Endogenous Fibrinolysis : An Important Mediator of Thrombus Formation and Cardiovascular Risk

© 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. PUBLISHED BY ELSEVIER INC.Most acute cardiovascular events are attributable to arterial thrombosis. Plaque rupture or erosion stimulates platelet activation, aggregation, and thrombosis, whilst simultaneously activating enzymatic processes that mediate endogenous fibrinolysis to physiologically maintain vessel patency. Interplay between these pathways determines clinical outcome. If proaggregatory factors predominate, the thrombus may propagate, leading to vessel occlusion. However, if balanced by a healthy fibrinolytic system, thrombosis may not occur or cause lasting occlusion. Despite abundant evidence for the fibrinolytic system regulating thrombosis, it has been overlooked compared with platelet reactivity, partly due to a lack of techniques to measure it. We evaluate evidence for endogenous fibrinolysis in arterial thrombosis and review techniques to assess it, including biomarkers and global assays, such as thromboelastography and the Global Thrombosis Test. Global assays, simultaneously assessing proaggregatory and fibrinolytic pathways, could play a role in risk stratification and in identifying impaired fibrinolysis as a potential target for pharmacological modulation.Peer reviewedFinal Published versio

Nitrates for the Management of Acute Heart Failure Syndromes, A Systematic Review

© The Author(s) 2016Intravenous nitrates are widely used in the management of acute heart failure syndrome (AHFS) yet with lack of robust evidence to support their use. We therefore sought to analyze all randomized studies that evaluated the effects of nitrates on clinical outcomes in patients with AHFS. In total, 15 relevant trials comparing nitrates and alternative interventions in 1824 patients were identified. All but 3 were conducted before 1998. No trials demonstrated a beneficial effect on mortality, apart from 1 trial reporting a reduction in mortality, which was related to the time of treatment. Retrospective review suggests that there is a lack of data to draw any firm conclusions concerning the use of nitrates in patients with AHFS. More studies are needed to evaluate the safety and efficacy of these agents in the modern era of guideline-directed use of heart failure therapy.Peer reviewedFinal Accepted Versio

Adjunctive therapies to reduce thrombotic events in patients with a history of myocardial infarction : role of vorapaxar

© 2015 Farag et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) LicenseAcute myocardial infarction (AMI) is generally attributed to coronary atherothrombotic disease. Platelet activation is essential for thrombus formation and is thus an important target for pharmacological intervention to prevent and treat AMI. Despite contemporary treatment with dual antiplatelet therapy, including acetylsalicylic acid and adenosine diphosphate receptor antagonists, patients with prior AMI remain at increased risk of future thrombotic events. This has stimulated the search for more potent antithrombotic agents. Among these is the oral protease-activated receptor-1 antagonist vorapaxar, which represents a new oral antiplatelet agent to reduce thrombotic risk in patients with atherothrombotic disease. The TRACER and the TRA 2°P-TIMI 50 trials concluded that vorapaxar in addition to standard therapy reduced ischemic adverse cardiac events. A remarkable benefit was observed in patients with stable atherosclerotic disease, particularly those with a previous history of AMI. Although favorable effects were seen in reduction of adverse cardiac events, this was associated with excess major and intracranial bleeding, particularly in patients at high risk of bleeding and those with a history of stroke or transient ischemic attack. Currently, the lack of a reliable individualized risk stratification tool to assess patients for thrombotic and bleeding tendencies in order to identify those who might gain most net clinical benefit has led to limited use of vorapaxar in clinical practice. Vorapaxar may find a niche as an adjunct to standard care in patients at high risk of thrombotic events and who are at low risk of bleeding.Peer reviewe

A rare cause of myocardial infarction with non-obstructive coronary arteries-case report of ST-segment elevation myocardial infarction caused by a mediastinal mass

© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.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 A 44-year-old man was admitted with retrosternal chest pain radiating to the left arm and jaw, and electrocardiogpresentation raphy 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 <3 ng/L on arrival to 549 ng/L at 12 h. Subsequent cardiac magnetic resonance imaging (MRI) showed a structurally normal heart (without late gadolinium enhancement) but detected an incidental large, lobulated (90 * 31 * 71 mm) mediastinal mass containing multiple cysts in the anterior mediastinum with inflammation and oedema of the parietal pericardium. Tissue biopsy confirmed Hodgkin's lymphoma and the patient was initiated on chemotherapy. Discussion Some 3% of ST-segment myocardial infarctions occur in the absence of obstructive coronary disease (MINOCA), is more frequent in younger patients. Cardiac MRI is a useful tool to both identify some of the potential causes of MINOCA and also to confirm the diagnosis of infarction. Some 26% of MINOCA patients have significant biochemical evidence of myocardial injury but have a normal cardiac MRI. This case illustrates a very rare cause of myocardial infarction in a young patient with unobstructed coronary arteries, and highlights the need in such cases for further detailed imaging of the myocardium and thorax to establish the diagnosis and initiate appropriate treatment.Peer reviewedFinal Published versio

Reduction in ACE2 may mediate the prothrombotic phenotype in COVID-19

© 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.This commentary refers to ‘Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy’, by R.M. Inciardi et al., doi: 10.1093/eurheartj/ehaa583.Peer reviewedFinal Accepted Versio

Incidence of thrombotic complications in COVID-19

A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.Peer reviewedFinal Published versio

Is there a role for oral triple therapy in patients with acute coronary syndromes without atrial fibrillation?

© 2018 Bentham Science PublishersBACKGROUND: Acute coronary syndrome (ACS) patients, despite treatment with dual antiplatelet therapy (DAPT), have up to 10% risk of recurrent major adverse cardiac events (MACE) in the short term. METHODS: Here we review studies using more potent antithrombotic agent combinations to reduce this risk, namely triple therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations of trials to date. RESULTS: Generally speaking, TT leads to an increase in bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an option for secondary prevention beyond the immediate subacute phase, particularly if prasugrel or ticagrelor are not available. Non-vitamin K oral anticoagulants (NOACs) all increased bleeding, with only modest reduction in MACE noted with low dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and clopidogrel in ACS patients at high ischaemic and low bleeding risk, without prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin, looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising a NOAC with a P2Y12 inhibitor. CONCLUSION: More potent antithrombotic regimens increase bleeding and should only be considered on an individual basis, after careful risk stratification. Accurate risk stratification of ACS patients, for both ischaemic and bleeding risk, is essential to allow individualised treatment.Peer reviewe

Peripartum cardiomyopathy- can the link between prolactin and PAI-1 provide a clue?

© 2020 Oxford University Press. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The version of record, Diana A Gorog, Gemma Vilahur, Peripartum cardiomyopathy: can the link between prolactin and PAI-1 provide a clue?, Cardiovascular Research, cvaa109, is available online at: https://doi.org/10.1093/cvr/cvaa109.Peer reviewe

Screening for venos thromboembolism in patient with COVID-19

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Pulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.Peer reviewe