Transcript Carotid disease

CAROTID ARTERY DISEASE
Jehanzeb Bilal, MD
PGY-3
Elias A. Iliadis, MD
Medical Director, Noninvasive Vascular Intervention
Cooper Heart Institute
Patient one
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49 year old female presents to her
primary care physician for a routine check
up.
PMH: unremarkable.
 Social hx: smoker (1PP-30yrs).
 Family History : CAD, HTN, CVA
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VS.:97 125/75
65
12
 Neurological exam : normal.
 Cardiovascular : right carotid bruit.
 The rest of the exam was unremarkable
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A carotid ultrasound was done.
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The ultrasound revealed a 95 % stenosis
of the left carotid.
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Would you screen for carotid disease in
asymptomatic patients?
What is the value of a carotid bruit on physical exam
in an asymptomatic patient?
What is a hemodynamically significant carotid
stenosis?
Would you further evaluate this patient ?
How would you manage her carotid stenosis?
The Framingham cohort
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Evaluation of carotid bruit in this cohort
In eight years, a bruit appeared in 66 men and
105 women, all asymptomatic.
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The incidence increased with age equally in the two sexes from
3.5% at 44 to 54 years, to 7.0% at 65 to 79 years.
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The eight-year incidence was greater in diabetes and
hypertensive subjects.
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These patients had a stroke rate more than twice expected for
age and sex.
JAMA 1981 Apr 10;245(14):1442-5.
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More often cerebral infarction occurred in a
vascular territory different from that of the carotid
bruit
Ruptured aneurysm, embolism from the heart, and
lacunar infarction was the mechanism of stroke in
nearly half the cases.
Incidence of myocardial infarction increased
twofold .
General mortality increased; 1.7-fold with men, and
1.9-fold in women, with 79% of the deaths owing to
cardiovascular disease, including stroke.
Conclusion of the study
Carotid bruit is clearly an indicator of increased
stroke risk
 General and non-focal sign of advanced
atherosclerotic disease
 Not necessarily an indicator of local arterial
stenosis preceding cerebral infarction
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The natural history of
asymptomatic carotid artery
occlusive lesions.
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Follow up of 640 neurologically asymptomatic
patients
292 had pressure-significant internal carotid
artery stenosis
348 had a carotid bruit only without a pressuresignificant lesion.
Patients with asymptomatic pressure-significant
carotid stenosis are at greater risk for stroke
than a non significant occlusion (twofold) and a
general population (sevenfold).
JAMA 1987Nov20;258(19):2704-7
The natural h/o carotid bruits in
the elderly
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To determine the relative risk for cerebrovascular
events in elderly patients with carotid bruits
241 NH residents were examined for carotid bruits and
signs of previous stroke.
 Twelve percent of residents had asymptomatic carotid
bruits.
 The 3-year cumulative incidence of strokes was 10%,
vs. 9%, yielding a relative risk of 1.1 (95% CI, 0.45 to 2.7).
 In 60% of surviving residents, baseline carotid bruits
were no longer present at the time of follow-up
examination.
 The disappearance of these bruits was not associated
with the occurrence of interval cerebrovascular events
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Ann Intern Med1990Mar12(5):340-3
SHEP
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The Systolic Hypertension in the Elderly Program
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To determine the association between asymptomatic
carotid bruits and the development of subsequent
stroke in older adults with isolated systolic
hypertension.
5-year randomized trial
• Average follow-up 4.2 years.
• Carotid bruits were found in (6.4%) of the participants .
• Stroke developed in (7.4%) of those with carotid bruits and
in (5.0%) of those without carotid bruits.
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J Gen Intern Med 1998 Feb;13(2):86-90
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Relative risk of stroke with asymptomatic carotid bruits
was 1.29 (95% CI 0.80, 2.06).
Subjects aged 60 to 69 years, trend (p=.08) toward
increased risk (relative risk [RR] 2.05; 95% CI 0.92, 4.68)
of subsequent stroke in persons with carotid bruits.
Subjects aged 70 or over, no relation between carotid
bruit and subsequent stroke (RR 0.98; 95% CI 0.55,
1.76).
The causes and risk of stroke in
patient with internal carotid artery
stenosis
patients with unilateral symptomatic carotidartery stenosis
 Patients with asymptomatic contralateral
stenosis
 The risk of stroke at five years after study entry
in a total of 1820 patients increased with the
severity of stenosis.
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N Engl J Med 2000; 343:1420-1421, Nov 9, 2000.
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Forty-five percent of strokes in patients
with asymptomatic stenosis of 60 to 99
percent are attributable to lacunes or
cardioembolism.
EVALUATION OF CAROTID
DISEASE
Conventional angiography
Gold standard
 Visualize the entire cerebrovascular
system
 Invasive test
 Expensive test
 Neurological morbidity/mortality
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Non invasive carotid artery testing.
A meta-analytic review.
Carotid angiography as the reference standard for
comparison.
 Carotid duplex ultrasonography, carotid Doppler
ultrasonography, and magnetic resonance angiography are all
similarly successful at predicting
-100% carotid artery occlusion (SN 82 to 86,SP 98)
-70% stenosis (SN 83 to 86,SP 89 TO 94 )
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Other factors, such as cost, availability, and local experience
may influence the decision to use these tests to screen for
carotid artery atherosclerosis that may respond to surgery
Ann Intern Med 1995 Mar 1;122(5):360-7.
Ann Int Med 1995,122,P360.
Duplex ultrasound and magnetic resonance
angiography compared with digital subtraction
angiography in carotid artery stenosis: a
systematic review
• 64 studies reviewed.
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MRA has a better discriminatory power compared with
DUS in diagnosing 70% to 99%
stenosis(SN95vs86/SP90vs87)
A sensitive and specific test compared with DSA in the
evaluation of carotid artery stenosis.
For detecting occlusion, both DUS and MRA are very
accurate.(SN 98 vs. 96/SP 100VS 100)
Stroke 2003 May;34(5):1324-32.
Non-invasive imaging compared with intraarterial angiography in the diagnosis of
symptomatic carotid stenosis: a metaanalysis
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CEMRA is superior to US,MRA and CTA, with
SN 94 versus 89, 88, and 76 percent,
respectively; specificities 93 versus 84, 84, and
94 percent, respectively
Lancet. 2006 May 6;367(9521):1503-12
Carotid US
Least expensive
 Easy to perform
 Defines the plaque
-The sensitivity and specificity are lower in asymptomatic
patients
-It can overestimate the stenosis: unnecessary surgery
-Less precise in less than 50% stenosis, and total occlusion
-It only defines cervical disease
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MRA
May be more Sensitive and Specific than
US (esp. CEMRA)
 Disadvantage:
-Cannot be done if patient is critically ill , or
has a pacemaker
-Expensive
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CTA
Used when US is not reliable:
-Severe calcific artery
-Severe kinking of the vessels
-Short neck
-High bifurcation
-Overview of surgical field
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Can we bypass invasive angiography?
Separate and combined test results of DUS and MRA were
compared with the reference standard DSA. Only the
stenosis measurements of the arteries on the symptomatic
side were included in the analyses.
 When MRA and DUS were combined , agreement between
these 2 modalities (84% of patients) gave a sensitivity of
96.3% (95% CI, 90.8% to 99.0%) and a specificity of 80.2%
(95% CI, 73.1% to 87.3%) for identifying severe stenosis(>70)
 This combination may obviate the need of an invasive
angiography ,if the results of both tests were similar.
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Stroke 2002 Aug;33(8):2003-8.
Guidelines
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The United States Preventive Services Task Force
(USPSTF) recommends against screening for
asymptomatic carotid artery stenosis in the general
population .
The American Heart Association and American Stroke
Association acknowledge that "screening of general
populations for asymptomatic carotid stenosis is
unlikely to be cost-effective" .
The American Society of Neuroimaging suggests that,
while screening for the general population is not
recommended, screening might be considered for
patients ≥65 years with significant risk factors for
cardiovascular disease .
PREVENTION OF STROKES IN
ASYMPTOMATIC BUT
HEMODYNAMICALLY
SIGNIFICANT CAROTID ARTERY
STENOSIS.
VA STUDY
Multicenter clinical trial
 444 men with asymptomatic carotid stenosis shown
arteriographically (50 percent or more).
 Randomly assigned to optimal medical treatment
including ASPIRIN plus carotid endarterectomy ( 211
patients) or optimal medical treatment alone (233
patients)
 The incidence of ipsilateral neurologic events was 8.0
percent in the surgical group and 20.6 percent in the
medical group (P 0.001), RR of 0.38 (95 confidence
interval,( 0.22 to 0.67).
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N Engl J Med 1993 Jan 28;328(4):221-7
ACAS(asymptomatic carotid
atherosclerosis study)
Randomized, multicenter trial
Total of 1662 patients with asymptomatic carotid artery
stenosis of 60% or greater
 medical risk factor management for all patients; carotid
endarterectomy for patients randomized to receive surgery.
 After a median follow-up of 2.7 years, the incidence of
ipsilateral stroke and any perioperative stroke or death rate
was significantly lower in the surgical group than with aspirin
alone (5 versus 11 percent) for a relative risk reduction of 0.53
(95% CI 0.22-0.72).
 Men had an absolute risk reduction of 8 percent; the absolute
risk reduction in women was only 1.4 percent.
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JAMA 1995 May 10;273(18):1421-8
ACST (asymptomatic carotid
surgery trial)
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3120 asymptomatic patients with 60% stenosis(US)
randomized between immediate CEA and indefinite
deferral of any CEA (4% per year)and were followed for
up to 5 years.
The net five-year risk for all strokes or perioperative
death in the CEA group was reduced by nearly half.
The absolute risk reduction over five years was greater
for men than for women 8.2 percent versus 4.08
Lancet 2004 May 8;363(9420):1491-502.
COCHRANE REVIEW
All completed randomized trials comparing CEA to medical
treatment in patients with asymptomatic carotid stenosis
 5223 patients were included.
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Despite about a 3% perioperative stroke or death rate, CEA
for asymptomatic carotid stenosis reduces the risk of ipsilateral
stroke, and any stroke, by approximately 30% over three years.
 The absolute risk reduction is small (approximately 1% per year
over the first few years of follow up in the two largest and
most recent trials) but it could be higher with longer follow up.
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Cochrane Database Syst Rev 2005;(4):CD001923
Factors to consider in assessing
risk and benefit of CEA
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Exclusion criteria (life expectancy of < five years)
The severity of stenosis.
The presence of newer drugs.
The frequency of TIA in carotid disease.
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The differentiation between the nature of
stroke(cardioembolic and lacunar).
The controlateral carotid artery.
The Late benefit of CEA.
The gender.
Postoperative complications.
Guidelines
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For asymptomatic patient with a stenosis of 60 to
99 %,CEA is recommended only for patients aged
between 45 and 75 with a life expectance of at
least five years. NNT 33
The benefit of CEA appears only after couple of
year.
ASA should be used pre and postoperatively.
Patient two
69 y old female was found to have b/l carotid
bruit on physical exam. She has no history of
strokes or transient ischemic attack.
 PMH: CAD with triple vessel disease , CHF with
diastolic dysfunction, DM, HTN, dyslipidemia.
 She is a past smoker(40 p/year)
 Meds: coreg, simvastatin, lisinopril, insulin, asa,
lasix.
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A carotid ultrasound and a conventional
angiography showed a severe stenosis(more
than 95%) of her right ICA ,
 Is she a candidate for a CEA? What is the
current data on Carotid Artery Stenting?
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SAPHIRE(stenting and angioplasty
with protection in patients at high
risk of endarterectomy
A randomized trial comparing carotid-artery stenting with
the use of an emboli-protection device to endarterectomy
 334 patients with coexisting conditions that potentially
increased the risk posed by endarterectomy and who had
either a symptomatic carotid-artery stenosis of at least 50
percent of the luminal diameter or an asymptomatic
stenosis of at least 80 percent.
 More than seventy percent of patients had asymptomatic
disease.
 Twenty percent had a restenosis after CEA.
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N Engl J Med 2004 Oct 7;351(15):1493-501.
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The primary end point was a combined incidence
of death, stroke and MI in the first thirty days
postoperatively or death/ipsilateral stroke from day
31 up to one year.
The study was designed to test the non-inferiority
of CAS to CEA in this population.
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The primary end point occurred in 20 patients
randomly assigned to undergo carotid artery stenting
and in 32 patients randomly assigned to undergo
endarterectomy (P=0.004 for noninferiority, and
P=0.053 for superiority).
At one year, carotid revascularization was repeated in
fewer patients who had received stents than in those
who had undergone endarterectomy (P=0.04).
CAS is non inferior to CEA in patient with carotid
artery disease and high risk for surgery.
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The FDA approved the stent used in this
trial for high risk patients with carotid
disease.
Guidelines
CAS should be considered in patients with
severe carotid stenosis(>70%) and one of the
following conditions:
-Severe medical comorbidities(cardiopulmonary).
-Difficult neck access for CEA.
-Stenosis after irradiation.
-Restenosis after CEA.
-Contralateral laryngeal palsy.
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Patient three
57 year old male presents to the ER with
acute weakness of his right arm and leg .The
symptoms started 12 hour ago.
 He has a h/o of HTN and dyslipidemia, currently
on lisinopril and simvastatin.
 Physical exam:97 170/100 85 15
-He had a 4/5 weakness of his right arm and leg
-Cardiovascular exam was unremarkable
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CT scan of the brain without contrast showed
chronic small vessel disease.
 MRI brain revealed an acute infarct of left
middle cerebral artery territory.
 MRA showed an 90 % stenosis of his left carotid
artery.
 He was admitted to the stroke unit.
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Is the management of
carotid disease different in symptomatic
patients?
NASCET TRIAL(North American
Symptomatic Carotid
Endarterectomy Trial)
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659 patients with a h/o of stroke in the past 120 days
had 70-90 %stenosis of the ipsilateral carotid artery.
Patients were randomized to medical management vs.
medical management with CEA.
The primary outcome was any stroke or death.
The study was prematurely terminated by the NIH because
of the clear evidence of benefit from surgery .
At the time of study termination, patients had been followed
for a mean of 18 months.
N Engl J Med 1991 Aug 15;325(7):445-53
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The risk of stroke and death was higher at 30 days in
the patients treated with CEA (5.8 versus 3.3 percent
with medical therapy)
longer follow-up revealed a lower cumulative risk at
two years of any ipsilateral stroke (9 versus 26 percent,
p<0.001)
A lower risk of major or fatal ipsilateral stroke (2.5
versus 13.1 percent, p<0.001)
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CEA was highly beneficial (9 vs. 26 %,p<0.001)for
patients with recent TIAs or nondisabling strokes with
ipsilateral stenosis of 70 to 99 %
moderate degree of benefit for patients with 50 to 69
percent symptomatic ipsilateral stenosis ( 15.7 versus
22.2) percent (p = 0.045)
Patients with stenosis of less than 50 percent did not
benefit from surgery.
Elderly patients with 50 to 99 percent stenosis
benefited more from CEA than younger patients
These findings suggest that CEA should not be withheld
from appropriately selected, fit patients over the age of
75.
ECST(European carotid surgery
trial)
A multicentre trial of 3024 patients
 randomized to carotid endarterectomy and medical
management vs. medical management alone
 All patients had a recent stroke or TIA in a carotid artery
distribution, and some degree of carotid stenosis.
 Median follow up was for six years.
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Lancet 1998 May 9;351(9113):1379-87
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The risk of major ischemic stroke ipsilateral to the
unoperated symptomatic carotid artery increased with
severity of stenosis, particularly above about 70-80% of
the original luminal diameter, but only for 2-3 years after
randomization.
On average, the immediate risk of surgery (7%)was
worth trading off against the long-term risk of stroke
without surgery when the stenosis was greater than
about 80% diameter.
For disabling or fatal stroke the control risks seemed to
diminish after the first year, so delay of surgery by just a
few months after clinical presentation might make this
overall difference non-significant.
SPACE TRIAL(stent-protected
angioplasty versus carotid
endarterectomy )
1200 patients with symptomatic carotid-artery stenosis
within 180 days of enrollment
 Patients were randomly assigned carotid-artery stenting
(n=605) or carotid endarterectomy (n=595).
 The primary endpoint was ipsilateral ischemic stroke or
death from time of randomization to 30 days after the
procedure.
 Non inferiority study.
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Lancet. 2006 Oct 7;368(9543):1239-47
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The trial was stopped after the second interim analysis,
mainly due to recruitment and funding problems.
SPACE failed to prove the non-inferiority of carotidartery stenting compared with carotid endarterectomy
expressed as the rate of ipsilateral stroke or death
within 30 days after treatment in symptomatic patients
with moderate to severe stenosis of the carotid artery.
The use of embolic protection devices with stenting
was optional, and were used in only 27 percent of
patients treated with CAS.
EVA-S trial(Endarterectomy vs.
angioplasty with stenting)
Multicenter, randomized, noninferiority trial to compare
stenting with endarterectomy in patients with a symptomatic
carotid stenosis of at least 60%.
 The primary end point was the incidence of any stroke or
death within 30 days and six months after therapy .
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N Engl J Med. 2006 Oct 19;355(16):1660-71
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The trial was stopped prematurely after the inclusion of
527 patient because of worse outcome with the CAS
branch.
The 30-day incidence of any stroke or death was 3.9%
after endarterectomy (95% confidence interval [CI],
2.0 to 7.2) and 9.6% after stenting (95% CI, 6.4 to 14.0);
At 6 months, the incidence of any stroke or death was
6.1% after endarterectomy and 11.7% after stenting (P =
0.02).
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Critics:
Lack of experience by many of the interventionalists doing
the CAS.
Five different stents and seven different cerebral protection
devices were used in EVA-3S
interventional clinicians were required to have performed
only two stenting procedures with any new device before its
use in the trial.
Embolic protection for patients assigned to CAS was
optional early in the trial, and the 30-day outcome of any
stroke or death was significantly lower in patients treated
with (n = 277) than in those treated without (n = 20)
embolic protection (7.9 and 25 percent, respectively).
Guidelines
For symptomatic carotid artery stenosis of 70
to 99% with no severe co-morbidities: CEA
.NNT of 6.3.
 For symptomatic stenosis of 50 to 69%:CEA.
NNT of 22.
 ASA should be started before surgery and
continued postoperatively.
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Conditions associated with less or
no benefit from CEA
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Severe disabling strokes
Transient monocular ischemia VS hemispheric
TIA
Younger population
Total carotid stenosis
Controlateral carotid stenosis increase
perioperative risk
Complication of Carotid artery
stenting
Stroke.
 Periprocedural bradycardia and
hypotension
 Technical difficulty.
 Restenosis(early 0.5 to 2%,late 0.6 to 6%)
 Hyperperfusion syndrome.
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Thank you