Please select the eligibility criteria that correspond to the clinical trial below.
Title: 'CLOSE'-Guided Pulmonary Vein Isolation as Cure for Paroxysmal Atrial Fibrillation?
Brief Summary: Title: CLOSE-guided pulmonary vein isolation (PVI) as Cure for Paroxysmal Atrial Fibrillation ('CLOSE to CURE' study)

Design: This is a prospective, observational, single-center, unblinded, clinical 3-year study.

Background: In a population of paroxysmal atrial fibrillation (AF) 'CLOSE'-guided PVI, a new approach to obtain single-procedure durable PVI, has been shown to virtually eliminate recurrence of AF at 1 year follow-up with repetitive but discontinuous Holter monitoring.

Objectives: (1) To objectively compare atrial tachyarrhythmia (ATA) burden before and after 'CLOSE'-guided based PVI using continuous monitoring. (2) To assess ATA burden using continuous monitoring up to 3 years after ablation. (3) To identify baseline structural and electrical properties of the atria or procedural characteristics that predict 1-year and 3-year outcome.

Enrollment: Up to 100 subjects will be enrolled in this observational, prospective study.

Clinical Sites: 1 site.

Subject Population: Eligible patients are patients with paroxysmal high-burden AF who are planned for a 'CLOSE'-guided PV isolation. At the time of procedural planning we will ask the patient his/her consent for (1) implantation of a subcutaneous continuous loop recorder (sCLR), (2) a concise electrophysiological study at the time of PVI, (3) a transthoracic echocardiogram at the time of PVI and (4) collection of data during 3 years. Anti-arrhythmic drug treatment (ADT) and oral anticoagulation (OAC) will be given according the updated 2012 European society of Cardiology (ESC) guidelines on AF (Camm et al, European Heart Journal 2012) and the 2012 Heart rhythm society (HRS)/European Heart Rhythm association/European cardiac arrhythmic society Expert Consensus Statement on catheter and surgical ablation of atrial fibrillation (Calkins et al, Heart Rhythm 2012).


Options:
A: Inclusion Criteria:

Prospective Cohort

* Written informed consent
* Age 18 years and older
* New diagnosis of non-valvular atrial fibrillation (diagnosed within the last 6 weeks) with at least one additional risk factor for stroke and regardless of therapy.

Retrospective validation cohort

* Written informed consent
* Age 18 years and older
* Diagnosis of non-valvular AF (diagnosed 6-24 months prior to enrolment) with at least one additional risk factor for stroke and regardless of therapy.

Exclusion criteria:

* No further follow-up envisaged or possible within enrolling hospital or with associated family practitioner.
* Patients with transient AF secondary to a reversible cause.
* Patients recruited in controlled clinical trials.
B: Inclusion Criteria:

1. Patients with symptomatic paroxysmal AF (history of self-terminating AF within 7 days or history of self-terminating AF with 1 or more cardioversions within 48 hours after onset), meeting following criteria at the out-patient clinic:

   * patient has at least 3 AF episodes in the last 3 months prior to the visit
   * AF episodes are symptomatic, and patient is drug-resistant (at least one class IC or III), or drug-intolerant (palpitations, fatigue, dyspnea, cardiomyopathy,...)
   * no advanced structural heart disease
   * patient has a CHA2DS2-VASc score of 0, 1, 2, 3 or 4
2. Signed Patient Informed Consent Form.
3. Age 18 years or older.
4. Able and willing to comply with all follow-up testing and requirements.

Exclusion Criteria:

1. Persistent atrial fibrillation (history of AF\>7days or history of cardioversion \> 48h of AF)
2. Previous ablation for AF
3. LA antero-posterior diameter \> 50 mm (parasternal long axis view , PLAX)
4. LVEF \< 35% (ejection fraction)
5. AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause
6. Coronary artery bypass grafting (CABG) procedure within the last three months
7. Awaiting cardiac transplantation or other cardiac surgery
8. Documented left atrial thrombus on imaging
9. Diagnosed atrial myxoma
10. Women who are pregnant or breastfeeding
11. Acute illness or active systemic infection or sepsis
12. Unstable angina
13. Uncontrolled heart failure
14. Myocardial infarction within the previous two months
15. History of blood clotting or bleeding abnormalities
16. Contraindication to anticoagulation therapy (ie, heparin or warfarin)
17. Life expectancy less than 12 months
18. Enrollment in any other study evaluating another device or drug
19. Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction
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:

* Type 2 diabetes
* Overweight
* BMI of 25 kg/m2 or greater
* If on insulin, BMI of 27 kg/m2 or greater
* Blood pressure less than 160/100 mmHg
* HbA1c less or equal to 11%
* Triglycerides less than 600 mg/dl
* Willingness to participate

Exclusion Criteria:

* Unable or unwilling to give informed consent or communicate with local study staff.
* Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder.
* Hospitalization for depression in past six months.
* Self-report of alcohol or substance abuse within the past twelve months.
* Current consumption of more than 14 alcoholic drinks per week.
* Current acute treatment or rehabilitation program for these problems.
* Plans to relocate to an area not served by Look AHEAD or travel plans that do not permit full participation in the study.
* Lack of support from primary care health provider or family members.
* Failure to complete the two-week run-in for dietary intake and exercise.
* Weight loss exceeding 10 lbs. in past three months.
* Current use of medications for weight loss.
* Self reported inability to walk two blocks.
* History of bariatric surgery, small bowel resection, or extensive bowel resection.
* Chronic treatment with systemic corticosteroids.
* Another member of the household is a participant or staff member in Look AHEAD.
* Currently pregnant or nursing.
* Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured.
* HIV positive (self-report), due to effects on weight and body composition of HIV and medications used to treat HIV.
* Active tuberculosis (self-report).
* Cardiovascular disease (heart attack or procedure within the past three months).
* Participation in a cardiac rehabilitation program within last three months.
* Stroke or history/treatment for transient ischemic attacks in the past three months.
* Pulmonary embolus in past six months.
* Unstable angina pectoris or angina pectoris at rest.
* A history of cardiac arrest.
* Complex ventricular arrhythmia at rest or with exercise (e.g., ventricular tachycardia).
* Uncontrolled atrial fibrillation (heart rate of 100 beats per minute or more).
* New York Heart Association (NYHA) Class III or IV congestive heart failure.
* Acute myocarditis, pericarditis or hypertrophic myocardiopathy.
* Clinically significant aortic stenosis.
* Left bundle branch block or cardiac pacemaker unless evaluated and cleared for participation by a cardiologist.
* Cardiac defibrillator.
* Heart transplant.
* History of aortic aneurysm of at least 7 cm in diameter or aortic aneurysm repair.
* Resting heart rate less than 45 beats per minute or greater than 100 beats per minute.
* Any abnormality during the maximum exercise stress test that indicates that it would be unsafe to participate in the Lifestyle Intervention.
* Angina pectoris.
* Significant ST segment depression at low levels of exercise. (ST segment is the flat, isoelectric section of the ECG between the end of the S wave (the J point) and the beginning of the T wave)
* Exercise induced ventricular arrhythmias.
* Abnormal hemodynamics, such as flat or decreasing systolic blood pressure with increasing workload.
* Those at moderate to high risk for cardiac complications during exercise.
* Those who are unable to self-regulate activity or understand the recommended activity level.
* Renal disease or dialysis.
* Chronic obstructive pulmonary disease that would limit ability to follow the protocol.
* Self-reported chronic hepatitis B or C or cirrhosis.
* Inflammatory bowel disease requiring treatment in past year.
* Cushing's syndrome.
* Acromegaly.
* Amputation of lower limbs as result of non-traumatic causes.
* Any major organ transplant.

Answer: B