Kansai Plus Atrial Fibrillation Trial (KPAF)

• Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy between 91 and 365 days after ablation. (Both trials) [ Time Frame: 91 - 365 days ] [ Designated as safety issue: No ]

  Atrial tachyarrhythmias include atrial fibrillation, atrial tachycardia, and common or uncommon atrial flutter.

  Antiarrhythmic drug (AAD) indicates Vaughan Williams class I or III drug.

  
  

• Repeat Ablation between 91 and 365 days after ablation. (Both trials) [ Time Frame: 91 - 365 days ] [ Designated as safety issue: No ]
  
• Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy* between 0 and 90 days after ablation. (Both trials) [ Time Frame: 0 - 90 days ] [ Designated as safety issue: No ]
  * In patients assigned to AAD group, AAD therapy between 0 and 90 days post ablation is not regarded as this secondary outcome.
  
  
• Atrial tachyarrhythmias lasting for > 30 seconds or requiring repeat ablation, hospital admission, cardioversion or antiarrhythmic drug (AAD) therapy* after ablation. (Both trials) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: No ]
  * In patients assigned to AAD group, AAD therapy between 0 and 90 days post ablation is not regarded as this secondary outcome.
  
  
• Quality of Life (QOL) score. (Both trials) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: No ]
  Atrial Fibrillation Quality of Life Questionnaire（AFQLQ) is used in this study.
  
  
• Procedural complications including cardiac tamponade, thromboembolism, PV stenosis/occlusion, left atrium-esophageal fistula, and peri-esophageal injury. (UNDER-ATP trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]
  
• Total procedure time. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  
• Total fluoroscopy time. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  
• Total radiation dose. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  
• Total number and duration of radiofrequency energy applications. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  
• Total number and duration of radiofrequency energy applications for pulmonary vein isolation. (UNDER-ATP trial) [ Time Frame: Day-0 ] [ Designated as safety issue: Yes ]
  
• Side effects of ATP including bronchial asthma, angina and sustained hypotension (<90mmHg or requiring vasopressor) during and after the procedure. (UNDER-ATP trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]
  
• Side effects of antiarrhythmic drugs (EAST-AF trial) [ Time Frame: 0 - 365 days ] [ Designated as safety issue: Yes ]
  

Atrial fibrillation (AF) is a common tachyarrhythmia causing disabling symptoms and stroke. Although catheter ablation has been developed as curative therapy for AF, it is still associated with considerably high rate of AF recurrence, approximately 30-40% in patients with paroxysmal AF and 50-80% among those with persistent AF.

Because most ectopic beats triggering AF originate from myocardial sleeves in pulmonary veins (PVs), the mainstay of catheter ablation for AF is PV isolation. The major cause of early and late AF recurrence following successful PV isolation is considered to be electrical reconnection between left atrium (LA) and PVs. Therefore, it is important to establish permanent LA-PV disconnection, although high energy application is associated with increased risk of procedural complications, including cardiac tamponade, PV stenosis/occlusion and LA-esophageal fistula.

Adenosine or adenosine triphosphate (ATP) has been reported to unmask dormant electrical conduction between LA and PVs after successful PV isolation. Thus, adenosine or ATP guide additional ablation until disappearance of dormant electrical conduction has been proposed as adjunctive approach to establish permanent LA-PV disconnection and thereby decrease AF recurrence post ablation. However, only several small observational studies showed the efficacy of adenosine or ATP guide ablation, and this approach is not recognized as standard therapy.

On the other hand, sizable portion of AF recurrence early after ablation is considered to be due to irritability in LA from the ablation. Thus, short term use of antiarrhythmic drugs (AADs) after ablation has been proposed as adjunctive approach not only to prevent early AF recurrence, but also to improve long-term outcome by promoting reverse remodeling of LA through maintenance of sinus rhythm during the first 2-3 months period after ablation.

The 5A study, a recently reported single-center study, randomized 110 patients with paroxysmal AF to AAD or control group. In the AAD group, AAD was used for 6 weeks after ablation. Although AAD significantly reduced early AF recurrence during the first 6 weeks, discontinuation of the drug resulted in similar AF-free rates at 6 months. Considering the small number of patients enrolled in the 5A study, the results were not conclusive, lacking statistical power to determine the effect of short-tem use of AAD following successful ablation for AF on long-term clinical outcome. Also, this approach is expected to be more effective in patients with persistent AF rather than those with 'self-terminating' paroxysmal AF. In addition, 6 weeks may have been too short to promote reverse remodeling of LA.

Accordingly, we planned a 2x2 factorial randomized controlled trial (KPAF trial), evaluating the efficacy of ATP guide additional ablation and 90 days use of AADs post ablation. Approximately 2,000 patients with paroxysmal or persistent AF will be randomized to ATP guide ablation or control group in a 1:1 ratio before the procedure (UNDER-ATP trial). Excluding those with severe procedural complications or those with substantial bradycardia identified first after ablation for persistent AF, patients will be randomized in a 1:1 ratio to AAD or control group after the procedure (EAST-AF trial). Approximately 5% of the patients are expected to be excluded from the EAST-AF trial after ablation, but those patients will not be excluded from the UNDER-ATP trial, whose data will be analyzed by intention-to-treat manner. The follow-up duration is one year.