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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, with an individual lifetime risk of approximately 37% in the United States. Broadly defined as a supraventricular tachyarrhythmia with disorganized atrial activation, AF results in an increased risk of stroke, heart failure, valvular heart disease, and impaired quality of life, and confers a significant burden on the health of individuals and society. AF in the perioperative setting is common and a significant source of perioperative morbidity and mortality worldwide. The latest iteration of the European Society of Cardiology AF guidelines published in 2020 provide the clinician a valuable road map for the management of this arrythmia. This expert review will comprehensively analyze the 2020 European Society of Cardiology guidelines and provide perioperative management tools for the clinician.

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder associated with an increased risk of stroke and systemic embolic events. The prevention of stroke using oral anticoagulants has been a pivotal component of AF management. The purpose of this review is to summarize recent advances in the treatment and prevention of stroke in AF over the last 5 years. We performed a comprehensive structured literature search using MEDLINE for publications from 11th March 2015 through to 31st December 2020. We focused mainly on primarily published research articles and systematic reviews including updates in different international guidelines. We found that improved awareness and detection of AF and use of clinical risk stratification are central to the identification of patients at risk of stroke who would benefit from oral anticoagulation. The recommendation of non-vitamin K antagonist oral anticoagulants over warfarin in both efficacy and safety perspective is represented in all international guidelines. Beyond stroke prevention, there is a move to more holistic or integrated care management of AF, which has been shown to improve outcomes. We conclude that stroke prevention remains a dominant part of the management of patients with AF. Not all stroke risk factors carry equal weight, and many require additional scrutiny (e.g. severity of CAD, type of diabetes, duration of hypertension). The utilization of clinical risk scores to help decision-making should take into account that these scores are mere simplification tools to aid decision-making and the additional clinical benefit with more complex risk scores and addition of biomarkers is limited. Also, stroke and bleeding risks are dynamic and require regular review. Instead of arbitrarily categorizing patients into (artificial) low, moderate, and high stroke risk strata, anticoagulation should be offered to all patients with AF unless they are low risk with no risk factors for stroke. Stroke prevention is also part of the proactive, integrated care approach to holistic management of patients with AF, which can be simplified in the ABC (Atrial fibrillation Better Care) pathway: ‘A’ Avoid stroke/Anticoagulation; ‘B’ Better symptom management emphasising patient-centred symptom directed decisions on rate or rhythm control strategies; and ‘C’ refers to Cardiovascular risk and comorbidity optimization, including lifestyle changes and attention to patient values and preferences, as well as the psychological morbidity associated with AF.

Background Impaired endogenous fibrinolysis is a risk factor for recurrent cardiovascular events in patients with acute coronary syndrome (ACS). Ongoing inflammation is also an adverse prognostic risk factor. While inflammatory markers are elevated in patients presenting with ST-segment elevation myocardial infarction (STEMI), whether there is a direct relationship between markers of inflammation at presentation, and the effectiveness of endogenous fibrinolysis in this setting, is unclear. Our study aimed to assess the relationship between markers of inflammation, coagulation and fibrinolysis, in patients with STEMI. Material and methods We conducted a prospective, observational study in consecutive patients presenting with STEMI. Blood was drawn on admission after dual antiplatelet therapy loading, but before administration of anticoagulants. The sample was immediately tested to assess endogenous fibrinolysis using the point-of-care Global Thrombosis Test. In addition, blood samples were tested for leucocyte and neutrophil count, neutrophil-to-leucocyte ratio (NLR), platelet-to-leucocyte ratio (PLR), fibrinogen, standard coagulation markers and high sensitivity C-reactive protein (hs-CRP). Results and conclusions The cohort consisted of 129 patients (aged 66 ± 13 years, 78% male). Whole blood endogenous fibrinolysis time correlated with fibrinogen (r = 0.300, P = 0.001) and hs-CRP (r = 0.236, P = 0.011). Hs-CRP correlated with fibrinogen (r = 0.631, P < 0.001). There was no relationship between whole blood lysis time and leucocyte count, NLR, PLR, international normalised ratio or activated partial thromboplastin time. The effectiveness of endogenous fibrinolysis in whole blood is related to fibrinogen and hs-CRP levels. Our findings strengthen the evidence for bi-directional cross talk between coagulation, fibrinolysis and inflammatory pathways, providing mechanistic insights that could help guide pharmacological strategies to treat hypofibrinolysis.

This abstract has been withdrawn. Please see: https://doi.org/10.1093/cvr/cvac183

Importance The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival. Objective To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality. Evidence review A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020. Findings Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the 3 most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE, and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated. Conclusions Clinicians should be aware of these risk scores, which can be used to provide objective, nonemotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.

© 2020 Elsevier Inc. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1016/j.amjcard.2020.12.014

IMPORTANCE: Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established. OBJECTIVE: To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021. INTERVENTIONS: Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy. MAIN OUTCOMES AND MEASURES: The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable. RESULTS: A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P

The introduction of transcatheter aortic valve implantation (TAVI) has revolutionised the management of aortic stenosis (AS), with procedure numbers rapidly increasing. Although there has been enth...

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug–drug and food–drug interactions. Bleeding risk is also not a static ‘one off’ assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing ‘best practice’ when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

Background Taxus baccata, also known as English yew, is a poison that causes cardiac arrhythmias and can result in death from cardiogenic shock. Case summary A 49-year-old gentleman was admitted following yew ingestion with suicidal intent. He was bradycardic at 30 b.p.m. and hypotensive on arrival. Electrocardiography revealed complete heart block with broad complex ventricular escape rate of 30 b.p.m. Bedside echocardiography revealed severe global impairment of right and left ventricular systolic function. Urgent temporary transvenous pacing was instituted, and the patient was considered for veno-arterial extracorporeal membrane oxygenation. Unfortunately, he deteriorated rapidly and cardiorespiratory arrest ensued, and despite prolonged in-hospital resuscitation, the patient died. Post-mortem examination revealed small needle-shaped plant leaves together with seeds found in the stomach. Ante mortem serum sample analysis sent to the Royal Botanical Gardens and revealed the presence of taxine Type B alkaloids in the patient’s blood. Discussion Yew poisoning is a rare occurrence, and there is currently no effective antidote. Treatment involves supportive management, comprising prolonged effective cardiopulmonary resuscitation, pacing, and mechanical cardiac support. This case illustrates the importance of prompt recognition of yew poisoning, alongside early consideration of pacing and mechanical cardiac support. Due to the rarity of this cause of heart block, and since patients may not always volunteer a history of yew ingestion, yew poisoning is something that physicians should be aware of and this should be considered in the differential diagnosis in patients with unexpected heart block. Serum analysis for taxine alkaloids can be used to confirm the diagnosis.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Aims Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF). Methods and results In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591–2300) vs. 2758 (2014–3502) vs. 2135 (1752–2463) s, P Conclusion Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study.

Patients with transient ST-elevation myocardial infarction (STEMI) or spontaneous resolution (SpR) of the ST-segment elevation on electrocardiogram could potentially represent a unique group of patients posing a therapeutic management dilemma. In this review, we discuss the potential mechanisms underlying SpR, its relation to clinical outcomes and the proposed management options for patients with transient STEMI with a focus on immediate versus early percutaneous coronary intervention. We performed a structured literature search of PubMed and Cochrane Library databases from inception to December 2020. Studies focused on SpR in patients with acute coronary syndrome were selected. Available data suggest that deferral of angiography and revascularization within 24–48 h in these patients is reasonable and associated with similar or perhaps better outcomes than immediate angiography. Further randomized trials are needed to elucidate the best pharmacological and invasive strategies for this cohort.

COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).

Funding Acknowledgements Type of funding sources: None. Background The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with Atrial Fibrillation (AF), standing on three main pillars: ‘A’ Avoid stroke (with Anticoagulants); ‘B’ Better symptom management; ‘C’ Cardiovascular and Comorbidity management. The ABC pathway is now recommended in several clinical guidelines, including the recent European Society of Cardiology (ESC) AF management guidelines. We performed a systematic review of the current evidence for use of the ABC pathway on clinical outcomes. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. Pubmed and EMBASE were searched for studies reporting the prevalence of ABC pathway adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Metanalysis of odds ratio (OR) was performed with random-effect models; subgroup analysis and meta-regression were performed to account for heterogeneity; a CHA2DS2-VASc-stratified sensitivity analysis was also performed. Results Among 2862 records retrieved from the literature search, 8 studies were included. The pooled prevalence of ABC adherent management was 21% (95% confidence intervals (CI), 13-34%), with a high grade of heterogeneity; in a multivariable meta-regression model, adherence to each criteria of the ABC pathway explained most part of the heterogeneity (R2 = 98.9%). Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR:0.42, 95%CI 0.31-0.56), cardiovascular death (OR:0.37, 95%CI 0.23-0.58), stroke (OR:0.55, 95%CI 0.37-0.82) and major bleeding (OR:0.69, 95%CI 0.51-0.94), with moderate heterogeneity. Meta-regressions showed that the increasing prevalence of diabetes mellitus, coronary artery disease, chronic heart failure and history of stroke were associated with a reduced effectiveness of the ABC pathway for all-cause and cardiovascular death; each comorbidity was able to explain a significant proportion of heterogeneity at univariate meta-regression. Conversely, longer follow-up time was associated with more effectiveness of the ABC pathway for all outcomes. Adherence to ABC pathway was associated with a progressively greater reduction of the all-cause death risk amongst patients with higher CHA2DS2-VASc scores; no difference in ABC pathway effectiveness was found across CHA2DS2-VASc strata for CV death and stroke occurrence. Conclusions Adherence to the ABC pathway was suboptimal, being adopted in 1 in every 5 patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes. Our data supports extensive application of the ABC pathway for the management of AF. Abstract Figure.

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p

Introduction Patients with diabetes mellitus (DM) are increased risk of myocardial infarction (MI) and following a MI, patients with DM have an increased risk of recurrent MI and cardiovascular (CV) death. Plasma turbidimetry studies show that hypofibrinolysis is a key abnormality in DM that may drive increased ischaemic risk. Such assays are cumbersome, require specialist expertise and do not provide information in a clinically-relevant timeframe. Assessment of fibrinolysis in whole blood, using a point-of-care assay, has revealed that in ACS patients, impaired fibrinolysis is predictive of adverse CV events. Whether this technique can identify residual risk in patients with DM, is unclear. Purpose It was our aim to compare thrombotic and endogenous fibrinolytic status between patients with and without DM, presenting with ACS. Methods We conducted a prospective, observational study of consecutive patients admitted with ACS. Venous blood was taken to assess thrombotic and thrombolytic status using the point-of-care Global Thrombosis Test, assessing time to occlusive thrombus formation under high shear (occlusion time, OT) and time taken for spontaneous lysis of the thrombus (lysis yime, LT). Blood was taken after dual antiplatelet therapy (DAPT) loading, but before administration of fondaparinux or low molecular weight heparin. Patients with renal or hepatic impairment, known bleeding diathesis, thrombocytopenia and those taking anticoagulation were excluded. Results A total of 775 patients were included, of whom 158 (20%) had DM. Patients with DM, compared to those without DM, more frequently had hypertension (70% vs. 39%, p Conclusions Amongst patients with ACS, those with DM exhibit markedly impaired endogenous fibrinolysis compared to those without DM, and this can be detected with a bedside assay using whole blood. This may explain the increased risk of secondary events in patients with ACS and DM. Funding Acknowledgement Type of funding source: None

Introduction Acute coronary syndrome (ACS) is caused by disruption of an atherosclerotic plaque with initiation of thrombosis, and outcome determined by the balance between prothrombotic drivers and the efficacy of endogenous fibrinolysis. Most patients have obstructive coronary artery disease (CAD), with high shear forces and turbulent flow across severe stenoses enhancing platelet activation. Recognition that some ACS patients have myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) has led to a search to identify drivers behind such presentations. Purpose To assess and compare the thrombotic status of patients with MINOCA and those with ACS due to obstructive CAD. Methods In a prospective observational study in patients with ACS, thrombotic and thrombolytic status was assessed from venous blood using the point-of-care Global Thrombosis Test, assessing time to in vitro occlusive thrombus formation under high shear (occlusion time,OT) and time taken for spontaneous lysis of the thrombus (lysis time,LT). Blood was taken after dual antiplatelet therapy loading, but before fondaparinux or heparin administration. Those with renal or hepatic impairment, bleeding diathesis, thrombocytopenia or on anticoagulation were excluded. MINOCA diagnosis was made according to the Fourth Universal Definition of MI, in the absence of obstructive CAD (no lesion ≥50%) and excluding patients with 1) other overt causes for elevated troponin, 2) overlooked obstructive CAD, and 3) nonischaemic causes for myocyte injury, according to the American Heart Association 2019 recommendation. Patients with Type 2, 4 and 5 MI were excluded. Results We assessed 746 patients, of whom 621 (83%) had ST-segment elevation MI (STEMI) and the rest non-STEMI. Of these, 706 (95%) had obstructive CAD and 40 (5%) had MINOCA. Apart from sex (78% obstructive CAD patients were male vs 50% MINOCA patients), cardiovascular risk factors were similar in MINOCA and obstructive CAD patients (smoking 28 vs 31%, p=0.615; hypertension 35 vs 47%, p=0.153; diabetes 20 vs 20%, p=0.948; hyperlipidaemia 30 vs 36%, p=0.475 and family history of premature CAD 35 vs 35%, p=1.000). There was no difference in time to form occlusive thrombus (OT 424 [371–471] vs 395 [287–512] s, p=0.093) or in endogenous fibrinolysis (LT 1450 [1082–2099] vs 1582 [1252–2130] s, p=0.178) between MINOCA and obstructive CAD patients. Even after propensity score matching with a ratio of 3:1 for clinical characteristics, there was no difference between patients with MINOCA and those with obstructive CAD, with respect to thrombus formation (OT 424 [371–471] vs 430 [300–538] s, p=0.602) or endogenous fibrinolysis (LT 1470 [1082- 2099] vs 1494 [1140–2074] s, p=0.625). Conclusion Amongst patients with ACS, those with MINOCA exhibit similar thrombotic profiles to patients with obstructive CAD with ACS. This represents a potential therapeutic target to modulate risk post myocardial infarction in patients with MINOCA and requires further research. Funding Acknowledgement Type of funding source: None

Percutaneous coronary intervention (PCI) is common in patients with prior coronary artery bypass graft surgery (CABG), however the data on the association between the PCI target-vessel and clinical outcomes are not clear. We aimed to investigate long-term clinical outcomes of patients with prior CABG who underwent PCI of either bypass graft or native artery. We performed a systematic review and meta-analysis of observational studies comparing PCI of either bypass graft or native artery in patients with prior CABG. Twenty-two studies comprising 40,984 patients were included. The median follow-up duration was 2 (1 to 3) years. Compared with bypass graft PCI, native artery PCI was frequent (61% vs 39%) and was associated with lower major adverse cardiac events (MACE) (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.45 to 0.57, p0.001), lower all-cause death (OR 0.65, 95% CI 0.49 to 0.87, p = 0.004), lower myocardial infarction (OR 0.56, 95% CI 0.45 to 0.69, p0.001), and lower target vessel revascularization (TVR) (OR 0.62, 95% CI 0.51to 0.76, p0.001). There was no significant difference in the early incidence of major bleeding or stroke between the 2 cohorts. In 6 studies involving 2,919 patients with ST-elevation myocardial infarction, there was no significant differences between the 2 cohorts. The increase in TVR risk with bypass graft PCI was associated with MACE. In conclusion, in observational studies involving patients with prior CABG, native artery PCI was associated with lower MACE, all-cause death, myocardial infarction, and TVR compared with bypass graft PCI at a median follow-up of 2 years. Native artery PCI might be considered the preferred treatment for bypass graft failure.

Identification of vulnerability to severe coronavirus disease 2019 (COVID-19) is extremely important and might allow optimised shielding and easing of lockdown. The disease is attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which enters host cells through binding to angiotensin converting enzyme 2 (ACE2) on the cell surface. Clinical syndromes such as hypertension that display reduced ACE2 expression tend to correlate with a more severe disease course, whereas treatments which upregulate ACE2 such as the use of angiotensin converting enzyme inhibitors (ACE-i) appear to have a protective effect against COVID-19. Pre-clinical studies have shown that plasma soluble ACE2 could render SARS-CoV-2 inactive in a dose-dependent manner. The association of clinical syndromes or treatments that impact ACE2 expression and clinical severity of COVID-19 infection combined with the reduction in viral load with human recombinant serum ACE2 shown in pre-clinical studies indicate a key role for ACE2 in determining COVID-19 severity. In conclusion, we propose that measurement of ACE2 level may help identify individuals at risk of severe infection where targeted shielding can be used and could provide a novel therapeutic target.

MI with non-obstructive coronary artery (MINOCA) is a condition previously thought to be benign that has recently been shown to have comparable mortality to that of acute coronary syndrome with obstructive coronary disease. The heterogeneity of the underlying aetiology makes the assessment, investigation and treatment of patients with MINOCA challenging. The majority of patients with MINOCA presenting with ST-segment elevation MI generally have an underlying coronary or myocardial cause, predominantly plaque disruption or myocarditis. In order to make the correct diagnosis, in addition to the cause of the presentation, a meticulous and methodical approach is required, with targeted investigations. Stratification of patients to guide investigations that are more likely to provide the diagnosis will allow the correct treatment to be initiated promptly. In this article, the authors review the contemporary incidence, aetiology, recommended assessment and treatment of patients with MINOCA presenting with ST-segment elevation MI.

Aims: The endogenous fibrinolytic system serves to prevent lasting thrombotic occlusion and infarction following initiation of coronary thrombosis. We aimed to determine whether impaired endogenous fibrinolysis can identify patients with ST-segment elevation myocardial infarction (STEMI) who remain at high cardiovascular risk despite dual antiplatelet therapy (DAPT). Methods and results: A prospective, observational study was conducted in 496 patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, at discharge and at 30 days to assess thrombotic status using the automated point-of-care global thrombosis test and patients followed for 1 year for major adverse cardiovascular events (MACEs). Endogenous fibrinolysis was significantly impaired [baseline lysis time (LT) ≥2500 s] in 14% of patients and was highly predictive of recurrent MACE [hazard ratio (HR) 9.1, 95% confidence interval (CI) 5.29-15.75; P 50% (P

© 2020 Oxford University Press. This is a pre-copyedited, author-produced PDF of an article accepted for publication in European Heart Journal following peer review. The version of record [Ying X Gue, Diana A Gorog, Reduction in ACE2 may mediate the prothrombotic phenotype in COVID-19, European Heart Journal, ehaa534] is available online at: https://doi.org/10.1093/eurheartj/ehaa534.

Background The association of atrial fibrillation (AF) with thromboembolic stroke due to stasis in the left atrium and left atrial appendage is well described. Whether AF is associated with a systemic prothrombotic state, detectable in peripheral blood, unclear. Previous studies have been inconsistent, with some very small previous studies ( Purpose It was our aim to compare, in peripheral venous blood, thrombotic and endogenous fibrinolytic profile of healthy volunteers and patients with newly diagnosed nonvalvular atrial fibrillation (NVAF), using a point-of-care technique. Methods In a prospective observational study, venous blood samples were taken from 98 healthy volunteers and 100 patients with newly diagnosed NVAF in the out-patient setting. Patients with newly diagnosed NVAF had venous blood tested before any treatment was initiated with aspirin or oral anticoagulation. Thrombotic status was assessed using the Global Thrombosis Test (GTT), a point-of-care test using native non-coagulated blood, assessed within 15 sec of blood withdrawal. The time to form an occlusive venous thrombus in native (non-citrated) blood, a measure of platelet reactivity (occlusion time, OT) and the time taken to spontaneous endogenous fibrinolysis to restore flow (lysis time, LT) were assessed. Results Basic blood tests (full blood count, renal and liver function, inflammatory markers) were normal in all subjects. The groups were matched for sex and race. Mean age of the healthy cohort was 34±8 years and patients 65±10 years. Endogenous fibrinolysis was markedly impaired in patients with NVAF compared to healthy individuals as shown by markedly prolonged LT (median 2015s [interquartile range IQR 1555–2507] vs. 1124s [IQR 919–1554], p Conclusion In the largest study to date and using a clinically-friendly automated point-of-care technique, we show that patients with NVAF exhibit a systemic prothrombotic state, attributable to significantly impaired endogenous fibrinolysis compared with healthy volunteers. Further studies are needed to see if this could become a screening test for the prothrombotic state in patients with NVAF. Acknowledgement/Funding None

Background Patients with ST-elevation myocardial infarction (STEMI) exhibit enhanced platelet reactivity and a rise in inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (hs-CRP). The extent of the prothrombotic and inflammatory state are predictive of adverse outcomes in patients with acute coronary syndromes. The relationship of these markers of inflammation and thrombosis in the hyperacute phase of STEMI and, whether together, they improve cardiovascular outcome prediction, is not known. Purpose The aim of this study was to assess the individual and combined predictive values of NLR, hs-CRP, and platelet reactivity for clinical outcomes in patients with STEMI. Method In a prospective study of 541 patients presenting with STEMI, acute admission bloods taken prior to emergency percutaneous coronary intervention, were analysed for NLR and hs-CRP. Platelet reactivity was measured using the point-of-care Global Thrombosis Test, which assesses platelet reactivity in native whole blood under high shear, and measures the occlusion time (OT, sec). Shorter occlusion time represents higher platelet reactivity. The study endpoint was occurrence of major adverse cardiovascular events (MACE, defined as composite of cardiovascular death [CVD], myocardial infarction [MI] or stroke [CVA]) at 30 days and 12 months. Results There was a weak, but significant, correlation between hs-CRP and NLR (r=0.25, p Conclusion Both hs-CRP and platelet reactivity are very weakly predictive of MACE, but in combination provide a strong predictor of adverse outcome in STEMI.

open access article Impaired endogenous fibrinolysis is an adverse prognostic biomarker in acute coronary syndrome (ACS). Abnormally dense in vitro fibrin thrombi have been demonstrated in ACS patients and related to hypofibrinolysis using cumbersome, laboratory-based methods. We aimed to assess endogenous fibrinolysis using a point-of-care technique and relate this to clot architecture. From patients with ST-segment elevation myocardial infarction (STEMI), venous blood was drawn immediately on arrival to assess thrombotic status. Blood was assessed using the point-of-care Global Thrombosis Test which measures occlusive thrombus formation under high shear and subsequently endogenous fibrinolysis (lysis time, LT). Two samples per patient were run in parallel. In one channel, the measurement was allowed to proceed as normal. In the other, after occlusion, thrombus was extracted, washed, fixed in glutaraldehyde, dried, sputter-coated, and assessed using scanning electron microscope. Endogenous fibrinolysis was strongly associated fibrin fibre thickness (p = 0.0001). As LT increased (less efficient fibrinolysis), the fibrin network of the thrombus was significantly more compact and dense, with thinner fibrin fibres and smaller gaps. Fibrin fibre thickness correlated inversely with LT (r = − 0.89, p = 0.001). Adverse clot architecture in vitro is directly related to impaired endogenous fibrinolysis using a relatively new point-of-care technique in patients with STEMI. This may transform the relevance of fibrin clot architecture from an off-line laboratory association to being directly relevant to endogenous fibrinolysis at the patient bedside, which could be used as a near-patient test to guide prognosis and assess the effect of treatment.

Asian patients with nonvalvular atrial fibrillation (NVAF) have a higher risk of stroke and systemic embolism than non-Asians, but experience more frequent major bleeding on oral anticoagulation (OAC), including intracranial hemorrhage. Although Asians constituted only a minority of patients in

Introduction ST-segment elevation myocardial infarction (STEMI) is attributable to an occluded coronary artery in almost 90% of patients. Accordingly, restoration of coronary perfusion as early as possible, preferably with primary percutaneous coronary intervention, is the recommended treatment by the European Society of Cardiology, to maximise myocardial salvage. However, not all cases of STEMI are because of coronary artery occlusion. ST-segment elevation myocardial infarction that occurs in the absence of obstructive coronary artery disease on angiography has been termed myocardial infarction with non-obstructive coronary arteries (MINOCA). Case presentation A 44-year-old man was admitted with retrosternal chest pain radiating to the left arm and jaw, and electrocardiography showed extensive anterior ST-segment elevation. Emergency coronary angiography showed all three coronary arteries were patent with Thrombolysis in Myocardial Infarction-3 flow and no evidence of dissection or thrombus. The ST-elevation and pain resolved spontaneously. Troponin-T level rose from

Background— Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established. Methods and Results— In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age P P value of P =0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort. Conclusions— A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction.

Asrac Caeor: 2. Chroc CAD/Sale Ischemc Hear Dsease: Clcalreseao Numer: 120-398Auhors: Nicholas A. Mantini, Danny Eapen, Frank Corrigan, Suliman Alradawi, Pankaj Manocha, Riyaz Patel, Muhammad Hammadah, Mohammad Tarek Kabbany, Ravi Nanjundappa, Rostam Zafari, James C. Lee, Hatem Al Kassem, Revanth Yendamuri, Ying X. Liu, Naureen Farook, Aliy M. Ahmed, Mohammad S. Qadir, Laurence Sperling, Arshed Quyyumi, Emory University School of Medicine, Atlanta, GA, USAIntroduction: sruce sleep apea (SA) s assocae wh oxae sress, rs acors clu hpereso, a wh ar presece o coroar arer sease (CAD). Howeer, wheher SA corues o he seer o CAD a o uure aerse ees paes wh CAD remas uow. We hpohesze ha SA wll e assocae wh reaer seer o coroar aheroscleross a worse caroascular oucomes.Methods: I a case-corol su o 893 paes recrue o he Emor Carolo oa who uerwe coroar aoraph, 402 ha ocumee SA a 491 were ree o SA. Seer o CAD was ocumee us he Ges score. aes were ollowe-up or 2.5 ears or prospece occurrece o maor aerse caroascular ees eie as eah, mocaral arco (MI) or reascularzao. Mularae lear reresso a Cox proporoal hazar moels were perorme o eerme he assocaos o SA wh CAD seer a oucomes.Results: Aer mularae ausme or ae, eer, smo, slpema, aees, o mass ex (MI), mecao, MI/SA eraco a eeco raco, SA remae a epee precor o hher Ges coroar seer score (p=.00). resece o SA was assocae wh a 3.4 (CI 1.48-8.2, p=0.007) reaer hazar or uure aerse CVD oucomes. Us Cox proporoal moel, here was worsee sural or hose wh SA compare o hose whou (p=.044).Conclusions: I uals wh ow CAD or a hh rs or aheroscleross, presece o SA s assocae wh a reaer seer o CAD a s prece o worse caroascular oucomes.