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.

Very Long Chain Marine n-3 Polyunsaturated Fatty Acids in Atherothrombotic Heart Disease. A Brief Review, with a Focus on Metabolic Effects.

The global burden of atherothrombotic heart disease should be considered as a life-style disorder where differences in dietary habits and related risk factors like limited physical activity and adiposity together play important roles. Related metabolic changes have been scientifically elucidated in recent decades, and the role of the very-long-chain marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been much focused on, especially their possible effects on processes like inflammation and thrombosis. In the present brief review of related metabolic mechanisms, the effects of these fatty acids in a clinical setting have been referred to, including some of the authors' work on this topic. The main focus is the divergent results in the field and the important differences between the study population, the type of supplements and fresh marine sources, the proportion of EPA versus DHA dosages, and the duration of supplementation in clinical trials. We conclude that daily intake of at least 1 g of EPA + DHA may improve a dysmetabolic state in the population. The potential to reduce the risk and progression of atherothrombotic heart disease is still a matter of debate.

Recurrent Type III Kounis Syndrome: Will Anti-Immunoglobulin E Drug Be Another Option?

Kounis syndrome was recognized as the concurrence of acute cardiovascular events with hypersensitivity reactions. We report a case of Kounis syndrome type III (coronary thrombosis) variant in a 48-year-old man who had experienced recurrent acute myocardial infarctions after scallion-induced hypersensitivity reactions. After appropriate antithrombotic, antihistamine, and reperfusion strategies, the patient was found to have elevated levels of immunoglobulin E and chronic urticaria. Upon administration of omalizumab, there was an improvement of chronic urticaria, a decrease in immunoglobulin E levels, and resolution of the ischemic attacks.

Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both.

Patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both remain at risk of cardiovascular events (including peripheral ischemic events), even when they receive the current guideline-recommended treatment. The phase III COMPASS trial demonstrated that treatment with rivaroxaban vascular dose 2.5 mg twice daily plus aspirin (dual pathway inhibition [DPI] regimen) significantly reduced the risk of major adverse cardiovascular events (including peripheral ischemic events) and increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, versus aspirin alone in patients with CAD, PAD, or both. The results of the COMPASS trial supported the regulatory approval of the DPI regimen in several geographic regions. However, it is unclear whether the patients selected for treatment with the DPI regimen in clinical practice will have a similar risk profile and event rates compared with the COMPASS trial population. The prospective post-approval XATOA registry study aims to assess treatment patterns, as well as ischemic and bleeding outcomes in patients with CAD, PAD, or both, who receive DPI therapy in routine clinical practice. Up to 10,000 patients from at least 400 centers in 22 countries will be enrolled and followed up for a minimum of 12 months, and all treatment will be at the discretion of the prescribing physician. The primary objective of the XATOA study will be to describe early treatment patterns, while ischemic and bleeding outcomes will be described as a secondary objective. TRIAL REGISTRATION NUMBER: NCT03746275.

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.

Emergence of omega-3 fatty acids in biomedical research.

Shortly after the discovery that linoleic acid was an essential fatty acid in 1930, α-linolenic acid also was reported to prevent the fatty acid deficiency syndrome in animals. However, several prominent laboratories could not confirm the findings with α-linolenic acid, and as a result there was a loss of interest in omega-3 fatty acids in lipid research. Even the findings that a prostaglandin can be synthesized from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is necessary for optimum retinal function generated only limited interest in omega-3 fatty acids. The breakthrough came in the 1970s when Dyerberg and Bang reported that the low incidence of atherosclerotic coronary disease in Greenland Eskimos was due to the high marine lipid content of their diet. They subsequently found that EPA, which was increased in Eskimo plasma, inhibited platelet aggregation, and they concluded that the low incidence of coronary artery disease was due to the anti-thrombotic effect of EPA. This stimulated widespread interest and research in EPA and DHA, leading to the present view that, like their omega-6 counterparts, omega-3 fatty acids have important physiological functions and are essential fatty acids.

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.

5-Year Outcome Following Randomized Treatment of All-Comers With Zotarolimus-Eluting Resolute Integrity and Everolimus-Eluting PROMUS Element Coronary Stents: Final Report of the DUTCH PEERS (TWENTE II) Trial.

OBJECTIVES: The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts). BACKGROUND: The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices. METHODS: In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated. RESULTS: Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; plog-rank = 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; plog-rank = 0.69), target vessel-related myocardial infarction (3.1% vs. 2.6%; plog-rank = 0.47), and target vessel revascularization (7.6% vs. 8.6%; plog-rank = 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; plog-rank = 0.83). CONCLUSIONS: At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.

[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.

CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.

PURPOSE: This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75 mg daily), universal alternative P2Y12 inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider. RESULTS: Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12 inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12 inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold = 50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively. CONCLUSIONS: Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12 inhibitor therapy for ACS patients with PCI.

[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.

Resolution of left ventricular postinfarction thrombi in patients undergoing percutaneous coronary intervention using rivaroxaban in addition to dual antiplatelet therapy.

Left ventricular (LV) thrombus is usually seen in situations with reduced LV function, and is mostly seen in patients with large anterior ST-elevation myocardial infarction (MI). Most embolic events, in patients with LV thrombus formation, occur within the first 3-4 months, thus the recommendations regarding the duration of anticoagulant therapy. According to guidelines, an oral vitamin K antagonist, warfarin, is being used as an anticoagulant for this period. Novel oral anticoagulants were found to be either non-inferior or superior compared with warfarin in prevention of thromboembolism in patients with non-valvular atrial fibrillation. However, the data about their role in the management of LV thrombus are limited to case reports. Here, we report on the dissolution of LV apical thrombus in 3 patients with anterior ST-elevation MI receiving dual antiplatelet therapy and rivaroxaban on a reduced dose for 3 months.

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial.

OBJECTIVES: The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). BACKGROUND: The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown. METHODS: The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial. RESULTS: Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups. CONCLUSIONS: In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy.

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.

The association of the coronary thrombus burden with all-cause mortality and major cardiac events in ST-segment elevation myocardial infarction patients treated with tirofiban.

BACKGROUND: The aim of this study was to investigate the association of the coronary thrombus burden with all-cause mortality and major adverse cardiac events (MACE) in ST-segment elevation myocardial infarction (STEMI) patients treated with 'in-cath lab' (downstream) high-dose bolus tirofiban. METHODS: This study included 2452 patients with STEMI treated with a primary percutaneous coronary intervention. All glycoprotein IIb/IIIa receptor inhibitor (GPI) (tirofiban) infusions were started in the catheterization laboratory according to the coronary thrombus burden; tirofiban was not administered to patients who did not have coronary thrombus burden. All patients with small, moderate, or large thrombus burden received tirofiban therapy. The primary study endpoint was the incidence of all-cause mortality. The secondary study endpoints were major bleeding and MACE, which included all-cause death, nonfatal acute coronary syndrome, and target lesion revascularization. RESULTS: The patients were followed up for a mean period of 28.3±10.4 months. The groups showed similar in-hospital and long-term event rates (MACE, major bleeding, and all-cause mortality). The 3-year Kaplan-Meier overall survivals for no thrombus, small thrombus, moderate thrombus, and large thrombus were 91.9, 92.6, 92.3, and 89.5%, respectively. CONCLUSION: Despite the fact that the large coronary thrombus was found to be a predictor of MACE and mortality in many previous studies, we found that the large thrombus was not associated with MACE or in-hospital mortality or long-term mortality. This can be an effect of downstream GPI therapy. We suggest the use of downstream GPI therapy for STEMI patients with large coronary thrombus without an increased risk of bleeding.

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.