Education in Heart Heart: first published as 10.1136/heartjnl-2012-301962 on 14 November 2012. Downloaded from ACUTE CORONARY SYNDROMES Left ventricular thrombus formation after acute myocardial infarction Ronak Delewi,1 Felix Zijlstra,2 Jan J Piek1 < Additional references are Cardiovascular disease remains the leading cause of thrombus after discharge, often in association with published online only. To view death in western society. Mortality from acute worsening LV systolic function. Spontaneous or these references please visit the journal online (http://dx.doi.org/ myocardial infarction (AMI) has decreased since the anticoagulant induced resolution is relatively 10.1136/heartjnl-2012-301962). introduction of primary percutaneous coronary common in LV thrombus formation after AMI. 1Department of Cardiology, intervention (PCI), which has proved to be superior Thrombus seems to disappear more often in Academic Medical Center, to thrombolytic therapy by demonstrating lower patients with apical akinesia than those with apical University of Amsterdam, mortality rates and reduced clinical adverse events. aneurysm or dyskinesia.1 Amsterdam, the Netherlands Nevertheless, postinfarct complications still lead to It has been speculated that LV thrombus plays 2 Department of Cardiology, morbidity and mortality in a large number of a positive role in the acutely infarcted myocardium, Erasmus Medical Center, Rotterdam, the Netherlands patients. by offering mechanical support to the infarcted One of the most feared complications is the myocardium and therefore protecting against LV Correspondence to occurrence of thromboembolic events (mostly rupture.w4 The thrombus becomes firmly attached Professor Dr Jan J Piek, cerebrovascular accidents) due to left ventricular to its site of origin, enhancing the underlying Department of Cardiology, (LV) thrombus formation. The risk of LV thrombus myocardial scar, limiting potential infarct expan- Academic Medical Center, fi University of Amsterdam, PO formation is highest during the rst 3 months sion, and partially restoring the thickness of the Box 22660, 1100 DD following acute myocardial infarction, but the myocardial wall. As a consequence, bulging is Amsterdam, The Netherlands; potential for cerebral emboli persists in the large reduced, resulting in a more effective myocardial [email protected] population of patients with chronic LV dysfunc- contraction. Often, however, expansion of the tion. Since these thromboembolic events are infarct zone occurs very early after infarction, usually unheralded by warning signs of transient before the thrombus has time to organise and is cerebral ischaemia, the only truly satisfactory able to prevent formation of LV aneurysm and medical approach is adequate management of these myocardial rupture. high risk groups. This article discusses the inci- dence, diagnosis and management of LV thrombus http://heart.bmj.com/ formation after an AMI. INCIDENCE Early data from the prethrombolytic and throm- bolytic eras suggest that in the setting of AMI, LV PATHOGENESIS OF LV THROMBUS thrombus was present in 7e46% of patients, most The combination of blood stasis, endothelial injury frequently in acute anterior or apical myocardial e e and hypercoagulability, often referred to as infarction.2 4 w3 w5 Differences in diagnostic Virchow’s triad, is a prerequisite for in vivo techniques, timing of examination and use of thrombus formation. In the presence of LV antithrombotic treatment cause substantial varia- on September 26, 2021 by guest. Protected copyright. thrombus formation after AMI, the three compo- tion in the reported frequency of thrombus from nents of this triad can also be recognised (figure 1). different series. In addition, it should be noted that LV regional wall akinesia and dyskinesia result in the incidence as reported in autopsy studies is blood stasis, often recognised on two dimensional consistently higher compared with clinical studies, echocardiography by the occurrence of spontaneous probably due to better accuracy but also due to LV contrast. Prolonged ischaemia leads to suben- patient selection. docardial tissue injury with inflammatory changes. Nowadays the reported incidence is lower. This is Finally, patients with an acute coronary syndrome probably due to (1) more aggressive anticoagulation display a hypercoagulable state with, for example, therapies in the acute phase (eg, the use of heparin, increased concentrations of prothrombin, fibrino- bivalirudin), (2) smaller infarctions, and (3) peptide A, and von Willebrand factor, and decreased improved LV remodelling. Although the use of ACE concentrations of the enzyme responsible for inhibitors is also thought to be associated with cleaving von Willebrand factor (ADAMTS13).w1 w2 improved LV remodelling, the GISSI-3 study found This triad can result in the formation of LV no difference in LV thrombus rates between thrombus composed of fibrin, red blood cells, and patients who did and did not receive lisinopril.5 platelets. There are limited data on the exact frequency of LV thrombus can occur within 24 h after AMI. LV thrombus in PCI treated AMI patients. Two One study performing serial echocardiographic studies found LV thrombus formation in 5.4% and studies showed that about 90% of thrombi are 7.1% of patients with acute anterior wall myocar- formed at a maximum of 2 weeks after the index dial infarctions.w6 w7 However, these studies were event.w3 However, some patients develop a new LV retrospective, non-serial and only assessed LV Heart 2012;98:1743–1749. doi:10.1136/heartjnl-2012-301962 1743 Education in Heart Heart: first published as 10.1136/heartjnl-2012-301962 on 14 November 2012. Downloaded from towards the posterolateral wall. In such cases the prevalence is similar to that observed in anterior wall AMIs of comparable extension.w5 Thrombi can also be found in small apical infarcts, with good global systolic function.w3 The presence of thrombi is significantly related to the region of most severe functional impairment and/or the region with myocardial enhancement (ie, infarction or scarring).7 LV thrombus appears earlier in the course of the disease when initial ejection fraction #40%, in the presence of multi- vessel coronary artery disease, or a high peak crea- tine kinase value.w8 There is conflicting evidence with respect to the influence of b-blockers. Several studies have reported a higher frequency of thrombus develop- Figure 1 The three components of the Virchow’s triad in b left ventricular thrombus formation. ACS, acute coronary ment in patients treated with -blockers which syndrome; LV, left ventricular. could be related to the negative inotropic action of these drugs and thus increased blood stasis. In particular, in a randomised study, Johannessen et al thrombus formation at a single point in time and reported an increased occurrence of thrombus in during the early phase of recovery after myocardial patients with anterior AMI after oral b-blocker infarction. therapy.w9 Turpie et al reported similar results after In the latter study a follow-up echocardiography treatment with b-blockers in a large population of was performed at 1e3 months, showing LV 9 w7 patients with AMI. The GISSI-2 study, however, thrombus in an additional 8% of the patients. observed the same rate of LV thrombi in patients et al Solheim reported a similar incidence of 15% in with or without atenolol.10 the first 3 months in a selected group of AMI 6 It has been demonstrated that mitral regurgita- patients treated by primary PCI. So, the timing of tion prevents thrombus formation in patients LV thrombus assessment is crucial, as assessment with dilated cardiomyopathy.w10 The protective too soon after the onset of myocardial infarction effect of mitral regurgitation may be the conse- will probably lead to failure to detect the thrombus quence of augmented early diastolic flow velocities fi in a signi cant percentage of patients. at the mitral annulus level, as well through the entire length of the left ventricle, protecting the CLINICAL FACTORS CONTRIBUTING TO LV LV cavity from a stagnant, thrombogenic blood http://heart.bmj.com/ THROMBUS FORMATION flow pattern. In addition, studies suggest abnormal Risk factors for the development of LV thrombus flow profiles are associated with the presence of an are consistently irrespective of infarct treatment LV thrombus.11 w11 However, to date no studies and include large infarct size, severe apical asynergy have demonstrated the same association in patients (ie, akinesis or dyskinesis), LV aneurysm, and with AMI. e anterior MI.2 5 8w6This is consistent with an There have been few studies on the use of increased contribution of at least two of the three biomarkers in the setting of LV thrombus forma- components of Virchow’s triad, namely a larger tion. It could be postulated that factors involved in on September 26, 2021 by guest. Protected copyright. area of blood stasis as well as an increased area of the coagulation cascade could serve as biomarkers to injured subendocardium. identify patients at increased risk for LV thrombus In a study of more than 8000 patients with ST development. Data presented at the European elevation myocardial infarction (STEMI), LV Society of Cardiology in 2011 demonstrated higher thrombus was found in 427 patients (5.1%). This soluble tissue factor and d-dimer concentrations in incidence is relatively low compared to other patients with LV thrombus formation.w12 Another studies, probably because of the exclusion of high study observed mildly