Review on "High-Density
Mapping of Atrial Fibrillation in Humans: Relationship Between High-Frequency
Activation and Electrogram Fractionation"
Triggers, drivers and substrate: the moving target?
Southlake Regional Health Center,Newmarket, Ontario, Canada
Corresponding Author:Yarriv Khaykin, 105-712 Davis Drive, Newmarket, ON, Canada, L3Y 8C3.
Catheter ablation has rapidly gained acceptance as a
mainstay of therapy for many symptomatic patients with atrial fibrillation
since the original publication by the Bordeaux group . Early on it became apparent that in most patients with
paroxysmal AF, the arrhythmia was initiated by focal firing in the pulmonary
veins. Ablation focused on elimination of such triggers and was largely limited
to patients who would stay in sinus rhythm long enough to allow successful
mapping within the pulmonary veins. As this was time consuming and was
associated with high risk of developing pulmonary vein stenosis, ablation lesions
were moved further and further away from the sources of focal firing with
co-development of Circumferential Pulmonary Vein Ablation (CPVA)  aiming to encompass pulmonary vein ostia with circular
lesions without verification of conduction block and Segmental Pulmonary Vein
Isolation  evolving into Pulmonary Vein Antrum Isolation  with the targeted area similar to that in CPVA but with
requisite documentation of entry and / or exit block of conduction. While
successful in the majority of patients with paroxysmal AF, these approaches
were lacking in patients with persistent and permanent AF. A concurrent
approach addressing the fibrillatory substrate was developed and proved to be a
successful standalone alternative to lesions encircling the pulmonary veins at
one center . This approach had the advantage of better tailoring the
lesion set to the individual patient and potentially limiting energy delivery
and associated risks. Addressing fibrillatory conduction as an adjunct to
ablating triggers had since become incorporated into the lesion set targeting
persistent and permanent atrial fibrillation in a stepwise approach popularized
by the Bordeaux group . At the same time better tools have enabled clinicians to
probe deeper into the complex interaction of the mechanisms initiating and
maintaining atrial fibrillation. So in experimental models of atrial
fibrillation “drivers” or areas of microreentry were seen surrounded by areas
of fibrillatory conduction [7-9]. Research
has pointed to the possibility of the “drivers” or “triggers” to be in close
proximity to areas of atrial myocardium innervated by autonomic ganglionated
plexi with areas of fibrillatory conduction 1-2 cm remote from these . Relationship between areas of high dominant frequency and
atrial tachyarrhythmias that follow AF ablation has been demonstrated  suggesting that such arrhythmias may actually drive AF
prior to defragmentation.
In their paper published last month , Drs Stiles and Brooks describe high-density bi-atrial mapping
during atrial fibrillation prior to ablation to identify areas of presumed
drivers and fibrillatory conduction. The investigators collected around 500
points in each of the 20 patients during atrial fibrillation using a PentaRay
(Biosense Webster, Diamond Bar, CA, USA) catheter and NavX software (St. Jude
Medical, St. Paul, MN, USA). Each point was screened manually to eliminate
points with unacceptable signal-to-noise ratio. Eight second recordings were
used. Points were stratified into one of 4 right atrial or 8 left atrial areas.
The authors then processed the collected signals to arrive at three-dimensional
maps of dominant frequencies (DF) and complex fractionated atrial electrograms
(CFAE). CFAE were mapped using integral “CFE-mean” included as part of the NavX
distribution with a refractory period set at 30ms, peak-to-peak sensitivity set
to 0.1 mV and signal duration set at 10 ms. Points with a CFE-mean value of 40
– 250 ms were included in the analysis. DF analysis occurred offline using Coperniqs
software (Medicalgorithmics, Austin, TX, USA) which allowed the investigators
to analyze only those points exhibiting high degree of signal regularity. They
confirmed prior findings of frequency gradients between the left and the right
atria and found that signal frequency was higher in patients with persistent
AF. Median CFE-mean and median DF correlated with AF cycle length. Clusters of
points with the shortest SFE-mean and highest DF were spatially compared.
Patients with paroxysmal AF had higher DF around the pulmonary veins, left
atrial appendage and the roof, whereas those with persistent AF had a more
uniform distribution of DF throughout the left atrium. Areas of highest
fractionation clustered around the left atrial roof, posterior, inferior and
anterior walls and the septum in all patients. Median distance between DF and
CFAE clusters was 5 mm with 80% of DF clusters within 10 mm of CFAE clusters.
This is an important contribution to the literature on the
mechanisms of atrial fibrillation highlighting frequency distribution
differences between paroxysmal and chronic AF, where patients with persistent
AF have a more uniform distribution of the areas with high DF and faster global
AF cycle lengths. These differences may be responsible for the difference in
ablation success rates between AF subtypes. The investigators demonstrated a
close spatial relationship between areas of high DF and surrounding areas of
high fractionation, suggesting that the two are indeed related and as was seen
in experimental optical mapping studies, fibrillatory activity represented by
CFAE surrounds more organized “drivers” with high DF. Such local frequency
gradients were further supported by limited activation mapping. No conclusions
could be drawn on whether or not ablation of the high DF sites could help
improve outcomes since DF analysis occurred offline and DF mapping was not used
to guide ablation. There is emerging evidence that ablation guided using DF or CFAE  mapping may result in higher success rates, but the
question of whether CFAE or DF is a more important ablation target remains to
be answered. While development of tools which will allow rapid high density
activation mapping to better delineate the relationship between DF and CFAE and
hopefully fine-tune the ablation strategy is ongoing, ablation targeting
anatomical substrate of the pulmonary veins with tailored adjunctive
defragmentation will likely remain at the core of invasive treatment for AF.
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