1. Κρυπτογενές ισχαιμικό έμφρακτο Γεώργιος Ντάιος Επίκουρος Καθηγητής Παθολογίας, Πανεπιστήμιο Θεσσαλίας 3 ο Συνέδριο ΙΜΕΘΑ Αθήνα, 24/4/2014

2. Disclosures Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis. Honoraria: Medtronic; Quintiles; CHUV; Belgian Stroke Council; Boehringer-Ingelheim. Speaker fees: Sanofi; Boehringer-Ingelheim, Galenica Support to attend conferences: Bayer; Sanofi-Aventis; Pfizer; Lundbeck; Boehringer- Ingelheim; Galenica; Elpen; Bristol Myers Squibb. Participation in trials: – NAVIGATE-ESUS / National Coordinator (Greece) – GLORIA-AF / Sub-investigator (Larissa). – FOURIER / Principal investigator (Larissa). – ENOS / National Coordinator (Greece). – EBBINGHAUS / Principal Investigator (Larissa). – PRECIOUS / National Coordinator (Greece). – BIOSIGNAL / Principal Investigator (Larissa). – PREVISE / Principal investigator (Larissa).

3. TOAST classification Adams. Stroke 1993

4. TOAST classification ?

5. Cryptogenic stroke: what actually do you mean? Cryptogenic Not investigatedMultiple causesReally cryptogenic

6. Cryptogenic stroke & antithrombotic treatment ♀, 77yrs Right hemiparesis - aphasia Arterial hypertension LDL: 83mg/dl

7. Cryptogenic stroke & antithrombotic treatment Which antithrombotic ? Aspirin Triflusal Clopidogrel Aspirin & Clopidogrel Acenocoumarol Apixaban Dabigatran Rivaroxaban

8. AHA Stroke Guidelines Furie. Stroke 2010

9. Cryptogenic stroke: not rare

10. Cryptogenic stroke: not innocent Ntaios, Vemmos. Eur J Neurol. 2014; 21:1108-14

11. Hart. Lancet Neurol 2014; 13: 429–38 ESUS: Embolic Strokes of Undetermined Source

13. Lacunar strokes are not embolic

14. ESUS: Embolic Strokes of Undetermined Source

15. ESUS: potential causes Hart. Lancet Neurol 2014; 13: 429–38

16. ESUS: diagnostic criteria Hart. Lancet Neurol 2014; 13: 429–38 Stroke detected by CT or MRI that is not lacunar. Absence of extracranial or intracranial atherosclerosis causing >50% luminal stenosis in arteries supplying the area of ischemia. No major-risk cardioembolic source of embolism ( permanent or paroxysmal AF, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) MI, LVEF<30%, valvular vegetations, or infective endocarditis ). No other specific cause of stroke identified.

17. ESUS: diagnostic algorithm Hart. Lancet Neurol 2014; 13: 429–38 Brain CT or MRI 12-lead ECG Precordial echocardiography Imaging of both extra- and intracranial arteries supplying the area of brain ischemia Cardiac monitoring for ≥24hours with automated rhythm detection

18. Sanna. N Engl J Med 2014;370:2478-86 CRYSTAL-AF

19. 30.0% vs. 3.0% CRYSTAL-AF Sanna. N Engl J Med 2014;370:2478-86

20. EMBRACE Gladstone. N Engl J Med 2014;370:2467-77

21. EMBRACE Gladstone. N Engl J Med 2014;370:2467-77

22. ESUS in the Athens Stroke Registry Ntaios, Vemmos. Stroke 2015; 46:176-81

24. Mitral valve Myxomatous valvulopathy with prolapse5 (1.8%) Mitral annular calcification8 (2.9%) Aortic valve Aortic valve stenosis3 (1.1%) Calcific aortic valve12 (4.4%) Non-atrial fibrillation atrial dysrhythmias and stasis Atrial asystole and sick-sinus syndrome3 (1.1%) Atrial high-rate episodes7 (2.6%) Atrial appendage stasis with reduced flow velocities or spontaneous echodensities6 (2.2%) Atrial structural abnormalities Atrial septal aneurysm10 (3.6%) Chiari network0 Left ventricle Moderate systolic or diastolic dysfunction (global or regional)42 (15.4%) Ventricular non-compaction12 (4.4%) Endomyocardial fibrosis1 (0.4%) Covert paroxysmal atrial fibrillation (detected during follow-up) Atrial fibrillation detected on stroke recurrence-3030 (11.0%) Atrial fibrillation detected on monitoring during follow-up50 (18.3%) Atrial fibrillation not confirmed but strongly suspected38 (13.9%) Cancer-associated Covert non-bacterial thrombotic endocarditis1 (0.4%) Tumor emboli from occult cancer2 (0.8%) Arteriogenic emboli Aortic arch atherosclerotic plaques9 (3.3%) Cerebral artery non-stenotic plaques with ulceration29 (10.6%) Paradoxical embolism Patent foramen ovale11 (4.0%) Atrial septal defect3 (1.1%)

25. ESUS: 5-yrs stroke recurrence Ntaios, Vemmos. Stroke, in revision

26. AHA Stroke Guidelines Furie. Stroke 2010

27. NAVIGATE- ESUS Rivaroxaban 15mg 1x1 Aspirin 100mg 1x1 R

28. RESPECT - ESUS Dabigatran 110/150 1x2 Aspirin 100mg 1x1 R

29. -Everybody gets happy! -Half stroke patients get an anticoagulant!

30. Take-home messages Cryptogenic  ESUS ~10% of all stroke patients ESUS needs a complete (?) diagnostic work-up Covert AF is the most common underlying factor High(est?) recurrence rate NOACs to replace antiplatelets?

31. www.stroke.gr Join the Hellenic Stroke Organization !