Abstract
Background:
Data on new onset postoperative atrial fibrillation (POAF) after Stanford type A dissection (STAAD) surgery was limited. This study aimed to detect the risk factors for developing POAF after STAAD procedures and the association between POAF and in-hospital mortality.
Methods:
A total of 1354 patients who underwent surgical treatment for STAAD in Beijing Anzhen hospital were enrolled in this single-center retrospective study from January 2015 to October 2020. POAF were defined as atrial fibrillation/flutter requiring treatment after surgery procedure. Logistic model was conducted to detect the predictors of POAF, and inverse probability of treatment weighting (IPTW) and subgroup analysis were used to compare the mortality of POAF and non-POAF groups.
Results:
There were 176 patients (13.0%) diagnosed with POAF according to the definition. Multivariate logistics analyses revealed that advanced age [odds ratio (OR), 1.07; 95% CI: 1.05–1.08; P<0.001)], creatinine (OR, 1.00; 95% CI: 1.00–1.01; P=0.001) and cross-clamp time (OR, 1.00; 95% CI: 1.00–1.01; P=0.021) were independent risk factors of developing POAF in STAAD patients. POAF patients were associated with significantly higher in-hospital mortality compared with non-POAF patients (6.5 vs. 19.9%, OR, 3.60; 95% CI: 2.30–5.54; P<0.001), IPTW and subgroup analysis had reached consistent conclusions.
Conclusions:
The incidence of POAF was 13.0% after STAAD surgery, advanced age, creatinine, and cross-clamp time were independent risk factors of developing POAF in STAAD patients. POAF is associated with increased mortality after STAAD procedures.
Keywords: aortic dissection, aortic surgery, atrial fibrillation, arrhythmia
Background
Highlights
This study investigated the predictors and mortality of postoperative atrial fibrillation (POAF) after Stanford type A dissection (STAAD) procedures, which would provide some suggestions and tips for surgeons in clinical practice.
We recommend enhanced perioperative monitoring in patients with high risks, such as advanced age, creatinine and cross-clamp time, to reduce the risk of POAF and minimize adverse outcomes.
POAF after STAAD procedures is associated with increased mortality.
Aortic dissection is one of the most insidious types of aortic disease, particularly the Stanford type A dissection (STAAD), which increases the mortality rate by 1–2% per hour in the early stage of onset, and as without surgical treatment, the 14 day mortality rate is up to 50%1,2. For the current treatment of STAAD, the guidelines recommend surgical intervention as the first choice3. Atrial fibrillation (AF) is one of the most common complications after cardiac surgery4. The overall incidence of postoperative atrial fibrillation (POAF) ranges from 15 to 60% and is highest in patients undergoing valve surgery, reaching 37–60%4–6. For thoracic aorta surgery, the probability of POAF is ~17%7, and 32.3% for patients undergoing total aortic arch replacement8. Studies have shown that the occurrence of POAF is associated with increased length of hospital stay, stroke risk, medical costs, in-hospital mortality and most short-term and long-term cardiovascular adverse events after cardiac surgery7–11.
However, there has been no literature on new onset AF after surgical intervention with STAAD, the present cohort study aimed to evaluate the incidence and associated risk factors of new onset POAF after STAAD surgery, and the association between POAF and in-hospital mortality. To provide a reference for the development of treatment options and prevention of complications during the post dissection period.
Methods
Study population
This study was a single-center retrospective cohort study that included 1512 STAAD patients undergoing surgical treatment at Beijing Anzhen hospital from January 2015 to October 2020. Exclusion criteria were as follows: (1) age <18 years old; (2) history of paroxysmal or persistent AF or atrial flutter prior to surgery; (3) death during or within 24 h after surgery; (4) patients with missing data. Ultimately, 1354 patients were included in the study, comprising 176 patients who developed POAF (POAF group) and 1178 patients who did not (non-POAF group) (Fig. 1).
Figure 1.
Flowchart of the study. AF, atrial fibrillation; IPTW, inverse probability of treatment weighting; POAF, postoperative atrial fibrillation; STAAD, Stanford type A dissection.
This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), the work has been reported in line with the strengthening the reporting of cohort, cross-sectional and case–control studies in surgery (STROCSS) criteria12, and the study was approved by local research ethics board of Beijing Anzhen hospital, individual consent for this retrospective analysis was waived.
Data collection and definition
The preoperative baseline data, intraoperative surgical characteristics, and postoperative outcomes were collected from the electronic medical records system of Beijing Anzhen hospital, which consist of medical history, medical progress note, operative record, test results, monitor records and nursing record, etc. The patient’s medical history would be routinely inquired in detail at the time of admission to ensure the accuracy of the medical history. We had built Case Report Form (CRF) table, two investigators would entry and double check the accuracy of the data, patients with incomplete data would be excluded. Continuous electrocardiogram monitoring was used in the ICU to determine patients’ cardiac rhythm, and the occurrence of cardiac arrhythmias was assessed by at least two physicians. According to the Society of Thoracic Surgeons (STS) adult cardiac surgery database data collection (Available at: https://www.sts.org/registries-research-center/stsnational-database/adult-cardiac-surgery-database/data-collection, accessed 9 December 2019). POAF was defined as: the patient experienced AF/flutter requiring treatment after surgery procedure, and exclude patients who were in AF at the start of surgery. In-hospital mortality was defined as: all-cause death during the entire hospitalization7.
Surgical procedure
The surgeries were performed under general anesthesia with cardiopulmonary bypass (CPB). A cooling cap was used to reduce cerebral oxygen consumption, and real-time monitoring of brain waves was conducted during the surgery. The choice of arterial cannulation (axillary artery, femoral artery, or combined axillary-femoral cannulation) for CPB was based on intraoperative considerations. The surgical approach was selected based on the extent of aortic dissection and the characteristics of aortic root pathology to ensure optimal treatment outcomes. For the treatment of the aortic root, various procedures such as Bentall procedure (composite valve graft aortic root replacement), David procedure (valve-sparing aortic root replacement), and Wheat procedure (replacement of aortic valve and ascending aorta) are utilized. In the treatment of the aortic arch, total or nontotal arch replacement is performed depending on the specific situation. In cases where the pathology extends to the descending aorta, the implantation of a distal elephant trunk graft can be considered. Depending on the intraoperative coronary artery and valve conditions, coronary artery bypass grafting (CABG) or valve surgery may be performed concurrently.
Statistical analysis
Continuous variables that follow a normal distribution are expressed as mean ±SD, and the t-test is used for comparing two groups. Non-normally distributed continuous variables are expressed as median (P25, P75), and the Mann–Whitney U test is used for comparing two groups. Categorical data are presented as percentages, and the χ2test or Fisher’s exact test is used for comparing groups. Univariate and multivariate logistic regression analysis is used to identify relevant risk factors for the occurrence of POAF.
In order to reduce the impact of potential confounding factors caused by unbalanced covariates, we performed inverse probability of treatment weighting (IPTW) via propensity score using a logistic regression model. Key variables and risk factors were involved in the model: age, male, BMI, hypertension, diabetes mellitus, hyperlipidemia, left ventricular ejection fraction (LVEF), creatinine, hemoglobin, D-Dimer, emergency surgery, nontotal arch replacement, Bentall, ascending aorta replacement, CABG, CPB time, deep hypothermia circulatory arrest (DHCA) time and blood loss. Standardized difference (SD) less than 0.1 indicated good balance after IPTW. Subsequently, a subgroup analysis was conducted to further exam the outcomes within different sub-populations.
All statistical data analysis was conducted using the SPSS software package (IBM SPSS Statistics for Windows, Version 22.0) and R 4.2.0, a P-value <0.05 was considered statistically significant.
Results
Baseline characteristics
A total of 1354 patients who underwent surgical treatment for STAAD were enrolled in this study. Among them, 176 patients were be diagnosed with POAF according to the definition (POAF group), and 1178 patients did not develop POAF (non-POAF group), the incidence of POAF was 13.0%. The POAF patients had older age (47.6±11.2 vs. 54.8±10.5, P<0.001), higher level of preoperative creatinine and D-Dimer, lower level of hemoglobin, longer time of cross-clamp and more volume of perioperative blood loss, also had higher male and nontotal arch replacement proportion. No other clinical characteristics differ significantly (Table 1).
Table 1.
Baseline characteristics of patients in non-POAF and POAF group.
| Variables | All patients (n=1354) | non-POAF (n=1178) | POAF (n=176) | P |
|---|---|---|---|---|
| Age | 48.5±11.3 | 47.6±11.2 | 54.8±10.5 | <0.001 |
| Male | 1043 (77.0) | 921 (78.2) | 122 (69.3) | 0.009 |
| BMI (kg/m2) | 26.0 (23.4, 28.5) | 26.0 (23.4, 28.6) | 26.1 (23.4, 28.4) | 0.629 |
| Hypertension, n (%) | 1008 (74.4) | 871 (73.9) | 137 (77.8) | 0.268 |
| Hyperlipidemia, n (%) | 89 (6.6) | 78 (6.6) | 11 (6.3) | 0.853 |
| Diabetes mellitus, n (%) | 54 (4.0) | 46 (3.9) | 8 (4.5) | 0.685 |
| LVEF (%) | 62 (58, 66) | 62.0 (58, 66) | 62 (59, 66) | 0.429 |
| Previous PCI | 11 (0.8) | 10 (0.8) | 1 (0.6) | 1.000 |
| Valvular disease (%) | 469 (34.6) | 410 (34.8) | 59 (33.5) | 0.739 |
| Creatinine (μmol/l) | 93.4 (72.5, 127.5) | 91.3 (71.4, 121.0) | 117.5 (82.6, 152.7) | <0.001 |
| D-Dimer (ng/ml) | 1459.5 (871.8, 2566.0) | 1396.0 (810.8, 2534.8) | 1931.0 (1197.0, 2908.8) | <0.001 |
| Hemoglobin, g/l | 121.0 (103.0, 133.0) | 122.0 (103.0, 134.0) | 118.0 (100.3, 125.8) | 0.004 |
| Emergency surgery | 1189 (87.8) | 1030 (87.4) | 159 (90.3) | 0.272 |
| Bentall | 593 (43.8) | 505 (42.9) | 88 (50.0) | 0.075 |
| David | 5 (0.4) | 5 (0.4) | 0 (0.0) | 1.000 |
| Wheats | 3 (0.2) | 3 (0.3) | 0 (0.0) | 1.000 |
| Total arch replacement + FET | 850 (62.8) | 745 (63.3) | 105 (59.7) | 0.359 |
| Nontotal arch replacement | 123 (9.1) | 98 (8.3) | 25 (14.2) | 0.011 |
| Ascending aorta replacement | 711 (52.5) | 625 (53.1) | 86 (48.9) | 0.299 |
| CABG | 60 (4.4) | 48 (4.1) | 12 (6.8) | 0.099 |
| Valve replacement (%) | 43 (3.2) | 39 (3.3) | 4 (2.3) | 0.464 |
| CPB time (min) | 194.0 (165.0, 244.0) | 193.0 (164.0, 222.0) | 203.5.0 (175.3.0, 232.8) | 0.001 |
| DHCA time (min) | 22.0 (17.0, 29.3) | 22.0 (17.0, 30.0) | 23.0 (17.0, 29.0) | 0.967 |
| Cross-clamp time (min) | 108.0 (90.0, 131.0) | 107 (89, 130) | 118 (100, 138) | <0.001 |
| Blood loss (ml) | 1200.0 (1000.0, 1500.0) | 1200.0 (1000.0, 1500.0) | 1300.0 (1000.0, 1800.0) | 0.015 |
| RBC transfusion (U) | 1.4±2.4 | 1.4±2.4 | 1.7±2.5 | 0.150 |
| Plasma transfusion (ml) | 196.9±307.0 | 193.2±303.4 | 221.6±329.5 | 0.253 |
CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; DHCA, deep hypothermia circulatory arrest; FET, frozen elephant trunk; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; POAF, postoperative atrial fibrillation; RBC, red blood cell.
Logistic regression analysis for risk factors of POAF in STAAD patients
All the potential risk factors were involved in the univariate logistic regression analyses, it showed that age, male, creatinine, hemoglobin, nontotal arch replacement, CPB time and cross-clamp time were risk factors for POAF, D-Dimer, and blood loss were not statistically significant risk factors. Then, multivariate logistic regression was performed with variables that had been significant in previous univariate analysis (age, male, creatinine, hemoglobin, nontotal arch replacement, CPB time, and cross-clamp time) for independent risk factors evaluation. Finally, it revealed that advanced age [odds ratio (OR), 1.07; 95% CI: 1.05–1.08; P<0.001), creatinine (OR, 1.00; 95% CI: 1.00–1.01; P=0.001) and cross-clamp time (OR, 1.00; 95% CI: 1.00–1.01; P=0.021) were independent risk factors of developing POAF in STAAD patients (Table 2).
Table 2.
Univariate and multivariate logistic regression of patients in non-POAF and POAF group.
| Univariate analysis | Multivariate analysis | |||||
|---|---|---|---|---|---|---|
| Risk factor | OR | CI | P | OR | CI | P |
| Age | 1.06 | 1.05–1.08 | <0.001 | 1.07 | 1.05–1.08 | <0.001 |
| Male | 0.63 | 0.45–0.89 | 0.010 | – | – | 0.057 |
| Creatinine | 1.00 | 1.00–1.01 | <0.001 | 1.00 | 1.00–1.01 | 0.001 |
| D-Dimer | 1.00 | 1.00–1.00 | 0.084 | – | – | 0.388 |
| Hemoglobin | 0.99 | 0.99–0.10 | 0.022 | – | – | 0.418 |
| Nontotal arch replacement | 1.83 | 1.14–2.92 | 0.012 | 1.86 | – | 0.159 |
| CPB time | 1.00 | 1.00–1.01 | <0.001 | 1.01 | – | 0.056 |
| Cross-clamp time (min) | 1.01 | 1.00–1.01 | 0.021 | 1.00 | 1.00–1.01 | 0.021 |
| Blood loss | 1.00 | 1.00–1.00 | 0.075 | – | – | 0.437 |
CPB, cardiopulmonary bypass; OR, odds ratio; POAF, postoperative atrial fibrillation.
In-hospital mortality
The outcome of in-hospital mortality of the two groups are shown in Table 3. There were 76 patients dead in non-POAF group, and 35patients dead in POAF group during the hospitalization. Patients with POAF were associated with significantly higher in-hospital mortality compared with non-POAF patients (6.5 vs. 19.9%, OR, 3.60; 95% CI: 2.30–5.54; P<0.001). After weighted by IPTW, baseline characteristics were similar between the two groups and the standardized differences of the covariates were less than 10%, indicated a well-balanced weighting (Fig. 2). The logistic regression after weighted still showed significant higher in-hospital mortality in POAF group (9.0 vs. 20.0%, OR, 2.49; 95% CI, 1.54–4.03; P<0.001) (Table 3).
Table 3.
In-hospital mortality of unweighted and weighted patients.
| No-POAF death No. (%) | POAF death No. (%) | OR (95% CI) | P | |
|---|---|---|---|---|
| Unweighted | 76 (6.5) | 35 (19.9) | 3.60 (2.30–5.54) | <0.001 |
| Weighted | 15.6 (9.0) | 35.1 (20.0) | 2.49 (1.54–4.03) | <0.001 |
CPB, cardiopulmonary bypass; OR, odds ratio; POAF, postoperative atrial fibrillation.
Figure 2.
Covariates distribution of unweighted and weighted patients. CPB, cardiopulmonary bypass; CABG, coronary artery bypass graft; DHCA, deep hypothermia circulatory arrest; FET, frozen elephant trunk; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention.
Additionally, we also performed a subgroup analysis including age, sex, hypertension, hyperlipidemia, anemia, LVEF, nontotal arch replacement, and ascending aorta replacement, the same results were detected in these subgroups that POAF is associated with increased risk of in-hospital mortality (Fig. 3).
Figure 3.
Subgroup analysis of in-hospital mortality. OR, odds ratio; LVEF, left ventricular ejection fraction.
Discussion
STAAD is a is an extremely perilous condition of the aorta, and with the advancements in surgical techniques, there has been a significant improvement in the success rate of surgery. However, the mortality rate after STAAD surgery remains disproportionately high compared to CABG and valve surgery13. POAF is the most common arrhythmia after cardiac surgery. A meta-analysis included 32 studies and 155 575 patients showed a 23.7% of POAF occurrence after cardiac surgery14, and an incidence ranges from 19.6 to 57.2% after aortic arch repair according to limited literatures8,15,16. In the present study, the incidence of POAF after STAAD is 13.0%, which is significantly lower than previously reported. This may be due to the following reasons: (1) We have adopted a strict definition of POAF according to the Society of STS adult cardiac surgery database data collection: the patient experienced AF/flutter requiring treatment after surgery procedure, which was different from some previous definitions in the literature (such as AF >30 s, any AF). (2) The present study focused on STAAD patients, who were younger in age (mean age 48.5 years old) compared to other cardiac procedures (CABG and valve replacement), and most patients did not combine with cardiac dysfunction. (3) Our center is one of the largest centers for aortic disease in the world, with extensive surgical experience and better intraoperative cardiac protection, which may also contribute to the low incidence of POAF.
POAF exhibits two peak incidence periods: 18 h and 24–48 h after surgery17. Approximately 80% of patients spontaneously revert to normal sinus rhythm within 24 h after surgery18. Despite being a transient and self-limiting postoperative complication, POAF still carries the risk of hemodynamic impairment and thromboembolism19. Previous studies have indicated a close correlation between POAF after aortic surgery and prolonged in-hospital stay, postoperative liver dysfunction, and in-hospital mortality8,20. Additionally, patients who experience POAF are at a five-fold increased risk of developing permanent AF21. Zhao et al. 8 found that POAF is associated with increased in-hospital mortality after total arch repair compared with non-POAF (10.7 vs. 2.4%). In the present study, in-hospital mortality was 6.5 versus 19.9% before IPTW, and 9.0 versus 20.0% after IPTW in POAF and non-POAF groups. The higher mortality may be due to the complexity of our surgical approaches: most patients received two or more surgical procedures simultaneously, such as Bentall combined with frozen elephant trunk implantation, ascending aorta replacement combined with frozen elephant trunk implantation, etc.
Several studies have indicated that age, male sex, surgery duration, LVEF <60%, valvular intervention, diabetes, and low hematocrit, etc. were risk factors for developing POAF after cardiac surgery8,18,22. Analysis about this topic in STAAD populations is still lacking. Our study detected that advanced age, creatinine level, and cross-clamp time were the independent risk factors for developing POAF after STAAD.
Age is currently recognized as an independent risk factor for POAF regardless of whether cardiac surgery is performed23. Patients with advanced age usually have a higher prevalence of comorbidities, as well as degenerative changes in cardiovascular structure and electrophysiological abnormalities. The relationship between age and the incidence of POAF is nonlinear. Patients older than 55 have a significantly higher rate of POAF compared with those under 55, and for every 10-year increase in age, the incidence of POAF approximately doubles24.
Creatinine level is another risk factor, patients with preexisting chronic kidney dysfunction have a threefold increased risk of developing POAF25. The degree of decline in glomerular filtration rate can be used to predict the risk of POAF. Auer et al.26 demonstrated that the incidence of POAF after cardiac surgery in patients with normal kidney function, mild kidney impairment, and severe kidney impairment was 29.7, 38.7, and 48.6%, respectively. Possible mechanisms include the activation of renal chemoreceptors and receptors leading to early activation of the sympathetic nervous system27, as well as oxidative stress and a state of microinflammation28,29.
We found cross-clamp time was another independent risk factor, the longer the duration of cross-clamp, which implies longer periods of cardiac arrest, prolonged hypothermia, longer myocardial ischemia and extended operation time. Previous studies have indicated that for every 15 min increase in aortic cross-clamp, the risk of POAF increases by 6% in conventional CABG30. The potential mechanism may be atrial ischemia caused by insufficient myocardial protection by cardiac arrest and hyperthermia and oxidative stress caused by myocardial ischemia and reperfusion injury31,32.
This study is the first study to detect the predictors and risk of mortality in STAAD procedures. Different from previous studies that only included patients undergoing aortic arch replacement, the current research included STAAD patients received various surgical procedures. Based on the condition of the aortic sinus, valve regurgitation, and coronary artery involvement, we select the Bentall/Wheat/David surgical procedure. These procedures often involve a larger surgical scope, which may potentially cause iatrogenic damage to the cardiac structures. Previous studies have suggested that cardiac structural damage is a contributing factor to the occurrence of AF18,33. However, in this study, we did not find any significant impact of different proximal treatment approaches on POAF. This may be attributed to the experience of the surgical team at our center. It is also worth noting that our center frequently adopts the traditional approach of proximal anastomotic inclusion graft34, which not only helps achieve hemostasis but also effectively reduces left atrial pressure.
For the treatment of POAF in our center, β-blocker or amiodarone therapy were our routine treatment measures when there were no contraindications. Generally, controlling the ventricular rate was sufficient for hemodynamically stable patients. For patients who had developed persistent AF, continuous rhythm monitoring and anticoagulation therapy were necessary when there were no contraindications.
Overall, in patient management, for the elderly and patients with renal insufficiency, we should more closely monitor the patient’s heart rhythm, creatinine levels, and electrolyte condition, while actively treating POAF after it occurs. In terms of surgical procedure, ultrafiltration can be used during the CPB procedure to reduce the accumulation of creatinine and renal load, then improve surgical techniques as much as possible to reduce cross-clamp time, for cases that do not involve proximal aortic repairment, a hybrid procedure might be rational instead of total arch replacement or frozen elephant trunk placement. These measures may lower the risk of POAF and minimize adverse outcomes.
There were some limitations of this study. First of all, this is a single-center retrospective study, selection bias was inevitable despite the benefits of IPTW. Secondly, some variables such as the size of left atrium, European System for Cardiac Operative Risk Evaluation (EuroSCORE II), were not included because of the limitation of the database. Thirdly, usage of inotropes, vasopressors and the electrolytes were not registered, due to the significant changes in these data at different time points within the same patient, these data might have a potential impact on the results. Finally, we did not follow up the long-term adverse events of patients with and without POAF, it will help validate the long-term impact of POAF.
Conclusions
The incidence of POAF was 13.0% after STAAD surgery, advanced age, creatinine, and cross-clamp time were independent risk factors of developing POAF in STAAD patients. POAF is associated with increased mortality after STAAD procedures. Further studies need to be conducted to verify these findings and detect high risk population, optimal prevention, and treatment strategies.
Ethical approval
This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and the study was approved by local research ethics board of Beijing Anzhen Hospital (No. 2018004), individual consent for this retrospective analysis was waived.
Sources of funding
This work was supported in part by the National Natural Science Foundation of China (8217020091, 82241205, and 82070483).
Author contribution
D.L., Z.F., and W.J.: conceived the study; D.L., Z.F., and H.L.: carried out the research; D.L., Z.F., and M.L.: prepared the first draft of the manuscript; Y.L. and H.Z.: directed the manuscript to completed. All authors were involved in the manuscript and have agreed with the final content.
Conflicts of interest disclosure
There were no conflicts of interest in this manuscript.
Guarantor
Yuyong Liu, MD and Wenjian Jiang, MD.
Data availability statement
The original contributions presented in the study are included in the article material, further inquiries can be directed to the corresponding authors.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Acknowledgements
None.
Footnotes
Dongjie Li and Zhou Fang contributed equally to this work.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 6 December 2023
Contributor Information
Dongjie Li, Email: ldjtmac@163.com.
Zhou Fang, Email: fangzhou@ccmu.edu.cn.
Maomao Liu, Email: lmm9603@126.com.
Haibin Li, Email: 15910681644@126.com.
Hongjia Zhang, Email: zhanghongjia722@ccmu.edu.cn.
Haiyang Li, Email: ocean0203@163.com.
Yuyong Liu, Email: az5ward@163.com.
Wenjian Jiang, Email: jiangwenjian@ccmu.edu.cn.
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Associated Data
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Data Availability Statement
The original contributions presented in the study are included in the article material, further inquiries can be directed to the corresponding authors.