Effect of Amiodarone on the Procedure Outcome in Long-standing Persistent Atrial Fibrillation Undergoing Pulmonary Vein Antral Isolation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 3

Summary: 
      This prospective randomized study aims to investigate the effect of continuous versus
      interrupted use of Amiodarone on the procedure outcome in long-standing persistent (LSP)
      atrial fibrillation patients undergoing pulmonary vein antral isolation (PVAI).
    

Detailed description: 
      Background: Atrial Fibrillation (AF) is the most prevalent sustained clinical arrhythmia
      encountered in clinical practice. Its prevalence is 0.4-1% in the general population and
      greater than 8% in individuals >80 years of age. An estimated 2.5million individual in North
      America and 4.5 million in Europe are affected by AF (1). There are two fundamental
      principles in the management of AF; 1) anticoagulation to reduce the risk of thromboembolism,
      2) ablation therapy or drugs or both to control the arrhythmia (2).

      Amiodarone, a potent antiarrhythmic drug, is recommended for both atrial and ventricular
      arrhythmia. It has a combination of Beta-blockade, calcium-, sodium- and potassium-channel
      blockade effect. Most importantly, the potassium-channel blockade slows repolarization,
      causing an increase in the action-potential duration and in the refractoriness of the cardiac
      musculature (3). As the myocardium remains unresponsive, the premature depolarizations which
      were previously causing AF are prevented from propagation.

      During the ablation procedure, mapping electrograms using circular mapping catheter and
      provocative maneuvers such as administration of isoproterenol in incremental doses are
      commonly used to aid in identification of pulmonary vein (PV) and non-PV triggers. In
      addition, areas with complex fractionated atrial electrograms (CFAE) are identified and
      eliminated by ablation. In patients with LSP, inclusion of PV and non-PV triggers as ablation
      targets, improves the procedure outcome.

      As Amiodarone increases the refractoriness of the myocardium, it is possible that under the
      effect of Amiodarone some of the focal triggers could be masked or remain unidentified during
      mapping or isoproterenol-provocation. These unrecognized triggers could cause recurrence of
      AF during the post-ablation period. In other words, discontinuation of Amiodarone at least
      5-months before ablation could result in unmasking of all the focal triggers that would have
      otherwise stayed unrecognized and eliminating those triggers would significantly improve the
      success rate of the procedure.

      Our study aims to investigate the role of Amiodarone in influencing the procedure outcome in
      LSP-AF patients undergoing catheter ablation.

      Hypothesis: Withdrawal of Amiodarone 4 months before procedure results in unmasking of
      additional focal triggers, ablation of which leads to an improved procedure outcome in LSP_AF
      patients.

      Inclusion Criteria:

        1. History of LSP AF

        2. Age > 18 years

        3. Willing and ability to understand and sign an informed consent

        4. Patients on chronic Amiodarone therapy (≥ 3 months)

      Exclusion Criteria:

        1. Unstable angina

        2. Concomitant treatment with other class I or III antiarrhythmic drugs

        3. Myocardial infarction within past 3 months)

        4. Presence of any disease that is likely to shorten life expectancy to < 1 year

        5. Symptomatic heart failure, NYHA III or IV

        6. Contraindications for Amiodarone

        7. Chronic liver diseases

        8. Pregnant or breast-feeding mothers

      Primary Outcome Measure:

      Recurrence of AF, atrial flutter or atrial tachycardia

      Secondary Outcome Measures:

      Difference in the occurrence of relapse between the control and the study groups

      Study design:

      This is a multi-center, prospective study in which consecutively enrolled patients treated
      with Amiodarone for long standing persistent AF will be randomized to either the study or the
      control group.

      Study group: Amiodarone therapy will be stopped at least 4-months before ablation procedure
      and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the
      blanking period (8 weeks post-ablation).

      Control group: Patient will continue taking Amiodarone before, during and after ablation (8
      weeks post-ablation).

      After the blanking period, everybody would be off Amiodarone unless they have recurrence.
      Anti-arrhythmic drugs other than Amiodarone would be tried if patient develops recurrence and
      repeat ablation would be considered.

      Follow-Up:

      Patients will be followed up for 3 years post-ablation. An ECG and telemetry transmission
      monitor report will be obtained in all patients at each follow-up examination.

      Patients will be supplied with an Event Recorder for trans-telephonic rhythm transmission
      (telemetry) for 5 months after ablation, and will be asked to transmit their rhythm data
      every time they had symptoms compatible with arrhythmias; and at least once a week, even if
      they were asymptomatic. Holter monitoring will be performed at 6-month post-ablation. The
      arrhythmic episodes will be documented based on ECG, Holter data, Event Recorder data and/or
      implanted device data (when available).

      In case of recurrence, if patients undergo repeat ablations, all procedures will happen off
      amiodarone. After redo, patients will be followed up for 1 year for recurrence in the same
      way as described above.
    

Intervention name(s): Amiodarone; Amiodarone
Intervention type(s): Drug; Drug
Intervention description(s): Patient will continue taking Amiodarone before, during and after ablation (8 weeks post-ablation).; Amiodarone therapy will be stopped at least 5-months before ablation procedure and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the blanking period (8 weeks post-ablation).
Intervention MeSH terms: Amiodarone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AF; Catheter Ablation; Recurrence of AF; Amiodarone