Feasibility Study of the FARAFLEX Mapping and PFA System

The objective of this study is to obtain First-in-Human (FIH) experience with the FARAFLEX mapping and PFA catheter in the treatment of persistent Atrial Fibrillation (persAF) or Paroxysmal Atrial Fibrillation (PAF).

Subjects with symptomatic Persistent Atrial Fibrillation or symptomatic Paroxysmal Atrial Fibrillation will be included in this study.

Inclusion criteria

• Age ≥ 18 years of age, or older if required by local law
• Symptomatic, documented, Persistent AF or Paroxysmal AF
• Willing and capable of providing informed consent
• Willing and capable of participating in all follow-up assessments and testing associated with this clinical investigation at an approved clinical investigational center

Exclusion criteria

• Atrial exclusions - Any of the following atrial conditions:

• Left atrial anteroposterior diameter ≥ 5.5 cm, or if LA diameter not available, non indexed volume >100 ml (by MRI, CT or TTE report or physician note)
• Any prior atrial endocardial, epicardial or surgical ablation procedure for atrial arrhythmia other than ablation for right sided SVT
• Current atrial myxoma
• Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible)
• Current left atrial thrombus
• Cardiovascular exclusions - Any of the following CV conditions:

• History of sustained ventricular tachycardia or any ventricular fibrillation AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes
• Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices, interatrial baffle, closure device, patch, or patent foramen ovale occluder, LA appendage closure, device or occlusion
• Valvular disease that is symptomatic or is the cause of heart failure.
• Hypertrophic cardiomyopathy
• Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty
• Known inability to obtain vascular access or other contraindication to femoral access
• Rheumatic heart disease
• Awaiting cardiac transplantation or other cardiac surgery within the next 12 months
• Known allergic drug reaction to nitroglycerin1
• Known severe non-revascularizable coronary disease
• Pre-existing right coronary artery stent and left circumflex artery
• Any of the following conditions at baseline:

• Heart failure associated with NYHA Class IV
• LVEF < 40%
• Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two (2) BP measurements at baseline assessment
• Severe right ventricular dysfunction with documented echocardiography and/or hemodynamic data.
• Any of the following events within 90 Days of the Consent Date:

• Myocardial infarction (MI), unstable or Prinzmetal angina or coronary intervention
• Any cardiac surgery
• Heart failure hospitalization
• Pericarditis or symptomatic pericardial effusion
• Gastrointestinal bleeding
• Stroke, TIA, or intracranial bleeding
• Any non-neurologic thromboembolic event
• Carotid stenting or endarterectomy
• Known coagulopathy disorder (e.g. von Willibrand's disease, hemophilia)
• Contraindication to, or unwillingness to use, systemic anticoagulation, or acceptable alternatives, pre-, intra- and post-procedure to achieve adequate anticoagulation.
• Women of childbearing potential who are pregnant, lactating, not using medical birth control or who are planning to become pregnant during the anticipated study period
• Any of the following health conditions that would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or modify outcome data or its interpretation, including but not limited to:

• Body Mass Index (BMI) > 42.0
• Solid organ or hematologic transplant, or currently being evaluated for a transplant
• Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis
• Severe lung disease, severe pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
• Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant
• Active malignancy at enrollment (other than squamous cell carcinoma)
• Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
• Active systemic infection
• Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour)
• Required use of phosphodiesterase inhibitors within 24 hours of the ablation procedure

• Predicted life expectancy less than one (1) year 11. Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the Sponsor to determine eligibility 12. Any of the following congenital conditions:

• Congenital heart disease with any clinically significant residual anatomic or conduction abnormality
• History of known congenital methemoglobinemia
• History of known G6PD deficiency

ELEVATE-COR (additional) Eligibility Criteria:

Inclusion criteria

• Meets all inclusion criteria according to the ELEVATE-PF Protocol
• Planned for adjunctive CTI ablation
• Willing and capable of participating in all assessments and testing associated with this sub-study protocol.

Exclusion criteria

• Meets any of the exclusion criteria outlined in the ELEVATE-PF Protocol
• Pre-existing right coronary artery stent and/or left circumflex artery stent
• Known severe non-revascularizable coronary disease
• Moderate to severe coronary artery disease that in the opinion of the investigator would put the patient at increased risk
• Known calcium score ≥1000
• Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant
• Contraindication to IVUS
• Body Mass Index (BMI) > 35.0