Cardiogenic Stroke: A Neurologist View. David Teeple, MD Center for Neurosciences Tucson Medical Center

Transcription

1 Cardiogenic Stroke: A Neurologist View David Teeple, MD Center for Neurosciences Tucson Medical Center

2 Disclosure I have one relevant relationship I need to disclose: I am currently working on a stroke-related research project named Socrates, which is funded by AstraZeneca. This relationship will in no way affect the discussion we will be having about Cardiogenic Stroke. Connolly SJ, Pogue J, Hart RG, et al. Effect

3 Objectives Define Cardiogenic Stroke and discuss its causes. Discuss treatment options for the different types of Cardiogenic Stroke. Discuss new research in Atrial Fibrillation and other types of Cardiogenic Stroke. Connolly SJ, Pogue J, Hart RG, et al. Effect

4 ~795,000 Strokes Annually Intracerebral hemorrhage 9% Subarachnoid hemorrhage 3% Ischemic stroke 88% Ischemic stroke Intracerebral hemorrhage Subarachnoid hemorrhage

5 Cerebral Ischemia Thrombosis Embolism Systemic Hypotension Cardioembolic Aortic Embolism Artery to Artery

6 Cardioembolic Stroke Accounts for substantial proportion of overall stroke burden 1 High prevalence Greater severity of stroke Less favorable prognosis High recurrence risk 1. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996;27(10):1760Y1764.

7 Cardioembolic Causes 1. Atrial Fibrillation Aortic Embolism 2. Valvular disease 3. Heart Failure 4. Patent Foramen Ovale

8 Atrial Fibrillation (AF) ~50% of cardioembolic strokes 2.7 million Americans have atrial fibrillation SURGE in AF related stroke Given increased risk of AF with age

9 Afib Embolization from left atrial appendage and left atrium Increased risk with left atrial enlargement Risk same for paroxysmal vs persistent afib How much afib is enough?

10 Afib Overall risk: 5% annual risk of stroke However, risk varies based on patient s risk factors: CHADS 2 1 Congestive Heart Failure 1 point Hypertension - 1 point Age > 75 years - 1 point Diabetes Mellitus - 1 point Stroke/TIA symptoms - 2 points 1. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285(22):2864Y2870.

11 Afib CHA 2 DS 2 VASc 1 Congestive Heart Failure - Hypertension - Age >75 years - Diabetes - Stroke - Vascular disease - Age Female sex - 1 point 1 point 2 point 1 point 2 points 1 point 1 point 1 point 1 Olesen JB, Lip GY, HansenML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011;342:d124.

12 Detecting Afib Based on characteristics of stroke AT LEAST 24 hours of monitoring after event In Cryptogenic embolic stroke, EMBRACE 1 Get longer study CRYSTAL AF 2 Loop monitor 30-day Holter 1. D. J. Gladstone, et all. Atrial Fibrillation in Patients with Cryptogenic Stroke N Engl J Med : Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:

13 Treatment Aspirin RR 21% Warfarin RR 68% Effectively reduces annual risk 5% to 1.4% Aspirin + Clopidogrel Better than Aspirin 1 But not as good as warfarin 1 Increased risk of bleed ~ similar to warfarin 1 1. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360(20):2066Y2078

14 Treatment Lower Renal Rates Impairment of Intracranial Significant Liver Disease Hemorrhage Mechanical Valves Anticipated Reversal of Anticoagulation

15 Treatment HAS-BLED Hypertension 1 point Systolic >160 Abnormal Liver or Renal Function points Dialysis, kidney transplant, or Cr >2.6 Cirrhosis, bilirubin >2X norm. AST/ALT/AlkP >3X norm Stroke - 1 point Bleeding history - 1 point Labile INR - 1 point TTR <60 Elderly - 1 point >65 years Drugs 1 point NSAIDs/Antiplatelets or excess alcohol use - Pisters R, Lane DA, Nieuwlaat R, et al. A novel user friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138(5):1093Y1100.

16 Infective Endocarditis Stroke often presenting feature Risk Factors Valvular issues related to Rheumatic Heart Disease Bicuspid Aortic Valve Prosthetic Valve IV Drug use (although more often right sided involvement) Clinical Picture Weight loss Fever New murmur Systemic embolization N Engl J Med 2013;368: Detection Transesophageal Echo! MRI better than CT

17 Multiple cortical and subcortical microbleeds on a T2* sequence. Anti-thrombotic therapy is associated with increased risk of hemorrhage Hess A et al. AJNR Am J Neuroradiol 2013;34: by American Society of Neuroradiology

18 Infective Endocarditis Vegetations most at risk for embolizing Large + Mobile vegetations Mitral Valve Staph Aureas N Engl J Med 2013;368:

19 Multiple macular spots of varying sizes over both feet (A) and hand (B), which were nontender and noncompressible. Khanna N et al. Circulation. 2013;127:861 Copyright American Heart Association, Inc. All rights reserved.

20 Prosthetic valves High risk especially Caged ball Tilting disc Mitral position Warfarin INR Stroke despite therapeutic INR Add aspirin 81mg

21 Heart Failure Mechanism Thrombus formation Borderzone Infarcts

22 Figure 1 Examples of borderzone infarcts on diffusion-weighted MRI Förster A et al. (2008) Mechanisms of Disease: pathophysiological concepts of stroke in hemodynamic risk zones do hypoperfusion and embolism interact? Nat Clin Pract Neurol /ncpneuro0752 Connolly SJ, Pogue J, Hart RG, et al. Effect

23 Heart Failure Secondary Prevention???? Aspirin vs Clopidogrel vs Extended release dipyridamole-asa vs Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) 1 Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm (WARCEF) 2 Both studies examined Heart Failure EF <35% Randomized Antiplatelet vs Warfarin PRIMARY PREVENTION Reduction in stroke Increase in hemorrhage NET NO BENEFIT Warfarin ANYTHING GOES 1. Massie BM, Collins JF, Ammon SE, et al. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation 2009;119(12). 2. Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012

24 Patent Foramen Ovale

25 PFO 20-25% of population with PFO In cryptogenic stroke ~50% of population with PFO

26 PFO

27 PFO Transthoracic Echo (TTE) With agitated bubble study Transesophageal echocardiogram (TEE) Atrial Septum Aortic arch Left atrial appendage Aortic valve

28 PFO Amplatzer StarFlex

29 Cumulative number of patients recruited in studies of different designs over a period of 16 years for the comparison of closure vs medical treatment. Kitsios G D et al. Stroke. 2012;43: Copyright American Heart Association, Inc. All rights reserved.

30 PFO Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenicmstroke. N Engl J Med 2013;368:

31 Prospective Randomized Trial 980 Crytpogenic Ischemic Stroke with PFO 481 Medical Therapy 499 PFO Closure with Amplatzer Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013;368:

32 PFO Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013;368:

33 414 Cryptogenic Stroke with PFO 204 PFO Closure 210 Medical Therapy Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013;368:

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35 PFO Medical Treatment Aspirin Clopidogrel Extended Release Dipyridamole-ASA Warfarin IF DVT or hyper-coagulable state Closure reasonable to consider Recurrent events Young Age Large PFO Atrial Septal Aneurysm

36 Aortic Arch Atherosclerosis Thromboembolism Cholesterol emboli TEE better than TTE Plaques >4mm Aggressive risk factor Control Anti-platelet vs warfarin Arch Related Cerebral Hazard Trial (ARCH) 1 ASA-Clopidogrel combo may be better 1. Amarenco P, Davis S. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke May;45(5):

37 Cardioembolic Strokes Account for large portion of stroke burden Afib we need to be aggressive about detection Anticoagulation reduces risk of future ischemic stroke dramatically CHADS and HAS-BLED LOOK AGGRESSIVELY Heart failure No warfarin as primary treatment Secondary stroke prevention best antithrombotic unknown PFO Most of the time closure not better than medical therapy Antiplatelet agent Aortic atheromas TEE Best antithrombotic unknown