(Stroke. 1999;30:2683.)
© 1999 American Heart Association, Inc.
Original Contributions |
Association Between Large Aortic Arch Atheromas and High-Intensity Transient Signals in Elderly Stroke Patients
Presented in part at the 24th American Heart Association International Conference on Stroke and Cerebral Circulation, Nashville, Tenn, February 4, 1999.
From the Neurological Institute (T.R., J.P.M., R.L.S.) and the Division of Cardiology (M.R.D.T., R.R.S., I.V.T., S.H.), New York Presbyterian Hospital, and the Division of Epidemiology and Gertrude H. Sergievsky Center (R.L.S.), School of Public Health, Columbia University, New York, NY.
Correspondence to Tanja Rundek, MD, Neurological Institute, Room 552, New York Presbyterian Hospital, 710 West 168th St, New York, NY 10032. E-mail tr89{at}columbia.edu
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—Aortic arch atheromas (AAs) have been shown to be a risk factor for ischemic stroke (IS) in the elderly because of their potential for cerebral embolization. However, the association between AAs and the presence of cerebral microemboli has not been clearly established. The aim of this study was to determine whether large AAs are associated with an increased frequency of high-intensity transient signals (HITS) in elderly patients with IS.
Methods—We performed bitemporal simultaneous HITS
monitoring of both middle cerebral arteries in 62 consecutive elderly
patients with acute IS (mean age 72.5±8.8 years, 65% men). In 16
patients, one or both temporal windows were inadequate; therefore, the
analysis of HITS was performed in the remaining 46 patients.
All patients underwent omniplane transesophageal
echocardiography (TEE), and they had no significant
extracranial or intracranial artery disease and no cardiac
prosthetic valves. Large AA was defined as 
4 mm in
thickness. Complex AA was defined as ulcerated or mobile, regardless of
plaque thickness. HITS monitoring was performed within 24 hours of TEE
and analyzed by an experienced neurologist-sonographer blinded
to TEE findings. A 9-dB threshold was chosen to discriminate HITS from
background Doppler signal. The HITS counts in the left and in the
right middle cerebral arteries were added and reported as a total
number of HITS in 30 minutes.
Results—HITS were detected in 14 (78%) of 18 patients with large AAs versus 8 (29%) of 28 patients with no or small AAs (odds ratio [OR] 8.8, 95% CI 2.2 to 34.8; P=0.001). The association was also present in 27 patients with no other cardiac embolic sources, such as atrial fibrillation, patent foramen ovale, spontaneous echo contrast, and thrombus (7 of 10 patients with large AAs versus 3 of 17 patients with small or no AA; OR 10.9, 95% CI 1.7 to 68.5; P=0.013). Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2.6, 95% CI 1.7 to 3.9; P=0.005).
Conclusions—HITS are significantly associated with large AAs in elderly stroke patients. This observation may support the causal role of large AAs in IS.
Key Words: aortic arch • embolism • stroke, ischemic • ultrasonography, Doppler, transcranial
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Aortic arch atheromas (AAs) have been shown to be associated with an increased risk of ischemic stroke (IS) in the elderly because of their potential for embolization in the cerebral circulation.1 2 3 4 After the embolic potential of AAs had been recognized from pathological studies,5 6 the introduction of transesophageal echocardiography (TEE) allowed for the accurate visualization of the proximal portion of the aorta and provided a tool for assessing the role of AAs as a risk factor for cerebral and peripheral embolism in vivo.4 5 6 7 8 9 10 11 12 AAs have been linked to an increased risk of embolic events in numerous case-control and cross-sectional studies as well as in some prospective cohort studies.2 4 13 However, the causal role of AA for cerebral microembolism in individual patients has not been clearly established.
Transcranial Doppler (TCD) ultrasound is capable of detecting microembolic material in the arteries of the circle of Willis by recording high-intensity transient signals (HITS) within regular Doppler frequency spectra.14 15 16 Although these HITS can be clinically silent, they may be clinically important as a marker of increased risk of stroke.17 18 19 20 21 22 The clinical relevance of HITS, however, remains uncertain. Their detection may be important in patients with AAs, indicating the propensity of AAs to act as a source of cerebral emboli. The examination of AAs by TEE and monitoring of HITS by TCD may therefore be helpful in the selection of stroke patient for prophylactic treatment.
Although multiple studies have linked the presence of AAs with cerebral embolism, the association of large AAs with HITS has never been shown in a series of consecutive elderly patients with IS. The present study was aimed at determining whether large AAs are associated with an increased frequency of HITS in elderly patients with acute IS.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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As part of the APRIS (Aortic Plaque and Risk of Ischemic Stroke) study, 62 consecutive patients over the age of 60 with first-ever acute IS in the anterior circulation were studied. All patients underwent omniplane TEE and TCD monitoring for HITS within 1 week of stroke onset. All patients also underwent color duplex Doppler of carotid and vertebral arteries, TCD scanning of the circle of Willis and vertebrobasilar system, and brain CT or MRI. Patients with stenosis of >40% of at least one artery in the extracranial (carotid or vertebral arteries) or intracranial (arteries of the circle of Willis or intracranial segment of the vertebral arteries and basilar artery) circulation and patients with prosthetic cardiac valves were excluded from the study before TCD monitoring because of the possible presence of a confounding embolic source.
Transesophageal Echocardiography
TEE was performed by use of a 5-MHz omniplane transducer. The
aorta was imaged in transverse and longitudinal views. The aortic arch
was defined as the portion of aorta between the curve at the end of the
ascending portion and the origination of the left subclavian artery. An
atheroma was defined as a discrete protrusion of the
intimal surface of the vessel at least 2 mm in thickness and
different in appearance and echogenicity from the adjacent intact
intimal surface. The presence and location of any atheroma
was recorded. In the case of multiple AAs, the most advanced lesion
was considered.
Aortic arch plaques were characterized according to previously
described criteria1 2 as large (4 mm in thickness),
small (<4 mm in thickness), or not present.
Atheromas with ulceration and/or mobile components were
classified as complex, according to the previously published
definition.23 An ulceration was defined as a discrete
indentation of the luminal surface of the plaque with base width and
maximum depth of at least 2 mm each. The videotapes were reviewed
by a single experienced echocardiographer who was blinded
to the TCD-HITS results.
TCD Monitoring
The bitemporal simultaneous HITS monitoring of both
middle cerebral arteries (MCAs) was performed within 24 hours of TEE
according to the standardized protocol published
previously.14 15 16 The recording was performed with
a 2-channel transcranial Doppler system (TC 2020
EME/Nicolet, 486 processor and 128–fast Fourier transform [FFT] and
2-MHz multigate probes) equipped with the automated software for HITS
detection (EME/Nicolet, version 1.0). The Doppler frequency spectra
of both MCAs were recorded continuously for 30 minutes by using a
standardized procedure (supine position of patient whenever possible,
depth of insonation of 45 to 58 mm from the probe, low to medium
gain, and sample volume 10 to 12 mm). The pulse repetition
frequency ranged from 4 to 8 kHz, and sweep time for
simultaneous monitoring was 3.1 seconds. Based on these
parameters, the FFT time-window overlap varied from 25% to
81%, missing <0.2% of embolic signals because of the inadequacy of
the equipment characteristics.
HITS were identified by their transient, short (<0.1 second), and unidirectional high-amplitude signal with a narrow spectrum. A 9-dB threshold was chosen to discriminate microembolic signals from background noise, which was in accordance with the recommendations of the International Consensus Group on Microembolus Detection.15
An experienced neurologist-sonographer who was blinded to the TEE findings identified HITS. The count was performed by a combination of different methods: (1) visual, by displaying the FFT of the color-coded Doppler spectra, (2) acoustical, by continuous on-line observation, and (3) off-line, by specially designed software for automated HITS detection. Artifacts were excluded during the on-line analysis by means of the characteristic bidirectional occurrence within the Doppler spectrum and of the chirping sounds produced by the probe movement, patient motion, coughing, narrow window, or inappropriate gain used during monitoring.
The HITS counts in the left and in the right MCAs were added, reflecting the total number of HITS in 30 minutes. The side of HITS was compared with the stroke side assessed clinically and by CT or MRI. The embolic signal amplitudes in decibels were also analyzed.
Statistical Analysis
The association of aortic plaque size and complexity with the
presence of HITS and HITS amplitude was analyzed by the
2 test or Fisher exact test when appropriate.
Crude odds ratios (ORs) for the association between AA size and
complexity and the presence of HITS were calculated. The Spearman
correlation coefficient (r) was calculated to determine the
relationship between AA thickness and the frequency of HITS. All
probability values were 2-tailed and considered significant at
P<0.05. In the case of multiple comparisons, a Bonferroni
correction was performed. For all statistical analyses, SAS
statistical package version 6.12 (SAS Institute) was used.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The initial study population consisted of 62 patients (mean age 72.5±8.8 years; 65% men; 50% Hispanics, 26% whites, and 24% African Americans). In 16 (26%) of 62 patients, TCD was not able to detect any signals in either MCA because of the temporal bone thickness ("poor or no" temporal windows). There was a greater proportion of women and African Americans among these 16 patients with inadequate temporal windows (13 women [81%] and 6 African Americans [38%]) compared with the 46 patients with adequate windows (16 women [35%] and 9 African Americans [20%]; P<0.05). Although the average age was slightly greater in patients with inadequate windows (76.6±7.4 years) than in those with adequate windows (72.6±8.9 years), the proportion of the patients aged >75 years was the same (44% in both groups).
Data analysis was therefore performed among the 46 patients
with the interpretable TCD findings. Demographic and clinical
characteristics of these 46 study patients are summarized in Table 1
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TCD detected HITS in 22 (48%) of 46 patients. The majority of these
patients showed a low frequency of HITS, with an average number of
1.6±1.1 per 30 minutes (range 1 to 5). Fifteen patients (68%) had 1
HITS, 3 patients (13%) had 2 HITS, 2 (9%) had 3 HITS, 1 (5%) had 4
HITS, and 1 (5%) had 5 HITS. The amplitude of HITS ranged from 9 to 13
dB (average 10.6±1.7 dB). Patients with HITS did not differ from those
without HITS with respect to age, sex, and race/ethnicity (except for
the higher proportion of HITS detected among African Americans, 8
[42%] of 22 versus 2 [10%] of 24; P=0.025) and with
respect to most of the common risk factors (Table 1
). There was
a higher frequency of HITS among patients with coronary heart
disease (8 [42%] of 22 versus 3 [14%] of 24; P=0.049)
or hypercholesterolemia (10 [53%] of 22
versus 4 [19%] of 24; P=0.026). HITS were detected more
frequently on the symptomatic side (14 [64%] of 22
versus 7 [29%] of 24; P=0.019). HITS were less frequently
observed in lacunar strokes (8 [33%] of 24 versus 1 [6%] of 22;
P=0.016).
TEE detected AAs in 36 (78%) of the 46 patients. Large AAs were found in 18 patients (39%), small AAs in 18 (39%), and no AA was found in 10 patients (22%). Complex AAs were found in 6 (17%) of 36 patients.
HITS were detected in 20 (56%) of 36 patients with AAs and in 2 (20%)
of 10 patients without AAs (OR 5.0, 95% CI 0.98 to 26.9;
P=0.064). Furthermore, HITS were detected in 14 (78%) of 18
patients with large AAs versus 8 (29%) of 28 patients with no or small
AAs (OR 8.8, 95% CI 2.2 to 34.8; P=0.001; Table 2). The AA thickness and the frequency of
HITS per 30 minutes were also highly correlated when analyzed
as continuous variables (r=0.501,
P<0.01).
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Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2.6, 95% CI 1.7 to 3.9; P=0.005).
After exclusion of patients with other possible TEE findings that may
contribute to HITS (7 patients with atrial fibrillation, 7 with patent
foramen ovale (PFO), 9 with spontaneous echo contrast (SPEC), and 2
with thrombi), the association between plaque size and HITS remained
statistically significant (Figure). Among the 27 patients
without other possible cardiac sources, HITS were detected in 7 (70%)
of 10 patients with large AAs versus 3 (18%) of 17 patients with small
AAs (OR 10.9, 95% CI 1.7 to 68.5; P=0.013).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The present study demonstrates that TCD-detected HITS are significantly associated with large AAs in elderly acute IS patients. To our knowledge, this is the first reported systematic TCD study of HITS in IS patients with AAs. Previous studies have included a smaller number of patients with AAs, mainly referred for echocardiography to rule out a cardiac source of embolization, and most of them had atrial fibrillation, prosthetic cardiac valves, or cardiac thrombus.1 3 7 8 9 10 11 12 18 23 24
The clinical relevance of HITS in the cerebral circulation in patients with cardiac and carotid artery disease is still uncertain. However, several studies have found an association between HITS and increased risk of stroke.14 17 18 19 25 26 27 28 29 Tong et al19 found an association of HITS with known cardioembolic risk factors and history of prior stroke. In patients with carotid stenosis, HITS have been related to the degree of stenosis and associated with an increased risk of subsequent stroke or transient ischemic attack.17 27 28 29 Early finding of HITS after carotid endarterectomy has also been related to early postoperative stroke recurrence.29
We found the association between HITS and large AAs to exist even after exclusion of patients with other possible TEE findings that may cause HITS (atrial fibrillation, PFO, SPEC, and thrombi). Additionally, we found HITS in all patients with complex AAs, which are known to be associated with the greatest increase in stroke risk.1 3 4 6 9 10 13 23 Although the clinical relevance of such finding is still uncertain, it may support the causal role of large AAs in IS in elderly patients.
The present study has some limitations. Although we reported a statistically significant association between large AAs and HITS, definitive conclusions cannot be drawn from the presented results. Data were obtained in a selected population of elderly patients with IS and with no evidence of significant extracranial or intracranial carotid artery disease. Furthermore, the number of patients analyzed in the study was small. A significant proportion of the patients (26%) was excluded because of an inadequate acoustical window. This was related to the higher proportion of African Americans and women in our study in whom we were unable to insonate intracranial vessels. This situation has also been previously reported.18 Also, results apply only to elderly patients. However, the reported prevalence of large atheromas in patients aged <60 years is low.4 Finally, the lack of a control group precludes the assessment of the association between HITS and AAs in stroke-free subjects. The presence of HITS and their association with large AAs in stroke-free subjects could make the relation between this finding and the risk of stroke less strong. However, this would not necessarily detract from the potential clinical relevance of HITS, because HITS could also be related to silent infarcts and increased future risk of stroke or other vascular events. Prospective follow-up studies are necessary to further determine the clinical significance of HITS.
The examination of AAs by TEE and the potential for cerebral microembolism by TCD-HITS monitoring might have a role in the management of patients with acute stroke. HITS monitoring in patients with large AAs may be important for determining the risk of stroke recurrence and may be important in stratifying patients into groups that may benefit from different stroke prevention medications. Larger prospective studies are required to confirm the clinical relevance of the association between HITS and AAs and to determine the predictive value of HITS detection.
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Acknowledgments |
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This study was supported by grants R01 NS-27517, R01 NS-29993, and R01 NS-36286 from the National Institute of Neurological Disorders and Stroke.
Received May 13, 1999; revision received August 10, 1999; accepted September 8, 1999.
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References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Amarenco P, Duyckaerts C, Tzourio C, Henin D, Bousser MG, Hauw JJ. The prevalence of ulcerated plaques in the aortic arch in patients with stroke. N Engl J Med. 1992;326:221–225.[Abstract]
2.
The French Study of Aortic Plaques in Stroke Group.
Atherosclerotic disease of the aortic arch as a risk factor for
recurrent ischemic stroke. N Engl J Med. 1996;334:1216–1221.
3. Jones EF, Kalman JM, Calafiore P, Tonkin AM, Donnan GA. Proximal aortic atheroma: an independent risk factor for cerebral ischemia. Stroke. 1995;26:218–224.
4.
Di Tullio MR, Sacco RL, Gersony D, Nayak H, Weslow RG,
Kargman DE, Homma S. Aortic atheromas and acute
ischemic stroke: a transesophageal
echocardiographic study in an ethnically mixed
population. Neurology. 1996;46:1560–1566.
5. Vaduganathan P, Ewton A, Nagueh SF, Weilbaecher DG, Safi HG, Zoghbi WA. Pathologic correlates of aortic plaques, thrombi and mobile ‘aortic debris’ imaged in vivo with transesophageal echocardiography. J Am Coll Cardiol. 1997;30:357–363.[Abstract]
6.
Amarenco P, Cohen A, Tzourio C, Bertrand B,
Hommel M, Besson G, Chauvel C, Touboul PJ, Bousser MG. Atherosclerotic
disease of the aortic arch and the risk of ischemic stroke.
N Engl J Med. 1994;331:1474–1479.
7. Nihoyannopoulos P, Joshi, Athanasopoulos G, Oakley GM. Detection of atherosclerotic lesion in the aorta by transesophageal echocardiography. Am J Cardiol. 1993;71:1208–1212.[Medline] [Order article via Infotrieve]
8.
Toyoda K, Yasaka M, Nagata S, Yamaguchi T. Aortogenic
embolic stroke: a transesophageal
echocardiography approach. Stroke. 1992;23:1056–1061.
9. Stone DA, Hawke MW, LaMontane M, Kittner SJ, Acosta J, Corretti M, Sample C, Price TR, Plotnick GD. Ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic stroke: a multiplane transesophageal echocardiography study. Am Heart J. 1995;130:105–108.[Medline] [Order article via Infotrieve]
10. Tunick PA, Rosenzweig BP, Katz ES, Freedberg RS, Perez JL, Kronzon I. High risk for vascular events in patients with protruding aortic atheromas: a prospective study. J Am Coll Cardiol. 1994;23:1085–1090.[Abstract]
11.
Mitusch R, Doherty C, Wucherpfenning H, Memmeshiemer C,
Tepe C, Stierle U, Kessler C, Sheikhzadeh A. Vascular events during
follow-up in patients with aortic arch atherosclerosis.
Stroke. 1997;28:36–39.
12. Karalis DG, Chandrasekarn K, Victor MF, Ross JJ, Mintz GS. Recognition and embolic potential of intraaortic atherosclerotic debris. J Am Coll Cardiol. 1991;17:73–78.[Abstract]
13. Tunick PA, Perez JL, Kronzon I. Protruding atheromas in the thoracic aorta and systemic embolization. Ann Intern Med. 1991;115:423–427.
14. Markus H. Transcranial Doppler detection of circulating cerebral emboli. Stroke. 1993;24:1247–1249.
15.
Ringelstein EB, Droste DW, Babikian VL, Evans DH,
Grosset DG, Kaps M, Markus HS, Rusell D, Siebler M. Consensus on
microembolus detection by TCD: International Consensus Group on
Microembolus Detection. Stroke. 1998;29:725–729.
16.
Markus HS, Brown MM. Differentiation between different
pathological cerebral embolic materials using transcranial
Doppler in an in vitro model. Stroke. 1993;24:1–5.
17. Molloy JE, Markus HS. Embolic signals predict risk of stroke and TIA in carotid artery stenosis. Stroke. 1999;30:238. Abstract.
18. Koennecke HK, Mast H, Trocio SH, Sacco RL, Ma W, Mohr JP, Thompson LP. Frequency and determinants of microemboli on transcranial Doppler in unselected patients with acute carotid territory ischemia. Cerebrovasc Dis. 1998;8:107–112.[Medline] [Order article via Infotrieve]
19. Tong DC, Bolger A, Alberts GW. Incidence of transcranial Doppler-detected cerebral microemboli in patients referred to echocardiography. Stroke. 1994;25:2138–2141.[Abstract]
20. Grosset DG, Georgiadis D, Abdulah I, Bone I, Lees KR. Doppler emboli signals vary according to stroke subtype. Stroke. 1994;25:382–385.[Abstract]
21. Tegeler CH, Burke GL, Delley GM, Stump DA. Carotid emboli predict poor outcome in stroke. Stroke. 1993;24:186. Abstract.
22.
Georgiadis D, Grosset DG, Lees KR. Transhemispheric
passage of microemboli in patients with unilateral internal artery
occlusion. Stroke. 1993;24:1664–1666.
23. Di Tullio MR, Savoia MT, Sacco RL, Sciacca RR, Homma S. Aortic atheroma morphology and the risk of ischemic stroke in a multiethnic population. Am Heart J. In press.
24. Rams JJ, Davis AD, Lolley MD, Berger PM, Spencer MP. Detection of microemboli in patients with artificial heart valves using transcranial Doppler: preliminary observation. J Heart Valve Dis. 1993;2:37–41.[Medline] [Order article via Infotrieve]
25. Britton M, Gustavson C. Non-rheumatic atrial fibrillation as a risk factor for stroke. Stroke. 1985;16:183–188.
26.
Timsit SG, Sacco RL, Mohr JP, Foulkes MA, Tatemichi TK,
Wolf PA, Price TR, Hier DB. Brain infarction severity differs according
to cardiac or arterial embolic source.
Neurology. 1993;43:728–733.
27.
Siebler M, Sitzer M, Steinmetz H. Detection of
intracranial emboli in patients with symptomatic
extracranial carotid artery disease. Stroke. 1993;23:1652–1654.
28.
Valton L, Laurre V, Pavy le Traon A, Massabuau P,
Geraud G. Microembolic signals and risk of early
recurrence in patients with stroke or transient
ischemic attack. Stroke. 1998;29:2125–2128.
29.
Spencer MP, Thomas GI, Nicholls SC, Sauvage LR.
Detection of middle cerebral artery emboli during carotid
endarterectomy using transcranial
Doppler ultrasonography. Stroke. 1990;21:415–423.
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