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11/12/2014 Stroke Update Symposium Nov. 14, 2014 Structural Heart Defects and Stroke George V. Moukarbel, MD Assistant Professor of Medicine Interventional Cardiology Director, Heart Failure & LVAD Program Associate Director, Cardiovascular Fellowship Program The University of Toledo Medical Center Objectives: • Review structural heart defects that are associated with stroke and the therapy to prevent stroke events • Discuss the cardiac evaluation of patients presenting with stroke • Outline the treatment of stroke patients who have underlying structural cardiac lesions Disclosures • I have no disclosures relevant to this presentation 1 11/12/2014 Patent foramen ovale Structural Heart Disease Spectrum Atrial septal defect Ventricular septal defect Paravalvular leak Hypertrophic cardiomyopathy Valvular heart disease Left atrial appendage Vascular fistulae sinus of valsalva aneurysm Left ventricular aneurysm Patent ductus arteriosus Heart Disease and Strokes: Leading Killers in the United States Cause 1 of every 3 deaths More than 1 of 3 (83 million) U.S. adults currently lives with one or more types of cardiovascular disease. Over 2 million heart attacks and strokes each year • $444 B in health care costs and lost productivity • Greatest contributor to racial disparities in life expectancy 7 Roger VL, et al. Circulation 2012;125:e2-e220 Heidenriech PA, et al. Circulation 2011;123:933–4 Stroke Subtypes Ischemic 80% Hemorrhagic 20% 2 11/12/2014 Stroke Ischemic Hemorrhagic Small vessel Lg. vessel Embolic Causes of Ischemic Stroke in Young Adults Eur Neurol 2007;57:212–218 CARDIOEMBOLIC SOURCES LV thrombus Valvular heart disease Prosthetic valves Acute MI 10% 10% 5% 15% Other less common sources (PFO, ASA, aortic debris, etc.) 10% 50% Nonvalvular Atrial Fibrillation 3 11/12/2014 Definition of Cardioembolic Stroke • Embolism of material forming on or crossing through the atrial or ventricular wall or heart valves • Particles/debris embolize to the arterial circulation of a brain region • Embolus is: Thrombus, fat, air, cancer cells, clumps of bacteria, etc… Clinical Characteristics of Cardioembolic Stroke • Sudden in onset, with maximum neurologic deficit at once • Decreased consciousness at onset • Embolism to other brain regions • Embolism to other organs • Palpitations at onset Clinical Characteristics of Cardioembolic Stroke • Generally worse prognosis than thrombotic strokes as the area infarcted is usually larger due to large emboli • Emboli from the heart most often lodge in the MCA, PCA, and infrequently ACA 4 11/12/2014 Cardiac Workup of the Patient with Stroke: What to Look For • • • • • • Cardiac arrhythmias Cardiac murmurs Signs of Heart Failure Recent MI Concomitant diseases ( eg. endocarditis) Signs of systemic embolism Physical Exam • Neurologic Exam • Cardiac Exam • Vascular Exam (Carotid Bruits, • • Peripheral Pulses) Dermatologic • Splinter hemorrhages and needle tracks (endocarditis) • Xanthoma (hyperlipidemia) Ophthalmologic Cardiovascular Diagnostic Testing for Patients With Stroke • • • • • • Carotid ultrasonography Transthoracic echocardiography Transesophageal echocardiography Electrocardiogram Prolonged ECG monitoring with Holter or event loop recorder (external or implantable) Blood studies (Thrombophilia panel) 5 11/12/2014 Embolic Risk of Various Cardiac Lesions High Risk Medium Risk Low/Unclear Risk Atrial fibrillation/flutter LV hypokinesia / aneurysm Patent foramen ovale Recent anterior MI Bioprostetic valve Mechanical valve LV systolic dysfunction Atrial septal aneurysm Rheumatic mitral stenosis Thrombus / tumor (myxoma) ? Myxomatous MVP Spontaneous echo contrast SSS Endocarditis Additional (Minor risk) sources • Calcific Aortic Valve or Bicuspid Aortic Valve • Mitral Annular Calcification • Fibroelastomas (benign tumors on valves) • Lambl’s excrescences (filliform • • outgrowths from free borders of valves) LV regional wall motion abnormality Aortic arch atheromatous plaques Treatment • Primary prophylaxis depends on • the particular risk factor but centers primarily around anti-coagulation, especially in the high-risk group (except for endocarditis and myxoma) Primary prophylaxis for medium or low risk factors is less clear as benefit of anti-coagulation is not yet proven 6 11/12/2014 Stroke Is the Most Common and Devastating Complication of AF • All-cause stroke rate with AF is 5% per year • AF - independent risk factor for stroke • ~5-fold increase in stroke risk • ~15% of all strokes caused by AF • Stroke risk increases with age • Stroke risk persists asymptomatic AF Fuster V, et al. Circulation. 2006;114:e257-e354. Wolf PA, et al. Stroke. 1991;22:983-988. Page RL, et al. Circulation. 2003;107:1141-1145. Hart RG, et al. J Am Coll Cardiol. 2000;35:183-187. 90% of Clots Reside in the Appendage Stroke Risk in AF: CHADS2 Score Risk Factor Points C Congestive HF 1 H Hypertension 1 A Age ≥ 75 1 D Diabetes 1 S2 Prior Stroke/TIA 2 Gage BF, et al. JAMA. 2001;285:2864-2870. 7 11/12/2014 Risk of Stroke Without Warfarin in National Registry of Atrial Fibrillation (NRAF) by CHADS2 Score 50 40 10 5 *Crude stroke rate per 100 patient-years 0 0 1 2 3 4 CHADS2 Score 5 6 Gage BF, et al. JAMA. 2001;285:2864-2870. Clot Prevention: Management Options Medical Management: Anticoagulant Surgical Excision (Appendectomy) Transcatheter Device Closure Warfarin vs Placebo in Stroke Prevention in AF AFASAK-1 SPAF BAATAF CAFA SPINAF EAFT ALL Trials 100% 50% Favors Warfarin Warfarin reduces incidence of stroke by ~64% 0% -50% -100% Favors Placebo/ Control Hart R, et al. Ann Intern Med. 2007;146:857-867. 8 11/12/2014 Aspirin vs Placebo in Stroke Prevention in AF AFASAK-1 SPAF I EAFT ESPS-II LASAF, daily LASAF, alternate day UK-TIA, 300 mg daily UK-TIA, 1200 mg daily JAST Aspirin Trials SAFT ESPS II, Dipyridamole ESPS II, Combination All Trials 100% 50% 0% Favors Antiplatelet Antiplatelet therapy reduces incidence of stroke by ~22% -50% -100% Favors Placebo/ Control Hart R, et al. Ann Intern Med. 2007;146:857-867. Warfarin vs Antiplatelet Therapy in Stroke Prevention in AF AFASAK I AFASAK II Chinese ATAFS EAFT PATAF SPAF II, ≤ 75 yrs SPAF II, >75 yrs Aspirin trials Warfarin reduces incidence of stroke by ~39% SIFA ACTIVE-W NASPEAF All Trials 100% 50% 0% Favors Warfarin -50% -100% Favors Antiplatelet Hart R, et al. Ann Intern Med. 2007;146:857-867. Antithrombotic Therapy – A CHADS2 Risk Score-based Approach 0 • None* • Aspirin 1 ≥2 • OA* • DAPT • OA* • DAPT CHA2DS2-VASc OA: oral anticoagulation DAPT: dual antiplatelet therapy (ASA/Clopidogrel) * Preferred strategy Additional risk factors: Female gender Age 65 to 74 y Vascular disease ACCP 2012 Guidelines 9 11/12/2014 Newer Therapies Factor Xa Inhibitors and Direct Thrombin Inhibitors Tissue Factor/VIIa IX X IXa VIIIa Rivaroxaban Apixaban Edoxaban (DU-176b) Va Xa II IIa Fibrinogen Dabigatran Fibrin Harenberg J. Semin Thromb Hemost. 2009;35:574-586. Novel Oral Anticoagulants in Atrial Fibrillation: A Meta-analysis of Large, Randomized, Controlled Trials vs Warfarin Trials included in analysis: SPORTIF III, SPORTIF IV, RE-LY, ROCKET AF, ARISTOTLE Dogliotti et al. Clin. Cardiol. 2013 Non-Pharmacologic Approaches • Surgery • Percutaneous left atrial exclusion Amplatzer Watchman Lariat Class IIb, level of evidence B 2014 AHA/ASA Stroke Guidelines 10 11/12/2014 When to start anticoagulation in patients with stroke in the setting of AF? Within 14 days for most patients. Delay beyond 14 days in patients with high risk of hemorrhagic conversion 2014 AHA/ASA Stroke Guidelines Mechanism of stroke with PFO • Paradoxical embolism • Valsalva inducing activities? • Occult DVT? • ASA and thrombus? • Large PFO? • Atrial arrythmias? Mas et al. 2001 11 11/12/2014 WARCEF: HF with EF≤ 35%, no AF; 2305 patients • Significant reduction in the occurrence of ischemic stroke among patients on warfarin. • This benefit was tempered by an increased risk of major hemorrhage in the warfarin group NEJM 2012 Mitral stenosis: 1ary prevention Associated condition Treatment Prior embolic event Anticoagulation Class of Rec. I, B Left atrial thrombus Anticoagulation I, B LA ≥55 mm Anticoagulation IIb, B Large atrium, Spontaneous Anticoagulation echocontrast IIb, C AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014 Valve replacement: 1ary prevention Associated condition Aortic, mechanical, no risk factors Treatment Warfarin (2-3), aspirin Class of Rec. I, B Aortic, mechanical, risk factors Warfarin (2.5-3.5), aspirin I, B Mitral, mechanical Warfarin (2.5-3.5), aspirin I, B Aortic, bioprosthetic Aspirin Warfarin (2-3) for 3 months Mitral, bioprosthetic Aspirin Warfarin (2-3) for 3 months IIa, B IIa, C IIa, B IIa, C AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014 12 11/12/2014 Other conditions: 1ary prevention Condition Treatment Class of Rec. Myxoma Surgery I, C Heart failure, no AF, no prior embolic event Anticoagulant/ antiplatelet IIa, B Fibroelastoma, symptomatic Surgery I, B Fibroelastoma, asymptomatic, Surgery >1 cm , mobile LV thrombus post MI Anticoagulation IIa, B IIa, C IIa, C LV aneurysm post MI Anticoagulation IIb, C PFO, no prior stroke Antithrombotic/ III, C catheter therapy AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014 Other conditions: 2ary prevention Condition Treatment Class of Rec. Heart failure, LA or LV thrombus Anticoagulation I, C Heart failure, LVAD LV thrombus post MI Anticoagulation Anticoagulation IIa, C IIa, C LV aneurysm post MI Anticoagulation IIb, C Aortic Arch Atheroma Antiplatelets I, A Statins I, B Anticoagulation IIb, C Surgery III, C AHA/ASA Guidelines for the secondary prevention of stroke. Stroke 2014 PFO: 2ary prevention Condition Treatment Class of Rec. If no indication for OAC DVT Antiplatelet Anticoagulation I, B I, A DVT, Anticoagulation C/I IVC filter IIa, C No DVT Closure III, A DVT Closure IIb, C AHA/ASA Guidelines for the secondary prevention of stroke. Stroke 2014 13 11/12/2014 Conclusions • Multiple structural heart defects are associated with embolic stroke • The diagnosis relies on detection of • • potential emboligenic sources in the absence of another etiology of equal or greater plausibility Imaging, including TEE is important Treatment (medical/catheter based/surgical) depends on the risk associated with the condition and requires a multidisciplinary approach [email protected] 14