were not randomised but often utilised patientsseen 3 h after symptom onset as a control group.Data from the GISSI-3 database, including morethan 8000 patients, showed no reduced incidence ofthrombus formation in patients who receivedeither thrombolytic therapy or heparin.5

Intravenous thrombolysis has also been used fortreatment of documented LV thrombus. In a reportof 16 patients with LV thrombus on echocardio-graphy, urokinase was infused intravenously ata rate of 60 000 U/h for 2e8 days in combinationwith intravenous heparin (200 units/kg3 12 h).LV thrombi were successfully lysed in 10 of 16patients. None of the patients suffered from clinicalembolism, and therapy had to be discontinued inonly one patient due to haematuria.w33 In a laterstudy, four patients with mobile LV thrombus weretreated with intravenous urokinase or strepto-kinase. In the first two cases, lysis of thrombus wasachieved without complication. In the latter twocases, however, systemic embolism occurred, withtransient diplopia in one and stroke followed bydeath in the other.1 It was concluded that fibrino-lytic agents are capable of lysing ventricularthrombi but that the risks of this therapy aretoo high.

HeparinData regarding the benefit of heparin treatment inpatients with documented LV thrombus on echo-cardiography during the first 2 weeks are somewhatconflicting, leading us to believe that there may bea benefit, at least in the short term. In a randomisedcontrolled trial, AMI survivors who were treatedwith high dose heparin (12 500 units subcutane-

ously every 12 h) showed a lower incidence ofLV thrombus formation than those administereda low dose (5000 units subcutaneously every 12 h)(11% vs 32%, p< 0.001) during a 10 day period.9

Results from the SCATI study showed a similarreduction in LV thrombus formation for the groupthat was treated with calciumeheparin comparedto the control group in patients undergoingthrombolysis.w34 In the GISSI-2-connected study,however, high dose heparin did not preventthrombus formation (27% vs 30%, pNS).10 Ina study with 23 consecutive patients with mobileand protruding thrombi, high dose heparin wasgiven intravenously over a period of 14e22 days(mean 146 4). In all 23 patients LV thrombidecreased in size, with disappearance of the highrisk features. No embolic events were detectedduring treatment, and the only complication wasan upper gastrointestinal haemorrhage.w35 Dalte-parin, a low molecular weight heparin, reduced theincidence of LV mural thrombus formation but hadno influence on the risk of systemic embolisation,and its use was associated with an increased risk ofhaemorrhage.w36

Vitamin K antagonistObservational studies conducted in the pre-thrombolytic and thrombolytic eras have providedsupport for the hypothesis that anticoagulationreduces the risk of embolisation.1 2 4 w3 w37ew39

A 1993 meta-analysis included 11 studies of 856patients who had an anterior myocardial infarction;the odds ratio (OR) for an embolic event was 5.5(95% CI 3.0 to 9.8).19 The meta-analysis includedseven studies with 270 patients that included dataon the relationship between anticoagulation for6 months and embolisation. Although all sevenstudies presented data suggesting that systemicanticoagulation reduces embolic complications, thistrend reached significance only in three trials. Whenpooling the data, anticoagulation compared withno anticoagulation was associated with a reductionin the rate of embolisation (OR 0.14, 95% CI 0.04to 0.52).Based on these data, both current European

Society of Cardiology and American College ofCardiology/American Heart Association guidelinesrecommend vitamin K antagonist therapy inpatients with an LV thrombus after myocardialinfarction.w40 w41

However, vitamin K antagonists do not appear toaffect the likelihood of resolution of the throm-busw3 and, unfortunately, no large randomised trialshave been performed to evaluate the efficacy of longterm anticoagulation to prevent embolisation inpatients with LV thrombus. Therefore the effects oflong term anticoagulants on the risk of embolisationare the subject of debate. Among the many ques-tions left unanswered is when to withdraw anti-coagulant medication when thrombus is identifiedsince the risk of embolisation decreases over time,likely as a result of organisation of thrombus whichincludes thrombus neovascularisation. However,retrospective studies documented ongoing embolic

Figure 3 Transthoracic echocardiographic appearance of a mobile, protruding leftventricular thrombus. Courtesy of J Vleugels and Rianne H A de Bruin, Department ofCardiology, Department of Cardiology, Academic Medical Center, Amsterdam, theNetherlands.

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risk in LV thrombus patients.w42 In indium-111platelet imaging studies most thrombi, regardless ofage, have been observed to have externally detect-able ongoing platelet accumulation, indicatingcontinued surface activity.20 The European guide-lines recommend vitamin K antagonist for at least3e6 months, while the American guidelinesrecommend indefinite treatment in patientswithout increased risk of bleeding.Although there are limited data regarding the

appropriate follow-up and timing of cessation ofvitamin K antagonists in these patients, thefollowing approach seems appropriate for mostpatients:< Assess LV thrombus within the first month

after AMI, preferably with CMR in high riskpatients, and start vitamin K antagonist whenLV thrombus is present and no contraindicationexists

< Re-evaluate LV thrombus formation after6 months since data show that LV thrombusresolution in the initial months is very common,also in patients treated with vitamin K antag-onistsw43

< When LV thrombus is not present and there isno other indication for vitamin K antagonist,assess bleeding risk and consider stoppingtherapy.Newer anticoagulants are presently being

developed and some of them are alreadyregistered.w44ew46 It can be envisioned that in thelonger term these new anticoagulants will replacevitamin K antagonists. However, at presentvitamin K antagonist therapy is still the standard ofcare for the treatment of LV thrombus. Moreimportantly, the newer anticoagulants also havethe risk of fatal and non-fatal bleedings and theirrole in LV thrombus patients should be furtherassessed.

Antiplatelet therapy and triple therapy inthe PCI eraAnother issue is that nowadays STEMI patients aretreated by primary PCI and receive long term dualantiplatelet therapy (including aspirin and a P2Y12inhibitor). Consequently, patients with LVthrombus or at increased risk of LV thrombus aftera myocardial infarction are frequently being treatedwith vitamin K antagonist in addition to dualantiplatelet therapy (triple antithrombotic therapy)and therefore are subjected to an increased bleedingrisk. It is unclear, however, if long term anti-coagulation is still necessary in STEMI patientstreated by primary PCI and subsequent dualantiplatelet therapy.Large prospective studies show a yearly incidence

of bleeding of approximately 3.7% for dual anti-platelet therapy and 12% for triple antithrombotictherapy.w47 The most common site of bleeding isthe gastrointestinal tract (30e40%) and cerebrum(9e10%), with 25% of episodes in the latter siteproving fatal. Furthermore, non-fatal bleedings arean important predictor of mortality post-PCI atfollow-up.w48 Also, in regard to hospitalisation

Left ventricular thrombus formation after myocardial infarction: keypoints

< Left ventricular (LV) regional wall akinesia and dyskinesia resulting in bloodstasis, prolonged ischaemia leading to subendocardial tissue injury withinflammatory changes and a hypercoagulable state, are consistent withVirchows triad, resulting in LV thrombus formation.

< Risk factors for the development of LV thrombus include: large infarct sizes severe apical asynergy LV aneurysm anterior myocardial infarction

< There is reported controversy regarding the negative influence of b-blockersand the protective effect of mitral regurgitation.

< Early data from the prethrombolytic and thrombolytic era suggest that in thesetting of acute myocardial infarction, LV thrombus was present in 7e46% ofpatients.

< Nowadays the reported incidence is lower, probably due to (1) moreaggressive anticoagulation therapies in the acute phase (eg, use of heparin,bivalirudin), (2) smaller infarctions, and (3) improved LV remodelling.

< Timing of LV thrombus assessment is crucial, as assessment too soon afterthe onset of myocardial infarction will miss LV thrombus formation.

< Transthoracic echocardiography is most often used for assessing LVthrombus. However, it is estimated that 10e46% of echocardiograms areinconclusive.

< Delay enhancement cardiac magnetic resonance imaging (CMR) is nowadaysconsidered the gold standard.

< Cine-CMR, transoesophageal echocardiography, radionuclide angiography,and CT seem less appropriate for LV thrombus detection.

< Conditions that increase the risk of systemic embolisation in patients with LVthrombus are: (1) severe congestive heart failure, (2) diffuse LV dilatation andsystolic dysfunction, (3) previous embolisation, (4) advanced age, and (5)presence of LV protruding or mobile thrombi.

< Observational studies conducted in the prethrombolytic and thrombolytic erashave provided support for the hypothesis that warfarin reduces the risk ofembolisation.

You can get CPD/CME credits for Education in Heart

Education in Heart articles are accredited by both the UK Royal College ofPhysicians (London) and the European Board for Accreditation in Cardiologydyou need to answer the accompanying multiple choice questions (MCQs). Toaccess the questions, click on BMJ Learning: Take this module on BMJLearning from the content box at the top right and bottom left of the onlinearticle. For more information please go to: http://heart.bmj.com/misc/education.dtl< RCP credits: Log your activity in your CPD diary online (http://www.

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after emergency department visits in the USA foradverse drug events in patients above 65 years,33.3% of the 99 628 hospitalisations concernedwarfarin.w49 Moreover, in the general STEMIpopulation treated with primary PCI and dualantiplatelet therapy but no anticoagulationtherapy, symptomatic cerebral infarction is rare,occurring in 0.75e1.2% of all STEMI patients.w50

Thus, the potential benefit of vitamin K antagonisttreatment on top of dual antiplatelet therapy maynot outweigh the increased bleeding risk. This callsfor a randomised trial to be conducted to determinewhether anticoagulation treatment preventsembolic complications in AMI patients treatedwith primary PCI.

Acknowledgements We gratefully acknowledge the valuablecontribution of ME Hassell, MD.

Contributors RD: drafting the manuscript; FZ: critical revision; JP:interpretation of the data.

Funding This work was supported by a grant from the Dutch HeartFoundation and National Health Insurance Board/ZON MW, theNetherlands to RD. Grant number 2011 T022 + 40-00703-98-11629.

Competing interests In compliance with EBAC/EACCME guidelines,all authors participating in Education in Heart have disclosed potentialconflicts of interest that might cause a bias in the article. Theauthors have no competing interests.

Provenance and peer review Commissioned; internally peerreviewed.

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< Excellent review on intracardiac thrombi and anticoagulanttreatment.

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< Relevant meta-analysis regarding the embolic potential andmanagement of LV thrombus.

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< Clinical study with indium-111 platelet imaging of LVthrombi.

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acute myocardial infarctionLeft ventricular thrombus formation after

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