aMAZE Trial Continued Access Protocol

Study Overview
=================
Brief Summary
-----------------
aMAZE CAP is an extension to the current aMAZE Trial investigation (IDEG150107/NCT02517397/Protocol Appendix 16) in the form of a nested, non-randomized registry, to allow ongoing treatment of subjects and the collection of additional safety and effectiveness data at existing aMAZE investigational sites.

Detailed Description
-----------------
For consistency, aMAZE CAP primary and secondary safety and efficacy endpoints, eligibility criteria and follow up visit assessments remain unchanged from the current aMAZE Trial investigation (NCT02517397).

Official Title
-----------------
Non-randomized, Multicenter Expanded Use Evaluation of the LARIAT® Suture Delivery Device (Appendix 16 to Ongoing Investigation)

Conditions
-----------------
Atrial Fibrillation

Intervention / Treatment
-----------------
* Device: LARIAT + PVI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented diagnosis of symptomatic continuous persistent or longstanding persistent non-valvular atrial fibrillation Failed at least one Class I or III Antiarrythmic drug (AAD) and therefore, eligible and intended for standard of care catheter ablation; Life expectancy ≥ 1 year; Willing and able to return to and comply with scheduled follow-up visits and tests; and Willing and able to provide written informed consent Exclusion Criteria: Prior procedure involving opening of the pericardium or entering the pericardial space (e.g., coronary artery bypass graft, heart transplantation, valve surgery) where adhesions are suspected; Any prior epicardial ablation or any type of left-sided atrial ablation procedure; LA diameter > 6 cm as measured by computerized tomography and confirmed by the imaging core laboratory; Documented embolic stroke, transient ischemic attach or suspected neurologic event within 3 months prior to the planned study intervention; Currently exhibits New York Heart Association Class IV heart failure symptoms; Documented history of right heart failure specifically when right ventricle exceeds the left ventricular size; Documented history of myocardial infarction (MI) within 3 months prior to the planned study intervention; Documented history of unstable angina within 3 months prior to the planned study intervention; Documented history of cardiogenic shock, hemodynamic instability or any medical condition in which intra-aortic balloon pump (IABP) therapy is clinically indicated within 3 months prior to the planned study intervention; Documented symptomatic carotid disease, defined as > 70% stenosis or > 50% stenosis with symptoms; Diagnosed active local or systemic infection, septicemia or fever of unknown origin at tme of baseline screening; Chronic renal insufficiency defined as eGFR < 30 mL/min/1.73m2 within 3 months prior to planned study intervention; End Stage Renal Disease (ESRD) or documented history of renal replacement / dialysis; Current documented history of clinically significant liver disease which predisposes the subject to significant bleeding risk (clinically defined by the treating physician); Any history of thoracic radiation with the exception of localized radiation treatment for breast cancer; Current documented use of long-term treatment with oral corticoid steroids, not including use of inhaled steroids for respiratory diseases; Active pericarditis; Active endocarditis; Any documented history or autoimmune disease associated with pericarditis; Evidence of Pectus Excavatum (documented and clinically defined by the treating physician); Untreated severe scoliosis (documented and clinically defined by treating physician); Documented Left Ventricular Ejection Fraction (LVEF) < 30% within 30 days prior to planned intervention; Documented presence of implanted congenital defect closure devices, (e.g., atrial septal defect, patent foramen ovale or ventricular septal defect device); Previously attempted occlusion of the left atrial appendage (by any surgical or percutaneous method); Inability, or unwillingness or contraindication to undergo TEE or CTA imaging or 24-hour Holter monitoring; Body Mass Index (BMI) > 40; Evidence of active Graves disease; Current untreated hypothyroidism; Any contraindication to suture, endovascular device, or other minimally invasive techniques including percutaneous, transseptal, and/or sub-xiphoid access; Subject is pregnant or plans / desires to get pregnant within next 12 months; Current enrollment in an investigation or study of an investigational device or investigational drug that would interfere with this study and the required follow up; Mental impairment or other psychiatric conditions which may not allow patient to understand the nature, significance and scope of the study; Any other criteria, medical illness or comorbidity which would make the subject unsuitable to participate in this study as determined by the clinical site Primary Investigator; Additional Exclusion Criteria: Based on Screening / Pre-procedure Imaging Subjects will also be excluded if they meet any of the following: Based on screening computed tomography angiography performed within 90 days prior to study intervention as confirmed by the core lab: Left atrial appendage morphology: Superior-posterior oriented left atrial appendage (i.e. superior C shape), that has Left atrial appendage distal apex extending posterior to the ostium of the appendage. Left atrial appendage positioned behind the pulmonary artery; or All other left atrial morphology: Left atrial appendage LARIAT approach width > 50 mm. Based on a peri-procedural imaging (transesophageal echocardiography) at time of LARIAT or catheter ablation) and confirmed by institution's designated LARIAT echocardiographer: Intracardiac thrombus; or Significant mitral valve stenosis (i.e., mitral valve stenosis < 1.5cm2) NOTE: It is anticipated that a majority of subjects enrolled in the aMAZE CAP Trial will be elderly US Medicare beneficiaries. Therefore, the results from the aMAZE CAP Trial are expected to be generalizable to the Medicare population

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LARIAT + PVI Treatment Group<br>Percutaneously isolate and ligate the Left Atrial Appendage (LAA) from the left atrium (LA) with the LARIAT System prior to planned pulmonary vein isolation (PVI) catheter ablation Subgroup 1: Radiofrequency (RF) PVI catheter ablation treatment (n<65) Subgroup 2: Cryoballoon PVI catheter ablation treatment (n<20) | Device: LARIAT + PVI<br>* LAA ligation with the LARIAT System initially performed followed by adjunctive PVI catheter ablation (RF or cryoballoon) in staged procedures<br>* Other names: LAA + Cryo PVI;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from episodes of atrial fibrillation > 30 seconds at 12 months post index pulmonary vein isolation | Measured by 24-hour Holter Monitoring | 12 months following Pulmonary Vein Isolation catheter ablation procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from any atrial fibrillation/atrial tachycardia/atrial flutter recurrence defined as any episode > 30 seconds with or without AAD | Measured by 24-hour Holter Monitoring | Following the 90 day blanking period through 12 months post-index pulmonary vein isolation | 
| Composite endpoint of stroke of any cause and systemic embolism as adjudicated by the clinical events committee |  | 12 months following index pulmonary vein isolation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Left Atrial Appendage