Blood Coagulation Disorders in Heart Failure: From Basic Science to Clinical Perspectives.

Heart failure (HF) is a clinical syndrome that is divided into 3 subtypes based on the left ventricular ejection fraction. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and sinus rhythm, initial reports suggest that such strategy might be beneficial in a subset of patients at especially high thromboembolic risk. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation disorders in acute and chronic HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in special-case scenarios and to outline future research directions so as to establish the optimal patient-tailored strategies for antiplatelet and anticoagulant therapy in HF. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy. Further studies are urgently needed to shed light on the pathophysiological role of platelet activation in HF and to evaluate whether antiplatelet or antithrombotic therapy could be beneficial in patients with HF. LAY SUMMARY: Heart failure (HF) is a clinical syndrome divided into 3 subtypes on the basis of the left ventricular systolic function. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing the risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and no atrial arrhythmia, initial reports suggest that such a strategy might be beneficial in a subset of patients at especially high risk of thrombotic complications. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation problems in stable and unstable patients with HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in specific patient groups and to outline future research directions to establish the optimal strategies for antiplatelet and anticoagulant therapy in HF, tailored to the needs of an individual patient. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy.

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience.

BACKGROUND: NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure. AIMS: We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure. METHODS: We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter. RESULTS: Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0-15.0) versus 13.3 mm (IQR 11.4-18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0-13.1) versus 12.5 mm (IQR 9.7-15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm3 (IQR 286-894) versus 985 mm3 (IQR 572-1550) (p = 0.016). CONCLUSION: In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.

Cardiac Arrhythmias in Oncological Patients-Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines.

PURPOSE OF REVIEW: To provide an update on epidemiology, risk factors, and management of cardiac arrhythmias in oncological patients within the context of the new European Society of Cardiology 2022 guidelines on cardio-oncology. RECENT FINDINGS: One of the side effects of different chemotherapeutics is their pro-arrhythmic activity. Both atrial and ventricular arrhythmias may be induced by cancer itself or by anticancer treatment. Recent studies report on the cardiotoxic activity of such promising therapies as BRAF and MEK inhibitors, or CAR-T therapy. Risk factors of arrhythmias in oncological patients overlap with cardiovascular diseases risk factors, but there are some groups of anticancer drugs that increase the risk of cardiotoxicity. It is crucial to be aware of the risks associated with the oncological treatment and know how to act in case of cardiotoxicity.

Sex differences in antiplatelet therapy: state-of-the art.

Antiplatelet therapy is a cornerstone of secondary prevention of cardiovascular diseases (CVDs). However, current guidelines are based on data derived primarily from men, as women are generally underrepresented in trials. Consequently, there are insufficient and inconsistent data on the effect of antiplatelet drugs in women. Sex differences were reported in platelet reactivity, patient management, and clinical outcomes after treatment with aspirin, P2Y12 inhibitor, or dual antiplatelet therapy. To evaluate whether sex-specific antiplatelet therapy is needed, in this review we discuss (i) how sex affects platelet biology and response to antiplatelet agents, (ii) how sex and gender differences translate into clinical challenges and (iii) how the cardiological care in women might be improved. Finally, we highlight the challenges faced in clinical practice regarding the different needs and characteristics of female and male patients with CVD and address issues requiring further investigation.

Antiplatelet therapy is a crucial part of cardiovascular disease prevention. Guidelines are based on data from men, as too few women participate in trials. We reviewed differences between women and men in antiplatelet therapy. Sex differences occur in platelet reactivity and in the response to the therapy with aspirin and/or P2Y₁₂ inhibitors. In primary prevention with aspirin, sex should be considered. In secondary prevention, aspirin, clopidogrel, ticagrelor, and prasugrel should be used in women as in men, according to individual patient needs. Female and male cardiac patients might present with different symptoms and risk factors. Healthcare professionals often treat women differently than men and do not satisfy women's needs. Education of researchers and healthcare professionals is required to provide highest standard of cardiological care to women. This review summarizes the evidence on sex differences in antiplatelet therapy ­ from diagnosis, through patient management, to treatment outcomes. It describes how molecular aspects translate into clinical practice and how to provide effective antiplatelet therapy to female patients.Abbreviations: ACS: acute coronary syndrome; ADP: adenosine 5'-diphosphate; BARC: Bleeding Academic Research Consortium; CAD: coronary artery disease; cAMP: cyclic adenosine 5'-monophosphate; COX-1: cyclooxygenase-1; CYP: cytochrome P; CVD(s): cardiovascular disease(s); DAPT: dual antiplatelet therapy; DES: drug-eluting stent; DM: Diabetes mellitus; GP: glycoprotein; MI: myocardial infarction; PCI: percutaneous coronary intervention; PGH₂: prostaglandin H₂; PKA: protein kinase A; TR: thromboxane receptor; TXA₂: thromboxane A₂; VASP: vasodilator-stimulated phosphoprotein; VWF: von Willebrand factor.

Extracellular Vesicles in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Despite recent progress in the diagnosis and treatment of CAD, evidence gaps remain, including pathogenesis, the most efficient diagnostic strategy, prognosis of individual patients, monitoring of therapy, and novel therapeutic strategies. These gaps could all be filled by developing novel, minimally invasive, blood-based biomarkers. Potentially, extracellular vesicles (EVs) could fill such gaps. EVs are lipid membrane particles released from cells into blood and other body fluids. Because the concentration, composition, and functions of EVs change during disease, and because all cell types involved in the development and progression of CAD release EVs, currently available guidelines potentially enable reliable and reproducible measurements of EVs in clinical trials, offering a wide range of opportunities. In this chapter, we provide an overview of the associations reported between EVs and CAD, including (1) the role of EVs in CAD pathogenesis, (2) EVs as biomarkers to diagnose CAD, predict prognosis, and monitor therapy in individual patients, and (3) EVs as new therapeutic targets and/or drug delivery vehicles. In addition, we summarize the challenges encountered in EV isolation and detection, and the lack of standardization, which has hampered real clinical applications of EVs. Since most conclusions are based on animal models and single-center studies, the knowledge and insights into the roles and opportunities of EVs as biomarkers in CAD are still changing, and therefore, the content of this chapter should be seen as a snapshot in time rather than a final and complete compendium of knowledge on EVs in CAD.

Autoantibodies in Atrial Fibrillation-State of the Art.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. To date, a lot of research has been conducted to investigate the underlying mechanisms of this disease at both molecular and cellular levels. There is increasing evidence suggesting that autoimmunity is an important factor in the initiation and perpetuation of AF. Autoantibodies are thought to play a pivotal role in the regulation of heart rhythm and the conduction system and, therefore, are associated with AF development. In this review, we have summarized current knowledge concerning the role of autoantibodies in AF development as well as their prognostic and predictive value in this disease. The establishment of the autoantibody profile of separate AF patient groups may appear to be crucial in terms of developing novel treatment approaches for those patients; however, the exact role of various autoantibodies in AF is still a matter of ongoing debate.

The Role of MicroRNAs in Aortic Stenosis-Lessons from Recent Clinical Research Studies.

Aortic stenosis (AS) is the most prevalent primary valve lesion demanding intervention. Two main treatment options are surgical aortic valve replacement or transcatheter aortic valve implantation. There is an unmet need for biomarkers that could predict treatment outcomes and become a helpful tool in guiding Heart Team in the decision-making process. Micro-ribonucleic acids (microRNAs/miRs) have emerged as potential biomarkers thoroughly studied in recent years. In this review, we aimed to summarize the current knowledge about the role of miRNAs in AS based on human subject research. Much research investigating miRNAs' role in AS has been conducted so far. We included 32 original human subject research relevant to the discussed field. Most of the presented miRNAs were studied only by a single research group. Nevertheless, several miRNAs appeared more than once, sometimes with high consistency between different studies but sometimes with apparent discrepancies. The molecular aspects of diseases are doubtlessly exciting and provide invaluable insights into the pathophysiology. Nevertheless, translating these findings, regarding biomarkers such as miRNAs, into clinical practice requires much effort, time, and further research with a focus on validating existing evidence.

Harnessing the parallax for better spatial awareness.

Despite easy access to imaging diagnostic procedures and an abundance of spatial data, most cardiac interventions are still performed under two-dimensional fluoroscopy. Incorporating anatomical data from scans into procedures plans has the potential to improve the swiftness and outcomes of percutaneous cardiac interventions. Therefore, procedure planning based on the specific anatomy is becoming a new standard of excellence in interventional cardiology. Still, we often tend to disregard specific spatial relations and the actual direction of catheter tip movement inside the body, relying on a try and error approach. The precise spatial orientation of instruments and prosthetic devices is crucial, especially during structural heart interventions. Here, we present how deliberate movements of objects under fluoroscopy can reveal the spatial orientation of catheters and other devices. We also propose a novel "two-point rule" for identifying three-dimensional relations between points in space. Understanding and applying this rule might substantially increase the spatial awareness of operators performing cardiovascular interventions. Although the concept is pretty simple, using it "live" during interventional cardiology procedures requires thorough understanding and practice. We propose the "two-point rule" as a crucial rule to develop expertise in spatial orientation under fluoroscopy and ensure high-quality outcomes.

Role of copeptin in diagnosis and outcome prediction in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND/CONTEXT: Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. OBJECTIVE: This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. MATERIALS AND METHODS: A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. RESULTS: Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= -4.69; 95% CI: -7.58 to -1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= -13.06; 95% CI: -25.28 to -0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). CONCLUSIONS: The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF.

Prostacyclin analogues decrease platelet aggregation but have no effect on thrombin generation, fibrin clot structure, and fibrinolysis in pulmonary arterial hypertension: PAPAYA coagulation.

Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.

Pre-operative platelet reactivity is a strong, independent predictor of bleeding complications after branched endovascular thoracoabdominal aortic aneurysm repair.

Endovascular aortic repair (EVAR) an alternative to open surgical repair of thoracoabdominal aortic aneurysm (TAAA). The effect of EVAR on platelet reactivity is unknown. We prospectively determined the effect of branched EVAR (bEVAR) on platelet reactivity in patients with TAAA, and evaluated the predictive value of preoperative platelet reactivity for post-operative bleeding in 50 consecutive patients undergoing elective bEVAR (mean age 70.9 ± 5.7 years, 66% male). Blood samples were collected within 24 hours before bEVAR, after bEVAR and at hospital discharge. Platelet reactivity was assessed with impedance aggregometry using ASPI, ADP and TRAP tests. Platelet reactivity decreased within 24 hours after bEVAR compared to the measurement before bEVAR in all tests (p ≤ 0.04), with a further decrease in hospital discharge in the ADP test (p = .004). Twenty-three patients experienced post-operative bleeding complications (transfusion ≥2 red blood cell [RBC] units). Preoperative platelet reactivity below the cutoff value of 30 AUC units predicted post-operative bleeding with 78% sensitivity and 59% specificity (p = .045). In the multivariable analysis, platelet reactivity was the only independent predictor of postoperative bleeding (OR 6.507, 95% CI 1.227-34.506, p = .028). We conclude that platelet reactivity decreases following bEVAR of TAAA and is a strong and independent predictor for postoperative bleeding complications.

EDTA stabilizes the concentration of platelet-derived extracellular vesicles during blood collection and handling.

Citrate is the recommended anticoagulant for studies on plasma extracellular vesicles (EVs). Because citrate incompletely blocks platelet activation and the release of platelet-derived EVs, we compared EDTA and citrate in that regard. Blood from healthy individuals (n = 7) was collected and incubated with thrombin receptor-activating peptide-6 (TRAP-6) to activate platelets, subjected to pneumatic tube transportation (n = 6), a freeze-thaw cycle (n = 10), and stored before plasma preparation (n = 6). Concentrations of EVs from platelets (CD61+), activated platelets (P-selectin+), erythrocytes (CD235a+), and leukocytes (CD45+) were measured by flow cytometry. Concentrations of EVs from platelets and activated platelets increased 1.4-fold and 1.9-fold in EDTA blood upon platelet activation, and 4.2-fold and 9.6-fold in citrate blood. Platelet EV concentrations were unaffected by pneumatic tube transport in EDTA blood but increased in citrate blood, and EV concentrations of erythrocytes and leukocytes were comparable. The stability of EVs during a freeze-thaw cycle was comparable for both anticoagulants. Finally, the concentration of platelet EVs was stable during storage of EDTA blood for six hours, whereas this concentration increased 1.5-fold for citrate blood. Thus, EDTA improves the robustness of studies on plasma EVs.

Patients with alopecia areata are at risk of endothelial dysfunction: results of a case-control study.

BACKGROUND: Alopecia areata (AA) is an autoimmune form of hair loss, which may affect any hair-bearing area. It has been suggested that AA is associated with an increased risk of metabolic and cardiovascular comorbidities. AIM: To evaluate the early predictors of cardiovascular disease [endothelial function (EF) and arterial stiffness (AS)] in patients with AA without prior cardiovascular disease, and compare with healthy controls (HCs). METHODS: In total, 52 patients with AA (38 women and 14 men; mean age 41 years, range 30-52 years) and 34 HCs, matched for age, sex and body mass index, were enrolled in the study. EF, expressed as reactive hyperaemia index (RHI), and AS, identified by augmentation index at 75 beats/min (AI@75) were assessed with the use of the Endo-PAT 2000 device. Endothelial dysfunction (ED) was defined as RHI value ≤1.67. RESULTS: ED was observed in 22 of 52 patients with AA (42%) and in 4 of 34 HCs (12%) (P < 0.01). Moreover, mean RHI was lower in patients with AA compared with HCs (1.90 ± 0.31 vs. 2.11 ± 0.45; P = 0.03). There was no significant difference in AI@75 between patients with AA and HCs. CONCLUSIONS: Patients with AA show abnormalities in early predictors of cardiovascular diseases. Regular cardiovascular screening might be appropriate for patients with AA.

The Role of MicroRNAs in Myocarditis-What Can We Learn from Clinical Trials?

Myocarditis is an inflammatory disease of the heart with a viral infection as the most common cause. It affects most commonly young adults. Although endomyocardial biopsy and cardiac magnetic resonance are used in the diagnosis, neither of them demonstrates all the required qualities. There is a clear need for a non-invasive, generally available diagnostic tool that will still remain highly specific and sensitive. These requirements could be possibly met by microribonucleic acids (miRNAs), which are small, non-coding RNA molecules that regulate many fundamental cell functions. They can be isolated from cells, tissues, or body fluids. Recently, several clinical studies have shown the deregulation of different miRNAs in myocarditis. The phase of the disease has also been evidenced to influence miRNA levels. These changes have been observed both in adult and pediatric patients. Some studies have revealed a correlation between the change in particular miRNA concentration and the degree of cardiac damage and inflammation. All of this indicates miRNAs as potential novel biomarkers in the diagnosis of myocarditis, as well as a prognostic tool for this condition. This review aims to summarize the current knowledge about the role of miRNAs in myocarditis based on the results of clinical studies.

Extracellular Vesicles in Atrial Fibrillation-State of the Art.

Extracellular vesicles are particles released from cells and delimited by a lipid bilayer. They have been widely studied, including extensive investigation in cardiovascular diseases. Many scientists have explored their role in atrial fibrillation. Patients suffering from atrial fibrillation have been evidenced to present altered levels of these particles as well as changed amounts of their contents such as micro-ribonucleic acids (miRs). Although many observations have been made so far, a large randomized clinical trial is needed to assess the previous findings. This review aims to thoroughly summarize current research regarding extracellular vesicles in atrial fibrillation.

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke.

BACKGROUND: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. METHODS: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). RESULTS: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63-0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76-0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65-0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57-0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79-0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74-0.10) p = 0.001). CONCLUSION: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment.

INTRODUCTION: Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. PROPHYLAXIS, DIAGNOSIS AND TREATMENT: COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients' clinical outcomes. RECOMMENDATIONS FOR CLINICIANS: Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. CONCLUSIONS: Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19.

Inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in ACS.

Inflammation leads to atherosclerosis and acute coronary syndromes (ACS). We performed a prospective, observational study to assess association between the concentrations of inflammatory markers (high sensitivity C-reactive protein, hsCRP; high sensitivity interleukin6, hsIL-6; soluble CD40 ligand, sCD40 L) and platelet reactivity in 338 patients with ACS treated with ticagrelor and prasugrel. We also assessed whether hsCRP, hsIL-6, and sCD40 L are associated with standard inflammatory markers (white blood cell [WBC] and fibrinogen), and whether they differ according to patient diabetic status and pre-treatment with statins. Concentrations of hsCRP and concentrations of hsIL-6 and sCD40 L were assessed using turbidimetric assay and enzyme-linked immunosorbent assay, respectively. Platelet reactivity was measured using multiple electrode aggregometry. There was only a weak inverse correlation between hsIL-6 and platelet reactivity (r≤-0.125). In contrast, concentration of hsIL6 and hsCRP positively correlated with WBC and fibrinogen (r ≥ 0.199). Insulin-dependent diabetes mellitus (IDDM) was associated with higher concentration of hsIL-6 (p = .014), whereas pre-treatment with statins - with lower concentration of hsIL-6 (p = .035). In conclusion, inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in the acute phase of ACS, confirming the safety and efficacy of potent P2Y12 inhibitors in patients with a high inflammatory burden.

Comparison of intravascular access methods applied by nurses wearing personal protective equipment in simulated COVID-19 resuscitation: A randomized crossover simulation trial.

BACKGROUND: Prehospital emergency care of children is challenging. In the era of the COVID-19 pandemic, when medical personnel should use personal protective equipment against aerosol-generating procedures, the efficiency of medical procedures may decrease. The study objective was to evaluate the effectiveness of different intravascular access methods applied by nurses wearing biosafety Level-2 suits in simulated paediatric COVID-19 resuscitation. METHODS: A prospective, randomized, crossover, single-blinded simulation trial was performed. Nursing staff attending Advanced Cardiovascular Life Support courses accredited by the American Heart Association participated in the study. A total of 65 nurses were recruited and randomly assigned to different study groups. They received standard training on intravascular access methods employing distinct devices. The participants wore biosafety Level-2 suits and performed vascular access with the following intraosseous devices: NIO-P, EZ-IO, and Jamshidi needle; intravenous (IV) access was used as a reference method. Both the order of participants and the access methods were random. Each participant performed intravascular access with each of the four methods tested. The effectiveness of the first attempt to obtain intravascular access and the following time parameters were analysed: the time between grasping the intravascular device out of the original packing until infusion line connection. The ease of the procedure was measured with a visual analogue scale (1 - easy; 10 - difficult). RESULTS: The first attempt success rate of intravascular access by using NIO-P and EZ-IO equalled 100% and was statistically significantly higher than that with the Jamshidi needle (80.0%; p = 0.02) and with the IV method (69.2%; p = 0.005). The time required to connect the infusion line varied and amounted to 33 ± 4 s for NIO-P compared to 37 ± 6.7 s for EZ-IO (p<0.001), 43 ± 7 s for Jamshidi (p<0.001), and 98.5 ± 10 s for IV access (p<0.001). The procedure was easiest in the case of NIO-P and EZ-IO (2 ± 1 points; p=1.0) compared with Jamshidi (5 ± 3 points; p<0.001) and IV access (7 ± 2 points; p<0.001). CONCLUSION: The study provides evidence that nurses wearing biosafety Level-2 suits were able to obtain intraosseous access faster and more effectively as compared with IV access during simulated COVID-19 paediatric resuscitation. The most effective method of intravascular access was the NIO-P intraosseous device. Further clinical trials are necessary to confirm the results.

Cardioprotective Effect of Low Level of LDL Cholesterol on Perioperative Myocardial Injury in Off-Pump Coronary Artery Bypass Grafting.

Background and Objectives: Coronary artery disease is still a major cause of death in developed countries. Low-density lipoprotein cholesterol (LDL-C) lowering with statin therapy is a key strategy in major acute coronary events' prevention. The aim of the study was to establish if there is a cardioprotective effect of pre-operative LDL lowering therapy on perioperative myocaridal injury in patients undergoing off-pump coronary artery bypass grafting (CABG). Moreover, the impact of pre-operative LDL level on long term outcome was analysed. Materials and Methods: The retrospective single center analysis included 662 consecutive patients (431 (65%) males and 231 (35%) female, mean age of 65 ± 8) referred for cardiac surgery due to stable chronic coronary syndrome between 2012-2018. The follow up was 9 years. Results: A statistically significant difference was found in postoperative serum Troponin-I for LDL thresholds of 1.8 mmol/L (p = 0.009), 2.6 mmol/L (p = 0.03) and 3.0 mmol/L (p = 0.001). The results indicate that cardioprotective role of LDL is achieved within LDL concentration rate below 1.8 mmol/L (<70 mg/dL). Five patients died perioperatively, whereas 1-year and 9-year overall mortality rates were 4% (n = 28) and 18.6% (n = 123), respectively. Comparing the survival group with diseased, Mann-Whitney U test showed a statistically significant difference in HDL-C (p = 0.007), Troponin (p = 0.009), Castelli index (p = 0.001) and atherogenic index (p = 0.004). Preoperative levels of total cholesterol, LDL-C and HDL-C did not significantly differ between survivors and diseased. The 9-year mortality risk did not differ significantly between subgroups divided according to LDL-C thresholds of 1.4 mmol/L (55 mg/dL), 1.8 mmol/L (70 mg/dL), 2.6 mmol/L (100 mg/dL) and 3.0 mmol/L (116 mg/dL). Conclusions: Preoperative low level of LDL-C cholesterol (below 1.83 mmol/L, 70 mg/dL) has a cardioprotective effect on perioperative myocardial injury in off-pump coronary artery bypass grafting.