Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with reductions in quality of life, functional status, cardiac performance, and overall survival.1 Catheter ablation, which is centered on electrical isolation of triggering foci within the pulmonary veins (PVI) through circumferential lesions around PV ostia, has been shown to result in sustained improvements in quality of life, decreased hospitalizations and, potentially, improved survival.2-4 PVI can be accomplished by percutaneous catheter-based thermo-coagulation (burning) with radiofrequency (RF) energy delivery or alternatively by thermo-cooling (freezing) with a cryoballoon catheter.5 Cryothermal ablation with a cryoballoon catheter offers an efficacious means to achieve PVI that is safer than the established technique. Although cryoballoon ablation has been used in clinical practice for sometime, the optimal duration of cryoballoon ablation has not been determined. Moreover, the biophysics of cryo-lesion formation suggests that repeated short freezes ("freeze-thaw-freeze" cycles) may be more efficacious in achieving deep homogenous lesion when compared to prolonged freezing durations. This grant proposal is to verify if repeated short freezing cycles are more efficacious (i.e., fewer recurrence of AF), and safer, than the established standard of long, single freeze cycles.

Inclusion Criteria:

- Non-permanent atrial fibrillation documented on a 12 lead ECG, TTM or Holter monitor within the last 12 months Low Burden Paroxysmal - ≥2 episodes of AF over the past 12 months; Episodes terminate spontaneously within 7 days or via cardioversion within 48 hours of onset.

High Burden Paroxysmal - ≥4 episodes of AF over the past 6 months, with ≥2 episodes >6 hours in duration; Episodes terminate spontaneously within 7 days or via cardioversion within 48 hours of onset.

Early Persistent - ≥2 episodes of AF over the past 12 months; Episodes are successfully terminated via cardioversion within 7 days of onset.

• Age of 18 years or older on the date of consent
• Candidate for ablation based on AF that is symptomatic and refractory (ineffective or intolerant) to at least one class 1 or 3 antiarrhythmic
• Continuous anticoagulation with warfarin (INR 2-3), low molecular weight heparin, or a novel oral antithrombotic (dabigatran, apixaban, rivaroxaban) for ≥4 weeks prior to the ablation; or a TEE that excludes LA thrombus ≤48 hours before ablation
• Informed Consent Form

Exclusion Criteria:

• Previous left atrial (LA) ablation or LA surgery
• Pre-existing pulmonary vein stenosis or PV stent
• Pre-existing hemidiaphragmatic paralysis
• Contraindication to anticoagulation or radiocontrast materials
• Anteroposterior LA diameter greater than 5.5 cm by TTE
• Cardiac valve prosthesis
• Clinically significant (moderately-severe, or severe) mitral valve regurgitation or stenosis
• Myocardial infarction, PCI / PTCA, or coronary artery stenting during the 3-month period preceding the consent date
• Cardiac surgery during the three-month interval preceding the consent date
• Significant congenital heart defect (including atrial septal defects or PV abnormalities but not including PFO)
• NYHA class III or IV congestive heart failure
• Left ventricular ejection fraction (LVEF) less than 35%
• Hypertrophic cardiomyopathy
• Significant CKD (eGFR <30 mL/min/m2)
• Uncontrolled hyperthyroidism
• Cerebral ischemic event (strokes or TIAs) during the six-month interval preceding the consent date
• Subject known to be pregnant
• Life expectancy less than one (1) year
• Currently participating or anticipated to participate in any other clinical trial of a drug, device or biologic during the duration of this study
• Unwilling or unable to comply fully with study procedures and follow-up