Comparison with Previous Studies
SCE is potentially associated with unfavorable neuropsychological
outcomes. Previous studies demonstrated that the uninterrupted OAC
minimized the risk of SCEs during AF ablation compared to interrupted
OAC;4 expert consensus and guidelines first recommend
the use of NOACs or VKA without interruption during the
procedure.12 However, recent studies have reported
that the incidence of MRI-detected SCEs still hovers at 2% to 27.2 %
in patients on uninterrupted OAC for AF
ablation.5,13-17 In the present study, the SCE
incidence remains at 23.1% in total, and was almost similar to or even
higher than the incidence in the previous studies.
Different protocols of intra-procedural UFH administration may affect
the incidence of SCEs despite of the same ACT target (>300
sec) during the procedure. Kirchhof et al. have reported that the SCEs
at postprocedural MRI were identified in 84 out of 323 patients on
uninterrupted apixaban or VKA (26.0%); a bolus of UFH (100 IU/kg, based
on body weight) was first administered prior to transseptal puncture, as
in the present study.13 On the other hand, Di Biase et
al. have demonstrated that the SCEs were detected in only 2 out of 86
patients on uninterrupted rivaroxaban (2.3%); the designated amount of
UFH was first injected (10,000/8,000 IU in male/female, irrespective of
body weight) before transseptal puncture.15 The amount
of the first UFH shot seems to be higher in the previous study by De
Biase et al. than in the present study (4000-6000IU, based on Japanese
body weight), which likely shortens the time to reach the optimal ACT.
UFH boluses were intermittently administered during the procedure in the
previous and the present studies, however the transseptal sheaths were
also continuously infused with UFH saline in the previous study by De
Biase et al.,15 which may advantage keeping ACT levels
constant and avoiding clot formation within the sheaths.
Different diagnostic criteria determined by brain MRI may also affect
the SCE incidence. Guijian et al. reported that SCE incidence was 8%
when using the definition of both abnormal diffusion-weighted image and
fluid-attenuated inversion recovery (FLAIR) image, but when considering
all abnormal diffusion-weighted images, the incidence rose to
27%.18 We diagnosed SCE using only diffusion-weighted
images according to a neuroimaging expert’s recommendation, which may
increase sensitivity.11
Previous studies have reported the risk factors for SCEs, including age,
spontaneous echo contrast, complex fractionated atrial electrograms
ablation, low left ventricular ejection fraction, perioperative coronary
artery imaging, low mean perioperative ACT, electrical/pharmaceutical
cardioversion, and arterial hypertension, etc.19-24However, these factors were identified in patients taking only VKA, but
not NOACs. Kimura et al. demonstrated that the presence of deep and
subcortical white matter hyper-intensity and the frequency of
cardioversions were associated with SCEs in patients taking rivaroxaban
or VKA without interruption during the procedure.17 In
this study, LAD, baseline ACT before UFH injection, and time to reach
the optimal ACT were significant risk factors for SCEs. To the best of
our knowledge, we first demonstrated that intra-procedural ACT kinetics
significantly affect the incidence of SCEs in patients on uninterrupted
NOACs/VKA for AF ablation. Nevertheless, the information on this issue
is still largely limited.
The ACT kinetics during the procedure are affected by the
peri-procedural anticoagulation strategy.10Microthrombus can form immediately after a sheath/catheter is inserted
into the body. Therefore, it is better for patients to achieve the
optimally anticoagulated condition as quickly as possible. The present
study demonstrated that different anticoagulants had different impacts
on the intra-procedural ACT. Martin et al. demonstrated that at
baseline, NOACs prolonged ACT differently; ACT was longer with
dabigatran and shorter with apixaban,25 being
consistent with our results. Dabigatran may have the advantage of
decreasing the risk of SCE in terms of baseline ACT prolongation. Martin
et al. also demonstrated that ACT prolongation in response to UFH was
significantly smaller in rivaroxaban/apixaban than in
dabigatran/VKA,25 which may underlie the longer time
needed to reach the optimal ACT in rivaroxaban/apixaban in our study.
Modifying the intraprocedural dosing of UFH may decrease the time to
reach the optimal ACT and reduce the incidence of SCEs. However, the
optimal ACT target (>300 sec) was validated in VKA-treated
patients and may not be directly applied to those on NOACs; a specific
regimen/monitoring of UFH in each NOAC may be required.
In the present study, apixaban and warfarin had the higher incidence of
SCEs than the other anticoagulants although the difference did not reach
statistical significance. Accumulating evidence has demonstrated a
unique anticoagulation profile in each anticoagulant. In this study, the
number of patients was relatively higher in dabigatran group than in the
other groups likely because of the favorable outcome of dabigatran in
RE-CIRCUIT study.26 Physicians may use and/or choose
an anticoagulant in a patient with a specific clinical background based
on the evidence; apixaban and warfarin tended to be prescribed in the
more elderly patients who had higher thromboembolic risk in the era of
uninterrupted NOACs/VKA.