William Humphries, MD, MPH - School of Medicine

8/22/2016
Carotid Atherosclerosis
Disclosure
• I have no funding sources or conflicts of interest to
disclose.
William Humphries M.D., MPH
Assistant Professor,
Division of Neurological Surgery
University of Missouri School of Medicine - Columbia
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Epidemiology
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Anatomy
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Objectives
Pathophysiology
Presentation
Imaging
Treatment Considerations
– Medical Management
– Carotid Endarterectomy
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– Stenting
Applications to Geriatric Population
• American Stroke Association
– Stroke Classifications
• Ischemic Stroke
• Hemorrhagic Stroke
– Subarachnoid Hemorrhage
– Intraparenchymal Hemorrhage
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Stroke Epidemiology
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95% of strokes at age >45, and
2/3 of strokes occur in those >65
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3rd leading cause death/disability
•
10% deaths worldwide
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795,000 strokes/yr
– 610,000 of these are first
strokes.
– About 185,000 people who
survive a stroke go on to
have another
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Time Lost = Brain Lost
Estimated
Pace of Neural Circuitry Loss in Typical Large Vessel,
Supratentorial Acute Ischemic Stroke
Neurons Lost
Synapses Lost Myelinated Fibers Lost Accelerated Aging Per Stroke
Per Stroke
1.2 billion
8.3 trillion
7140 km/4470 miles
Per Hour
120 million
830 billion
714 km/447 miles
36 y Per Hour
3.6 y Per Minute
Per minute
Per second
1.9 million
32 000
14 billion
230 million
12 km/7.5 miles
200 meters/218 yards
3.1 wk Per Second
8.7 h
Stroke 2006;37;263-266
In 2010, stroke cost the US $53.9
billion
Etiologies of Ischemic Stroke
– Large-artery
atherosclerosis: 2030%
– Cardiac: 20-30%
– Small-vessel or
lacunar stroke: 2030%
– Cryptogenic:
Ischemic Stroke
• Embolic
– Small vessel
– Large vessel
• Hypoperfusion / Watershed
– Stenosis or occlusion leads to cerebral hypoperfusion
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Carotid Artery Stenosis
Epidemiology
• 15-20% of acute ischemic strokes
• Framingham Heart Study
– Carotid Artery Stenosis > 50%
• 7% of women age 66-93
• 9% of men age 66-93
• North Manhattan Stroke Study
– 62% of patients over 40 years old
Case Presentation
• 75 yo WF presents for evaluation of acute
onset of word finding difficulty and
subjective weakness.
– Symptoms witnessed while patient was on the
phone
– EMS called
• Plaque thickness ≥ 0.9mm
Exam
• Gen: NAD, mildly distressed
• Neuro: Eyes open, awake, alert, impaired
repetition, paraphasia, word finding difficulty,
mild facial droop, MAE X4 with mild RUE
weakness
• CV: RRR, nl s1, s2
• Resp: CTA B
• Abd: NTND
• PMH: DM II, HTN, COPD, Polymyalgia, Gout,
Hypothyroidism, Parkinson’s Disease
• Meds: Metformin, ASA, Lisinopril, Metoprolol, Sertraline,
Omeprazole, Pravastatin, Diltaizem
• FH: Mother/Father with PD
• SH: stopped smoking 40 years ago, no etoh, no illicit
drug use
• Allergies: NKA
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–NIHSS 3
–Out of window for tPA
–Neurological imaging obtained
–Symptoms resolved after arrival to
ICU
–Echo: (-)
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80% Stenosis of the L. ICA
• Symptomatic or Asymptomatic?
• Treatment Strategy?
– Conservative Medical Management?
– Carotid Stenting?
– Carotid Endarterectomy?
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• Plaque accumulation
Pathophysiology
• Cytokine-mediated
oxidation
– Macrophage recruitment
• Smooth muscle migration
– Lipid rich necrotic core
• Disruption of plaque
– Thrombosis
– Embolic phenomenon
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Mechanisms of ischemia
Thromboembolic
• Artery to artery
– Thrombotic material
– Cholesterol emboli
• Hollenhurst plaques
• Flow limiting stenosis
• Thrombosis/Occlusio
n
• Dissection
Hemodynamic
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What is
Association with cardiovascular
atherosclerosis
Carotid stenosis vs Coronary disease
• Many patients with CAS have systemic disease
– CAD seen in up to 70% of patients with ischemic strokes
• Risk factors are similar
• Carotid disease is a predictor of worse cardiac outcomes
• CAD is a major risk in patients being treated for carotid
stenosis
– Increased MI risk in patients
• Similar Plaque morphology
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Presentation
Cerebral Blood Flow
Anatomy
• CBF = CPP/CVR
• CPP = MAP - ICP
– Normal
• CBF: 50-60 cc/ 100 g (brain tissue)/min
– Ischemia
• CBF < 18 cc/100g/min = electrical activity failure occurs
• CBF < 12 cc/100g/min = ionic channel failure occurs
– Infarction and cell death
• CBF 10cc/100g/min or less
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Anterior
Circulation
☐
Posterior
Circulation
Ischemic Stroke
• Embolic
– Small vessel
– Large vessel
• Hypoperfusion / Watershed
– Stenosis or occlusion leads to cerebral hypoperfusion
Anterior Circulation Infarction
• Limb Weakness
• Speech difficulty
– Dysarthria
– Aphasia
• Facial Asymmetry
• Amaurosis fugax
• Visual field cut/loss
• Sensory Loss
– (parasthesia)
• Eye Deviation
– Dysconjugate Gaze
• Hemineglect
• Personality Changes
• Horner’s Syndrome
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Imaging
Imaging
• Duplex Ultrasound
• MRI/MRA
• CTA
• Diagnostic cerebral angiogram
– DSA
Ultrasound
• Measures blood flow velocity
– Peak systolic velocity (PSV)
• Correlates velocity with stenosis
• Categories
– <50%: <125
– 50-69% : PSV 125cm/s-230cm/s
– ≥70 %: > 230cm/s
– Ratio: ICA/CCA
Ultrasound
Positives
• Non-invasive
• Relatively cheap
• Quick
• Can be done in the office
Considerations
• Does not directly
measure stenosis
• Variable/Operator
dependant
• Difficulty with high grade
stenosis/calcification
• Calcifications
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Ultrasound
Magnetic Resonance Angiography
(MRA)
Advantages
Considerations
• Non-invasive
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• Visualization of regional
anatomy
• Contraindications
• No iodinated contrast
• 3D reconstruction
Metal Artifact
– AICD
• Body habitus
• Visualization of the arch
• Can be combined with MRI
MRA
CT Angiography (CTA)
Advantages
• Non-invasive
• Safe for patients with
cardiac implants
• Visualization of regional
anatomy
• 3D reconstruction
• Visualization of the arch
Considerations
• Requires iodinated
contrast
• Ionizing Radiation
• Metal artifact
• Calcification
• Can be combined with CT
Perfusion
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CTA
Digital Subtraction Angiography (DSA)
Digital Subtraction Angiography
Digital Subtraction Angiography
Advantages
• Catheter based
angiography
• Gold standard
• Allows for identification of
additional vascular
lesions
• Surgical planning
Considerations
• Invasive Procedure
– < 1% complication rate
• Uncomfortable
• Iodinated contrast
• Ionizing radiation
• Cost
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Imaging for Carotid Stenosis
• Screen with non-invasive imaging
• Confirm with angiography
• Understand the limitations of the imaging modality used
– Calcification
Treatment
– Variability
– Concordance is best
• Angiography is the goal standard
Treatment
• Carotid Endarterectomy
AHA Guidelines
• Antiplatelet Therapy
• Carotid Artery Stenting
• Role of Medical Management
• Historical Perspective
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Carotid Endarterectomy
www.nhlbi.nih.gov/health/health-topics/topics/carend/
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NASCET
50-center Randomized Prospective Trial
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659 patients
Patients with 70-99% stenosis, < 80 years old
Risk of any stroke at 2 years
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CEA vs. Medical Management
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Medical arm: 26%
Surgical arm: 9%
ARR: 17%
Major or fetal stroke ARR: 10.6 for CEA cohort
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ACAS
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1659 patients
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Prospective, randomized clinical trial (1987-1993)
Median f/u 2.7 yrs
Asymptomatic carotid of at least 60%
Patients randomized to medical arm with 325mg ASA vs CEA with ASA
Outcomes: (TIA), cerebral infarction, death
5 year stroke risk 11% in the medical vs 5.1 in CEA arm
CEA morbidity ~3%
Carotid Stenting
www.nhlbi.nih.gov/health/health-topics/topics/carend/
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SAPPHIRE
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SAPPHIRE 2004
Prospective, multicenteted, randomized trial ; N= 334
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CAS with distal protection vs CEA
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Symptomatic: > 50% stenosis
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Asymptomatic: 80% stenosis
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Hypothesis: CAS is not inferior to CEA
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Primary Outcomes:
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Death, myocardial infarction, ipsilateral stroke at 30days
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Ipsilateral stroke at 1 year
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Endpoint (CAS vs CEA): 12.2% vs 20.1%, p=.004 (Non-inferiority)
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1 year revascularization: 0.6 % vs 4.3% p=.04
Findings:
Conclusion: CAS with distal protection device is not inferior to CEA in patients with coexisting conditions
Stenting and Aggressive Medical
Management for Preventing Recurrent
Stroke in Intracranial Stenosis
SAMMPRIS
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Carotid Revascularization vs Stenting (CREST)
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Outcome : Composite of stroke, myocardial infarction, death at 4 year follow-up.
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Prospective randomized trial, N= 2502, symptomatic and asymptomatic
Endpoint (stent vs. CEA): 6.4% vs 4.7%, HR: 1.5, p=.51
Periprocedure Stroke (stent vs CEA): 4.1% vs 2.3% p=.01
Periprocedure MI (stent vs CEA): 1.1% vs 2.3% p=.03
Periprocedure Death (stent vs CEA): 0.7% vs 0.3%, p= 0.18)
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What about asymptomatic patients with
carotid stenosis?
• Incidental finding
• CREST 10year follow-up, N= 2502
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Composite of stroke, myocardial infarction, death at 10 year follow-up
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Ipsilateral Stroke (CAS vs CEA): 6.9% vs 5.6%, HR: .99 CI: .64-1.52)
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– CAS vs CEA: (11.8% vs 9.9%, HR: 1.10 CI: 0.83-1.44)
Conclusion: No difference in composite endpoint or Ipsilateral Stroke at
10years.
ACT 1 Trial
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ACT I trial : N= 1453, prospective, randomized, stenting vs. surgery
– Asymptomatic patients, Not high risk
– Stenting?
– Carotid Endarterectomy?
What about medical management?
• Many of the recent prospective trials do not have a
medical randomization arm
• Can asymptomatic patients be managed
conservatively with best medical therapy?
– (CAS vs. CEA): (3.8% vs. 3.4%, p= .01 for non-inferiority)
• CREST II coming soon (2014-2020)
Composite endpoint: Death, Stroke, MI at 30days
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Stroke or Death at 30 days : (CAS vs CEA): 2.9% vs 1.7%, p= .33)
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– Medically?
– Non-inferiority test with 5 year follow up
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– Elderly population
• How should these patients be managed ?
Cumulative 5 year stroke free rate
– (CAS vs. CEA): 93.1% vs 94.7% , p=.44
Conclusion : Carotid stenting is not inferior to CEA for asymptomatic
patients at 1 year and 5 years
– SAMMPRIS : Intracranial Atherosclerotic disease
– 3 arm study
– Stroke + death composite
– Cognitive function
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Stenting Considerations
How does this apply to the Geriatric
Population
How does this apply to the Geriatric
Population ?
• Age is often NOT the issue
• Age is often used a surrogate for underlying comorbid
disease and physiological disease
Frailty
– Is he a “good looking 80”?
– Unfavorable Anatomy
– Functional Status
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• NSQIP database N=44,832
• Risk Analysis Index
– RAI
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• Meta-analysis, N= 4754
– EV-3, SPACE, CREST, ICSS
• Stroke and death risk
• CAS:
– 65-69: HR: 2.16
– >70: HR: 4.0
• CEA vs CAS:
– 70-74: HR: 2.09 (1.32-3.32)
• Favored CEA in patients over 70
Case Revisited
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80% Stenosis of the L. ICA
• Symptomatic or Asymptomatic?
• Treatment Strategy?
– Conservative Medical Management?
– Carotid Stenting?
– Carotid Endarterectomy?
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Things to Remember Regarding
Stenting vs CEA
• Both have their place in the treatment of carotid stenosis in
select patient populations.
• Both are relatively safe if performed on the correct patients.
• CEA is the gold standard for treatment in asymptomatic
patients < 70% stenosis and symptomatic patients >50-60%
– But there is a trend toward stenting
• CEA appears to have a more favorable outcomes for stroke
prevention.
• Carotid stenting appears to have more favorable outcome for
perioperative MI.
• Patient selection is critical.
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Unanswered Questions
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When is medical management the preferred method of treatment?
– Asymptomatic Patients
– Better treatment options
• Brandi French, M.D., Vascular Neurology, Stroke
Director
• Nick Tarlov, M.D., Vascular Neurology, Interventional
Neurology
• William Humphries, M.D.,MPH Vascular/Endovascular
Neurosurgery
• Statins
• Antihyperglycemic Agents
• Antihypertensives
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• Antithrombotics
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CREST II coming soon!
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Which Frailty Index should we be using?
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University of Missouri Neurovascular Stroke
Team
Should we be using Frailty instead of Age for preoperative
evaluation?
•
Tami Harris, RN, BSN Stroke Coordinator
Debbie Self, RN
Admission Advice (573 882 6985)
?
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