Assessing the Safety and Efficacy of the LAmbre™ Plus Device

Inclusion Criteria:

• The patient is a male or non-pregnant female ≥18 years of age

• The patient has documented paroxysmal, persistent, or permanent non- valvular atrialfibrillation

• The patient has a CHADS2 score ≥ 2 or a CHA2DS2-VASc score of ≥ 3, and isrecommended for oral anticoagulation therapy

• The patient is deemed by their physician to be suitable for short-term warfarintherapy, but there is an appropriate rationale for seeking a non-pharmacologicalternative to oral anticoagulation

• The patient is deemed suitable for LAA closure by a multidisciplinary heart team,including at least 1 investigator (e.g. cardiologists) and 1 clinician not involvedas part of the procedure team using a shared decision making process, and thisdetermination has been documented in the patient's medical record

• The patient is willing and able to comply with protocol-specified treatment andfollow-up evaluations

• The patient (or his or her legally authorized representative) has been informed ofthe nature of the study, agrees to its provisions, and has been provided writteninformed consent approved by the appropriate Institutional Review Board (IRB) orEthics Committee (EC)

Exclusion Criteria:

• Pregnant or nursing patients and those who plan pregnancy in the period up to 1 yearfollowing index procedure. Female patients of childbearing potential must have anegative pregnancy test done within 7 days prior to index procedure per sitestandard test.

• Patients with atrial fibrillation that is defined by a single occurrence, or that istransient or reversible (e.g., secondary to CABG, an interventional procedure,pneumonia, or hyperthyroidism)

• Patients who require long-term anticoagulation for a condition other than atrialfibrillation

• Patients with an indication for chronic P2Y12 platelet inhibition therapy

• Patients not suitable for short term warfarin (including due to bleeding diathesisor coagulopathy or absolute contraindication warfarin) or who will refusetransfusion

• Patients with rheumatic mitral valve disease, known severe aortic stenosis requiringsurgical or percutaneous valve replacement, or existing mechanical valve prosthesis

• Active infection with bacteremia

• Known hypersensitivity or contraindication to aspirin, clopidogrel,heparin/bivalirudin, any device material or component (nitinol, nickel, titanium,PET), and/or contrast sensitivity that cannot be adequately pre-medicated

• Anatomic conditions that would prevent performance of the LAA occlusion procedure (e.g., prior atrial septal defect [ASD] or patient foramen ovale [PFO] surgicalrepair or implanted closure device, or obliterated left atrial appendage)

• Recent (within 30 days pre-procedure) or planned (within 60 days post- procedure)cardiac or non-cardiac interventional or surgical procedure (e.g., cardioversion,ablation, percutaneous coronary intervention, cataract surgery, etc.)

• Recent (within 90 days pre-procedure) stroke, transient ischemic attack, ormyocardial infarction

• Severe heart failure (New York Heart Association Class IV)

• Known asymptomatic carotid artery disease with>70% diameter stenosis OR symptomaticcarotid disease (>50% diameter stenosis with ipsilateral stroke or TIA). Subjectswith prior carotid endarterectomy or carotid stent placement may be enrolled,provided that known diameter stenosis is <50%.

• Past or pending heart or any other organ transplant, or on the waiting list for anyorgan transplant

• Known other medical illness or known history of substance abuse that may causenon-compliance with the protocol, confound data interpretation, or is associatedwith a life expectancy of less than 2 years

• Current participation in another investigational drug or device studyEchocardiographic Exclusion Criteria

• Left atrial appendage anatomy cannot accommodate either the LAmbre Plus LAAO deviceor the Control device per manufacturer IFU (e.g., the anatomy and sizing must be forboth device to be enrolled in the trial or maximum LAAO length < maximum ostiumwidth by TEE)

• LVEF <30%

• Intracardiac thrombus or dense spontaneous echo contrast, as visualized by TEEwithin 2 days prior to implant

• Moderate or large circumferential pericardial effusion >10 mm or symptomaticpericardial effusion, signs or symptoms of acute or chronic pericarditis, orevidence of tamponade physiology. In the event of a treatable pericardial effusion,the subject may undergo implantation at a later time after it is adequately treated.

• Atrial septal defect that warrants closure.

• Presence of a high risk patent foramen ovale (PFO), defined as an atrial septalaneurysm (excursion >15 mm or length >15 mm) or large shunt (early, within 3 beatsand/or substantial passage of bubbles)

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

• Complex atheroma with mobile plaque of the descending aorta and/or aortic arch (Grade 4 or higher)

• Evidence of a Cardiac Tumor