative day 6, he presented to A&E with chest pain requiring emergency intervention for a confirmed myocardial infarction. A drug-eluting stent was inserted into his right coronary artery and he was started on dual antiplatelet therapy of aspirin and clopidogrel. On day 7, the patient developed significant haematuria requiring transfusion and an obstructive uropathy, requiring an emergency laparotomy and 1 L of organised clot evacuation from his bladder. The dual antiplatelet treatment was restarted on day 4 postlaparotomy, following debate between both the cardiology and urology teams regarding its appropriate reintroduction. On day 7, he was rushed back to the theatre for a re-laparotomy after CT confirmed reaccumulation of clot following an acute deterioration at ward level. The patient made an excellent recovery and was discharged home with regular outpatient follow-up.

Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium.

We describe the case of a previously healthy 22-year-old man who presented with anginal chest pain and was diagnosed with a non-ST-elevation myocardial infarction. For 3 weeks, he had been ingesting the dietary supplements Jack3d® (principal ingredient, 1,3-dimethylamylamine) and Phenorex™ (principal ingredient, Citrus aurantium) daily, before undertaking physical activity. Coronary angiograms revealed a proximal left anterior descending coronary artery thrombus with distal embolization. A combined medical regimen led to resolution of the thrombus. Three months later, the patient was asymptomatic with no evidence of ischemia. The primary ingredients in the sympathomimetic supplements taken by our patient are controversial in the medical community and have been individually associated with adverse cardiac events. There are no safety data on their simultaneous use. We discuss other reports of adverse effects associated with these supplements and recommend that the relevant safety guidelines be revised.

Selective blockade of P2Y12 receptors by prasugrel inhibits myocardial infarction induced by thrombotic coronary artery occlusion in rats.

We evaluated the effects of prasugrel, a third-generation thienopyridyl prodrug, on P2Y12 receptors, adenosine 5'-diphosphate (ADP)-induced platelet aggregation, and myocardial infarction (MI) in rats. Oral administration of prasugrel (0.3-3 mg/kg) resulted in the dose-related inhibition of washed platelet aggregation induced by ADP (1-10 µM). Ex vivo [H]-2-MeS-ADP binding to platelet P2Y12 receptors was also inhibited by prasugrel in a similar dose range. The antiaggregatory effects of prasugrel correlated strongly with P2Y12 blockade with correlation coefficients of 0.85-0.92, suggesting that the antiaggregatory activity of prasugrel largely reflected P2Y12 blockade achieved in vivo. We further examined the effects of the in vivo P2Y12 inhibition by prasugrel (1-10 mg/kg, po) on MI induced by thrombotic coronary artery occlusion in rats. In surviving rats, infarct size at 24 hours after photoirradiation was evaluated. In the vehicle group, necrosis area/total left ventricular area was 37.9% ± 6.8% (mean ± SE, n = 7). At all prasugrel doses tested (n = 7 for each dose), necrosis area/total left ventricular area was significantly smaller than that in the vehicle group: 14.4% ± 4.0% for 1 mg/kg (P < 0.01), 19.8% ± 4.5% for 3 mg/kg (P < 0.05), and 14.8% ± 3.6% for 10 mg/kg (P < 0.01). At the highest administered dose of prasugrel (10 mg/kg), blood pressure and heart rate were unchanged. Arrhythmia was observed in 5 of 7 animals in the vehicle group at 24 hours after irradiation; in contrast, no arrhythmia was found in the group treated with prasugrel (10 mg/kg). Taken together, these results demonstrate that prasugrel is a selective P2Y12 inhibitor in vivo, providing effective inhibition of platelet aggregation and MI in rats.

Ent-16ß,17-dihydroxy-kauran-19-oic acid, a kaurane diterpene acid from Siegesbeckia pubescens, presents antiplatelet and antithrombotic effects in rats.

The antiplatelet and antithrombotic effects of ent-16ß,17-dihydroxy-kauran-19-oic acid (DDKA) isolated from Siegesbeckia pubescens were investigated with different methods both in vitro and in vivo. We tested the antithrombotic activity of DDKA in arterio-venous shunt model. The effects of DDKA on adenosine diphosphate (ADP)-, Thrombin-, Arachidonic acid-induced rat platelets aggregation were tested in vitro. We also assessed its bleeding side effect by measuring coagulation parameters after intravenous administration for 5 days and investigated the potential mechanisms underlying such activities. In vivo, DDKA significantly reduced thrombus weight in the model of arterio-venous shunt. Meanwhile, DDKA increased plasma cAMP level determined by radioimmunoassay in the same model. Notably, DDKA prolonged PT and APTT in rats after intravenous administration DDKA for successive 5 days. In vitro, pretreatment with DDKA on washed rat platelets significantly inhibited various agonists stimulated platelet aggregation and caused an increase in cAMP level in platelets activated by ADP. These findings support our hypothesis that DDKA possesses antiplatelet and antithrombotic activities. The mechanisms underlying such activities may involve the anticoagulatory effect and cAMP induction.

The balance between anti-ischemic efficacy and bleeding risk of antithrombotic therapy in percutaneous coronary intervention: a Yin-Yang paradigm.

BACKGROUND: The development of newer and more potent antithrombotic agents and strategies has markedly reduced cardiovascular mortality and ischemic complications in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). With every approach to reduce coronary thrombosis, however, there is an accompanying risk of increasing bleeding complications elsewhere. Conversely, reducing bleeding complications may increase coronary thrombotic (ischemic) events. This is the Yin-Yang principle of antithrombotic therapy and strategies in PCI. Balancing both ends of the spectrum is essential, and an individualized approach to therapy is advocated. This article reviews the efficacy and bleeding risk profile of the different antithrombotic agents and strategies in PCI, including aspirin, thienopyridines, glycoprotein IIb/IIIa-inhibitors, heparin-based antithrombins, synthetic antithrombins and oral anticoagulants. Recommendations for reducing thrombotic and bleeding complications are also discussed.

[Clopidogrel resistance]. / Klopidogrel direnci.

Platelets play a critical role in pathogenesis of atherothrombotic diseases such as acute coronary syndromes and ischemic stroke. Clopidogrel, a thienopyridine derivative is an effective antiplatelet drug mostly used in combination with aspirin or as a single drug in aspirin intolerant patients. However, despite its proven efficacy in various clinical trials, some patients exhibit impaired response to clopidogrel and have activated platelets while on usual clopidogrel treatment. Although definition and mechanism(s) of this therapeutic failure are poorly understood, it is associated with higher morbidity and mortality as in aspirin resistance. Various causes have been implicated in clopidogrel resistance and alternative therapies are recommended. The aim of this review is to evaluate possible mechanisms, its clinical relevance and alternative treatments of this significant issue.