Early Feasibility Study (EFS) Evaluating Percutaneous Repair of the Atrial Septum With a Novel PFO Occluder: The PROTEA-PFO Study

Inclusion Criteria:

1. Patient must be ≥ 18 and ≤ 65 years of age

2. 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.

3. Ischemic stroke, defined as acute focal neurological deficit, presumed to be due tofocal ischemia and confirmed by MRI or CT to have a neuroanatomically relevantcerebral infarct.

4. Modified Rankin score (mRS) ≤ 3.

5. Appropriate PFO anatomy for implantation of the investigational device as evaluatedand determined by independent committee.

6. Patient is willing and capable of providing informed consent.

7. Prior to index procedure (7-day window), persons of childbearing potential must havea negative pregnancy test.

Exclusion Criteria:

1. Other identifiable causes of stroke, including but not limited to aortic archplaques (protruding >4 mm into the lumen), large artery atherosclerotic diseaseproximal to the territory of the index stroke, an established cardioembolic source,small-vessel occlusive disease, or arterial dissection, presence of left atrialappendage thrombus.

2. Other arteriopathy of the intracranial or extracranial vessels with >50% stenosisproximal to the territory of the index stroke.

3. Intracardiac thrombus or tumor.

4. Myocardial Infarction (MI) or unstable angina within the previous 180 days.

5. Life expectancy < 2 years.

6. Left ventricular aneurysm or akinesis.

7. Moderate to severe mitral valve stenosis or severe mitral regurgitation.

8. Aortic valve stenosis (mean gradient >20 mmHg) or severe regurgitation.

9. Active endocarditis or other infection that may preclude implantation of theinvestigational device.

10. Any valve vegetation or Lambl's excrescence of any left-sided valve.

11. Left ventricular dilated cardiomyopathy with LVEF <35%.

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

13. History of atrial tachycardia, atrial fibrillation or flutter, AV block, orventricular arrhythmia requiring antiarrhythmic medication, pacemaker, or AICD.

14. Severe renal failure ( Stage 4 CKD, eGFR <30) or patient requiring dialysis.

15. Severe liver disease (e.g., documented cirrhosis or active hepatitis).

16. Severe lung insufficiency (e.g., need for supplemental oxygen or chronic steroidmedications).

17. Uncontrolled hypertension, defined as sustained elevated blood pressure >140/90 mmHg.

18. Severe pulmonary artery hypertension, defined as pulmonary systolic pressure of >50mmHg.

19. Uncontrolled hyperglycemia, defined as HbA1c value >8% (IFCC: >64 mmol/mol).

20. Increased bleeding risk such as severe liver failure, active peptic ulcer,proliferative diabetic retinopathy, history of severe bleeding (e.g.:gastrointestinal bleeding, macroscopic hematuria, intraocular bleeding, intracranialor cerebral hemorrhage), or other history of bleeding or coagulopathy.

21. Known hypercoagulable state that would require full anticoagulation. Minimum testingto include lupus anticoagulant, anticardiolipin antibodies, beta-2-glycoprotein,homocysteine.

22. Subjects contraindicated for aspirin or clopidogrel.

23. Subjects not able to discontinue anticoagulation for indications other than thenindex stroke.

24. Any disorder in the investigator's opinion that could interfere with compliance ofsafety evaluation or require premature discontinuation of antiplatelet regimepost-implantation, as well as any severe concurrent illness that would limit lifeexpectancy (e.g., malignancies).

25. Currently an active subject in an investigational drug or device study that couldconfound the results of this study.

26. Any significant valve dysfunction that contraindicates PFO closure or increasedpulmonary vascular resistance/severe pulmonary hypertension.

27. Contraindication for transesophageal echocardiography (TEE) or intracardiacechocardiography (ICE).

28. Any prior percutaneous cardiovascular intervention for AF ablation.