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Blood group as a novel predictor of postoperative atrial fibrillation after off-pump coronary artery bypass grafting

SUMMARY

OBJECTIVE:

The objective of this study was to reveal whether there was a possible relationship between the blood group and postoperative atrial fibrillation after off-pump coronary artery bypass grafting.

METHODS:

Between January 2020 and January 2022, 452 patients undergoing off-pump coronary artery bypass grafting surgery consisted of the research population. Patients were divided into two groups based on the occurrence of new-onset atrial fibrillation from the time of operation until discharge. Group 1 (atrial fibrillation group) had 122 patients, whereas group 2 (non-atrial fibrillation group) contained 350 patients. Patients’ baseline clinical characteristics and operative and postoperative data were recorded and then compared between the groups. Moreover, a multivariate logistic regression analysis was also conducted to identify the predictors of postoperative atrial fibrillation.

RESULTS:

Non-O blood groups were substantially more common in the atrial fibrillation group than in the non-atrial fibrillation group. Patient age differences between the atrial fibrillation and non-atrial fibrillation groups were statistically significant, and patients in the atrial fibrillation group were detected to be older. Mean left atrial diameter, rates of obesity and prior percutaneous coronary intervention history, and perioperative intraaortic balloon pump requirement were significantly greater in the atrial fibrillation group than in the non-atrial fibrillation group. According to logistic regression analysis, blood group, age, left atrial diameter, obesity, and prior percutaneous coronary intervention were identified as predictors of postoperative atrial fibrillation.

CONCLUSION:

We demonstrated for the first time in the literature that ABO blood type was a novel and significant predictor of new-onset atrial fibrillation after off-pump coronary artery bypass grafting.

Keywords
Atrial fibrillation; Blood group; Coronary artery bypass grafting

INTRODUCTION

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia caused by irregular atrioventricular activity, which is characterized by atrial mechanical functional loss11. Kornej J, Börschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ Res. 2020;127(1):4-20. https://doi.org/10.1161/CIRCRESAHA.120.316340
https://doi.org/10.1161/CIRCRESAHA.120.3...
. Depending on the atrioventricular node’s conduction function, the ventricular rate is variable and irregular. Instead of P waves, an electrocardiogram shows rapid, irregular fibrillation waves of various shapes and sizes22. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498. https://doi.org/10.1093/eurheartj/ehaa612
https://doi.org/10.1093/eurheartj/ehaa61...
. AF is the most common arrhythmia after coronary artery bypass grafting (CABG). It occurs most frequently on the second and third days after the operation33. Velioglu Y, Yuksel A. Predictors of postoperative atrial fibrillation after beating-heart coronary artery bypass surgery: ıs cardiopulmonary bypass a risk factor?. Acta Cardiol Sin. 2019;35(5):468-75. https://doi.org/10.6515/ACS.201909_35(5).20190325A
https://doi.org/10.6515/ACS.201909_35(5)...
. Previously, cardiac surgery-related postoperative atrial fibrillation (POAF) was considered a minor complication. However, in recent research, POAF has been shown to increase early and late mortality and morbidity. POAF is associated with lower left ventricular hemodynamic performance and an increased risk of heart failure and cerebrovascular events, resulting in more extended hospital stays, higher costs, and higher mortality33. Velioglu Y, Yuksel A. Predictors of postoperative atrial fibrillation after beating-heart coronary artery bypass surgery: ıs cardiopulmonary bypass a risk factor?. Acta Cardiol Sin. 2019;35(5):468-75. https://doi.org/10.6515/ACS.201909_35(5).20190325A
https://doi.org/10.6515/ACS.201909_35(5)...
. As a result, it causes problems for both patients and medical professionals and increases the expense of healthcare44. Yuksel A, Velioglu Y, Tecimer ME, Kan II, Bicer M, Gurbuz O, et al. Is there any relationship of postoperative atrial fibrillation with the use of blood products and postoperative hemoglobin levels in patients undergoing coronary artery bypass grafting? Med Sci. 2019;8(1):16-20. https://doi.org/10.5455/medscience.2018.07.8861
https://doi.org/10.5455/medscience.2018....
. Therefore, identifying individuals at risk of POAF and taking appropriate precautions during the perioperative phase is critical.

The presence of A and B antigens on the surface membranes of red blood cells determines the ABO blood group. In addition to red blood cells, the corresponding antigens are expressed on platelets, vascular endothelium, and epithelium. Furthermore, they are found in saliva and body fluids55. Ravn V, Dabelsteen E. Tissue distribution of histo-blood group antigens. APMIS. 2000;108(1):1-28. https://doi.org/10.1034/j.1600-0463.2000.d01-1.x
https://doi.org/10.1034/j.1600-0463.2000...
. According to the current literature, there appears to be a link between the ABO blood groups and several autoimmune diseases including Crohn’s disease (CD), psoriasis, multiple sclerosis (MS), lupus erythematosus, and type 1 diabetes mellitus (DM)66. Forni D, Cleynen I, Ferrante M, Cassinotti A, Cagliani R, Ardizzone S, et al. ABO histo-blood group might modulate predisposition to Crohn’s disease and affect disease behavior. J Crohns Colitis. 2014;8(6):489-94. https://doi.org/10.1016/j.crohns.2013.10.014
https://doi.org/10.1016/j.crohns.2013.10...
,77. Tirant M, Scala J, Jafferany M, Goldust M, Sadoughifar R, Lotti T. Therapeutic and etiologic considerations related to blood group and triggers in psoriasis-A retrospective study. Dermatol Ther. 2020;33(3):e13401. https://doi.org/10.1111/dth.13401
https://doi.org/10.1111/dth.13401...
,88. Lopetegi I, Muñoz-Lopetegi A, Arruti M, Prada A, Urcelay S, Olascoaga J, et al. ABO blood group distributions in multiple sclerosis patients from Basque Country; O- as a protective factor. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319888957. https://doi.org/10.1177/2055217319888957
https://doi.org/10.1177/2055217319888957...
,99. Tamega Ade A, Bezerra LV, Pereira FP, Miot HA. Blood groups and discoid lupus erythematosus. An Bras Dermatol. 2009;84(5):477-81. https://doi.org/10.1590/s0365-05962009000500005
https://doi.org/10.1590/s0365-0596200900...
,1010. Parente EB, Harjutsalo V, Lehto M, Forsblom C, Sandholm N, Groop PH, et al. Relationship between ABO blood groups and cardiovascular disease in type 1 diabetes according to diabetic nephropathy status. Cardiovasc Diabetol. 2020;19(1):68. https://doi.org/10.1186/s12933-020-01038-z
https://doi.org/10.1186/s12933-020-01038...
. In addition, according to a recent review, many studies have demonstrated the links between ABO blood groups and thromboembolic diseases. Myocardial infarction, atherosclerotic vascular disease, venous thromboembolism, and cardiovascular ischemic events have all been connected, and those with non-O blood groups were shown to be at a higher risk than those with O blood groups in all cases1111. Clark P, Wu O. ABO blood groups and thrombosis: a causal association, but is there value in screening?. Future Cardiol. 2011;7(2):191-201. https://doi.org/10.2217/fca.10.191
https://doi.org/10.2217/fca.10.191...
. Moreover, a recent study also showed a significant relationship between blood groups and idiopathic high-degree atrioventricular block associated with myocardial fibrosis and sclerosis1212. Acar E, İzci S, Inanir M, Yılmaz MF, Kılıçgedik A, Güler Y, et al. Non-O-blood types associated with higher risk of high-grade atrioventricular block. Arch Med Sci Atheroscler Dis. 2019;4:e243-7. https://doi.org/10.5114/amsad.2019.90072
https://doi.org/10.5114/amsad.2019.90072...
.

To the best of our knowledge, there is no study in the literature examining a possible relationship between the blood group and POAF, which is associated with inflammatory, thrombogenic, and fibrotic processes. Therefore, we designed this study to reveal whether there was a relationship between the blood group and new-onset POAF after off-pump CABG.

METHODS

Ethical considerations

The study obtained approval from the local ethics committee (Decision No: 2022/97, Date: 12/04/2022). All patients were informed about the operation and perioperative process, and their verbal and written consent was taken before the operation. The study was conducted in accordance to the ethical principles of the Declaration of Helsinki.

Study design and population

This cross-sectional study population included 452 patients who underwent off-pump beating-heart CABG surgery in our institution between January 2020 and January 2022. The patients’ medical data were gathered from the hospital records and then evaluated retrospectively. The patients were divided into two groups according to the development of new-onset AF during the postoperative period until discharge. There were 122 patients in group 1 (AF group) and 350 individuals in group 2 (non-AF group). Both groups were compared in terms of the baseline clinical parameters, intraoperative data, and postoperative results.

For this study, POAF was defined as new-onset AF of any duration that required pharmacological treatment (i.e., beta-blockers, calcium channel blockers, amiodarone, anticoagulants, etc.).

Exclusion criteria of the study were as follows: a history of paroxysmal, persistent or permanent AF prior to surgery, conventional on-pump CABG surgery, emergency surgery, re-operative surgery, concomitant valve surgery, and surgical techniques other than isolated off-pump CABG.

Surgical procedure

All patients were operated under general anesthesia. Internal thoracic artery and vena saphena magna were the most common harvested bypass grafts. Following the standard median sternotomy and pericardiotomy, coronary arteries and ascending aorta were examined. Coronary anastomoses were initiated following an intravenous heparin administration of 200 IU/kg and obtaining a target-activated clotting time of above 300 s. Distal anastomoses were performed first, followed by proximal anastomoses. Octopus tissue stabilizer was used for providing the proper position of the beating heart. Bulldog clamp and air blowing were used providing a blood-free space during distal anastomosis. The effect of unfractionated heparin was neutralized by protamine infusion after the anastomoses were completed, and the procedure was terminated in the standard fashion.

Arrhythmia monitoring

After the operation, all patients were transferred to the intensive care unit (ICU) and were continuously monitored with a cardiac rhythm monitor during ICU follow-up. All patients had standard 12-lead ECG recordings taken before the operation, immediately after the operation, and then twice a day during their postoperative hospital stay in both the ICU and the acute inpatient ward. Additional ECG recordings were obtained when there was a clinical suspicion of arrhythmia.

Laboratory analysis

The AB0-Rh blood groups were identified using the lam agglutination technique with a blood grouping reagent (Dia-Gast, Loos, France), the microplate agglutination procedure with the Galileo System (Stratec, Frankfurt, Germany), or the gel centrifugation assay with the IH-1000 Fully Automated System (DiaMed, Cressier, Switzerland).

Statistical analysis

Data were collected, tabulated, and statistically analyzed. Before statistical analysis, the distributional properties of the data were evaluated using the Shapiro-Wilk test. For normally distributed data, continuous variables were expressed as mean±standard deviation, and group comparison was performed using an independent two samples t-test. Non-normally distributed data were expressed as median (min.–max.), and group comparison was performed using the Mann-Whitney U test. Categorical variables were presented as the frequency and percentage, and the22. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498. https://doi.org/10.1093/eurheartj/ehaa612
https://doi.org/10.1093/eurheartj/ehaa61...
test was used for bivariate comparison. The single and multiple explanatory variable(s) logistic regression (LR) analysis methods were employed. In the single explanatory variable LR analysis, we estimated the odds ratios with 95% confidence intervals of SSI for each study variable, and the significance level of each factor/covariate was determined. In the multiple explanatory variable LR analysis, the initial model was fit including all significant independent variables. Then, a backward-elimination approach in a multiple explanatory variable LR model was conducted to evaluate the model for potential confounding effects. In this model, the factors/covariates were removed one at a time, starting with the factor/covariate that had the largest p-value, until all remaining factors had a two-sided p-value<0.05. The goodness of fit was tested using the Hosmer-Lemeshow test. The result was considered significant when the P-value was less than 0.05. The statistical software package 21.0 SPSS was used.

RESULTS

The study comprised 122 subjects with POAF and 330 subjects without POAF, and the frequency of POAF was 27% (122/452). When the blood types of the patients were analyzed, the O blood group (23.9%) and the non-O blood group (i.e., A, B, and AB blood group) were detected (73.9%). The majority of patients (86.2%) were Rh (D) positive, whereas 13.7% were Rh (D) negative. The AF and non-AF groups’ preoperative demographic and clinical features, as well as intraoperative and postoperative data, were compared (Tables 1 and 2).

Table 1.
Preoperative baseline characteristics of the study groups.
Table 2.
Intraoperative and postoperative variables.

Patients in the AF group were significantly older than those in the non-AF group (67.9±7.7 vs. 63.5±10.5 years, p<0.001). A non-O blood group (p<0.004) was significantly more prevalent in the AF group than in the non-AF group. Additionally, mean left atrial (LA) diameter, incidences of obesity, previous percutaneous coronary intervention (PCI) history, and intraaortic balloon pump requirement (IABP) requirement were found to be significantly higher in the AF group than in the non-AF group. Other preoperative demographics and clinical characteristics, as well as all intraoperative and postoperative variables, revealed no significant differences between the groups.

The independent effects of probable demographic and perioperative parameters associated with POAF were evaluated by univariate and multivariate LR analysis. After applying the univariate analysis, six parameters were found as statistically significant for POAF (i.e., age, non-O blood groups, obesity, LA diameter, previous PCI, and IABP requirement), and then these variables were included in the multivariate analysis. The multivariate analysis revealed that age, non-O blood groups, obesity, LA diameter, and previous PCI were independently linked with POAF (Table 3).

Table 3.
Results of multıvariate logistic regression analysis for the prediction of atrial fibrillation.

DISCUSSION

This study was designed to examine whether there was a potential predictive relationship between blood groups and the development of new-onset POAF after off-pump CABG. Our findings suggested that patients with non-O blood group types had a higher risk for developing POAF than O blood group patients, as expected. According to multivariate regression analysis, age, LA diameter, obesity, and previous PCI history also caused a higher risk of developing POAF, which is consistent with the literature. The most intriguing and significant finding of our study was that blood group types independently predicted the development of POAF, for the first time in the literature.

The pathophysiology of POAF after CABG is still being researched. According to current evidence, POAF is thought to be caused by a combination of factors. Increased inflammation, Ischemia, oxidative stress, atrial fibrosis, excessive catecholamine delivery to the systemic circulation, autonomic tonus imbalance, and changes in connexin expression all contribute to forming a predisposing anatomic substrate33. Velioglu Y, Yuksel A. Predictors of postoperative atrial fibrillation after beating-heart coronary artery bypass surgery: ıs cardiopulmonary bypass a risk factor?. Acta Cardiol Sin. 2019;35(5):468-75. https://doi.org/10.6515/ACS.201909_35(5).20190325A
https://doi.org/10.6515/ACS.201909_35(5)...
.

Previous research has found a link between blood type and diseases caused by inflammation, thromboembolism, and fibrosis. Rumley et al. described that patients with non-O blood groups have lower plasma levels of factor VIIIc and von Willebrand factors than those with blood group O, so their risk of thrombosis differs1313. Rumley A, Lowe GD, Sweetnam PM, Yarnell JW, Ford RP. Factor VIII, Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study. Br J Haematol. 1999;105(1):110-6. PMID: 10233372. In a population-based meta-analysis, Kole et al. reported an association between ABO blood groups and cardiovascular disease risk profiles1414. Kole TTM, Suthahar N, Damman K, Boer R. ABO blood group and cardiovascular outcomes in the general population: a meta-analysis. Eur J Heart Fail. 2017;19:175.. Astarcıoğlu et al. found that non-O blood type was an independent risk factor for prosthetic valve thrombosis in research that included patients with mechanical prosthetic valve thrombosis1515. Astarcıoğlu MA, Kalçık M, Yesin M, Gürsoy MO, Şen T, Karakoyun S, et al. ABO blood types: impact on development of prosthetic mechanical valve thrombosis. Anatol J Cardiol. 2016;16(11):820-23. https://doi.org/10.14744/AnatolJCardiol.2016.6544
https://doi.org/10.14744/AnatolJCardiol....
. According to Clark et al., the ABO blood group altered the pathogenesis and prognosis in individuals with cerebral Ischemia of arterial origin1616. Clark P, Meiklejohn DJ, O’Sullivan A, Vickers MA, Greaves M. The relationships of ABO, Lewis and Secretor blood groups with cerebral ischaemia of arterial origin. J Thromb Haemost. 2005;3(9):2105-8. https://doi.org/10.1111/j.1538-7836.2005.01535.x
https://doi.org/10.1111/j.1538-7836.2005...
. In the Framingham study population, peripheral vascular disease was also more prevalent in people with non-O blood types1717. Garrison RJ, Havlik RJ, Harris RB, Feinleib M, Kannel WB, Padgett SJ. ABO blood group and cardiovacular disease: the Framingham study. Atherosclerosis. 1976;25(2-3):311-8. https://doi.org/10.1016/0021-9150(76)90036-8
https://doi.org/10.1016/0021-9150(76)900...
.

According to a previous study, there appears to be a link between the ABO blood types and a number of autoimmune illnesses. Studies have shown that ABO blood type significantly impacts circulating glycoprotein levels, which are essential for endothelial function and inflammation1818. Yang M, Xie J, Ouyang Y, Zhang X, Shi M, Li X, et al. ABO blood type is associated with renal outcomes in patients with IgA nephropathy. Oncotarget. 2017;8(43):73603-12. https://doi.org/10.18632/oncotarget.20701
https://doi.org/10.18632/oncotarget.2070...
. Type A blood was linked to high-sensitivity C-reactive protein levels and the number of antibiotic purchases yearly in prospective cohort research by Parente et al., which looked at ischemic heart disease occurrences in 4531 type 1 DM patients1010. Parente EB, Harjutsalo V, Lehto M, Forsblom C, Sandholm N, Groop PH, et al. Relationship between ABO blood groups and cardiovascular disease in type 1 diabetes according to diabetic nephropathy status. Cardiovasc Diabetol. 2020;19(1):68. https://doi.org/10.1186/s12933-020-01038-z
https://doi.org/10.1186/s12933-020-01038...
. Furthermore, according to Oner et al., type A blood was the most prevalent genotype in all diabetes groups in both genders. However, type AB was substantially more common among type 1 DM patients1919. Oner C, Dogan B, Telatar B, Celik Yagan CF, Oguz A. Frequency of ABO/rhesus blood groups in patients with diabetes mellitus. J Coll Physicians Surg Pak. 2016;26(1):74-5. PMID: 26787039. This points to an inflammatory/infectious mediator in diabetes individuals that connects the non-O blood association to specific outcomes. The AB0 antigens have been related to the fructosyltransferase 2 (FUT2) gene, which is also a recognized CD locus. A study on CD patients found that individuals who lacked the FUT2 gene and were non-O blood-type carriers were less protected than type O blood group carriers66. Forni D, Cleynen I, Ferrante M, Cassinotti A, Cagliani R, Ardizzone S, et al. ABO histo-blood group might modulate predisposition to Crohn’s disease and affect disease behavior. J Crohns Colitis. 2014;8(6):489-94. https://doi.org/10.1016/j.crohns.2013.10.014
https://doi.org/10.1016/j.crohns.2013.10...
.

Similarly, another study showed that non-O blood type was linked to an increased risk of complications such as invasive illness and structures2020. Yu Q, Wang L, Zhang S, Feng T, Li L, Chen B, et al. The role of ABO blood groups in Crohn’s disease and in monitoring response to infliximab treatment. Blood Transfus. 2016;14(5):460-4. https://doi.org/10.2450/2016.0199-15
https://doi.org/10.2450/2016.0199-15...
. Several studies have also shown a link between MS and the ABO blood group. In Basque research, blood group 0 was protective against MS compared with blood groups A, B, or Rh(+)88. Lopetegi I, Muñoz-Lopetegi A, Arruti M, Prada A, Urcelay S, Olascoaga J, et al. ABO blood group distributions in multiple sclerosis patients from Basque Country; O- as a protective factor. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319888957. https://doi.org/10.1177/2055217319888957
https://doi.org/10.1177/2055217319888957...
. As a result, evidence indicates that ABO blood types can alter the prognosis of various diseases by influencing the inflammatory status. Most research indicates type 0 as a protective factor and a risk factor for people who do not have type 0.

Furthermore, some research suggests that the AB0 gene may have a role in the fibrotic/sclerotic process. According to Hakyemez et al., blood types may be a hereditary risk factor for progression to severe hepatic fibrosis and cirrhosis.2121. Hakyemez IN, Durdu B, Bolukcu S, Aslan T. Evaluation of the relationship between ABO/Rh blood groups and severity of liver fibrosis in patients with chronic hepatitis B. Viral Hepatitis J. 2016;22(1):23-7. https://doi.org/10.4274/vhd.49368
https://doi.org/10.4274/vhd.49368...
Again, some links between blood types and cancer fibrosis have been discovered2222. Rai P, Acharya S, Hallikeri K. Assessment of ABO blood grouping and secretor status in the saliva of the patients with oral potentially malignant disorders. J Oral Maxillofac Pathol. 2015;19(2):164-9. https://doi.org/10.4103/0973-029X.164527
https://doi.org/10.4103/0973-029X.164527...
. A significant association was found between blood types and the cardiac conduction system related to myocardial fibrosis and sclerosis in a recent study by Acar et al., with the non-O blood group being associated with increased risk1212. Acar E, İzci S, Inanir M, Yılmaz MF, Kılıçgedik A, Güler Y, et al. Non-O-blood types associated with higher risk of high-grade atrioventricular block. Arch Med Sci Atheroscler Dis. 2019;4:e243-7. https://doi.org/10.5114/amsad.2019.90072
https://doi.org/10.5114/amsad.2019.90072...
.

The findings of our research are relevant and useful in clinical practice. Due to the rise in hospitalization and complications, POAF is now highly significant. Before the procedure, it is critical to identify high-risk individuals. According to this research, POAF is linked to fibrosis and inflammation. Fibrosis and inflammation are more likely in people with blood group 0 than those with other blood groups. Consequently, by looking at blood group values that are regularly evaluated during pre-operative evaluation, we may anticipate individuals at risk for POAF.

Limitations

Our study has the following limitations. First, the major limitations of the study were retrospective design and a limited number of cases which included reflection of the experience of a single institution. The second limitation was that due to the need for mid- and long-term data from the research population, it was unable to establish a link between POAF and mid- and long-term survival. Finally, postoperative cardiac rhythm monitoring was not performed constantly after the ICU stay. It is possible to miss the asymptomatic short and silent attacks of POAF.

CONCLUSION

This research demonstrated for the first time in the literature that the ABO blood group was a novel and independent predictor of new-onset AF after CABG surgery. The blood group determination is an inexpensive and easily applicable test routinely performed in the preoperative period, and it may help us predict the new-onset AF after CABG surgery based on the results of our study. Nevertheless, further prospective, large-scale, well-designed studies are required to support our findings and obtain stronger scientific evidence.

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  • Funding: none.

Publication Dates

  • Publication in this collection
    18 Sept 2023
  • Date of issue
    2023

History

  • Received
    11 June 2023
  • Accepted
    13 June 2023
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