Amiodarone Prophylaxis Is Reasonably Safe and Potentially Beneficial After CF-LVAD

In Response: We are grateful for the opportunity to address Drs. Kataoka and Imamura’s1 thoughts regarding our paper: “Safety and Efficacy of Prophylactic Amiodarone After Left Ventricular Assist Device.”2 Drs. Kataoka and Imamura1 are correct that the data supporting the definitive impact of preventing all postoperative arrhythmias is uncertain. While the studies they have referenced suggest no association between early ventricular arrhythmias and in hospital morbidity and mortality after left ventricular assist device (LVAD) implantation,3, and that the presence of atrial fibrillation is not associated with the development of hemocompatibility-related adverse events in patients with an LVAD,4 there is other evidence that demonstrates postoperative arrhythmias may lead to negative outcomes in LVAD patients. For example, the study Drs. Kataoka and Imamura1 reference asserting that ventricular arrhythmias do not impact hospital morbidity and mortality also demonstrates that ventricular arrhythmias early after LVAD were associated with an increased incidence of cardiogenic shock, mechanical ventilation, tracheostomy, or percutaneous endoscopic gastrostomy (PEG) tube placement.3 Kilic et al.5 reported that development of a cardiac arrhythmia during index hospitalization after LVAD was associated with a ~2-fold increased risk of developing secondary adverse events including respiratory failure, infection, and bleeding. Furthermore, a study by Jedeon et al.6 conducted in the United States found that patients with early post–continuous-flow left ventricular assist device (CF-LVAD) ventricular arrhythmias had a significantly higher 3-month mortality (20.2% vs. 9.3%, p = 0.004). Of note, the case report Drs. Kataoka and Imamura1 mention regarding catheter ablation for ventricular arrhythmia management occurs 1 year after LVAD implantation, which does not fit the same scope as our original study.7 It is worth noting that the implementation of the prophylactic (new start in patients not already receiving the medication before LVAD placement) amiodarone loading protocol (which was in place from 2014 to 2018 at our institution) was in response to a small series of early postoperative arrhythmias that led to readmission to the hospital shortly after the index CF-LVAD implantation. In addition, the use of early postoperative amiodarone prophylaxis was intended to prevent hemodynamic instability that could directly lead to right ventricular failure. We elected to monitor for liver and thyroid toxicities given their well-established prevalence during amiodarone use. Amiodarone-related transaminitis is reported to occur in up to 25% of patients with more severe clinically significant liver disease occurring in up to 3% of patients.8 Similarly, thyroid abnormalities occur in up to 24% of patients.9 By comparison, pulmonary toxicities occur more infrequently, only up to 10%.10 Risk typically correlates with prolonged treatment, higher daily doses, and higher cumulative doses. Since the median duration of amiodarone for prophylaxis in our study was 85 days, we elected to study only the more prevalent indicators of amiodarone toxicity. We did not collect the use of KL-6 or SP-D biomarkers for this study. While there are reports of their use in amiodarone pulmonary toxicity, these biomarkers are not readily available or utilized in the United States for regular amiodarone monitoring. Renin-angiotensin-aldosterone system inhibitors are routinely discontinued early during the preimplant hospitalization at our institution to prevent intraoperative vasoplegia and are not restarted for several days to a week after implant (at the earliest), so this was unlikely to confound the effect of amiodarone on arrhythmias in our study. Finally, Drs. Kataoka and Imamura1 inquire about the patients in the amiodarone group that encountered death or CF-LVAD exchange. Unfortunately, the specific cause of death in our study was not collected, so we cannot offer further comment. In summary, given the relatively low risk of a short course of amiodarone, its association with an overall lower risk of tachyarrhythmias in our study, and prior data indicating that early arrhythmias after LVAD placement are associated with hemodynamic instability and other poor short-term outcomes, we consider it very reasonable to consider short-term prophylaxis with amiodarone early after LVAD placement. As a closing note, we would again like to thank Drs. Kataoka and Imamura1 for their careful review of our paper. We agree that it would be of great interest to continue to investigate tachyarrhythmia-induced hemodynamic deterioration as a primary outcome and look forward to any future contributions regarding this topic.