Efficacy of DE-MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation

There is a strong association between AF and atrial tissue ;fibrosis. Recently,
a novel DE-MRI (Delayed-Enhancement MRI) based imaging modality has been
demonstrated to reveal the degree of fibrotic atrial tissue in patients
suffering from AF. When applied in various studies, including a multi-center
study, extent of fibrotic atrial changes was shown to be the strongest
independent predictor of a successful treatment in patients undergoing ablation
of AF. Moreover, in the multi-center observational study DE-MRI Determinant of
Successful Radiofrequency Catheter Ablation of Atrial Fibrillation (DECAAF),
the strongest independent predictor of successful outcome was the surface area
of fibrosis covered by ablation lesions. In fact, the number of encircled
pulmonary veins, the most common adopted approach to ablate AF today, did not
predict catheter ablation success.

Results from the DECAAF study show that one of the most important predictors of
ablation outcome was the degree of ablation of the fibrotic tissue; the more
fibrotic tissue that was overlapped with scar during ablation, the better the
outcome. These results were the impetus for the primary objective of DECAAF II.
Patients will be randomized to receive conventional pulmonary vein isolation
(PVI) ablation or PVI + fibirosis-guided ablation. We will follow patients
longitudinally to assess recurrence of persistent atrial arrhythmias (AA)
(atrial fibrillation, atrial flutter or atrial tachycardia as defined by
recent AHA/ACC/HRS guidelines2). We hypothesize that patients receiving
brosis-guided ablation in addition to conventional PVI ablation will have fewer
AA recurrences than those who receive PVI ablation alone.
This proposal is aiming at modifying and improving persistent AF management
guidelines by evaluating targeting DE-MRI detected atrial fibrosis during AF
ablation and its related effect on procedural outcome.

To examine the efficacy of targeting atrial fibrotic tissue during an ablation
procedure in treating persistent AF.
We will also examine the efficacy of the fibrosis-guided ablation on a number
of secondary or exploratory outcomes including the individual components of the
primary endpoint (recurrence of atrial fibrillation, atrial flutter and atrial
tachycardia), symptomatic atrial arrhythmia, AF cycle
length/regularity/termination, cardiovascular (CV)-related hospitalization,
CV-related mortality, quality of life measurements (University of Toronto
Atrial Fibrillation Severity Scale (AFSS), and AF burden.

The safety of the two interventions will be evaluated by evaluating
peri-procedural complications including stroke, pulmonary venous stenosis,
bleeding, esophageal injury,cardiac perforation, heart failure, and death.

DECAAF II is a prospective, randomized, multi-center trial of patients with
persistent AF and presence of atrial fibrosis.
After consenting to participate in the study, the subject will undergo a DE-MRI
scan to assess for extent of atrial fibrosis. After verifying adequate quality
of the DE-MRI study, subjects will be randomized to one of two study groups to
receive conventional PVI ablation (Group 1) or PVI + fibrosis-guided ablation
(Group 2). In Group 1, PVI ablation will be performed as recommended by the HRS
consensus statement2 and physicians will be blinded to the pre-ablation MRI
fibrosis results. In Group 2, physicians will receive the DE-MRI scan prior to
the ablation procedure, will complete conventional PV isolation, and will also
target left atrial fibrosis detected by MRI.

This is an event-driven trial, in which patient enrollment and follow-up will
continue until approximately 517 randomized subjects experience the primary
endpoint of AA recurrence. Under the assumptions described in Section 6 on page
29, it is anticipated that 888 subjects will be randomized, including 444
assigned to Group 1 and 444 assigned to Group 2. The actual number enrolled and
the duration of the follow-up period will be adjusted as necessary to achieve
the 517 required events.

After verifying adequate quality of the DE-MRI study, subjects will be
randomized to one of two study groups to receive conventional PVI ablation
(Group 1) or PVI + fibrosis-guided ablation (Group 2)

There are potential risks related to the fibrosis-guided ablation procedures.
Due to the longer time under anesthesia, more areas being ablated and longer
total procedure time, subjects in the fibrosis-guided ablation group are at
greater potential risk for scarring, injury to peri-esophageal vagal nerves,
esophageal injury, cardiac perforation, and atrial esophageal fistulas.
this risk is offset in part by the potential benefit from fibrosis-guided
ablation, which may provide better clinical outcomes.