Discussion
This study represents the largest, “real-world” analysis of AF
ablation outcomes in patients with continuous, pre- and post-ablation
monitoring using a CIED showing how the measure and definition of
recurrence following ablation can alter interpretation of procedural
success. In short, the incidence of any perceived recurrence of AF
following ablation varies substantially depending on definitions of the
minimum duration of required AF used to define procedural failure and
the surveillance method by which the outcome is assessed. Success rates
quoted in the published literature vary substantially depending on the
above factors as well as whether patients had paroxysmal or persistent
AF at baseline, the ablation technique, the number of ablations and
presence of antiarrhythmic drugs, with recurrences in the first year
after the blanking period being most commonly reported between 60 to
75%20,21,22.
Detection of AF recurrence following ablation is significantly
influenced by the method of monitoring, as is shown in the monitoring
strategy simulation. The strategies of a single 24-hour, 48-hour or
7-day monitor had the poorest test characteristics, especially for AF
events > 6 min where sensitivity and NPV were <
50%, worse than an unbiased coin flip. These results are likely due to
patients having their first recurrences distributed over the year
following the blanking period, and when these AF recurrences occur, they
tend to cluster over consecutive days, as is shown in the heat maps
(Supplement Figure 1 and 2). A 2018 meta-analysis of 66 studies (6941
patients) of AF ablation success in paroxysmal AF found that the method
of AF detection following ablation was predictive of whether recurrence
was detected rather than the specifics of the ablation procedure itself,
with studies using long term CIEDs for monitoring being associated with
higher perceived treatment failures than those using intermittent
discrete monitoring methods13.
Our findings are concordant with the LINQ AF study, which enrolled 419
patients undergoing radiofrequency (RF) ablation to have a LINQ
implantable loop recorder implanted following the procedure. They found
success rate varied with the definition of AF recurrence from 46 –
79%, findings overall similar to our study, and the authors suggest
that > 6 minutes of AF after a 90 days blanking and/or an
AF burden >0.1% be used in future studies as measure of
clinically significant success10.
While historically most clinical trials of AF ablation have used time to
first recurrence as an endpoint3,4,23,24,25 due to
relative ease of measurement, AF burden may be a more objective and
clinically relevant endpoint2,12,26,11. In the
CIRCA-DOSE trial, 346 paroxysmal AF patients were randomized 1:1:1 to RF
pulmonary vein isolation (PVI), 2minute cryoballoon PVI or 4 minute
cryoballoon PVI at least 30 days after implantable loop recorder
implantation. At 12 months, despite only 51.7% - 53.9% of patients
being free of AF, AF burden was reduced by 98.4 –
99.9%14. These results are similar to what was found
in the present study, where in patients with paroxysmal AF, the survival
estimates for the event AF >6 minutes at one year was
28.2% but had a reduction of 99.6% in the overall median percentage of
time in AF. Similarly, in patients with persistent AF, despite the
survival estimate at one year of only 24.9% for AF events
>6 minutes, there was a 99.3% reduction in the overall
median percentage of time in AF.
While improvement in symptoms is the major clinical endpoint of ablation
for AF, AF duration and burden appear to correlate with risk of stroke15,16,18,27, raising the hypothesis that strategies
that reduce AF burden could potentially mitigate stroke risk, even in
the absence of completely eliminating recurrent AF. This hypothesis,
along with the data that AF burden reduction may similarly reduce heart
failure hospitalization and mortality was tested in a recent
random-effect model meta-analysis of large databases, registries and a
single randomized control trial (the CABANA trial1)
with a total of 241,372 patients. It showed that catheter ablation was
associated with a decreased risk of mortality (hazard ratio [HR]
0.62), stroke (HR 0.63) and hospitalization for heart failure (HR 0.64)
when compared to medical therapy alone19. While the
CABANA trial individually was negative for the primary outcome of
death, disabling stroke, serious bleeding, or cardiac arrest, it was
subject to substantial crossover and low event rates, and the
per-protocol analysis findings are largely consistent with the findings
of the aforementioned meta-analysis1.
This analysis has a number of important limitations. It is retrospective
and observational in nature; thus, unmeasured confounding cannot be
eliminated. The population studied were by definition required to have
had prior Medtronic CIEDs implanted, thus introducing significant
selection bias in this group, therefore the results may not be
generalizable to patients without implanted CIEDs. Furthermore, we do
not have accurate data on antiarrhythmic drug use post-ablation, so the
actual success rates of ablation alone may be overestimated. Lastly, in
order to reduce the false positive rate associated with short
unadjudicated AF episodes found on CIEDs, the minimum duration of AF
evaluated was 6 minutes, longer than the 30 second threshold recommended
in guidelines.