The GLACE Study: Evaluating CLAAS With ICE Guided LAA Closure

Inclusion Criteria:

1. Male or non-pregnant female aged ≥18 years.

2. Documented non-valvular AF (paroxysmal, persistent, or permanent).

3. High risk of stroke or systemic embolism, defined as CHADS2 score of ≥2 orCHA2DS2-VASc score of ≥3.

4. Has an appropriate rationale to seek a non-pharmacologic alternative to long-termoral anticoagulation including contraindications to long term oral anti-coagulationinclusive of history of intracranial bleed, subdural hematoma, gastrointestinalbleeding, hematuria, epistaxis, falls, and other less common conditions. Alsoincluded is the inability to reliably take medications and reluctance to take ablood thinner.

5. Deemed by investigator to be suitable for short term oral anticoagulation therapybut deemed less favorable for long-term oral anticoagulation therapy.

6. Deemed appropriate for LAA closure by the site investigator and a clinician not apart of the procedural team using a shared decision-making process in accordancewith standard of care.

7. Able to comply with the protocol-specified medication regimen and follow-upevaluations.

8. The patient has been informed of the nature of the study, agrees to its provisions,and has provided written informed consent approved by the appropriate institutionalreview board (IRB)/Regional Ethics Board (REB)/Ethics Committee (EC).

Exclusion Criteria:

1. Pregnant or nursing patients and those who plan pregnancy in the period up to oneyear following the index procedure. Female patients of childbearing potential musthave a negative pregnancy test (per site standard test) within 7 days prior to indexprocedure.

2. Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., prior atrial septal defect [ASD] or patent foramen ovale [PFO], surgicalrepair or implanted closure device, or obliterated or ligated left atrialappendage).

3. Atrial fibrillation that is defined by a single occurrence or that is transient orreversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma,recent major surgical procedures).

4. A medical condition (other than atrial fibrillation) that mandates long-term oralanticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonaryembolism, or mechanical heart valve).

5. History of bleeding diathesis or coagulopathy, or patients in whom antiplateletand/or anticoagulant therapy is contraindicated.

6. Documented active systemic infection.

7. Symptomatic carotid artery disease (defined as >50% stenosis with symptoms ofipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateralhemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stentor endarterectomy the subject is eligible if there is <50% stenosis noted at thesite of prior treatment.

8. Recent (within 30 days of index procedure) or planned (within 60 dayspost-procedure) cardiac or non-cardiac interventional or surgical procedure.

9. Recent (within 30 days of index procedure) stroke or transient ischemic attack.

10. Recent (within 30 days of index procedure) myocardial infarction.

11. Vascular access precluding delivery of implant with catheter-based system.

12. Severe heart failure (New York Heart Association Class IV).

13. Prior cardiac transplant, history of mitral valve replacement or transcathetermitral valve intervention, or any mechanical valve implant.

14. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation).

15. Platelet count <75,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <3,000 cells/mm3.

16. Known allergy, hypersensitivity or contraindication to aspirin, heparin, or devicematerials (e.g., nickel, titanium) that would preclude any P2Y12 inhibitor therapy,or the patient has contrast sensitivity that cannot be adequately pre-medicated.

17. Actively enrolled or plans to enroll in a concurrent clinical study in which theactive treatment arm may confound the results of this study.

18. Unable to undergo general anesthesia.

19. Known other medical illness or known history of substance abuse that may causenon-compliance with the protocol or protocol-specified medication regimen, confoundthe data interpretation, or is associated with a life expectancy of less than 5years.

20. A condition which precludes adequate transesophageal echocardiographic (TEE)assessment or ICE guided imaging during the procedure.

Imaging Exclusion Criteria:

1. Left atrial appendage anatomy which cannot accommodate the CLAAS device permanufacturer IFU (e.g., the anatomy and sizing must be appropriate for the test (CLAAS) device in order to be enrolled in the trial).

2. Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus,as visualized by pre-procedural imaging (TEE or Cardiac CT) or baseline proceduralICE prior to implant.

3. Left ventricular ejection fraction (LVEF) <30%.

4. Moderate or large circumferential pericardial effusion >10mm or symptomaticpericardial effusion, signs or symptoms of acute or chronic pericarditis, orevidence of tamponade physiology.

5. Atrial septal defect that warrants closure.

6. High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion >15mm or length >15mm) or large shunt (early [within 3 beats] and/orsubstantial passage of bubbles, e.g., ≥20).

7. Moderate or severe mitral valve stenosis (mitral valve area <1.5cm2).

8. Complex atheroma with mobile plaque of the descending aorta and/or aortic arch.

9. Evidence of cardiac tumor.