Please select the eligibility criteria that correspond to the clinical trial below.
Title: NAVISTAR® THERMOCOOL® Catheter for the Radiofrequency Ablation of Symptomatic Paroxysmal Atrial Fibrillation
Brief Summary: This trial compares the safety and effectiveness of catheter ablation for PAF with antiarrhythmic drug therapy. The investigational catheter being studied is the NAVISTAR® THERMOCOOL® irrigated-tip catheter. At the time of this study, the NAVISTAR® THERMOCOOL® catheter was FDA-approved for commercial distribution in the U.S. for treating patients with Type I atrial flutter and drug refractory monomorphic ventricular tachycardia post myocardial infarction. The catheter was approved for use in Europe for endocardial ablation for treating cardiac arrhythmias.


Options:
A: Key Inclusion Criteria:

* Males and females aged 18 years and older
* Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* History of PAF documented within the prior 12 months

  - Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible
* Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities
* AFB ≥ 1% and ≤ 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB ≥ 2% and ≤ 70% during the Run in period
* Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication

Key Exclusion Criteria:

Disease - specific:

* Persistent AF or Permanent AF
* History of atrial flutter or atrial tachycardia without successful ablation
* Other acutely reversible causes of AF, including but not limited to: hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism
* New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening.
* Recent history of left ventricular ejection fraction (LVEF) \< 40%
* Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening
* Clinically significant valvular disease in the opinion of the Investigator
* Stroke within 3 months prior to Screening
* History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
* Family history of long QT syndrome
* Corrected QT interval (QTc) ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening
* Prior heart transplant
* Cardiac ablation within 4 months prior to Screening, or planned ablation during the course of the study

Concomitant medications/food

* Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of cytochrome P450 3A (CYP3A), or inducers of CYP3A

  - Such medications should be discontinued 5-half lives prior to the Run-in period
* Use of grapefruit juice or Seville orange juice during the study
* Use of Class I and Class III antiarrhythmic drugs other than amiodarone within 5-half lives prior to the Run-in period
* Use of amiodarone within 3 months prior to Screening
* Use of drugs that prolong the QT interval
* Previous use of ranolazine or dronedarone within 2 months prior to screening
* Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability
* Use of dabigatran during the study
* Use of digitalis preparations (eg, digoxin) during the study
* Use of a greater than 1000 mg total daily dose of metformin during the study

Laboratory tests:

* Hypokalemia (serum potassium \< 3.5 mEq/L) at Screening that cannot be corrected to a level of potassium ≥ 3.5 mEq/L prior to randomization
* Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin \> 2 x upper limit of normal (ULN) at Screening
* Severe renal impairment defined as creatinine clearance ≤ 30 mL/min at Screening

Others:

* Females who are pregnant or are breastfeeding
* In the judgment of the Investigator, any clinically-significant ongoing medical condition that might jeopardize the individual's safety or interfere with the study, including participation in another clinical trial within the previous 30 days using a therapeutic modality which could have potential residual effects that might confound the results of this study
* Any device-related technical issue which in the judgment of the investigator would disrupt adequate data collection or interpretation (eg, anticipated pulse generator change or lead revision)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
B: You may be eligible to participate in this study if you: Have failed to respond to drug treatment for your AFib, or find the side effects of your medication intolerable.

Inclusion Criteria

* Patients with symptomatic PAF who have had three (3) AF episodes in the six (6) months prior to randomization, one of which must be documented. Documentation may include electrocardiogram (ECG), transtelephonic monitor (TTM), Holter monitor (HM), or telemetry strip.
* Failure of at least one AAD for PAF \[class I or III or AV nodal blocking agents such as beta blockers (BB) and calcium channel blockers (CCB)\] as evidenced by recurrent symptomatic PAF, or intolerable side effects due to AAD.
* Signed Patient Informed Consent Form.
* Age 18 years or older.
* Able and willing to comply with all pre-, post- and follow-up testing and requirements.

Exclusion Criteria

* Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause.
* Previous ablation for atrial fibrillation.
* Patients on amiodarone therapy at any time during the previous six (6) months.
* AF episodes that last longer than 30 days and are terminated via cardioversion.
* Any valvular cardiac surgical procedure.
* CABG procedure within the last 180 days (six months).
* Awaiting cardiac transplantation or other cardiac surgery within the next 360 days (12 months).
* Documented left atrial thrombus on imaging (e.g. TEE).
* History of a documented thromboembolic event within the past one (1) year.
* Diagnosed atrial myxoma.
* Presence of implanted ICD.
* Significant pulmonary disease, (e.g. restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms.
* Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study.
* Women who are pregnant (by history of menstrual period or pregnancy test if the history is considered unreliable).
* Acute illness or active systemic infection or sepsis.
* Unstable angina.
* Myocardial infarction within the previous 60 days (two months).
* LVEF \< 40%.
* History of blood clotting or bleeding abnormalities.
* Contraindication to anticoagulation (i.e. heparin or warfarin).
* Contraindication to CT/MRA procedure.
* Life expectancy less than 360 days (12 months).
* Enrollment in an investigational study evaluating another device or drug.
* Uncontrolled heart failure or NYHA class III or IV heart failure.
* Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction or manipulation.
* Presence of a condition that precludes vascular access.
* Left atrial size ≥ 50 mm
C: Inclusion Criteria:

* Over the preceding 6 months have:

  1. ≥2 paroxysmal (electrocardiographic documentation of at least 1) atrial fibrillation (AF) episodes lasting ≥1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or
  2. electrocardiographic documentation of 1 persistent AF episode: (sustained for ≥7 days or cardioversion is performed more than 48h after AF onset): or
  3. electrocardiographic documentation of 1 longstanding persistent AF episode: (continuous AF of duration \>1 year).
* Warrant active therapy (within the past 3 months) beyond simple ongoing observation
* Be eligible for catheter ablation and ≥2 sequential rhythm control and/or ≥2 rate control drugs.
* Be ≥65 yrs of age, or \<65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a blood pressure \>140/90 mmHg) \[90\], Diabetes (treated and/or defined as a fasting glucose ≥126 mg/dl) \[91\], Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, transient ischemic attack or systemic emboli, Atherosclerotic vascular disease (previous myocardial infarction (MI), peripheral arterial disease or aortic plaque), left atrial (LA) size \>5.0 cm (or volume index ≥40 cc/m2), or ejection fraction (EF) ≤35.
* Have the capacity to understand and sign an informed consent form.
* Be ≥18 years of age.

  * NOTE- Subjects \<65 yrs of age whose only risk factor is hypertension must have a second risk factor or left ventricular (LV) hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.

Exclusion Criteria:

* Lone AF in the absence of risk factors for stroke in patients \<65 years of age
* Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
* Patients who have failed \>2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy or side effects (Table 5.2.2)
* An efficacy failure of full dose amiodarone treatment \>8 weeks duration at any time
* Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
* Recent cardiac events including MI, percutaneous intervention (PCI), or valve or bypass surgery in the preceding 3 months
* Hypertrophic obstructive cardiomyopathy (outflow track)
* Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation)
* Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. ventricular tachycardia (VT), ventricular fibrillation (VF))
* Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
* Prior LA catheter ablation with the intention of treating AF
* Prior surgical interventions for AF such as the MAZE procedure
* Prior AV nodal ablation
* Patients with other arrhythmias requiring ablative therapy
* Contraindication to appropriate anti-coagulation therapy
* Renal failure requiring dialysis
* Medical conditions limiting expected survival to \<1 year
* Women of childbearing potential (unless post-menopausal or surgically sterile)
* Participation in any other clinical mortality trial (Participation in other non-mortality trials should be reviewed with the clinical trial management center)
* Unable to give informed consent

  * NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.
D: Inclusion Criteria:

* Subject is ≥ 18 years of age
* Subject must be diagnosed with Persistent and/or Longstanding Persistent Atrial fibrillation as classified by the HRS Guidelines 8 \[0\]
* Subject must be selected as a candidate to undergo the Cox- Maze procedure for ablation of atrial fibrillation
* The Cox Maze procedure may be done as a stand alone procedure or combined with other cardiac surgical procedures either via a median sternotomy or a right thoracotomy:
* Subject has a Left Ventricular Ejection Fraction (LVEF) ≥ 30%
* Subject would normally be prescribed Amiodarone as an anti arrhythmic medication post surgical ablation
* Subject is able and willing to provide written informed consent and HIPAA authorization
* Subject is able and willing to comply with all study requirements including attending all follow-up visits as deemed necessary by personal physician (cardiologist)
* Subject has a life expectancy of at least one year

Exclusion Criteria:

* Subject has undergone previous attempts at surgical Maze procedure or other AF operation, including surgical or catheter ablation Subject has an accessory pathways disorder (e.g. Wolff-Parkinson-White syndrome)
* Subject is in Class IV NYHA
* Subject has had a documented MI within 6 weeks prior to study enrollment
* Subject needs emergent cardiac surgery (i.e. cardiogenic shock)
* Subject has known carotid artery stenosis greater than 80%
* Subject has a current diagnosis of active systemic infection
* Subject is pregnant, planning to become pregnant within 12-14 months, or lactating
* Subject requires preoperative intra-aortic balloon pump or intravenous inotropes
* Subject has renal failure requiring dialysis
* Subject is diagnosed with hepatic failure
* Subject is on anti-arrhythmic drug therapy for the treatment of a ventricular arrhythmia
* Subject has a known connective tissue disorder
* Subject is incarcerated
* Subject has previous or current therapy that could compromise tissue integrity including thoracic radiation, chemotherapy, long-term oral or injected steroids
* Subject is an intravenous drug and/or alcohol abuser
* Subject is participating in concomitant research studies of investigational products ( e.g. Appendage closure devices, atrial septal defect patches)

Answer: B