The Validation of the ATRIA and CHA2DS2-Vasc Scores in Predicting Atrial Fibrillation after Coronary Artery Bypass Surgery

Objective The aim of this study was to evaluate the value of CHA2DS2-VASc and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scores for prediction of postoperative atrial fibrillation (AF) development in patients undergoing coronary artery bypass grafting (CABG) operation. Methods The population of this observational study consisted of 370 patients undergoing CABG operation. CHA2DS2-VASc and ATRIA risk scores were calculated for all patients and their association with postoperative AF (AF episode lasting > 5 min) were evaluated. Predictors of postoperative AF were determined by multiple logistic regression analysis. Results During follow-up, 110 patients (29.7%) developed postoperative AF. With multiple logistic regression analysis, risk factors for postoperative AF were determined: ATRIA risk score (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.11-1.36; P<0.001), fasting glucose level (OR 1.006; 95% CI 1.004-1.009; P<0.001), and 24-hour drainage amount (OR 1.002; 95% CI; 1.001-1.004; P<0.001). Receiver operating characteristic curve analyses showed that CHA2DS2-VASc and ATRIA risk scores were signiﬁcant predictors for new-onset AF (C-statistic 0.648; 95% CI 0.59-0.69; P<0.001; and C-statistic 0.664; 95% CI 0.61-0.71; P<0.001, respectively). Conclusion CHA2DS2-VASc and ATRIA risk scores predict new AF in patients undergoing CABG.


INTRODUCTION
Postoperative atrial fibrillation (POAF) is the most common type of arrhythmia after cardiac surgery with the incidence ranging from 10 to 65%, and its prevalence is even higher in elderly patients with heart failure and severe left ventricular impairment [1] . Patients with developing atrial fibrillation (AF) after cardiac surgery have higher risk for morbidity, such as cerebrovascular accidents, pulmonary edema, longer hospital stays, and mortality compared to those who do not develop AF [1] . Preoperative determination of patients who may develop POAF m 2 ) (3 points), age ≥ 75 years (2 points), prior bleeding, and hypertension. An ATRIA score of 0 to 3 is defined as "low risk", a score of 4 is defined as "intermediate risk", and a score ≥ 5 is defined as "high risk" [3] . The maximum value of the score is 12.

Rhythm Follow-up
The rhythms were followed by continuous electrocardiogram monitoring during intensive care unit stay and by all-day Holter during the rest of hospitalization. A 12-lead electrocardiogram was recorded every morning routinely and whenever the patients had symptoms suggestive of dysrhythmia. AF was defined as an irregular rhythm with the absence of discrete P waves in the 12-lead electrocardiogram. An AF episode lasting five minutes during hospitalization was defined as POAF [6] . In case of POAF, antiarrhythmics and electrical cardioversion were allowed based on the discretion of the physician.

Statistical Analysis
Statistical Package for the Social Sciences version 16.0 software package was used for statistical analyses in this study. Categorical variables were expressed as frequency (%) and compared using the χ 2 test. Kolmogorov-Smirnov test was used to test the distribution of numeric variables; those with normal distribution were expressed as mean ± standard deviation and were compared with Student's t-test. Data without normal distribution were expressed as median (interquartile range of 25%-75% percentiles) and were compared with the Mann-Whitney U test. In all statistical analyses, P-value < 0.05 was considered as statistically significant. The correlations between CHA 2 DS 2 -VASc and ATRIA risk scores, POAF, and other clinical, laboratory, and echocardiographic parameters were performed with Pearson's or Spearman's correlation analysis where appropriate. Univariate analysis and backward conditional binary logistic regression were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the prediction of POAF. We carried out multivariate analysis in two models. Firstly, risk factors involved in CHA 2 DS 2 -VASc score were excluded from this analysis to avoid multicollinearity. Secondly, risk factors and other factors except CHA 2 DS 2 -VASc score were put to multivariate analysis. Receiver operating characteristics (ROC) curve analysis was used to analyze the prognostic value of CHA 2 DS 2 -VASc and ATRIA risk scores for POAF. C-statistic (area under the curve [AUC]) was presented as a unified estimate of sensitivity and specificity according to the cutoff value that was obtained by a ROC curve analysis. The optimal cutoff value was defined as the value yielding the maximal Youden index [7] , or the best combined sensitivity and specificity. All ROC comparisons were performed using the DeLong test [8] . C-statistic (AUC) was presented as a unified estimate of sensitivity and specificity.

RESULTS
A total of 370 patients (mean age: 62.34±12 years; range, 28-84 years) were included in this study. During the follow-up period, 110 patients (29.7%) developed POAF. Demographic and clinical characteristics of the patients with and without POAF and taking necessary precautions will decrease the mortality and morbidity rates. Therefore, scoring systems should be developed to predict the development of POAF.
The CHA 2 DS 2 -VASc and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scores are cheap and easy scoring systems that are used to predict the risk of thromboembolism in non-valvular AF patients [2,3] . Additionally, these scoring systems have been shown to accurately predict worse clinical outcomes in patients undergoing coronary artery bypass grafting (CABG) regardless of having AF [4] . The components of these scoring systems, such as advanced age, presence of hypertension, presence of diabetes mellitus, low ejection fraction, and female gender, have been associated with poor outcomes, including recurrent ischemic events after cardiac surgery [5] .
In this study, we aimed to investigate the predictive value of different thromboembolic risk scores in AF for the development of POAF.

Study Population
This study included patients who underwent isolated CABG at the Suleyman Demirel University, Education and Research Hospital, between June 2017 and March 2019. The study population was retrospectively and consecutively analyzed by using our database, which was collected as a part of routine clinical practice. The overall study population included 400 patients undergoing CABG. Exclusion criteria were hyperthyroidism, age < 18 years, prior cardiac surgery, class III or IV heart failure, previous AF, left atrial diameter > 55 mm, left ventricular ejection fraction < 0.25, sepsis, heart rate < 60 bpm, systolic blood pressure < 90 mm Hg, inflammatory disease, and being already on antiarrhythmic treatment. According to these criteria, 30 patients were excluded due to previous AF (n=10), heart rate < 60 bpm (n=15), and hyperthyroidism (n=5). Therefore, 370 patients were included in this substudy. Informed consent was obtained from each patient, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee (Date: 28.05.2019, Decision no: 181). Similar operative techniques were used in all of the patients.

Diagnosis of Thromboembolic Risk
The CHA 2 DS 2 -VASc risk score is calculated by assigning a score of 1 point for each of the following conditions: congestive heart failure (ejection fraction < 40%), hypertension, age between 65 and 74 years, diabetes mellitus, vascular disease (myocardial infarction or peripheral arterial disease), and female gender; and a score of 2 points for the following conditions: history of stroke or transient ischemic attack (TIA) and age > 75 years. The score is then used to predict the risk of thromboembolism in nonvalvular AF patients [2] . The maximum value of the score is 9.
The ATRIA score was developed from the ATRIA study cohort and calculated using the following: anemia (hemoglobin < 13 g/dL in men and < 12 g/dL in women) (3 points), severe renal disease (estimated glomerular filtration rate < 30 mL/min/1.73 are listed in Table 1. Patients with POAF were significantly older and of the male gender when compared to patients without POAF (P<0.001 and P=0.03, respectively). Diabetes mellitus, hypertension, congestive heart failure, peripheral vascular disease, and stroke/transient ischemic event rates were higher in patients with POAF than in patients without POAF. There were no statistically significant differences between patients with and without POAF with regards to cholesterol parameters (for all parameters P>0.05). Left ventricular ejection fraction was significantly lower in patients with POAF than in patients without POAF (P<0.001). Preoperative fasting glucose levels were higher in patients with POAF than in patients without POAF (P<0.001).
The postoperative drainage amounts in the first 24 hours and 48 hours were higher in patients with POAF than in patients without POAF (P=0.001 and P=0.05, respectively) ( Table 2). Cardiopulmonary bypass time was longer in patients with POAF than in patients without POAF (P=0.02) but there is no statistically difference between patients with and without POAF with regards to clamp time. The duration of the hospitalization at the intensive care unit was longer in patients with POAF than in patients without POAF (P<0.001). There was no statistically difference between patients with and without POAF with regards to reoperation due to hemorrhage and intraoperative and in-hospital mortalities (for all parameters P>0.05) ( Table 2).

Prediction of Postoperative Atrial Fibrillation
Univariate analyses showed that high CHA 2 DS 2 -VASc and ATRIA risk scores, diabetes mellitus, hypertension, congestive heart failure, peripheral vascular disease, stroke/TIA, low left ventricular ejection fraction, advanced age, fasting glucose level, serum alanine aminotransferase (ALT) level, 24-hour drainage amount, pumping time, and male gender were significantly associated with a higher risk of development of POAF (Table 3)   Additionally, the present study showed that older age, male gender, drainage amount, pumping time, and ALT levels were associated with POAF. The results corroborated with the previous studies [1,6,9,16,19,21] . Age is the most common risk factor of POAF because of occurred myocardial fiber loss, fibrosis, and collagen deposition [22] . Previous studies showed that cross-clamp duration and pumping time are associated with POAF, and reducing crossclamp duration may reduce POAF [1,21,23] .

Limitations
This study has several limitations: it has a single-center design, it is nonrandomized study, and the sample size was small. Additionally, we recruited patients with AF for at least five minutes. In previous studies, patients with AF may be separated according to AF duration.

CONCLUSION
In conclusion, we have shown in the current study that ATRIA and CHA 2 DS 2 -VASc scoring systems were useful for detecting AF following CABG. Additionally, when the ATRIA risk score was compared with the CHA 2 DS 2 -VASc scoring system, it was found to be powerful in predicting the development of POAF. Patients at high risk according to ATRIA and CHA 2 DS 2 -VASc scoring systems should be followed up for rhythm disturbance after the procedure and it should be administrated the suggestions of the guidelines prior to the procedure.

DISCUSSION
The current study showed that higher CHA 2 DS 2 -VASc and ATRIA scores were independently associated with the development of AF in patients undergoing CABG; consequently, both scores could be helpful and appropriate scoring systems for predicting AF after CABG.
Previous studies showed that hypertension, diabetes mellitus, obesity, valvular disease, increased age, and left atrial characteristics, such as size, volume, and scarring, contribute to the development of POAF [9] . Similarly, hypertension and diabetes mellitus rates were higher in patients with POAF than without POAF. The risk factors of POAF are similar to the components of CHA 2 DS 2 -VASc and ATRIA risk scores [1] . Furthermore, these scores can be used to predict the risk of POAF. Kashani et al. [10] showed that the CHA 2 DS 2 -VASc score can be used as a simple and useful tool for predicting POAF in patients with undergoing CABG. Borde et al. [11] carried out a study including 729 CABG patients and showed that higher CHA 2 DS 2 -VASc scores predict POAF. Parallel results were attained by Chua et al. [12] , based on a prospective study including 277 patients undergoing CABG and/or valve procedures. Moreover, we showed that CHA 2 DS 2 -VASC score have been predicting AF following STelevation myocardial infarction and associated with epicardial fat tissue and mitral annular calcification [13][14][15] . The data of the current study corroborate with the results of previous studies. Additionally, we showed that the ATRIA score can also be used for the prediction of AF following CABG. Moreover, ATRIA score was similar with CHA 2 DS 2 -VASc score in predicting POAF.
POAF is a serious complication of CABG and is associated with worse clinical outcomes such as prolonged length of hospital stay, rising costs, and increased short-and long-term morbidity and mortality [16] . Several guidelines recommended suggestions for prophylaxis against POAF [17][18][19] . However, these suggestions reveal unnecessary exposure to medications and for this reason, many physicians do not regularly apply them. These propositions may expose up to 70% of undergoing CABG patients to antiarrhythmic drugs and their subsequent side effects [20] . In a randomized study, Ozaydın et al. [6] showed that carvedilol plus N-acetylcysteine decreased POAF incidence compared with metoprolol or carvedilol. Therefore, it is important to anticipate which patients may develop POAF. In this study, we demonstrated that CHA 2 DS 2 -VASc and ATRIA scoring systems could be used to determine patients at the highest risk of developing POAF, thus these scoring systems may decrease nonselective prophylaxis.

Authors' roles & responsibilities
DU FA EI Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published Substantial contributions to the conception or design of the work; or the acquisition, final approval of the version to be published