Post-transplant atrial tachyarrhythmias: Epidemiology, mechanisms, outcomes, and management across solid organs

Abstract

Post-transplant atrial tachyarrhythmias - including atrial fibrillation (AF), atrial flutter, and organized atrial tachycardias - occur after solid-organ transplantation and follow distinct time- and organ-dependent patterns. Early arrhythmias are mainly postoperative, resulting from inflammatory and autonomic stress, hemodynamic and metabolic shifts, and atrial injury. Thoracic transplantation bears the highest burden: Early postoperative AF is frequent, while late arrhythmias typically present as macroreentrant tachycardias at anastomotic or incisional sites. These late arrhythmias can signal graft pathology or atrial remodeling. In heart transplantation, late atrial tachyarrhythmias depend on surgical technique and often coincide with rejection or cardiac allograft vasculopathy. In abdominal transplantation, AF is less common but remains relevant. In liver transplantation, AF links closely to advanced disease and perioperative instability, with poorer outcomes. Across organs, post-transplant AF leads to longer hospitalization and higher risks of thromboembolism, mortality, and graft loss, emphasizing its significance beyond a brief postoperative event. Management is complex and multidisciplinary, requiring careful evaluation for reversible causes, patient-specific rate-control or rhythm-control, and attention to interactions among antiarrhythmics, anticoagulants, and immunosuppressive agents. Rhythm control is increasingly mechanism-driven. Catheter ablation, at experienced centers, is effective for late organized tachyarrhythmias, achieving high acute and durable success in recent single-center series. Stroke prevention remains difficult due to changing bleeding risk, organ function, and limited relevant trial evidence. Anticoagulation requires ongoing reassessment. Left atrial appendage occlusion is an emerging alternative for patients ineligible for long-term anticoagulation. Evidence, mainly from registry data and small series, suggests potentially higher vascular complication rates. This review summarizes current knowledge, clarifies knowns and unknowns, and describes future goals, including standardized definitions, phenotyping, surveillance windows, transplant-specific risk stratification, and comparative studies of anticoagulation, ablation, and appendage-closure strategies to improve outcomes.

Key Words: Atrial fibrillation; Atrial flutter; Atrial tachyarrhythmia; Solid-organ transplantation; Heart transplantation; Lung transplantation; Kidney transplantation; Liver transplantation; Catheter ablation; Anticoagulation

Core Tip: Post-transplant atrial fibrillation and other atrial tachyarrhythmias are not a uniform postoperative complication. Rather, they form a time-dependent and organ-dependent syndrome with distinct mechanisms and clinical implications across solid-organ transplantation. Thoracic transplantation carries the greatest arrhythmic burden, whereas abdominal transplantation shows a lower incidence but important prognostic consequences. Early atrial fibrillation is usually trigger-mediated, while later atrial arrhythmias often reflect fixed structural substrates, graft-related pathology, or progressive remodeling. Effective management requires a transplant-specific approach that integrates timing, graft status, organ function, drug interactions, thromboembolic risk, bleeding risk, and the growing role of mechanism-guided catheter ablation.

INTRODUCTION

Atrial fibrillation (AF) and other atrial tachyarrhythmias (AT) are increasingly recognized after solid-organ transplantation. They should be interpreted within a transplant-specific clinical and pathophysiologic framework[1-5]. Unlike conventional postoperative AF after non-transplant surgery, post-transplant atrial arrhythmias reflect interactions among the recipient’s cardiovascular substrate, procedure-related atrial injury, perioperative inflammation, hemodynamic stress, donor-graft physiology[1-3], and the long-term effects of immunosuppressive therapy[4-6]. The arrhythmic burden varies across organ types. AF remains clinically relevant across all transplant populations because it is associated with longer hospitalization and higher risks of thromboembolism, graft dysfunction, and mortality. Therefore, it should not be regarded as merely a transient postoperative event[3-5,7-9].

In this review, post-transplant AT is used as an umbrella term encompassing AF, atrial flutter, and focal or macroreentrant atrial tachycardias. AF-specific statements are used when the evidence pertains specifically to fibrillation. This broader terminology is intentional. Atrial flutter and organized atrial tachycardias are included because, particularly after thoracic transplantation, they may reflect distinct scar-related substrates. Rhythm-control strategies differ from those used for trigger-mediated early AF.

Operationally, early post-transplant AT was defined as episodes occurring during the index hospitalization or within 30 days after transplantation, with a very-early postoperative window of 0-7 days highlighted separately when relevant. Arrhythmias occurring 1-6 months after surgery are considered an intermediate phase, whereas those occurring > 6 months are considered late and are more likely to reflect fixed anatomic, scar-related, or graft-related substrates rather than transient perioperative triggers. This time-dependent variation has direct therapeutic implications: Early arrhythmias arising from transient perioperative triggers rarely require the same management as late organized AT anchored to stable scar or graft-related remodeling, particularly in thoracic transplantation[1,2,5,9]. Recognizing this distinction is therefore essential for interpreting outcome data and for appropriately guiding clinical decisions.

This review presents current evidence on post-transplant AF and other AT - summarizing epidemiology, mechanisms, outcomes, and management across heart, lung, kidney, and liver transplantation. It highlights shared patterns and organ-specific features.

SEARCH STRATEGY AND SELECTION CRITERIA

Data for this narrative review were identified through searches of PubMed/MEDLINE, EMBASE, and the Cochrane Library. The search included original research articles, narrative reviews, systematic reviews, meta-analyses, clinical practice guidelines, and consensus statements published in English through May 10, 2026. Search terms included “atrial fibrillation”, “atrial flutter”, “atrial tachycardia”, “macroreentrant atrial tachycardia”, “atrial tachyarrhythmia”, “solid-organ transplantation”, “heart transplantation”, “lung transplantation”, “kidney transplantation”, “renal transplantation”, “liver transplantation”, “hepatic transplantation”, “pancreas transplantation”, “intestinal transplantation”, “multivisceral transplantation”, “postoperative atrial fibrillation”, “calcineurin inhibitor”, “tacrolimus”, “cyclosporine”, “mTOR inhibitor”, “amiodarone”, “direct oral anticoagulants”, “catheter ablation”, “left atrial appendage occlusion”, “implantable loop recorder”, “wearable devices”, and “artificial intelligence electrocardiography”. These terms were combined with Boolean operators (AND/OR) and adapted to each database.

Studies were selected if they provided clinically relevant data on epidemiology, mechanisms, risk factors, outcomes, rhythm surveillance, rate or rhythm control, antiarrhythmic drug interactions, anticoagulation, catheter ablation, or left atrial appendage occlusion in transplant recipients or candidates. Studies were excluded if they did not involve transplantation, did not report atrial arrhythmia-related data, duplicated another included analysis without including pertinent information, or were available only as non-peer-reviewed abstracts. Because this was a narrative review rather than a systematic review or meta-analysis, no formal Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram, risk-of-bias assessment, or de novo quantitative synthesis was performed. The pooled estimates reported in the text were derived from prior meta-analyses and were not recalculated for the present review.

POST-TRANSPLANT AT AS A HETEROGENEOUS SYNDROME

The incidence and phenotypic expression of post-transplant atrial arrhythmias vary substantially across organ types, reflecting distinct procedural, hemodynamic, immunologic, and recipient-related contexts.

Among thoracic recipients, orthotopic heart transplantation occupies a paradoxical position: Atrial arrhythmias are not uncommon overall, yet AF itself appears less frequent than after most other forms of cardiac surgery, with reported incidence ranging from 0.3% to nearly 24% and pooled estimates of approximately 10%, depending on monitoring strategy, definitions, and follow-up duration[10-13]. This comparatively lower incidence is generally attributed to surgical pulmonary vein isolation, donor-heart denervation, and the structurally healthier profile of donor hearts[10,12,13]. When AF or other atrial arrhythmias do occur, they may reflect rejection, graft ischemia, altered atrial geometry, or chronic graft pathology, such as cardiac allograft vasculopathy[14-16].

Lung transplantation, by contrast, carries the highest early postoperative arrhythmic burden. Early AF occurs in approximately 20% to 35% of recipients, most commonly between postoperative days 2 and 7, and has been associated with advanced age, interstitial lung disease, hypertension, coronary artery disease, vasopressor use, left atrial enlargement, and bilateral transplantation[17-19]. Later events, particularly beyond 6 months, more commonly present as organized atrial tachycardias or atrial flutter related to anastomotic scar and atrial remodeling[2,9].

In kidney transplantation, AF is less frequent than in thoracic transplantation, but its epidemiology is comparatively well characterized, given the large recipient population and the high cardiovascular burden of end-stage kidney disease. Early United States Renal Data System-based data showed that new-onset AF occurred in 3.6% of recipients at 12 months and 7.3% at 36 months[7], whereas pre-transplant AF was present in approximately 6.4% and was associated with higher risks of death, graft failure, and ischemic stroke after transplantation[20]. A subsequent meta-analysis estimated a pooled prevalence of pre-existing AF of 7.0% [95% confidence interval (CI): 5.6%-8.8%, I² = 86%] and a pooled incidence of post-transplant AF of 4.9% (95%CI: 1.7%-13.0%, I² = 99%), with meta-regression showing no significant trend over study year for either estimate[4]. More contemporary cohorts confirm this relevance: A Spanish national hospitalization cohort identified AF/flutter in 5.3% of kidney transplant admissions with an increase over time[21], and a modern United States Renal Data System analysis reported newly diagnosed AF in approximately 7% of recipients within 3 years, with higher risk among patients previously treated with hemodialysis than peritoneal dialysis[22].

In liver transplantation, perioperative AF has been reported in approximately 5% to 15% of recipients, with a pooled incidence of around 8.5%[3,23-25]. These lower absolute rates should be interpreted in the context of recipient vulnerability and the dynamic perioperative physiology inherent to this procedure.

For less common abdominal and multivisceral procedures, epidemiological data remain sparse. In simultaneous pancreas-kidney transplantation, large registry datasets document procedure volumes and graft outcomes although they do not routinely capture AF as a dedicated endpoint; reported or inferred perioperative rates generally range from 5% to 15%, extrapolated from diabetic surgical cohorts[26,27], while the convergence of long-standing diabetes, cardiac autonomic neuropathy, and chronic kidney disease may further enrich the arrhythmic substrate[28,29].

Combined liver-kidney transplantation likely represents a higher-risk abdominal subgroup, but available estimates derive largely from liver transplant cohorts or mixed populations rather than dedicated analyses[24,30,31]. Intestinal, liver-intestinal, and multivisceral transplantation remain the least characterized settings: International registry reports document their rarity and complexity, but no prospective study has systematically quantified AF incidence, leaving current estimates entirely inferential[32,33].

Sequential and combined-organ transplantation should be treated as a distinct evidence gap rather than a simple extension of single-organ data. AF risk may be amplified when renal dysfunction, cirrhotic cardiomyopathy, pulmonary hypertension, diabetes-related autonomic neuropathy, or prior thoracic surgery coexist in the same recipient, and attribution is further complicated when graft dysfunction, infection, rejection, or drug toxicity occur simultaneously. Available data rarely separate heart-kidney, heart-liver, simultaneous liver-kidney, simultaneous pancreas-kidney, or retransplantation cohorts, and current estimates for these groups should therefore be considered inferential. Future registries should capture prior transplantation history, graft-to-graft interactions, and sequential organ failure as dedicated covariates.

CLINICAL PATTERNS IN THORACIC AND ABDOMINAL TRANSPLANTATION

The arrhythmic expression of transplantation varies not only in magnitude but in its mechanistic origin: In thoracic recipients, the substrate is largely procedural, whereas in abdominal recipients, it is largely pretransplant in origin. In heart transplantation, this procedural substrate is shaped by surgical technique, donor-recipient atrial geometry, and chronic graft pathology such as cardiac allograft vasculopathy and rejection-related conduction injury[34-36]. In lung transplantation, late atrial arrhythmias frequently reflect procedure-related structural injury and progressive left atrial remodeling at the anastomotic zone[9,37,38].

In abdominal transplantation, recipient-related cardiovascular disease predominates over procedure-specific atrial injury. Kidney recipients present with a chronic cardiorenal substrate that predisposes to AF, largely independent of the transplant procedure[39-41]. Liver recipients are characterized by marked systemic hemodynamic alterations and perioperative metabolic instability[42-44], rendering the perioperative window particularly vulnerable[45-47].

This distinction carries direct clinical implications: Late AT in thoracic transplantation regularly denotes a defined anatomic substrate amenable to mapping-guided intervention, whereas AF in abdominal transplantation more commonly signals systemic vulnerability or hemodynamic derangement.

SHARED MECHANISMS AND ORGAN-SPECIFIC SUBSTRATES

Early postoperative AF across solid organs generally emerges from the interaction between a vulnerable atrial substrate and acute perioperative triggers. Common contributors include systemic inflammation, oxidative stress, catecholamine excess, fluid shifts, electrolyte abnormalities, atrial stretch, and hemodynamic instability[48-53]. Chronic conditions such as aging, hypertension, diabetes, obesity, heart failure, and sleep apnea amplify susceptibility by promoting atrial enlargement, fibrosis[6,48-50], and conduction heterogeneity[51-53].

In heart transplantation, these shared mechanisms are substantially modified by graft denervation. Transection of vagal and sympathetic fibers eliminates conventional autonomic triggers and reduces pulmonary vein ectopy, likely accounting for the comparatively lower AF burden relative to other cardiac procedures[12,13,54]. Procedurally, biatrial anastomosis may distort atrial geometry and promote conduction heterogeneity, whereas bicaval techniques appear to preserve atrial architecture more effectively[14,16,34]. These two approaches should not be conflated: The biatrial technique retains larger portions of recipient atrial tissue and introduces suture lines that alter conduction, whereas bicaval anastomoses represent a discrete surgical component of the contemporary bicaval repair[34].

Beyond the perioperative window, graft-related pathology constitutes a distinct and ongoing arrhythmic driver. Acute rejection promotes myocardial edema, inflammatory infiltration, myocyte injury, and fibrosis - changes that slow conduction and facilitate reentry[14-16]. Repeated rejection episodes and progressive cardiac allograft vasculopathy may sustain this remodeling into later phases, giving rise to organized AT[5,14,16]. De novo atrial flutter in this population should therefore prompt systematic evaluation for rejection or graft dysfunction rather than being attributed to a primary arrhythmic event.

In lung transplantation, the mechanistic transition from early AF to late organized arrhythmias reflects a shift in the dominant substrate. Early AF is driven by inflammation, atrial stretch, ischemia, and vasopressor exposure[17-19]. Late arrhythmias arise from macroreentrant circuits anchored to pulmonary vein-left atrial anastomotic lines, posterior wall scar, mitral annular substrate, cavotricuspid isthmus-dependent circuits, and low-voltage atrial zones[2,9,37,38]. Electrical reconnection across surgically isolated pulmonary veins has also been documented as a contributor to late recurrent AF[37,38].

In kidney transplantation, the arrhythmogenic substrate is largely established before transplantation. Chronic kidney disease drives atrial fibrosis, chamber enlargement, conduction heterogeneity, and autonomic imbalance through renin-angiotensin-aldosterone system activation, uremia, inflammation, oxidative stress[39-41], and volume overload[55-57]. Left ventricular hypertrophy and diastolic dysfunction elevate left atrial pressure and promote dilation[40], while uremic toxins such as p-cresyl sulfate may contribute directly to atrial remodeling[57]. Longer pretransplant dialysis exposure, particularly hemodialysis, is associated with greater post-transplant AF risk, likely showing the cumulative burden of this uremic atrial substrate[22]. Transplantation superimposes acute triggers - reperfusion stress, corticosteroid exposure, and electrolyte derangements[48,49] - and long-term calcineurin inhibitor exposure further perpetuates proarrhythmic conditions through hypertension, renal dysfunction, electrolyte wasting, and QT prolongation[58,59]. Tacrolimus-induced QT prolongation appears dose- and exposure-dependent, making therapeutic drug monitoring a reasonable mitigation strategy, particularly during the early postoperative phase when organ function remains unstable.

Liver transplantation shares this pretransplant disease burden but adds a uniquely arrhythmogenic perioperative event. Cirrhotic cardiomyopathy, characterized by diastolic dysfunction, corrected QT interval prolongation, chronotropic incompetence, hyperdynamic circulation, and biatrial enlargement, predisposes to atrial vulnerability before the procedure begins[42-44]. Autonomic dysfunction and heightened adrenergic tone shorten atrial refractoriness further[42-44]. Post-reperfusion syndrome then introduces an abrupt systemic insult: The release of cold, acidotic, hyperkalemic preservation fluid triggers hemodynamic instability and a highly arrhythmogenic metabolic environment[45-47]. AF in this setting reflects the convergence of advanced recipient disease, reperfusion-related stress, and sustained perioperative vulnerability.

CLINICAL IMPACT AND PROGNOSTIC IMPLICATIONS

The prognostic significance of post-transplant AF varies by organ and by timing, and its interpretation requires distinguishing between direct hemodynamic and thromboembolic consequences and its role as a marker of underlying graft or recipient susceptibility[4-8].

In heart transplantation, atrial arrhythmias have been associated with worse short- and intermediate-term outcomes, with all-cause mortality reaching 43% in AF/atrial flutter recipients compared with 23% in those in sinus rhythm (hazard ratio = 2.45; 95%CI: 1.2-4.8), although the survival difference appears to attenuate over longer follow-up in some series[5,11,14-16]. Notably, this excess mortality is predominantly driven by arrhythmias occurring in the late (> 6 months) phase, suggesting that AF functions less as a direct causal driver and more as a marker of graft vulnerability, particularly in the setting of rejection or cardiac allograft vasculopathy[11,14-16].

In lung transplantation, AF has consistently been linked to longer hospitalization, greater postoperative morbidity, and worse long-term survival, with atrial arrhythmias associated with an approximately threefold increase in adjusted mortality risk[17-19]. Arrhythmias occurring after the index hospitalization carry an even greater mortality hazard, identifying a subgroup with sustained rather than transient arrhythmic burden[19].

In kidney transplantation, meta-analytic data link AF to mortality [pooled odds ratio (OR) = 1.86; 95%CI: 1.03-3.35], death-censored graft loss (OR = 1.55; 95%CI: 1.02-2.35), and stroke (OR = 2.54; 95%CI: 1.11-5.78)[4], findings corroborated by registry-based analyses showing adjusted hazard ratios of 1.46 for death, 1.41 for graft failure, and 1.36 for ischemic stroke[20]. In liver transplantation, postoperative AF has been associated with primary graft nonfunction, acute kidney injury, prolonged intensive care unit stay, increased mortality, and independently predicted later stroke and thromboembolic events[8,24,25,30,60]. Across both abdominal populations, AF was independently associated with higher in-hospital mortality in a large Spanish national cohort - an association not observed in heart transplant recipients, further supporting the organ-specific interpretation of these outcome data[21].

Taken together, these findings support the interpretation of post-transplant AF as both a complication and a clinical signal. Depending on the organ and timing, it may independently contribute to hemodynamic instability and thromboembolic risk, but it may also behave as a biomarker of competing risks such as graft failure, rejection, infection, malignancy, renal dysfunction, or advanced recipient frailty. Future outcome studies should therefore adjust for time-varying graft function and competing post-transplant complications rather than treating AF as an isolated exposure.

POSTOPERATIVE MANAGEMENT

The initial management of AF after solid-organ transplantation is broadly similar across organs and begins with assessment of hemodynamic stability, identification of reversible triggers, and correction of electrolyte abnormalities[6,48,49]. Rate control is generally the first-line strategy in stable patients, most commonly with beta-blockers. Nondihydropyridine calcium channel blockers are reasonable alternatives in selected patients, and digoxin may be used as an adjunct when hypotension or heart failure limit other options[6].

Rhythm control, whether electrical or pharmacologic, is generally reserved for persistent symptoms, inadequate rate control, or hemodynamic compromise[6]. In heart transplant recipients, new-onset AF should prompt a low threshold for evaluation of rejection, ischemia, infection, or graft dysfunction, since these may be the primary drivers rather than generic postoperative arrhythmia[1,14,16]. In lung recipients, it is especially useful to distinguish early postoperative AF, usually occurring during the index hospitalization or within 30 days and driven by perioperative triggers, from persistent, recurrent, or late (> 6 months) arrhythmias, which more often suggest a stable substrate[2,9]. A practical stepwise approach to early stabilization and longitudinal follow-up is summarized in Figure 1.

Figure 1 Early and follow-up management of post-transplant atrial tachyarrhythmias. The timeline separates very early postoperative management (0-7 days), early reassessment (7-30 days), intermediate follow-up (1-6 months), and late arrhythmia evaluation (> 6 months). AF: Atrial fibrillation; HR: Heart rate.

Prevention deserves more emphasis than it has usually received in transplant literature. Although transplant-specific prophylaxis trials remain limited, several preventive strategies are biologically plausible and supported indirectly by broader postoperative AF literature and organ-specific experience. These include aggressive correction of hypokalemia and hypomagnesemia, careful volume management, avoidance of excessive catecholaminergic stimulation when feasible, and optimization of blood pressure control[2,6,48,49]. In lung transplantation, perioperative AF prophylaxis remains incompletely standardized, and available evidence remains uncertain about the optimal pharmacologic strategy[2,17]. In abdominal transplantation, prevention is likely to depend more on correction of perioperative metabolic and hemodynamic instability than on routine antiarrhythmic prophylaxis.

Beyond snapshot electrocardiography, modern arrhythmia management has increasingly transitioned toward continuous assessment of AF burden and atrial high-rate episodes (AHREs). In transplant populations monitored with cardiac implantable electronic devices, implantable loop recorders, or contemporary wearable devices, subclinical AHREs are frequently detected and carry prognostic implications that extend beyond symptomatic AF alone. Although the precise duration threshold that mandates anticoagulation in transplant recipients remains undefined, evidence from broader populations and heart failure cohorts suggests that higher cumulative AHRE burden is associated with increased thromboembolic risk and worse long-term outcomes[61,62]. This paradigm shift supports continuous rhythm surveillance as the preferred monitoring framework when tailoring rhythm-control and antithrombotic decisions in this population.

A dedicated surveillance strategy should therefore be considered in all transplant recipients with known or suspected atrial arrhythmias. Early post-transplant rhythm surveillance is typically based on telemetry and serial electrocardiographic assessment during the index hospitalization, which is appropriate for detecting early postoperative AF. Later arrhythmias may be underdetected, particularly when intermittent or minimally symptomatic. In selected recipients, ambulatory monitoring is therefore warranted - especially when cryptogenic neurologic events, unexplained graft dysfunction, or recurrent symptoms raise concern for undetected atrial arrhythmia.

The organ-specific features of post-transplant atrial arrhythmias, their dominant mechanisms, clinical impact, and management caveats are summarized in Table 1.

Table 1 Organ-specific features of post-transplant atrial tachyarrhythmias.

Organ	Typical burden of AF/atrial arrhythmias	Dominant early mechanisms	Dominant late mechanisms	Main clinical impact	Key management caveats
Heart	(1) Lower AF incidence than other thoracic procedures; and (2) But clinically meaningful atrial arrhythmia burden overall	(1) Perioperative inflammation; (2) Atrial suture lines and altered atrial geometry; and (3) Rejection and ischemia	(1) Scar-related reentry; (2) Rejection-related remodeling; and (3) Cardiac allograft vasculopathy	(1) Worse early and intermediate outcomes; and (2) May signal graft dysfunction rather than isolated rhythm disease	(1) Evaluate promptly for rejection or ischemia; (2) DOACs are increasingly feasible; and (3) Ablation is effective for organized arrhythmias
Lung	(1) Highest thoracic burden; (2) Early AF is common; and (3) Late flutter or atrial tachycardia is frequent	(1) Postoperative stress; (2) Atrial stretch and ischemia; and (3) Vasopressors and recipient comorbidity	(1) Anastomotic scar and low-voltage substrate; (2) Pulmonary vein reconnection; and (3) Macroreentry	(1) Prolonged hospitalization; and (2) Worse long-term outcomes in several series	(1) Amiodarone use is debated because of pulmonary toxicity; and (2) Ablation is a major option for late organized arrhythmias
Kidney	(1) Lower incidence than thoracic transplantation; and (2) But strong prognostic relevance	(1) Reperfusion stress; (2) Steroids and electrolyte shifts; and (3) Hemodynamic instability	(1) CKD substrate, including fibrosis and left ventricular hypertrophy; (2) Autonomic dysfunction; and (3) Persistent immunosuppressive effects	(1) Mortality, stroke, and graft loss; and (2) Longer hospitalization	(1) Early graft-function fluctuation complicates DOAC dosing; and (2) Calcineurin inhibitor interactions are clinically important
Liver	(1) Intermediate burden; and (2) Strongly linked to disease severity and perioperative instability	(1) Cirrhotic cardiomyopathy; (2) Autonomic dysfunction; and (3) Post-reperfusion syndrome	(1) Persistent metabolic and hemodynamic vulnerability; and (2) Chronic cardiovascular stress	(1) Acute kidney injury and graft dysfunction; (2) Prolonged intensive care unit stay and mortality; and (3) Later thromboembolism	(1) Anticoagulation is complicated by thrombocytopenia and unstable liver function; and (2) Amiodarone hepatotoxicity is a concern

AF: Atrial fibrillation; CKD: Chronic kidney disease; DOAC: Direct oral anticoagulant.

ANTICOAGULATION IN TRANSPLANT RECIPIENTS

Anticoagulation remains one of the most challenging aspects of post-transplant AF management. Because transplant-specific randomized trials are lacking, most decisions still follow general AF guidelines, usually based on CHA₂DS₂-VASc or CHA₂DS₂-VA risk assessment, while also accounting for transplant-specific factors such as fluctuating graft function, repeated invasive procedures, bleeding risk, and drug-drug interactions[63]. According to the 2024 European Society of Cardiology AF Guidelines[6], a CHA₂DS₂-VA score ≥ 2 represents a class I recommendation for anticoagulation, whereas a score of 1 may support anticoagulation initiation (class IIa, level of evidence C). However, these recommendations are extrapolated from non-transplant populations and should be interpreted cautiously in transplant recipients, in whom thrombotic and bleeding risks are highly dynamic.

Bleeding risk should be actively assessed and mitigated, but it should not automatically be used to deny anticoagulation when stroke risk is substantial. Direct oral anticoagulants (DOACs) are increasingly favored over warfarin in selected transplant recipients because they avoid routine international normalized ratio monitoring and may simplify periprocedural management. Observational data in heart, kidney[64-68], and liver recipients suggest acceptable safety and efficacy[69-71], especially beyond the immediate postoperative period. In heart transplant recipients, observational data suggest similar thromboembolic protection with fewer bleeding complications compared with vitamin K antagonists (VKAs)[67,68]. Current International Society for Heart and Lung Transplantation recommendations also support DOACs as reasonable alternatives to VKAs in selected heart transplant recipients receiving tacrolimus- or proliferation signal inhibitor-based immunosuppression[71].

In kidney transplant recipients, early postoperative graft dysfunction may increase the risk of DOAC accumulation, as many agents undergo partial renal clearance. Observational studies have associated early postoperative anticoagulation with bleeding complications, surgical interventions, delayed graft function, and readmissions[64,65]. More recent observational analyses of recipients beyond the immediate postoperative period suggest that DOAC therapy may be associated with lower rates of composite adverse outcomes and graft rejection compared with VKAs[65]. Nonetheless, these findings remain hypothesis-generating and have not yet been confirmed in randomized studies.

Evidence in liver transplant recipients is also limited and largely observational. Thrombocytopenia, impaired hepatic synthetic function, and portal hypertensive bleeding risk complicate both anticoagulation decisions and agent selection[72,73]. Small observational studies suggest that DOACs may be used safely in selected liver transplant recipients once hepatic function stabilizes, although careful, individualized assessment remains essential[66].

Drug-drug interactions represent another major transplant-specific challenge. All currently available DOACs depend on P-glycoprotein transport, whereas rivaroxaban and apixaban also partially rely on cytochrome P450 3A4 (CYP3A4) metabolism[63]. This creates clinically relevant interaction potential with tacrolimus, cyclosporine, azole antifungals, and other transplant medications. Pharmacokinetic studies and observational experience suggest that apixaban may be preferred in patients receiving cyclosporine and that edoxaban, given its lower reliance on CYP3A4 metabolism, may be favored in the setting of azole antifungal therapy[70]. However, these recommendations are based primarily on limited pharmacologic and observational evidence rather than randomized comparative data. Accordingly, anticoagulant selection should be individualized with careful attention to calcineurin inhibitor exposure, renal function, hepatic function, and bleeding risk. To approach the complexities of thromboembolic and bleeding risks, fluctuating organ function, and specific drug-drug interactions, a proposed clinical management flowchart for anticoagulation is presented in Figure 2.

Figure 2 Clinical management flowchart for anticoagulation after solid-organ transplantation. The figure integrates general CHA₂DS₂-VA-based thromboembolic risk assessment with organ-specific bleeding and pharmacokinetic considerations, including delayed graft function or unstable renal clearance after kidney transplantation, thrombocytopenia or unstable hepatic synthetic function after liver transplantation, and drug-drug interactions with calcineurin inhibitors, proliferation signal inhibitors, azole antifungals, and protease inhibitors. OAC: Oral anticoagulant; VKA: Vitamin K antagonist; NSAIDs: Non-steroidal anti-inflammatory drugs; PPI: Proton pump inhibitor; GI: Gastrointestinal; DOAC: Direct oral anticoagulant; PSI: Proliferation signal inhibitor; CYP3A4: Cytochrome P450 3A4; CrCl: Creatinine clearance.

Left atrial appendage occlusion may be considered in selected transplant recipients with AF when long-term anticoagulation is not feasible. Limited transplant-specific evidence, consisting mainly of registry-based analyses and small case series, suggests that the procedure can be performed successfully in selected patients. However, comparative outcome data remain sparse, and its role in routine transplant-specific management has not yet been established[74,75]. Registry data also suggest that vascular complications may be more frequent in transplant recipients, pointing out the importance of careful patient selection[74].

RHYTHM CONTROL AND INTERVENTIONAL THERAPIES

Antiarrhythmic drug selection must account for the transplanted organ, graft function, and immunosuppressive regimen. Amiodarone is effective and commonly used, but its risk-benefit profile varies considerably across organ populations. Pulmonary toxicity is a major concern in lung recipients[2,9], hepatotoxicity may confound graft dysfunction assessment in liver recipients[76-78], and interactions with calcineurin inhibitors may increase immunosuppressant exposure and arrhythmic risk in kidney recipients, particularly when tacrolimus levels become supratherapeutic[58,59].

At the pharmacokinetic level, amiodarone and desethylamiodarone inhibit CYP3A4 and P-glycoprotein - pathways involved in the clearance and transport of cyclosporine, tacrolimus, sirolimus, and everolimus. Initiation, discontinuation, or major dose changes of amiodarone should therefore prompt early trough-level monitoring, renal and hepatic reassessment, electrocardiogram/corrected QT interval surveillance, and transplant-pharmacy involvement[78-80]. Key interactions and practical management strategies are summarized in Table 2.

Table 2 Key drug-drug interactions involving amiodarone and immunosuppressants.

Interacting immunosuppressant	Mechanism	Clinical action
Cyclosporine	CYP3A4/P-gp inhibition may increase cyclosporine exposure and nephrotoxicity	Check trough levels after starting or stopping amiodarone; monitor creatinine, BP, K/Mg, and QTc; reduce dose if needed
Tacrolimus	CYP3A4/P-gp inhibition may increase tacrolimus exposure; additive QT prolongation is clinically relevant	Use early frequent trough monitoring, ECG/QTc and renal assessment; correct K/Mg; consider dose reduction in high-risk patients
Sirolimus/everolimus	mTOR inhibitors are CYP3A4/P-gp substrates; exposure and toxicity may increase	Coordinate with transplant pharmacy; adjust to troughs; monitor cytopenias, lipids, proteinuria, wound healing, and liver function

CYP3A4: Cytochrome P450 3A4; P-gp: P-glycoprotein; mTOR: Mammalian target of rapamycin; BP: Blood pressure; K: Potassium; Mg: Magnesium; QTc: Corrected QT interval; ECG: Electrocardiogram.

In heart transplantation, pretransplant amiodarone exposure has raised concerns because of its long half-life and possible redistribution into the donor heart. Nevertheless, some data suggest that long-term pretransplant amiodarone may reduce early post-transplant AF without worsening longer-term survival[81], illustrating how transplant pharmacology can differ meaningfully from standard non-transplant AF management.

Catheter ablation has become an increasingly important rhythm-control strategy in transplant recipients, particularly when arrhythmias are recurrent, symptomatic, or persistent beyond the immediate postoperative period. Three-dimensional electroanatomic mapping is often essential, given that the arrhythmogenic substrate is frequently scar-based and surgically altered[35-38,82].

In lung transplantation, ablation is especially useful for late organized AT, targeting pulmonary vein reconnection, posterior wall scar, mitral annular flutter, cavotricuspid isthmus-dependent flutter, and incisional reentry circuits[2,9,37,38]. Observational studies using radiofrequency ablation suggest durable rhythm control in many patients, with long-term success rates of 70% to 75% and a relatively low rate of major procedural complications[9,38].

Cardiac ablation is particularly effective for cavotricuspid isthmus-dependent flutter and arrhythmias arising from recipient-donor atrioatrial conduction or donor atrial scar circuits[35,36]. A larger single-center series of 30 orthotopic heart transplant recipients with organized atrial arrhythmias found that macroreentry was the underlying mechanism in 96% of cases, with cavotricuspid isthmus-dependent atrial flutter accounting for 93% of arrhythmias regardless of surgical anastomosis type - though the time from transplantation to arrhythmia onset was shorter in recipients with bicaval anastomosis. Electrical repermeation between the recipient and donor atria was identified in 20% of patients but did not serve as a substrate for any observed clinical arrhythmia.

Despite this substrate complexity, catheter ablation has demonstrated acceptable efficacy, with acute success rates of 93% and arrhythmia-free survival of 79% at 60 months[83]. A representative case from our center illustrates the complexity of substrate characterization in this population: Electroanatomical mapping identified recipient-donor atrioatrial conduction and posterior wall scar as the arrhythmogenic substrate, guiding effective radiofrequency isolation of the left pulmonary veins and posterior wall, as shown in Figure 3.

Figure 3 Representative original case from our center showing electroanatomical mapping and radiofrequency catheter ablation in a patient with atrial fibrillation following orthotopic heart transplantation, demonstrating recipient-donor atrial conduction across the left inferior pulmonary vein region. A: Posterior view of the left atrium obtained using the CARTO 3 system (Biosense Webster, CA, United States). The bipolar voltage map uses a 0.10-0.50 mV display scale and demonstrates electrical continuity between recipient and donor atrial tissue in the area adjacent to the left inferior pulmonary vein, suggesting a recipient-graft atrioatrial conduction pathway and posterior wall scar that served as a trigger for atrial fibrillation. This finding guided the ablation strategy, which targeted isolation of the left pulmonary veins and posterior left atrial wall; B: Final electroanatomical map confirming complete electrical isolation of the posterior left atrial wall and left pulmonary veins following ablation, with no residual conduction across the previously identified recipient-donor atrial connection; C: Three-dimensional reconstruction showing radiofrequency ablation lesions placed to achieve circumferential isolation of the left pulmonary veins and posterior wall.

In abdominal transplantation, experience is more limited, but existing single-center data suggest that ablation can be feasible and effective in selected kidney and liver recipients, with outcomes approaching those seen in non-transplant controls[82].

To date, no direct comparative studies have evaluated radiofrequency ablation, cryoballoon ablation, or pulsed field ablation specifically in solid-organ transplant recipients. Most available transplant-specific ablation data, therefore, remain based on radiofrequency series. Cryoballoon strategies may be limited by altered pulmonary venous anatomy, anastomotic geometry, or non-pulmonary-vein macroreentrant substrates, particularly after lung transplantation. Pulsed field ablation is theoretically attractive because of its tissue-selective nonthermal mechanism and favorable safety profile in non-transplant AF ablation, including low reported rates of esophageal injury, pulmonary vein stenosis, and phrenic nerve damage. However, this rationale remains indirect and should not be interpreted as transplant-specific comparative evidence[84].

A practical principle is that timing matters. Very early postoperative AF is often managed conservatively because transient triggers usually predominate. Persistent arrhythmias beyond the early postoperative period, recurrent arrhythmias after initial recovery, and late (> 6 months) arrhythmias are more likely to reflect a stable anatomic or electrophysiologic substrate and may therefore benefit from ablation.

FUTURE DIRECTIONS

Emerging artificial intelligence (AI) and machine-learning approaches may help refine post-transplant AF prediction and surveillance, although they remain investigational. In kidney transplantation, a recent multicenter retrospective study reported that a pre-transplant AI-enabled electrocardiography score was associated with new-onset AF at 30 days, 3 years, and 5 years after transplantation and also correlated with mortality and allograft failure[85]. Future models should integrate preoperative echocardiographic parameters, intraoperative hemodynamic data, immunosuppressant exposure, electronic health record data, and signals from wearable devices and implantable loop recorders. They should also address external validation, calibration, fairness across ancestry groups, and whether AI-guided monitoring improves clinical outcomes.

Population diversity and pharmacogenomic heterogeneity should also be incorporated into future transplant-arrhythmia research. Race/ethnicity and genetic ancestry are not interchangeable biological categories[86,87]; however, observed AF epidemiology, stroke-risk calibration, immunosuppressant exposure, and anticoagulant pharmacokinetics may vary across populations through genetic, comorbidity-related, pharmacokinetic, and healthcare-access mechanisms. Current evidence derives largely from European and North American cohorts, limiting generalizability to admixed Latin American, African, Asian, Indigenous, and other underrepresented populations[86,87]. Cytochrome P450 3A5 expresser status can increase tacrolimus dose requirements[88], and emerging data suggest that ATP-binding cassette subfamily B member 1/CYP3A4/cytochrome P450 3A5 variants may influence DOAC pharmacokinetics in AF, although clinical implementation is yet unknown[89]. Future models and registries should therefore incorporate ancestry-aware calibration and pharmacogenomic data without treating race as a simple biological surrogate.

Several methodological gaps limit the current evidence base. The optimal duration and intensity of rhythm monitoring after transplantation are not standardized, and arrhythmia definitions vary considerably across studies - notably concerning the distinction between transient perioperative AF and clinically meaningful later arrhythmias. Outcome studies will also need to more rigorously separate the independent prognostic contribution of AF from the confounding effects of illness severity, graft pathology, and competing post-transplant complications. Transplant-specific risk stratification tools for both stroke and bleeding remain lacking, and no randomized transplant-specific studies have defined the comparative effectiveness of DOACs, VKAs, catheter ablation, or left atrial appendage occlusion[6,65,74,75,82].

Addressing these gaps will require prospective, multicenter designs with explicit transplant-specific covariates and adjudicated arrhythmia endpoints. Priority areas include standardized definitions of early and late post-transplant atrial arrhythmias, transplant-specific surveillance windows, improved risk stratification for thromboembolism and bleeding, and comparative effectiveness studies evaluating rhythm-control and antithrombotic strategies across organ populations. Reporting should use pre-specified surveillance windows - ideally 0-7 days, 7-30 days, 1-6 months, and beyond 6 months - both to capture the full arrhythmic trajectory and to enable meaningful cross-study comparisons. Structured arrhythmia recognition and long-term follow-up are particularly critical after thoracic transplantation, where the transition from early postoperative AF to later, substrate-driven, organized AT carries distinct, clinically actionable therapeutic implications.

CONCLUSION

Post-transplant AT should be understood not simply as rhythm disturbances, but as dynamic markers of the interaction between recipient vulnerability, surgical anatomy, graft physiology, perioperative stress, and long-term immunosuppressive exposure. Their clinical meaning depends on timing and phenotype: Early episodes frequently reflect transient inflammatory, metabolic, or hemodynamic triggers, whereas late, organized arrhythmias may point to a fixed atrial substrate, altered conduction, or evolving graft-related disease.

Translating this framework into practice requires a transplant-specific approach that integrates arrhythmia burden, rhythm mechanism, graft status, renal and hepatic function, bleeding and stroke risks, drug-drug interactions, and eligibility for invasive strategies such as catheter ablation and left atrial appendage occlusion. General AF guidelines do not fully address these competing variables, and their uncritical extrapolation to transplant recipients may oversimplify clinical decision-making. Ultimately, the management of post-transplant atrial arrhythmias should reflect the individualized, graft-aware reasoning that defines transplant medicine itself.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge Timothy Charles Wilkens for his independent English language review and editing of the manuscript.