Abstract:
While pulmonary vein isolation (PVI) remains the cornerstone for
invasive treatment of atrial fibrillation (AF), patients with persistent
AF still have a high rate of recurrence with this method. Stochastic
Trajectory Analysis of Ranked signals (STAR) mapping uses data from
multiple individual wavefronts during ongoing AF to identify local
drivers of persistent AF. In this non-randomized study, STAR mapping and
ablation showed significantly lower recurrence of atrial arrhythmias
compared to a consecutive PVI-only cohort and a propensity-matched
’conventional ablation’ cohort (consisting of PVI plus complex
fractionated atrial electrogram ablation or linear ablation). This
benefit was driven by a much lower rate of AF recurrence in the STAR
(6.2%) cohort vs PVI-only (44%) or ’conventional’ (40%) with no
significant difference in atrial tachycardia recurrence. Additionally,
AF termination rates during ablation were approximately three times
higher in the STAR cohort. While the analysis is retrospective and not
randomized, the STAR cohort was also the only cohort with complete
cessation of anti-arrhythmic drugs at three months and Holter monitoring
at 6 and 12 months post-ablation per protocol. While STAR mapping
appears to be a very promising new tool for treating persistent AF,
history predicts at least some regression to the mean when future
randomized comparisons are made. The authors have planned a multicenter
randomized trial of PVI plus STAR mapping vs PVI-only for persistent AF.
The global community of electrophysiologists and patients with AF
eagerly awaits the results.
Keywords:
Multipolar mapping, electroanatomic mapping, atrial fibrillation,
persistent atrial fibrillation, atrial fibrillation ablation
While pulmonary vein isolation (PVI) remains the cornerstone for
invasive treatment of atrial fibrillation (AF), patients with persistent
AF still have a high rate of recurrence with this
method.1, 2 Over the last two decades, a multitude of
strategies beyond PVI (such as ablation of lines connecting two
unexcitable structures, complex fractionated atrial electrograms
ablation, or rotor ablation) have shown promise as adjunctive treatments
for patients with persistent or longstanding persistent
AF.3-6 However, most of these initially-promising
strategies have failed to show benefit in multicenter randomized
trials.1, 7 Furthermore, methods that have shown
additional benefit over PVI in multicenter RCTs may raise the risk of
procedural or post-procedure complications (as in the case of hybrid
surgical ablation or left atrial appendage isolation) or require a
different skillset while still leaving a relatively large proportion of
patients with recurrence (vein of Marshall ethanol
injection).8-12
It is in this setting that Honarbakhsh et al present their most recent
retrospective analysis of a novel technique for mapping and ablation of
persistent AF substrate, referred to as Stochastic Trajectory Analysis
of Ranked signals (STAR) mapping.(cite the paper you are publishing
along with the editorial) In brief, STAR mapping uses data from multiple
individual wavefront trajectories during ongoing AF in search of regions
of the atrium that usually precede all nearby areas (thereby acting as
the local source). Areas that activate earliest most often are targeted
for ablation first, and no further sites are targeted if ablation
terminates AF. The computation is carried out via a script in Matlab
(Mathworks, MA, USA) written by one of the authors. In this study, data
collection was performed using either whole-chamber basket catheters or
standard multipolar catheters.13
This study consists of two separate contemporary comparisons: STAR
mapping compared to a propensity-matched ‘conventional ablation’ cohort
and STAR mapping compared to consecutive patients undergoing PVI-only.
In the first analysis, 65 consecutive patients who underwent STAR
mapping with PVI were compared to a propensity-matched cohort who had
‘conventional ablation’ (PVI plus CFAE and/or linear ablation) from the
same operators during the same time period. The second analysis compared
the same STAR patients to 50 consecutive patients who underwent PVI-only
for persistent AF. All three cohorts had an average duration of ongoing
AF > 12 months, though no patient had been in
continuous AF > 24 months (per study protocol). The authors
state that a majority of patients had AF duration >12
months.
The principal finding was a significant decrease in AF/atrial
tachycardia (AT) recurrence in the STAR group (20.0%) compared to
either the PVI-only group (50.0%) or the ‘conventional’ group (50.8%)
driven by a reduction in AF, but not AT, at ≥20 months. Only 6.2% of
patients in the STAR group had documented AF recurrence, while 13.8%
recurred with AT compared to 40% AF and 10.8% AT recurrence in the
‘conventional’ group and 44% AF and 6% AT recurrence in the PVI-only
cohort. AF termination rates during ablation were also significantly
higher in the STAR cohort (69.2%) compared to the conventional ablation
cohort (15.4%) or the PVI-only cohort (26.0%; p<0.001 for
both comparisons). It is not clear how or why the rate of AF termination
was higher in the PVI-only group than the conventional ablation group,
but the overall numbers of AF terminations in these two groups was
small, and these two groups were not matched in any way to one another.
Therefore, this apparent discrepancy between the ‘control’ groups could
be due to chance or selection bias.
Procedure time was not statistically different in the STAR,
conventional, and PVI-only groups (225.4±65.6 min vs. 219.0±64.8 min vs.
208.5±59.4min; p=NS for both comparisons), though the total RF time was
greater in the STAR group than the PVI-only group. The fact that the
STAR method appeared to add only 17 minutes to the procedure time over
PVI seems like a reasonable concession for a method that appears to
improve outcomes. However, the fact that the ‘conventional’ ablation
group procedure time was only 11 minutes longer than the PVI-only group
suggests that this group did not, in general, have extensive substrate
modification (seven had only cavotricuspid isthmus ablation as the only
ablation beyond PVI).
The overall methods of the paper are somewhat complex given two separate
comparisons with different types and degrees of matching between the
groups. Additionally, the analysis is retrospective in nature, and it
cannot be known why a patient would receive STAR mapping, ‘conventional
ablation,’ or PVI-only. Therefore, this study is useful for hypothesis
generation, but it does not prove causation with regard to differential
outcomes as the groups are very likely different. That being said, the
methods (other than assignment to groups) would likely favor the STAR
group having more complete detection of clinically-silent
recurrence as this was the only group with mandated rhythm monitoring
(Holter at 6 and 12 months). The STAR cohort was also the only group in
whom all AADs were stopped at 3 months post-ablation per protocol.
There is potentially a lot to like about the STAR method as described.
The overall idea behind it (identify sites that repeatedly seem to
activate prior to all nearby sites) seems more intuitive to the
proceduralist and takes less time than, for example, focal impulse and
rotor modulation as initially described.5 While this
technique seems somewhat similar in concept to non -invasive AF
mapping that has been described previously, the present study seemed to
show greater likelihood of AF termination when ablating AF drivers in
those with AF lasting longer than 12 months and may not be associated
with the same high rates of post-ablation AT.14, 15The exceptionally low rate of AF (rather than AT) recurrence (6.2%) in
the STAR group provides cause for hope that this method is effectively
targeting the sources of initiation and perpetuation of persistent AF.
For comparison, the three arms of the STAR AF 2 trial (PVI-only, PVI
plus lines, PVI plus CFAE) which enrolled patients with perhaps more
advanced AF (lasting up to 3 years with left atrial size 4.4 cm as
opposed to 3.8 cm in the current study) had AF recurrence rates of
41-59% at 18 months.1 Providing at least a small dose
of reality to the results of the current study, the 13.8% rate of AT
recurrence with STAR mapping seems generally in-line with the 11-14%
seen across the three arms of the STAR AF 2 trial.
Again, this is not a randomized study, and as such, assignment of
causation is hazardous. While it is certainly possible that STAR mapping
is much more effective than PVI alone or ‘conventional ablation’ as
defined in this study for persistent AF, that would mean that this
method is likely more successful than any prior endocardial method that
has been tested in randomized trials for persistent AF. While that is
very possible, and may even be likely, history predicts at least some
regression to the mean in a randomized, multicenter evaluation.
Looking more generally to the horizon of AF treatment, we should
anticipate therapies to improve the effectiveness and safety of our
lesions (electroporation), to ablate tissue previously unreachable
(ethanol injection into the vein of Marshall), and, perhaps, to identify
ongoing non-pulmonary vein drivers of AF (STAR mapping). While we can
hope that this is a breakthrough, the field of persistent AF ablation is
littered with abandoned methods (beyond PVI) that have not been borne
out in randomized studies. The authors have planned a multicenter
randomized trial of PVI plus STAR vs PVI-only.
The global community of
electrophysiologists and patients with AF eagerly awaits the results.
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