Introduction
Atrial fibrillation (AF) is the most common arrhythmia occurring postoperatively in cardiac surgery patients, with an incidence ranging from 20% to 40% [1–5]. It typically manifests between the second and fourth postoperative days and gradually declines over the subsequent 4–7 days [1–5]. AF is associated with significant complications, including cognitive decline, stroke, renal dysfunction and infection, which prolong hospital stays and increase healthcare costs [1, 2].
The pathophysiology of postoperative AF (POAF) is complex and not fully understood. It has been linked to preoperative, intraoperative, and postoperative factors. Recent studies associate postoperative AF with local intrapericardial inflammation and oxidative stress. Emerging evidence suggests that shed mediastinal blood may trigger POAF by initiating an inflammatory response [3, 4]. Inflammation decreases the effective refractory period of myocytes and reduces the production of sarcolipin, a protein that inhibits the sarcoplasmic reticulum Ca-ATPase. This disruption increases myocardial calcium levels, which can trigger AF [3, 4].
Aim
The aim of this study was to investigate whether the amount of mediastinal fluid correlates with new onset atrial fibrillation during the in-hospital postoperative period.
Material and methods
Between February 2021 and March 2024, 1140 patients undergoing open cardiac surgery with cardiopulmonary bypass (CPB) at our institution were included, excluding those with permanent or paroxysmal preoperative AF. The mean age of the patients was 66.1 ±10.1 years, and 857 (75.2%) were men. Surgical procedures included coronary artery bypass grafting (CABG) (680 patients, 59.6%), isolated valvular surgery (245 patients, 21.5%), combined CABG and valvular surgery (98 patients, 9.8%), and replacement of the ascending aorta (117 patients, 10.26%). Patients who underwent off-pump CABG were excluded from the study. Patient characteristics are shown in Table I.
Table I
Preoperative parameters of total group (N = 1140)
Preoperative parameters for the entire cohort included diabetes mellitus (419 patients, 36.8%), current smoking (627 patients, 55%), hypertension (794 patients, 69.6%), dyslipidemia (663 patients, 58.2%), stroke (63 patients, 5.5%) and chronic obstructive pulmonary disease (COPD) (78 patients, 6.8%). The mean left ventricular ejection fraction (EF) was 54.3 ±10.2%.
Patients were divided into two groups: Group I: Patients who maintained sinus rhythm postoperatively, Group II: Patients who developed new-onset AF during the in-hospital postoperative period.
Statistical analysis
Data analysis was conducted using IBM SPSS Statistics version 21.0 (IBM Corp., Chicago, IL). Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as percentages. Pearson’s χ2 test or Fisher’s exact test was used for categorical comparisons. Depending on normality, continuous variables were analyzed using the Mann-Whitney U test or Student’s t-test. The Kolmogorov-Smirnov test was used to assess normality. Stepwise logistic regression analysis identified significant predictors of AF development. A two-sided p-value < 0.05 was considered statistically significant. To improve interpretability, the odds ratio for mediastinal drainage was recalculated per 100 ml.
Results
POAF developed in 388 (33.59%) patients. According to univariate analysis, preoperative factors revealed as significant predictors of POAF were: age (p < 0.001) and hypertension (p = 0.001) (Table II). Also, all 3 investigated intraoperative and postoperative factors were found to be significant predictors of POAF: duration of CPB (p < 0.001), aortic cross-clamping (ACC) time (p = 0.01), and the amount of mediastinal drainage (p = 0.008) (Table III).
Table II
Preoperative factors
Table III
Intraoperative parameters
Factors without any statistical relationship with POAF were: male sex (p = 0.3), diabetes mellitus (p = 0.2), current smoking (p = 0.2), dyslipidemia (p = 0.6), COPD (p = 0.6), history of stroke (p = 0.7) and left ventricular ejection fraction (p = 0.4).
In the multivariate logistic regression analysis, age (OR = 1.03, 95% CI: 1.01–1.05, p = 0.001), hypertension (OR = 0.61, 95% CI: 0.41–0.90, p = 0.01), CPB time (OR = 1.004 per minute, 95% CI: 1.00–1.008, p = 0.04), and the amount of mediastinal drainage (OR = 1.036 per 100 ml, 95% CI: 1.00–1.07, p = 0.04) were identified as independent predictors of POAF. Recalculating the odds ratio for drainage in 100 ml increments better illustrates the clinical significance: for each additional 100 ml of mediastinal drainage, the odds of developing POAF increased by approximately 3.6% (Table IV).
Discussion
Up to 50% of patients who undergo cardiac surgery experience postoperative AF within 1 week after open-heart surgery, and 70% of patients undergoing CABG experience episodes of AF within the first 3 days. AF is associated with postoperative complications that prolong hospital stays and increase costs [1, 2, 6, 7].
The pathophysiology of postoperative AF involves a combination of preoperative, intraoperative, and postoperative risk factors such as age, COPD, diabetes mellitus, pericarditis, atrial injury, ischemia-reperfusion, heightened sympathetic tone, hemodynamic and metabolic derangements, structural abnormalities, and pre-existing electrophysiological atrial abnormalities. Recent studies suggest a role of local pericardial inflammation and postoperative pericardial effusion in triggering AF in patients with long-standing structural changes in the electrophysiological atrial substrate [1, 2, 6, 7]. These changes in the atrium occur due to damage from various forms of structural heart disease and long-standing myocardial stress. All these factors can lead to abnormal dispersion of refractoriness, making the atrium vulnerable to the development of fibrillation [5].
During cannulation, AF can be triggered, as neutrophil infiltration and inflammation in the atrial wall around the atriotomy correlate with inhomogeneities and alterations in action potential duration in the atrial substrate. These factors may trigger re-entrant circuits around the atriotomy [8–12].
Recent studies have demonstrated a relationship between procedures involving the opening of the pericardium and the exposure of the intrapericardial environment to blood, which can trigger POAF. Lower AF incidence was observed in procedures without pericardiotomy (82%) compared to those with pericardiotomy [5]. Inflammation and oxidative stress lead to lipid peroxidation and are associated with cell membrane disruption, mitochondrial dysfunction, calcium overload, apoptosis, cell death, increased cardiac myocyte dysfunction, atrial damage, electrical and structural remodeling, and atrial conduction abnormalities. The primary source of inflammation and oxidative stress is shed mediastinal blood within the pericardium, which triggers the onset of POAF through several mechanisms [8–10].
During surgery, due to operative trauma and cardiopulmonary bypass, shed mediastinal blood undergoes substantial procoagulant and proinflammatory modifications that persist for hours and days after surgery. Intrapericardial blood activates the clotting cascade, producing thrombin and fibrin. Thrombin recruits and activates platelets, which rapidly express P-selectin. This initiates the translocation of neutrophils from the surface of the heart and vessels into the pericardial space. Neutrophils and platelets generate inflammatory cytokines such as interleukins IL-1 and IL-8, which recruit leukocytes. IL-6 stimulates neutrophils, leading to oxidative bursts and the release of reactive oxygen species. The highly concentrated fibrin in clot areas interacts with activated neutrophils to maximize damage, release cytokines, and increase the recruitment and activation of additional neutrophils [10, 12, 13].
Hemolysis, which occurs postoperatively due to the resolution of hematomas, is another important factor in postoperative inflammation. Red blood cells release hemoglobin, which is oxidized to methemoglobin. Methemoglobin is a strong activator of endothelial cells via nuclear factor kappa-B upregulation of cell adhesion molecules such as E-selectin and the expression of cytokines and chemokines. The main source of oxidative stress is hydrogen peroxide (H2O2), produced by neutrophils and monocytes through NADPH oxidase-2 activity. In the presence of methemoglobin and myoglobin, hydrogen peroxide promotes lipid peroxidation of cellular fats or myocardial tissue directly or via ferrylhemoglobin [11, 14].
Until recently, it was unclear whether inflammation and oxidative stress act through damage to the surrounding fatty tissue and atrial surface, or whether autonomic regulation modulates atrial rhythm. A significant target of inflammation is periatrial fat, which is induced by mediastinal blood. Periatrial fat is highly metabolically active and a critical source of cytokines and adipokines, which can influence the onset of AF [14, 15]. All cardiac surgeries involve pericardiotomy, allowing bleeding into the intrapericardial space. Although chest tubes are used to evacuate mediastinal blood, they can sometimes become occluded due to sustained blood loss, stasis, or high fibrinolytic activity. Retained blood around the heart may cause mechanical compression, resulting in oxidative stress and an increased incidence of AF [5, 16].
Further investigations are needed to correlate the amount of mediastinal blood with the degree of intrapericardial inflammation. Reducing mediastinal blood and ensuring chest tube clearance can significantly reduce AF incidence (by 33%). If chest tubes remain free of clots during the first few hours, AF incidence can be reduced by up to 50% [17–19]. Surgical techniques to minimize postoperative bleeding and improved management of bleeding may reduce the quantity of retained blood and intrapericardial clotting [20]. Samuel et al. reported that limiting exposure to mediastinal blood may be more effective in reducing postoperative atrial fibrillation (PAF) after cardiac surgery than antiarrhythmic drugs [5]. Gaudino et al. demonstrated that pericardial blood provokes atrial fibrillation after cardiac surgery [9]. Our study found that shed mediastinal blood is a statistically significant factor in the development of postoperative paroxysmal atrial fibrillation. Although the initial odds ratio for drainage per ml appeared close to 1, recalculating per 100 ml demonstrates that greater volumes of mediastinal blood loss are significantly associated with an increased risk of POAF. This finding reinforces the clinical importance of effective mediastinal drainage management to reduce the inflammatory trigger for atrial fibrillation.
However, further research is needed to elucidate the mechanisms through which mediastinal blood influences AF onset and to assess the degree of correlation between inflammation caused by chest tube obstruction and the amount of blood remaining in the pericardial space.
