Book chapter - Atherosclerotic carotid artery disease

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Atherosclerotic carotid artery disease.
It is less important to invent new operations and new techniques of operating than to find ways and
means to avoid surgery.
(Bernard von Langenbeck, 1820—1887)
History
Anatomy
Symptoms due to carotid artery disease
Ocular symptoms
Transient ischaemic attack
Stroke
Risk factors for TIA and stroke
Carotid endarterectomy and symptomatic patients
Non conventional symptoms as indications for CEA.
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Carotid endarterectomy – asymptomatic patients
CEA and coronary artery bypass grafting (CABG)
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Patching
High disease/bifurcation
GA vs. LA debate
Neuromonitoring and shunts
Intraoperative and post operative stroke
Quality control
CREST
ICSS
Meta-analysis of CAS vs. CEA for symptomatic carotid stenosis
Scoring system to predict stroke following CAS
Intracranial disease
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History.
 4th century BC - Hippocrates used the term apoplexy (to strike down) to describe strokes and
transient ischaemic attacks (TIA’s). He knew that lesions of the carotid artery resulted in
contralateral hemiplegia.
 100 AD – Rufus of Ephesus – The word carotid was derived from the Greek word karotide
or karos meaning to stun, stupefy or fall into a deep sleep as compressing the artery caused
loss of consciousness or sleep.
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Figure 1 – Sculpture from Parthenon in Athens depicting carotid occlusion to cause
unconsciousness
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1552 - Ambrosie Pare also described the carotid arteries as the arteries for sleep. He wrote
the first report of operative carotid ligation but the patient developed aphasia and
hemiplegia.
Thomas Willis (1621 – 1675) was not the first to describe the intra cranial vascular ring
which bears his name, but it was not until his treatise (Cerebri Anatome), illustrated by Sir
Christopher Wren (of St Paul’s cathedral fame), that its’ true significant was understood.
William Heberden (1710 – 1801) from London described transient cerebral insufficiency
recurring hours, days or months before hemiplegia.
1793 – Hebenstreit reported the first successful carotid ligation.
1809 – Sir Astley Cooper recognised the possibility of stroke after carotid ligation.
1856 – Virchow described carotid thrombosis associated with ipsilateral blindness.
1878 – John Wyeth, an American surgeon, reported 898 cases of common carotid ligation
with a mortality of 43%.
1898 – Gluck was the first to replace a segment of the common carotid artery with a vein
graft in an animal.
1905 – Chiari described ulcerating plaques at the carotid bifurcation and suggested that
emboli could break away and cause stroke.
1914 – Ramsay Hunt (New York) described contralateral hemiplegia and ipsilateral
amaurosis fugax due to carotid disease causing brain softening and stroke. He described
cerebral intermittent claudication.
1918 – LeFevre (France) reported external carotid to internal carotid anastomosis following
tumour excision.
1927 – Egas Moniz (Lisbon) – first description of cerebral angiography using direct intra
carotid injection of contrast.
1951 – documented treatments for carotid artery occlusive disease were Stellate ganglion
block, cervical sympathectomy, thrombectomy, ligation and excision of carotid bifurcation,
intra cranial carotid ligation with clips.
1951 – Carrea, Molins and Murphy perform the first successful reconstruction of the carotid
artery in Buenos Aires but only reported this in 1955. In a 41 year old male with recurring
right hemiparesis, aphasia and left amurosis, they performed end to end anastomosis
between left external carotid and distal internal carotid after partial resection of the stenosed
segment plus a cervical sympathectomy. The patient suffered loss of vision in left eye.
1953 – First successful carotid endarterectomy performed by De Bakey (Figure 2), but he
did not report it till much later. A severely stenotic atherosclerotic plaque with overlying
fresh clot completely occluding the left internal carotid was removed.
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Figure 2. Micheal De Bakey.
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1954 - First report of successful carotid reconstruction by Harold Eastcott (the surgeon),
Pickering (the professor of medicine) and Rob (the professor of surgery) at St. Mary’s
Hospital, London (probably the best medical school in the world!). A 66 year old female had
recurrent amaurosis fujax and TIA’s. The ICA was resected and an end to end anastomosis
performed. Hypothermia was used for cerebral protection.
Anatomy.
Platysma is part of the panniculus carnosus with muscle fibres attached to the skin at one end and
the deep fascia at the other, the same as palmaris brevis, corrugator cuti ani and the dartos muscle.
The vertebral artery is the first branch of the subclavian artery. Colateralization is via the Circle of
Willis (Figure 3). A complete circle is found in only 50% of the population. Peri-orbital collaterals
are also effective in internal carotid occlusion. A thoracic carotid bifurcation is found in 2%.
See embryology and anatomy chapter for more interesting carotid related anatomy.
Figure 3. Right carotid anatomy
Figure 4. Circle of Willis
Symptoms due to carotid artery disease.
Ocular symptoms
Symptomatic patients can present with ipsilateral amaurosis fugax (transient monocular blindness)
or retinal infarction, which may affect an area of monocular vision (branch occlusion) or the entire
retina (central occlusion).
Transient ischaemic attack (TIA).
Definition – a transient episode of neurological dysfunction caused by focal brain ischaemia,
without acute infarction, where the symptoms last for less than 24 hours.
Stroke.
Definition - sudden onset of focal neurological deficit lasting more than 24 hours. Typically, the
ipsilateral anterior cerebral circulation is affected, resulting in contralateral (to the artery and
cerebral hemisphere) homonymous hemianopia; visuospatial neglect; or weakness or paraesthesia
of the face, arm, or leg. In left sided carotid atherosclerosis, dysphasia may result from involvement
of language centres typically found in the left cerebral hemisphere. Visuospatial neglect can occur
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in patients with intact visual fields, typically through involvement of the right temporoparietal
cortex.
After cardiac disease and cancer, stroke is the third most common cause of death in the Western
World. Each year more than 60 000 Australians, 110 000 English patients and 600 000 Americans
have a stroke. About one-third of those who have had a stroke are permanently disabled. Stroke
accounts for 12% of all deaths in the UK and is the commonest cause of morbidity and long term
disability in Europe. It accounts for 5% of the UK’s NHS expenditure (£2.8 billion).
Pathophysiology of stroke and TIA.
Causes of stroke:
 Primary haemorrhage (10 - 20%)
o Subarachnoid haemorrhage – most commonly due to rupture of a Berry aneurysm.
Secondary vasospasm may result in ischaemia.
o Intracerebral haemorrhage – usually secondary to hypertension which causes
microaneurysms in the small perforating arteriols. Other causes – AV malformations,
brain tumours, systemic haematological disorders, anticoagulation.
 Ischaemic stroke (80 - 90%)
o Small vessel disease (lacunar stroke)
o Large vessel disease (carotid and vertebral disease) – accounts for 20% of all strokes
o Cardioembolic e.g. atrial fibrillation which accounts for 20% of all strokes
o In situ thrombosis
o Vasculitis
o Carotid and vertebral dissection
o Pro-thrombotic disorders
o Infections
o Fibromuscular dysplasia
o Undetermined
Advances in medical stroke management.
Hypertension – Cochrane review in 2000 concluded that there was not enough evidence to evaluate
the effect of altering blood pressure on outcome after acute stroke. However, most would treat
hypertension aggressively, aiming for a blood pressure of 120/80 mmHg. Recommended first line
medication is a diuretic or ACE inhibitor in diabetics.
Statins – meta analysis shows that statins reduce the risk of stoke (by 18%) and recurrent stroke.
Antiplatelets - aspirin reduces further stroke mortality or morbidity by 33%. MATCH trial (Lancet
2004) randomised 7599 patients with recent TIA or stroke to either clopidogrel or aspirin plus
clopidogrel. Combination therapy did not reduce the long term risk of stroke but did increase the
risk of life threatening bleeding (1.9% vs. 0.6%). The CARESS trial showed that in patients with
recently symptomatic more than 50% ICA stenosis and micro-embolic signals (MES) on
transcranial Doppler, aspirin plus clopidogrel significantly reduced MES and there were fewer
strokes compared to aspirin alone. The FASTER trial also showed trend to benefit in dual therapy.
In the CLAIR study (Wong Lancet Neurol 2010), 100 patients with acute ischaemic stroke or TIA
were randomised to clopidogrel plus aspirin or aspirin alone. 93 of the 100 patients had intracranial
stenosis (carotid or middle cerebral artery). Fewer patient in the dual antiplatelet group had MES as
detected by TCD (p= 0.025).
Thrombolytic therapy – In the NINDS rTPA stroke study, a CT brain was used to exclude
haemorrhage then 0.9mg/kg rTPA (alteplase) given IV over 1hr within 3hours of symptom onset.
There was improved recovery in those who had lysis. PROTACT II trial used intra-arterial
thrombolysis and had lower complication rate. Current recommendations are that thrombolysis can
be used up to 4.5 hours after symptom onset. ECASS III trial showed similar benefit for
thrombolysis vs. placebo but there was benefit in patients who had had a previous stroke. In patients
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with no prior stroke there was no benefit to lysis. IST-3 was the largest placebo controlled trial.
This study showed no significant benefit from lysis. In a 2010 meta-analysis, 44.6% of alteplase
patients were modified rankin 0 – 1 at 3 months vs. 37.7% of placebo group. NNt = 15. In a 2014
meta-analysis, for patients treated in the 3 – 4.5 window, at 6 months there was 35.3% had modified
rankin 0 – 1 and 30.1% of placebo group. Current American Stroke Association guidelines
recommend rTPA if given within 4.5 hours of ischaemic stroke onset. SYNTHESIS Expansion was
a randomised trial of IV rTPA vs. intra-arterial TPA, mechanical clot disruption or retrieval. There
was no difference in primary outcome (percentage with good outcome). The interventional
management of stroke trial III (IMS III) randomised patients with major stroke. The trial was
stopped early after 656 patients due to futility as the addition of endovascular techniques to IV
rTPA did not alter outcomes. MR and recanalization of stroke clots using embolectomy (MR
RESCUE) was a randomised trial of patients who were ineligible for IV rTPA or had persistent
vessel occlusion after rTPA randomised to standard medical care vs endovascular therapy. There
was again no advantage to endovacular therapy. The multicentre randomised clinical trial of
endovascular treatment for acute ischaemic stroke (MR CLEAN) randomised 500 patients with
acute ischaemic stroke caused by proximal intracranial occlusion in anterior circulation. Patients
were randomised to usual care or endovascular treatment. Functioanl independence was improved
in the endovascular group (19.1% vs 32.6%). There was no difference in mortality or intra cranial
haemorrhage. ESCAPE trail was a randomised trail which showed benefit to endovascular
treatment. Mortality at 90 days was 10.4% in intervention group and 19% in control group.
Acute stroke units – 18 - 46% reduced mortality compared to care on general medical ward.
Anticoagulation – warfarin reduces the risk of further stroke in patients with ischaemic stroke due
to high risk cardiac embolus e.g. cardiac thrombus, prosthetic heart valve. The Cerebral Embolism
Study Group reported a randomised trial of immediate anticoagulation with IV heparin within 48
hours of stroke vs. no anticoagulation. The study was stopped due to a recurrent stroke rate of 10%
in the no anticoagulation group vs. 0% in the heparin group. In the International Stroke Trial,
patients with AF who were not anticoagulated had a recurrent stroke rate of 4.9% within 14 days,
use of heparin reduced this to 2.3% but at the expense of serious bleeding complications of 2.4%.
Rivaroxaban, a direct factor Xa inhibitor has proved efficacy in stroke prevention in patients with
non valvular AF.
Cooling – induction of moderate hypothermia following sever stroke may improve outcome (COOL
AID).
Intra-cranial stenting – SARIS – as study to assess this using a nitinol stent (see later).
Vinpocetine - Cochrane review 2007 – there is not enough evidence to evaluate vinpocetine on
survival or dependency in patients with acute ischaemic stroke.
Effect of urgent medical treatment for TIA and minor stroke on early recurrent stroke, EXPRESS
(Rothwell Lancet 2007).
A prospective study to compare the outcome of urgent assessment and treatment in a hospital clinic
compared to care in primary care in patients with TIA and minor stroke. The risk of a major stoke in
first month after a minor stroke or TIA was 10% (see below), reduced to 2.1% if patients undergo
rapid investigation and initiation of treatment.
Risk factors for TIA and stroke.
70% of carotid territory ischaemic symptoms are due to arterial embolisation which can come from
the heart (25% of all cerebral infarcts), aorta, great vessels or carotid arteries.
Prior TIA or stroke - Symptoms of TIA increase the risk of stroke by approximately 17 times. From
the time of a TIA, the risk of stroke is 5% within the first 48 hours, 10% at 7 days and 15% within
the first 30 days. This increases to 20% at two weeks in those with a carotid stenosis of 50% or
more. Of those who have had an ischaemic stroke, 23% recall a warning TIA before their stroke, of
whom 17% report the TIA occurred on the day of the stroke, 9% on the preceding day and 43% in
the preceding week. Patients who experience TIA’s prior to a stroke are found to have a more
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favorable neurological outcome, possibly due to ischaemic preconditioning and smaller volume
infarcts on MRI. None the less, TIA should be treated as a medical emergency.
Older age group Hypertension - Treating all hypertensives would reduce stroke mortality by 15%. Target BP is
120/80 mmHg.
Smoking – 50% increased risk of atheroembolic brain infarction
Diabetes – 2 - 4 times higher risk of stroke than non diabetics.
Dyslipidaemia Physical inactivity Obesity Atrial fibrillation (AF) - The risk of stroke is 5 - 6 times higher in patients with AF. The risk of AF
increases with age, 1.5% for ages 50 – 59 years, 23.5% for ages 80 – 89 years. If associated with
mitral stenosis, the risk of embolism is much higher. There is an average stroke rate of 5% per year
for all patients with AF. Aspirin reduces the risk of stroke by 21% in patients with AF when
compared to placebo but is less efficacious than warfarin (70% reduction in risk of stroke in patients
with AF (Laupacis 1998)). Patients with AF and no other cardiovascular disease who are less than
65 years of age should have aspirin alone (75 - 300mg/day). Patients over 65 with lone AF could
have aspirin or warfarin. In the absence of AF, warfarin reduces the incidence of TIA but not stroke
and increases mortality.
Carotid ulceration – type A (less than 10mm2 ) annual stroke risk 0.9%, type B (10 – 40mm2 )
annual stroke risk 4.5%, type C (greater than 40mm2 ) 7.5% annual stroke risk. Thus CEA may be
recommended for all type C ulcers, type B associated with significant stenosis and type A in whom
medical treatment has failed.
Hormone replacement therapy (HRT) – The Womens Estrogen for Stroke Trial (WEST)
randomised 652 post menopausal women who had had a stroke or TIA to 17-β oestradiol or
placebo. Although there was no difference in recurrent stroke or death at mean follow up of 2.7
years, there was a higher stroke rate in those on estrogen in the first 6 months. It may be that an
interaction between HRT and a genetic variant predisposes some women to an increased risk of
thrombotic events. Meta-analysis (BMJ 2005) showed that HRT was associated with an increased
risk of stroke, particularly ischaemic type, and of those who had a stroke, those on HRT had a
worse outcome. The increased risk of stroke was also seen in the WHI study.
Nature of the plaque - Echolucency is associated with lipid deposition and intraplaque
haemorrhage. Echogenic plaques are fibrous and calcified. Echolucency can be measured as the
grey scale median (GSM), graded from I to V, (I being echolucent and V being echogenic).
Echolucent plaques and ulcerated plaques are more common in symptomatic patients (83% vs. 44%
and 23% vs. 14% Golledge). Some have suggested that a GSM of less than 25 is a contraindication
to carotid stenting as this results in higher embolisation rates at carotid angioplasty and stenting
(CAS). Echolucent plaques are also associated with more embolic material in filter devices at CAS
– see later (Giannakopoulos ESVS abstracts Athens 2011). Echolucent plaques are more prone to
develop restenosis following treatment. The Asymptomatic Carotid Stenosis and Risk of Stroke
(ACSRS) study showed that in patients with 70 – 99% stenosis and an echogenic plaque had a 7
year risk of stroke of 1%, compared to 14% in patients with echolucent plaques (Nicholides
Vascular 2007). A number of studies have associated carotid plaque echolucency with increased
risk of atherothrombotic events in unrelated vascular areas e.g. MI. This supports the concept of a
systemic destabilizing process. MRI features of plaque instability e.g. thin fibrous cap, large
necrotic core, intraplaque haemorrhage have been associated with increased risk of ipsilateral
ischaemic events. There is also a significantly increased microvessel density and expression of
hepatocyte growth factor (HCF) and its receptor MET in symptomatic plaques (Chowdhury EJVES
2010).
Transcranial Doppler assessment for micro embolic signals (MES) – The risk of ipsilateral stroke
or TIA was 17% at 5 years in patients who were positive for MES and 9% for asymptomatic
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patients who were negative. But – 11% of patients have inadequate temporal window for
transcranial Doppler.
Circulating biomarkers – some have been found to be elevated in symptomatic patients e.g. MMP2,
MMP9, sICAM-1, osteoprotegrin, fibrinogen, homocysteine, anti chylamydia pneumonie
antibodies, CRP.
Excessive alcohol consumption - increases haemorrhagic and ischaemic stroke.
Activation of renin-angiotensin-aldosterone system Chronic haemodialysis – the risk of stroke is increased in those on chronic haemodialysis.
Intracerebral haemorrhage is the main subtype of stoke to cause death in this patient group.
Antiplatelets - Aspirin reduces the overall incidence of strokes by 1 – 2%.
Race – the incidence of stroke among African Americans is double that seen among white
American.
A number of features have been associated with plaque rupture, including a thin fibrous cap,
accumulation of macrophages within the cap, reduced numbers of matrix producing vascular
smooth muscle cells and a large lipid filled core. Neurological events are more likely in those with
plaque rupture, fibrous cap thinning and infiltration with macrophages and T cells. But, plaque
rupture is seen in only 48% of plaques removed from recently symptomatic patients at CEA.
Currently, the best predictor of high risk carotid atherosclerotic disease is the presence of recent
focal neurological symptoms. For details, see studies below. The results are summarised in Table 1.
Table 1. Incidence of stroke in patients with carotid artery disease treated medically.
Symptomatic patients
Asymptomatic patients
NASCET
ECST
ACAS
ACST
%
FU Stroke
%
FU Stroke
%
FU Stroke
%
FU
stenosis
risk
stenosis
risk
stenosis
risk
stenosis
<50
5 y 19%
50 – 69 5 y 22%
60 – 69 3 y 11%
60 – 69 3 y 6%
60 – 79 5 y
70 – 79 2 y 21%
70 – 79 3 y 17%
70 – 79 3 y 5%
80 – 89 2 y 27%
80 – 89 3 y 20%
90 – 99 2 y 35%
90 – 99 3 y 35%
80 – 99 2 y 31%
80 – 99 3 y 24%
80 – 99 3y 3%
80 – 99 5 y
NASCET – North American symptomatic Carotid endarterectomy trial
ECST – European carotid surgery trial
ACAS – Asymptoamtic carotid atherosclerosis study
ACST – Asymptomatic carotid surgery trial
Note – stenosis was measured differently in each trial.
Stroke
risk
10%
10%
Carotid artery stenosis (see table above).
Significant carotid artery disease is present in 33% of patients with peripheral vascular disease, 7%
with coronary disease and 5% of all subjects aged 65 years or more. 10% of TIA’s or non disabling
strokes have a carotid stenosis of 70% or more and 10 - 20% of strokes are thought to be due to
carotid artery disease. Of those with carotid stenosis, if they go on to occlude, about 20% will have
a stroke, presumably at the time of the occlusion.
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Carotid bruits
There is no well documented relationship between carotid bruit and the incidence of stroke. Only
47% of patients with a bruit have a haemodynamically significant stenosis. A bruit is often absent
with severe ICA stenosis. NASCET (see below) showed that over a third of high-grade carotid
stenosis (70 – 99%) had no bruit. For high grade stenosis, presence of a bruit has a sensitivity of
63% and specificity of 61%. Carotid bruit can be caused by:
 mild ICA stenosis
 aortic stenosis
 proximal CCA disease
 contralateral carotid occlusion
 ECA stenosis
 non atheromatous vessel distortion
So do not bother listening for one – unless you are in an exam!
Scoring systems.
Models are available to predict the early risk of stroke after TIA.
ABCD2 score –
Age – more than 60 years = 1
Blood pressure – systolic more than 140mmHg and/or diastolic more than 90mmHg = 1
Clinical features – unilateral weakness = 2, speech disturbance only = 1, other = 0
Duration of symptoms – more than 60min = 2, 10 – 59 min = 1, less than 10min = 0.
Diabetes = 1.
The ABCD score may be useful to triage patients for imaging and surgery.
Figure 3. Incidence of stroke according to ABCD score.
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Differential diagnosis of TIA.
 Migraine
 Partial epileptic seizure
 Encephalopathy - metabolic or toxic
 Labyrinthine disorder
 Panic attack and somatisation
 Multiple sclerosis
 Mononeuropathy
 Space occupying lesion
 Transient global amnesia
Thus they can be difficult to diagnoses and a friendly neurologist may be helpful.
Dizziness and funny turns in the elderly.
A common referral to vascular surgeons is of patients with the above symptoms and a duplex
requested by a general practitioner which reports carotid artery disease. The inference is that the
carotid artery disease is the cause of the symptoms and by intervention on the carotid artery the
patients symptoms may be improved. This is rarely true. For most patients, dizziness is
multifactorial. Syncope is a transient loss of consciousness associated with loss of postural tone as
opposed to a fall where there is no loss of conciousness to cause the fall. Dizziness is more common
in women and frequency increases with age.
Table 2. Clinical classification of dizziness. (Sloane PD Clin Geriatrics Med)
Subtype
Definition
Clinical implications
Vertigo
Sensation that either the
Suggests disorder of inner ear e.g. BPPV,
environment or the individual labyrinthitis, vestibular neuronitis, Menieres
is spinning
disease or disorder of brainstem, cerebellum.
May be drug induced.
Presyncope
Feeling of being about to
Indicates cerebral hypoperfusion, either low
black out
blood pressure e.g. orthostatic hypotension or
bradycardia, other arrhythmia or mechanical
obstruction to cardiac outflow
Dysequilibrium Sensation of imbalance or
Can be non specific in elderly – virtually any
unsteadiness, worse when
disturbance of neurosensory structure related to
patient stands or on walking
postural control e.g. peripheral neuropathy,
cerebellar disease, physical deconditioning,
stroke, vestibular loss
Other
Vague or difficult to describe Could be psychological or drug induced.
Continuous
Dizziness or the ability to
Disease causing permanent structural damage
temporal pattern provoke it is present every
e.g. stroke, cerebellar disorders, uncomplicated
day
vestibular lesions, drugs, peripheral neuropathy,
deconditioning and psychological states
Episodic
Dizziness occurring in
Diseases causing temporary disruption of
temporal pattern distinct episodes separated by structures affecting postural control and its
periods during which
perception e.g. BPPV, recurrent vestulopathy,
symptoms are absent
TIA, migraine
BPPV = benign paroxysmal positional vertigo
Cardiovascular causes of dizziness (accounts for 28% of all causes):
o Orthostatic hypotension – a 20mmHg fall in systolic pressure during the first two mins of
standing. Repeated systolic pressure measurements in the morning are necessary to make the
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diagnosis. Older people are more susceptible to orthostatic hypotension due to hypertension
and medications which blunt the compensatory reflexes.
o Carotid sinus hypersensitivity – three seconds of more of asystole or 50mm Hg drop in
blood pressure following unilateral carotid sinus massage for five seconds in either supine or
upright posture
o Vasovagal syncope – usually a precipitating event with hypotension/bradycardia induced by
prolonged head up tilt
Positional vertigo. Usually due to BPPV. Brief episodes of vertigo lasting less than one minute with
specific head positions e.g. rolling over in bed, bending over. Diagnosis confirmed by Hallpike
manoeuvre – rapid movement of patient head from seated position to head hanging over end of bed,
head tilted to 30° to left and then repeated moving head to right. There may be rotatory nystagmus.
Vertebrobasilar TIA’s are rare – the vertigo is normally accompanied by other neurological
symptoms e.g. diplopia, demiparesis, demianaesthesia, dysarthria.
Causes of syncope:
Carotid sinus syndrome (46%)
Vasovagal (12%). Myoclonic jerks are common (exaggerated faints)
Orthostatic hypotension (30%)
Arrhythmias (13%)
Situational syncope e.g. cough syncope
Aortic stenosis
MI or arrythmia
Aortic dissection
Other causes of dizziness:
Concussion
Normal pressure hydrocephalus
Epilepsy
Hypoglycaemia
Alcohol or drug overdose
Hypoxia
Anxiety/hyperventilation
Hysterical conversion reaction
Subclavian steal
Unexplained in 20%
Vascular causes of stroke to consider in younger patients with no atherosclerosis.
Carotid dissection.
Fibromuscular dysplasia
Investigations.
Duplex scan.
Most centres will rely on a duplex scan alone to select patients for carotid intervention (Walker SR
Vascular 2005). However, a number of organisations have recommended that duplex results should
be confirmed by another imaging modality. Traditionally this was by contrast angiography but more
recent recommendations having suggested MRA or CTA e.g. Intercollegiate Stroke Working Group
(UK) 2004. The Doppler angle should be 45 - 60°. A high resistance waveform (steep systolic
acceleration and low diastolic flow velocity) may indicate severe distal disease and this may require
angiography.
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Table 3. Consensus panel Gray-Scale and Doppler ultrasound criteria for diagnosis of ICA stenosis
and Joint recommendations for Ultrasound Investigations in UK (Oates EJVES 2009).
% stenosis
ICAPSV (cm/s)
Plaque
ICA/CCA
ICAEDV St. Mary’s ratio
(ICAPSV/CCAEDV)
estimate (%)
PSV ratio
(cm/s)
<125
None
<2.0
<40
Less than 8
Nil
Less than 125
<50
Less than 2.0
<40
Less than 8
Less than 50
125 – 230
>50
2.0 – 4.0
>100
8 – 13
50 – 69
>230
>50
>4.0
>100
More than 14
More than 70
More than 400
More than 5
More than 30
90 – 99
High, low or
Visible
Variable
Variable
Variable
Near
undetectable
occlusion
Undetectable
No detectable
NA
NA
NA
Occluded
lumen
PSV = peak systolic velocity, EDV = end diastolic velocity
MRI and MRA.
These tend to overestimate stenosis severity but can identify ischaemic areas in patients with TIA’s
with diffusion weighted imaging able to identify the exact symptom-causing lesion. Some MR
sequences will identify older bleeds. T2 weighted images can be used to assess carotid plaque
characteristics as above.
Figure 4. Diffusion weighted image of areas of ischaemia.
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Figure 5. MRA showing intracrania carotid stenosis
CT and CTA.
Excludes haemorrhage as the cause of stroke or TIA if done within 4–5 days of symptom onset and
identifies space occupying lesions but may not show ischaemic change. CTA (including the aortic
arch) is used in the pre procedure work up prior to carotid angioplasty and stenting (CAS).
A.
B.
Figure a. Calcified stenosis left ICA. B. Occluded right ICA
Carotid angiography.
Carotid angiography has been replaced by CTA but it may be indicated when the distal extend of
the plaque is unclear on duplex, there is inflow or distal disease, difficult duplex due to acoustic
shadowing (calcification) or sub-occlusion. The distal ICA string sign may be due to underfilling
due to a very tight stenosis but may also be due to hypoplasia of the vessel. Angiography is useful
in these patients. Significant arch lesions are found in 1% and can be predicted by unequal arm
blood pressures or abnormal flow signals (spectral broadening, damped low velocity waveform in
CCA) on duplex. The 1 – 2% risk of neurological event with selective carotid angiography can be
reduced if an arch aortogram is used.
Carotid endarterectomy and symptomatic patients.
Conventional symptoms of embolisation from the ICA include amaurosis fugax (transient
monocular blindness), retinal infarction, carotid territory TIA, non disabling stroke or RIND
(reversible ischaemic neurological deficit).
Only 20% of the brain is clinically evocative and 30% of life is spent asleep. Thus 87% of all
cerebral ischaemic attacks will go undetected.
Early surgery might be indicated in those who make a rapid recovery from stroke and who have a
small infarct on CT. Those with larger defects and significant neurological deficit, particularly
altered consciousness, should have surgery deferred for 6 – 8 weeks due to the risk of haemorrhagic
transformation of the ischaemic area. However, some of this data came from studies that included
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operations on occluded ICA’s. In addition, the risk of recurrent stroke in the waiting period is up to
9.5%. It appears as though it is safe to operate soon after intravenous thrombolysis for stroke (Yong
VSSGBI 2012).
European carotid surgery trial (ECST) Lancet 1991 and 1998.
A randomised trial of best medical management (BMT) vs. CEA for any degree of carotid stenosis.
See Table 1 for the risk of stroke in those treated with BMT and Table 3 for a summary of both
ECST and NACET (see below).
ECST showed that there was no benefit for surgery in patients with near occlusion.
The late results (1998) of ECST narrowed the range of carotid stenosis over which CEA could be
considered beneficial in symptomatic patients to more than 80% in men and more than 90% in
women.
Factors that predicted a higher probability of stroke included:
 Cerebral rather than ocular events
 Plaque surface irregularity
 Events within 2 months
 Increasing degree of stenosis
North American symptomatic Carotid endarterectomy trial (NASCET) NEJM 1991 and 1998.
Principal investigator – Henry Barnett.
A randomised trial of BMT vs. CEA for moderate (30 – 69%) and severe (70 – 99%) stenosis. As
with the ECST, operative risk was lower in those with severe stenosis (5.8%) vs. those with
moderate disease (6.7%).
Pooled data from ECST, NASCET and VA trials suggest that a surgeon who performs CEA within
14 days of symptoms but has a 10% procedural risk will still prevent more stokes in the long term
than a surgeon who defers intervention for 4 weeks and has a 0% procedural risk (Naylor EJVES
2010.)
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Table 4. Comparison of ECST and NASCT.
ECST
NASCET
Entry criteria for participating centres
Patient exclusion criteria
Nil
Nil
Number recruited/randomised
Method of stenosis measurement on angiogram
3018/2518
Minimum diameter of ICA divided by estimated diameter
of carotid bulb
Aspirin dose
RESULTS
Morbidity, mortality and stroke rate with 70 – 99%
stenosis
ARR/RRR
30 day mortality
Risk of fatal or disabling stroke due to CEA
Risk of non fatal stroke within 30 days of CEA
Risk of major stroke or death within 30 days of CEA
Risk of any stroke or death following CEA
Risk of any stroke or TIA following CEA
Cranial nerve injury following CEA
Neck haematoma requiring surgery following CEA
Wound infection
Myocardial infarction
Congestive cardiac failure
Increased risk of operative stroke with:
30 day outcome of death with 70 – 99% stenosis
30 day outcome of death with 50 – 69% stenosis
30 day outcome of death with 30 – 49% stenosis
30 day outcome of death with 0 – 29% stenosis
Risk of ipsilateral stroke over 2 years with 70 - 99%
stenosis.
Risk of fatal or disabling stroke over 2 years with 70 –
99% stenosis
Risk of fatal or disabling stroke over 3 years with 70 –
99% stenosis
Risk of stroke over 3 years with 70 – 99% stenosis
ARR/RRR
Risk of ipsilateral stoke over 3 years with 70 – 99%
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BMT
21.9%
CEA
12.3%
9.6% / 56%
1% - half of these due to stroke
3.7%
6.1%
7.1%
7.5%
8.7% - in 91% on the operated side
6.4%
3.1%
Females, PVD, systolic BP above 180mmHg, quick
operations (less than 60 min), cerebral symptoms vs. ocular
12.7%
9.9%
1.4%
0.8%
7.7%
11.4%
Stroke and death rate for CEA less than 6% (50 centres)
Older than 79, significant cardiac, renal, pulmonary or
hepatic disease and those not expected to live for 5 years
1212/659
Minimum diameter of ICA divided by the diameter of the
ICA distal to the stenosis
1300mg
BMT
CEA
2.5%
5.5%
6.7%
5.8%
7.6%
5.5%
3.4%
0.9%
0.6%
Females, PVD, hypertension, age over 75, contra-lateral
occlusion, cerebral events vs. ocular events.
26%
Increased risk of stroke
with plaque ulceration.
13.1%
8.4%
9%
2.5%
7.0%
12.3%
21.9%
9.6%/56%
16.8%
2.8%
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15
stenosis
Risk of stroke or death over 5 years with 30 – 49%
stenosis
ARR/RRR
Risk of stroke or death over 5 years with 50 – 69%
stenosis
ARR/RRR
Risk of stroke or death over 5 years with 70 – 99%
stenosis
ARR/RRR
Risk of ipsilateral stroke over 8 years with 70 – 99%
stenosis
Annual incidence of ipsilateral stroke in those with 70 99% stenosis managed medically
18.7%
14.9%
3.8%/20.3%
22.2%
15.7%
6.5%/29.8%
26%
9.0%
17%/65.4%
27%
6%
14%
10%
ARR = absolute risk reduction
RRR = relative risk reduction
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Pooled data from ECST and NASCET.
There was a clear benefit in stroke reduction in symptomatic patients with 70 – 99% stenosis who
had CEA. CEA could not be justified in symptomatic patients with moderate stenosis (30 – 69%) as
although the risk of any stroke or surgical death was reduced, there is no reduction in the risk of
ipsilateral stroke, surgical stroke or surgical death. The benefit from CEA was greatest in men, age
over 75, with hemispheric as opposed to ocular events, irregular as opposed to smooth plaques, and
those treated within 2 weeks of symptoms. NNT (CEA) to prevent one ipsilateral stoke in 5 years
were:
9 for men, 36 for women
5 for age 75 or older, 18 for younger than 65
5 for those treated within 2 weeks of randomisation, 125 for those treated after 12 weeks.
13 with 50 – 69% stenosis, 15 with stenosis 30 – 69%.
The absolute risk reduction for CEA after TIA is 19% if done within 2 weeks of the TIA, 9% if 2 –
4 weeks of TIA and 1% after 3 months. 5 days risk of stroke after TIA is 5%.
For symptomatic women, there was no benefit for CEA if CEA was done after 2 weeks following
symptoms. The benefit from surgery was greatest in patients with stroke and least in those with
retinal events. There is no benefit for CEA in patients with subocclusion (trickle flow).
Data from the Swedvasc registry has showed that CEA had a combined mortality and stroke rate of
11.5% if performed within 2 days of symptom onset versus 3.6% for those treated 3 to 7 days after
symptom onset (Stromberg Stroke 2012).
Non conventional symptoms as indications for CEA.
CEA improves pulsatile tinnitus in 70% of cases with significant carotid stenosis (Kirkby EJVES
2004). CEA may also be helpful in ischaemic optic neuritis.
A cross-sectional study on 4006 patients with no history of a TIA or stroke found that a more than
75% stenosis of the internal carotid artery was associated with a nearly 7 fold increased risk of
cognitive impairment and a nearly 3 fold increase in the risk of cognitive decline. (Johnson Annal
of internal medicine 2004). Some studies have shown a cognitive improvement after both CEA and
CAS whereas others have shown no change or even a decline. A systematic review (Paraskevas
EJVES 2014) concluded that neither clearly affects cognition.
There have been case reports of hemichorea resolving after CEA (Galea I Neurology 2008).
Retinal artery occlusion, cholesterol emboli and Hollenhorst plaque.
Asymptomatic retinal cholesterol emboli are associated with decreased survival. These patients
have a higher prevalence of hypertension, smoking, echolucent carotid plaques, carotid stenosis
greater than 50% and IHD. Bruno et al concluded that these emboli indicate systemic
atherosclerosis rather than ipsilateral carotid artery stenosis (Stroke 1992). Retinal artery occlusion
and Hollenhorst plaque are not associated with a high risk for hemispheric neurological events
(Dunlap JVS 2007) but not everyone agrees with this (Spence Vascular 2010).
Carotid endarterectomy for patients with crescendo TIA’s or recent stroke.
Early studies reported stroke and death rates of up to 42%. But in these studies, there were some
patients with severe neurological deficits and even coma, and there was no reliable way to
diagnoses haemorrhagic strokes. In addition some patients underwent CEA when the ICA was
occluded. We now know this is the wrong thing to do. Traditionally vascular surgeons advocated a
delay of 6 weeks following stoke before performing CEA. It was said that this reduced the
incidence of haemorrhagic transformation of large ischaemic areas. In a meta-analysis (Patterson
Vascular 2009), CEA for crescendo TIA resulted in a 6% stroke rate and a 3.2% death rate. For
progressive stroke, the perioperative stroke rate was 10.5% and the death rate 6.5%.
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Carotid endarterectomy - asymptomatic patients.
The risk of stroke in patients with asymptomatic ICA stenosis was thought to be about 2% per year
but with more intensive medical treatment, it is more like 1% per year (Abbott Stroke 2009). One of
the original asymptomatic CEA trials was stopped early due to the high incidence of MI in the
surgical group, who were not prescribed aspirin (Mayo study). The Carotid artery stenosis with
asymptomatic narrowing – operation vs. aspirin (CASANOVA) study found no difference in stroke
or death rates between those who had CEA and those that did not but there were lots of problems in
this study e.g. 118 CEA were performed on the 204 subjects randomised to the medical arm, those
with 90% or more stenosis were excluded. Other studies in asymptomatic patients showed the
perioperative stroke rate to be 4 – 5%, indicating that surgery might cause more stokes than it
prevented. With occlusion of the contralateral ICA, perioperative stroke and deaths may be as high
as 12% in asymptomatic patients. This stimulated the ACAS study.
Asymptomatic Carotid Atherosclerosis Study (ACAS) (JAMA 1995)
A randomised study of CEA vs. medical therapy in low risk, asymptomatic patients with 60% or
more carotid stenosis. There were 1662 patients in 39 centres with very tight selection – 25 patients
were screened for every 1 entered into the trial. Non whites represented only 5% of those enrolled.
313 of the 834 patients randomised to BMT had a carotid angiogram. 4.2% had a greater than 90%
stenosis, 28% had a greater than 80% stenosis. 45 (5.4%) of the BMT patients went on to have
CEA. The trial was stopped early due to the benefit of CEA. Overall, the risk of stroke or death in
surgical patients was 5.1% compared to 11% in medical patients with a 60% or more stenosis,
estimated over 5 years, giving a 53% relative risk reduction, but an absolute risk reduction of only
1.2% per year (5.9% at 5 years). There was a very low perioperative stroke and death rate of 2.3%
(1.2% due to pre op angiography). CEA did not prevent fatal or disabling stroke and there was little
benefit in women. ACAS showed an inverse correlation between stenosis severity and the risk of
stroke:
Degree of stenosis
5 year stroke risk
60 - 69%
11.4%
70 - 79
6.7%
80 - 99
3.7%
The symptomatic studies had shown that overall 13 patients with symptomatic significant stenosis
require a CEA to prevent 1 stroke. ACAS showed that 53 patients with asymptomatic significant
stenosis require CEA to prevent 1 stroke.
ACAS also gave information on restenosis – see restenosis section below.
Asymptomatic Carotid Surgery Trial (ACST). Lancet 2004, ESVS Nice 2008 and Lancet 2010 (A.
Halliday and Thomas).
Participating surgeons had to have a stroke and death rate of less than 6%. Patients were included
with a 60% or greater stenosis on ultrasound causing no symptoms within 6 months. Exclusions poor surgical risk e.g. recent MI, cardiac source of emboli. 3120 patients from 126 centres in 30
countries were included. Only 88% of those randomised to CEA had surgery within one year of
randomisation. In those randomised to BMT, 18% had undergone CEA by 5 years following
randomisation and 26% by 10 years, mainly due to a change of mind by patient or surgeon, not
because they had symptoms (148 of the 407 patients who were randomised to BMT but had CEA
had CEA due to symptoms). Medical management was left to discretion of each centre, thus only
17% of patients were on a statin, increasing to 58% by 2003. The incidence of stoke in the BMT
group was 2% per year.
Table 5. Summary of ACST results.
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Risk of stroke or death within 30 days of CEA
5 year risk of stroke
ARR
5 year risk of fatal or disabling stroke
5 year risk of fatal stroke
Any stroke or death
Risk of stroke 0 – 4 years
Risk of stroke 5 – 10 years
CEA
3.1%, 2.7% in males, 4.0% in females
6.4%
5.4%
3.5%
2.1%
2.9%
0.9%
1.5%
BMT
11.8%
6.1%
4.2%
4%
2.2%
1.6%
Contralateral strokes were significantly reduced by ipsilateral CEA - why? Men less than 75 years
benefit more from surgery than women. The greatest benefit was in men less than 65 years of age.
Benefit was seen with stenoses greater than 70% on duplex scan.
Only 10% of all deaths were due to stroke i.e. patients were more likely to die from other causes.
Other information relevant to asymptomatic patients.
In 2005, 135701 carotid revascularisations were performed in the USA of which 122986 (92%)
were in asymptomatic patients. If every patient with an asymptomatic 60 – 90% stenosis were to
have carotid intervention, this would prevent fewer than 5% of all strokes (Naylor EJVES 2010). In
the ANZSVS audit, 40% of carotid interventions are for asymptomatic disease.
In a presentation at the SVS 2008, Kakkos reported that silent embolic infarcts identified on a CT
scan indicates a high risk for ipsilateral neurological events and so this may be an indication for
intervention in the asymptomatic patients. Diffusion weighted MRI might also be useful.
Cochrane review 2005 – asymptomatic males gained benefit from CEA but females did not. This
may be due to the slightly higher operative risk in females (4.0% vs. 2.4% in ACST and 3.6% vs.
1.7% in ACAS).
An improvement in medical management of patients with asymptomatic disease might have equally
impressive results in stroke reduction when compared to CEA. The 5 year risk of any stroke in
ACAS (1995) was 17.5% and in ACST (2004) it was 11.8%, a 33% risk reduction. In later ACST
results, the risk may be even lower at 7.2%. In a 2013 systematic review, Raman reported a 1.68%
annual risk of stroke in asymptomatic carotid patients treated medically (Annals of Internal
Medicine 2013).
To put the role of surgery in asymptomatic patients into perspective, consider the number needed to
treat by CEA to prevent one stroke in two years:
Symptomatic patients aged less than 75 years with more than 70% stenosis
6
Symptomatic patients aged 75 years or more with more than 70% stenosis
3
Symptomatic patients with 50 – 69% stenosis
15
Asymptomatic patient
83
In the second manifestations of arterial disease study (SMART), (2007), the risk of stroke during
3.6 years of follow up was 3% in patients with asymptomatic stenosis of more than 50% vs. 2% for
those with no stenosis. As with other studies there was no difference in stroke risk according to
degree of stenosis. Patients were three times more likely to have an MI and 4.5 times more likely to
have a vascular death than they were to have a stroke.
When looking for MES on TCD of asymptomatic patients, (Spence Stroke 2005), the 10% who
have MES have a one year stroke risk of 15.6%. Those with no MES have an annual stroke risk of
1%. However, in a follow up study, the number of patients having MES fell dramatically, possibly
due to more intensive medical management.
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Current data on asymptomatic 50 – 99% stenosis who receive best medical therapy suggests that the
annual stroke risk is less than 1% and may be as low as 0.34% (Marquardt Stroke 2010).
Revascularisation of asymptomatic carotid stenosis is not appropriate in patients on dialysis as the
combined stroke and death rate at 30 days is 10.2% and 33.5% at one year (Sidaoui SVS San
Francisco 2013).
The most recent audit data from Australia and new Zealand shows that 40.8% of CAS and 28.8% of
CEA are for asymptomatic disease. Stroke or death occurred in 0.6% of CAS and 1.7% of CEA.
Risk of stroke and death was increased with contralateral occlusion. Females had greater risk of
death stroke or MI.
In asymptomatic patients, progression of stenosis increases the risk of stroke. This may provide
some rational for surveying those with asymptomatic moderate stenosis.
Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification study
(ACSRS).
In this observational study of patients with asymptomatic carotid artery disease, the following were
found to be risk factors for stroke: severity of stenosis, age, systolic blood pressure, increased serum
creatinine, smoking history of more than 10 pack years, history of contralateral TIA or stroke, low
grey scale median, increased plaque area, plaque types 1, 2 and 3 and presence of discrete white
areas without acoustic shadowing.
Near total occlusion.
Although several terms, that is, ‘‘pseudoocclusion’’, ‘‘incomplete occlusion’’, ‘‘near occlusion’’,
‘‘subtotal occlusion’’, ‘‘string sign’’, ‘‘slim sign’’, ‘‘small distal ICA’’, or ‘‘poststenotic
narrowing’’, have been applied to describe this entity, Fox suggested 4 angiographic criteria to
define near-total ICA occlusion:
1. reduction in ICA diameter compared with the ipsilateral external carotid artery (ECA),
2. obviously reduced diameter of the ICA compared with the opposite ICA,
3. intracranial collaterals seen as cross-filling of contralateral vessels or ipsilateral contrast
dilution,
4. delayed cranial arrival of ICA contrast compared with that of the ECA.
Although it can be argued that reduction in blood
flow across the stenosis may reduce the risk of brain
embolization, the natural history of near-total ICA
occlusion has not been well defined. The results of our meta-analysis evidenced that
BMT was presented with almost 3-fold higher stroke
IR per 100 p-ys compared with CEA and CAS
Studies (Annals of vascular surgery 2015)
Cost effectiveness of carotid endarterectomy.
CEA costs £3000. Stroke costs £45000.
The number of carotid revascularisation procedures in the USA has decreased by 30% in the last 10
years (Wallaert SVS San Francisco 2013).
Screening for carotid artery disease.
In December 2007 the US Preventative Services Task Force (USPSTF) recommended that
asymptomatic carotid artery disease should not be screened for in the general adult population.
Summary of recommendations of the Society of Vascular Surgery (JVS 2008).
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1. In symptomatic patients with stenosis of less than 50% and asymptomatic patients with a
stenosis of less than 60% medical therapy was recommended.
2. Symptomatic patients with a 50% or more stenosis are recommended to have carotid
endarterectomy plus best medical management.
3. In patients with carotid stenosis more than 50% who are high risk for CEA, carotid
angioplasty and stenting is an alternative. High risk includes recurrent stenosis, neck
radiotherapy, previous neck surgery, common carotid stenosis below the clavicle,
contralateral vocal cord paralysis, presence of a tracheostomy, dialysis dependant renal
failure, low left ventricular ejection fraction, oxygen or steroid dependant lung disease.
CEA and coronary artery bypass grafting (CABG).
The overall risk of stroke following CABG is 2%. The risk is less than 2% when there is no
significant carotid artery disease, 3% in asymptomatic patients with unilateral significant stenosis, 5
- 8% with significant bilateral carotid stenosis and 7 – 11% with carotid occlusion. The risk of
stroke also increases with age – less than 0.5% in those aged less than 50 years, 8 – 9% for those
over 80 years. 60% of the strokes occur more than 24 hours after surgery. The fatality of stroke
following CABG is 23%. 50% of patients who have a stroke following CABG will have normal
carotid arteries or stenosis less than 50%. 6% of CABG patients have an 80 – 99% stenosis or
occlusion, the remainder have no significant carotid disease. A one year community based
prospective audit of CEA+CABG in USA showed a 17.4% risk of death/stroke at 30 days. In a
meta-analysis, operative mortality for CEA+CABG was 4.6%, CABG followed by CEA had
highest stroke rate (ipsilateral 5.8%, any stroke 6.3%). The risk of any operative stroke was lowest
with CEA followed by CABG (2.7%) but this had the highest MI rate. In summary, there was no
good evidence to support one line of management over another (Naylor EJVES 2003). Prophylactic
CEA would prevent less than 40% of post CABG stroke (Naylor EJVES 2002). The
recommendation was therefore to do the most symptomatic disease first and reserve combined
procedures for both systems being symptomatic. Aortic arch embolism may be a more important
cause of stroke following CABG.
In a report of LA CEA prior to CABG, (Birchley Annals R Coll Surg Engl 2010), there was a 1%
major stroke rate, 2% MI rate and 2% death (LVF and respiratory failure) rate following CEA.
Following CABG, the stroke rate was 2% (all affecting the contralateral hemisphere to the CEA)
and there were 5% deaths.
An updated meta-analysis (Naylor EJVES 2011), in patients with more than 50% carotid stenosis
(including carotid occlusion) who did not undergo prophylactic CEA or CAS, within 30 days, the
risk of stroke was 7.4% (0 – 27%), risk of death was 7.4% (0 – 15.8%) and the risk of death and
stroke was 8.3% (0 – 21.4%).
In asymptomatic patients with carotid stenosis of 50 – 99% who undergo CABG, the 30 day risk of
stroke was 3.8%, mortality was 3.8% and combined stroke and death 3.8%. In patients with a
stenosis of 70 – 99%, the numbers were 2%, 4.8% and 4.8%. The summary was that patients with
asymptomatic carotid disease (excluding unilateral or bilateral carotid occlusion) who have CABG
without CEA or CAS had a lower risk of stroke and death than all patients with carotid artery
disease. However, in patients with bilateral, severe asymptomatic carotid stenosis, there was an
increased risk of stroke if they have CABG but no carotid intervention. This therefore might be the
only group where intervention (CEA or CAS) might be useful prior to or at the same time as
CABG.
Cresendo TIA’s.
Dextran IV on admission to time of urgent surgery reduces the number of cerebral emboli.
Alternatively can use glycoprotein IIb/IIIa receptor antagonist (Tirofibran, 400ng/kg for 30 min
followed by 100ng/kg IV).
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My indications for carotid intervention.
Symptomatic patients with 50% or more stenosis, women if they are done within 2 weeks of
symptoms.
Asymptomatic patients aged less than 70 years with 70% or more stenosis, women only if they have
a contralateral occlusion.
I have opinions of my own, strong opinions, but I don’t always agree with them (George Bush).
Carotid endarterectomy – how to do it.
Pre operatively, patients should undergo a repeat of their duplex scan. This allows the sonographer
to mark the carotid bifurcation and so can be a warning if there is a high bifurcation. It also
identifies those who have occluded their ICA pre operatively and so do not require an operation.
Finally it ensures that there is the correct indication for intervention (Devalia EJVES 2004 and
Subramaniam EJVES 2006). A pre operative duplex scan will result in the cancellation of about 5%
of patients.
Some surgeons prefer not to operate on patients on both aspirin and clopidogrel due to fear of
bleeding. However, there is some evidence of possible benefit from being on both aspirin and
clopidogrel with a 10 fold reduction in number of patients with more than 20 embolic on TCD
postoperatively (Payne, Circulation 2004).
A short incision (5cm) for CEA has been shown to be feasible and safe with fewer nerve
complications (Bastounis EJVES 2007). A meta-analysis of the retrojugular approach versus the
more traditional antejugular approach (the one I use) for CEA concluded that there was no
conclusive evidence to favour one approach over another although cranial nerve injury was higher
for the retrojugular approach (Antoniou Ann R Coll Surg Engl 2014). It is reported to be useful in
redo surgery and when there is a high bifurcation.
A technically precise repair is the most important determinant of successful CEA. Inadvertent
technical error complicates up to 60% of all perioperative strokes. Use no touch technique,
dissecting the patient off the carotid arteries.
Reversal of heparin with protamine was shown to increases perioperative stroke but more recent
data from the GALA study and other publications have shown there was no increase (Mazzalai
World Journal of Surgery 2014)). In a metaanalysis (Newhall JAMA surgery 2016) concluded that
the use of protamine following CEA is associated with a reduction in bleeding complications,
without increasing major thrombotic outcomes, including stroke, myocardial infarction, or death.
Use of protamine was associated with a significant decrease in major bleeding complications
requiring reoperation (RR, 0.57; 95% CI, 0.39-0.84; I2 = 32%; 10 studies).
In a randomised study, dalteparin 2500 IU, when compared to 5000 IU unfractionated heparin,
reduced the number of operative emboli as detected on transcranial Doppler (McMahon GS EJVES
2009). There is no evidence that routine sinus nerve blockade is beneficial and in a meta-analysis,
routine carotid sinus blockade was shown to increase the risk of hypotension (31.8% vs. 23%) and
arrhythmia (24.1% vs. 15.6%) (Tang EJVES 2007). Sinus nerve division should be avoided. Use
proximal and distal tacking sutures to secure intimal flaps. Initial reperfusion up the external
carotid. Small study showed no difference in outcomes between those randomised to wound drain
vs. no drain (EJVES 2005).
Dextran 40 at incrimental doses of 20 – 40ml/hr to reduce postoperative emboli. Role of Dextran
being assessed in a randomised study.
Quality control methods:
 TCD – for shunt function and emboli during dissection and post operatively.
 Angioscopy – abnormalities requiring revision found in 12%.
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 Completion angiography
 Intraoperative Duplex scan
My opinion is that completion angiography and duplex scan, which require flowing blood, are a
waste of time as you will have missed the opportunity to correct an abnormaility. For this reason I
use completion angioscopy using flexible cystoscope, hystereoscope or ureteroscope.
Intraplaque haemorrhage as detected by MRI can predict intraoperative embolisation (JVS 2007).
Figure 3. Beware of potentially unusual anatomy. In this case of a right CEA, the external carotid is
coming off laterally. The image also shows a Pruit shunt in place.
Pre-operative antiplatelet therapy.
Subgroup analysis in NASCET showed that CEA patients receiving low dose aspirin (<325mg/day)
incurred higher operative risk (6.9% vs. 1.8%) compared to those who received a higher dose. The
ACES study however showed the converse to be true. Low dose aspirin remains the first line agent
in CEA patients and should not be stopped prior to surgery. Clopidogel should be stopped 7 days
before CEA although not all surgeons agree with this. Post operative carotid thrombosis may be
prevented by 75mg clopidogel on the night before surgery (Payne D JVS 2003).
Pre operative statin treatment.
Leads to lower incidence of in hospital adverse events (Stroke 2005).
Patching.
Cochrane review (2004 and 2009) of patch angioplasty vs. primary closure – In 2004, the review
concluded that routine patching was safer than routine primary closure with an 88% reduction in
early thrombosis, 66% reduction in early stroke and reduced late restenosis, stroke and death rate.
Patching reduced 30 day ipsilateral strokes (1.6% vs. 4.5%) and restenosis (4.8% vs. 18.6%). The
2009 conclusion was that limited evidence suggests that patching may reduce the risk of
perioperative arterial occlusion and restenosis (. It reduces the risk of ipsilateral stroke.
Some use patches selectively, when the ICA diameter is less than 5mm, usually in women. The
choice of patch has been subjected to randomised studies, with no definitive answer.
Table 6. Comparison of CEA patch materials.
Patch
Advantages
Vein patch – GSV, arm
Autologous, enhanced
vein, facial vein,
endotheliailisation,
external or internal
resistance to infection,
jugular (useful for LA
easy to handle
operations)
Dacron or PTFE
Readily available
Bovin pericardium
Easy to handle
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Disadvantages
Risk of early rupture, (especially when
harvested from ankle or arm), groin
wound complications, late aneurysmal
change. Patch rupture carries a high
mortality.
Infection
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(Vascu-Guard)
PTFE vs. Dacron - Randomised trial of Acuseal (PTFE (WL Gore) vs. Finesse (collagen
impregnated Dacron (Boston Scientific)) (AbuRahma JVS 2007). Patches were sutured with 6/0
Prolene. Thrombin soaked oxidized cellulose was applied to bleeding sites. 100 patients in each
group of whom 35% were on clopidogrel pre operatively and 45% were asymptomatic. The
operative time for the two groups was the same (95 min) but haemostasis time was less with Finesse
(5.2min vs. 3.7 min, p = 0.01). There were no neck haematomas that required surgery. Combined
perioperative neurological events (TIA, stroke), more than 50% restenosis or carotid occlusion was
2% with PTFE and 8% with Dacron, p = 0.1. TIA and stroke in this study was 3%, 2% for stroke
which was the same in both groups. There was a 2% incidence of asymptomatic carotid thrombosis
on the 30 day scan, both with Dacron patch.
Prosthetic patch infection. A systematic review (Knight BC EJVES 2009) found the incidence of
Dacron patch infection to be 0.25 – 0.5%. Early infection is usually preceded by a wound
haematoma or infection. Other risk factors include poor general or dental hygiene,
immunosupression including steroids, smoking and diabetes. There may be wrinkling of the patch
as seen on duplex scan. May present as a false aneurysm. Usually due to staphylococcus or
streptococcus infection. Surgery for patch infection involves exposure of the CCA just above the
clavicle and vein bypass or venous patch. Do not use another synthetic patch as 50% of these will
become reinfected. If the ICA is occluded, the patch is removed and the CCA ligated. 30 day stroke
and death rate 9.5%, re infection 8%, cranial nerve injury 8%. An endovascular approach has been
described where an endovascular stent graft is placed in the carotid artery. The wound is then
debrided and the patch removed. A VAC dressing is applied and long term antibiotics administered.
High disease/bifurcation.
Definition – carotid bifurcation above C2 or the upper limit of the stenosis lies above a line drawn
between the tip of the mastoid process and the angle of the mandible. Occurs in less than 5% of
CEA’s. At operation it can be defined as being high if it extends above the level of the digastric
muscle. May be helped by nasotrachael intubation and mandibular subluxation. The hypoglossal
nerve should be mobilised by dividing its descending branch and the occipital artery and vein that
tether it. Vessels to sternomastoid may also need division. Small vessels overlying the vertical
portion of the nerve must be ligated to avoid bleeding. When the posterior belly of digastric is
divided care must be taken to identify the glossopharyngeal nerve, which passes superficial to the
ICA and then deep to ECA. A little more exposure can be obtained by fracture of the styloid
process. Division of the styloglossus, stylopharyngeus and stylohyoid may be required. Division of
origin of sternocleidomastoid may sometimes help.
Nerve injuries associated with CEA.
There is a higher risk of nerve injury with neck haematoma, re-exploration for bleeding, shunting,
patch closure, trainee surgeon, high bifurcation and redo surgery.
Transverse cervical nerve - injury in 100% in the first few days, 70% at 3 months, but most improve
over time.
Greater auricular nerve - at risk at the top of the wound causing numbness of lower pinna and
mastoid area (42% at one week).
Vagus nerve (X nerve) – usually lies posterior to the CCA but can be anterior, lateral or medial to
the jugular vein. If not identified it can be injured by a vascular clamp. The recurrent laryngeal
nerve loops around the subclavian artery on the right and the ligamentum arteriosum on the left to
lie in the tracheo-oesophageal groove. Injury occurs in 6 - 8% of CEA and causes paralysis of the
ipsilateral vocal cord causing hoarseness and an ineffective cough. Bilateral injuries may be life
threatening. Thus bilateral CEA should be staged and with vocal cord inspection between cases. A
non recurrent laryngeal nerve passes behind the carotid bifurcation and is at risk of injury. The
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superior laryngeal nerve is also a branch of the vagus. It lies posterior to both the internal and
external carotid, close to the superior thyroid artery and supplies the cricothyroid muscle, inferior
pharyngeal constrictor and laryngeal mucosa. Injury leads to voice fatigue, high pitch phonation
difficulty and an unpleasant posterior pharyngeal sensation. Minor swallowing problems can occur.
Injury is minimised by careful identification and non circumferential dissection.
Hypoglossal nerve (XII nerve) - exits the skull base at the hypoglossal canal and passes lateral to
the ICA. 3 – 5cm above the bifurcation it crosses the bifurcation to enter the base of the tongue.
Invariably it is tethered by its descending branch which joins the cervical nerves to form the ansa
cervicalis, the motor supply to omohyoid, transection of which has little impact. It is also tethered
by the occipital artery and sternomastoid artery and vein, division of which may aid hypoglossal
nerve mobilisation. The hypoglossal nerve is the motor supply to intrinsic and extrinsic muscles of
the tongue (except palatoglossus), division of which causes ipsilateral tongue paralysis and wasting,
the tongue protruding to the affected side. Bilateral injuries can cause life threatening airway
obstruction. Injury is usually due to retraction and occurs in 5 – 17% of CEA, 80% of which are
transient. It is at risk of injury when ligating the facial vein.
Glossopharyngeal nerve (IX nerve) – sensory fibres to the pharynx and the posterior ⅓ of the
tongue, motor supply to stylopharyngeus, the middle pharyngeal constrictor, the soft palate and
secretory fibres to the parotid gland. It also gives a branch to the carotid body. It exits the skull
through the jugular foramen between the internal carotid and jugular vein. It passes in front of ICA
and then behind the ECA. Injury causes difficulty in swallowing solid food and nasopharyngeal
reflux of fluids. Most injuries are transient. NG feeding may be required.
Accessory nerve (XI nerve) – Exits the skull through the jugular foramen and passes beneath the
posterior belly of digastric to reach the deep surface of sternocleidomastoid which it supplies. It
passes through sternocleiodmastoid to enter the posterior triangle of neck. It lies anterior to the
distal ICA.
Facial nerve (VII nerve) – marginal mandibular branch passes parallel to the ramus of the mandible.
Injury causes drooping of the corner of the mouth. Injury is avoided by curving the superior extent
of the incision posteriorly.
General Anaesthetic vs. Local Anaesthetic debate.
The potential advantages of LA CEA include accurate assessment of neurological function (awake
testing) following carotid clamping and clear identification of those who require a shunt. The onset
of the neurological deficit can occur up to 12min following carotid clamping. In some reports, those
that use LA have a reduced operative times, possibly due to less intraoperative assessment and
patching, which may compromise results.
GA allows precise BP and heart rate control and avoids hypoxia. A protective effect against
cerebral ischaemia is suggested by the ability of barbiturates to reduce oxygen metabolism and thus
oxygen demand by reducing electrical activity. Etomodate and propofol provide cerebral protection
by similar mechanisms but also by redistribution of cerebral blood flow but without the
cardiovascular side effects of barbiturates. However, both can cause seizures and myoclonus. GA is
most commonly achieved with volatile anaesthetics which reduce neuronal activity and cerebral
oxygen requirements. Other actions include suppression of sympathetic activity.
Moderate hypertension can improve outcome and stump pressure in animals. Pharmacological
hypertension can also improve the neurological deterioration seen in some patients operated on
under LA. This however could have detrimental effects on the heart. Haematomas seem to be less
common in GA group.
In LA operations there is a reflex hypertension on carotid clamping which may protect cerebral
oxygenation. This is not dependant on the carotid body. LA operations are also associated with
higher catecholamine levels (in patients and the surgeon). LA patients are more likely to have
perioperative hypertension and GA patients more likely to have hypotension. Contraindications to
LA – confused patient, patient refusal, contralateral phrenic nerve paralysis, communication
difficulties. Complications of cervical plexus block – injection into external jugular vein, Horner’s
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syndrome, vertebral artery injection (can result in seizures and LOC), subarachnoid injection
resulting in spinal block and apnoea, embolisation from carotid artery, transient phrenic, recurrent
laryngeal and glossopharyngeal paralysis, toxic dose of LA. Conversion rate to GA 5 - 17% (Ritter
ESVS Amsterdam 2010). Two examples of complications arising from LA are well described by
Coress (2009, Ref 72 and 73).
2004 Cochran review showed no significant difference in outcome between GA and LA. However a
systematic review showed that compared to GA, LA results in:
reduction of stroke
2.0 vs. 4.8%
reduced death/any stroke
2.4 vs. 5.8
reduced myocardial infarction
1.1 vs. 3.3
reduced pulmonary complications 0.4 vs. 2.1
reduced requirement of shunt
13.3 vs. 50%
The GALA (Lancet 2008) study aimed for 5000 symptomatic or asymptomatic patients and
achieved 3526 in 95 centres in 24 countries. Patients were randomised to LA or GA. See table 5.
Table 5. Summary of GALA results.
N=
Asymptomatic
Crossed over
Occluded before surgery
Stroke or death
Cranial nerve injury
With a contralateral occlusion, risk of stroke
Patched
Shunt
Stroke
Death
MI
Hypertension pharmacologically induced
GA
1753
38%
92
8
4.6%
11%
10%
40%
4.0%
1.5%
0.2%
43%
LA
1773
39%
75
8
4.2%
11%
5%
30%
14%
3.7%
1.1%
0.5%
17%
More cardiac complications with LA was a suprise. No difference in length of hospital stay, use of
ICU/HDU or quality of life. Overall risk of stroke or death in symptomatic patients was 5.1%
compared to 3.4% in asymptomatic patients. Survival analysis to one year gave an advantage to the
GA group.
In a small study, LA was shown to cause temporary ipsilateral vocal cord paralysis in 50%. They
advocated pre-operative vocal cord function tests to avoid bilateral paralysis. In patients with
contralateral vocal cord paralysis, surgery under GA was recommended (Thermann JVS 2007).
Monitoring during CEA and shunts.
Risks of shunts – intimal damage resulting in thrombosis, distal ICA spasm, dissection (Tamaki Int
J Vasc Med 2010) or late stenosis, air emboli, compromised surgical exposure, higher risk of cranial
nerve injury.
Cochrane review suggests a non significant trend in benefit for routine shunt with fewer strokes.
Shunt intimidation theory (SHIT) as suggested by P. Bell.
Haemodynanic failure is responsible for less than 20% of intraoperative strokes, the rest are due to
thromboembolism.
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Pre-operative angiography can help to predict those who will require a shunt. With cross filling
from the contra-lateral carotid artery a shunt is rarely required. With cross flow away from the
operated side there is an increased risk of shunt use (Aleksic EJVES 2004). But overall,
angiography is poor at predicting requirement for shunt.
Pre operative MRI looking for leukaraiosis or white matter hyperintense lesions has been shown to
be useful in predicting those who will require an intra-operative shunt. It is an indicator of cerebral
haemodynamic compromise (Arshad ASGBI Abstracts 2007 Nottingham).
Table 6. Summary of intra-operative assessment tools for shunt requirements.
CRITERIA FOR
SHUNT
FALSE
POSITIVE
FALSE
NEGATIVE
COMMENTS
Awake testing under
LA
Hesitancy in
response, LOC.
Squeaky toy in
contralateral hand
and counting used
for assessment
Gold standard
Gold standard
Stump pressure
<50mmHg
20 – 40%
0 – 23%
Requires LA, good communication with
patient who is able to communicate and move
the limb with squeaky toy. Contralateral
phrenic nerve palsy is a contraindication to
LA. Neurological deterioration can occur as
late as 45min after clamping. Conversion to
GA in 1 - 5%. Shunts required in 5 – 20%
(Ritter EJVES 2011)
Cheap, universally available. Not continuous
High shunt rate – 50%
Stump pressure index
SP x 100 / systemic
pressure
Transcranial Doppler
<33
40%
0
MCAV fall of 50 –
70% or MCA flow
of less than 15cm/s
4 – 45%
17%
Cerebral blood flow
(133Xe clearance)
<18ml/100g/min
EEG
>50% reduction in
alpha or beta waves.
Appearance of delta
waves also used as
indication for shunt.
Prolongation of
conduction time
>1ms and reduction
in amplitude of 50%
or more
5 – 13%
5 – 25%
Somatosensory
evoked potentials
(SSEP)
Near infrared
spectroscopy –
cerebral oximetry
Jugular venous
oximetry
Cerebral O2 fall of 5
- 20%
<50%
No temporal acoutic window in 5 – 10%
Technician required. Can detect intraoperative
and postoperative emboli
Shunt required in 20%
Limited availability, Radiation, Technician
required
Shunt required in 50%
Expert interpretation, Anaesthetic agent and
diathermy interference. Influenced by previous
CVA. Superficial cortex only
Shunt required in 15 – 30%
Expert interpretation required.
Influenced by anaesthetic agents and
diathermy. Influenced by previous CVA
Shunts required in 8.7%.
50% of patients who suffer a stroke have
normal SSEP (SVS San Diego 2008)
Contamination of signal by scalp and skull
blood, but simple, non invasive, continuous,
real time.
Catheter position difficult to maintain
Some develop a deficit despite normal monitoring.
If you shunt selectively, the only way to reliably identify patients at risk of haemodynamic
intraoperative stroke is to do CEA under LA.
In a randomised study of routine shunting or selective shunting (based on stump pressure), there
was no difference in outcome.
Given the above difficulties in patient selection for shunt use, this author always uses a shunt (Pruit
Inahara).
In a review of 3153 patients having CEA (Bennett JVS 2014), 2023 had no shunt, concluded that
there was no clinical benefit for shunting.
Post operative carotid thrombosis (POCT).
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Stroke due to POCT may be preceded by increasing rates of embolisation as detected on TCD
monitoring. 3 – 5% of patients develop clinically relevant post operative embolisation of which
50% of the high rate embolisers will suffer a stroke. In some centres 25 or more emboli in a 10min
period results in IV Dextran 40 therapy (20ml bolous followed by incremental infusion staring at
20ml/h to a maximum of 50ml/h). Rheomacrodex (Meda AS) is an alternative.
Clopidogrel also reduces the rate of post operative embolisation. In Leicester, they now give 75mg
Clopidogrel the night before surgery, in addition to continuation of aspirin.
Quality control.
Options:
On table angiogram.
On table duplex scan
Angioscopy – can use flexible hysteroscope or utereroscope.
In a report of over 1000 patients having completion angiography (Ricco EJVES 2011), 6.1% of
patients had defects identified that required revision. Most of these were ECA flaps (which could
probably have been ignored, except for those where thrombus was seen protruding into the lumen)
but other defects included ICA filling defects with thrombus on the patch, ICA flap, incomplete
endarterectomy and CCA flap. To this author, this group were lucky as to do an angiogram requires
flowing blood. Surly it is better to identify these defects before blood flow is restored. So this
author uses completion angioscopy.
The study of Ricco also reported good results in terms of carotid occlusion (0.3%), wound
haematoma (0.6%), MI (0.5%), facial nerve injury (0.3%), hypoglossal nerve injury (0.3%) and
recurrent laryngeal nerve injury (0.9%).
In a CT follow up of patients who had CEA (van der Kolk EJVES 2011), 89.2% of patients had
residual defects in the CCA, ICA or ECA, intimal steps and residual stenosis being most common.
Hyperperfusion syndrome (HS) and intracerebral haemorrhage (ICH).
The incidence of intra-cerebral haemorrhage following CEA is 0.5%. The median duration from
surgery to haemorrhage is 4 days and mortality is 67%. Risk factors for post CEA ICH include
recent cerebral infarction, hypertension, high grade carotid stenosis, contra-lateral occlusion or
severe stenosis, impaired cerebrovascular reserve, post reperfusion hyperaemia and anticoagulant
therapy.
Hyperperfusion syndrome – headache (ipsilateral), hypertension, seizures, focal neurological
deficit. It is caused by brain oedema leading to ICH and possible death. It is thought to be due to
defective cerebral autoregulation of blood flow. It usually occurs several days after surgery. TCD
shows very high MCA blood flows. Risk factors for HS include incomplete circle of Willis, preoperative hypertension, previous cerebral infarction, postoperative hypertension and bilateral ICA
stenosis. Hypertension is treated aggressively with intravenous β blocker e.g. metoprolol or
labetalol (an α and β blocker) and not a vasodilator. Hypocarbic ventilation may also help. Consider
sumatriptan (used for migraine) as this causes cerebral vasoconstriction. If patients have a post
operative severe headache, start prophylactic phenetoin. Can also occur following carotid artery
stenting.
Usually occurs 2 – 3 days after CEA. Risk factors include hypertension. Those who get
hyperperpusion syndrome are more likely to get it is they require contralateral surgery.
Cardiac mortality.
Severe, correctable coronary disease is present in 60% of those with carotid atherosclerosis
resulting in an annual cardiac related mortality of 6.5% in patients with >75% carotid stenosis.
After stroke, MI and cardiac dysrrhthmias are the principal cause of death following CEA. This risk
might be reduced by LA procedure.
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Intra operative and post operative stroke.
Table . Causes of stroke following carotid endarterectomy
Intraoperative (patient recovers from
Postoperative (patient suffers stroke some
anaesthetic with new neurological
time after normal recovery from
deficit) – approx. 2% of all CEA’s
anaesthetic) – approx. 1% of all CEA’s
Embolism
Spontaneous embolism (unstable
Particulate emboli from endarterectomy
plaque)
site
Particulate emboli during carotid
Particulate emboli following external
dissection, particularly when thrombus
carotid artery thrombosis
seen on pre op duplex scan
Particulate emboli dislodged by shunt
Major emboli (air or thrombus) due to
shunt malfunction
Particulate emboli from endarterectomy
zone
Thrombosis Peri shunt thrombosis
Secondary to technical error e.g.
dissection flap 1%
On table carotid thrombosis 1%
Secondary to hypotension
Secondary to siphon disease
Secondary to coagulation disorder
Others
Haemodynanic failure (shunt not used
Hypertensive encephalopathy
or malfunction) – 15%
Primary intracerebral haemorrhage 1%
(associated with pre op hypertension,
hyperperfusion syndrome and intra cranial
aneurysms)
Haemorrhagic transformation of infarct
Hyperperfusion syndrome
Watershed infarct with due to hypotension
Intraoperative and post operative embolisation can be detected using transcranial Doppler. Most
emboli are detected at shunt opening and at restoration of flow through the endarterectomised
segment (Gaunt BJS 1994). Most of this is air emboli which is thought to have no adverse clinical
outcome. Emboli detected during carotid dissection and in recovery are mainly particulate and are
associated with important clinical effects. Persistent post operative emboli are thought to be an early
sign of carotid thrombosis.
If the patient is slow to recover from anaesthesia and has hemiplegia, homonymous hemianopia or
higher cortical dysfunction (aphasia, visuospatial neglect), an immediate carotid exploration is
necessary to exclude carotid thrombosis and if necessary deal with the problem. Intravenous
dexamethazone (8mg) should be given to reduce cerebral oedema. Care should be taken during the
dissection to prevent further embolisation of new thrombus. If back bleeding is poor a small Fogarty
catheter can be passed distally. On table thrombolysis is another option. The patient should be
electively ventilated overnight to minimize laryngeal oedema.
For post operative strokes within 6 – 12 hours, if patency of the operation site cannot be confirmed
urgently, the carotid artery should be explored. If imaging shows the endarterectomy site to be
widely patent, re-exploration is probably not warranted.
The impact of contralateral carotid disease on the incidence of stroke following CEA is unclear.
Some publications show and increased risk, others do not. Patel (SVS San Francisco 2013) reported
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that there was no increase in ipsilateral stroke or death but there was an increase in all stokes and
death. He suggested that use of shunt in these cases may be indicated.
Restenosis
In ACAS, restenosis was noted in 7.6% at 18 months and from 18 – 60 months the rate was 1.9%.
There was a 4% incidence of occlusion. However, by life table analysis, the true rate of restenosis
has been calculated to be approximately 30% at 7 years. In the first month after surgery it is
common to find haemodynamic disturbances on ultrasound which were not present intraoperatively but later these disappear. This is probably related to post operative inflammation. Early
restenosis is due to intimal hyperplasia (smooth, white and rarely ulcerates), late restenosis is due to
progression of atherosclerosis. The risk of ipsilateral stroke with recurrent stenosis is about 5.5%
over 3 years. Overall stroke and death rate following redo CEA is 5% - thus little benefit from
surgery.
Risk factors for restenosis:
 residual defect at original operation – but see above
 female sex
 continued smoking
 hypercholesterolaemia
 diabetes
 hypertension
 young age at CEA
 non patch closure - 21% in primary closure and 7% in patch closure (ACAS data).
There is no association between restenosis and plasma homocysteine levels (Assadian EJVES
2007).
Because of the benign nature of restenosis, I can find little data to support routine post operative
duplex surveillance.
Operations for restenosis.
These are more difficult than the primary operation. They are associated with a high stroke rate
(4.3%), higher incidence of cranial nerve palsies (19.8%) and a higher restenosis rate (11 - 19.5%).
The surgical options are to perform a vein patch angioplasty or reversed vein bypass. Carotid artery
stenting may be a good option – see below.
Eversion CEA (ECEA).
This involves transection of the ICA at its origin, a quicker anastomosis and a reported reduced
restenosis rate. It is ideal for kinks and coils as it allows shortening of ICA more easily. A shunt can
still be used. Disease that extends a long way up the ICA is more difficult to deal with by the
eversion technique. Eversion endarterectomy is possible with some recurrent lesions but it is
contraindicated in others e.g. when original operation was by conventional arteriotomy and patch
closure. Circumfrential dissection of the ICA can be performed after the vessels have been clamped
and the ICA divided. The line of transection must be exactly within the bifurcation. The plaque is
grasped and the adventitia everted until the plaque feathers off. 0.2% asymptomatic early occlusion
and 0.7% restenosis rate in series from Albany, USA.
In a randomised study of standard vs. ECEA there were no differences in outcome apart from
shorter operation and non significant reduction in restenosis (Ballotta Ann Surg 2000). Provided a
standard arteriotomy is closed with a patch, there is no advantage to eversion CEA.
In a meta-analysis of ECEA vs. conventional carotid endarterectomy (Antonopoulos EJVES 2011)
ECEA was associated with significant reduction in peri operative stroke (OR = 0.46), peri operative
stroke and death (OR = 0.49), with no difference in restenosis, carotid occlusion, peri operative
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TIA, cranial nerve injury, MI or neck haematoma. ECEA was associated with a significant
reduction in late carotid occlusion.
CEA in the presence of a contra lateral carotid occlusion.
The early randomised studies suggested that there was a higher incidence of operative stroke when
CEA was performed in the setting of a contra lateral occlusion. More recent single centre studies
and registries have suggested that this is not true. A 2013 meta-analysis (Faggioli EJVES 2013)
suggested that contra lateral occlusion was a risk factor for stroke and death in both symptomatic
and asymptomatic patients following CEA. In patients who underwent CAS, contralateral occlusion
did not increase the risk of stroke of death. They proposed that the presence of a contra lateral
occlusion could be an indication for CAS rather than CEA.
Relationship between hospital volume and outcome following CEA (Holt EJVES 2007).
Mainly based on data from the USA, hospitals doing more than 79 CEA per year had a lower stroke
and death rate than those doing less. Lower volume surgeons achieved results similar to higher
volume surgeons when operating in higher volume hospitals.
Carotid angioplasty and stenting (CAS)
CAS has been descried as “conspiracy against surgery” (Bell 2004). CAS has also been described as
working best for patients who need it the least. In USA, 50% of CAS procedures are done by
cardiologists (Wallaert SVS San Francisco 2013). The first carotid angioplasty was performed by
Klaus Mathias in 1979. Initial indications for CAS were:
 hostile necks e.g. radiation therapy, tracheostomy
 High bifurcation
 recurrent stenosis
 high risk for anaesthetic
It is recommended that some form of pre procedure imaging of the aortic arch and circle of Willis
be performed. This is best achieved with MRA but CTA can be used.
The stents.
All nitinol stents foreshorten by less than 15%. The stainless steel Wallstent (Boston Scientific) can
foreshorten by up to 20%. Some carotid stents are more flexible than others. Flexible stents include
the Precise (Cordis), Zilver (Cook) nitinol stents and the Wallstent. These are useful with tortuous
anatomy.
It had been suggested that in symptomatic patients, late complication rates were highest for open
stent design e.g. Precise, Exponent (Medtronic), Acculink (Guidanet) compared to those with a
closed stent design e.g. Wallstent, X-act (Abbott). But there does not seem to be any great
difference in outcome when closed or open cell stent designs are compared (Jim JVS 2011).
NexStent (Boston Scientific) is FDA approved to treat patients at high risk for CEA. Wallstent is
available for investigation use only in the USA.
Precise Pro RX (Cordis) – a nitinol self expanding stent.
Protection devices.
The first protection device was the Theron concept of a distal balloon and then aspiration proximal
to the balloon prior to deflation.
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’s
ue
90
ystem
er and
Figure 4. Theron concept.
Pore size of current filters is 60 – 140 µ.
a.
b.
Figure 5a. Angioguard (Cordis) – polyurethane membrane with 100 µm pore size. B. Filtrewire
(Boston Scientific).
Figure 6. Embosheild
Proximal or distal occlusion balloons (Theron, Percusurge (Medtronic)).
6 – 10% of patients do not tolerate balloon occlusion.
Silkroad has been assessed in the Roadster trial. It is a reverse flow device where the proximal
common carotid is exposed and accessed in the lower neck. The proximal common carotid is
occluded and blood flowing backwards down the internal and external carotid is returned to the
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patient via common femoral vein assess. One of the advantages of this devise is that no
manipulation in the aortic arch is required.
Technique.
It is recommended that patients should be loaded with clopidogrel pre operatively (either 300mg the
night before the procedure or 75mg per day for at least one week prior to the procedure). This
should be continued for 3 – 12 months post procedure. There is, however, little evidence to support
this (De Rango ESVS Amsterdam 2010). In a review of a large data base, there was a non significant
reduction of peri-operative stroke and death in patients treated with clopidogrel (4.2% vs. 2.4%),
stroke (3.9% vs. 2.4%), and disabling stroke (1.2% vs. 1%).
The procedure should be performed with ECG monitoring due to the risk of bradycardia and with
invasive arterial monitoring. Most procedures are performed by percutaneous common femoral
artery access although right brachial or radial for the left ICA or left brachial for the right ICA can
be used. Right arm access is useful with a bovin origin to the left common carotid. A wire via the
common femoral vein and positioned in the right atrium can be placed should emergency pacing be
required.
Catheters used for access to the common carotid from the aortic arch include Vitek, JB1, JB2 or
Vertebral. Internal mammary catheter useful to getting into acute angled ICA.
A guidewire is positioned in the external carotid artery and a guidecatheter or sheath positioned in
the common carotid artery.
Most recommend routine pre dilatation of the stenosis with a 3 or 4mm balloon prior to passage of
the protection device. The stent is sized to the common carotid, which can be measured on pre
operative duplex, CTA or using the sheath as a sizer. Usually 6 – 9mm diameter self expanding
stent is used. The stent usually covers the origin of the external carotid, which invariably remains
patent.
If there are tandem lesions, usually at the origin of the common carotid, this should be dealt with
first by angioplasty and stenting before the ICA is stented.
The results seem to be worse with very calcified lesions. Using a cutting balloon in this situation
may be helpful.
Complications.
Bradycardia - Atropine (which can cause agitation) or glycopyrolate should be given routinely to
avoid this.
Hypotension - Aramine is used
Intracranial haemorrhage – More common than with CEA (0.15% vs. 0.016%), possibly due to dual
antiplatlet therapy. This complication has a 12.5% mortality. The incidence of intracranial
haemorrhage is increased with a very tight stenosis, hypertension, contralateral occlusion, increased
age, renal failure and females. Thus aim to keep the blood pressure less than 160mmHg. The risk is
also increased with the use of IIb IIIa inhibitors.
If cerebral emboli or clot complicate the procedure, a Renegade catheter and wire can be used to
access the intracranial vessels and administer thrombolysis. Reapro can be used for platelet plugs.
Topical or intra arterial GTN can be used for arterial spasm.
Export catheter (Medtronic) can be used for aspiration.
If there is vessel occlusion during the procedure, thrombolysis can be used (2mg of TPA). If there is
no vessel occlusion but there are new neurological symptoms, use Repro.
Diffusion weighted MRI (DWI) has shown that 23 – 57% of patients have new cerebral lesions
following CAS. These may have an effect on cognitive function. Using transcranial Doppler, most
embolic showers occur during passage of the filter device through the stenosis and during post stent
dilatation.
Rapp (JVS 2007) reported 48 patients undergoing 54 CAS in which 67% of patients had new
lesions on DWI at 48 hours, 97% of these being on the ipsilateral side. In this study, the clinical
incidence of TIA and stroke was less than 4%. So not all DWI abnormalities are clinically evident.
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It appears that the risk of stroke following CAS is higher in the first few days following the
procedure rather than at the time of the procedure.
If at the completion of the procedure, there is no or slow flow in the ICA, the ICA should be
aspirated though the sheath and the filter device removed.
There appears to be an increased risk of complications in elderly females, probably related to aortic
arch calcification. Type II aortic arches (see below) are also associated with increased age and
calcification (Bazan JVS 2007).
If there is spasm of the ICA, wait, the spasm may resolve.
As will be seen below elderly patients seem to have worse neurological results, possibly due to a
decreased cerebral reserve.
Indications for not doing CAS.
No access
Bad aortic arch anatomy – Type A (I) – branches from aortic arch arise from a horizontal plan,
Type B (II) – vessels arise off the horizontal plan, Type C (III) – almost vertical origin of vessels. A
Bovine arch is where the left common carotid artery arises from the right common carotid artery.
Heavily calcified carotid disease.
Figure 7. A long irregular ICA stenosis not suitable for angioplasty and stent. Long arrow shows
stump of proximal ICA, short arrows shows distal ICA (which also has a stenosis).
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Figure 8. Heavy carotid calcification – a contraindication to CAS
CAVATAS.
One of the first randomised studies. 504 patients from 24 centres randomised to CEA or carotid
angioplasty (CA). 96.5 % of patients were symptomatic. Almost half of strokes and deaths occurred
after randomisation but before treatment.
Table 6. Summary of CAVATAS results.
CA
Major stroke and death
6.3%
Cranial nerve injury
0%
Wound haematoma
1.2%
Restenosis after 3 years
19%
30 day risk of stroke and death
10%
CEA
5.9%
8.7%
6.7%
5%
9.8%
This study concluded that both treatments were equally effective at stroke prevention. But stents
were only used in 26% of angioplasty cases and protection devises were not used.
Carotid revascularization endarterectomy versus stenting trial (CREST) (NEJM 2010).
Initially started in symptomatic patients but recruitment was slow so ended up recruiting both
asymptomatic (n = 1326 (53%)) and symptomatic (n = 1176 (47%)) patients. CAS used the Abbott
Laboratories Rx Acculink stent and Rx Accunet filter device. Primary end point was a combination
of MI, stroke and death. Octogenerians had a 12.1% rate of periprocedural adverse events, an 8.1
fold increased risk compared with younger patients. Patients aged less than 70 years had better
results following CAS and patients aged more than 70 years had better outcomes following CEA.
More procedural stokes after CAS were classified as major and ipsilateral compared to CEA.
Table 7. CREST results.
N=
Primary end point to 4 years - %
Primary end point periprocedural
4 year ipsilateral stroke (excluding peri procedural)
Periprocedural major stroke
Periprocedural MI, %
Cranial nerve palsy
Ipsilateral stroke after preiprocedural period to 4 years
30 day risk of death, stroke or MI
30 day risk of stroke, %
Peri-operative stroke and death – asymptomatic patients
Peri-operative stroke and death – symptomatic patients
Peri-procedural death, n =
Peri-proceudrual stroke, n =
Major ipsilateral stroke, n =
Minor ipsilateral stroke, n =
4 year rate of stroke and death, %
Risk of any stroke or death in symptomatic patients between
randomisation and 30 days post treatment
01 June 2016
CAS
1262
7.2
5.2
2
0.9
1.1
CEA
1240
6.8
4.5
2.3
0.7
2.3
P
0.3
2.0
5.2
4.1
4.8
2.4
4.5
2.3
1.4%
3.2%
4
29
4
17
4.7
3.2
0.0001
0.85
0.38
0.01
9
52
11
37
6.4
6.0
0.51
0.38
0.85
0.52
0.03
0.18
0.01
0.09
0.009
0.03
34
35
The conclusion from this trial was that there was no difference in the estimated 4 year primary end
point between CAS and CEA. But, note that periprocedural death was twice as common with CAS
but due to the low numbers this difference was not statistically significant. Vascular surgeons
performed 65% of the CEA’s and 21% of the CAS procedures. In this subgroup, periprocedural
stroke and death rates were significantly higher after CAS than CEA for symptomatic (6.1% vs.
1.3%) but not for asymptomatic patients (2.6 vs. 1.1%). MI and cranial nerve injury were less
following CAS (1.3% vs. 2.6% and 0 vs. 5%).
Could the use of dual antiplatelet treatment in the CAS group account for the lower MI rate in this
group?
The estimated 10-year rate of ipsilateral stroke (excluding the perioperative period) was 6.9% after
stenting (i.e., 0.7% per year) and 5.6% (0.6% per year) after endarterectomy.
CREST 2.
This will be a randomised study of asymptomatic patients to CAS, CEA and best medical
management and will include cognitive function as one of the outcome measures.
SAPPHIRE (J. Yadav (Cleveland Clinic) NEJM 2004 and 2008).
Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy. A
randomised trial of the Cordis Precise stent plus the Angioguard distal protection devise vs. CEA in
patients at high risk for endarterectomy. There were 334 patients in 29 centres in the USA. Another
407 patients were entered into a stent register. Inclusion criteria: symptomatic more than 50%
stenosis, asymptomatic more than 80% stenosis plus one high risk feature e.g. age over 80 years,
contralateral carotid occlusion, clinically significant heart disease, restenosis, neck radiotherapy.
Table 7. Summary of SAPPHIRE results.
334 randomised patients
30 day major adverse events (death, stroke, MI)
One year major event rate
MI
30 day stroke rate
Carotid revascularisation due to restenosis at one year
At three years
Perioperative death and stroke
CAS
4.8%
12.%
2.5%
3.0%
4.3% in asymptomatic
0% in symptomatic
0.7%
3%
6.7%
CEA
9.8%
20.1%
8.1%
p
0.05
0.03
4.6%
7.1%
The higher rate of MI in the CEA arm shifted the balance in favour of CAS. More than 20% of
patients were being treated for restenosis. The increased risk of stroke and death in asymptomatic
patients when compared to symptomatic patients raised the question of whether asymptomatic
patients require any intervention apart from medical management. This trial was stopped early due
to slow recruitment. The 3 year results showed no advantage of CAS over CEA in terms of death or
stroke prevention.
SPACE.(Lancet 2006 and Lancet Neurology 2008)
Stent protected percutaneous angioplasty vs. carotid endarterectomy study (35 centres in Germany,
Austria and Switzerland). A randomised study of 1200 patients who had a TIA or stroke (modified
Rankin score of 3 or less) and a 70% or more stenosis. All patients underwent intervention within
30 days of randomisation.
Table 8. Summary of SPACE results.
Stroke, death or ipsilateral stroke at 2 years (primary end point)
01 June 2016
CAS
9.2%
CEA
8.5%
35
36
Death or ipsilateral stroke from randomisation to 39 days after intervention
Ipsilateral stroke within 30 days of intervention
6.8%
6.5%
6.3%
5.1%
They concluded that CAS was not justified for symptomatic stenosis. Only 27% of the CAS
patients had embolic protection. Primary end point occurred in 7% with protection and 7% without,
raising the question of the necessity for protection. The trial was stopped early due to a lack of
funding and no difference in results. A higher stroke rate was noted in octogenerians who had CAS.
Subset analysis showed that there was a significantly lower risk of stroke in those who has a closed
cell stent e.g. Wallstent, vs. those who had open cell stent design and that stenting was more
dangerous if performed within 2 weeks of onset of symptoms.
SPACE 2.
This is a trial in asymptomatic patients who will be randomised to CEA, CAS or BMT. It has been
abandoned due to poor recruitment.
CAPTURE(carotid acculink/accunet postapproval trial to uncover rare events).
Included 2500 patients of which 2300 were asymptomatic, in 137 hospitals. 55% of procedures
were performed by cardiologists. The overall risk of stroke, death and MI following CAS was 5.7%,
being lower in asymptomatic patients (4.9%) than symptomatic patients (14.2%). Octogenerians did
worse as did diabetics. The stroke risk was 4.8% of which 18% of strokes occurred on the
contralateral side. 78% of strokes occurred after the procedure, 38% after 24 hours. This raises the
question of whether LMWH should be used following CAS.
BEACH trial.
Wallstent and filter wire non randomised trial. 480 high risk symptomatic and asymptomatic
patients. Major stroke rate 1.7% at 30 days and 8.1% at 3 years. Ipsilateral stroke rate 3.1% at 30
days and 7.7% at 3 years. Stroke rate was 4.4%, improved in asymptomatic patients. Stroke and
death rate at 1 year was 8.9%.
EVA-3S.
Endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis. A
randomised trial performed in France. 527 patients following TIA’s, amurosis fujax or non
disabling stroke within 120 days, stenosis 60 – 99% in 30 centres. Early in the study there was a
change in protocol to stenting with cerebral protection due to high incidence of stroke in those
without protection. Procedures were performed within 2 weeks of randomisation.
The safety committee stopped the trial due to the increased risk of stoke in those undergoing CAS
without cerebral protection.
Table 8. Summary of EVA-3S.
N = 527
Conversions
30 day stroke or death
30 day disabling stroke or death
Any stroke or death within 6 months
Cranial nerve injury
Median hospital los
4 year risk of ipsilateral stroke
30 day incidence of non fatal stroke
CAS
13 – all due to femoral access issues
9.6%
3.4%
11.7%
1.1%
3 days
11.1%
8.8%
CEA
3.9%
1.5%
6.1%
7.7%
4 days
6.2%
2.7%
One additional stroke or death resulted when 17 patients underwent stenting rather than CEA. More
strokes occurred on the day of stenting than on the day of surgery. No difference in centre or
individual experience. The relative risk of stroke or death for CAS over CEA did not differ
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37
significantly before systemic use of protection – 2.0 vs. 3.4%. Only 19.5% of CEA patients were
shunted, only 50.2% were patched, 25.8% had cerebral monitoring. 30 day risk of stroke and death
without cerebral protection was 25% vs. 7.7% in those who had protection. Dual antiplatelet
therapy was recommended but not uniformly administered in CAS patients. The study was
critisized as many patients were recently symptomatic and this is thought to increase the risk of
neurological complications following CAS.
Acculink for revascularisation of carotids in high risk patients (ARCHeR) (Gray JVS 2006).
Prospective non randomised trial of high risk patients. 581 patients (24% symptomatic). ARCHeR 1
– no filter. ARCHeR 2 – filter (Accunet). ARCHeR 3 – rapid exchange for stent delivery and filter.
In symptomatic patients, 30 day stroke, death and combined stroke and death rates were 10.9%,
2.2%, 11.6%. In asymptomatic patients, 3.8%, 2.0% and 5.4%. 5% significant restenosis (70% or
more) at one year.
TACIT.
A randomised trial for asymptomatic patients comparing best medical management vs. CEA plus
BMT vs. CAS plus BMT. Yet to start.
CABERNET (Carotid artery revascularisation using Boston Scientific Filterwire and Endo Tex
NexStent).
Major stoke rate 1.3% at 30 days and 2.8% at 3 years. Ipsilateral stroke rate 2.9% at 30 days and
4.9% at 3 years. Major event rate at 1 year was 11.6%.
ICSS trial (Lancet 2010 and NEJM 2013).
An international randomised trial of CEA vs. CAS for recently symptomatic patients. 1710 patients
randomised in 50 centres in 15 countries. Stroke, death or peri-procedure occurred in 8.5%
following CAS and 5.1% following CEA (p = 0.004).
Table 9. Intention to treat results to 120 days from ICSS.
CAS n = 853
Any stroke
65 (7.7%)
Fatal stroke 9
Disabling stroke 17
Non disabling stroke 39
Haemorrhagic stroke 3
Ischaemic stroke 63
Uncertain stroke type 0
Ipsilateral stroke 58
Any MI
3
Fatal MI 3
Non stroke non MI death
7
Cranial nerve palsy
1
Haematoma
31
All cause death
19 (2.3%)
30 day risk of stroke or death
72 (8.5%)
CEA n = 857
34 (4.0%)
2
19
14
5
27
2
29
4
0
5
44
50
7 (0.8%)
39 (4.6%)
P=
0.001
0.017
0.001
In the per protocol analysis, 30 day risk of stroke or death was 7.4% following CAS and 3.4%
following CEA.
In an MRI sub study, serial MRI scans showed more new ischaemic brain lesions following CAS
than following CEA, despite the use of cerebral protection.
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38
The conclusion from ICSS was that CEA remained the treatment of choice for symptomatic
patients.
In the long term results, there was no difference in fatal or disabling strokes at 5 years between CAS
(6.4%) and CEA (6.5%) nor all cause mortality (17.4% vs. 17.2%). However, there were more any
strokes (15.2% vs. 9.4%) in the CAS group.
ACT 1 (Rosenfield New England Journal of Medicine March 2016).
A randomised trial in the US of standard risk asymptomatic patients using the Abbott Xact Rapid
Exchange Carotid Stent System and Emboshield. 3:1 stenting vs CEA. the 5-year rate of ipsilateral
stroke (excluding the perioperative period) was 2.2% after stenting (i.e., 0.4% per year) and 2.7%
after endarterectomy (0.5% per year).
Post stenting duplex criteria for significant restenosis, PSV 150cm/sec or more, IC:CC ratio of
2.16:1.
Lal has reported restenosis following CAS of 80% or more in 6.4% of patients after a mean follow
up of 19 months (Lal JVS 2007). There was a higher incidence of lesser stenosis. Predictive factors
for restenosis – diabetes, previous carotid intervention (CEA or CAS), type of stent used (Acculink
> Wallstent). The most common pattern of restenosis was intimal proliferation at the ends of the
stent (type 1). Intrastent stenosis (types II and III) were more common in patients initially treated
for primary atherosclerotic lesions. Carotid occlusion following CAS was rare, less than 0.5%.
CAS associated with lesser catecholamine response than CEA
Risk of stroke during CAS rises with age, probably due to increased aortic arch atherosclerosis.
Cochrane review 2005 – no significant difference in the major risks of treatment between CEA and
CAS. Minor complications favour CAS. There is insufficient evidence to support a widespread
change in practise. CAS should only be offered within a randomised trial.
As of the end of 2005, CAS was only funded in the USA for high risk patients.
Following publication of the SAPPHIRE results, in a 6 to 5 vote, the Centres for Medicare and
Medicaid Services approved Medicare reimbursement for carotid stenting in the USA. Six
cardiologists voted for approval. Those who voted against were two vascular surgeons, two
interventional radiologists and one neurologist.
Meta-analysis of CAS vs. CEA for symptomatic carotid stenosis (Lancet 2010 and EJVES 2011).
When the results of EVA-3S, SPACE and ICSS were combined, 1725 patients had CAS and 1708
had CEA. The risk of stroke or death in patients 70 years or less was the same with CEA and CAS,
but in older patients the risk with CAS doubled.
Table 10. Combined results of EVA-3S, SPACE and ICSS within 120 days of randomisation
(Intention to treat analysis).
CAS
CEA
P
Any stroke or death
8.9% 5.8% 0.0006
Any stroke
8.2% 4.9% 0.00001
Non disabling stroke
4.2% 2.1% 0.00004
Ipsilateral stroke
7.3% 4.4% 0.00003
In terms of stroke severity, the largest difference was seen in the occurrence of non disabling
strokes which were twice as frequent in the CAS group compared to the CEA group. There was no
01 June 2016
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39
difference in the incidence of MI between the two groups (0.2% (CAS) vs. 0.4% (CEA)). The
incidence of cranial nerve palsy in the CEA group was 6%.
Pre stenting of radiation stenosis.
Post stenting of radiation stenosis.
Figure 8. Carotid stenting for symptomatic radiation induced stenosis.
Age and risks of stroke with CEA and CAS.
In a combined analysis of EVA-3S, SPACE, ICSS and CREST (Howard Lancet 2016), the risk of
stroke with CAS increased from 3% in those aged less than 60 to 12% in those aged more than 80.
Whereas for CEA it was 3% for those aged less than 60 and 4% for those aged over 80. They
concluded that age over 70 significantly increases the risks of stroke with CAS when compared to
CEA but there was no difference in late strokes.
The same group has also reported that performing CAS within 7 days of index symptom was
associated with three fold excess risk of death or stroke compared to CEA.
Neuro-rescue during carotid angioplasty and stenting.
Mechanical removal of embolus – Merci retriever, a tapered wire of memory encoded nitinol with 5
helical loops of decreasing diameter (Concentric Medical), Catch retriever (Balt Extrusion),
Proboscis Rx catheter (Medical braiding AG). The Merci retriever is passed through a microcatheter
positioned beyond the embolus. 2 – 3 of the helical coils are deployed and the system slightly
withdrawn to contact the embolus. The microcatheter is then withdrawn enabling the remaining
coils of the retriever to be deployed. A balloon is used to occlude the proximal internal carotid
artery and 5 clockwise rotations of the retriever are made to ensnare the embolus. Continuous
aspiration is applied to the balloon catheter while the retriever and microcatheter are removed
simultaneously. The procedure can be repeated if required. The devise has most experience is acute
stroke unrelated to CAS. The Catch devise is a self expanding basket. A microcatheter is advanced
distal to the occlusion. The basket is passed up the catheter and deployed beyond the occlusion. The
whole system is withdrawn into a guiding catheter. These mechanical devised can be associated
with vessel spasm. Use of a proximal occlusion balloon and aspiration with the Catch devise may
reduce distal microemboli.
Aspiration of embolus/thrombus – requires an end hole catheter and 50ml syringe, smaller syringe
may be required with smaller catheters. Microcatheters which can be used in the intracranial portion
include Vasco +35 (Balt), Proboscis, quickcat (kensey nash), diver (invatec), export (Medtronic).
Fragmentation – using angioplasty balloon or guidewire e.g. flexible J tip hydrophilic wire 0.008 –
0.010) manipulation. With these techniques there is a high risk of distal embolisation.
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40
Thrombolysis – a microcatheter, passed through a diagnostic catheter, is placed in the proximal
third of the thrombus. 250 000units urokinase as a bolus is used or 5mg rTPA. Intra-arterial
abciximab 5mg (Reopro, Lilly Pharmaceutical) followed by 5mg intravenous dose has been shown
to be effective.
Thrombosis during CAS – treatment consists of abciximab or thrombus aspiration. Acute stent
thrombosis is rare but can be treated with intra arterial thrombolysis.
Scoring system to predict complications from carotid angioplasty and stent.
The Siena carotid artery stenting score (Setacci Stroke 2010) has been used to predict the risk of
CAS causing stroke. The following have been shown to increase the risk of stroke following CAS:
cardiac disease, recent neurological symptoms, diabetes, calcification or ulceration of the carotid
lesion, lesion length more than 15mm, the need for pre dilatation, type III arch, bovin arch, arch
calcification, procedure time mote than 30 mins, operator experience of less than 50 cases.
Intracranial disease.
Patients with intracranial atherosclerotic disease (ICAD) have a more significant risk of stroke than
those with extracranial disease. ICAD accounts for 5 – 10% of all strokes and TIA’s (McTaggart et
al. Medicine and Health/Rhode Island 2009).
Table . German Stroke Study Collaboration of 4157 patients with acute ischaemic events
Incidence % 100 day mortality %
Intracranial carotid stenosis of more than 50% 6.5
10.1
Proximal middle cerebral artery occlusion
Basilar artery occlusion
3.7
1.2
21.4
44.7
GESICA study (Groupe d’Etude des Stenoses Inta-Cranieenes Atheromateuses symptomatiques),
ICAD in 122 patients with single stenosis of 50% or more. Mean follow up 23.4 months, 13.7%
stroke and 24.5% TIA.
Risk factors for ICAD.
Age
Hypertension
Diabetes
Men
African American, Hispanic and chinese population
Sickle cell disease
meningitis
Investigations.
MRA – brain can be imaged at same time, no radiation, no contrast
CTA – radiation and contrast but improved spatial resolution.
TCD – non invasive, cheap, bedside but operator dependant, 10% have no acoustic window
Conventional angiography - invasive
Stroke outcomes and neuroimaging of intracranial atherosclerosis (SONIA) trial compared TCD
and MRA with conventional angiography. TCD and MRA negative predictive value 86% and 91%.
Positive predictive values – 36% and 59%. Concluded – TCD and MRA can be used for initial
imaging but abnormal result requires conventional angiography for confirmation. So CTA might be
a better initial investigation and angiography reserved for those in whom intervention is planned.
Treatment.
EC/IC (extracranial/intracranial) Bypass Study.
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SSYLVIA (Stenting of symptomatic atherosclerotic lesions in the vertebral or intracranial arteries).
Clopidogrel plus aspirin vs. aspirin alone for reducing embolisation in patients with acute
symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open label, blindedendpoint trial (Wong Lancet Neurol 2010) where acute stroke or TIA patients with carotid or
cerebral large artery stenosis and TCD microemboli were randomised within 7 days of symptom
onset. They had TCD monitoring on day 2 and 7 following initiation of treatment. The primary end
point was embolic signals on day 2. 47 patients had clopidogrel and aspirin, 53 aspirin alone.
93/100 had symptomatic intracranial stenosis of ICA or MCA. 14/45 patients in dual group and
27/50 in the aspirin group had at least one microemboli (p = 0.025). There was no intracranial or
severe systemic haemorrhage. Conclusion – dual therapy is more effective than aspirin alone in
reducing microemboli in patients with intracranial symptomatic stenosis.
Warfarin-Aspirin symptomatic intracranial disease (WASID) trial. Multicentre, double blind study
of symptomatic ICAD of 50% stenosis or more. Patients randomised to warfarin (INR 2 – 3) or
aspirin (1300mg/day). Study terminated early due to risks of haemorrhage with warfarin. No benefit
to the addition of warfarin in stroke prevention. Primary end point – ischaemic stroke, brain
haemorrhage or vascular death 22% vs. 21%. Rates of death (4 vs. 10%), major haemorrhage (3 vs.
8%) and MI or sudden death (3 vs. 7%) were all higher in the warfarin group. Those with more than
70% stenosis had a 23% chance of stroke at 1 year and 25% at 2 years, despite medical therapy
TOSS II trial ongoing will compare cilostazol and aspirin vs. clopidogrel and aspirin in
symptomatic ICAD.
In 1980 Thoralf Sundt reported the first successful intracranial angioplasty. Initial reports of 38%
complication rate (Higashida et al). Sub-maximal angioplasty – use balloon smaller than native
artery and slow inflation have been advocated to reduce complicatons with 30 day major
complication rate down to 4 – 6%. Annual stroke rates 0 – 3.2%. Restenosis occurs in 10 – 30%,
symptomatic in 5 – 10%.
Stenting of symptomatic atherosclerotic lesions in the vertebral or intracranial arteries (SSYLVIA)
trial was a non randomised study. Technical success was 95%. Frequency of stroke – 30 days –
7.2% and one year 10.9%.
Stenting seems to have a higher complication rate than angioplasty alone.
Wingspan stent (Boston Scientific) – self expanding
Phase 1 study – 30 day death and ipsilateral stroke 4.5%, one year stroke rate 9.3%
High restenosis rate
Maybe reserve for dissections, elastic recoil or recurrent stenosis
Stenting vs. aggressive medical management for preventing recurrent stroke in intracranial stenosis
(SAMMPRIS). NIH funded. 640 patients. Symptomatic 70% or more stenosis published in New
England Journal of medicine 2011 concluded that aggressive medical management of intracranial
arterial stenosis was preferable to angioplasty and stenting.
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