1. No category

Cardio-embolic strokes
Risk & Prevention
Dr. Naeem Dean FRCP (UK)
Clinical Associate Professor,
Director Stroke Program,
Royal Alexandra Hospital,
Edmonton,
Canada
Mr. Atherosclerosis
Large vessel injury
Stroke Subtypes
Ischemic 80%
Hemorrhagic
20%
Diagnosis of Cardioembolic Stroke
“The presence of a potential cardioembolic
source in the absence of cerebrovascular
disease in a patient with a non-lacunar
stroke”
Cerebral Embolism Task Force, 1989
How Often are Lacunes
Cardioembolic?
• About 20% have potential cardiac sources
• About 5 - 10% attributed to cardioembolism
• Cardioembolic lacunes often large(>1.5cm)
Clinical Features of
Cardioembolic Stroke
• Abrupt non-progressive onset
• Decreased consciousness at onset
• Embolism to other organs
• Palpitations at onset
• Hemianopia without hemiparesis
Multiple Acute Ischemic Lesions in
Different Vascular Territories on DWI
T2
DWI
ADC
“Embolic Pattern” on DWI
Frequency of Cardioembolic Stroke*
N
Patient Age (Mean)
Presumed
Cardioembolic, %
Oxfordshire, UK
(1989)
224
73
20 †
Melbourne,
Australia (1989)
353
--
19
Lausanne,
Switzerland (1991)
1311
65
18
Klosterneuburg,
Austria (1992)
365
68
19
Umea, Sweden
(1992)
953
72
31
Barcelona, Spain
(1993)
736
71
17
Guayaquil,
Ecuador (1993)
313
61
14
250 ††
--
17
166
73
28
Study
Giessen, Germany
(1994)
Lund, Sweden
(1994)
Frequency of Cardioembolic Stroke*
Maastricht,
Holland (1994)
813
71
22
Paris, France
(1995)
250
--
29
Warsaw, Poland
(1995)
297
69
22
Barcelona, Spain
(1997)
1267
--
18
Taipei, Taiwan
(1997)
676
65
20
Riyadh, Saudi
Arabia (1999)
756
--
19
Athens, Greece
(2000)
885
70
38
Bensaçon,
France (2000)
1776
69
31
Aggregate
11391
69
22
Etiological work up for
cardioembolic strokes
• ECG and 24- hour Holter monitoring
• Echocardiography ( TTE, TEE)
• Cardiac MRI ( under investigation)
Utility of Holter
• AF and flutter account for 50% of
cardioembolic strokes and 10% of all
strokes
• 30% of AF patients are unaware
• 25% of AF associated stroke have no prior
diagnosis
• Intermittent AF may be detected in 30% of
patients with stroke
Utility of Holter
• Poor sensitivity of 12 lead ECG to detect
PAF
• 24-hour recording may detect previously
unrecognized AF in 2% of stroke patients
• Extending monitoring from 24H – 72 H
increases prevalence of AF after stroke from
1.2% - 6.1%
Utility of Holter
( stroke2004;35:1647-51)
• AF detected in 22 out of 149 patients with
IS and TIA
• ECG detected 6.7% of AF
• 24-Holter detected AF in an additional 5%
• ELR ( 7 days monitoring) detected AF in an
additional 5.7%
Echocardiography
• Low yield in patients with no history of cardiac
disease, normal exam, ECG and CXR. ( 2% VS
19% )
• TTE vs TEE:
TTE: LV thrombus, LVH , VHD
TEE: PFO , ASA, AAA, LA thrombus
• CV MR perhaps better than Echo in detecting
heart conditions contributing to thrombus
formation
Cardioembolic Sources
High Risk
Atrial fibrillation
Recent anterior MI
Mechanical valve
Medium Risk
LV hypokinesia /
aneurysm
Patent foramen
ovale
Bioprostetic valve
Atrial septal
aneurysm
Congestive failure
Rheumatic mitral
stenosis
Cardiomyopathy
Thrombus / tumor
Myxomatous MVP
Endocarditis
Low / Unclear Risk
Spontaneous
echo contrast
Causes of cardioembolic strokes
•
•
•
•
•
Atrial Fibrillation 45 %
LV dysfunction 25%
Valvular heart disease 10%
Prosthetic valves 10%
Misc. ( tumors, IE, etc.) 10%
Embolic Sources for
Cryptogenic Strokes
•
•
•
•
•
Patent foramen ovale
Atrial septal aneurysms
Spontaneous echo contrast
Occult atrial fibrillation
Aortic atheromas
Cardioembolic strokes
•
•
•
•
Atrial Fibrillation
Patent Foramen Ovale
LV dysfunction
Aortic Arch Atheroma
Atrial Fibrillation
Pathophysiology of AF-associated ischemic stroke
Hart, R. G. et al. Stroke 2001;32:803-808
Copyright ©2001 American Heart Association
Atrial Fibrillation
• Persistent and PAF predictors of first and
recurrent strokes
• Overall RR with warfarin is 68%
• Estimated RR with ASA compared to
placebo is 21%
Risk factors for thrombo-embilisim in AF
Less Validated or Weaker
Risk Factors
Moderate-Risk Factors
High-Risk Factors
Female gender
Age greater than or equal to 75 y
Age 65 to 74 y
Hypertension
Mitral stenosis
Coronary artery disease
Heart failure
Prosthetic heart valve*
Thyrotoxicosis
Previous stroke, TIA or
embolism
LV ejection fraction 35% or less
Diabetes mellitus
*If mechanical valve, target international normalized ratio (INR) greater than 2.5.
INR indicates international normalized ratio; LV, left ventricular; and TIA, transient ischemic
attack.
Stroke Risk in Patients with Nonvalvular AF Not
Treated With Anticoagulation According to the
CHADS2 Index
CHADS2 Risk Criteria
Score
Prior stroke or TIA
2
Age >75 y
1
Hypertension
1
Diabetes mellitus
1
Heart failure
1
Stroke Risk in Patients With Nonvalvular AF
Not Treated With Anticoagulation According
to the CHADS2 Index
Patients
(N = 1733)
120
463
523
337
220
65
5
Adjusted Stroke
Rate (%/y)
(95% Cl)
CHADS2 Score
1.9 (1.2 to 3.0)
2.8 (2.0 to 3.8)
4.0 (3.1 to 5.1)
5.9 (4.6 to 7.3)
8.5 (6.3 to 11.1)
12.5 (8.2 to 17.5)
18.2 (10.5 to 27.4)
0
1
2
3
4
5
6
Anticoagulation Patients with Atrial Fibrillation:
The ACCP Guidelines
High stroke risk
(e.g. age > 75, prior ischemic stroke or TIA, LV dysfunction,
hypertension, diabetes):
• Oral Vitamin K antagonist. (e.g. warfarin)
Intermediate stroke risk (age 65-75, no other risk factors):
• Oral VKA or ASA 325 mg daily
Lower stroke risk (age <65, no other risk factors):
• ASA 325 mg daily
Singer DE, et al. Chest 2004;126:429-256
Gage BF, et al. JAMA 2001;285:2864-70
Antithrombotic Therapy for Patients
With Atrial Fibrillation
Risk Category
No risk factors ( ASR 1%)
One moderate-risk factor (ASR 4%)
Any high-risk factor or more than 1
moderate-risk factor (ASR 8-12%)
Recommended Therapy
Aspirin, 81 to 325 mg daily
Aspirin, or warfarin
Warfarin
ACC/AHA/ESC guide lines for management of AF; Circulation
2 Aug 06
AC in elderly with AF
•
•
•
•
12% > 75 have AF
56% of AF patients are >75
AF increases risk of stroke by 5 fold
AC increases the risk of bleeding by 13%/Y
• Increase risk of serious hemorrhage in
elderly
BAFTA study ( Lancet 2007;370: 490503)
• RCT of >75 years of age ; Warfarin ( INR
2-3) vs ASA 75 mg
• AC was twice as effective as ASA and no
difference in bleeding
• Close monitoring , lower INR, BP control
• >75 years of age with high risk of bleeding
but no absolute CI to AC a low target INR
of 2 ( 1.6-2.5) (ACC,AHA & ESC guidelines;
circulation Aug 2006)
Alternatives to AC in AF
• ASA 81-325 mg
• Oral direct thrombin inhibitors vs warfarin
(Ximelegatran in SPORTIF-III and V )
• Combination of antiplatelets
ACTIVE-W : ASA + P VS Warfarin
ACTIVE-I : ASA + P VS ASA
• Occlusion of LAA ( WATCHMAN device
and PROTECT-AF trial)
Figure 1. WATCHMAN(r) Left Atrial Appendage System. The WATCHMAN device
is comprised of a self-expanding nitinol frame structure with fixation barbs and a
permeable polyester fabric that covers the atrial face of the device. The device is
constrained in a 12F delivery catheter and is available in 5 sizes: 21, 24, 27, 30,
and 33 mm.
Secondary prevention of stroke in AF
ASA guide lines: stroke 2006;37;577-617
• IS or TIA with persistent or PAF AC with
warfarin ( INR 2-3) is recommended ( class
1, Level of evidence A)
• Unable to take warfarin , ASA 325 mg / d
( Class1, Level of evidence A)
Timing of
starting
Anticoagualtion
?
Recent Trial Results
Trial
Recurrent Stroke (%)
IST (AF subgroup)
(N = 3169)
TOAST (cardioembolism)
(N = 266)
HAEST (all with AF)
(N = 449)
TAIST*
(N = 1484)
*no benefit in cardioembolism subgroup
Heparin
No heparin
Danaparoid
Placebo
Dalteparin
Aspirin
HD Tinzaparin
LD Tinzaparin
Aspirin
2.8
4.9
0
1.6
8.5
7.5
3.3
4.7
3.1
Current Recommendations
• In patients with IS and AF, AC can be safely
delayed for 7-10 days
• Reasonable to start ASA and prophylactic
dose of Heparin
Patent foramen ovale
“Smoking gun guilty by association”
PFO
• 20-25% of normal population has a PFO
• Yearly risk of cryptogenic stroke in healthy
persons with a PFO may be as low as 0.1%
PFO
• 43% of strokes in young adults are
cryptogenic
• PFO detected in more than half of these
individuals
• Meta-analysis of studies looking at
cryptogenic strokes: Overell JR, Neurology
2000;55:1172-9
• Meta-analysis of case control studies in patients with cryptogenic
stroke
Mechanism of stroke with PFO
•
•
•
•
•
•
Paradoxical embolisim
Valsalva inducing activities?
Occult deep vein thrombosis?
ASA and thrombus?
Large PFO?
Atrial arrythmias?
Investigations for suspected PFO
• Younger patients with IS of unknown cause
• TCD bubble study /TEE
• Tests for DVT and thrombophilia
Stroke Recurrence Following
Cryptogenic Stroke in Young Patients
Group
4 yr Stroke Risk
No atrial septal abnormality
(N = 304)
4.2% (1.8 – 6.6)
PFO alone (N = 216)
2.3% (0.3 – 4.3)
PFO and ASA (N = 51)
15.2% (1.8 – 28.6)*
NEJM 2001; 345:740-746
*p = 0.007 (compared with no atrial septal abnormality)
All patients received ASA 300 mg/day; ages 18 – 55 years
PFO in cryptogenic strokes
(PICCS)
Circulation 2002;105:2625-31
• WARSS ( warfarin-Aspirin Recurrent
Stroke Study) NEJM 2001;345:1444-51
• PICCS substudy of WARRS, 630 patients
underwent TEE
Table 2. Two-Year Rates of Recurrent Stroke or Death in Patients
With Different PFO Size From: Homma: Circulation, Volume
105(22).June 4, 2002.2625-2631
Antithrombotic Therapy for
PFO-Associated Stroke
The PICSS Sub-study of WARSS
Group
Stroke or Death (2 yrs)
Warfarin (N = 97)
16.5%
Aspirin (N = 106)
13.2%
No increase in stroke rate with large PFOs; 51 patients
with ASA +PFO had similar event rates and no
differential response to warfarin vs. aspirin
Treatment of PFO
(ASA. Stroke 2006;37;577-617)
• Aspirin first line
• Warfarin for high risk e.g. venous
thrombosis, hypercoagulable state
• Closure may be considered for recurrent
cryptogenic strokes despite optimal medical
therapy
• CLOSURE study
Left ventricular dysfunction
&
stroke risk
LV dysfunction
• RR of stroke associated with CHF is about
4.1 among 50-59 years of age
• RR about 1.5 by age 80-89 years
• SAVE: Neurology, Volume 54(2).January 25, 2000.288
LV dysfunction and recurrent
stroke
• 5 year recurrent stroke risk in patients with
cardiac failure reported to be as high as
45%
• Uncertainity around use of antiplatelets vs
warfarin ( WATCH & WARCEF trials)
ASA recommendation
Stroke 2006;37;577-617
• Patients with IS or TIA with dilated
cardiomyopathy either warfarin ( INR 2.03.0) or antiplatelet therapy may be
considered for prevention of recurrent
events ( class II b, Level of evidence C)
Aortic Arch Atheroma
Amarenco, NEJM 1992
Aortic Plaque Autopsy Study
• Aortic plaques not associated with
extracranial carotid stenosis
• Frequency of plaques increase with age
(rarely seen in patients <60 years)
• 3-fold increase in aortic plaques among
cryptogenic stroke cases after adjusting
for stroke risk factors
Amarenco, NEJM 1992
Pathologic Evaluation of the Aortic Arch
in 500 Patients with Neurologic Diseases
Patient Group
N
Ulcerated Aortic
Plaques
Other neurologic disease
261
5%
Ischemic stroke
183
28%*
identified cause
155
22%
unexplained stroke
28
61%*
*p <0.001
Amarenco, NEJM 1994
TEE Case-Control Study
• Enrolled 250 consecutive stroke patients and
250 controls > 60 years of age. Proximal
plaques separated from distal plaques.
• After adjustment for stroke risk factors stroke
patients were 9 times more likely to have large
plaques (≥ 4mm) proximal to the left
subclavian artery (large mobile plaques 14x).
Amarenco, NEJM 1994
TEE Case-Control Study
N
Ascending or Transverse
Plaques (≥4mm)
Elderly Controls
250
2%
Stroke Patients
250
14%*
74
44
54
22
5%
9%
11%
28%*
Patient Group
Stroke Subtypes
Another likely cause
Presumed lacunar infarct
Another possible cause
No other apparent cause
*p <0.001
French Study Group, NEJM 1996
Risk of Stroke Recurrence in
Patients with Aortic Plaques
• Prospective follow-up study of 331
consecutive stroke patients ≥ 60 years of age
• All underwent TEE; size and thickness of
proximal aortic plaques assessed
• 2.4 year mean follow-up to determine the
incidence of recurrent stroke and other
vascular events
Atherosclerosis of the Aortic Arch
and Recurrent Ischemic Stroke
Atherosclerosis of the Aortic Arch
and Recurrent Vascular Events
French Study Group, NEJM 1996
Results – Stroke Recurrence
Patient Group
N
No plaques
Small plaques (1-3.9mm)
Large plaques (≥ 4mm)
* p< 0.001
Stroke
Recurrence
(% / yr)
2.8
3.5
11.9*
Vascular
Events
(% / yr)
5.9
9.1
26.0*
Possible therapies for AAA
• No therapy has been adequately
evaluated
• Options: antiplatelet agents, Statins,
anti-hypertensives, anticoagulants,
surgery
The Aortic arch-related cerebral
hazard trial ( ARCH)
• ASA + Plavix vs warfarin in patients with
an embolic event and complex atheroma
• Start date Feb 2002
• Expected completion date Oct 2008
Thank you