Abstract
Introduction. Red cell distribution width (RDW) has been associated with poor outcomes in patients with cardiovascular diseases. However, little is known about the role of RDW in prediction of new-onset atrial fibrillation (AF) after coronary artery bypass grafting (CABG). We aimed to investigate the relation between the RDW and postoperative AF in patients undergoing CABG. Methods. A total of 132 patients undergoing nonemergency CABG were included in the study. Patients with previous atrial arrhythmia or requiring concomitant valve surgery were excluded. We retrospectively analyzed 132 consecutive patients (mean age, 60.55 ± 9.5 years; 99 male and 33 female). The RDW level was determined preoperatively and on postoperative Day 1. Results. Preoperative RDW levels were significantly higher in patients who developed AF than in those who did not (13.9 ± 1.4 vs. 13.3 ± 1.2, p = 0.03). There was not any correlation between postoperative RDW levels and AF. Using a cutpoint of 13.45, the preoperative level correlated with the incidence of AF with a sensitivity of 61% and specificity of 60%. Conclusion. Preoperative RDW level predicts new-onset AF after CABG in patients without histories of AF.
Introduction
Atrial fibrillation (AF) is the most common complication and arrhythmia after cardiothoracic surgery. The mechanism of postoperative AF is not fully elucidated and an optimal strategy has not been established for postoperative AF. However, inflammation, both systemic and local, may play a role in its pathogenesis, and beta blockers and amiodarone appear to be effective in the prevention of postoperative AF (Citation1,Citation2). The incidence of AF was reported to be 17–33% after coronary artery bypass grafting (CABG) (Citation3). New-onset AF following CABG is associated with an increase in morbidity, mortality, thromboembolic events, heart failure and cost (Citation4).
Recent reports have suggested that the inflammation plays a key role in the pathophysiology of postoperative AF (Citation5,Citation6). Elevated pre and postoperative neutrophil/lymphocyte ratios and white blood cell count have been associated with an increased occurrence of AF after CABG (Citation7,Citation8). Recent studies have identified red cell distribution width (RDW) as a predictor of cardiac mortality and systemic inflammation (Citation9,Citation10). However, the relation between the RDW level and postoperative AF has not been investigated. We aimed to investigate the relation between the RDW and postoperative AF in patients undergoing CABG.
Methods
Between May 2010 and June 2012, a total of 132 patients undergoing nonemergency CABG were included in the study. Patients with previous atrial arrhythmia, renal failure and undergoing concomitant valve surgery were excluded. We retrospectively analyzed 132 consecutive patients (mean age, 60.55 ± 9.5 years; 99 male and 33 female). No patient had a recent history of an acute infection, hematologic disease or an inflammatory disease. In the postoperative period, heart rate and rhythm were continuously monitored for the first 48–72 hours and daily 12-lead electrocardiograms were performed from the first postoperative day until discharge. Electrocardiographic monitor recordings were analyzed by a cardiologist.
The primary end point was the development of postoperative AF, defined as an irregular rhythm in the absence of identifiable P waves, lasting for 30 s on Holter monitoring. Baseline characteristics of patients are shown in .
Table I. Basal characteristics of patients.
Echocardiographic assessment
Transthoracic 2-dimensional and Doppler echocardiographic assessment was performed by Philips HD11 XE with a 2.5 MHz phased-array transducer (Philips Medical Systems, Andover, MA, USA). Measurements of the left atrium, left ventricle and right ventricle were obtained from parasternal long axis view according to standard criteria. Left ventricular ejection fraction (LVEF) was calculated using the modified Simpson's rule in the 2- and 4-chamber apical views (Citation11).
Blood samples
The blood samples were determined immediately before surgery and on postoperative Day 1. Fasting blood samples were drawn from a large antecubital vein of each patient for determination of biochemical and hemostatic parameters before operation. The tubes with EDTA were used for automatic blood count. The blood counts were measured on a Sysmex XT-1800i Hematology Analyzer (Sysmex Corporation, Kobe, Japan). Total cholesterol, low-density lipoprotein (LDL) cholesterol, albumin, creatinine levels and sedimentation rate were measured using conventional methods.
Statistical analysis
Statistical analysis was assessed with SPSS statistical package for Windows 15.0 (SPSS Inc, Chicago, Illinois, USA). Parametric values were given as mean ± standard deviation and non-parametric values were given as percentage. All parametric values of the patients group were compared by unpaired Student's t-test. Categorical data were compared by Chi-square distribution. Receiver-operating characteristic (ROC) curves were obtained for RDW to explore the sensitivity and specificity. ROC curve analysis was used to determine the optimum cutoff levels of RDW level to predict the occurrence of AF. Forward, stepwise, multivariate, logistic regression models were created to identify independent predictors of postoperative AF.
Ethical considerations
The study was conducted in accordance with Declaration of Helsinki and approved by institutional ethics committee. All patients and controls gave informed consent prior to entry into this study.
Results
The study cohort was predominantly male (n = 99, 75%), with a mean age of 60.85 ± 10 years. The patients in both groups were prescribed similar medical therapy. None of them were treated with amiodarone or other anti-arrhythmic medication preoperatively. After CABG operation, 33 (25%) patients developed AF. No difference was found in the cross-clamp times between the AF group and non-AF. Cardio-pulmonary bypass times were significantly higher in the postoperative AF group (p = 0.02) ().
Preoperative RDW levels were significantly higher in patients who developed AF than in those who did not (13.9 ± 1.4 vs. 13.3 ± 1.2, p = 0.03). There was not any correlation between postoperative RDW levels and AF (p = NS). Also, no difference was found in the preoperative and postoperative total white cell count, lymphocyte and neutrophile between the 2 groups. Preoperative LVEF and left atrium dimensions were similar between the 2 groups ().
Table II. Comparison of the preoperative echocardiografic and laboratory parameters among patients with or without postoperative AF.
The area under the receiver operator characteristic curve (95% confidence interval) for preoperative RDW, as a predictor of postoperative AF, was 0.62 (0.50–0.73) (p = 0.04). Using a cutpoint of 13.45, the preoperative level correlated with the incidence of AF with a sensitivity of 61% and specificity of 60% ().
Figure 1. Receiver-operating characteristic (ROC) curve analysis for prediction of postoperative atrial fibrillation (AF) by RDW (red blood cell distribution width).
Using stepwise, multivariate Cox proportional, hazards regression analyses, RDW was a significant and an independent predictor of postoperative AF (hazard ratio 1.48, %95 CI 1.07–2.06, p = 0.02).
Discussion
RDW is a quantitative description of anisocytosis and has been reported to be an independent predictor of adverse outcomes in the general population (Citation12). Also, association between higher RDW levels and adverse outcomes has been identified in patients with coronary artery disease, acute and chronic heart failure (Citation13–15). It is reported that inflammation, transfusions and chronicity of heart failure might explain the higher RDW values in patients with cardiovascular diseases (Citation13,Citation14). It has been reported that an exaggerated inflammatory response is associated with a higher risk of postoperative AF (Citation16).
Unfortunately, the current approach to postoperative AF is unsatisfactory. Postoperative AF prevention should be directed at the patients at risk. A marker that would predict the postoperative AF might prevent its occurrence. It has been revealed that some markers predict the potential risk for postoperative AF. Inflammatory markers such as C-reactive protein, complement, neutrophil/ lymphocyte ratios, white blood cell count and interleukin-6 have been associated with an increased incidence of postoperative AF (Citation7,Citation8,Citation17,Citation18). RDW has been associated with poor outcomes in patients with cardiovascular diseases. RDW has been identified as a strong prognostic marker in chronic heart failure, coronary artery disease, acute myocardial infarction, non-ST elevation myocardial infarction and unstable angina pectoris (Citation19–20). However, to the best of our knowledge, the relation between the RDW level and new-onset postoperative AF has not been investigated before.
The main finding of the present study was that the preoperative RDW level is associated with an increased risk of new-onset AF after CABG. However, there was not any association between postoperative AF and other inflammatory markers. Also, a relation was seen between the postoperative AF and the bypass duration. Bypass duration was significantly higher in the AF group.
Limitations of the study
The number of patients who were included in the study was a limitation of our study. Our analysis is retrospective in nature and prospective data regarding the RDW and postoperative AF are awaited.
Conclusion
AF remains the most common complication after CABG. Targeting patients at the risk of postoperative AF may prevent AF occurrence. In summary, RDW is an inexpensive and valuable marker which can be beneficial in predicting the postoperative AF.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- DiDomenico RJ, Massad MG. Pharmacologic strategies for prevention of atrial fibrillation after open heart surgery. Ann Thorac Surg. 2005;79:728–40.
- Kaw R, Hernandez AV, Masood I, Gillinov AM, Saliba W, Blackstone EH. Short and long-term mortality associated with new-onset atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2011;141:1305–12.
- Hakala T, Hedman A. Predicting the risk of atrial fibrillation after coronary artery bypass surgery. Scand Cardiovasc J. 2003;37:309–15.
- Mitchell LB; CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery. Can J Cardiol. 2011;27:91–7.
- Ishida K, Kimura F, Imamaki M, Ishida A, Shimura H, Kohno H, et al. Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 2006;29:501–5.
- Anselmi A, Possati G, Gaudino M. Postoperative inflammatory reaction and atrial fibrillation: simple correlation or causation?Ann Thorac Surg. 2009;88:326–33.
- Abdelhadi RH, Gurm HS, Van Wagoner DR, Chung MK. Relation of an exaggerated rise in white blood cells after coronary bypass or cardiac valve surgery to development of atrial fibrillation postoperatively. Am J Cardiol. 2004;93:1176–8.
- Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/ lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol. 2010; 105:186–91.
- Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med. 2009;133:628e–32.
- Lippi G, Filippozzi L, Montagnana M, Luca SG, Franchini M, Cesare GG, Targher G. Short communication: clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med 2009;47:353–;e7.
- Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358–67.
- Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009;169:515–23.
- Felker GM, Allen LA, Pocock SJ, Shaw LK, McMurray JJ, Pfeffer MA, et al. Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. J Am Coll Cardiol. 2007;50:40–47.
- Tonelli M, Sacks F, Arnold M, Moye L, Davis B, PfefferM; for the Cholesterol and Recurrent Events (CARE) Trial Investigators. Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease. Circulation. 2008;117:163–8.
- van Kimmenade RR, Mohammed AA, Uthamalingam S, van der Meer P, Felker GM, Januzzi JL Jr. Red blood cell distribution width and 1-year mortality in acute heart failure. Eur J Heart Fail. 2010;12:129–36.
- Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, et al. Inflammation as a risk factor for atrial flbrillation. Circulation. 2003;108:3006–10.
- Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt FW, de Beaumont EM, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation. 1997;96:3542–8.
- Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial flbrillation. Am J Cardiol. 2005;95:764–7.
- Gul M, Uyarel H, Ergelen M, Karacimen D, Ugur M, Turer A, et al. The relationship between red blood cell distribution width and the clinical outcomes in non-ST elevation myocardial infarction and unstable angina pectoris: a 3-year follow-up. Coron Artery Dis. 2012. [Epub ahead of print]
- Uyarel H, Ergelen M, Cicek G, Kaya MG, Ayhan E, Turkkan C, et al. Red cell distribution width as a novel prognostic marker in patients undergoing primary angioplasty for acute myocardial infarction. Coron Artery Dis. 2011; 22:138–44.