Cardio embolic strokes Powerpoint Presentation

Cardio embolic strokes

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Slide 1 :

Cardio-embolic strokes Risk & Prevention Dr. Naeem Dean FRCP (UK) Clinical Associate Professor, Director Stroke Program, Royal Alexandra Hospital, Edmonton, Canada

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Large vessel injury Mr. Atherosclerosis

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Stroke Subtypes Ischemic 80% Hemorrhagic 20%

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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

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How Often are Lacunes Cardioembolic? About 20% have potential cardiac sources About 5 - 10% attributed to cardioembolism Cardioembolic lacunes often large(>1.5cm)

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Clinical Features of Cardioembolic Stroke Abrupt non-progressive onset Decreased consciousness at onset Embolism to other organs Palpitations at onset Hemianopia without hemiparesis

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T2 DWI ADC Multiple Acute Ischemic Lesions in Different Vascular Territories on DWI

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“Embolic Pattern” on DWI

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Economy class stroke syndrome

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Frequency of Cardioembolic Stroke*

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Etiological work up for cardioembolic strokes ECG and 24- hour Holter monitoring Echocardiography ( TTE, TEE) Cardiac MRI ( under investigation)

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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

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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%

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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%

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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

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High Risk Medium Risk Low / Unclear Risk LV hypokinesia / aneurysm Bioprostetic valve Congestive failure Cardiomyopathy Myxomatous MVP Patent foramen ovale Atrial septal aneurysm Spontaneous echo contrast Cardioembolic Sources Atrial fibrillation Recent anterior MI Mechanical valve Rheumatic mitral stenosis Thrombus / tumor Endocarditis

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Causes of cardioembolic strokes Atrial Fibrillation 45 % LV dysfunction 25% Valvular heart disease 10% Prosthetic valves 10% Misc. ( tumors, IE, etc.) 10%

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Embolic Sources for Cryptogenic Strokes Patent foramen ovale Atrial septal aneurysms Spontaneous echo contrast Occult atrial fibrillation Aortic atheromas

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Cardioembolic strokes Atrial Fibrillation Patent Foramen Ovale LV dysfunction Aortic Arch Atheroma

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Atrial Fibrillation

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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%

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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 Previous stroke, TIA or embolism Age 65 to 74 y Hypertension Mitral stenosis Coronary artery disease Heart failure Prosthetic heart valve* Thyrotoxicosis 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.

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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

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Stroke Risk in Patients With Nonvalvular AF Not Treated With Anticoagulation According to the CHADS2 Index Adjusted Stroke Patients Rate (%/y) (N = 1733) (95% Cl) CHADS2 Score 120 1.9 (1.2 to 3.0) 0 463 2.8 (2.0 to 3.8) 1 523 4.0 (3.1 to 5.1) 2 337 5.9 (4.6 to 7.3) 3 220 8.5 (6.3 to 11.1) 4 65 12.5 (8.2 to 17.5) 5 5 18.2 (10.5 to 27.4) 6

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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

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Antithrombotic Therapy for Patients With Atrial Fibrillation Risk Category Recommended Therapy No risk factors ( ASR 1%) Aspirin, 81 to 325 mg daily One moderate-risk factor (ASR 4%) Aspirin, or warfarin Any high-risk factor or more than 1 Warfarin moderate-risk factor (ASR 8-12%) ACC/AHA/ESC guide lines for management of AF; Circulation 2 Aug 06

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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 1-3%/Y Increase risk of serious hemorrhage in elderly

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BAFTA study ( Lancet 2007;370: 490-503) 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)

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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)

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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.

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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)

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Timing of starting Anticoagualtion ?

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Recent Trial Results Trial Recurrent Stroke (%) IST (AF subgroup) Heparin 2.8 (N = 3169) No heparin 4.9 TOAST (cardioembolism) Danaparoid 0 (N = 266) Placebo 1.6 HAEST (all with AF) Dalteparin 8.5 (N = 449) Aspirin 7.5 TAIST* HD Tinzaparin 3.3 (N = 1484) LD Tinzaparin 4.7 Aspirin 3.1 *no benefit in cardioembolism subgroup

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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

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Patent foramen ovale “Smoking gun guilty by association”

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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%

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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

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Meta-analysis of case control studies in patients with cryptogenic stroke

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Mechanism of stroke with PFO Paradoxical embolisim Valsalva inducing activities? Occult deep vein thrombosis? ASA and thrombus? Large PFO? Atrial arrythmias?

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Investigations for suspected PFO Younger patients with IS of unknown cause TCD bubble study /TEE Tests for DVT and thrombophilia

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Stroke Recurrence Following Cryptogenic Stroke in Young Patients Group 4 yr Stroke Risk No atrial septal abnormality 4.2% (1.8 – 6.6) (N = 304) 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

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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

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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

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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

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Table 3. Two-Year Rates of Recurrent Stroke or Death* in Patients With and Without PFO Assigned to Warfarin or Aspirin From: Homma: Circulation, Volume 105(22).June 4, 2002.2625-2631

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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

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Risk Factors for Ischemic Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation Risk Factors Relative Risk Previous stroke or TIA 2.5 Diabetes mellitus 1.7 History of hypertension 1.6 Heart failure 1.4 Advanced age (continuous, per decade) 1.4 Data derived from collaborative analysis of 5 untreated control groups in primary prevention trials

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Left ventricular dysfunction & stroke risk

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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

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SAVE: Neurology, Volume 54(2).January 25, 2000.288

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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)

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ASA recommendation Stroke 2006;37;577-617 Patients with IS or TIA with dilated cardiomyopathy either warfarin ( INR 2.0-3.0) or antiplatelet therapy may be considered for prevention of recurrent events ( class II b, Level of evidence C)

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Aortic Arch Atheroma

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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

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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

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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).

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Amarenco, NEJM 1994 TEE Case-Control Study Ascending or Transverse Patient Group N Plaques (=4mm) Elderly Controls 250 2% Stroke Patients 250 14%* Stroke Subtypes Another likely cause 74 5% Presumed lacunar infarct 44 9% Another possible cause 54 11% No other apparent cause 22 28%* *p <0.001

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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

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Atherosclerosis of the Aortic Arch and Recurrent Ischemic Stroke

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Atherosclerosis of the Aortic Arch and Recurrent Vascular Events

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French Study Group, NEJM 1996 Results – Stroke Recurrence Stroke Vascular Patient Group N Recurrence Events (% / yr) (% / yr) No plaques 2.8 5.9 Small plaques (1-3.9mm) 3.5 9.1 Large plaques (= 4mm) 11.9* 26.0* * p< 0.001

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Possible therapies for AAA No therapy has been adequately evaluated Options: antiplatelet agents, Statins, anti-hypertensives, anticoagulants, surgery

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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

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Frequency of Cardioembolic Stroke. Etiological work up for cardioembolic strokes. ECG and 24- h more Frequency of Cardioembolic Stroke. Etiological work up for cardioembolic strokes. ECG and 24- hour Holter monitoring. Echocardiography ( TTE, TEE) ... less