AtriClip® Left Atrial Appendage Exclusion Concomitant to Structural Heart Procedures (ATLAS)

Patients without a documented history of AF but who present with a CHA2DS2- VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category) of => 2 and HASBLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) of => 2 and will undergo a valve or CABG (structural heart) procedure with direct visual access to the LAA will be eligible to participate based upon the inclusion and exclusion criteria defined in this protocol. Up to 2000 patients will enroll at up to 40 sites and will be randomized 2:1 (2 with AtriClip to 1 without AtriClip. Subjects who not develop Post-operative Atrial Fibrillation (POAF) will be followed for 30 days for safety. Subjects who develop POAF and receive the AtriClip will be followed for 365 days post index procedure.

• AtriClip® Gillinov-Cosgrove™ LAA Exclusion Systems (Device), also known as AtriClip FLEX (ACH2), AtriClip Long (LAA), AtriClip Standard (ACH1)
• Anticoagulation Therapy (Drug), also known as Warfarin/Coumadin, New oral anticoagulants (NOACs): dabigatran, rivaroxaban, apixaban: Anticoagulation Therapy- Standard of Care at the discretion of the Investigator.

Primary outcomes

• Number of Perioperative Complications Associated With AtriClip Placement [Within any 24 hour period during the first 2 days post-index procedure]: Defined as: stroke, major bleeding that requires re-operation and/or transfusion of > 2 U packed red blood cells (PRBC), myocardial infarction (MI), or death.

Secondary outcomes

• Number of Subjects With Intraoperative Successful Exclusion of LAA. [Intraoperative period]: Successful exclusion of LAA is defined as no (0 mm) flow between LAA and LA and < 5 mm LAA remnant by intraoperative TEE with Doppler.
• Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) [365 days post index procedure]: Events to be evaluated include: Thromboembolic \& Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
• Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) [30 days Post-Procedure]: Events to be evaluated include: Thromboembolic \& Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
• Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days [365 Days Post-Procedure]: Events to be evaluated include: Thromboembolic \& Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) [365 Days Post-Procedure]: Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions.
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) [365 Days Post-Procedure]: Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions.
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) [365 Days Post-Procedure]: Specifically, reoperation for bleeding, neurologic consults for stroke or TIA, and emergency department (ED) visits.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Patients satisfying the following criteria will be considered the screening population and will be eligible for participation:

* Age > 18 years male or female.
* Scheduled for any non-mechanical valve and/or CABG (structural heart) procedure where direct access to the LAA is expected.
* No documented preoperative AF.
* CHA2DS2-VASc score of => 2.
* HASBLED score of => 2.
* Acceptable surgical candidate, including use of general anesthesia.
* Willing and able to provide written informed consent.

Exclusion Criteria:

Patients satisfying the following criteria will not be eligible for participation:

* Redo cardiac surgery.
* Mechanical heart valve or other anticipated or current requirement for anticoagulation therapy during the post-operative (30 day) period.
* Hypercoagulability conditions that may confound the study.
* Ejection Fraction < 30.
* Left Atrium > 6 cm.
* Severe Diastolic Dysfunction.
* Requires anticoagulation therapy.
* Patient had a stroke/cerebrovascular accident (CVA) within previous 30 days prior to signing informed consent.

Intra-Operative Exclusion Criteria

* Presence of thrombus in the left atrium or LAA.
* LAA tissue is deemed friable or has significant adhesions (as evaluated by the surgeon) near or on the LAA making AtriClip placement overly risky.
* Left atrial appendage is outside the range of manufacturer's recommendations - width < 29mm or > 50mm.
* Direct visualization access is not available for AtriClip placement.

Participant flow

Outcome results

• Number of Perioperative Complications Associated With AtriClip Placement (Primary), Number, perioperative complications reported: AtriClip® 0
• Number of Subjects With Intraoperative Successful Exclusion of LAA. (Secondary), Number, percentage of participants: AtriClip® 82.2 (77.9 to 85.9)
• Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) (Secondary), Number, percent of participants: AtriClip With OAC 19.6; AtriClip Without OAC 8.2; Standard of Care With OAC 16.0; Standard of Care Without OAC 6.5; Combined Standard of Care 9.9 (p 0.2593)
• Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) (Secondary), Number, percent of participants: AtriClip With OAC 5.0; AtriClip Without OAC 5.1; Standard of Care With OAC 0.0; Standard of Care Without OAC 8.0; Combined Standard of Care 7.8 (p 1.000)
• Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days (Secondary), Number, percent of participants: AtriClip With OAC 15.8; AtriClip Without OAC 6.7; Combined AtriClip 8.5; Standard of Care With OAC 14.8; Standard of Care Without OAC 7.5; Combined Standard of Care 8.6 (p 0.1238)
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) (Secondary), Mean, days: AtriClip With OAC 9.1 +/- 7.0; AtriClip Without OAC 8.1 +/- 5.2; Standard of Care With OAC 8.4 +/- 3.5; Standard of Care Without OAC 7.3 +/- 4.4 (p 0.6603)
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) (Secondary), Median, days: AtriClip With OAC 7.0 (3.0 to 43); AtriClip Without OAC 7.0 (1.0 to 49.0); Standard of Care With OAC 9.0 (3.0 to 17.0); Standard of Care Without OAC 6.0 (2.0 to 32.0) (p 0.6603)
• Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) (Secondary), Number, percentage of participants: AtriClip With OAC 3.9; AtriClip Without OAC 2.7; Standard of Care With OAC 3.7; Standard of Care Without OAC 1.3 (p 0.5442)

Adverse events

Time frame: 365 days post-procedure

Serious adverse events by term

Other adverse events by term

Limitations and caveats: ATLAS was an exempt post-market study therefore the use of oral anticoagulants could not be directed or standardized across the study sites. This led to a wide variation to the medical post-operative management in both the types drugs used for oral anticoagulation and dosage prescribed. Furthermore, the sample size for this feasibility study is relatively small to allow for a definitive conclusion on the impact of LAA occlusion and thromboembolic events.

• Study Protocol and Statistical Analysis Plan (PDF, 2017-02-15)

• Sydney Gaynor, MD, Study chair, AtriCure, Inc.