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.