The Management of Postoperative Atrial Fibrillation (POAF): A Systematic Review

Postoperative atrial fibrillation (POAF) refers to new-onset atrial fibrillation (AF) that develops after surgery and is associated with an increased risk of mortality and thromboembolic events. The optimal management and treatment methods for POAF complications are not yet fully established. This systematic review aimed to evaluate the various treatment and management approaches currently available in terms of their suitability, efficacy, and side effects in handling POAF incidence post-surgery. Google Scholar and PubMed electronic databases were searched extensively for relevant articles examining the various management techniques currently used to manage POAF and published between 2018 and 2023. Data were collected on the type of surgery the patients underwent, POAF definition period, intervention, and outcome of interest. Following a systematic assessment guided by the inclusion criteria, 10 of the 579 studies retrieved were included in this study, and 293,417 POAF cases were recorded. Three of these studies used different rhythm control and rate control treatments to manage POAF cases, while seven studies used various anticoagulation therapies to manage POAF incidence. For asymptomatic patients within one to three days of surgery, rate control is sufficient to manage POAF, and routine rhythm control is not needed; rhythm control should be reserved for patients who develop complications such as hemodynamic instability. Anticoagulation was performed in patients whose POAF exceeded four days after surgery. Anticoagulation was associated with an increased risk of mortality, stroke, thromboembolic events, and major bleeding in patients who underwent coronary artery bypass graft (CABG) surgery. In contrast, in a few other studies, anticoagulation treatment led to improved outcomes in patients who developed POAF. A wide range of management methods are available for POAF after different types of surgery. However, there is only limited evidence to guide the clinical practice. The data available are mainly retrospective and insufficient to accurately evaluate the efficacy of the various management methods available for POAF. Future research should make efforts to standardize the treatment for this condition.


Introduction And Background
Postoperative atrial fibrillation (POAF) is defined as new-onset atrial fibrillation (AF) occurring immediately after surgery and is the most common type of secondary AF (AF attributed to identifiable, primary, and acute conditions) [1].POAF is the most prevalent and potentially fatal cardiac complication occurring postoperatively.POAF affects approximately 25-55% of cardiac surgery patients [2].In approximately 90% of cases, patients develop POAF within the first six days following the operation, coinciding with the peak of the systemic inflammation response after surgery [3].POAF is an indicator of both short-term and long-term cardiovascular problems, such as stroke, infarction, thromboembolism, and cardiac arrest, and may require reoperation owing to internal bleeding [4,5].In addition to spending an average of 3.7 more days in the hospital, POAF patients have a two-fold greater risk of all-cause 30-day and six-month mortality [6,7].
POAF is distinguishable from other forms of AF since it is characterized by a unique presentation compared to other forms of AF.POAF typically arises in patients within the first six days post-surgery and then returns to a normal sinus rhythm.Although the definitive mechanism behind POAF is still not fully understood, etiologies currently associated with POAF usually require a trigger as well as a vulnerable atrial substrate change, normally originating from the pulmonary veins and other atrial areas [8].Moreover, numerous biochemical events that cause metabolic derangements in cardiomyocytes affect electrophysiological, contractile, and structural cellular characteristics in AF pathogenesis [9,10].Medical management or treatment is usually based on the understanding of etiology, and given that the mechanism of the pathology of POAF is still elusive, the scope for successful preventative and treatment measures for POAF is limited.Recent developments and research have shown that POAF is partly preventable [11].However, scarce and controversial data, lack of knowledge on independent risk factors, and effective interventions coupled with inconsistent clinical databases have limited the progress of any milestone advancement in the prevention of POAF.Despite the continuous and rapid growth of the POAF-related literature, the prevalence of POAF has remained constant over the past 30 years.Several factors such as myocardial infarction (MI), hypertension, heart failure, atrial fibrosis, heart disease, male sex, obesity, and a history of arrhythmias have been associated with a higher risk of developing POAF [11].This systematic review provides a comprehensive and updated summary of the therapeutic management and treatment procedures that are currently available for POAF, including an analysis of the efficiency and side effects of these strategies.

Material and methods
This systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.For the bibliographies, a systematic search was exhaustively performed on two electronic databases (PubMed and Google Scholar) to retrieve studies that evaluated the management of POAF.The systematic review protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) CRD42022369158.

Search Strategy
A comprehensive and systematic computerized search was conducted using a set of keywords or phrases in addition to Boolean expressions "OR" and "AND."The keywords and phrases used to navigate the databases were as follows: ("management" OR "treatment" OR "therapeutic measures") AND "postoperative atrial fibrillation" OR "POAF" OR "PAF" or "atrial fibrillation after surgery").The search was customized to retrieve studies published between January 2018 and February 2023.

Eligibility Criteria
Three independent reviewers applied the following inclusion criteria to select studies for inclusion in this review: • Primary and secondary studies evaluating the treatment or management of POAF.
• Studies published from January 2018 to February 2023 in the English language.
Studies were excluded based on the following exclusion criteria: • Studies that used non-human populations.
• Studies published before 2018, to ensure that only up-to-date information was used.
• Case series and case reports.

Data Extraction
Two independent investigators were tasked with performing data extraction, adhering to the predefined eligibility features of the studies and the PICO (population, intervention, control, and outcomes) guidelines.The extracted data included author information, population (size and characteristics), case intervention, and outcome of interest in POAF management.

Data Synthesis and Quality Appraisal
Applying a thematic approach, the two reviewers synthesized and screened the results of the publications included, thereby making it possible to analyze the results of all studies considered in this review.The reviewers independently inspected the abstracts and titles.The full texts of related studies were retrieved and reviewed.Relevant data were extracted from the studies, and the risk of bias was assessed using appropriate quality assessment tools.Consensus was sought through debate with a third author to resolve discrepancies, if necessary.

Ethical Approval
This systematic review required no ethical approval since it was a completely literature-based analysis of full-text primary and secondary published studies.

Search Results
The electronic search of the two databases yielded 579 articles, out of which 115 studies and another 52 were eliminated for unrelated titles and abstracts.After careful screening of the remaining 412 articles, 370 were excluded since they failed to meet the inclusion criteria.The 42 retrieved studies were assessed for eligibility.Among these, six did not discuss POAF management or treatment, and 26 were published before 2018 and were thus excluded.This review was based on the remaining 10 studies that fully met the inclusion criteria.The PRISMA flow chart for study selection is illustrated below in Figure 1 [12].

Study Characteristics
The characteristics of all the studies included in the review are summarized in Tables 1-2.Two investigators independently evaluated the risk of bias of the included studies using the Newcastle-Ottawa Quality Assessment Scale for case-control studies and cohort studies, GRADE (Grading of Recommendations Assessment, Development, and Evaluation) certainty rating, and Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist for meta-analysis, which are depicted in Table 3, Table 4, and Table 5 respectively.All the studies were of low risk of bias with no effect on the outcomes of our results.

Discussion
This systematic review aims to evaluate the management approaches for POAF following different surgical procedures.POAF is typically transient and often requires no intervention or treatment.However, therapeutic management is required in high-risk patients with abnormal cardiac function, cerebral thromboembolism, or POAF duration >48 hours.The immediate postoperative setting presents unique challenges for the management of patients with POAF.Our findings showed that several methods have been used for the treatment and management of POAF.Approaches for the treatment of POAF include heart rate control, rhythm control, and antithrombotic therapy, which are the same approaches for treating chronic AF.
Our findings show that rhythm control strategies (such as antiarrhythmic, cardioversion, and amiodarone management) and rate control strategies (including β-blockers/non-dihydropyridine calcium channel blockers) are used to manage short-term complications when POAF is defined in a patient within the first 48 or 72 hours (or within three days) post-surgery (P1) [13,14,18].Rhythm control and rate control are two broad therapies used for treating patients with POAF.Rhythm control is a strategy that focuses on returning to normal sinus rhythm and maintaining it using anti-arrhythmic drugs [23].In contrast, rate control applies a single medication or a combination of negatively chronotropic medications to control heart rate.Rhythmic control methods for POAF have been favored to reduce the risk of systematic anticoagulation, promote faster recovery of full operation capacity, and reduce the duration of hospital stay and costs of hospitalization [23].This study further illustrates that the rate control technique is sufficient for most asymptomatic patients with POAF.
Another study also reached the same conclusions, arguing that for asymptomatic patients within one to three days of surgery, rate control is sufficient to manage POAF, and that routine rhythm control is not needed; rhythm control should be used for patients who develop complications, such as hemodynamic instability [24].Rate control techniques include β-blockers and antiarrhythmic drugs such as amiodarone and sotalol.Beta-1 receptor antagonists or blockers are inhibitors of β1-adrenergic receptors, which play a role in sympathetic stimulation in the myocardium.Increased sympathetic stimulation is one of the etiologies of POAF.β-blockers block these receptors, thereby reducing the stroke volume and cardiac output and decreasing the heart rate.β-blocker prophylaxis prior to cardiac surgery has been demonstrated as a highly effective POAF preventive strategy [24].A Cochrane review and meta-analysis of 33 studies suggested that β-blockers resulted in a significant decrease in POAF incidence [odds ratio (OR): 0.33, 95% CI: 0.26-0.43)[5].Cochrane analysis showed substantial heterogeneity among the studies (I 2 =55%).Notably, the Cochrane study might have overestimated β-blocker efficacy since the study relied on the discontinuation of background therapy with β-blockers with the potential to increase the POAF incidence due to control group withdrawal [5].Despite this, a trial that did not warrant any control group withdrawal yielded consistent results and confirmed the high efficacy of β-blockers.However, β-blockers did not significantly affect mortality, stroke, or length of hospitalization [5].In addition, a Cochrane systematic review of 63 randomized trials also inferred that β-blockers decreased the risk of POAF [with a relative risk (RR) of 0.50 (95% CI: 0.42-0.59;heterogeneity I 2 =59%] [25].Although these studies agree that the use of βblockers is an effective therapy for managing POAF after cardiac surgery, β-blockers are not commonly used for prophylaxis.This has been confirmed by our review, where the studies reviewed hardly reported βblockers as an intervention for POAF.Another study carried out by the European Association of Cardiovascular Anesthetists (EACA) and the Society of Cardiovascular Anesthesiologists (SCA) reported alternative approaches to the perioperative use of β-antagonists [26].
The study also reported the use of amiodarone and sotalol [19] in the management of POAF after cardiac surgery.Other trials have proven that amiodarone is effective for POAF prevention [5] and has been granted Class IIA indication by European and American guidelines.Amiodarone is classified as an antiarrhythmic agent responsible for peripheral and coronary vasodilation.However, amiodarone poses serious risks such as increased liver enzymes, bradycardia, thyrotoxicosis, hyperthyroidism, and interstitial pneumonitis.These side effects may significantly outlast the discontinuation of use [27].
In contrast, anticoagulation resulted in better outcomes in the treatment of POAF after non-CABG cardiac surgery.This outcome is consistent with other studies that have shown that anticoagulation reduces the risk of mortality in patients who develop POAF after non-CABG cardiac surgery but increases the risk of mortality, stroke, and major bleeding in those who develop POAF following noncardiac surgery [9,28].This is a challenge because anticoagulation therapy presents two distinct patient groups, each with a high or low risk of AF recurrence.Therefore, a predictive framework should be developed to ensure that risks are eliminated in both these distinct populations.
This review further revealed that in cases where anticoagulation was used, POAF was defined beyond four days to 30 and 30 to 180 days post-surgery, and direct oral anticoagulation was preferred [15,16].The duration of anticoagulation is critical because of the risk of early stroke or AF recurrence.Limited data are available to guide the timing and duration of anticoagulation therapy.However, studies show that timing should vary between 48 and 72 hours or earlier if there is a greater risk of thromboembolic events.The risk of gross complications and bleeding due to platelet dysfunction and cardiopulmonary bypass decreased in the early preoperative period.Other studies have shown that the risk of stroke and recurrent AF is highest within the first year of surgery, after which there is a steady decline [29,30].Our review adds to the 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures [11].However, data on the long-term significance of POAF episodes are currently unavailable, and more research should be conducted to develop properly defined standard procedures for treating and managing POAF.

Limitations of the study
Despite our rigorous and comprehensive approach, this systematic review has some limitations that warrant consideration.Firstly, most of the studies were retrospective, and RCTs were scarce.Retrospective studies may be prone to sample bias, which may compromise the accuracy of the conclusions inferred.Moreover, the sample sizes in the studies reviewed were low, thus affecting our ability to assess outcomes and allow adjustments for covariables.Another limitation was the small number of articles that met our inclusion criteria, which means that we could not gather a substantial amount of evidence or data.

Conclusions
There are several approaches that have been employed in the management of POAF after various types of surgeries.The different strategies or therapies for the treatment of POAF include rate control, rhythm control, and antithrombotic therapy.These techniques consist of a wide range of pharmacological and nonpharmacological treatments with variations in the duration of initiation, efficacy, and side effects.Our review contributes to the current guidelines for POAF; however, data on the long-term significance of POAF episodes are scarce, and further research should be conducted to develop properly defined standard procedures for treating and managing POAF.

FIGURE 1 :
FIGURE 1: PRISMA flow chart depicting the selection of studies PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

TABLE 4 : Quality assessment of the included studies using the GRADE certainty rating
GRADE: Grading of Recommendations Assessment, Development, and Evaluation

TABLE 5 : Quality assessment of the included studies using the AMSTAR 2 grading
AMSTAR 2: Assessment of Multiple Systematic Reviews 2