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768 lACC Vol g, No 6 December 1986.76B-87B

Thrombosis and From Cardiac Chambers and Infected Valves

PHILIP C. ADAMS, BA, MRCP,* MARC COHEN, MD, FACC,* JAMES H. CHESEBRO, MD, FACC,t VALENTIN FUSTER, MD, FACC*

New York. New York and Rochester, Minnesota

In a number of cardiac conditions (acute myocardial orrhage is high, and the efficacy of conventional anti• infarction, chronic left ventricular aneurysm, dilated coagulants unclear; thus, anticoagulation should not be , infective and atrial fi• instituted for the cardiac condition as such. However, brillation in the absence of valvular disease), the risk of in prosthetic valve endocarditis, the risk of embolism embolism gives cause for concern. Although anticoag• seems to be very high, and therapy should ulation with warfarin (Coumadin)-derivatives has been be continued, but with great care because there is a shown to be effective in some of these situations, there substantial risk of cerebral hemorrhage. is no evidence regarding the role of antiplatelet agents. Atrial in patients with valvular heart dis• The common factor in the thromboembolic potential ease is dealt with in a previous review. Patients with of acute , chronic left ventricular nonvalvular are at varying risk of em• aneurysm and is mural throm· bolism, depending on the etiology of the ; bus. This can be detected by two-dimensional echocardi· trials of antithrombotic therapy are needed for the var• ography and indium-Ill platelet scintigraphy. Although ious subsets of patients. In most elderly patients, the of value in elucidating the natural history of mural etiology is not known, and their stroke risk is high. The , in most cases, management is not substan• risk of embolism in younger patients with idiopathic tially aided by these investigations. atrial fibrillation is so low as to make any antithrombotic In patients with extensive myocardial infarction, par• therapy unnecessary. Patients with atrial fibrillation due ticularly anterior infarction, moderate intensity anti• to hypertrophic cardiomyopathy are at a high risk of started soon after hospital admission reduces embolism, while for patients with atrial fibrillation due the rate of embolism. After 8 to 12 weeks, embolic risk to ischemic heart disease, the risk is uncertain. Anti• is low so that can usually be discontinued. coagulation is appropriate in some patients around the Patients with chronic left ventricular aneurysm have a time ofdirect current cardioversion. In addition, in those low incidence ofembolism; anticoagulation is, therefore, conditions that would of themselves merit long-term an· inappropriate. Dilated cardiomyopathy is associated with ticoagulation, this should be continued after cardio• a high risk of embolism; moderate intensity anticoagu• version. lation may be advisable in many such cases. Little in• For each patient, the potential benefits of anticoag• formation is available regarding the incidence of throm• ulation have to be carefully balanced against the risks boembolism or the role of antithrombotic therapy in the of bleeding. The intensity of anticoagulant therapy ap• patient with a diffusely dilated left ventricle due to isch• plied should be matched to the patient's clinical condi• emic heart disease. tion. In native valve , the risk of hem- (J Am Coil CardioI1986;8:76B-87B)

In this presentation, we will discuss intracavitary diomyopathy. infective endocarditis and atrial fibrillation. and consequent embolism in patients with acute myocardial Embolism makes an important contribution to the morbidity infarction, chronic left ventricular aneurysm, dilated car- and mortality associated with each of these conditions, but there is considerable controversy regarding their optimal antithrombotic management because few large randomized From the *Division of , Department of Medlcme, Mount Sinai School of Medicine of the City University of New York, New York, New York and the tDivision of Cardiology, Mayo Clinic, Rochester, Address for reprints: Valentm Fuster, MD, DivisIOn of Cardiology, Minnesota, Dr. Adams is a recipient of a BritJsh-American Research Fel• Mount Sinai Medical Center, One Gustave Levy Place, New York, New lowship of the American Heart Association and British Heart Foundation, York 10029,

©1986 by tbe Amencan College of Cardiology 0735-1097/86/$350 lACC Vol. 8, No 6 ADAMS ET AL 77B December 1986 76B-87B 1NTRACARDIAC THROMBOSIS AND EMBOLISM

studies have addressed this issue, Our analysis aims to de• Two-dimensional echocardiography has been applied to scribe the impact of thromboembolism and define the po• the detection of mural thrombi in the three left ventricular tential risks and benefits of anticoagulation in this group of conditions under consideration (18,19) (Fig. 1). Adequate conditions, We offer guidelines for therapy on the basis of images are obtained in most patients (19), and the technique our own clinical practice and the recommendations of the is suitable for repeated observations. Correct interpretation American College of Chest Physicians (ACCP)-National of intracavitary echoes as thrombus is clearly essential. Heart, Lung, and Institute Committee (1), Thrombi are almost always associated with an abnormality of wall motion (12), commonly at the apex. The margins of the thrombus are distinct, with occasionally free motion Mural Thrombi of protruding parts of the mass. The texture of the mass is Intraventricular mural thrombi are common in patients usually different from that of the underlying myocardium. with acute myocardial infarction, chronic left ventricular The mass may vary in appearance in serial examinations. aneurysm and dilated cardiomyopathy, The improvements In some cases, the center of the thrombus is lucent (19,20), in imaging of thrombi by both two-dimensional echocardi• a feature seen shortly before the thrombus becomes unde• ography and scintigraphy with indium-labeled platelets has tectable, and thought to be due to spontaneous lysis (19). led to increased interest in the detection of mural thrombi. Sources of difficulty may include apical trabeculation in with several reviews (2-7) appearing over the last few years, patients with left , false chordae and Underlying pathology. Two major mechanisms con• tangential imaging of normal left ventricular myocardium tribute to intracavitary thrombus formation in patients with (21). Near field artifact is a particular problem when imaging acute myocardial infarction, chronic left ventricular aneu• from the apex, especially in the presence of increased myo• rysm and dilated cardiomyopathy, namely, abnormalities of cardial echogenicity (20), Despite these problems, studies the and stasis, In the first 2 days after myo• (18,20,22) of the performance of echocardiography suggest cardial infarction, leukocytic infiltration lifts off the endo• a sensitivity and specificity of 80 to 90% or greater. cardium (8), exposing subendothelial tissue. Consequently, Scintigraphy after the administration of indium-ill-la• the circulating blood is exposed to a thrombogenic surface, beled platelets, unlike two-dimensional echocardiography, and thrombi become common by 4 to 5 days after infarction provides pathophysiologic data by detecting continuing dep• (9), If a left ventricular aneurysm develops, endocardial osition of platelets on the thrombus (18). Images have to abnormalities persist and may be fibroelastic or thrombotic be obtained soon after injection and later after time has (10), The latter is more likely to be the source of emboli, elapsed to allow platelets to accumulate on the thrombus, Endocardial abnormalities may also be seen in patients with typically 3 to 4 days. Only those thrombi actively incor• cardiomyopathy (11). porating platelets are imaged. Because of this, the technique Thrombi developing in patients with myocardial infarc• has a sensitivity of only about 70%, although false positive tion are always adherent to regions of akinesia or dyskinesia studies are unusual (6,23). It is not known whether contin• (12), with stasis of adjacent blood. Stasis of intracavitary uing platelet incorporation into the thrombus, as detected blood within some left ventricular aneurysms can be de• by indium-labeled platelet scintigraphy, is a marker for greater tected by the demonstration of swirling smoke-like echoes embolic potential when compared with the echocardio• by two-dimensional echocardiography (13,14). Stasis in the graphic detection of thrombus that does not take up platelets atria in patients with atrial fibrillation predisposes to throm• actively, bus formation in a similar way. Both two-dimensional echocardiography and indium-la• In patients with myocardial infarction, a third factor, the beled platelet scintigraphy are reliable and efficient tech• systemic reaction to the event, with fever, leukocytosis and niques and have furthered our understanding of the fre• increased plasma concentrations of acute phase proteins, quency and significance of mural thrombi. However, their may also contribute to the tendency to form thrombi (15), value to the clinician in the management of the individual Imaging techniques for the detection of mural throm• patient is not well defined. We believe that the results of bus. Angiography may detect left ventricular thrombus. these tests have only limited value in therapeutic decision However, it is not suited for repeated observations and is making. insensitive, detecting only about 30% of pathologically con• firmed mural thrombi (16,17). In addition, angiography in Mural Thrombosis and Thromboembolism in patients with left ventricular aneurysm may fail to detect Specific Clinical Settings thrombus because the apex may not be well filled during left ventriculography, and the thrombus often conforms to Acute Myocardial Infarction the outline of the rest of the ventricle, Computed tomog• Myocardial infarction predisposes to both mural throm• raphy and nuclear magnetic resonance imaging have been bus formation and subsequent embolism. Only a small pro• used to detect mural thrombus and are promising techniques. portion of patients with myocardial infarction and mural 788 ADAMS ET AL lACC Vol ~. No () INTRACARDIAC THROMBOSIS AND EMBOLISM December 1986 76B-87B

thrombus will develop clinical embolism, although most infarction (Fig. I). Most echocardiographic studies show an patients with clinical arterial embolism have or have had incidence rate of 30 to 40% in patients with anterior in• mural thrombus. We, therefore, consider both mural throm• farction, and up to 5% in patients with inferior myocardial bus formation, detected pathologically and by the imaging infarction. The thrombi are seen most frequently on the third techniques discussed, and embolism detected clinically. to sixth days after the infarction. Asinger et a1. (12) reported Natural history and risk factors. Autopsy studies (24,25) the results of echocardiography in 70 patients with a first suggest that about 40% (range 17 to 66) of patients dying infarction studied prospectively, in whom echocardiograms after myocardial infarction have mural thrombus at the time were performed at intervals of approximately 3 days. De• of death. This figure may overestimate the actual frequency spite the adminstration of low dose anticoagulants, 12 of in life because it includes patients with larger infarcts (those 35 patients with anterior infarction developed mural throm• who died) and patients with infarcts of various ages. bus compared with none of 35 patients with inferior in• Mural thrombus detection. Echocardiography frequently farction. Thrombi were first detected between I and 11 reveals mural thrombus in patients with acute myocardial (mean 5) days after infarction. A similar study (26) of 54 patients with anterior infarction revealed mural thrombus in Figure l. Mural thrombus detected by echocardiography. Upper 17 (31 %) in the absence of anticoagulation. More detail of panel, Thrombus (T) protruding into the left ventricular cavity in this apical four chamber view. Lower panel, Multilobular. pe• the natural history was provided by a study (27) of 96 dunculated thrombus (TH), in a patient with a dyskinetic apex due patients treated with 10,000 IU/day subcutaneously, to recent infarction, again in an apical four chamber view. (Lower with additional warfarin for patients with anterior infarction. panel reprinted with permission from Goldman ME, Friedman S. These patients were imaged within 24 hours of infarction Introduction to Cross-sectional Echocardiography. an AV Pro• and at 3 days, 4 days and 4 months. A total of 18 patients gram. Medical Education Programs Ltd, 1984.) developed thrombus. Two thrombi were present within 24 hours of admission, a further 3 by 2 days and a further 10 by 3 days. Three additional patients had developed thrombus by the 4 month examination. In all three studies, thrombus was much more frequent in patients with a large anterior wall infarct, particularly those with apical dyskinesia. How• ever, mural thrombus has been detected in 30% of patients with inferior infarction in one series (28). Platelet scintigraphy detects a similar number of mural thrombi. For example, 48% of patients with anterior in• farction studied in the first week after infarction had a pos• itive scan, despite the use of prophylactic subcutaneous heparin (29). Embolism. Mural thrombosis, as just described, predis• poses to embolism, most emboli arising from mural thrombi. In the 1930s, some 10% of the deaths of patients with myocardial infarction were attributed to emboli (30). Fur• thermore, autopsy studies (24,25) reveal emboli in 25 to 50% of cases of myocardial infarction, most commonly to the viscera. These were likely to be clinically important in only 5 to 8% of the population studied. In the British Med• ical Research Council study (31) of anticoagulation in acute myocardial infarction, 3.4% of the control group (no anti• coagulation) developed clinical systemic embolism. Em• bolic stroke occurs in some 2 to 3% of patients within 4 weeks of myocardial infarction, 90% of these strokes oc• curring in patients with anterior infarction (32,33). The risk of embolism peaks late in the first week after infarction, and then decreases rapidly so that after about 6 to 8 weeks, it is very low (0.35/100 patient-years) (34). Although riskfactorsfor embolism and mural thrombosis are similar, clinical prediction of embolism is clearly most important. Emboli occur most frequently in patients with echocardiographic evidence of mural thrombus (12,26,35). JACC Vol. 8, No 6 ADAMS ET AL 79B December 1986:76B-87B INTRACARDIAC THROMBOSIS AND EMBOLISM

Mural thrombus is detected most commonly in patients with thrombus formation and subsequent embolism are not greatly a large anterior myocardial infarction and poor hemody• reduced by low dose or inappropriately timed anticoagu• namic status. Whether the detection of a mural thrombus in lation. This is revealed by the echocardiographic studies such patients suggests that they are at greater risk of em• mentioned before, in which patients received anticoagu• bolism than otherwise similar patients in whom such thrombi lants, in low doses (that is, heparin subcutaneously 5,000 are not detected is at present unknown. However, if a throm• units twice daily) (12) or the addition of coumadin to initial bus is detected, certain features of the thrombus at echo• low dose heparin only after mural thrombus was detected cardiography are associated with a higher rate of embolism. (27). However, heparin (to maintain the activated partial Protruding thrombi, particularly if they are mobile (13), are thromboplastin time at 70 to 140 seconds) and warfarin (to more likely to embolize than are flat thrombi (36,37). maintain the Thrombotest at 5 to 10%; prothrombin time of Detection ofhigh risk factors. Other features than those 1.4 to 2.2 times control) prevented the development ofmural detected by echocardiography may also be helpful in defin• thrombus in a single-blind study (41), this treatment being ing a group of patients at high risk of embolism. Site of started within 12 hours of the onset of symptoms of infarc• infarction is important, with emboli being more frequent, tion. as mentioned, in patients with anterior infarction. However, Some studies (12,42) suggest that resolution of mural in one series (38), 30% of strokes were in patients with thrombi is more rapid and complete if anticoagulants are inferior infarctions. Patients with a large infarction are at given. However, another study (43) showed no increase in higher risk of embolism. In one study (38), nine cases of the late resolution of mural thrombus with anticoagulants, stroke occurred in 480 patients receiving no anticoagulants. despite a definite reduction in the incidence of embolic events. All the strokes occurred in patients with a peak creatine The differences between the results of the studies on acute kinase concentration of more than nine times the upper limit infarction may relate to differences in the groups of patients of normal. Venous thromboembolic phenomena were also studied, in particular, the time at which the echocardiogram confined to this group of patients. Similar findings were is performed and the time at which the patient enters the reported by Johannessen et al. (19), who found that patients hospital after the onset of symptoms. In summary, the evi• developing stroke had a larger heart and higher peak enzyme dence suggests that full anticoagulation when given within concentration than did those without stroke. Another study 12 hours of the onset of pain moderately reduces the inci• (33) failed to confirm these findings, although up to 25% dence of mural thrombus. of the patients with stroke in that series may have had a Three large studies (31,44,45) tested whether short-term nonembolic stroke, and no information is given about ther• anticoagulation can reduce mortality in acute myocardial apy. Atrial fibrillation was, however, more common in pa• infarction and examined the prevention of embolic events tients who developed stroke (33). Plasma fibrinogen con• by this therapy. Anticoagulation in these studies consisted centration, which peaks 4 to 6 days after infarction, is also of full dose heparin, either intravenously (31) or subcuta• strongly associated with thromboembolism. In one study neously (44,45), followed by oral anticoagulants to prolong (15) of 120 patients with infarction, all 10 thromboembolic the prothrombin time to up to 1.5 times control. In the events recorded (including 4 pulmonary emboli) occurred Medical Research Council (MRC) study (31), for example, in those patients with a fibrinogen concentration greater than the incidence of systemic emboli during the hospital ad• 650 mg/dl, with 9 occurring when the concentration was mission was reduced by treatment from 3.4% (24 of 715 greater than 800 mg/dl. In that study (15), fibrinogen con• patients) in the control group to 1.3% (9 of 712 patients) centration was the best predictor of embolism in a multi• in the treated group. Overall, the three studies (31,44,45) variate model. It is clear from the foregoing discussion that suggest a 24 to 75% reduction in relative risk with this patients at high risk of embolism are those with a large moderate intensity of oral anticoagulation. infarction, particularly if anterior, whether or not they have Mural thrombosis and systemic embolism may not be mural thrombus. affected by therapy in the same way. Most likely no treat• Studies of preventive therapy. The frequency both of ment will prevent the development of minor mural thrombus mural thrombus and embolism may be reduced by antico• due to exposure ofdamaged tissue. However, further growth agulant therapy, although the two may not be reduced to of thrombus with the potential for clinically significant em• the same extent. To be effective in the prevention of mural bolism is inhibited by anticoagulants, the rate of embolism thrombus, anticoagulation has to be given in adequate dose being reduced in the three large trials (31,44,45). Although and as early as possible in the course of the condition before the evidence that less intense anticoagulation reduces mural the thrombus has had time to become established. Autopsy thrombus formation is contradictory, the evidence is con• studies (39,40) reveal a reduction in frequency of mural vincing that full dose intravenous heparin followed by oral thrombus of 50 to 70% and an approximate halving in the vitamin K antagonists protects against embolism. rate of systemic embolism with high dose subcutaneous The risks of anticoagulation in patients with no clear anticoagulation given soon after arrival in hospital. Mural contraindications were accurately defined by the three large 80B ADAMS ET AL JACC Vol X. No 6 INTRACARDIAC THROMBOSIS AND EMBOLISM December IYX6 76B-X7B

studies of acute myocardial infarction (46). In the Veterans ousthrombosis in patients with acute myocardial infarction Administration study (44), there were 13 major bleeding is dealt with elsewhere in this symposium (48,49). episodes (2.6% of 500 patients) in the treated group and 6 (1.2% of499) in the untreated group (the anticoagulant agent was heparin, adjusted according to the clotting time, to• Chronic Left Ventricular Aneurysm gether with coumadin until the prothrombin time was greater Natural history, epidemiology and risk factors. Vari• than 1.3 times control, then the heparin was discontinued). ation in the definition of this condition makes valid com• In the MRC study (31), clinically obvious hemorrhage was parison of various series difficult, particularly because dif• recorded in 36 (5%) o£112 treated patients and in 9 (1.3%) ferent techniques may be used to define the abnormality of 715 untreated patients. Most of these bleeding episodes (autopsy, surgery, angiography, echocardiography). How• were minor, and no deaths occurred. The risks of short• ever, there is agreement that mural thrombus within a left term anticoagulation in this group of patients are therefore ventricular aneurysm is common. Surgical series (2) have low. reported an overall frequency of 47%, with up to 95% in The demonstration of mural thrombus on an echocar• one series (50). As most of the surgical data are retrospec• diogram is unlikely to materially alter the decision about tive, these figures may be underestimated. Necropsy data anticoagulation. Anticoagulation has been shown to be ef• (again almost entirely retrospective) (2) suggest a very sim• fective if given on admission to hospital, not at other times. ilar (49%) frequency of mural thrombus. The thrombus in A delay until an echocardiogram is at hand may miss the most cases persists from the acute phase of the infarction, time in which therapy can be most valuable. The prevention persistence being favored by the stasis within the aneurysm. of the development of a mural thrombus is the most im• Despite the frequent persistence of thrombus, the inci• portant goal of therapy in the acute phase. In one study dence of clinical systemic embolism gradually decreases (19), warfarin was added to prophylactic heparin only after after acute infarction to a low level of 0.35 events per 100 a mural thrombus was demonstrated by echocardiography. patient-years (34) after about 3 months. The prevalence of Five strokes occurred in the series of 90 patients, and three embolism at necropsy in cases ofchronic aneurysm is higher were in patients who had been given warfarin after mural (up to almost 40%) (2). In one study (17) of 100 surgical thrombus had been detected (19). Because the majority of cases of chronic aneurysm, five patients had had clinical mural thrombi develop only after 3 days after infarction, emboli, of which four were within 3 months of infarction; echocardiography in the first 2 days would fail to detect the the date of the fifth patient's infarction was unknown. An• majority of the patients who would develop mural thrombus other series (16) of 58 patients described 2 patients with (27). Echocardiography later in the hospital course, for ex• embolism of which one event occurred despite anticoagu• ample, at 10 days (47), might detect thrombi only after a lation. In a study in which follow-up and event rate were significant proportion of the emboli had occurred (33). Mul• carefully documented, Lapeyre et al. (34) described a low tiple echocardiographic examinations are impractical, ex• incidence ofemboli in a medically managed population with cept as a research tool. Indeed, as discussed, clinical fea• aneurysm. One event occurred in 288 patient-years of fol• tures, available in all patients, usefully define a high risk low-up in 69 patients without anticoagulation (34). group. Suggested management. There are no clear data to show Suggested management. All patients with a large in• that anticoagulants reduce the rate ofembolism in the setting farction should receive anticoagulants on admission, with of chronic left ventricular aneurysm (more than 3 months intravenous heparin in full doses. We favor treating patients after infarction). However, even if there were, because the who have an anterior infarction or a very extensive inferior rate of embolism is so low in medically managed patients, infarction. Although not specifically addressed in this pre• the benefits of anticoagulation are unlikely to outweigh the sentation, the potential for venous thromboembolism is taken risks (32,34). If a stroke does occur in a patient with an into account when deciding to initiate anticoagulant therapy aneurysm, it may be due to associated cerebrovascular dis• in a patient with myocardial infarction. Some risk factors ease rather than to an embolus arising from the heart. The are common for both arterial and venous thromboembolism, efficacy of anticoagulants in the prevention of recurrent namely, high peak enzyme concentration, and embolism is not known, but most patients who have had an atrial fibrillation. embolus would receive anticoagulants. Oral anticoagulation ofmoderate intensity (prothrombin Occasionally a left ventricular thrombus is discovered at time of 1.2 to 1.5 times control, international normalized echocardiography or angiography, most often in a patient ratio of 1.6 to 2.5) should be started 2 to 3 days before within 6 to 8 weeks of infarction, with features that suggest heparin is to be discontinued, and continued for 8 to 12 that a high risk of embolism is likely. Some investigators weeks. Anticoagulation at this intensity is recommended (51) have successfully used urokinase to lyse such a throm• because it prevented embolism in the MRC and Veterans bus. This approach was successful in the 16 patients in Administration studies (31,44). The prevention of ven- whom it was attempted, with no embolism in association lACC Vol. 8. No.6 ADAMS ET AL 81B December 1986.76B-87B INTRACARDIAC THROMBOSIS AND EMBOLISM

with the treatment. However, embolism was seen in another infarction and left ventricular aneurysm. In one series (57), group of patients undergoing lysis of thrombus in the left 123 patients with diffuse hypokinesia were studied; in about side of the heart, those with thrombosed left-sided prosthetic 60%, this was due to cardiomyopathy and in the remainder valves (52). The clinical outcome in these cases was good, it was due to coronary disease. Thirty-six percent of the despite the embolism. We, therefore, believe that further entire group had left ventricular thrombus by echocardi• experience is necessary before lysis of intracardiac thrombus ography. Of the 96 patients followed up, 11 % developed can be considered standard therapy. These observations sug• systemic embolism over a mean follow-up period of21 years gest that the use of thrombolytic therapy for patients with (range 9 months to 4 years; 192 patient-years). The risk of acute infarction will reduce the rate of mural thrombus for• embolism was not increased in patients with left ventricular mation (53). Surgery (thrombectomy or aneurysmectomy) thrombus (40%) by echocardiography. Neither was the cause has been used rarely in patients with large, freely mobile of the hypokinesia related to the embolic risk, emboli being thrombi or if recurrent embolism has failed to respond to equally frequent in those with coronary disease. The echo• anticoagulation. cardiogram seems unlikely to be useful in defining a high risk population by the detection of intracardiac thrombus in patients with cardiomyopathy. Dilated Cardiomyopathy Other factors that determine the risk ofembolism in car• Natural history, epidemiology and risk factors. Au• diomyopathy have been scantily addressed. There are poorly topsy studies reveal a high incidence of mural thrombi in substantiated suggestions that patients with alcoholic car• patients with dilated cardiomyopathy. For example, Roberts diomyopathy have a particularly high incidence of embo• and Ferrans (II) found intracardiac thrombus in 53% of 60 lism. A 100% incidence of mural thrombus at postmortem patients with dilated cardiomyopathy (excluding those with study has been reported in a well defined group of patients coronary disease). Thrombi were found in the left ventricle with (58). There is a high inci• in 27 cases, in the right ventricle in 15, in the right atrium dence of embolism in peripartum cardiomyopathy (59) and in 12 and in the left atrium in 5. In 19 cases, thrombi were in the cardiomyopathy of hypereosinophilia (60). Patients found in more than one chamber. The endocardium under with hypertrophic cardiomyopathy and atrial fibrillation have the thrombus was commonly abnormal. This suggests that a high incidence of embolism, particularly in association in addition to the slow flow seen in these cases, endocardial with rhythm changes (61). In contrast, cardiac rhythm does abnormalities predispose to thrombus formation. Indeed, the not seem to be a major consideration in the majority of preponderance of left ventricular over left atrial thrombus patients with dilated cardiomyopathy, presumably because supports this view because there is a greater degree of stasis the thrombi that are the source of the emboli are usually in the atrium, particularly in the appendage. ventricular, while in hypertrophic cardiomyopathy, they are Clinical studies (54) of patients with dilated cardio• atrial. Fourteen percent of patients with sinus rhythm in one myopathy suggest that the cumulative incidence of clinical series (54) of patients with dilated cardiomyopathy devel• embolism, secondary in most cases to left ventricular throm• oped emboli, while only 2 of 10 patients developing emboli bus, is 18% in patients not taking anticoagulants. Because in another series (62) had atrial fibrillation. Eight of 15 two-thirds of the patients in this Mayo Clinic study died patients with emboli had sinus rhythm in the series of Hatle within 2 years of diagnosis, the rate of embolism was high. et al. (55). Hemodynamic factors have only rarely been Similar results (15 emboli occurring in 106 patients followed correlated with the likelihood of embolism in this group of up to 2 to 22 years) were obtained by Hatle et aI. (55). patients. In one study (57), there was no difference in echo• There is also a high risk of pulmonary embolism in these cardiographic left ventricular dimensions or ejection fraction patients, almost 5% in this series (55). Of 100 patients between patients with and without left ventricular thrombus. studied prospectively in another series (56), II had systemic Thrombus morphology was not, in this study, associated emboli, while the same number had pulmonary emboli. with embolic rate. Pulmonary embolism, which may contribute to the clinical Suggested management. Little information is available condition despite being undiagnosed during life, is frequent regarding the role of antithrombotic treatment in the dif• in these patients; thus, the 7% mortality rate due to pul• fusely dilated left ventricle due to ischemic heart disease. monary embolism in this series probably reflects a higher Although there is no prospective study of anticoagulation undiagnosed rate. Embolism in patients with cardio• in dilated cardiomyopathy, the data from the Mayo Clinic myopathy is more frequent than in patients with chronic left (54) support the use ofanticoagulants in patients with dilated ventricular aneurysms, probably because in the latter, the cardiomyopathy. No patient on anticoagulant therapy de• wall adjacent to the thrombus is static. There is, therefore, veloped a thromboembolic event in 101 patient-years of less stimulus to dislodge the thrombus. follow-up, whereas emboli occurred in 18% of patients not Left ventricular thrombus can be detected noninvasively receiving anticoagulants followed up for 624 patient-years in patients with dilated cardiomyopathy as in myocardial (that is, an event rate of 3.5/100 patient-years). Although 828 ADAMS ET AL JACC Vol g. No 6 INTRACARDIAC THROMBOSIS AND EMBOLISM December I9g6 76B-g7B

the patients were not randomized to the two treatment groups, ically apparent; autopsy data revealed splenic and renal em• the groups were comparable. Thus, it is recommended that boli in 44 and 56% of patients, respectively (70). Coronary patients with dilated cardiomyopathy receive long-term an• emboli with small areas of myocardial infarction may occur ticoagulation with coumadin to moderate intensity (32,54). in up to 40 to 60% of autopsy cases (64). Pulmonary emboli Furthermore, this is particularly indicated in the presence are common in right-sided endocarditis. Although these phe• of heart failure, prolonged bed rest or other conditions that nomena are common, emboli occluding large vessels like predispose to venous thromboembolism, an important ad• the femoral artery are uncommon, and are more usually due ditional indication for anticoagulant therapy in these pa• to fungal or marantic endocarditis. Left atrial myxoma may tients. The stage in the natural history of the disorder at also embolize to large peripheral arteries. Emboli remain which therapy should be started is not known, but the num• an important cause of death in endocarditis, causing 16% ber of emboli in the Mayo Clinic study (54) in the first year of the deaths in one series (71) performed in the early 1970s. after diagnosis suggests that early anticoagulation may be Emboli occasionally occur despite successful antibiotic ther• valuable. The role of antiplatelet agents is unknown. We apy, even long after the illness. see no role for noninvasive detection of thrombi in decision• Emboli occurring in the early phase of the illness are making in these patients. most likely to be in the context of Staphylococcus aureus infection (69,71). The slower growing but less common fungi (Aspergillus and Candida) and the carbon dioxide• Infective Endocarditis requiring bacteria (Hemophilus spp., Cardiobacterium hom• Thrombosis and the Pathology of Endocarditis inis and Actinobacillus) produce large vegetations with a high risk of embolism (68). In the later phase of the illness, Normal valvular is resistant to infection. streptococcol infection accounts for almost half of the cases Trauma to the valve promotes deposition of fibrin and plate• of embolism. lets (63), producing the lesion of nonbacterial thrombotic Some studies (69) find that injections lead endocarditis. Experimentally, many forms of stress can to embolism more commonly than do aortic value injections, produce nonbacterial thrombotic endocarditis (for example, while others (71) reach the opposite conclusion. Overall, it severe infections and high cardiac output states). Similar seems likely that involvement leads to emboli lesions in all stages of development have been seen in hu• more frequently (72). The reported rate of recurrence of mans and appear to lead to all cases of infective endocarditis emboli is variable; in the Massachusetts General Hospital (64). The same pathologic findings are seen in marantic series (69), only I of 37 patients had a second major cerebral endocarditis without infection (for example, with some ma• embolus. However, 47% of patients with cerebral embolism lignancies and connective tissue disorders). had systemic embolism, and almost 30% of patients with In experimental animals, treatment with anticoagulants stroke (both embolic and hemorrhagic) had a premonitory (65), aspirin (66) and sulfinpyrazone (67) has been used in transient ischemic attack. Also, recent unpublished retro• an attempt to reduce the deposition of platelets and fibrin spective data from our institution (72) in a group of patients during the induction of endocarditis. Although with echocardiographically detected vegetations show that size was reduced by sulfinpyrazone in one study (67) of the rate of recurrent emboli is twice that of first emboli. sterile vegetations, aspirin in large doses had no effect in This opinion is not universal: to quote a recent review (73), another study (66). Survival of rabbits with experimental "there are no data to suggest that a patient with one or two infective endocarditis was reduced by warfarin (65), even major emboli is at increased risk of having more..." De• in the presence of penicillin. There are no data regarding spite these reservations, we believe that the occurrence of the effect of antiplatelet agents or anticoagulants on the one embolic event does presage a further event. Finally, prevention of endocarditis in human subjects (63). there is little doubt that patients with mechanical prosthetic valve endocarditis have a high rate ofembolism, particularly Embolism in Endocarditis if anticoagulant treatment has been discontinued for some Natural history, epidemiology and risk factors. Sys• reason (74). temic embolism, including to the brain, is the major com• Patients in whom vegetations are detected by echocardi• plication of endocarditis after congestive failure. Cerebral ography are at higher risk oj embolism than are those in embolism with stroke occurs in 6 to 31 % of cases treated whom they are not detected. A recent review (75) sum• currently (68), in 17% in one large series from the Mas• marized the findings in 442 patients from several studies. sachusetts General Hospital (69). Strokes occur most com• Thirty-four percent of patients with vegetations on echo• monly in the territory of the middle cerebral artery. Mi• cardiography had systemic embolism, whereas this occurred croemboli to the cerebral circulation are also common; in only 7% of patients without vegetations. Other workers sometimes silent, they may lead to confused mental states (76,77) have shown that patients with large vegetations are or mood changes. Emboli to other organs may not be clin- more likely to develop a first embolism than are those with JACC Vol. 8, No.6 ADAMS ET AL 83B December 1986 76B-87B INTRACARDIAC THROMBOSIS AND EMBOLISM

small vegetations (0,1 em). Similar observations have been of a mycotic aneurysm. In summary, the diagnosis of a made in our institution (72); patients with vegetations of an mycotic aneurysm is a very strong contraindiction to anti• area greater than 1.8 cm2 as judged by two-dimensional coagulation (32). Thus, in a patient in whom anticoagulation echocardiography were more than 2.5 times more likely to is necessary (for example for cardiopulmonary bypass), full have emboli than were those with smaller vegetations. Fur• neurologic evaluation including angiography should be con• thermore, in one study (78), multiple emboli occurred in sidered, particularly in the presence ofprior neurologic man• patients with large vegetations. Although the echocardio• ifestations. graphic detection of vegetations defines a population with Anticoagulants in prosthetic valve endocarditis. It a high incidence of embolic events, the predictive value in would seem appropriate not to institute prophylactic anti• the individual is not high; in general, 50 to 75% of patients coagulation in patients with endocarditis on a bioprosthetic have echocardiographic vegetations, whereas only about 33% valve, although continuing established antithrombotic ther• will have clinically apparent emboli. The detection of large apy is a reasonable policy. To our knowledge, there is little vegetations may be of greater predictive value. information regarding these issues. Several studies have Can anticoagulant therapy prevent embolism in na• addressed the matter ofcontinuing anticoagulants in patients tive valve infective endocarditis without excessive risk? with mechanical prosthetic valve endocarditis. A retrospec• The role of anticoagulants in native valve infective endo• tive study from the Mayo Clinic (74) strongly supports con• is controversiaL with contradictory opinions being tinuing anticoagulants in these patients; stroke occurred in expressed in the literature. Portions of established vegeta• 3 (8%) of 38 patients on anticoagulant therapy and in 10 tions may embolize despite adequate anticoagulation, An (71 %) of 14 patients in whom anticoagulants were with• alternative view is that anticoagulants could prevent layering drawn or were at doses producing inadequate anticoagula• and extension of additional friable thrombus, Clinical stud• tion. Other studies (82,83) report a high incidence of neu• ies have not provided an answer. One author states: "An• rologic complications despite anticoagulation. For example, ticoagulants do not prevent emboli in infective endocardi• one study (82) reports that 10 (24%) of 42 patients on tis" (79). For example, in the Massachusetts General Hospital anticoagulant therapy experienced embolic (four patients) series (69), a subset of seven patients were treated with or hemorrhagic (six patients) events. In each study, hem• anticoagulants and yet five experienced embolism. In con• orrhage was associated particularly, but not exclusively, trast, other investigators (32) clearly believe that antico• with excessive anticoagulation. Although anticoagulants agulants are effective, There are no data regarding the use should be continued in the setting of prosthetic endocarditis, of antiplatelet agents in this setting, it has to be accepted that the risk of both embolic and Although the possible benefits of anticoagulation are un• hemorrhagic events remains high. clear, the risk of cerebral hemorrhage in patients with in• Suggested management. In native valve endocarditis, fective endocarditis is certainly high, In the early 1940s, there is no evidence for efficacy, whereas there is certainty heparin was used in the treatment of patients with endo• that anticoagulant treatment increases the risk of hemor• carditis in an attempt to improve penicillin penetration into rhage. Therefore, anticoagulation is not recommended to vegetations (80), However an unacceptably high rate (at prevent emboli, Neither is there good evidence that anti• least 20%) of cerebral hemorrhage occurred (81), after only coagulation reduces the risk of recurrent embolism once an short courses of heparin. Warfarin therapy shortens survival initial event has occurred. If anticoagulation becomes nec• in experimental endocarditis in rabbits (65), In the Mas• essary (for example, if cardiopulmonary bypass is needed), sachusetts General Hospital series (69), three of seven pa• consideration should be given to the possibility of a mycotic tients receiving anticoagulants developed hemorrhagic cere• aneurysm. In mechanical prosthetic valve endocarditis, an• bral infarction. Cerebral hemorrhage occurred in only 10 of ticoagulation should be discontinued temporarily if cerebral 211 patients not receiving anticoagulants, embolism does occur. Care should be taken to minimize the Anticoagulation increases the likelihood ofcerebral hem• likelihood of excessive anticoagulation. Bioprosthetic valve orrhage in endocarditis. which may be due to bleedingfrom endocarditis should be treated in the same way as infection mycotic aneurysms hemorrhagic transformation of embolic on a native valve, with previous antithrombotic therapy infarction or subarachnoid or intracerebral hemorrhage with being continued. Again, care has to be taken to avoid ex• no identifiable cau~e. Mycotic aneurysms are detected in cessive anticoagulation. life in a small percent of patients (69,70) and in up to 10% at autopsy, Because these aneurysms may resolve sponta• neously, the true incidence is unknown. Such aneurysms Atrial Fibrillation commonly arise after septic emboli to the vessel wall. Per• Natural history, epidemiology and risk factors. As haps 50% of patients with a mycotic aneurysm will have discussed elsewhere in this symposium (84) patients with had preceding cerebral signs or symptoms. Certainly, the atrial fibrillation and have a high rate absence of neurologic manifestations reduces the likelihood ofembolism. However, nonvalvular atrial fibrillation occurs 848 ADAMS ET AL lACC Vol x, No 6 INTRACARDIAC THROMBOSIS AND EMBOLISM December 1986 76B-87B

much more commonly and is numerically a more important by Forfang et al. (91) in secundum atrial defect with atrial potential cause of embolism. fibrillation. Thyrotoxic atrial fibrillation is associated with Atrial fibrillation is a relatively common arrhythmia, oc• a high risk of embolism (8 to 39%, average 14). In one curring in 2 to 3 people per 1,000 from ages 25 to 34 years series (92), 12 of 30 patients with thyrotoxic atrial fibril• and 30 to 40 per 1,000 from ages 55 to 64 years in the lation developed emboli, 53% of which were cerebral; as Framingham Study (85). In people aged 62 to 90 years in only 4 patients were in chronic atrial fibrillation, the rate Edinburgh, Scotland, the rate was 50 to 90 per 1,000 (86). of embolism was very high. In an earlier report (87) from the Framingham Study, the Stability of cardiac rhythm and left atrial size have not risk of stroke in nonvalvular atrial fibrillation was 41.8 per been clearly related to the risk ofembolism in nonvalvular 1,000 patient-years, a relative risk of 5.6 (87). An overall atrial fibrillation. Detection of left atrial thrombus by echo• annual stroke risk in nonvalvular atrial fibrillation of 3 to cardiography is unreliable, and by other modalities (for ex• 5% has been suggested (32), with a 35% cumulative lifetime ample, computed tomography) is not established. In patients incidence. Nonvalvular atrial fibrillation is found in 45% of with atrial fibrillation, recurrent stroke after an initial event patients with cardiac embolic strokes, accounting for 5 to is common, occurring in up to 10 to 20% per year (32). 6% of all strokes (32). Of course, many of the patients with Thus, the best predictor of stroke in these patients is an nonvalvular atrial fibrillation have other associated cardiac initial event. conditions (for example, hypertensive or ischemic heart dis• Role ofanticoagulation. The first stroke in patients with ease). They, therefore, differfrom the patients with "lone" nonvalvular atrial fibrillation is likely to be clinically very atrial fibrillation. significant. Therefore, prevention of stroke in these patients Thrombus formation in the left atrium in nonvalvular is important. There are no data regarding the use of anti• atrial fibrillation is likely related to stasis, but the role of platelet agents in this context. Anticoagulation has been used additional endocardial abnormalities has not been addressed. frequently, but there are no good controlled studies. How• The best predictor of stroke in patients with nonvalvular ever, it is likely that they are efficacious, by analogy with atrial fibrillation is a first stroke since recurrence occurs in their efficacy in valvular heart disease, and in the prevention up to 10 to 20% patients per annum (32). The rate of em• of embolism in acute myocardial infarction. bolism is partly determined by the etiology of the arrhyth• In a comparative study with historic controls, Freeman mia. In patients with coronary disease, the incidence of and Wexler (93) showed a reduction in the rate of throm• clinical embolism is relatively low. However, because coro• boembolism in patients with" arteriosclerotic" heart disease nary disease is so common, it is a frequent cause of atrial and atrial fibrillation from 4.9% in untreated patients to fibrillation and embolism. Subclinical emboli, often of un• 0.6% in patients receiving anticoagulants, with a similar certain clinical significance, are common at autopsy in these reduction in embolism detected at autopsy. A careful anal• patients. In one autopsy series (88), 35% of patients with ysis of the risks and benefits of anticoagulation in the brady• atrial fibrillation due to ischemic heart disease had systemic cardia- syndrome (94) suggests that anticoagu• emboli, while only 7% of a control group with ischemic lation is beneficial in this condition, even when the heart disease and sinus rhythm had emboli; in most patients, assumptions made were generally unfavorable to antico• embolization involved the brain (73%). Many patients with agulation. coronary disease and atrial fibrillation, who are at an in• Suggested management. Prevention of recurrent em• creased risk of embolism, also have other relative indica• bolism should be considered in each of the patient groups tions for anticoagulation (for example, congestive failure discussed here by long-term moderate intensity anticoagu• with its high risk of pulmonary embolism). Patients with lation (prothrombin time with rabbit thromboplastin 1.2 to cardiomyopathy have already been dealt with. Patients 1.5 times control). This recommendation is based on anal• younger than 65 years of age with lone atrial fibrillation ogy with venous thromboembolism, in which stasis prob• (with no other detectable heart disease) have a low incidence ably plays a similar pathologic role, and against which mod• ofembolism; 94% of98 patients were free ofembolic events erate intensity oral anticoagulation provides effective at 10 years in a study from the Mayo Clinic (89). The rate prophylaxis (32). However, because many of the patients is much higher in older patients with the -tachy• with nonvalvular atrial fibrillation are elderly, careful con• cardia syndrome. Thus, in one study (90) of 100 such pa• sideration of the potential risks and benefits in the individual tients, 16 had had systemic embolism during a median pe• is crucial. Aspirin might well be considered in some cases, riod of 4 years (range of a to 50). In this study, other risk although in the absence of evidence for its efficacy. factors included age greater than 50 years and prolonged Anticoagulation for cardioversion for atrial fibrilla• atrial , emphasizing the effect of stasis on thrombus tion. Several studies document the risk of embolism after formation in the left atrium. Atrial fibrillation occurs in cardioversion for atrial fibrillation (reviewed by Mancini congenital heart disease, but the risk of stroke is not well and Goldberger [95]) as being 1 to 3%, the highest figure documented. A high incidence of embolism was reported of 5.3% being found in a comparative study (96) in which JACC Vol 8. No 6 ADAMS ET AL 85B December 1986 76B-87B INTRACARDIAC THROMBOSIS AND EMBOLISM

embolism occurred in 0.8% of patients on anticoagulant Serial evaluation by two-dimensional echocardiography N Engl 1 Med therapy. Although this risk may seem low, it is a much 1981 ;305:297-302 higher rate per patient-year than for most other considera• 13. Haugland 1M, Asmger RW, Mikell FL, Elsperger 1, Hodges M. Em• bolic potential of left ventncular thrombi detected by two dimensional tions. This comparative study suggests that long-term an• echocardiography. Circulation 1984;70:586-98. ticoagulation before cardioversion reduces the risk of em• 14. Mikell FL, Asmger RW. Elsperger Kl, Anderson Wl, Hodges M. bolism. However, the issue is one of administering short• Regional stasis of blood m the dysfunctional left ventricle: echocar• term anticoagulation before cardioversion in patients who dIOgraphlc detection and differentiation from early thrombosis. Cir• would otherwise not be given an anticoagulant. There are culation 1982;66.755-63. no data regarding the rate of development of intraatrial 15 Fulton RM, Duckett K. Plasma fibrinogen and thromboembolI after myocardial infarction. Lancet 1976. li:1161-4. thrombus or the time needed for it to become adherent to 16 Simpson MT. Oberman A. Kouchoukos NT. Rogers Wl. Prevalence the atrial wall once present. A 2 week period is assumed of mural thrombi and systemic embolization with left ventncular an• to be needed (97) and, therefore, 2 to 3 weeks of moderate eurysm: effect of anticoagulant therapy. Chest 1980;77:463-9. intensity anticoagulation is recommended to allow thrombus 17. Reeder GS. Lengyel M. TaJlk Al, Seward JB. Smith He. Danielson to become adherent before cardioversion. This should be GK. Mural thrombus m left ventricular aneurysm: incidence, role of angiography. and relation between anticoagulation and embolization. continued for about 3 to 4 weeks thereafter because atrial Mayo ClIn Proc 1981;56:77-81. mechanical activity may take 3 to 4 weeks to resume despite 18. Ezekowltz MD. WIlson DA. Smith EO. et al. Companson of indium• electrical sinus rhythm (98). Indeed, the cardiac condition III platelet ,cmtlgraphy and two-dimensional echocardiography in predisposing to atrial fibrillation will, in many patients, the diagnosis of left ventricular thrombi. N Engl 1 Med 1982; warrant long-term anticoagulation. 306'1509-13. Whether all patients should receive an anticoagulant be• 19. 10hannes,en KA. Nordrehaug lE, von der Lippe G. Left ventricular thrombus and cerebrovascular accident in acute myocardial mfarction. fore cardioversion is unknown. The risk of embolism is Br Heart 1 1984;51 :553-6. higher in patients with cardiac conditions that in themselves 20 Stratton lR. Lighty GW lr, Pearlman AS. Ritchie lL. Detection of produce a significant risk of embolism and in whom long• left ventricular thrombus by two-dimensional echocardiography: sen• term anticoagulation would be considered. In lower risk SItivity. specifiCity. and causes of uncertamty. Circulation 1982; 66:156-66. patients (for example, those with ischemic heart disease), 21. A,mger RW. Mikell FL, Sharma B, Hodges M. Observations on some authorities would use aspirin given for 2 to 3 weeks detecting left ventricular thrombus with two dimensional echocardi• before cardioversion. ography. emphasis on aVOIdance of false positive diagnosis. Am 1 Cardiol 1981;47:145-56. 22. Visser CE, Kan G, David GK. Durrer D. Two dimenSIOnal echo• References cardiography m the diagnOSIs of left ventncular thrombus: a prospec• tive study of67 patients with anatomic validation. Chest 1983;83:228-32 I. Dalen JE, Hirsh 1. ACCP-NHLBI National Conference on Antlthrom• botic Therapy Che,t 1986.89(suppl): IS-106S. 23. Ezekowltz MD, Burrow RD. Heath PW. Streitz T. Smith EO. Parker DE. Diagnostic accuracy of mdium-III platelet scmtigraphy m Iden• 2. Cabm HS. Roberts We. Left ventricular aneurysm. mtraaneurysmal tifying left ventncular thrombi Am J Cardiol 1983;51: 1712-6. thrombus and sy,temlc embolus in coronary heart disease. Chest 1980.77:586-90. 24. Hellerstem HK. Martin JW. Incidence of thrombo-embolIc lesions accompanying myocardial infarction. Am Heart 1 1947;33:443-52. 3. Stratton lR. Mural thrombi of the left ventricle. Chest 1983,83.166-8. 4. Nixon IV. Left ventricular mural thrombus Arch Intern Med 25. DaVies Ml, Woolf N. Robertson WB. Pathology of acute myocardial mfarction with particular reference to occlusive coronary thrombi. Br 1983;143: 1567-71 Heart 1 1976;38:659-64. 5. Arvan S. Mural thrombi m : recent advances m pathogenesis. diagnosis. and approaches to treatment Arch Intern 26. Keatmg EC, Gross SA. Schlamowltz RA. et al. Mural thrombi in Med 1984;144:113-6. myocardIal infarctions: pro,pectlve evaluation by two-dimenSional echocardIOgraphy. Am 1 Med 1983;74:989-95. 6. Chesebro IH. Ezekowitz MD. Badimon L. Fuster V. Intracardiac thrombi and systemic thromboembolIsm: detection. mcidence and 27 Visser CA, Kan G. Lie KI. Durrer D. Left ventricular thrombus treatment. Ann Rev Med 1985.36:579-605 followmg acute myocardial infarction: a prospective serial echocar• dlographic study of 96 patients. Eur Heart 1 1983;4:333-7. 7. Meltzer RS. VIsser CE, Fuster V. Intracardmc thrombi and systemic embolIzation. Ann Intern Med 1986;104:689-98. 28. Kothan AJ. PaczkowskI K. Baker KM, et al. Ventncular thrombi in acute myocardial infarction. mcidence. complications. and effects of 8 10hnson RC, Crissman RS. DiDio LJA. Endocardial alteration, m anticoagulation (abstr). 1 Am Coli Cardiol 1984;3:601. myocardial mfarctIOn Lab Invest 1979;40: 183-93 9. Mallory GK, White PD. Salcedo-Salgar 1. The speed of healmg of 29. Ezekowitz MD. Kellerman OJ, Smith EO. Streizt TM. The detection myocardial mfarctlon: a study of the pathologic anatomy m seventy of active left ventncular thrombOSIS during acute mycardial infarction two cases Am Heart 1 1939;18'647-71. usmg mdium-III platelet scintigraphy Chest 1984;86 35-9. 10. Hochman IS. Platia EB. Bulkley BH. Endocardial abnormalities m 30 Solandt DY, Nassim R. Best CH. Production and prevention ofcardiac left ventncular aneurysms. a climcopathologlc study. Ann Intern Med mural thrombosis in dogs. Lancet 1939; 11:592-5. 1984;100:29-35. 31 Working Party on Anticoagulant Therapy in Coronary ThrombOSIS to II. Roberts WC, Ferran, Vl PathologICal aspects of certain cardiomy• the Medical Research Council Assessment of short-term anticoagulant opathie, Circ Res 1974,34/35(suppl 11):11-128-44 admmistratlon after cardiac mfarctlon. Br Med 1 1969;1:335-42. 12. Asmger RW. Mikell FL. EI,perger 1. Hodges M. Incidence of left 32. Sherman DG. Dyken ML. Fisher M, Harrison MJG. Hart RG. Cere• ventricular thrombosIs after acute transmural myocardial mfarction bral embolIsm. Chest 1986;89(suppl):82S-98S 868 ADAMS ET AL lAce Vol S, No 6 INTRACARDIAC THROMBOSIS AND EMBOLISM Dccemher l'iS6 76B- 87B

33. Komrad MS, Coffey CEW, Coffey KS, et al. Myocardial infarcllon ical picture related to long term prognosis. Acta Med Scand and stroke. Neurology 1984;34:1403-9. 1976; 199:399-405, 34. Lapeyre AC Ill, Steele PM, Kazmler Fl, Chesebro le. Vlietstra RE, 56. Hamby Rl. PrImary myocardial disease MedICIne 1970;49:55-78. Fm,ter V Systemic embolism in chromc left ventricular aneurysm: 57. Gottdlener IS, Gay lA. VanVoorhees L, DlbIanco R, Fletcher RD. incidence and the role of anllcoagulallon. 1 Am Coil Cardiol Frequency and embolic potential of left ventricular thrombus in dilated 1985,6.534-8. cardiomyopathy: assessment by two-dimenSIOnal echocardiography. 35. Arvan S. Left ventrIcular mural thrombi secondary to acute myocardial Am 1 Cardiol 1983;52:1281-5. infarctIOn: predisposIng factors and embolic phenomenon. 1 Clin Ul• 58. Demakls IG, Proskey A, Rahimtoola SH, et al. The natural course trasound 1983; II :467-73. of alcoholic cardiomyopathy. Ann Intern Med 1974;80:293-7 36. Kinney EL. The SIgnificance of left ventrIcular thrombi in patients 59. lulian DG, Szekely P. PerIpartum cardiomyopathy Prog Cardiovasc with coronary heart disease: a retrospective analySIS of pooled data. DIS 1985;27:223-40. Am Heart 1 1985;109:191-4 60. Gottdlener IS. Maron Bl, Schooley RT, Harley lB, Roberts WC, 37 Visser CA, Kan G, Meltzer RS. Embolic potential of left ventrIcular FaUCI AS. Two-dimensional echocardlOgraphic assessment of the IdiO• thrombus after myocardial infarction: a two-dimenSIOnal echocardio• pathic hypereosinophilia syndrome: anatomic basis of mitral regur• graphiC study of 119 patients 1 Am Coil CardlOl 1985;5: 1276-80 gltallon and perIpheral embolizallon. CirculatIOn 1983;67:572-8 38. Thompson PL, Robinson IS. Stroke after acute myocardIal Infarction: 61. Henry WL, Morganroth 1. Pearlman AS, et al. Relation between relallon to infarct size. Br Med 1 1978;2:457-9. echocardiographlcally determined left atrial size and atrial fibrillatIOn. 39. Steffensen KA Coronary occlUSIOn treated WIth small doses of hep• Circulation 1976;53:273-9. arin. Acta Med Scand 1969;186:519-21. 62. Johnson RA, Palacios I. DIlated cardiomyopathy of the adult (part I) 40. Hilden T, Iversen K, Raaschou F. Anticoagulants in acute myocardial N Engl 1 Med 1982;307:1051-8. Infarction. Lancet 1961; n:327-31. 63. WeInsteIn L, Schlesinger 11. Pathoanatomic, pathophySIOlogic and 41. Nordrehaug lE, lohannessen K-A, von der Lippe G. Usefulness of climcal correlations In endocarditIS. N Engl 1 Med 1974,291: 832-7.1122-6. high-dose anticoagulants In preventIng left ventrIcular thrombus In acute myocardial Infarction Am 1 Cardlol 1985;55 1491-3. 64 ScheId WM. Pathogeneis and pathophySiology of Infective endocar• dillS. In: Sande MA, Root RK. eds. Contemporary Issues In Infectious 42. Tramarin R, Pozzoli M, Febo 0, et al. Two-dimenSional echocardio• Diseases, Volume 2 Endocardills. Edinburgh: ChurchIll Livingstone, graphiC assessment of anllcoagulant therapy In left ventricular throm• 1984. boSIS early after acute myocardial Infarclton Eur Heart 1 1986;7:482-92. 65. Hook EW III, Sande MA. Role of the vegetation In experimental 43 WeInreich 01, Burke IF, Pauletto Fl. Left ventrIcular mural thrombi Streptococcus vlridans endocardItIS Infect Immun 1974:1 0: 1433-8. complicating acute myocardial Infarcllon: long-term follow-up with serIal echocardlOgraphy. Ann Intern Med 1984:100:789-94. 66. LeVison ME. CaITIsoza 1, Tanphaichitra 0, SchICk PK, Rubin W. Effect of aspmn on thrombogenesls and on productIOn ofexperimental 44. Veterans' AdmInistration Co-operative Study Group. Anllcoagulants aortic valvular Streptococcus vmdans endocarditis In rabbIts. Blood In acute myocardial Infarcllon. results of a co-operative climcal trial. 1977,49645-50. lAMA 1973;225'724-9 67 Johnson CE, Dewar HA. Effect of sulfinpyrazone on the development 45. Drapkin A, Merskey C. Anllcoagulant therapy after acute myocardial of experImental endocardial vegetations. CardlOvasc Res 1982; 16: infarcllon: relation of therapeutic benefit to patients' age, sex and 657-62. severity of infarction. lAMA 1973;225:41-8. 68. Lerner PI. Neurologic complications of Infective endocarditis Med 46. Levine MN, Raskob G, Hirsh 1. HemorrhagIC complications of long• CIIn North Am 1985;69:385-98 term anticoagulant therapy. Chest I986;89(suppl): 16S-25S 69. Pruitt AA. Rubin RH, Karchmer AW, Duncan GW. Neurologic com• 47. Ezekowitz MD. Acute Infarcllon, left ventrIcular thrombus and sys• plicatIons of bacterial endocarditis. MediCIne 1978,57:329-43. temic embolizatIon: an approach to management. 1 Am Coil Cardiol 1985;5:1281-2. 70 Lerner PI, Weinstein L. Infective endocardItiS in the antibiotic era. N Engl 1 Med 1966;274:259-66. 48. Hirsh 1, Hull RD, Raskob GE. Epidemiology and pathogenesis of 71 Garvey Gl, Neu HC Infective endocarditis-an evolving disease: a venous thrombosis 1 Am Coil CardlOl 1986;8.I04B-113B. revIew of endocarditIs at the Columbia-PresbyterIan Medical Center. 49. Kakkar VV, Adams Pc. PreventIve and therapeutic approach to ve• 1968-1973. MediCIne 1978;57: 105-27. nous thromboembolic disease and pulmonary embolism-can death 72. Goldman ME. WInters S, RelChstein R. Staville K, Gorlin R. Fuster from pUlmonary embolism be prevented') 1 Am Coil Cardiol V Early Identificallon of pallents With native valve endocardItis at 1986.8.146B-158B. high rIsk for major complications: the value of echocardiography (un• 50 Cooley DA, Hallman GL. Surgical treatment of left ventricular an• published data), eurysm: experience with exciSion of post Infarction lesions in 80 pa• 73. Alsip SG, Blackston EH, KIrklin lW, Cobbs CG. Indications for tIents. Prog Cardiovasc Dis 1968;11:222-8. cardiac surgery in patients with acllve endocarditis. 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Am 1 Cardiol 1984;54:261-3. endocarditIs: climcal implicatIOns. Circulation 1980;61:374-80. 54 Fuster V. Gersh Bl, Giuliani ER, Tajlk Al, Brandenburg RO. Frye 77. Wong 0, Chandraratna PAN, Wlshnow RM, Dusitnanond V. NI• RL. The natural hIstory of idiopathiC dilated cardiomyopathy. Am 1 malasurIya A. Climcal Implicallons of large vegetatIons In InfectIOUS CardloI1981;47.525-31. endocarditis. Arch Intern Med 1983;143:1874-7. 55. Hatle L. Orjavik O. StorsteIn O. Chromc myocardial disease. I ClIn- 78. Nasser FN. Gura GM, Seward JB. TaJlk Al. Embolism In infective lACC Vol 8, No 6 ADAMS ET AL 878 December 1986 76B-87B INTRACARDIAC THROMBOSIS AND EMBOLISM

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