- Email: [email protected]
Red blood cell distribution width and left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation
International Journal of Cardiology 180 (2015) 63–65
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Red blood cell distribution width and left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation Jianping Zhao a, Tong Liu a,⁎, Panagiotis Korantzopoulos b, Huaying Fu a, Qingmiao Shao a, Ya Suo a, Chenghuan Zheng a, Gang Xu a, Enzhao Liu a, Yanmin Xu a, Changyu Zhou a, Guangping Li a a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China b Department of Cardiology, University of Ioannina Medical School, Greece
a r t i c l e
i n f o
Article history: Received 17 November 2014 Accepted 23 November 2014 Available online 26 November 2014 Keywords: Red cell distribution width Hemoglobin Uric acid Left atrial thrombus Left atrial spontaneous echo contrast Atrial fibrillation
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of cardio-embolic stroke and mortality. AF patients are under an increased risk of thromboembolism and stroke primarily from the development of thrombi within the left atrium. Pathological changes in blood constituents like slow blood flow, stasis, form a vortex, promote atrial endothelial damage and left atrial thrombus (LAT) formation [1]. Transesophageal echocardiography (TEE) can help us to identify LAT and left atrial spontaneous echo contrast (LASEC) which has been demonstrated as a precursor of LAT [2]. Previous studies have shown that several inflammatory and oxidative stress biomarkers, such as C-reactive protein [3,4], interleukin-6 [4] and uric acid [5] could predict the LAT or LASEC in patients with nonvalvular AF. Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes and has been traditionally used in the differential diagnosis of anemia [6]. RDW has been routinely reported in complete blood count (CBC) tests and is available in most clinical settings. There is very limited data regarding the predictive value of RDW for the development of LAT or LASEC in patients with non-valvular AF [7]. The aim of our study was to investigate the ⁎ Corresponding author at: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. E-mail address: [email protected] (T. Liu).
http://dx.doi.org/10.1016/j.ijcard.2014.11.145 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
predictive value of RDW and uric acid levels for the development of LAT or LASEC in patients with non-valvular AF. We retrospectively searched the echocardiology database at our department for all the patients with AF who underwent TEE examination prior to electrical cardioversion or prior to AF catheter ablation between May 2012 and April 2014. We initially screened 105 patients. Of note, we excluded patients with valvular heart disease, concomitant infection, incomplete medical records on baseline CBC or uric acid, moderate to severe anemia (hemoglobin level b 10 g/dL) as well as those with a history of blood transfusion within the previous 3 months. Thus, 88 patients were included in our final analysis. All baseline demographic and clinical characteristics and laboratory examinations including CBC and uric acid levels were carefully recorded. TEE examination was performed in all patients using the Vivid-7 system. Two experienced echocardiographers who were blinded to the patients' clinical and laboratory data reviewed all the TEE images to determine whether the LAT or LASEC was present. LAT was defined as a fixed or mobile echogenic mass within the left atrium. LASEC was defined as a dense persistent echogenic swirling pattern that can be identified in all TEE views regardless of ultrasound frequency or gain setting. The baseline characteristics of our study population were shown in Table 1. LATs or LASECs were evident in 24 (27.3%) patients (LATs: n = 11; LASECs: n = 13) during TEE examination. Persistent AF during hospitalization and history of previous stroke were more frequent in LAT/LASEC group compared with non-LAT/LASEC group. The RDW level and percentage of warfarin usage were significantly increased while hemoglobin was decreased in the patients with LAT/LASEC. There was no significant difference in age, sex, CHADS2 score, creatinine and uric acid levels; the same was true regarding LAD and LVEF (Table 1). Receiver operating characteristics (ROC) curve analysis also showed the predictive value of RDW level for the presence of LAT/ LASEC (sensitivity of 63.6% and specificity of 60% area under the ROC curve = 0.641, P = 0.05) was 12.55% (Fig. 1). However, further multivariate logistic regression analysis (Table 2) showed that only persistent AF during hospitalization (OR, 5.967, 95% CI: 1.578–22.566, P = 0.008) and decreased hemoglobin level (OR, 1.05, 95% CI: 1.01–1.09, P = 0.014) were the independent predictors of LAT/LASEC in patients with non-valvular AF. RDW is a quantitative measure of variability in the size of circulating erythrocytes and has been traditionally used in the differential diagnosis
64
J. Zhao et al. / International Journal of Cardiology 180 (2015) 63–65
Table 1 Baseline characteristics of included patients with and without LAT/LASEC during transesophageal echocardiography examination. LAT/LASEC group (n = 24)
Non-LAT/LASEC group (n = 66)
P
Clinical characteristics Age (yrs) Male (n, %) Persistent AF (n, %) Coronary artery disease (n, %) Hypertension (n, %) Diabetes mellitus (n, %) Previous stroke (n, %) SBP (mm Hg) DBP (mm Hg) Heart rate (bpm) CHADS score
62.88 ± 10.16 15 (62.50) 17 (70.83) 13 (54.17) 13 (54.17) 3 (12.50) 5 (20.83) 132.54 ± 17.02 81.79 ± 10.16 85.13 ± 21.78 1.96 ± 1.43
59.08 ± 10.59 39 (59.10) 22 (33.33)⁎⁎ 36 (54.54) 34 (51.52) 13 (19.70) 4 (6.06)⁎ 127.95 ± 16.95 79.53 ± 8.83 82.70 ± 25.46 1.62 ± 1.24
0.135 0.770 0.001 0.975 0.824 0.430 0.039 0.264 0.311 0.423 0.324
Laboratory examinations WBCs (×109/L) Hemoglobin (g/L) Platelets (×109/L) RDW (%) Cr (μmol/L) BUN (mmol/L) UA (μmol/L) cTnI (ng/mL) CK-MB (U/L)
6.31 ± 1.48 136.61 ± 15.93 187.83 ± 52.34 12.99 ± 0.91 76.11 ± 33.10 5.93 ± 2.95 321.58 ± 91.17 0.02 ± 0.03 12.55 ± 5.41
6.29 ± 1.67 144.72 ± 16.27⁎ 207.52 ± 59.08 12.55 ± 0.78⁎ 77.96 ± 50.68 7.43 ± 7.21 327.15 ± 137.37 0.04 ± 0.07 12.89 ± 4.28
0.962 0.044 0.167 0.036 0.877 0.340 0.864 0.090 0.772
Echocardiogram parameters LAD (mm) LVEDD (mm) LVEF (%)
42.92 ± 8.81 48.03 ± 11.70 58.35 ± 7.50
39.48 ± 8.39 48.19 ± 7.38 57.46 ± 9.96
0.098 0.936 0.693
Medications Aspirin (n, %) ACEIs or ARBs (n, %) β-Blocker (n, %) CCBs (n, %) Statins (n, %) Diuretics (n, %) Warfarin (n, %)
18 (75.00) 12 (50.00) 11 (45.83) 8 (33.33) 17 (70.83) 1 (4.17) 16 (66.67)
53 (80.30) 21 (31.82) 38 (57.58) 14 (21.21) 43 (65.15) 5 (7.58) 26 (39.40)⁎
0.586 0.113 0.323 0.430 0.613 0.566 0.022
LAT = left atrial thrombus; LASEC = left atrial spontaneous echo contrast; AF = atrial fibrillation; SBP = systolic blood pressure; DBP = diastolic blood pressure; Hb = hemoglobin; RDW = red cell distribution width; WBCs = white blood cells; Cr = creatinine; BUN = blood urine nitrogen; UA = uric acid; LAD = left atrial diameter; LVEDD = left ventricular end diastolic diameter; LVEF = left ventricular ejection fraction; ACEIs = angiotensin-converting enzyme inhibitors; ARBs = angiotensin receptor blockers; CCBs = calcium channel blockers. ⁎ P b 0.05 ⁎⁎ P b 0.01
of anemia [6]. RDW has been routinely reported in CBC tests and is available in most clinical settings. Recently, several studies have shown that higher RDW level is a strong independent predictor of increased morbidity and mortality in patients with acute and chronic heart failure [8–10], in patients with myocardial infarction [11,12], in peritoneal dialysis [13], and in patients following coronary artery bypass grafting (CABG) [14], coronary angiography [15] or transcatheter aortic valve implantation [16]. The potential mechanisms between elevated RDW level and poor clinical outcome in cardiovascular disease have not yet been fully understood [17]. Recent studies indicate that high levels of RDW may reflect an activated inflammatory state [18,19], and increased immature erythrocytes may reflect higher RDW levels [20]. On the other hand, accumulating evidence suggests that inflammation and oxidative stress play an important role in the development and maintenance of AF [21–23]. Our recent work indicates the potential association between RDW, inflammation, and oxidative stress in the setting of AF using a canine model of rapid atrial pacing [24]. Another recent study also showed that higher baseline levels of RDW could predict the development of postoperative AF in patients undergoing CABG [25]. We have also demonstrated that RDW is an independent predictor for paroxysmal AF and its best cutoff value for the presence of paroxysmal AF is 12.55% [26]. Another large prospective study [27] which enrolled 27,124 subjects
Fig. 1. Receiver operating characteristic curve (ROC) of red cell distribution width for predicting the presence of left atrial appendage thrombus and dense spontaneous echocardiographic contrast in non-valvular atrial fibrillation.
from the general population (age 45–73 years, 62% women) found that the incidence of AF was 33% higher in the patients at the fourth compared to the first quartile of RDW following a mean follow-up of 13.6 years. Of note, high RDW levels were directly associated with the risk of stroke regardless of anemia status, and improved the predictive accuracy for stroke in the patients with AF. RDW was also an independent predictor of high CHA2DS2-VASc score in non-anemic patients with AF [28]. However, there are very limited data regarding the predictive value of RDW for the development of LAT or LASEC [7]. Providencia et al. [7] performed a single center cross-sectional study comprising 247 consecutive patients admitted to the emergency department due to symptomatic AF and undergoing TEE, and suggested that mean corpuscular volume and RDW may be associated with the presence of LAT and LASEC in patients with non-valvular AF. Nevertheless, only mean corpuscular volume was the independent predictor for LAT/LASEC after adjusting the other clinical risk factors present within CHADS2 and CHA2DS2-VASc classifications. Our present study also suggests that baseline RDW levels were significantly higher in patients with LAT/ LASEC compared to the patients without LAT/LASEC. However, the multivariate logistic regression analysis showed that RDW was not an independent predictor for LAT/LASEC. There are several limitations to our study. First, we enrolled a relatively small number of patients. Second, we did not evaluate other inflammatory biomarkers for the prediction of LAT/LASEC in AF patients, such as hs-CRP, interleukin, and tumor necrosis factor-α. Also, only hemoglobin levels were measured in this study and not other factors such
Table 2 Multivariate logistic regression analysis on predictors of LAT or LASEC in patients with non-valvular AF.
History of stroke Persistent AF Warfarin Hemoglobin RDW
B
S.E.
Wald
P
OR
OR (95% CI)
1.111 1.786 0.792 −0.049 0.271
0.904 0.679 0.612 0.020 0.360
1.512 6.926 1.676 5.990 0.567
0.219 0.008 0.195 0.014 0.452
3.038 5.967 2.208 0.952 1.312
0.517 1.578 0.666 0.916 0.647
−17.860 −22.566 −7.323 −0.990 −2.657
LAT = left atrial thrombus; LASEC = left atrial spontaneous echo contrast; AF = atrial fibrillation; RDW = red cell distribution width.
J. Zhao et al. / International Journal of Cardiology 180 (2015) 63–65
as levels of iron, ferritin, vitamin B12, and folate. Finally, the observational design of the study identifies only an association and not causality. In conclusion, RDW may be associated with the presence of left atrial appendage thrombus and dense spontaneous echocardiographic contrast in non-valvular AF, although it was not an independent predictor after adjusting AF type and hemoglobin levels. Indeed, RDW is a simple, inexpensive, routinely reported test as a part of CBC, and it may also play an important role in the risk stratification for stroke and thromboembolism in patients with non-valvular AF. Larger studies are needed in order to clarify its exact value in this setting. Conflicts of interest None. Financial disclosures None. Acknowledgments This work was partly supported by grant (81270245 to T.L.) from the National Natural Science Foundation of China. References [1] C.W. Khoo, S. Krishnamoorthy, H.S. Lim, G.Y. Lip, Atrial fibrillation, arrhythmia burden and thrombogenesis, Int. J. Cardiol. 157 (2012) 318–323. [2] E. Donal, H. Yamada, C. Leclercq, D. Herpin, The left atrial appendage, a small, blindended structure: a review of its echocardiographic evaluation and its clinical role, Chest 128 (2005) 1853–1862. [3] C. Cianfrocca, M.L. Loricchio, F. Pelliccia, et al., C-reactive protein and left atrial appendage velocity are independent determinants of the risk of thrombogenesis in patients with atrial fibrillation, Int. J. Cardiol. 142 (2010) 22–28. [4] D.S. Conway, P. Buggins, E. Hughes, G.Y. Lip, Relation of interleukin-6, c-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation, Am. J. Cardiol. 93 (2004) 1368–1373 (A1366). [5] S. Numa, T. Hirai, K. Nakagawa, et al., Hyperuricemia and transesophageal echocardiographic thromboembolic risk in patients with atrial fibrillation at clinically lowintermediate risk, Circ. J. 78 (2014) 1600–1605. [6] T.C. Evans, D. Jehle, The red blood cell distribution width, J. Emerg. Med. 9 (Suppl. 1) (1991) 71–74. [7] R. Providencia, M.J. Ferreira, L. Goncalves, et al., Mean corpuscular volume and red cell distribution width as predictors of left atrial stasis in patients with nonvalvular atrial fibrillation, Am. J. Cardiovasc. Dis. 3 (2013) 91–102. [8] Q. Shao, L. Li, G. Li, T. Liu, Prognostic value of red blood cell distribution width in heart failure patients: a meta-analysis, Int. J. Cardiol. (2014) (Epub ahead of print).
65
[9] C. Jung, B. Fujita, A. Lauten, et al., Red blood cell distribution width as useful tool to predict long-term mortality in patients with chronic heart failure, Int. J. Cardiol. 152 (2011) 417–418. [10] B.F. Makhoul, A. Khourieh, M. Kaplan, F. Bahouth, D. Aronson, Z.S. Azzam, Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure, Int. J. Cardiol. 167 (2013) 1412–1416. [11] M.B. Sangoi, S.H. Da Silva, J.E. da Silva, R.N. Moresco, Relation between red blood cell distribution width and mortality after acute myocardial infarction, Int. J. Cardiol. 146 (2011) 278–280. [12] M. Tonelli, F. Sacks, M. Arnold, et al., Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease, Circulation 117 (2008) 163–168. [13] F. Peng, Z. Li, Z. Zhong, et al., An increasing of red blood cell distribution width was associated with cardiovascular mortality in patients on peritoneal dialysis, Int. J. Cardiol. 176 (2014) 1379–1381. [14] U. Benedetto, E. Angeloni, G. Melina, et al., Red blood cell distribution width predicts mortality after coronary artery bypass grafting, Int. J. Cardiol. 165 (2013) 369–371. [15] E. Cavusoglu, V. Chopra, A. Gupta, et al., Relation between red blood cell distribution width (rdw) and all-cause mortality at two years in an unselected population referred for coronary angiography, Int. J. Cardiol. 141 (2010) 141–146. [16] C.J. Magri, A. Chieffo, A. Latib, et al., Red blood cell distribution width predicts oneyear mortality following transcatheter aortic valve implantation, Int. J. Cardiol. 172 (2014) 456–457. [17] H. Uyarel, T. Isik, E. Ayhan, M. Ergelen, Red cell distribution width (RDW): a novel risk factor for cardiovascular disease, Int. J. Cardiol. 154 (2012) 351–352. [18] M.E. Emans, C.A. Gaillard, R. Pfister, et al., Red cell distribution width is associated with physical inactivity and heart failure, independent of established risk factors, inflammation or iron metabolism; the epic-norfolk study, Int. J. Cardiol. 168 (2013) 3550–3555. [19] F. Ozcan, O. Turak, A. Durak, et al., Red cell distribution width and inflammation in patients with non-dipper hypertension, Blood Press. 22 (2013) 80–85. [20] C.N. Pierce, D.F. Larson, Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device, Perfusion 20 (2005) 83–90. [21] Y. Guo, G.Y. Lip, S. Apostolakis, Inflammation in atrial fibrillation, J. Am. Coll. Cardiol. 60 (2012) 2263–2270. [22] D. Tousoulis, K. Zisimos, C. Antoniades, et al., Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension, Int. J. Cardiol. 136 (2009) 258–262. [23] P. Korantzopoulos, T.M. Kolettis, D. Galaris, J.A. Goudevenos, The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation, Int. J. Cardiol. 115 (2007) 135–143. [24] Z. Zhao, T. Liu, J. Li, W. Yang, E. Liu, G. Li, Elevated red cell distribution width level is associated with oxidative stress and inflammation in a canine model of rapid atrial pacing, Int. J. Cardiol. 174 (2014) 174–176. [25] G. Ertas, C. Aydin, O. Sonmez, et al., Red cell distribution width predicts new-onset atrial fibrillation after coronary artery bypass grafting, Scand. Cardiovasc. J. 47 (2013) 132–135. [26] T. Liu, Q. Shao, S. Miao, et al., Red cell distribution width as a novel, inexpensive marker for paroxysmal atrial fibrillation, Int. J. Cardiol. 171 (2014) e52–e53. [27] S. Adamsson Eryd, Y. Borne, O. Melander, et al., Red blood cell distribution width is associated with incidence of atrial fibrillation, J. Intern. Med. 275 (2014) 84–92. [28] M. Kurt, I.H. Tanboga, E. Buyukkaya, M.F. Karakas, A.B. Akcay, N. Sen, Relation of red cell distribution width with CHA2DA2-VASc score in patients with nonvalvular atrial fibrillation, Clin. Appl. Thromb. Hemost. 20 (2013) 687–692.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Red blood cell distribution width and left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation Jianping Zhao a, Tong Liu a,⁎, Panagiotis Korantzopoulos b, Huaying Fu a, Qingmiao Shao a, Ya Suo a, Chenghuan Zheng a, Gang Xu a, Enzhao Liu a, Yanmin Xu a, Changyu Zhou a, Guangping Li a a Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China b Department of Cardiology, University of Ioannina Medical School, Greece
a r t i c l e
i n f o
Article history: Received 17 November 2014 Accepted 23 November 2014 Available online 26 November 2014 Keywords: Red cell distribution width Hemoglobin Uric acid Left atrial thrombus Left atrial spontaneous echo contrast Atrial fibrillation
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of cardio-embolic stroke and mortality. AF patients are under an increased risk of thromboembolism and stroke primarily from the development of thrombi within the left atrium. Pathological changes in blood constituents like slow blood flow, stasis, form a vortex, promote atrial endothelial damage and left atrial thrombus (LAT) formation [1]. Transesophageal echocardiography (TEE) can help us to identify LAT and left atrial spontaneous echo contrast (LASEC) which has been demonstrated as a precursor of LAT [2]. Previous studies have shown that several inflammatory and oxidative stress biomarkers, such as C-reactive protein [3,4], interleukin-6 [4] and uric acid [5] could predict the LAT or LASEC in patients with nonvalvular AF. Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes and has been traditionally used in the differential diagnosis of anemia [6]. RDW has been routinely reported in complete blood count (CBC) tests and is available in most clinical settings. There is very limited data regarding the predictive value of RDW for the development of LAT or LASEC in patients with non-valvular AF [7]. The aim of our study was to investigate the ⁎ Corresponding author at: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. E-mail address: [email protected] (T. Liu).
http://dx.doi.org/10.1016/j.ijcard.2014.11.145 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
predictive value of RDW and uric acid levels for the development of LAT or LASEC in patients with non-valvular AF. We retrospectively searched the echocardiology database at our department for all the patients with AF who underwent TEE examination prior to electrical cardioversion or prior to AF catheter ablation between May 2012 and April 2014. We initially screened 105 patients. Of note, we excluded patients with valvular heart disease, concomitant infection, incomplete medical records on baseline CBC or uric acid, moderate to severe anemia (hemoglobin level b 10 g/dL) as well as those with a history of blood transfusion within the previous 3 months. Thus, 88 patients were included in our final analysis. All baseline demographic and clinical characteristics and laboratory examinations including CBC and uric acid levels were carefully recorded. TEE examination was performed in all patients using the Vivid-7 system. Two experienced echocardiographers who were blinded to the patients' clinical and laboratory data reviewed all the TEE images to determine whether the LAT or LASEC was present. LAT was defined as a fixed or mobile echogenic mass within the left atrium. LASEC was defined as a dense persistent echogenic swirling pattern that can be identified in all TEE views regardless of ultrasound frequency or gain setting. The baseline characteristics of our study population were shown in Table 1. LATs or LASECs were evident in 24 (27.3%) patients (LATs: n = 11; LASECs: n = 13) during TEE examination. Persistent AF during hospitalization and history of previous stroke were more frequent in LAT/LASEC group compared with non-LAT/LASEC group. The RDW level and percentage of warfarin usage were significantly increased while hemoglobin was decreased in the patients with LAT/LASEC. There was no significant difference in age, sex, CHADS2 score, creatinine and uric acid levels; the same was true regarding LAD and LVEF (Table 1). Receiver operating characteristics (ROC) curve analysis also showed the predictive value of RDW level for the presence of LAT/ LASEC (sensitivity of 63.6% and specificity of 60% area under the ROC curve = 0.641, P = 0.05) was 12.55% (Fig. 1). However, further multivariate logistic regression analysis (Table 2) showed that only persistent AF during hospitalization (OR, 5.967, 95% CI: 1.578–22.566, P = 0.008) and decreased hemoglobin level (OR, 1.05, 95% CI: 1.01–1.09, P = 0.014) were the independent predictors of LAT/LASEC in patients with non-valvular AF. RDW is a quantitative measure of variability in the size of circulating erythrocytes and has been traditionally used in the differential diagnosis
64
J. Zhao et al. / International Journal of Cardiology 180 (2015) 63–65
Table 1 Baseline characteristics of included patients with and without LAT/LASEC during transesophageal echocardiography examination. LAT/LASEC group (n = 24)
Non-LAT/LASEC group (n = 66)
P
Clinical characteristics Age (yrs) Male (n, %) Persistent AF (n, %) Coronary artery disease (n, %) Hypertension (n, %) Diabetes mellitus (n, %) Previous stroke (n, %) SBP (mm Hg) DBP (mm Hg) Heart rate (bpm) CHADS score
62.88 ± 10.16 15 (62.50) 17 (70.83) 13 (54.17) 13 (54.17) 3 (12.50) 5 (20.83) 132.54 ± 17.02 81.79 ± 10.16 85.13 ± 21.78 1.96 ± 1.43
59.08 ± 10.59 39 (59.10) 22 (33.33)⁎⁎ 36 (54.54) 34 (51.52) 13 (19.70) 4 (6.06)⁎ 127.95 ± 16.95 79.53 ± 8.83 82.70 ± 25.46 1.62 ± 1.24
0.135 0.770 0.001 0.975 0.824 0.430 0.039 0.264 0.311 0.423 0.324
Laboratory examinations WBCs (×109/L) Hemoglobin (g/L) Platelets (×109/L) RDW (%) Cr (μmol/L) BUN (mmol/L) UA (μmol/L) cTnI (ng/mL) CK-MB (U/L)
6.31 ± 1.48 136.61 ± 15.93 187.83 ± 52.34 12.99 ± 0.91 76.11 ± 33.10 5.93 ± 2.95 321.58 ± 91.17 0.02 ± 0.03 12.55 ± 5.41
6.29 ± 1.67 144.72 ± 16.27⁎ 207.52 ± 59.08 12.55 ± 0.78⁎ 77.96 ± 50.68 7.43 ± 7.21 327.15 ± 137.37 0.04 ± 0.07 12.89 ± 4.28
0.962 0.044 0.167 0.036 0.877 0.340 0.864 0.090 0.772
Echocardiogram parameters LAD (mm) LVEDD (mm) LVEF (%)
42.92 ± 8.81 48.03 ± 11.70 58.35 ± 7.50
39.48 ± 8.39 48.19 ± 7.38 57.46 ± 9.96
0.098 0.936 0.693
Medications Aspirin (n, %) ACEIs or ARBs (n, %) β-Blocker (n, %) CCBs (n, %) Statins (n, %) Diuretics (n, %) Warfarin (n, %)
18 (75.00) 12 (50.00) 11 (45.83) 8 (33.33) 17 (70.83) 1 (4.17) 16 (66.67)
53 (80.30) 21 (31.82) 38 (57.58) 14 (21.21) 43 (65.15) 5 (7.58) 26 (39.40)⁎
0.586 0.113 0.323 0.430 0.613 0.566 0.022
LAT = left atrial thrombus; LASEC = left atrial spontaneous echo contrast; AF = atrial fibrillation; SBP = systolic blood pressure; DBP = diastolic blood pressure; Hb = hemoglobin; RDW = red cell distribution width; WBCs = white blood cells; Cr = creatinine; BUN = blood urine nitrogen; UA = uric acid; LAD = left atrial diameter; LVEDD = left ventricular end diastolic diameter; LVEF = left ventricular ejection fraction; ACEIs = angiotensin-converting enzyme inhibitors; ARBs = angiotensin receptor blockers; CCBs = calcium channel blockers. ⁎ P b 0.05 ⁎⁎ P b 0.01
of anemia [6]. RDW has been routinely reported in CBC tests and is available in most clinical settings. Recently, several studies have shown that higher RDW level is a strong independent predictor of increased morbidity and mortality in patients with acute and chronic heart failure [8–10], in patients with myocardial infarction [11,12], in peritoneal dialysis [13], and in patients following coronary artery bypass grafting (CABG) [14], coronary angiography [15] or transcatheter aortic valve implantation [16]. The potential mechanisms between elevated RDW level and poor clinical outcome in cardiovascular disease have not yet been fully understood [17]. Recent studies indicate that high levels of RDW may reflect an activated inflammatory state [18,19], and increased immature erythrocytes may reflect higher RDW levels [20]. On the other hand, accumulating evidence suggests that inflammation and oxidative stress play an important role in the development and maintenance of AF [21–23]. Our recent work indicates the potential association between RDW, inflammation, and oxidative stress in the setting of AF using a canine model of rapid atrial pacing [24]. Another recent study also showed that higher baseline levels of RDW could predict the development of postoperative AF in patients undergoing CABG [25]. We have also demonstrated that RDW is an independent predictor for paroxysmal AF and its best cutoff value for the presence of paroxysmal AF is 12.55% [26]. Another large prospective study [27] which enrolled 27,124 subjects
Fig. 1. Receiver operating characteristic curve (ROC) of red cell distribution width for predicting the presence of left atrial appendage thrombus and dense spontaneous echocardiographic contrast in non-valvular atrial fibrillation.
from the general population (age 45–73 years, 62% women) found that the incidence of AF was 33% higher in the patients at the fourth compared to the first quartile of RDW following a mean follow-up of 13.6 years. Of note, high RDW levels were directly associated with the risk of stroke regardless of anemia status, and improved the predictive accuracy for stroke in the patients with AF. RDW was also an independent predictor of high CHA2DS2-VASc score in non-anemic patients with AF [28]. However, there are very limited data regarding the predictive value of RDW for the development of LAT or LASEC [7]. Providencia et al. [7] performed a single center cross-sectional study comprising 247 consecutive patients admitted to the emergency department due to symptomatic AF and undergoing TEE, and suggested that mean corpuscular volume and RDW may be associated with the presence of LAT and LASEC in patients with non-valvular AF. Nevertheless, only mean corpuscular volume was the independent predictor for LAT/LASEC after adjusting the other clinical risk factors present within CHADS2 and CHA2DS2-VASc classifications. Our present study also suggests that baseline RDW levels were significantly higher in patients with LAT/ LASEC compared to the patients without LAT/LASEC. However, the multivariate logistic regression analysis showed that RDW was not an independent predictor for LAT/LASEC. There are several limitations to our study. First, we enrolled a relatively small number of patients. Second, we did not evaluate other inflammatory biomarkers for the prediction of LAT/LASEC in AF patients, such as hs-CRP, interleukin, and tumor necrosis factor-α. Also, only hemoglobin levels were measured in this study and not other factors such
Table 2 Multivariate logistic regression analysis on predictors of LAT or LASEC in patients with non-valvular AF.
History of stroke Persistent AF Warfarin Hemoglobin RDW
B
S.E.
Wald
P
OR
OR (95% CI)
1.111 1.786 0.792 −0.049 0.271
0.904 0.679 0.612 0.020 0.360
1.512 6.926 1.676 5.990 0.567
0.219 0.008 0.195 0.014 0.452
3.038 5.967 2.208 0.952 1.312
0.517 1.578 0.666 0.916 0.647
−17.860 −22.566 −7.323 −0.990 −2.657
LAT = left atrial thrombus; LASEC = left atrial spontaneous echo contrast; AF = atrial fibrillation; RDW = red cell distribution width.
J. Zhao et al. / International Journal of Cardiology 180 (2015) 63–65
as levels of iron, ferritin, vitamin B12, and folate. Finally, the observational design of the study identifies only an association and not causality. In conclusion, RDW may be associated with the presence of left atrial appendage thrombus and dense spontaneous echocardiographic contrast in non-valvular AF, although it was not an independent predictor after adjusting AF type and hemoglobin levels. Indeed, RDW is a simple, inexpensive, routinely reported test as a part of CBC, and it may also play an important role in the risk stratification for stroke and thromboembolism in patients with non-valvular AF. Larger studies are needed in order to clarify its exact value in this setting. Conflicts of interest None. Financial disclosures None. Acknowledgments This work was partly supported by grant (81270245 to T.L.) from the National Natural Science Foundation of China. References [1] C.W. Khoo, S. Krishnamoorthy, H.S. Lim, G.Y. Lip, Atrial fibrillation, arrhythmia burden and thrombogenesis, Int. J. Cardiol. 157 (2012) 318–323. [2] E. Donal, H. Yamada, C. Leclercq, D. Herpin, The left atrial appendage, a small, blindended structure: a review of its echocardiographic evaluation and its clinical role, Chest 128 (2005) 1853–1862. [3] C. Cianfrocca, M.L. Loricchio, F. Pelliccia, et al., C-reactive protein and left atrial appendage velocity are independent determinants of the risk of thrombogenesis in patients with atrial fibrillation, Int. J. Cardiol. 142 (2010) 22–28. [4] D.S. Conway, P. Buggins, E. Hughes, G.Y. Lip, Relation of interleukin-6, c-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation, Am. J. Cardiol. 93 (2004) 1368–1373 (A1366). [5] S. Numa, T. Hirai, K. Nakagawa, et al., Hyperuricemia and transesophageal echocardiographic thromboembolic risk in patients with atrial fibrillation at clinically lowintermediate risk, Circ. J. 78 (2014) 1600–1605. [6] T.C. Evans, D. Jehle, The red blood cell distribution width, J. Emerg. Med. 9 (Suppl. 1) (1991) 71–74. [7] R. Providencia, M.J. Ferreira, L. Goncalves, et al., Mean corpuscular volume and red cell distribution width as predictors of left atrial stasis in patients with nonvalvular atrial fibrillation, Am. J. Cardiovasc. Dis. 3 (2013) 91–102. [8] Q. Shao, L. Li, G. Li, T. Liu, Prognostic value of red blood cell distribution width in heart failure patients: a meta-analysis, Int. J. Cardiol. (2014) (Epub ahead of print).
65
[9] C. Jung, B. Fujita, A. Lauten, et al., Red blood cell distribution width as useful tool to predict long-term mortality in patients with chronic heart failure, Int. J. Cardiol. 152 (2011) 417–418. [10] B.F. Makhoul, A. Khourieh, M. Kaplan, F. Bahouth, D. Aronson, Z.S. Azzam, Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure, Int. J. Cardiol. 167 (2013) 1412–1416. [11] M.B. Sangoi, S.H. Da Silva, J.E. da Silva, R.N. Moresco, Relation between red blood cell distribution width and mortality after acute myocardial infarction, Int. J. Cardiol. 146 (2011) 278–280. [12] M. Tonelli, F. Sacks, M. Arnold, et al., Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease, Circulation 117 (2008) 163–168. [13] F. Peng, Z. Li, Z. Zhong, et al., An increasing of red blood cell distribution width was associated with cardiovascular mortality in patients on peritoneal dialysis, Int. J. Cardiol. 176 (2014) 1379–1381. [14] U. Benedetto, E. Angeloni, G. Melina, et al., Red blood cell distribution width predicts mortality after coronary artery bypass grafting, Int. J. Cardiol. 165 (2013) 369–371. [15] E. Cavusoglu, V. Chopra, A. Gupta, et al., Relation between red blood cell distribution width (rdw) and all-cause mortality at two years in an unselected population referred for coronary angiography, Int. J. Cardiol. 141 (2010) 141–146. [16] C.J. Magri, A. Chieffo, A. Latib, et al., Red blood cell distribution width predicts oneyear mortality following transcatheter aortic valve implantation, Int. J. Cardiol. 172 (2014) 456–457. [17] H. Uyarel, T. Isik, E. Ayhan, M. Ergelen, Red cell distribution width (RDW): a novel risk factor for cardiovascular disease, Int. J. Cardiol. 154 (2012) 351–352. [18] M.E. Emans, C.A. Gaillard, R. Pfister, et al., Red cell distribution width is associated with physical inactivity and heart failure, independent of established risk factors, inflammation or iron metabolism; the epic-norfolk study, Int. J. Cardiol. 168 (2013) 3550–3555. [19] F. Ozcan, O. Turak, A. Durak, et al., Red cell distribution width and inflammation in patients with non-dipper hypertension, Blood Press. 22 (2013) 80–85. [20] C.N. Pierce, D.F. Larson, Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device, Perfusion 20 (2005) 83–90. [21] Y. Guo, G.Y. Lip, S. Apostolakis, Inflammation in atrial fibrillation, J. Am. Coll. Cardiol. 60 (2012) 2263–2270. [22] D. Tousoulis, K. Zisimos, C. Antoniades, et al., Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension, Int. J. Cardiol. 136 (2009) 258–262. [23] P. Korantzopoulos, T.M. Kolettis, D. Galaris, J.A. Goudevenos, The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation, Int. J. Cardiol. 115 (2007) 135–143. [24] Z. Zhao, T. Liu, J. Li, W. Yang, E. Liu, G. Li, Elevated red cell distribution width level is associated with oxidative stress and inflammation in a canine model of rapid atrial pacing, Int. J. Cardiol. 174 (2014) 174–176. [25] G. Ertas, C. Aydin, O. Sonmez, et al., Red cell distribution width predicts new-onset atrial fibrillation after coronary artery bypass grafting, Scand. Cardiovasc. J. 47 (2013) 132–135. [26] T. Liu, Q. Shao, S. Miao, et al., Red cell distribution width as a novel, inexpensive marker for paroxysmal atrial fibrillation, Int. J. Cardiol. 171 (2014) e52–e53. [27] S. Adamsson Eryd, Y. Borne, O. Melander, et al., Red blood cell distribution width is associated with incidence of atrial fibrillation, J. Intern. Med. 275 (2014) 84–92. [28] M. Kurt, I.H. Tanboga, E. Buyukkaya, M.F. Karakas, A.B. Akcay, N. Sen, Relation of red cell distribution width with CHA2DA2-VASc score in patients with nonvalvular atrial fibrillation, Clin. Appl. Thromb. Hemost. 20 (2013) 687–692.