Discussion
To the best of our knowledge, this is the first study addressing the
outcomes of CA in renal and hepatic transplant patients with AF. We
found no significant differences between the transplant group and
control group with respect to atrial arrhythmia event-free rate after
the initial and repeated procedures. Furthermore, there was no
significant difference in the incidence of procedure-related
complications between the two groups, and there was no transient
allograft dysfunction in the transplant recipients after CA.
AF is common in abdominal solid-organ transplant
recipients11. Previous studies have demonstrated that
the prevalence of preexisting AF in renal and hepatic transplant
recipients is 7.0% and 5.6%, respectively, and that the incidence of
AF after kidney and liver transplantation is 4.9% and 8.5%,
respectively7, 8. The high prevalence of AF may mean
that patients receiving kidney or liver transplants appear to be at
higher risk22-24. Besides, long-term application of
immunosuppressants after transplantation might lead to or accelerate
cardiovascular diseases. 25, 26. Patients with AF
carry a higher risk of mortality and adverse cardiovascular
events3. Previous studies have shown that AF is
associated with inferior survival in abdominal solid organ transplant
recipients, and the impact of AF on morbidity and mortality in these
recipients is striking11-13.
The beneficial effect of CA on maintaining SR and improving quality of
life has already been confirmed27,
28.
The CASTLE-AF study noted that compared with medical therapy, CA for
treating AF in patients with HF was associated with a 47% lower rate of
mortality29. The present study showed that the
SR
maintenance rate in the abdominal solid-organ transplant recipients
after the initial (71.4%) and repeated (78.6%) CA sessions did not
differ from that in the matched group. In addition, there was no
significant difference in the incidence of procedure-related
complications between the two groups. These findings indicated that the
ablation procedure might be an appropriate choice for the treatment of
AF in renal and hepatic transplant
recipients. In this study, none of the recipients died during the
follow-up period. Considering the higher cardiovascular risk factors in
solid organ transplant recipients with AF, they might benefit from CA in
the long term. Next, studies should focus on whether CA could improve
the long-term survival of abdominal transplant recipients with AF.
AF is associated with a higher risk of stroke, and AF-related stroke
leads to more fatalities and is more disabling than non-AF
stroke30. Anticoagulants are an effective therapy to
prevent AF patients from suffering stroke31. However,
in
renal and hepatic transplant recipients with AF, who are populations at
high cardiovascular risk, evidence regarding the efficacy and safety of
anticoagulation for AF is lacking. A retrospective study highlighted
that only 24% of kidney transplant recipients with newly diagnosed AF
received warfarin, which was less than the general population (51%).
The retrospective study also found that warfarin was associated with a
small nonsignificant reduction in the composite outcome of death, stroke
or gastrointestinal bleeding in renal transplant recipients with AF
[hazard ratio=0.92, 95% confidence interval
0.83-1.02]32.
In the general population with nonvalvular atrial fibrillation, NOACs
are increasingly used, replacing vitamin K antagonist anticoagulants and
demonstrating efficacy and safety in thromboembolism
prevention33. To date, data regarding the clinical use
of NOACs in renal and hepatic transplant recipients are
limited34, 35. NOACs may interact with
immunosuppressive therapy18, 19. All NOACs are
substrates of the multidrug
transporter P-glycoprotein (P-gp), with apixaban and rivaroxaban also
being substrates of CYP450 3A4. Calcineurin inhibitors (CNIs) are known
substrates of CYP450 3A4 and P-gp, and also inhibitors of P-gp. In the
present study, all the allograft recipients were maintained by CNIs.
Concomitant prescription with NOACs might increase NOAC plasma levels
and lead to an increased risk of bleeding.
In
this particular condition, pharmacokinetic/pharmacodynamic drug
monitoring might be helpful to limit the risks of drug-drug
interactions. In our study, there were no thrombotic or bleeding events
in renal and hepatic transplant recipients using NOACs during the
perioperative and follow-up periods.
Abdominal solid organ recipients are
vulnerable groups suffered variations in kidney or liver functions and
are at higher risk of thrombotic and bleeding complications, with
possible interactions with immunosuppressive agents. Given these issues,
achieving long-term SR maintenance by CA in renal and hepatic transplant
recipients may be a good choice to minimize the need
for oral anticoagulants.
The treatment options available to achieve effective rhythm control in
renal and hepatic transplant recipients are limited. The coexistence of
comorbidities and risk of drug interactions caused by
polypharmacological therapy restrain the use of AADs.
Amiodarone-tacrolimus interactions leading to QT prolongation and fatal
arrhythmias in transplant recipients have been
reported16, 17. In addition, dronedarone might
increase tacrolimus levels, promote tacrolimus toxicity and potentially
extend the QT interval in the electrocardiogram14, 15.
Accordingly, AADs are rarely prescribed for >3 months due
to the increased risk of drug interactions in solid organ transplant
recipients. In the present study, all transplant recipients with AF
discontinued AADs
after
successful ablation. With these premises, achieving long-term SR
maintenance through CA in renal and hepatic transplant recipients
appears crucial to minimize the need for AADs.