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.