Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: The Effect of Double Short vs. Standard Exposure Cryoablation Duration During Pulmonary Vein Isolation.

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

Intervention / Treatment
-----------------
* Procedure: Pulmonary Vein Isolation


Participation Criteria
=================
Eligibility Criteria
-----------------
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

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard cryoablation<br>Patients randomized to the standard group will undergo cryoablation with target duration of 240 seconds. Once PVI is achieved a single bonus application of 240 seconds will be delivered after the rewarming phase (to +20oC). | Procedure: Pulmonary Vein Isolation<br> <br> |
| Active Comparator: Irrigated RF Ablation<br>Patients randomized to irrigated RF group will undergo standard wide circumferential PVI with an irrigated radiofrequency catheter | Procedure: Pulmonary Vein Isolation<br> <br> |
| Experimental: Short Cryoablation<br>Patients randomized to the multiple-freeze group will undergo cryoablation with target duration of 120 seconds. Once PVI is achieved a single bonus application of 120 seconds will be delivered after the rewarming phase (to +20oC). | Procedure: Pulmonary Vein Isolation<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrence of AF, atrial flutter, or left atrial tachycardia documented by 12-lead ECG, surface ECG rhythm strips, ambulatory ECG monitor, or implantable loop recorder and lasting 30 seconds or longer |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrence of symptomatic electrocardiographically documented AF/AFL/AT between days 91 and 365 after ablation |  | 1 year | 
| Total arrhythmia burden (daily AF burden - hours/day; overall AF burden - % time in AF) |  | 1 year | 
| Repeat ablation procedure because of documented recurrence of symptomatic AF/AFL/AT |  | 1 year |