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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

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.