Heart 1996;75:252-256

Long term follow up of patients with anteriormyocardial infarction complicated by leftventricular thrombus in the thrombolytic era

Thomas Mooe, Dag Teien, Kjell Karp, Peter Eriksson

AbstractObjectives-To examine the appearanceand resolution of left ventricular thrombiand to study the relation between throm-bus and mortality during long term followup after anterior myocardial infarction.Design-Ninety nine consecutive patientswere prospectively studied until the lastincluded patient had been followed for oneyear. Streptokinase and aspirin were usedroutinely, anticoagulants only after a deci-sion by the attending physician. Echo-cardiography was performed within 3 d ofadmission, before discharge, and afterone, three, and 12 months.Setting-Umeai University Hospital, ateaching hospital in Northern Sweden.Main outcome measures-Left ventricularthrombus, segmental myocardial function,and mortality during follow up.Results-Thirty patients (30%/6) had athrombus on discharge. One month, threemonths, and 12 months after hospital dis-charge, the thrombus had resolved in 81%,84%, and 90% of the patients, respectively.The proportion of resolved thrombi at onemonth was high irrespective of whetheranticoagulants were given (10/11, 91%) ornot (12/16, 75/6), P = 0-4. New thrombiappeared in 12 patients after discharge andresolution and reappearance of thrombicontinued during the follow up period.Patients who developed a thrombus duringthe hospital stay (n = 44, 44%) had moreextensive myocardial dysfunction on dis-charge (P < 0.001) and significantly highermortality during the follow up period thanthose without a thrombus (23% v 7%,P < 0.01).Conclusions-With routine thrombolyticand aspirin treatment of anterior myocar-dial infarction, left ventricular thrombiusually resolve during the first month afterhospital discharge. Appearance and reso-lution of thrombi continue, however, in a

Table 1 Clinical and laboratory characteristics ofpatients with and without thrombus atdischarge

No thrombus, n = 69 Thrombus, n = 30 P value

Age, mean (range) 66 2 (41-85) 67-0 (41-84) NSMen 79% 80% NSPrevious myocardial infarction 12% 30% < 0 05Hypertension 35% 40% NSDiabetes 16% 10% NSSmokers 31% 11% < 0 05Peak LD1, mean (SD) 15-4 (12-3) 20-8 (9-5) < 0 01Peak CK, mean (SD) 32-5 (29-5) 45-6 (25-2) < 0 01Peak CKMB, mean (SD) 4-1 (3 8) 5-4 (3-1) < 0 05

LD1, thermostable lactate dehydrogenase; CK, creatine kinase.

significant proportion of the patients dur-ing long term follow up. A left ventricularthrombus during the initial hospital stay isassociated with high long term mortality.

(Heart 1996;75:252-256)

Keywords: myocardial infarction; left ventricular throm-bosis; streptokinase; aspirin; mortality.

Patients with acute anterior myocardial infarc-tion often develop a left ventricular thrombusduring the hospital stay.'-3 Echocardiography isthe preferred diagnostic method with a highsensitivity and specificity for ventricularthrombi.4 The finding of a thrombus has beenassociated with a more favourable prognosis,5hypothetically by stabilising the left ventricularwall. Others, however, recommend anticoagu-lant treatment to achieve resolution of thrombiand to reduce the risk of embolisation.67 Therecent introduction of thrombolytics andaspirin as a routine treatment in patients withacute myocardial infarction may, however, havechanged the incidence of thrombi and theirclinical significance. We therefore performed astudy with serial echocardiographic examina-tions during the first year after anterior myocar-dial infarction. The aims of the study were toexamine the appearance and disappearance ofthrombi in consecutive patients dischargedfrom hospital after an anterior myocardialinfarct, to record embolic, cerebrovascular, andbleeding complications, and to study the longterm prognosis in patients in whom a left ven-tricular thrombus was found during the hospitalstay.

MethodsPATIENTSNinety nine consecutive patients surviving thehospital stay after an acute anterior myocardialinfarction were included in the study. Duringthe recruitment period three patients wereexcluded because of poor echocardiographicimage quality and five patients died in hospital.Clinical and laboratory characteristics of the 99study patients are shown in table 1.

DIAGNOSTIC STUDIESA diagnosis of anterior myocardial infarctionwas based on typical chest pain resistant toglyceryl trinitrate, a diagnostic rise in serumcreatine kinase, and the following electrocardio-graphic findings: (1) the development of patho-logical Q waves in two or more precordial leads,or (2) ST segment elevation of 0 15 mV in two

Norrland UniversityHospital, S-901 85UmeA, Sweden:Department ofInternal Medicine,Cardiology SectionT MooeP ErikssonDepartment of ClinicalPhysiologyD TeienK KarpCorrespondence to:Thomas Mooe MD,Department of InternalMedicine, NorrlandUniversity Hospital, S-90185 Umea, Sweden.Accepted for publication20 September 1995

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Long term follow up ofpatients with anterior myocardial infarction complicated by left ventricular thrombus in the thrombolytic era

Figure 1 Resolution andreappearance of leftventricular thrombi inpatients with a thrombus atdischarge.Echocardiographicexaminations duringfollowup were performed one,three, and 12 months afterdischarge. T thrombus;0, no throml us.

T n = 30

TjWn = 5

Drop ouT, rn=2 n= 1

Drop out

n = 1

T n =O0 On= 1

Drop outn =3

it

0nn=2 T n=2 C

Drop out

Tn=0 On=l Tn=l On=l

o0n = 22

)rop oun = 1

it

n= 19

Drop outn = 2

T n = 1 O n = 16

or more of leads V1-V3, or 0 1 mV in two ormore of leads V4-V6. Creatine kinase (CK) andcreatine kinase-MB (CKMB) were measuredon admission and at fixed hours four timesdaily. The time to peak CK from start of treat-ment was noted. Thermostable lactate dehy-drogenase (LD1) was measured on admissionand thereafter daily until the maximum levelcould be identified. Cross sectional echocardio-graphic examinations were performed within3 d of admission, before discharge, and at onemonth, three months, and 12 months followup. An Acuson XP-10 (Acuson Corporation)or a Vingmed CFM 750 (Vingmed Sound)equipped with 2-5-5-0 MHz transducers wereused. The examinations were recorded on aPanasonic AG 7330 video tape recorder andreviewed by two investigators unaware of treat-ment and previous findings. A left ventricularthrombus was defined as an echodense massadjacent to an abnormally contracting myocar-dial segment. It should be distinguished fromthe underlying myocardium, have a clearthrombus-blood interface, and be seen in atleast two transducer positions.48 A 16 segmentmodel was used for scoring the severity of seg-mental wall motion abnormalities according tothe American Society of Echocardiography.9The scoring scale ranged from 1 to 5. A nor-mally contracting or hyperkinetic segment wasassigned a score of 1, hypokinesis 2, akinesis 3,dyskinesis 4, and aneurysmal segments (dias-tolic deformation) 5. The sum of all scores wascalculated for each patient and used in the sta-tistical analysis. The diagnosis of cerebralinfarction required a sudden onset of focal neu-rological deficit and exclusion of haemorrhageby computerised tomography. Diuretics wereused when there were clinical signs of heart fail-ure according to the attending physician. Anincreased dose of peroral diuretics or the needfor parenteral diuretics was thus used as amarker of congestive heart failure. All patientswere prospectively followed and clinical eventsrecorded until the last included patient hadcompleted the 12 months echocardiographicexamination. The mean follow up time was 23months. The follow up time was more than oneyear for 91% (n = 90) and more than twoyears for 48% (n = 48) of the patients.

TREATMENTSeventy four patients admitted within 6 h fromonset of chest pain or with clinical signs ofongoing myocardial ischaemia and electrocar-diographic evidence of an evolving myocardial

infarct received streptokinase as an intravenousinfusion of 1-5 million units over 1 h. Heparinwas not used. Twenty five patients did notreceive streptokinase because of a long delaybetween onset of symptoms and hospitaladmission (20 patients), contraindication forthrombolytics (one patient), or for unknownreasons (four patients). Sixty six patients (67%)without contraindications were given aspirin160 mg daily. Peroral anticoagulants were notroutinely used, but 24 patients (24%) weretreated with warfarin at discharge, decided bythe attending physician. No patient was givenboth warfarin and aspirin.

STATISTICAL ANALYSISData were analysed with the STATISTICA 4 0software modules (StatSoft Inc). Group datawere expressed as mean (SD) for continuousvariables and as rates for variables on a nominalscale. Differences between two means wereassessed with t test for unpaired data or theMann Whitney U test when appropriate.Differences between proportions were analysedwith the x2 test, or for small sample sizes, byFisher's exact test. Differences were consideredsignificant for P values less than 0 05. The rela-tion between deteriorating left ventricular seg-mental function and clinical, laboratory, andechocardiographic data was examined by multi-ple logistic regression analysis. Kaplan-Meiersurvival curves were calculated for patients withand without a diagnosed thrombus during thehospital stay and survival times comparedbetween groups with the log-rank test. The haz-ard ratio was calculated as a measure of relativesurvival.

ResultsPATIENTS WITH A THROMBUS AT HOSPITALDISCHARGEThe resolution and reappearance of left ventric-ular thrombi during the follow up period inpatients with a thrombus present at discharge isshown in fig 1. Most thrombi resolved duringthe first month. Resolution and reappearance ofthrombi continued, however, during follow up,and no patient had a thrombus at all examina-tions. The proportion of patients with a throm-bus at one month was 19% (5/27), at threemonths 16% (4/25), and at 12 months 10%(2/21). There were nine dropouts in this group,of whom six died. Two patients did not partic-ipate in the three months examination, one ofwhom had a thrombus at 12 months. One

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Figure 2 Appearance andresolution of left ventricularthrombi in patients withoutthrombus at discharge.Echocardiographicexaminations during followup were performed one,three, and 12 months afterdischarge. T, thrombus;0, no thrombus.

O n = 69

T n = 2

Table 2 Frequency of left ventricular thrombi at echocardiographic examinations during one yearfollow up after anteriormyocardial infarction

Discharge 1 month 3 months 1 year

T 0 T 0 T 0 T 0% (n) % (n) % (n;n) % (n) % (n;n') % (n) % (n;n') % (n)

All patients 30 (30) 70 (69) 12 (1 1;6) 88 (78) 13 (1 1;7) 87 (74) 10 (8;5) 90 (76)Streptokinase 31 (23) 69 (51) 11 (7;4) 89 (59) 16 (10;6) 84 (53) 8 (5;3) 92 (57)No streptokinase 28 (7) 72 (18) 17 (4;2) 83 (19) 5 (1;1) 95 (21) 14 (3;2) 86 (19)Warfarin 54 (13) 46 (11) 6 (1;0) 94 (17) 12 (2;0) 88 (15) 0 (0) 100 (9)Nowarfarin 23 (17) 77 (58) 14 (10;6) 86 (61) 13 (9;7) 87 (59) 11 (8;5) 89 (67)

T, thrombus; 0, no thrombus; n, number of patients; n', number of patients in the subgroup with new thrombi formed after dis-charge.

patient did not participate in the 12 monthsexamination.

PATIENTS WITHOUT A THROMBUS AT HOSPITAL

DISCHARGEFigure 2 shows the appearance and resolutionof left ventricular thrombi during follow up inpatients without a thrombus at discharge. Anew thrombus was found in some patients atevery interval of follow up examination, includ-ing 12 months after discharge. The proportionof patients with a thrombus after one monthwas 10% (6/62), three months 12% (7/58), and12 months 9% (5/57). There were 12 drop outsin this group, of whom five died. One patientwent through a mitral valve replacement with acomplicated postoperative period. Two olderpatients did not want to participate in furtherfollow up after discharge. Four patients did notundergo the one month or the three monthsexamination. None of them had a thrombus atthe remaining examinations.

Table 2 shows the prevalence of left ventricu-lar thrombi during follow up in all patients inrelation to treatment with streptokinase andwarfarin. After a rapid decrease in prevalence ofthrombi during the first month, no significantdifference between the groups was seen duringfurther follow up. The proportion of resolvedthrombi in surviving patients one month afterdischarge was 85% (17/20) in those given strep-tokinase and 71% (5/7) in those not givenstreptokinase. Similarly, the proportion ofresolved thrombi was 91% (10/11) in thosegiven warfarin and 75% (12/16) in those notgiven warfarin (P = 0-4). After hospital dis-charge, new thrombi appeared in patients givenstreptokinase (20%, 9/46) as well as in patientsnot given streptokinase (19%, 3/16), while nonew thrombi appeared in patients on warfarin(0/7). New thrombi appeared in 22% (12/55)of the patients who were not given warfarin (P= 0-3). Left ventricular segmental dysfunctionat discharge was significantly more extensive in

patients with a thrombus during the hospitalstay compared with those without a thrombus(segmental score 25-7 v 21-4, P < 0-001), fig 3.Patients with a thrombus also had more exten-sive segmental dysfunction at the follow upexaminations.Twenty nine patients (35%) had more exten-

sive segmental myocardial dysfunction at theone year follow up compared with the examina-tion at discharge. The maximum level of LD1was the most important predictor of deteriorat-ing left ventricular function. An increase of 1SD (11-7) in LD1 was associated with a four-fold increase in the risk of further impairmentof left ventricular function (odds ratio 4-2, 95%confidence interval 1-5 to 11-8). Fourteenpatients died during the follow up period, 10 ofwhom had a thrombus during the hospital stay.Eight of these deaths were cardiovascular (sud-den death, myocardial infarction, congestive

100

90

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500

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20

10

0

= No thrombus1 Thrombus

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Long term follow up ofpatients with anterior myocardial infarction complicated by left ventricular thrombus in the thrombolytic era

0.1

0-95

0)

Eu

400 500 600 700 800 900 1000 1100Survival time (d)

Figure 4 Cumulative survival duringfollow up for the entire study group and in patientswith (n = 44, 10 deaths) and without (n = 55, 4 deaths) a left ventricular thrombusduring the hospital stay. RR, relative risk.

heart failure, ruptured aortic aneurysm), onewas a terminal malignant disease in combina-tion with a cerebral infarct, and one was causedby a subdural haematoma. All four deaths inthe patients without a thrombus were cardio-vascular (sudden death, myocardial infarction),in one case in combination with a disseminatedcolon cancer. At the time of death two out offour patients in the non-thrombus group andfour out of 10 patients in the thrombus groupwere treated with warfarin. Three patients hadan ischaemic cerebral event during follow upand none of them was treated with warfarin.One patient had a right sided amaurosis fugaxsix months after inclusion. No thrombus wasseen at echocardiography, but a severe stenosisin the right internal carotid artery was identi-fied. The second patient had a cerebral infarct,verified by computed tomography, 17 monthsafter inclusion. This patient was in the terminalstage of a malignant disease and died two weekslater. The third patient had a second myocar-dial infarct and a cerebral infarct during thesame day, 10 months after inclusion in thestudy. The two last patients did not have athrombus at the proceeding echocardiographicexamination. Two patients had serious bleedingcomplications-one fatal and one non-fatalsubdural haematoma. Both were treated withwarfarin with anticoagulation levels within thetherapeutic range. Figure 4 shows the cumula-tive survival during follow up for the entirestudy group and in patients with (n = 44) andwithout (n = 55) a diagnosed thrombus duringthe hospital stay. Patients with thrombus had asignificantly higher mortality (P < 0-01), with arelative risk of death of 3-6 (95% confidenceinterval 1-2 to 10-8).

DiscussionEchocardiography is the method of choice forthe serial identification of ventricular thrombibecause of its wide availability, low cost, and

non-invasive nature.4 The method is accurate,with a sensitivity ranging between 77% and100% and a specificity ranging between 8%and 100% when compared with findings atsurgery or necropsy, or with platelet imaging.The accuracy of echocardiography is dependentof the image quality, and small thrombi, belowthe level of detection, may be present in areas ofdisturbed flow conditions. Potential diagnosticerrors may, however, be minimised by strictadherence to echocardiographic criteria.'0 Inthis study we showed that the majority of leftventricular thrombi formed during the courseof an anterior myocardial infarction resolveduring the first three months after discharge(21/25, 84%). The proportion of thrombireported to resolve during long term follow upin most previous studies was smaller, rangingbetween 20% and 58%.2 In one study oralanticoagulants were used routinely and resolu-tion of thrombi were reported in 33% (4/14)after 12 months of follow up.' Treatment of leftventricular thrombi with oral anticoagulantshas been examined in a controlled trial, andresolution of thrombi occurred in 59% and88% of the patients after three and 12months." The high proportion of thrombiresolving during follow up in our study may beassociated with new treatment routines aftermyocardial infarction. Aspirin reduces throm-boembolic complications in patients with atrialfibrillation'2 and may modify platelet depositionin some patients with left ventricular thrombi.'3The use of thrombolytics and aspirin mayhypothetically influence the thrombus structureand make it more susceptible to endogenousthrombolysis. Thirty patients had a thrombusat discharge (fig 1) and in 29% (12/42) a newthrombus appeared during follow up (fig 2). Intwo previous reports the proportion of thrombiappearing after discharge was similar, 31% and32%, respectively.' 3Thrombi formed after dis-charge constituted a large proportion ofthrombi diagnosed after one month (55%),three months (64%), and one year (62%).Warfarin treatment seemed to prevent the for-mation of new thrombi after discharge, but thenumber of patients given warfarin was small.The dynamic process of resolution and reap-pearance of thrombi makes it difficult to useechocardiography to identify patients at risk forthromboembolic complications. If a thrombushas resolved at one examination, a new throm-bus may well appear later on. Early thrombusformation (during the hospital period) has beenreported to be associated with a high mortal-ity.2 14 We found that a left ventricular thrombusdiagnosed during the hospital stay is a markerfor high mortality after discharge. In one previ-ous study, early in-hospital mortality was higherin patients without a thrombus.5 However, sev-eral patients did not survive long enough for aventricular thrombus to form.'5 In the samestudy no difference in myocardial infarct sizewas found in patients with and without athrombus, in contrast to our findings and toseveral previous reports""-8 where patients with athrombus had more extensive myocardial dys-function. Three cerebral ischaemic events wererecorded during the follow up period. The

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Mooe, Teien, Karp, Eriksson

episode of amaurosis fugax was probably asso-ciated with a right sided internal carotid stenosis,whereas the other two events may have beenembolic. It is, however, very difficult to differ-entiate between embolic and thrombotic eventsin patients with advanced atherosclerotic dis-ease.'9 The incidence of cerebral embolisationwas approximately 1% in large scale post-infarction trials investigating thrombolytic ther-apy.20 21 Two serious bleeding episodesoccurred, a reminder that warfarin may be asso-ciated with fatal complications, reported tooccur in 1% to 4.8%.22 We conclude that aftertreatment of anterior myocardial infarction withthrombolytics and aspirin most left ventricularthrombi resolves during the first month afterdischarge, but formation and resolution ofthrombi continues during further follow up.The dynamic process of left ventricular throm-bus formation and resolution makes it difficultto use echocardiography to identify patients atrisk for thromboembolic complications. Theformation of a thrombus during the hospitalstay is associated with high mortality after dis-charge. Warfarin may prevent formation of newthrombi after hospital discharge, but the lowincidence of cerebral embolisation aftermyocardial infarction and the risk of seriousbleedings during warfarin treatment should beconsidered before instituting treatment withanticoagulants.

This study was supported by grants from the Medical Faculty,Umea University and the Joint Committee of the NorthernSwedish Health Care Region.

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2 Spirito P, Bellotti P, Chiarella F, Domenicucci S, SementaA, Vecchio C. Prognostic significance and natural historyof left ventricular thrombi in patients with acute anteriormyocardial infarction: a two-dimensional echocardio-graphic study. Circulation 1985;72:774-80.

3 Keren A, Goldberg S, Gottlieb S, et al. Natural history ofleft ventricular thrombi: their appearance and resolutionin the posthospitalization period of acute myocardialinfarction. JAm Coil Cardiol 1990;15:790-800.

4 Ezekowitz MD. Identifying left ventricular thrombi. ClinCardiol 1990;13(suppl 6):VI31-3.

5 Nihoyannopoulos P, Smith GC, Maseri A, Foale RA. Thenatural history of left ventricular thrombus in myocardialinfarction: a rationale in support of masterly inactivity. JAm Coil Cardiol 1989;14:903-11.

6 Fuster V, Halperin JL. Left ventricular thrombi and cere-bral embolism. NEnglJMed 1989;320:392-4.

7 Vaitkus PT, Bamathan ES. Embolic potential, preventionand management of mural thrombus complicating ante-rior myocardial infarction: a meta-analysis. _J Am CoilCardiol 1993;22: 1004-9.

8 Asinger RW, Mikell FL, Sharma B, Hodges M.Observations on detecting left ventricular thrombus withtwo dimensional echocardiography: emphasis on avoid-ance of false positive diagnoses. Am Jf Cardiol 1981;47:145-56.

9 Schiller NB, Shah PM, Crawford M, et al. Recommenda-tions for quantitation of the left ventricle by two-dimensional echocardiography. American Society ofEchocardiography Committee on Standards, Sub-committee on Quantitation of Two-DimensionalEchocardiograms. JAm Soc Echocardiogr 1989;2:358-67.

10 Stratton JR, Lighty G, Pearlman AS, Ritchie JL. Detectionof left ventricular thrombus by two-dimensional echocar-diography: sensitivity, specificity, and causes of uncer-tainty. Circulation 1982;66:156-66.

11 Tramarin R, Pozzoli M, Febo 0, et al. Two-dimensionalechocardiographic assessment of anticoagulant therapy inleft ventricular thrombosis early after acute myocardialinfarction. EurHeartJ 1986;7:482-92.

12 Stroke prevention in atrial fibrillation investigators.Warfarin versus aspirin for prevention of thromboem-bolism in atrial fibrillation: stroke prevention in atrial fib-rillation II study. Lancet 1994;343:687-91.

13 Stratton JR, Ritchie JL. The effects of antithrombotic drugsin patients with left ventricular thrombi: assessment withindium- 11 platelet imaging and two-dimensionalechocardiography. Circulation 1984;69:561-8.

14 Domenicucci S, Chiarella F, Bellotti P, Lupi G, Scarsi G,Vecchio C. Early appearance of left ventricular thrombiafter anterior myocardial infarction: a marker of higherin-hospital mortality in patients not treated with anti-thrombotic drugs. EurHeartJ 1990;11:51-8.

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