Second Study to Assess Different Ablation Strategies in Achieving Long-Term Arrhythmia Control in Patients With Persistent or Long Standing Persistent Atrial Fibrillation

The AF ablation procedure has evolved considerably and currently the most accepted technique
involves creation of circumferential Radiofrequency Ablation lesions around PV ostia
(encircling wide areas around the left and right sided veins). We have found that targeting
areas outside the pulmonary veins that trigger atrial premature beats of AF is important for
optimizing the success of AF ablation. The methodology of additional lesion creation
remains non-uniform, lacks mechanistic insights, and there is paucity of prospective
randomized comparison on the long term efficacy and safety of various lesion combinations in
achieving AF control. Our group recently conducted randomized study (RASTA Trial) that
compared PVI combined with ablation of documented non-PV triggers (standard AF ablation
strategy) of AF to two other strategies i.e. 1. PVI combined with empiric ablation at common
non-PV trigger sites of AF, 2. PVI combined with ablation of locations demonstrating complex
fractionated electrograms. In this study comprising 156 subjects with persistent and /or
long standing persistent AF, the investigators found that the standard AF ablation strategy
was as efficacious as PVI combined with empiric ablation at common non-PV trigger sites of
AF and both of these approaches were significantly better than PVI combined with ablation of
locations demonstrating complex fractionated electrograms. Our study also showed that when
compared to the standard AF ablation strategy (PVI combined with ablation of documented non
PV AF triggers), PVI combined with empiric ablation at common locations of AF triggers in
the left and right atria showed 22% higher odds of achieving freedom from atrial arrhythmias
and 33% higher odds of achieving arrhythmia control at one year. Although this difference
may have been clinically meaningful, it did not reach statistical significance because this
study was powered to test for a difference of ≥30% between groups. Thus, in the current
proposal the investigators hope to show statistical difference in the outcomes between these
two strategies by increasing the sample size which will provide adequate power to show a 20%
difference in the primary outcome. Also, the investigators hope to enhance the outcome in
the study arm (PVI combined with empiric ablation at common locations of AF triggers) by
also targeting empirically locations in the left and right atria that have been shown in
recent studies to be focal sources and rotors that maintain AF.

Inclusion Criteria:

- All patients of age ≥ 18 years, undergoing their first ablation procedure that meet
American College of Cardiology / American Heart Association defined criteria for
persistent or long standing persistent AF will be eligible to participate in the
proposed study. This includes patients with a history of AF episodes lasting at least
7 days and requiring at least 2 cardioversions.

Exclusion Criteria:

- Patients with paroxysmal AF (self-terminating episodes lasting < 7 day)

- Patients who have had a previous AF ablation procedure

- Failure to obtain informed consent

- Patients < 18 years of age. Investigators will plan to exclude paroxysmal AF patients
and concentrate on patients with persistent or long standing persistent AF who may
require further ablation to achieve better outcomes. Patients who have undergone
previous AF ablation procedure will be excluded since the prior methodology used may
confound the results of this study.