Encore PFO Closure Device - The PerFOrm Trial

Inclusion Criteria:

1. Diagnosis of PFO, defined as visualization of microbubbles per TEE in the leftatrium within three cardiac cycles from the right atrial opacification demonstratingright-to-left shunting at rest and/or during Valsalva release

2. Cryptogenic stroke within the last 270 days; stroke is defined as acute focalneurological deficit, presumed to be due to focal ischemia, and confirmed by MRI orCT to be a new, neuroanatomically relevant cerebral infarct

Exclusion Criteria:

1. Age <18 years and age >60 years

2. Greater than 50% lumen diameter stenosis of intracranial or extracranial vessels

3. Intracardiac thrombus or tumor

4. Acute or recent (within 6 months) myocardial infarction (MI) or unstable angina

5. Left ventricular aneurysm or akinesis

6. Mitral valve stenosis (mitral valve area less than 1.5cm2) or severe mitralregurgitation

7. Aortic valve stenosis (gradient >40 mmHg) or severe aortic valve regurgitation

8. Mitral or aortic valve vegetation or prosthesis

9. Left ventricular ejection fraction <35%

10. Other identifiable cause of stroke, including but not limited to aortic arch plaques (protruding >4 mm into the lumen), large artery atherosclerotic disease, anestablished cardioembolic source, small-vessel occlusive disease, or arterialdissection

11. Evidence of a hypercoagulable disorder requiring anticoagulation therapy; thisdetermination will be based on the evaluation of: anticardiolipin antibody (Ab) ofthe IgG or IgM type, Lupus anticoagulant, B2-glycoprotein-1 Ab, and fasting plasmahomocysteine

12. Another source of right-to-left shunts identified at baseline, including an atrialseptal defect and/or fenestrated septum

13. Any history of atrial fibrillation/atrial flutter (chronic or intermittent)

14. Active endocarditis or other untreated infections

15. Chronic kidney disease stage 4 or higher or end-stage renal failure requiringdialysis (eGFR less than 30)

16. Severe liver disease (ALT 3X ULN) or documented cirrhosis

17. Lung disease requiring continuous home oxygen

18. Uncontrolled hypertension, defined as sustained elevated blood pressure >160/90 mmHg on medication

19. Uncontrolled diabetes mellitus, defined as HbA1c greater than 9 (based on mostrecent test which must have been collected within the last year)

20. Anatomical or physiological structures that do not permit TEE

21. Anticipated need for treatment of structural cardiac defects other than PFO

22. Concomitant cardiac anomalies requiring an operative procedure

23. Hemorrhagic diseases (e.g., coagulopathy, tendency to hemolysis)

24. Hypersensitivity to contrast medium or nickel

25. Contraindication to aspirin or clopidogrel

26. The required sheaths cannot be passed through the relevant vessels for access to thePFO

27. Vulnerable patient (e.g., incarcerated or cognitively challenged adults); seeSection 7.2.1

28. Subject is unable or unwilling to provide informed consent

29. Subject is unable to comply with the protocol

30. Any other clinical reasons for which the patient would not be an appropriatecandidate for the study, as determined by the site investigators