DISCUSSION
A protocol guided approach which accounted for pre-procedure oral
anticoagulation and weight resulted in a higher administered dose,
increased proportion of therapeutic ACT values, and a decreased time to
therapeutic ACT. The findings were driven by a large number of those on
pre-procedure DOAC, which reflects contemporary practice. The complexity
of left atrial ablation procedures requires attention to multiple
variables, and the standardization of peri-procedural anticoagulation by
means of protocol guidance may result in a reduction in untoward
outcomes.
Much attention and investigation has been directed towards the optimal
choice of pre-procedural oral anticoagulation, and whether to proceed
with an interrupted versus uninterrupted strategy. For those randomized
trials which investigated uninterrupted pre-procedure oral anticoagulant
administration during AF ablation, a fixed dose based on sex or weight
was given. These trials did not address both body weight and prior oral
anticoagulation strategy while dosing UFH to achieve a therapeutic
ACT.8–12 However, intravenous unfractionated heparin
pharmacokinetics should be considered, as they are dose and weight
dependent. The half-lives of 25, 100, and 400 U/kg UFH are 30, 60, and
150 min, respectively. At lower doses, the infused heparin binds
directly to macrophages and endothelial cells, where it gets
depolymerized. At higher doses, this mechanism becomes
saturated.13 Continuous infusion after bolus may allow
for a steady state UFH plasma level, and lead to increased proportion of
therapeutic ACT levels.14
In addition to weight, pre-procedure OAC should be considered given the
preponderance of data indicates that ACT response differs when warfarin
is compared to DOAC therapies.4,15 Pre-procedure DOAC
results in larger required weight-based peri-procedural UFH bolus to
achieve a desired ACT of > 300
seconds.15,16 Additionally, body weight has been
suggested as a predictor of UFH requirement for those who are on
pre-procedure rivaroxaban, during left atrial
ablation.17
To minimize the burden on the operator and decrease the proportion of
sub-therapeutic ACT values, an institutional protocol was initiated with
previously validated safety outcomes.6 We leveraged
the temporal initiation of the peri-procedural anticoagulation protocol
to evaluate whether it had an effect on dosing practices, and ACT
outcomes. A peri-procedural anticoagulation protocol resulted in a
higher dose of heparin administered as the initial bolus and
improved ACT outcomes, primarily driven by dosage changes in patients
receiving a pre-procedure DOAC. Those on DOAC (particularly the
Factor Xa inhibitors) were the majority of patients evaluated,
reflecting contemporary anticoagulation practices. Heparin under-dosing
in patients receiving DOACs may have been influenced by the omnipresent
risk of bleeding complications and the lack of an easily obtained
reversal agent for the factor Xa inhibitors. The initiation of a
peri-procedural anticoagulation protocol may have empowered the
operators in the study to administer larger bolus doses of UFH, which
resulted in earlier and increased proportion of therapeutic ACT values.
Sub-therapeutic ACT values have been correlated to silent ischemic
events identified on MRI,5 which further highlights
the value of peri-procedural anticoagulation strategies to balance
safety with efficacy.
The small numbers of patients on warfarin limit meaningful conclusion.
Patients receiving warfarin were administered larger bolus dose than
initially recommended by our protocol, resulting in both a high number
of therapeutic and supra-therapeutic ACT values. Patients receiving no
pre-procedure oral anticoagulation received larger doses than the
protocol recommended, yet had lower rates of therapeutic ACTs. The
employed protocol mirrored weight based recommendations based on
previous data with adequate safety profile, for which those on no pre
procedure anticoagulation received a lower heparin bolus than those on
DOAC. Linear regression analysis of these patients revealed that a dose
of at least 120 U/Kg was likely required to achieve an ACT of 300
seconds in half of the patients, however prospective validation is
required before delivering a definitive weight-based recommendation in
those without pre-procedure oral anticoagulant.