Amiodarone for the Management of Acute Atrial Arrhythmias After Lung Transplant

Amiodarone for the Management of Acute Atrial Arrhythmias After Lung Transplant | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Amiodarone for the Management of Acute Atrial Arrhythmias After Lung Transplant Jesus Escamilla, Spenser January, Keith Fester, Laura Hencken, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6206184/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 May, 2025 Read the published version in Cardiovascular Drugs and Therapy → Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: Dosing, safety, and outcomes of amiodarone in acute post-operative atrial arrhythmias (POAAs) after lung transplantation are not well understood. Current literature suggests amiodarone may increase mortality in lung transplant recipients (LTRs). This study described outcomes associated with amiodarone use in POAAs after lung transplantation. Methods: This single-center, retrospective cohort study analyzed LTRs who received amiodarone after developing a POAA within 30 days of transplant surgery and prior to hospital discharge from their index transplant admission. Primary safety outcomes included mortality and the incidence of adverse drug reactions (ADRs). Secondary efficacy outcomes included time to normal sinus rhythm (NSR) attainment, intensive care unit (ICU) and hospital length of stay, and atrial arrhythmia (AA) recurrence. Results: A total of 131 LTRs who developed an acute POAA received amiodarone. The 1-year mortality did not differ between this cohort and our overall lung transplant population, and ADR incidence was similar to that observed in non-LTRs. The median time to NSR attainment was 28 hours after amiodarone initiation; ICU and hospital lengths of stay were 4.5 and 18.5 days, respectively; and AA recurrence occurred in 32.8% of patients. Conclusion: The findings of this study suggest that amiodarone use may be safe in LTRs with acute atrial arrhythmias, and may also effectively terminate acute POAAs in this population. lung transplantation arrhythmias amiodarone safety Figures Figure 1 Background The process of lung transplantation exposes patients to risk of post-operative complications, which may include cardiovascular complications such as post-operative atrial arrhythmias (POAAs).[ 1 ] POAAs after lung transplantation are a common occurrence with a reported incidence of 20–46% and may manifest at any timepoint post-transplant, with early atrial arrhythmias (AAs) occurring in the first week post-transplant, being most common.[ 2 – 5 ] These AAs, which include atrial fibrillation and atrial flutter, have been associated with hemodynamic instability, atrial thrombosis, and decreased long-term survival.[ 6 ] Precipitating factors include perioperative fluid shifts, activation of the renin-angiotensin-aldosterone system, utilization of inotropic or vasopressor support, pain, and the presence of inflammatory mediators. These contributory factors are temporary and POAAs are usually transient.[ 7 ] POAAs are most often managed with amiodarone and beta 1 receptor antagonists.[ 7 ] Literature in LTRs has identified that anti-arrhythmic drugs such as amiodarone may be associated with reduced survival, but the extrapolation of these studies is difficult given lack of information on the amount of amiodarone patients received, broad grouping of patients into anti-arrhythmic and rate-control strategies, and reported one-year mortality rates much higher than the national average.[ 3 , 8 , 9 ] Given these gaps in literature, this study sought to describe the management and outcomes in LTRs with early acute POAAs that were treated specifically with amiodarone. Materials and Methods This was a single-center retrospective cohort study of adult LTRs at Barnes-Jewish Hospital/Washington University in Saint Louis, Missouri that were transplanted between June 1st, 2018 and November 15th 2022. Patients were included if they developed an acute POAA post-transplant. Acute POAA were defined as an atrial arrhythmia that occurred within 30 days following transplant surgery and prior to hospital discharge from their index transplant hospitalization. Patients were excluded if they received a multi-organ transplant or if they experienced ventricular arrhythmias. Patients were followed from their date of lung transplantation through one-year post-transplant or death, whichever occurred first. The patient cohort was identified from a list of LTRs via ICD-10 codes for atrial fibrillation and atrial flutter or the receipt of amiodarone post-transplant, and POAA development was confirmed via 12-lead electrocardiogram (ECG). This study was approved by the local institutional review board. At Barnes-Jewish Hospital, patients with POAA following lung transplantation may be treated with a rate-control strategy, rhythm-control strategy, or a combination based on physician preference and patient hemodynamics at the time of POAA. Dosing of POAA treatment is not standardized. Patients were categorized as having been managed with amiodarone if they received any amount of amiodarone prior to attainment of normal sinus rhythm (NSR). In addition to amiodarone monotherapy, patients may have received a combination of amiodarone and rate control strategies consisting of beta 1 receptor antagonists, non-dihydropyridine calcium channel antagonists (non-DHP CCB), or digoxin. Dosing of amiodarone was defined as bolus only (single 150 mg dose), partial amiodarone load (less than 6 grams of amiodarone), full amiodarone load (defined as greater than 6 grams of amiodarone), or maintenance (defined as receipt of amiodarone 100–200 mg daily). Duration of amiodarone post-transplant is not protocolized but in general, given the transient nature of POAA, amiodarone is discontinued by month three post-transplant. Data related to pain score was collected using the Numeric Rating Scale (NRS) pain score, which is an 11-point scale that ranges from 0 to 10 to describe pain severity, where a score of 0 indicates no pain while a score of 10 indicates the worst pain possible. Outcomes evaluated included one-year all-cause mortality, time from POAA development to NSR (defined as NSR on ECG for at least 48 hours without recurrence of an AA), incidence of AA recurrence (defined as the development of a new AA after previous attainment of NSR for at least 48 hours), length of hospital stay of index transplant visit, length of ICU stay after transplant, incidence of hospital readmissions within the first year post-transplant, and the incidence of adverse drug reactions associated with amiodarone use within one-year after transplant. Adverse drug reactions assessed were hypotension, bradycardia, thyroid derangements, and hepatotoxicity. Hypotension was defined as discontinuation of amiodarone with the reason being cited in the electronic health record (EHR) to be due to low blood pressure, the initial use of vasopressors or inotropes while receiving amiodarone, or a blood pressure of less than 90/60 mmHg while receiving amiodarone. Bradycardia was defined as discontinuation of amiodarone with the reason being cited in the EHR to be due to low heart rate or a heart rate of less than 60 beats per minute. Thyroid derangements were defined as hypo- or hyperthyroidism based on thyroid stimulating hormone and free T 4 outside of the normal range. Hepatotoxicity was defined as defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 150 units/L. Data were collected via review of the EHR. Descriptive statistics were utilized for reporting of results. Results A total of 323 patients received a lung transplant during the study timeframe, and 156 of those patients developed a POAA after lung transplant (48%). Twenty-five of those patients did not receive amiodarone, and therefore a total of 131 patients were included in this study (Figure 1). Baseline characteristics can be found in Table 1. A history of atrial arrhythmia prior to transplantation was noted for 31.3% of the patients. The median time from transplant to POAA development was 119 hours. Seventy-two percent of the amiodarone group were receiving pain medications in the form of a bupivacaine epidural, hydromorphone patient-controlled analgesia, or a lidocaine intravenous infusion prior to POAA development. The most common amiodarone management strategy consisted of a partial amiodarone load, which 81.7% of patients received. The mean cumulative amiodarone dose at the time of NSR attainment was 2,670 mg (range: 150 mg- 17,001 mg). Amiodarone maintenance following a partial or full load was initiated in 79.4% of patients, and the median duration of amiodarone therapy was 44 days. A total of 49.5% patients received a combination of amiodarone and rate control agents at the time of NSR attainment. No patients were receiving amiodarone therapy at 1-year post-transplant. Table 1: Baseline Characteristics Characteristics (n=131) Age, years, median (IQR) 61 (57-66) Female, n (%) 34 (26) Caucasian, n (%) 120 (91.6) BMI, kg/m 2 , mean ± SD 26.4 ± 4.26 Etiology of lung disease, n (%) Cystic fibrosis ILD IPF COPD PH Other Unknown 5 (3.8) 16 (12.2) 62 (47.3) 20 (15.3) 22 (16.8) 4 (3.1) 2 (1.5) LAS, median (IQR) 38.2 (35.3-43.8) PGD score, median (IQR) 1.00 (1.00-1.25) History of CABG, PCI, or CAD, n (%) 25 (19.1) History of lung wedge resection at time of transplant, n (%) 20 (15.3) History of atrial arrhythmia, n (%) 41 (31.3) CVP at time of POAA, mmHg, median (IQR) 7.50 (5.00-11.0) Pain score at time of POAA, median (IQR) 5.00 (2.00-7.00) Pressor or inotrope use at time of POAA, n (%) 48 (36.6) Concomitant rate control agent use, n (%) 65 (49.6) Time from transplant to POAA, hours, median (IQR) 119 (72.0-185) Abbreviations: AA, atrial arrhythmia; BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; CVP, central venous pressure; ILD interstitial lung disease; IPF, idiopathic pulmonary fibrosis; IQR, interquartile range; LAS, lung allocation score; PCI, percutaneous coronary intervention; PGD, primary graft dysfunction; PH, pulmonary hypertension; POAA, post-operative atrial arrhythmia Mortality within the first post-transplant year occurred in 6.1% of patients, with no cause of death attributable to amiodarone-related toxicity. Causes of death within 1-year post-transplant consisted of bronchiolitis obliterans syndrome (0.8%), COVID-19 infection (1.5%), complications of cirrhosis which developed after completion of amiodarone therapy (0.8%), septic shock (1.5%), spontaneous bleed and altered mental status resulting in transition to comfort care (0.8%), and unknown (0.8%). The most common adverse drug reaction in patients treated with amiodarone was hypotension, which occurred in 20.6% of patients. Thyroid derangements occurred in 13.7% of patients, while hepatoxicity was noted in 15% of patients. Bradycardia had the lowest incidence, at 7.6%. The median time from POAA development to NSR attainment was 28 hours, and the median ICU and hospital lengths of stay post-transplant were 4.5 days and 18.5 days, respectively. AA recurred in 32.8% patients with a median time to recurrence of 5 days from initial NSR attainment, and 9.9% patients were on amiodarone at the time of AA recurrence. Six (4.6%) patients were readmitted for AA within the first-year post-transplant, and only one of these patients had still been taking amiodarone at the time of their readmission for AA. The number of patients who progressed to direct current cardioversion (DCCV) or catheter ablation within 1-year post-transplant was 19 (14.5%) and 2 (1.5%), respectively. Discussion In this study of 131 LTRs, short term treatment with amiodarone did not increase mortality and demonstrated a low incidence of side effects with restoration of NSR in most patients. Previous literature has asserted that amiodarone increased the risk of mortality after lung transplant.[ 3 , 8 , 9 ] Our comprehensive analysis of amiodarone treatment revealed a 1-year mortality rate of 6.1%, which is lower than the 1-year mortality of the lung transplant cohort reported by the Scientific Registry of Transplant Recipients of 9.7%.[ 10 ] In contrast, the study by Isiadinsio et al. reported a much higher mortality rate of 63% in the first 200 days post-transplant in patients given amiodarone.[ 3 ] However, 16% of their patient population remained in atrial fibrillation/flutter by study end and it was reported that patients with a persistent AA may have higher mortality. All patients in our study converted to NSR by the end of the study, therefore it is possible that the higher incidence of mortality observed by Isiadinsio et al may have been a manifestation of a higher proportion of patients in a persistent AA. Furthermore, the patients in their study had a longer hospital length of stay, which may reflect in a more ill patient population and thus increased mortality risk. The large proportion of patient deaths in their study resulted in the authors concluding that amiodarone increased short term mortality, an assertion that the present study with a comparatively much larger cohort of amiodarone-receiving LTRs does not support. Magnussen et al. similarly identified with their Cox regression analysis that amiodarone use was independently associated with an increased risk of death/retransplantation.[ 8 ] However, their study compared patients who received amiodarone to those patients who did not receive amiodarone, regardless of whether they had an AA or not. Additionally, more than 90% of amiodarone treated patients received a second concomitant anti-arrhythmic medication calling into question whether increased graft loss was due to amiodarone or a reflection of a more difficult to treat POAA requiring multiple medications. Orrego et al. identified an increased risk of mortality with antiarrhythmic drugs when compared to rate control strategies, however patients in the antiarrhythmic drug group may have received amiodarone, flecainide or propafenone, and thus these results may be confounded by the use of these additional agents.[ 9 ] Conversely, a study by Hathaway et al. has identified similar patient survival among amiodarone and non-amiodarone recipients; which is similar to the findings of this study. Of note, patients in their study received amiodarone if initial POAA management with rate-control strategies was deemed unsuccessful, suggesting that a delayed amiodarone initiation approach may yield similar outcomes to no amiodarone.[ 11 ] The incidence of amiodarone adverse drug reactions within the first-year post-lung transplant has not been well-described in previous literature, despite amiodarone having a wide-ranging toxicity profile. The 7.6% incidence of bradycardia in this study is similar to that of the general population, which has been reported as 4.9% with IV amiodarone.[ 12 ] Additionally, IV amiodarone use has been reported to have a 15–26% incidence of hypotension, which is similar to the 20% incidence identified in this study.[ 13 ] The incidence of thyroid derangements in the present study were also comparable to that of the general population, 18% versus 14–18%.[ 14 ] Hepatoxicity occurred at a lower rate of 15% in the present study, compared to an estimated 25% in the general population.[ 15 ] No patients in our cohort discontinued amiodarone due the development of adverse drug reactions. Thus, amiodarone does not appear to have a different toxicity profile in the lung transplant population when compared to the general population and was overall well tolerated within our population. In this study, POAA episodes most often terminated through the utilization of a partial amiodarone load, which consisted of a load less than 6 g, but greater than a single 150 mg intravenous bolus, with an average dose received at time of NSR attainment of 2,670 mg. However, AA recurrence occurred in 32.8% of patients and the median time to recurrence was five days after NSR attainment, and it is possible that receipt of a full load (greater than 6 g) may have decreased the incidence of AA recurrence. Of note, only 9.9% of patients were on amiodarone at the time of recurrence, suggesting that amiodarone continuation after NSR attainment may be warranted regardless of the degree of amiodarone load required to achieve NSR. Further research to evaluate effects of partial versus full loads and the effects of maintenance amiodarone on AA recurrence in this population is warranted. POAA development, regardless of amiodarone receipt, occurred in 156 out of 323 LTRs (48%) which is higher than previously reported incidences of 20–46%.[ 2 ] This may have manifested due to a higher proportion of patients who had a history of AA prior to transplant or received inotropes or vasopressors post-transplant when compared to other studies evaluating POAA incidence.[ 2 , 4 ] This higher POAA incidence, when combined with the potential efficacy of safety of short-term amiodarone use observed in this study, may suggest a possible need for POAA prevention strategies in this patient population. This study reported real-world efficacy and safety data of amiodarone use in the immediate post-lung transplant setting for POAA. There are limitations to note, especially the retrospective, single center design reliant upon accurate EHR charting. Our analysis relied on the documentation of 12-lead ECG rhythms in the EHR, so there may have been inaccuracies regarding the time of POAA, NSR, or AA recurrence since delays in obtaining a 12-lead ECG were possible. As with previous studies, patients included in this cohort could have been on a combination amiodarone and rate control strategy; an area of future study would be comparison of amiodarone monotherapy compared to rate control monotherapy to gain more insight into whether there are clinically meaningful differences in patient outcomes without potential confounding of other POAA medications. Conclusion This study identified that short-term use of amiodarone was safe in LTRs who developed acute POAAs, as evidenced by the lack of increased post-transplant mortality and lack of significant adverse effects. Furthermore, amiodarone appears to effectively terminate POAAs following lung transplantation. Future prospective studies are warranted to further explore the impact of amiodarone dosing on outcomes as well as compare the overall outcomes of amiodarone versus alternative agents. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: There are no conflicts of interest or other financial disclosures from any of the authors of this manuscript. Data, material, and code availability: All data and materials support the published claims of this study and comply with field standards. No custom code was used in the publication of this study. Author contributions: JE, SJ, KF, LH, TW were involved in the concept/design of the study, data analysis/interpretation, drafting of the article, critical revision of the article, approval of the article, statistics, and data collection. TP and JM were involved in the data collection, concept/design of the study, drafting of the article, critical revision of the article, and approval of the article. DEB was involved in the concept/design of the study, data analysis/interpretation, drafting of the article, critical revision of the article, and approval of the article. Ethics approval: This study was approved by the local institutional review board. Consent to participate: Not applicable to this study. Consent to publish: Not applicable to this study. Acknowledgements: none References Soetanto V, Grewal US, Mehta AC, et al. Early postoperative complications in lung transplant recipients. Indian J Thorac Cardiovasc Surg . Jul 2022;38(Suppl 2):260-270. doi:10.1007/s12055-021-01178-1 Barnes H, Gurry G, McGiffin D, et al. Atrial Flutter and Fibrillation Following Lung Transplantation: Incidence, Associations and a Suggested Therapeutic Algorithm. Heart Lung Circ . Oct 2020;29(10):1484-1492. doi:10.1016/j.hlc.2019.10.011 Isiadinso I, Meshkov AB, Gaughan J, et al. Atrial arrhythmias after lung and heart-lung transplant: effects on short-term mortality and the influence of amiodarone. J Heart Lung Transplant . Jan 2011;30(1):37-44. doi:10.1016/j.healun.2010.07.006 Chaikriangkrai K, Jyothula S, Jhun HY, et al. Incidence, Risk Factors, Prognosis, and Electrophysiological Mechanisms of Atrial Arrhythmias after Lung Transplantation. JACC Clin Electrophysiol . Aug 1 2015;1(4):296-305. doi:10.1016/j.jacep.2015.05.009 Jesel L, Barraud J, Lim HS, et al. Early and Late Atrial Arrhythmias After Lung Transplantation - Incidence, Predictive Factors and Impact on Mortality. Circ J . Apr 25 2017;81(5):660-667. doi:10.1253/circj.CJ-16-0892 Waldron NH, Klinger RY, Hartwig MG, Snyder LD, Daubert JP, Mathew JP. Adverse outcomes associated with postoperative atrial arrhythmias after lung transplantation: A meta-analysis and systematic review of the literature. Clin Transplant . Apr 2017;31(4)doi:10.1111/ctr.12926 Marazzato J, Eikermann M, Di Biase L. Management of Atrial Arrhythmias After Lung Transplant. JACC Clin Electrophysiol . Aug 2023;9(8 Pt 3):1824-1835. doi:10.1016/j.jacep.2023.01.021 Magnusson JM, Bobbio E, Danielsson C, Wallinder A, Dellgren G, Bollano E. A Retrospective Study of Posttransplant Amiodarone Exposition on Clad Development and Survival After Lung Transplantation. Transplant Proc . Apr 2022;54(3):789-794. doi:10.1016/j.transproceed.2021.11.031 Orrego CM, Cordero-Reyes AM, Estep JD, et al. Atrial arrhythmias after lung transplant: underlying mechanisms, risk factors, and prognosis. J Heart Lung Transplant . Jul 2014;33(7):734-40. doi:10.1016/j.healun.2014.02.032 Barnes-Jewish Hospital Lung Transplant Program. https://www.srtr.org/transplant-centers/interactive-report?center=MOBH&type=TX1&organ=lu Hathaway T, Klipsch E, Rachwan R, et al. Amiodarone Use in Lung Transplant Recipients with New Onset Atrial Arrhythmias. The Journal of Heart and Lung Transplantation . 2021;40(4):S375-S376. doi:10.1016/j.healun.2021.01.1058 Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. J Geriatr Cardiol . Jul 2019;16(7):552-566. doi:10.11909/j.issn.1671-5411.2019.07.004 Cheung AT, Weiss SJ, Savino JS, et al. Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients. Ann Thorac Surg . Aug 2003;76(2):535-41. doi:10.1016/s0003-4975(03)00509-5 Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. Can J Cardiol . Jul 2009;25(7):421-4. doi:10.1016/s0828-282x(09)70512-4 Lewis JH, Ranard RC, Caruso A, et al. Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104 patients. Hepatology . May 1989;9(5):679-85. doi:10.1002/hep.1840090504 Cite Share Download PDF Status: Published Journal Publication published 30 May, 2025 Read the published version in Cardiovascular Drugs and Therapy → Version 1 posted Editor assigned by journal 20 Apr, 2025 Reviewers agreed at journal 25 Mar, 2025 Reviewers invited by journal 22 Mar, 2025 Editor invited by journal 20 Mar, 2025 First submitted to journal 19 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6206184","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432505448,"identity":"add42c05-bc43-4a10-af14-83a8682abec4","order_by":0,"name":"Jesus 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legend.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6206184/v1/8ccb126cae6928d73ac9bae7.png"},{"id":83782807,"identity":"e9d6659e-149f-41af-b624-d4c907093ddc","added_by":"auto","created_at":"2025-06-02 16:06:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":461819,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6206184/v1/48c5ad58-2dcb-4030-a687-9eb412a380d2.pdf"}],"financialInterests":"","formattedTitle":"Amiodarone for the Management of Acute Atrial Arrhythmias After Lung Transplant","fulltext":[{"header":"Background","content":"\u003cp\u003eThe process of lung transplantation exposes patients to risk of post-operative complications, which may include cardiovascular complications such as post-operative atrial arrhythmias (POAAs).[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] POAAs after lung transplantation are a common occurrence with a reported incidence of 20\u0026ndash;46% and may manifest at any timepoint post-transplant, with early atrial arrhythmias (AAs) occurring in the first week post-transplant, being most common.[\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] These AAs, which include atrial fibrillation and atrial flutter, have been associated with hemodynamic instability, atrial thrombosis, and decreased long-term survival.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Precipitating factors include perioperative fluid shifts, activation of the renin-angiotensin-aldosterone system, utilization of inotropic or vasopressor support, pain, and the presence of inflammatory mediators. These contributory factors are temporary and POAAs are usually transient.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePOAAs are most often managed with amiodarone and beta\u003csub\u003e1\u003c/sub\u003e receptor antagonists.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Literature in LTRs has identified that anti-arrhythmic drugs such as amiodarone may be associated with reduced survival, but the extrapolation of these studies is difficult given lack of information on the amount of amiodarone patients received, broad grouping of patients into anti-arrhythmic and rate-control strategies, and reported one-year mortality rates much higher than the national average.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Given these gaps in literature, this study sought to describe the management and outcomes in LTRs with early acute POAAs that were treated specifically with amiodarone.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis was a single-center retrospective cohort study of adult LTRs at Barnes-Jewish Hospital/Washington University in Saint Louis, Missouri that were transplanted between June 1st, 2018 and November 15th 2022. Patients were included if they developed an acute POAA post-transplant. Acute POAA were defined as an atrial arrhythmia that occurred within 30 days following transplant surgery and prior to hospital discharge from their index transplant hospitalization. Patients were excluded if they received a multi-organ transplant or if they experienced ventricular arrhythmias. Patients were followed from their date of lung transplantation through one-year post-transplant or death, whichever occurred first. The patient cohort was identified from a list of LTRs via ICD-10 codes for atrial fibrillation and atrial flutter or the receipt of amiodarone post-transplant, and POAA development was confirmed via 12-lead electrocardiogram (ECG). This study was approved by the local institutional review board.\u003c/p\u003e \u003cp\u003eAt Barnes-Jewish Hospital, patients with POAA following lung transplantation may be treated with a rate-control strategy, rhythm-control strategy, or a combination based on physician preference and patient hemodynamics at the time of POAA. Dosing of POAA treatment is not standardized. Patients were categorized as having been managed with amiodarone if they received any amount of amiodarone prior to attainment of normal sinus rhythm (NSR). In addition to amiodarone monotherapy, patients may have received a combination of amiodarone and rate control strategies consisting of beta\u003csub\u003e1\u003c/sub\u003e receptor antagonists, non-dihydropyridine calcium channel antagonists (non-DHP CCB), or digoxin. Dosing of amiodarone was defined as bolus only (single 150 mg dose), partial amiodarone load (less than 6 grams of amiodarone), full amiodarone load (defined as greater than 6 grams of amiodarone), or maintenance (defined as receipt of amiodarone 100\u0026ndash;200 mg daily). Duration of amiodarone post-transplant is not protocolized but in general, given the transient nature of POAA, amiodarone is discontinued by month three post-transplant. Data related to pain score was collected using the Numeric Rating Scale (NRS) pain score, which is an 11-point scale that ranges from 0 to 10 to describe pain severity, where a score of 0 indicates no pain while a score of 10 indicates the worst pain possible.\u003c/p\u003e \u003cp\u003eOutcomes evaluated included one-year all-cause mortality, time from POAA development to NSR (defined as NSR on ECG for at least 48 hours without recurrence of an AA), incidence of AA recurrence (defined as the development of a new AA after previous attainment of NSR for at least 48 hours), length of hospital stay of index transplant visit, length of ICU stay after transplant, incidence of hospital readmissions within the first year post-transplant, and the incidence of adverse drug reactions associated with amiodarone use within one-year after transplant. Adverse drug reactions assessed were hypotension, bradycardia, thyroid derangements, and hepatotoxicity. Hypotension was defined as discontinuation of amiodarone with the reason being cited in the electronic health record (EHR) to be due to low blood pressure, the initial use of vasopressors or inotropes while receiving amiodarone, or a blood pressure of less than 90/60 mmHg while receiving amiodarone. Bradycardia was defined as discontinuation of amiodarone with the reason being cited in the EHR to be due to low heart rate or a heart rate of less than 60 beats per minute. Thyroid derangements were defined as hypo- or hyperthyroidism based on thyroid stimulating hormone and free T\u003csub\u003e4\u003c/sub\u003e outside of the normal range. Hepatotoxicity was defined as defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 150 units/L. Data were collected via review of the EHR. Descriptive statistics were utilized for reporting of results.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 323 patients received a lung transplant during the study timeframe, and 156 of those patients developed a POAA after lung transplant (48%). Twenty-five of those patients did not receive amiodarone, and therefore a total of 131 patients were included in this study (Figure 1). Baseline characteristics can be found in Table 1. A history of atrial arrhythmia prior to transplantation was noted for 31.3% of the patients. The median time from transplant to POAA development was 119 hours. Seventy-two percent of the amiodarone group were receiving pain medications in the form of a bupivacaine epidural, hydromorphone patient-controlled analgesia, or a lidocaine intravenous infusion prior to POAA development. The most common amiodarone management strategy consisted of a partial amiodarone load, which 81.7% of patients received. The mean cumulative amiodarone dose at the time of NSR attainment was 2,670 mg (range: 150 mg- 17,001 mg). Amiodarone maintenance following a partial or full load was initiated in 79.4% of patients, and the median duration of amiodarone therapy was 44 days. A total of 49.5% patients received a combination of amiodarone and rate control agents at the time of NSR attainment. No patients were receiving amiodarone therapy at 1-year post-transplant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n=131)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e61 (57-66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e34 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eCaucasian, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e120 (91.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e, mean\u0026nbsp;\u0026plusmn;\u0026nbsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e26.4\u0026nbsp;\u0026plusmn; 4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eEtiology of lung disease, n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Cystic fibrosis\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;ILD\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;IPF\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;COPD\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;PH\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (3.8)\u003c/p\u003e\n \u003cp\u003e16 (12.2)\u003c/p\u003e\n \u003cp\u003e62 (47.3)\u003c/p\u003e\n \u003cp\u003e20 (15.3)\u003c/p\u003e\n \u003cp\u003e22 (16.8)\u003c/p\u003e\n \u003cp\u003e4 (3.1)\u003c/p\u003e\n \u003cp\u003e2 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eLAS, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e38.2 (35.3-43.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003ePGD score, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1.00 (1.00-1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eHistory of CABG, PCI, or CAD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e25 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eHistory of lung wedge resection at time of transplant, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e20 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eHistory of atrial arrhythmia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e41 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eCVP at time of POAA, mmHg, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e7.50 (5.00-11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003ePain score at time of POAA, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e5.00 (2.00-7.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003ePressor or inotrope use at time of POAA, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e48 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eConcomitant rate control agent use, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e65 (49.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 425px;\"\u003e\n \u003cp\u003eTime from transplant to POAA, hours, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e119 (72.0-185)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: AA, atrial arrhythmia; BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; CVP, central venous pressure; ILD interstitial lung disease; IPF, idiopathic pulmonary fibrosis; IQR, interquartile range; LAS, lung allocation score; PCI, percutaneous coronary intervention; PGD, primary graft dysfunction; PH, pulmonary hypertension; POAA, post-operative atrial arrhythmia\u003c/p\u003e\n\u003cp\u003eMortality within the first post-transplant year occurred in 6.1% of patients, with no cause of death attributable to amiodarone-related toxicity. Causes of death within 1-year post-transplant consisted of bronchiolitis obliterans syndrome (0.8%), COVID-19 infection (1.5%), complications of cirrhosis which developed after completion of amiodarone therapy (0.8%), septic shock (1.5%), spontaneous bleed and altered mental status resulting in transition to comfort care (0.8%), and unknown (0.8%). The most common adverse drug reaction in patients treated with amiodarone was hypotension, which occurred in 20.6% of patients. Thyroid derangements occurred in 13.7% of patients, while hepatoxicity was noted in 15% of patients. Bradycardia had the lowest incidence, at 7.6%.\u003c/p\u003e\n\u003cp\u003eThe median time from POAA development to NSR attainment was 28 hours, and the median ICU and hospital lengths of stay post-transplant were 4.5 days and 18.5 days, respectively. AA recurred in 32.8% patients with a median time to recurrence of 5 days from initial NSR attainment, and 9.9% patients were on amiodarone at the time of AA recurrence. Six (4.6%) patients were readmitted for AA within the first-year post-transplant, and only one of these patients had still been taking amiodarone at the time of their readmission for AA. The number of patients who progressed to direct current cardioversion (DCCV) or catheter ablation within 1-year post-transplant was 19 (14.5%) and 2 (1.5%), respectively.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study of 131 LTRs, short term treatment with amiodarone did not increase mortality and demonstrated a low incidence of side effects with restoration of NSR in most patients.\u003c/p\u003e \u003cp\u003ePrevious literature has asserted that amiodarone increased the risk of mortality after lung transplant.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Our comprehensive analysis of amiodarone treatment revealed a 1-year mortality rate of 6.1%, which is lower than the 1-year mortality of the lung transplant cohort reported by the Scientific Registry of Transplant Recipients of 9.7%.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In contrast, the study by Isiadinsio et al. reported a much higher mortality rate of 63% in the first 200 days post-transplant in patients given amiodarone.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] However, 16% of their patient population remained in atrial fibrillation/flutter by study end and it was reported that patients with a persistent AA may have higher mortality. All patients in our study converted to NSR by the end of the study, therefore it is possible that the higher incidence of mortality observed by Isiadinsio et al may have been a manifestation of a higher proportion of patients in a persistent AA. Furthermore, the patients in their study had a longer hospital length of stay, which may reflect in a more ill patient population and thus increased mortality risk. The large proportion of patient deaths in their study resulted in the authors concluding that amiodarone increased short term mortality, an assertion that the present study with a comparatively much larger cohort of amiodarone-receiving LTRs does not support. Magnussen et al. similarly identified with their Cox regression analysis that amiodarone use was independently associated with an increased risk of death/retransplantation.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, their study compared patients who received amiodarone to those patients who did not receive amiodarone, regardless of whether they had an AA or not. Additionally, more than 90% of amiodarone treated patients received a second concomitant anti-arrhythmic medication calling into question whether increased graft loss was due to amiodarone or a reflection of a more difficult to treat POAA requiring multiple medications. Orrego et al. identified an increased risk of mortality with antiarrhythmic drugs when compared to rate control strategies, however patients in the antiarrhythmic drug group may have received amiodarone, flecainide or propafenone, and thus these results may be confounded by the use of these additional agents.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Conversely, a study by Hathaway et al. has identified similar patient survival among amiodarone and non-amiodarone recipients; which is similar to the findings of this study. Of note, patients in their study received amiodarone if initial POAA management with rate-control strategies was deemed unsuccessful, suggesting that a delayed amiodarone initiation approach may yield similar outcomes to no amiodarone.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe incidence of amiodarone adverse drug reactions within the first-year post-lung transplant has not been well-described in previous literature, despite amiodarone having a wide-ranging toxicity profile. The 7.6% incidence of bradycardia in this study is similar to that of the general population, which has been reported as 4.9% with IV amiodarone.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Additionally, IV amiodarone use has been reported to have a 15\u0026ndash;26% incidence of hypotension, which is similar to the 20% incidence identified in this study.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] The incidence of thyroid derangements in the present study were also comparable to that of the general population, 18% versus 14\u0026ndash;18%.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Hepatoxicity occurred at a lower rate of 15% in the present study, compared to an estimated 25% in the general population.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] No patients in our cohort discontinued amiodarone due the development of adverse drug reactions. Thus, amiodarone does not appear to have a different toxicity profile in the lung transplant population when compared to the general population and was overall well tolerated within our population.\u003c/p\u003e \u003cp\u003eIn this study, POAA episodes most often terminated through the utilization of a partial amiodarone load, which consisted of a load less than 6 g, but greater than a single 150 mg intravenous bolus, with an average dose received at time of NSR attainment of 2,670 mg. However, AA recurrence occurred in 32.8% of patients and the median time to recurrence was five days after NSR attainment, and it is possible that receipt of a full load (greater than 6 g) may have decreased the incidence of AA recurrence. Of note, only 9.9% of patients were on amiodarone at the time of recurrence, suggesting that amiodarone continuation after NSR attainment may be warranted regardless of the degree of amiodarone load required to achieve NSR. Further research to evaluate effects of partial versus full loads and the effects of maintenance amiodarone on AA recurrence in this population is warranted.\u003c/p\u003e \u003cp\u003ePOAA development, regardless of amiodarone receipt, occurred in 156 out of 323 LTRs (48%) which is higher than previously reported incidences of 20\u0026ndash;46%.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] This may have manifested due to a higher proportion of patients who had a history of AA prior to transplant or received inotropes or vasopressors post-transplant when compared to other studies evaluating POAA incidence.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] This higher POAA incidence, when combined with the potential efficacy of safety of short-term amiodarone use observed in this study, may suggest a possible need for POAA prevention strategies in this patient population.\u003c/p\u003e \u003cp\u003eThis study reported real-world efficacy and safety data of amiodarone use in the immediate post-lung transplant setting for POAA. There are limitations to note, especially the retrospective, single center design reliant upon accurate EHR charting. Our analysis relied on the documentation of 12-lead ECG rhythms in the EHR, so there may have been inaccuracies regarding the time of POAA, NSR, or AA recurrence since delays in obtaining a 12-lead ECG were possible. As with previous studies, patients included in this cohort could have been on a combination amiodarone and rate control strategy; an area of future study would be comparison of amiodarone monotherapy compared to rate control monotherapy to gain more insight into whether there are clinically meaningful differences in patient outcomes without potential confounding of other POAA medications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study identified that short-term use of amiodarone was safe in LTRs who developed acute POAAs, as evidenced by the lack of increased post-transplant mortality and lack of significant adverse effects. Furthermore, amiodarone appears to effectively terminate POAAs following lung transplantation. Future prospective studies are warranted to further explore the impact of amiodarone dosing on outcomes as well as compare the overall outcomes of amiodarone versus alternative agents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest or other financial disclosures from any of the authors of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData, material, and code availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data and materials support the published claims of this study and comply with field standards. No custom code was used in the publication of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJE, SJ, KF, LH, TW were involved in the concept/design of the study, data analysis/interpretation, drafting of the article, critical revision of the article, approval of the article, statistics, and data collection.\u003c/p\u003e\n\u003cp\u003eTP and JM were involved in the data collection, concept/design of the study, drafting of the article, critical revision of the article, and approval of the article.\u003c/p\u003e\n\u003cp\u003eDEB was involved in the concept/design of the study, data analysis/interpretation, drafting of the article, critical revision of the article, and approval of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the local institutional review board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSoetanto V, Grewal US, Mehta AC, et al. Early postoperative complications in lung transplant recipients. \u003cem\u003eIndian J Thorac Cardiovasc Surg\u003c/em\u003e. Jul 2022;38(Suppl 2):260-270. doi:10.1007/s12055-021-01178-1\u003c/li\u003e\n\u003cli\u003eBarnes H, Gurry G, McGiffin D, et al. Atrial Flutter and Fibrillation Following Lung Transplantation: Incidence, Associations and a Suggested Therapeutic Algorithm. \u003cem\u003eHeart Lung Circ\u003c/em\u003e. Oct 2020;29(10):1484-1492. doi:10.1016/j.hlc.2019.10.011\u003c/li\u003e\n\u003cli\u003eIsiadinso I, Meshkov AB, Gaughan J, et al. Atrial arrhythmias after lung and heart-lung transplant: effects on short-term mortality and the influence of amiodarone. \u003cem\u003eJ Heart Lung Transplant\u003c/em\u003e. Jan 2011;30(1):37-44. doi:10.1016/j.healun.2010.07.006\u003c/li\u003e\n\u003cli\u003eChaikriangkrai K, Jyothula S, Jhun HY, et al. Incidence, Risk Factors, Prognosis, and Electrophysiological Mechanisms of Atrial Arrhythmias after Lung Transplantation. \u003cem\u003eJACC Clin Electrophysiol\u003c/em\u003e. Aug 1 2015;1(4):296-305. doi:10.1016/j.jacep.2015.05.009\u003c/li\u003e\n\u003cli\u003eJesel L, Barraud J, Lim HS, et al. Early and Late Atrial Arrhythmias After Lung Transplantation - Incidence, Predictive Factors and Impact on Mortality. \u003cem\u003eCirc J\u003c/em\u003e. Apr 25 2017;81(5):660-667. doi:10.1253/circj.CJ-16-0892\u003c/li\u003e\n\u003cli\u003eWaldron NH, Klinger RY, Hartwig MG, Snyder LD, Daubert JP, Mathew JP. Adverse outcomes associated with postoperative atrial arrhythmias after lung transplantation: A meta-analysis and systematic review of the literature. \u003cem\u003eClin Transplant\u003c/em\u003e. Apr 2017;31(4)doi:10.1111/ctr.12926\u003c/li\u003e\n\u003cli\u003eMarazzato J, Eikermann M, Di Biase L. Management of Atrial Arrhythmias After Lung Transplant. \u003cem\u003eJACC Clin Electrophysiol\u003c/em\u003e. Aug 2023;9(8 Pt 3):1824-1835. doi:10.1016/j.jacep.2023.01.021\u003c/li\u003e\n\u003cli\u003eMagnusson JM, Bobbio E, Danielsson C, Wallinder A, Dellgren G, Bollano E. A Retrospective Study of Posttransplant Amiodarone Exposition on Clad Development and Survival After Lung Transplantation. \u003cem\u003eTransplant Proc\u003c/em\u003e. Apr 2022;54(3):789-794. doi:10.1016/j.transproceed.2021.11.031\u003c/li\u003e\n\u003cli\u003eOrrego CM, Cordero-Reyes AM, Estep JD, et al. Atrial arrhythmias after lung transplant: underlying mechanisms, risk factors, and prognosis. \u003cem\u003eJ Heart Lung Transplant\u003c/em\u003e. Jul 2014;33(7):734-40. doi:10.1016/j.healun.2014.02.032\u003c/li\u003e\n\u003cli\u003eBarnes-Jewish Hospital Lung Transplant Program. https://www.srtr.org/transplant-centers/interactive-report?center=MOBH\u0026amp;type=TX1\u0026amp;organ=lu\u003c/li\u003e\n\u003cli\u003eHathaway T, Klipsch E, Rachwan R, et al. Amiodarone Use in Lung Transplant Recipients with New Onset Atrial Arrhythmias. \u003cem\u003eThe Journal of Heart and Lung Transplantation\u003c/em\u003e. 2021;40(4):S375-S376. doi:10.1016/j.healun.2021.01.1058\u003c/li\u003e\n\u003cli\u003eColunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. \u003cem\u003eJ Geriatr Cardiol\u003c/em\u003e. Jul 2019;16(7):552-566. doi:10.11909/j.issn.1671-5411.2019.07.004\u003c/li\u003e\n\u003cli\u003eCheung AT, Weiss SJ, Savino JS, et al. Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients. \u003cem\u003eAnn Thorac Surg\u003c/em\u003e. Aug 2003;76(2):535-41. doi:10.1016/s0003-4975(03)00509-5\u003c/li\u003e\n\u003cli\u003eTsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. \u003cem\u003eCan J Cardiol\u003c/em\u003e. Jul 2009;25(7):421-4. doi:10.1016/s0828-282x(09)70512-4\u003c/li\u003e\n\u003cli\u003eLewis JH, Ranard RC, Caruso A, et al. Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104 patients. \u003cem\u003eHepatology\u003c/em\u003e. May 1989;9(5):679-85. doi:10.1002/hep.1840090504\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cardiovascular-drugs-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cdty","sideBox":"Learn more about [Cardiovascular Drugs and Therapy](https://www.springer.com/journal/10557)","snPcode":"10557","submissionUrl":"https://submission.nature.com/new-submission/10557/3","title":"Cardiovascular Drugs and Therapy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"lung transplantation, arrhythmias, amiodarone, safety","lastPublishedDoi":"10.21203/rs.3.rs-6206184/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6206184/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e Dosing, safety, and outcomes of amiodarone in acute post-operative atrial arrhythmias (POAAs) after lung transplantation are not well understood. Current literature suggests amiodarone may increase mortality in lung transplant recipients (LTRs). This study described outcomes associated with amiodarone use in POAAs after lung transplantation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eThis single-center, retrospective cohort study analyzed LTRs who received amiodarone after developing a POAA within 30 days of transplant surgery and prior to hospital discharge from their index transplant admission. Primary safety outcomes included mortality and the incidence of adverse drug reactions (ADRs). Secondary efficacy outcomes included time to normal sinus rhythm (NSR) attainment, intensive care unit (ICU) and hospital length of stay, and atrial arrhythmia (AA) recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eA total of 131 LTRs who developed an acute POAA received amiodarone. The 1-year mortality did not differ between this cohort and our overall lung transplant population, and ADR incidence was similar to that observed in non-LTRs. The median time to NSR attainment was 28 hours after amiodarone initiation; ICU and hospital lengths of stay were 4.5 and 18.5 days, respectively; and AA recurrence occurred in 32.8% of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eThe findings of this study suggest that amiodarone use may be safe in LTRs with acute atrial arrhythmias, and may also effectively terminate acute POAAs in this population.\u003c/p\u003e","manuscriptTitle":"Amiodarone for the Management of Acute Atrial Arrhythmias After Lung Transplant","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-01 10:00:43","doi":"10.21203/rs.3.rs-6206184/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2025-04-20T22:27:41+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-03-25T10:35:34+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-22T15:32:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Cardiovascular Drugs and Therapy","date":"2025-03-20T06:25:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardiovascular Drugs and Therapy","date":"2025-03-19T14:44:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cardiovascular-drugs-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cdty","sideBox":"Learn more about [Cardiovascular Drugs and Therapy](https://www.springer.com/journal/10557)","snPcode":"10557","submissionUrl":"https://submission.nature.com/new-submission/10557/3","title":"Cardiovascular Drugs and Therapy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3c158916-d908-4e48-9d88-57bc0609a03a","owner":[],"postedDate":"April 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-02T15:59:37+00:00","versionOfRecord":{"articleIdentity":"rs-6206184","link":"https://doi.org/10.1007/s10557-025-07725-x","journal":{"identity":"cardiovascular-drugs-and-therapy","isVorOnly":false,"title":"Cardiovascular Drugs and Therapy"},"publishedOn":"2025-05-30 15:57:09","publishedOnDateReadable":"May 30th, 2025"},"versionCreatedAt":"2025-04-01 10:00:43","video":"","vorDoi":"10.1007/s10557-025-07725-x","vorDoiUrl":"https://doi.org/10.1007/s10557-025-07725-x","workflowStages":[]},"version":"v1","identity":"rs-6206184","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6206184","identity":"rs-6206184","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}