1. Transthoracic Echocardiography in Cerebrovascular Disease Nisha I Parikh, MD MPH Noninvasive Imaging Conference May 14 th 2008

2. Overview Pathophysiology of CVA Pathophysiology of CVA Role of TTE in CVA Role of TTE in CVA Role of PFO testing in CVA Role of PFO testing in CVA Cost Effectiveness of TTE in Stroke Cost Effectiveness of TTE in Stroke Epidemiologic TTE Markers of Incident CVA Epidemiologic TTE Markers of Incident CVA

3. Pathophysiology of CVA Ischemic Stroke Thrombotic Embolic Large Vessel Small Vessel ExtracranialIntracranial Definite Cardioembolic Source Possible Cardioembolic Source Ascending Aortic Atheroma True Unknown Embolic Source * Common Carotid * ICA, ECA * Vertebral artery * Circle of Willis * Proximal Branches

4. Cerebrovascular Circulation Up to date

5. Cardioembolic Sources- Definite Left atrial thrombus Atrial fibrillation Sustained atrial flutter Recent AMI Rheumatic mitral or aortic disease Mechanical or bioprosthetic valve Low EF < 30% Chronic AMI EF < 28% Dilated Cardiomyopathy Endocarditis Atrial myxoma

6. Cardioembolic Sources-Possible PFO Atrial septal aneurysm PFO with atrial septal an. Mitral Annular Calcium Mitral Valve Strands LV aneurysm Isolated left atrial smoke

7. LV thrombus

8. Large Atrial Myxoma

9. Role of TTE in CVA Diagnosis and Management

10. Echocardiography in CVA Appropriateness Criteria for Echocardiography “ Symptoms potentially due to suspected cardiac etiology, including but not limited to dyspnea, shortness of breath, lightheadedness, syncope, TIA, cerebrovascular events” Score: 9 (Max=9) Douglas et al. JACC

11. Review: TTE abnormalities in patients < 45 years of age Beattie, Cohen, Manning, Douglas, Journal of Internal Medicine, 1998

12. Review: TTE abnormalities in patients ≥ 45 years of age Beattie, Cohen, Manning, Douglas, Journal of Internal Medicine, 1998

13. “Therapy Implications of Transthoracic Echocardiography in Acute Ischemic Stroke Patients ” Prospective observational study Prospective observational study Évora, Portugal Évora, Portugal TTE on all patients admitted to hospital with ischemic stroke, in sinus rhythm (mean age 76) TTE on all patients admitted to hospital with ischemic stroke, in sinus rhythm (mean age 76) January 7, 2002, to October 16, 2003. January 7, 2002, to October 16, 2003. Findings compatible with heart diseases that would indicate anticoagulation as beneficial were identified. Findings compatible with heart diseases that would indicate anticoagulation as beneficial were identified. de Abreu et al, J. Stroke 2005

14. Findings #(%) No findings suggesting need of anticoagulation 273 (62.8) Dilated cardiopathy 83 (19.1) Anterior wall dyskinesis 27 (6.2) Left ventricle ejection fraction <35% 16 (3.7) Mitral valve stenosis with left atria >55 mm 9 (2.1) Intracardiac masses 2 (0.5) Valve prosthesis 1 (0.2) Mitral valve stenosis with left atria >55 mm+dilated cardiopathy 7 (1.6) Dilated cardiopathy+anterior wall dyskinesis 9 (2.1) Dilated cardiopathy+left ventricle ejection fraction <35% 8 (1.8) Total 435 (100.1) Echocardiography Findings (n=435) de Abreu et al, J. Stroke 2005

15. Author Conclusions “In our study, transthoracic echocardiography had therapy implications in 37.2% of ischemic stroke patients in sinus rhythm.” “In our study, transthoracic echocardiography had therapy implications in 37.2% of ischemic stroke patients in sinus rhythm.” “Transthoracic echocardiography should be considered an essential test in all ischemic stroke patients in sinus rhythm.” “Transthoracic echocardiography should be considered an essential test in all ischemic stroke patients in sinus rhythm.” de Abreu et al, J. Stroke 2005

16. Usefulness of Cardiovascular Investigations in Stroke Management The outcome of cardiovascular investigations in 200 patients with stroke/transient ischemic attack The outcome of cardiovascular investigations in 200 patients with stroke/transient ischemic attack Stroke Prevention Clinic Stroke Prevention Clinic Ontario, Canada Ontario, Canada TTE in 71% (142/200) of patients TTE in 71% (142/200) of patients Pertinent cardiac findings were uncovered in only 6 (4%) patients Pertinent cardiac findings were uncovered in only 6 (4%) patients TTE did not alter antithrombotic therapy in any of the 142 patients studied TTE did not alter antithrombotic therapy in any of the 142 patients studied Douen et al., Stroke 2007

17. Patent Foramen Ovale  10-20% of Adults  Usually Asymptomatic

18. Echo: PFO

19. Therapeutic options for PFO associated with CVA Anticoagulation Anticoagulation Antiplatelet therapy Antiplatelet therapy Surgical PFO closure Surgical PFO closure Transcatheter closure Transcatheter closure

20. PFO Closure Device

21. “Effect of Medical Treatment in Stroke Patients With Patent Foramen Ovale Patent Foramen Ovale in Cryptogenic Stroke Study“ The PFO in Cryptogenic Stroke Study The PFO in Cryptogenic Stroke Study 42-center study 42-center study TEE findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study TEE findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study 630 stroke patients were enrolled 630 stroke patients were enrolled - 312 (49.5%) were randomized to warfarin - 318 (50.5%) to aspirin 265 with cryptogenic stroke and 365 with known stroke subtypes 265 with cryptogenic stroke and 365 with known stroke subtypes End points, recurrent ischemic stroke or death End points, recurrent ischemic stroke or death PFO present in 203 patients (33.8%) PFO present in 203 patients (33.8%) Homma et al, Circ 2002

22. Copyright ©2002 American Heart Association Homma, S. et al. Circulation 2002;105:2625-2631 Kaplan-Meier curves of cumulative risk of recurrent stroke or death stratified by baseline PFO status

23. Authors Conclusion We demonstrate that when the stroke patients are treated medically, the rate of recurrent stroke or death is similar between patients with and without PFO. We demonstrate that when the stroke patients are treated medically, the rate of recurrent stroke or death is similar between patients with and without PFO. Homma et al, Circ 2002

24. Cost Effectiveness of TTE in CVA

25. McNamara, R. L. et. al. Ann Intern Med 1997;127:775-787 Nine possible diagnostic strategies for patients with stroke

26. Cost-effectiveness of diagnostic strategies compared with the treat-none strategy McNamara, R. L. et. al. Ann Intern Med 1997;127:775-787

27. Cost Effectiveness of TTE in CVA Transthoracic echocardiography, alone or in sequence with transesophageal echocardiography, was not cost-effective compared with transesophageal echocardiography* Transthoracic echocardiography, alone or in sequence with transesophageal echocardiography, was not cost-effective compared with transesophageal echocardiography* All strategies containing TTE were dominated by others and were eliminated from the analysis** All strategies containing TTE were dominated by others and were eliminated from the analysis** Current evidence on cost-effectiveness is insufficient to justify widespread use of echocardiography in stroke patients. Current evidence on cost-effectiveness is insufficient to justify widespread use of echocardiography in stroke patients. Additional research on recurrent stroke risk may contribute to a better understanding of the circumstances under which echocardiography will be cost-effective Additional research on recurrent stroke risk may contribute to a better understanding of the circumstances under which echocardiography will be cost-effective - in patients with intracardiac thrombus - in patients with intracardiac thrombus - on the efficacy of AC in reducing that risk - on the efficacy of AC in reducing that risk * McNamara, R. L. et. al. Ann Intern Med 1997;127:775-787 ** Meenan RT et al, Med Dec Making, 2007

28. Echocardiographic Predictors of CVA from Epidemiologic Studies

29. Valvular Calcification

30. Valvular Calcification: Framingham Heart Study MAC and stroke of RR=2.10 (95% CI 1.24 to 3.57; P = 0.006). MAC and stroke of RR=2.10 (95% CI 1.24 to 3.57; P = 0.006). Continuous relation between the incidence of stroke and the severity of MAC; each millimeter of thickening as shown on the echocardiogram represented RR of stroke of 1.24 (95% CI, 1.12 to 1.37; P less than 0.001). Continuous relation between the incidence of stroke and the severity of MAC; each millimeter of thickening as shown on the echocardiogram represented RR of stroke of 1.24 (95% CI, 1.12 to 1.37; P less than 0.001). Even when subjects with coronary heart disease or CHF were excluded from the analysis, subjects with MAC still had twice the risk of stroke. Even when subjects with coronary heart disease or CHF were excluded from the analysis, subjects with MAC still had twice the risk of stroke. Benjamin EJ et al, NEJM 1992

31. Copyright ©2005 American Heart Association Kizer, J. R. et al. Stroke 2005;36:2533-2537 Strong Heart Study B. MAC and incident stroke. B. AV sclerosis and incident stroke

32. LA Size

33. Copyright ©1995 American Heart Association Benjamin, E. J. et al. Circulation 1995;92:835-841 Age-adjusted cumulative incidence of stroke by tertile of left atrial (LA) size in men and women MEN WOMEN

34. LV Mass: ARIC Fox ER, Stroke, 2007

35. Conclusions Cardioembolic Source of CVA may be present in 6-40% of patients depending on the population studied Cardioembolic Source of CVA may be present in 6-40% of patients depending on the population studied TTE is recommended as initial evaluation in CVA TTE is recommended as initial evaluation in CVA Assessment of PFO is controversial given a high population prevalence of this condition, uncertain treatment efficacy and lack of definite link to the disease state Assessment of PFO is controversial given a high population prevalence of this condition, uncertain treatment efficacy and lack of definite link to the disease state The Cost Benefit of TTE in CVA has not been established and widespread use may preclude estimates The Cost Benefit of TTE in CVA has not been established and widespread use may preclude estimates MAC, LA size and LVM predict incident stroke MAC, LA size and LVM predict incident stroke