(Stroke. 1999;30:2679.)
© 1999 American Heart Association, Inc.
Original Contributions |
Cerebral Microembolism in Acute Myocardial Infarction
Presented in part at the 34th Meeting of Canadian Congress of Neurological Sciences (Edmonton, Alberta, Canada, June 15–19, 1999) and awarded the Canadian Stroke Society Prize.
From the Stroke Research Unit (Z.G.N., Z.C., D.B., J.W.N.) and Division of Cardiology(C.J.), Sunnybrook & Women’s College Health Sciences Centre, University of Toronto, Canada.
Correspondence to Zurab Nadareishvili, MD, PhD, Stroke Branch, NINDS, NIH, Bldg 36, Room 4A03, 36 Convent Dr, MSC4128, Bethesda, MD 20892-4128. E-mail znadareishvili1i19{at}hotmail.com
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Abstract |
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Background and Purpose—This study was undertaken to determine the frequency of cerebral microemboli (high-intensity transient signals; HITS) detected by transcranial Doppler (TCD) in patients with acute myocardial infarction (AMI) and to relate them to the various putative risk factors and clinical embolic events.
Methods—We investigated 112 consecutive patients within 72 hours of admission to an acute coronary care unit using TCD to monitor for cerebral microemboli. Twelve patients were excluded because of failure of ultrasound insonation. All patients had 2-dimensional echocardiograms within the study period.
Results—HITS were detected in 17% of patients, with significantly higher frequency in patients with reduced (<65%) left ventricular (LV) ejection fraction (P=0.019), akinetic LV segments (P=0.002), and LV thrombus (P=0.015). A marginally significant (P=0.059) increase of HITS was found in patients with anterior AMI. Stroke was significantly more frequent in patients with cerebral microemboli (P=0.01).
Conclusions—HITS were detected in 17% of patients in spite of adequate antithrombotic therapy and were increased in patients with reduced LV function, akinetic myocardial segments, and LV thrombus. They were present in all 3 patients with stroke and may represent a predictor of clinical embolic events.
Key Words: embolism • myocardial infarction • ultrasonography, Doppler, transcranial
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Of the 50 000 patients in Canada who experience a stroke each year,1 almost 35 000 have ischemic stroke, and cardioembolism accounts for 25% to 38%.2 3 Most of these are due to atrial fibrillation (AF), and only 2% to 3% of strokes result from acute myocardial infarction (AMI).4 The annual incidence of ischemic stroke after AMI varies from 1.5% in the general population5 to 7% in individuals with diabetes mellitus.6 The reported incidence of stroke during hospitalization for AMI is 0.9% to 2.4%. Thirty-three percent of these cases occur within 24 hours and
70% within the first
week.7 8 There are various causes for systemic embolism,
including mural thrombus usually associated with anterior wall
infarction, cardiac arrhythmias (especially AF), and impaired
left ventricular ejection fraction
(LVEF).9 10 Many asymptomatic patients with potential sources of cardiac embolism have signs of cerebral embolism on brain-imaging studies.11 The ability to detect circulating asymptomatic emboli might have predictive value for future embolic events.
Transcranial Doppler (TCD) sonography can detect circulating cerebral microemboli (high-intensity transient signals; HITS), and these have been observed in a variety of potential embolic sources, including symptomatic and asymptomatic carotid stenosis,12 13 prosthetic heart valves,14 15 AF,16 17 cardiac aneurysm, and severe ventricular dysfunction.18 However, there have been no studies in patients with AMI.
We decided to perform an initial study to determine the incidence of HITS and relate various putative risk factors (such as left ventricular [LV] dysfunction) to the presence of microemboli.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We prospectively studied consecutive patients admitted to the coronary care unit of Sunnybrook and Women’s College Health Sciences Center with AMI between January 1997 and April 1999, excluding those with AF, carotid stenosis >50%, or prosthetic heart valves and patients with no significant transmural myocardial damage (non–Q-wave AMI). AMI was diagnosed according to the established clinical and electrocardiographic criteria.6 Sources of aortic emboli were excluded either by angiography performed for other reasons (preoperative and interventional procedures) or at operation by direct palpation of aorta.19
Demographics, history of ischemic heart disease, stroke, or transient ischemic attack (TIA), and other clinical details were recorded for all patients. In addition, standardized neurological examination was performed before the TCD monitoring. All reports of cerebral, neurovascular, and cardiac imaging were recorded.
Two-Dimensional Echocardiography
Two-dimensional echocardiographic studies were
performed in all patients with 2.5-MHz phased-array transducer (Hewlett
Packard Sonos 2000 or Sonos 5500). LVEF was assessed with a visual
quantitative grading system. Patients were divided into groups
according to LVEF function: those with normal LVEF (>65%) and those
with decreased LVEF (
65%). The presence of LV wall-motion
abnormalities (hypokinetic/akinetic segment) was also recorded for
each subject. LV thrombus was diagnosed when an echogenic mass adjacent
to but distinguishable from LV endocardium was detected in an area of
wall-motion abnormality.20 The echocardiograms were
interpreted by experienced cardiologists blinded to the results of the
TCD recordings.
TCD Monitoring
TCD was performed with a Pioneer TC 2020 (Nicolet-EME Ltd) with
a 2-MHz transducer in the first 72 hours after the patient’s admission
to the coronary care unit. A sample volume of 10 mm was
used for all patients. After identification of the middle cerebral
arteries (MCAs) via the transtemporal windows, the probes
were fixed on the temporal skull by use of a standard headset, and
recordings were performed for 30 minutes. Depth of insonation
of the MCA was 56 to 60 mm. The TCD device was equipped with a
software program that permitted the online detection of HITS, which
were all saved on hard disk. During monitoring, the investigator was
present to watch for patient movement and to detect the HITS
acoustically online. All HITS were analyzed offline by 3
experienced observers blinded to the clinical presentation
of the patient. In cases of disagreement between the observers, the
HITS were not accepted as microemboli and were considered an artifact.
HITS were identified as a predominantly unidirectional short-duration
intensity increase, accompanied by a characteristic clicking or
chirping sound.21
Statistical Analysis
Statistical analyses were performed with the Excel
software package. Continuous data are summarized as mean±SD. We used
2-sided Student’s t test for comparison of means (±SD).
Proportional differences between the groups were evaluated with
Fisher’s exact 
2 test.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Subject Characteristics
We evaluated 112 patients; because of failure to find acoustic windows (12 cases), TCD recordings were performed only in 100 patients. There were 68 men and 32 women (mean age 68±11 years). Women were significantly (P<0.05) older than men (66.0±11.2 versus 73.1±11.0 years). Fifty-three patients had anterior and 47 had inferior AMIs. Thirty patients had normal LVEF on their echocardiograms. In the remaining 70 with decreased LVEF (<65%), 25 had LVEF 20% to 35%, 16 had LVEF 35% to 50%, and 29 had LVEF 50% to 65%.
Carotid duplex sonography was performed in all patients with and 25 patients without cerebral microemboli. Only 4 patients had LV thrombus. Normal LV wall motion was documented in 29 patients, whereas 71 patients had significant LV wall-motion abnormalities, including akinetic segments.
Forty-five patients had thrombolytic treatment, 94 had been given intravenous heparin, and 93 received aspirin. There was a large overlap between these groups, and 99% of patients were treated either with heparin or aspirin. There was no significant difference in the presence of anterior lesions, LV thrombus, decreased LVEF, or LV akinetic segments between patients treated with or without thrombolysis.
Microemboli Detection
HITS were detected in 17 patients, with a mean rate of 0.5±1.6
per 30 minutes. Twelve patients had 1 HITS, 3 had 2 HITS, 1 had 3 HITS,
and 1 had 14 HITS. HITS were detected significantly more frequently in
patients with reduced LVEF (22.8% versus 3.3%; P=0.019)
and LV thrombus (75.0% versus 14.6%; P=0.019). No patients
with normal LV motion had HITS, but they were seen in 23.9% of the 67
patients with akinetic LV segments (P=0.002). HITS were
documented in 24.5% of patients with anterior and 8.5% of those with
inferior infarctions. This finding is marginally
significant (P=0.059;
Table
).
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There was a trend toward an increase in the frequency of HITS in
patients treated with thrombolysis (22.2% versus
12.7%; P=0.285) and in patients who had not received
aspirin(16.1% versus 28.5%; P=0.339), but heparin
treatment made no difference (P=1.000; Table
).
During the follow-up period (median 8 days), 3 patients experienced stroke. Two had ischemic stroke and 1 a hemorrhagic transformation of cerebral infarction after thrombolysis. All 3 patients had anterior myocardial infarctions with a decreased LVEF (20% to 35%) and severe LV motion abnormalities, but none of them had LV thrombus. HITS were documented in all of these patients. Twenty percent (3/17) of HITS-positive patients had strokes, but none occurred in the 83 patients without them (P=0.01). TCD recording was performed in 2 cases before the stroke. One patient had 14 HITS per 30 minutes. Despite treatment with intravenous heparin and aspirin, this 73-year-old woman developed a right-sided dense hemiplegia and aphasia the next day. Carotid ultrasound did not reveal any significant stenosis. TCD monitoring after 2 days continued to reveal 6 HITS/30 minutes. The second patient had an ischemic stroke within 24 hours of treatment with tissue plasminogen activator, and HITS were documented before the event. The first CT scan was negative, and the repeated (after 24 hours) CT scan showed minor bleeding within the MCA infarct.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Seventeen percent of our patients with AMI had cerebral microembolism in spite of adequate antithrombotic treatment started immediately after admission. HITS were significantly more frequently detected in patients with decreased LVEF in the presence of akinetic myocardial segments and LV thrombus. A nearly significant increase of HITS was documented in patients with anterior AMI.
Decreased LVEF was an independent risk factor for stroke in a post hoc analysis of the SAVE study, and every decrease of 5% in LVEF increased the risk of stroke by 18%.9 In another study,18 HITS were detected in 26% of patients with severe LV dysfunction (LVEF <30%), but these patients also had idiopathic dilated cardiomyopathy.
Anterior AMI is an established risk factor for stroke.8 10 In a study of 77 patients with anterior AMI, 46% had LV thrombi,22 and the frequency increased progressively with the extent of myocardial dyskinesia and LV end-diastolic pressure. Van Danzig et al23 also noted that hypokinetic segments were risk factors for LV thrombi formation.
LV thrombus is a major cause of cerebral embolism in AMI,24 and in the present study, HITS were more frequently seen in patients with LV thrombi. Only 4 patients in our series had LV thrombus, probably because most patients were given heparin, which prevents thrombus formation.25 The Healing and Early Afterload Reducing Therapy (HEART) study26 also reported a lower incidence of LV thrombus than previously reported and ascribed this to changes to AMI management. In the present study, none of the patients had transesophageal echocardiography, which is a more sensitive method of LV thrombi detection than transthoracic echo. This may be another explanation for the low incidence of LV thrombi in our study population.
Three percent of our patients had a stroke during the first week, similar to rates reported in other studies.7 8 27 All 3 patients with stroke had HITS. In addition to the established risk factors for stroke in AMI, including anterior lesions, mural thrombus, impaired LV function, and atrial fibrillation, HITS may be also be an independent risk factor for clinical embolic events.
Almost 99% of our study population were treated with anticoagulant or antiplatelet drugs, and although antithrombotic therapy prevents the formation of large emboli,28 our results show that it may not suppress microemboli. Nearly half the patients had thrombolytic therapy, and cerebral microemboli were more frequent in this group. The incidence of LV thrombus is reduced after thrombolytic therapy,29 but the risk of ischemic cerebral infarction is not influenced by thrombolytic therapy.30 31 The increase of cerebral microemboli documented in the present study may represent disintegrating LV thrombus.32
The relevance of cerebral microemboli detection to clinical events is uncertain. At present, there is limited direct evidence that HITS have predictive value in determining clinical embolic events. However, there is extensive indirect evidence.33 Embolic signals were more common in symptomatic than in asymptomatic patients with carotid stenosis,34 in those with prosthetic heart valves,35 and in AF.18 The present study is another example of indirect evidence that HITS are predictors of stroke in patients with AMI.
Received July 22, 1999; revision received September 23, 1999; accepted September 23, 1999.
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References |
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|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Hodgson C. Prevalence and disabilities of community-living seniors who report the effects of stroke. CMAJ. 1998;159(suppl 6):S9–S14.
2. Castilo V, Bogouslavsky J. Brain embolism. In: Welch KMA, Caplan LR, Reis D. Primer on Cerebrovascular Diseases. San Diego, Calif: Academic Press; 1997:286–289.
3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Ann Neurol. 1998;44:3:445. Abstract.
4. Kanter MC, Sherman DG. Neurological aspects of cardiogenic embolism. In: Daniel WG, Kronzon I, Mugge A, eds. Cardiogenic Embolism. Baltimore, Md: Williams & Wilkins: 199621–25.
5. Feinberg WM. Anticoagulation for prevention of stroke. Neurology. 1998;51(suppl 3):S-20–S-22.
6. Pullicino PM, Xuereb M, Aquilina J, Piedmonte MR. Stroke following acute myocardial infarction in diabetics. J Intern Med. 1992;231:287–293.[Medline] [Order article via Infotrieve]
7. Behar S, Tanne D, Abinader E, Agmont J, Barzilai J, Friedman Y, Kaplinsky E, Kauli N, Kishon Y, Palant A, Peled B, Reisin L, Schlesinger Z, Zahavi I, Zion M, Goldourt U, for the SPRINT Study Group. Cerebrovascular accident complicating acute myocardial infarction: incidence, clinical significance and short- and long-term mortality rates. Am J Med. 1991;91:45–50.[Medline] [Order article via Infotrieve]
8.
Komrad MS, Coffey E, Coffey KS, McKinnis R, Masey EW,
Calliff RM. Myocardial infarction and stroke. Neurology. 1984;34:1403–1409.
9.
Loh E, Sutton MSJ, Wun CCC, Roulleau J, Flaker GC,
Gotlieb SS, Lamas GA, Moye LA, Goldhaber SZ, Peffer MA.
Ventricular dysfunction and risk of stroke after myocardial
infarction. N Engl J Med. 1997;336:251–257.
10. Tanne D, Reicher -Reiss H, Boyko V, Behar S, for the Sprint Study Group. Stroke risk after anterior wall acute myocardial infarction. Am J Cardiol. 1995;76:825–826.[Medline] [Order article via Infotrieve]
11.
Peterson P, Madsen EB, Brun B, Pedersen F, Gydensted C,
Boysen G. Silent cerebral infarction in chronic atrial fibrillation.
Stroke. 1987;18:1098–1100.
12.
Markus HS, Thomson ND, Brown MM.
Asymptomatic cerebral embolic signals in
symptomatic and asymptomatic carotid artery
disease. Brain. 1995;118:1005–1011.
13.
Forteza AM, Babikian VL, Hyde C, Winter M, Pochay V.
Effect of time and cerebrovascular symptoms on the prevalence of
microembolic signals in patients with cervical carotid
stenosis. Stroke. 1996;27:687–690.
14. Georgiadis D, Grosset DG, Kelman A, Faichey A, Lees KR. Prevalence and characteristics of intracranial microembolic signals in patients with different types of prosthetic cardiac valves. Stroke. 1994;25:587–592.[Abstract]
15.
Sliwka U, Georgiadis D. Clinical correlates of
Doppler microembolic signals in patients with
prosthetic cardiac valves: analysis of 580 cases.
Stroke. 1998;29:140–143.
16. Tegler CH, Hitchings LP, Eicke M, Leighton J, Fredercks RK, Downs TR, Stump DA, Burke GL.. Microemboli detection in stroke associated with atrial fibrillation. J Cardiovasc Tech. 1990;9:283–284.
17.
Cullinane M, Wainwright R, Brown A, Monaghan M, Markus
H. Asymptomatic embolization in subjects with atrial
fibrillation not taking anticoagulants: a prospective study.
Stroke. 1998;29:1810–1815.
18. Nabavi DG, Arato S, Droste DW, Schulte-Altendonebourg G, Kemeny V, Reinecke H, Borggrefe M, Breithardt G, Ringelstein EB. Microembolic load in asymptomatic patients with cardiac aneurysm, severe left ventricular dysfunction and atrial fibrillation. Cerebrovasc Dis. 1998;8:214–221.[Medline] [Order article via Infotrieve]
19.
Wolman RL, Nussmeier NA, Aggarwal A, Kanchuger MS,
Roach GW, Newman MF, Mangano CM, Marschall KE, Ley C, Boisvert DM,
Ozanne GM, Herzkowitz A, Graham SH, Mangano DT, for the Multicenter
Study of Perioperative Ischemia Research Group
and the Ischemia Research and Education Foundation
Investigators. Cerebral injury after cardiac surgery: identification of
a group at extraordinary risk. Stroke. 1999;30:514–522.
20.
Meltzer KS, Guthner D, Rakowski H, Popp RL, Martin RP.
Diagnosis of left ventricular thrombi by two-dimensional
echocardiography. Br Heart J. 1979;42:261–263.
21.
Consensus Committee of the 9th International Cerebral
Hemodynamic Symposium. Basic identification criteria of
Doppler microembolic signals. Stroke. 1995;26:1123.
22. Lamas GA, Vaughan DE, Pfeffer MA. Left ventricular thrombus formation after first anterior wall acute myocardial infarction. Am J Cardiol. 1988;62:31–35.[Medline] [Order article via Infotrieve]
23. Van Danzig JM, Delemurre BJ, Bot H. Doppler left ventricular flow pattern versus conventional predictors of left ventricular thrombus after acute myocardial infarction. J Am Coll Cardiol. 1995;25:1341–1346.[Abstract]
24.
Johansen KA, Nordrehang JE, von der Lippe G, Volset SE.
Risk factor for embolization in patients with left
ventricular thrombi and acute myocardial infarction.
Br Heart J. 1988;60:104–110.
25. The SCATI group: randomized controlled trial of subcutaneous calcium-heparin in acute myocardial infarction. Lancet. 1989;2:182–186.[Medline] [Order article via Infotrieve]
26. Greaves SC, Zhi G, Lee RT, Solomon SD, MacFaydyen J, Rapaport E, Menapace FJ, Rouleau JL, Pfeffer MA. Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction. Am J Cardiol. 1997;80:442–448.[Medline] [Order article via Infotrieve]
27. Bodenheimer MM, Sauer D, Shareef B, Brown MW, Fleiss JL, Moss AJ. Relation between myocardial infarction and stroke. J Am Coll Cardiol. 1994;24:61–66.[Abstract]
28.
Cairns JA, Theroux P, Lewis HD Jr, Ezekowitz M, Meade
TW Sutton GS. Antithrombotic agents in coronary artery disease.
Chest. 1998;114:611S–633S.
29. Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993;22:1004–1009.[Abstract]
30. Hess DC, D’Cruz IA, Adams RJ, Nichols FT III. Coronary artery disease, myocardial infarction, and brain embolism. Neurol Clin. 1993;11:399–417.[Medline] [Order article via Infotrieve]
31.
Sloan MA, Price TR, Terrin ML, Forman S, Gore JM,
Chaitman BR, Hodges M, Mueller H, Rogers WJ, Knatterud GL, Braunwald E.
Ischemic cerebral infarction after rt-PA and heparin therapy
for acute myocardial infarction: the TIMI-II pilot and randomized
clinical trial combined experience. Stroke. 1997;28:1107–1114.
32. Stafford PJ, Strachan CJ, Vincent R, Chamberlain DA. Multiple microemboli after disintegration of clot during thrombolysis for acute myocardial infarction. BMJ. 1989;299:1310–1312.
33. Van Zuilen EV, Van Gijn J, Ackerstaff RGA. The clinical relevance of cerebral microemboli detection by transcranial Doppler ultrasound. J Neuroimaging. 1998;8:32–37.[Medline] [Order article via Infotrieve]
34.
Siebler M, Natchman A, Sitzer M, Rose G, Kleinschmidt
A, Radmacher J, Steinmetz H. Cerebral microembolism and the risk of
ischemia in asymptomatic high-grade internal
carotid artery stenosis. Stroke. 1995;26:2184–2186.
35.
Geiser T, Sturzeneger M, Genewein U, Haeberli A, Beer
JH. Mechanism of cerebrovascular events as assessed by procoagulant
activity, cerebral microemboli, and platelet microparticles in
patients with prosthetic heart valves. Stroke. 1998;29:1770–1777.
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