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Ann Thorac Surg 2005;79:859-864
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

P-Wave Signal-Averaged Electrocardiogram for Predicting Atrial Arrhythmia After Cardiac Surgery

Nobuhiko Hayashida, MD*, Takahiro Shojima, MD, Yoshinori Yokokura, MD, Hidetsugu Hori, MD, Kazuhiro Yoshikawa, MD, Hiroshi Tomoeda, MD, Shigeaki Aoyagi, MD

Department of Surgery, Kurume University, Kurume, Japan

Accepted for publication August 23, 2004.

* Address reprint requests to Dr Hayashida, Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, Japan, 830-0011 (E-mail: nobuhiko{at}med.kurume-u.ac.jp).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Atrial arrhythmias (AF) are usually benign, but occur frequently after cardiac surgery. P-wave signal-averaged electrocardiogram has been used to characterize atrial conduction delay as a marker of risk of AF during sinus rhythm.

METHODS: Ninety-five patients undergoing either primary isolated coronary artery bypass grafting or aortic valve replacement were enrolled. The duration and the root mean square voltage for the last 20 ms of filtered (40 to 300 Hz) P-wave of the spatial magnitude were recorded before surgery. Any episode of postoperative atrial fibrillation, atrial flutter, or paroxysmal atrial fibrillation lasting longer than 1 hour was considered as AF.

RESULTS: Twenty-eight patients (29%) exhibited AF 3.0 ± 2.3 days after surgery. The P-wave duration recorded with P-wave signal-averaged electrocardiogram was significantly prolonged in patients with AF (135 ± 14 ms versus 127 ± 9 ms; p = 0.002). Patients with AF more often had dilated left atrium (p = 0.003), left ventricular hypertrophy (p = 0.03), and advanced age (p = 0.02). Logistic regression analysis identified the following three variables as predictive of AF: P-wave duration of 135 ms or greater (p = 0.02; odds ratio, 3.5), patients 70 years of age and older (p = 0.03; odds ratio, 3.2), and left atrial dimension of 35 mm or greater (p = 0.03; odds ratio, 3.2). If a patient had two or more of these three risk factors, the occurrence of AF was predicted with a sensitivity of 75%, specificity of 76%, positive predictive accuracy of 57%, and negative predictive accuracy of 88%.

CONCLUSIONS: The prolonged P-wave duration recorded with P-wave signal-averaged electrocardiogram, together with advanced age and left atrial enlargement, is a potent and independent predictor of AF after cardiac surgery. Patients with these risk factors may benefit from prophylactic antiarrhythmic treatment.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Atrial fibrillation and flutter are the most common complications after cardiac operations, with a reported incidence ranging from 20% to 50% [1, 2]. In the majority of cases, these arrhythmias are transient and are not life-threatening; however, they may cause marked subjective symptoms, prolong hospital stay, and necessitate pharmacologic treatment, resulting in additional cost of medical care [3]. Moreover, in patients with compromised health status, this complication may be associated with major morbidities, such as hemodynamic instability and thromboembolic events [3]. Despite the recent improvements in surgical techniques and postoperative patient care, the incidence of this complication has been reported to increase, owing mostly to an increasing number of elderly patients with comorbidity [3].

The R wave–triggered signal-averaged electrocardiogram (ECG) has emerged as a valuable and noninvasive diagnostic tool to identify patients at risk for ventricular tachyarrhythmias caused by ischemic heart disease [4]. The presence of late potentials in the terminal portion of the QRS complex, which reflect delayed ventricular activity in ischemic myocardium, was found to be an independent predictor of life-threatening ventricular tachyarrhythmias or sudden cardiac death in patients recovering from myocardial infarction [4]. It has been demonstrated that the ventricular late potentials disappeared after elimination of myocardial ischemia by complete surgical revascularization [5]. With this methodology, P wave–triggered signal-averaged ECG modified for P-wave analysis has been used to detect atrial conduction delay that is not apparent on the standard ECG [6, 7]. It has been demonstrated that the P-wave duration recorded by the technique was significantly longer in patients with a history of atrial fibrillation than in control subjects without a history of atrial arrhythmia [6, 7]. The prolonged duration of the P-wave, therefore, has been considered as an accurate marker of risk for development of atrial arrhythmias. We therefore hypothesized that preoperative P-wave duration recorded by this technique would predict the development of atrial arrhythmias after cardiac operations.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
All patients scheduled for primary isolated elective coronary artery bypass surgery or aortic valve replacement at the Kurume University Hospital between February 2002 and March 2003 were enrolled. Patients were eligible if the preoperative rhythm was sinus, if there were no significant mitral or tricuspid lesions requiring surgical treatment, and if there was no requirement for class I or III antiarrhythmic drugs for at least 1 week before surgery. All patients signed a consent form approved by the Human Experimental Committee of Kurume University.

The signal-averaged ECG was recorded from a modified X, Y, and Z lead system using the VCM-3000 (Fukuda Denshi, Tokyo, Japan) in an electrically shielded room 1 to 3 days before surgery. The X lead was between the right and left shoulder, the aVF lead was used as the Y lead, and the precordial V1 lead was used as the Z lead. The signal from each lead was amplified up to 5 µV/cm and passed through a low-pass filter of 300 Hz and a high-pass filter of 40 Hz. A specially filtered P wave derived from the dominant P wave of the standard II lead served as a reference signal for all processing. The signals were averaged on a trigger point within a specially filtered P wave, after passing through a P wave template recognition program. The P waves were acquired until a noise endpoint less than 0.3 µV was achieved. The filtered signals for the X, Y, and Z leads were combined into a special magnitude (X2 + Y2 + Z2)1/2 that allowed the detection of high-frequency voltage in any lead. The P-wave onset and offset were determined manually, and the P-wave duration was measured preoperatively by cardiologists who were unaware of patient clinical status (Fig 1). The onset was defined as signals within the interval showing a persistent level of greater than 1 µV, and the offset was defined as noise signals showing a persistent level of less than 1 µV. The root mean square voltage for the last 20 ms of the filtered P wave of the spatial magnitude as atrial late potential (LP20) was also measured.



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  		Fig 1. Examples of signal-averaged P-waves. (Top, case 1) Signal-averaged P-wave from a patient who developed postoperative atrial arrhythmias (AF), with a measured P-wave duration of 155 ms. (Bottom, case 2) Signal-averaged P-wave from a patient who did not develop postoperative atrial arrhythmias, with a measured P-wave duration of 104 ms.

 
The left atrial dimension, left ventricular ejection fraction, and left ventricular mass index (LVMI) were also measured by echocardiography preoperatively. The left atrial anterior-to-posterior dimension was measured in the parasternal view at end-systole from the M mode echocardiogram at the level of the aortic root. The LVMI (in grams per square meter) was calculated using the following formula:


{4017941.859.si1}

(1)
where LVIDd is the left ventricular internal dimension at end-diastole, IVSd is the interventricular septum thickness, PWTd is the ventricular posterior wall thickness at end-diastole, and BSA is the body surface area.

Cardiopulmonary bypass was established with an ascending aortic cannula and either with a single two-stage right atrial cannula or bicaval venous cannula. Before cardiopulmonary bypass was initiated, heparin sodium was administered at an initial dose of 300 IU/kg. Additional heparin was administered if the celite-activated clotting time became less than 500 seconds. During cardiopulmonary bypass, the hematocrit was maintained between 18% and 25%, perfusion flows were kept between 2.4 and 2.8 L · min–1 · m–2, and mean arterial pressure was maintained between 50 and 70 mm Hg. Systemic temperature was maintained between 30° and 34°C. Myocardial protection was achieved with cold blood cardioplegia given either by an intermittent antegrade technique or a combined antegrade and retrograde technique. Heparin was neutralized by continuous intravenous administration of protamine sulfate during a 5-minute period. Minimal dose of catecholamines was used to maintain a cardiac index of greater than 2.0 L·min–1·m–2 and systolic blood pressure of greater than 80 mm Hg after cardiopulmonary bypass. Packed red blood cells were administered when hematocrit was less than 24%, and platelets were administered when platelet count was less than 2 x 104/µL postoperatively. Postoperative volume repletion and intensive care unit care followed a standard protocol of this institute.

During the first 4 days after surgery, all patients were monitored with continuous ECG telemetry as well as standard 12-lead ECGs recorded twice a day. After this period, standard 12-lead ECGs were recorded on days 5, 7, and 9, and on the day of discharge. In addition, ECGs were recorded in all instances when clinical evaluation suggested atrial arrhythmias. Any episode of atrial fibrillation, atrial flutter, or paroxysmal atrial tachycardia lasting longer than 1 hour was considered as an occurrence of atrial arrhythmias.

Statistical analysis was performed with JMP 5.0 software (SAS Institute, Cary, NC). Continuous variables are expressed as mean ± standard deviation. Unpaired Student's t test was used to compare continuous variables, and categorical data were analyzed using the {chi}2 test or Fisher's exact test as appropriate. Univariate and stepwise multivariate logistic regression were used to screen for risk factors of postoperative atrial arrhythmias. Statistical significance was assumed at a probability level of less than 0.05.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Preoperative patient characteristics and operative information were summarized in Table 1. Operative procedures performed in this study were coronary artery bypass grafting in 67 patients and aortic valve replacement in 28 patients. None of the patients died in this study. Twenty-eight patients (29%) experienced atrial arrhythmias (atrial fibrillation in 26 and atrial flutter in 2) during the period of observation. Atrial arrhythmias occurred at 3.0 ± 2.3 days after surgery (range, 0 to 10 days). The arrhythmias were restored to normal sinus rhythm in all patients; however, 21 patients required class I-A antiarrhythmic drugs and 5 required electrical cardioversion. Univariate analysis demonstrated that patients who experienced postoperative atrial arrhythmias more often had dilated left atrium (39 ± 6 versus 35 ± 5 mm; p = 0.002), greater LVMI (151 ± 50 versus 131 ± 34 g/m2; p = 0.03), and advanced age (71.8 ± 6.2 versus 66.7 ± 9.5 years; p = 0.02).


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  		Table 1. Clinical Characteristics of Study Patients
 
P-wave duration recorded with P-wave signal-averaged ECG was significantly prolonged in patients with atrial arrhythmias (135 ± 14 versus 127 ± 9 ms; p = 0.002). There were no significant differences in LP20, sex, use of ß-blocker, left ventricular ejection fraction, presence of significant right coronary artery lesion, and operative procedures between the groups with or without atrial arrhythmias. The incidence of postoperative atrial arrhythmias divided into four groupings of P-wave duration of less than 125 ms, between 125 and 134 ms, between 135 and 144 ms, and 145 ms or greater is shown in Figure 2. The incidence increased stepwise with increasing P-wave duration.



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  		Fig 2. The incidence of postoperative atrial arrhythmias (AF). The incidence was divided into four groups according to the P-wave duration by signal-averaged electrocardiogram of less than 125 ms, between 125 and 134 ms, between 135 and 144 ms, and 145 ms or greater.

 
Receiver-operating characteristic curves were used to evaluate the various sensitivities and specificities at different cut points of significant univariate predictors (P-wave duration, left atrial dimension, LVMI, and age) of postoperative atrial arrhythmias. The {chi}2 analyses demonstrated that a P-wave duration of 135 ms or greater, left atrial dimension of 35 mm or greater, LVMI of 150 g/m2 or greater, and age of 70 years or older significantly separated patients with and without postoperative atrial arrhythmias. P-wave duration of 135 ms or greater predicted atrial arrhythmias with a sensitivity of 50%, specificity of 81%, positive predictive accuracy of 52%, and negative predictive accuracy of 79%. Left atrial dimension of 35 mm or greater predicted atrial arrhythmias with a sensitivity of 71%, specificity of 52%, positive predictive accuracy of 38%, and negative predictive accuracy of 81%. An LVMI of 150 g/m2 or greater predicted atrial arrhythmias with a sensitivity of 17%, specificity of 79%, positive predictive accuracy of 44%, and negative predictive accuracy of 76%. Age of 70 years or older predicted atrial arrhythmias with a sensitivity of 71%, specificity of 57%, positive predictive accuracy of 41%, and negative predictive accuracy of 83%.

Stepwise logistic regression analysis was performed for each of the variables that were found to be significant predictors on univariate analysis (Table 2). The analysis identified that P-wave duration of135 ms or greater (p = 0.02; odds ratio, 3.5), age of 70 years (p = 0.03, odds ratio, 3.2), and left atrial dimension of 35 mm or greater (p = 0.03, odds ratio, 3.2) were the independent predictors of postoperative atrial arrhythmias. If a patient had two or more of these three risk factors, the occurrence of atrial arrhythmias was predicted with a sensitivity of 75%, specificity of 76%, positive predictive accuracy of 57%, and negative predictive accuracy of 88%.


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  		Table 2. Multivariable Analysis for the Prediction of Atrial Arrhythmias
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
Postoperative atrial arrhythmia is one of most common problems after cardiac surgery [1–3]. Although this complication is ordinarily transient and not life-threatening, it causes subjective discomfort and hemodynamic compromise, necessitates medications, and lengthens the hospital stay. Moreover, postoperative atrial arrhythmias have been shown to increase the incidence of serious ventricular arrhythmias, thromboemboli, stroke, and iatrogenic complications of treating the arrhythmias [3]. All of these problems increase the health-care resource utilization. Although the mechanisms of postoperative atrial arrhythmias have not been clearly identified, several factors, such as pericarditis, hyperadrenergic state, ischemic injury, hemodynamic changes, and fluid shifts, may work synergistically to bring about this condition [1, 2]. Previous studies have shown that being an elderly male and having the presence of significant right coronary artery disease, longer aortic cross-clamp time, withdrawal of ß-blocker, and preoperative use of digoxin were the independent predictors of postoperative atrial arrhythmias [1–3, 8, 9]. Despite the improvement in surgical techniques, cardiopulmonary bypass circuit, and postoperative patient care, the incidence remains unchanged or is even increasing as a result of increasing patient age and advances in monitoring technology [3]. Therefore, identification of subgroups of patients at increased risk and prophylaxis of this disorder are definitely worthwhile.

Numerous prophylactic and therapeutic approaches for management of postoperative atrial arrhythmias have been studied. Administration of ß-adrenergic blockers, antiarrhythmic drugs, and magnesium sulfate have been studied, and their prophylactic and therapeutic effects have been shown to some extent [1, 2, 10–12]. The overall efficacy, however, was unsatisfactory to reach a consensus for standard care. Moreover, because adverse effects of these drugs, such as hypotension, bradycardia, congestive heart failure, asthma, toxicity, and arrhythmogenicity, have been reported, their routine prophylactic use may not be accepted universally [2]. Therefore, exploration of sensitive and accurate predictors of postoperative atrial arrhythmias is essential to avoid iatrogenic complications caused by unnecessary prophylaxis and to manage patients at increased risk intensively.

The signal-averaged ECG has emerged as a valuable tool for predicting life-threatening ventricular arrhythmic events after myocardial infarction [4]. Delayed low-amplitude cardiac signals in the terminal portion of the QRS complex (late potentials), which are thought to reflect delayed ventricular activity in an ischemic zone, have been shown to be the marker of potential reentrant circuits in patients with coronary artery disease [4]. These late potentials have been shown to disappear after the elimination of myocardial ischemia by complete surgical revascularization [5]. Similar to ventricular arrhythmias, atrial arrhythmias are associated with atrial reentrant mechanisms that are initiated and maintained at atrial slow conduction areas. Prolonged P-wave duration, therefore, is thought to represent atrial conduction disturbances [6, 7]. Buxton and colleagues [13] first reported that the surface P-wave duration on the standard ECG was significantly longer in patients with atrial arrhythmias after coronary bypass surgery. Their results, however, have not been reproduced by other investigators, and the specificity and positive predictive value were somewhat low. Recently a P wave–triggered signal-averaged system, which enables the cardiologist to detect accurate atrial activity by eliminating the effects of ectopic atrial beats and variation of the PQ interval, has been developed [6, 7]. It has been shown that a prolonged atrial duration detected by this method was an independent predictor for development of paroxysmal atrial fibrillation in nonsurgical patients with a history of atrial fibrillation [6, 7]. In the cardiac surgical field, the utility of signal-averaged P-wave duration in predicting postoperative atrial arrhythmias has also been evaluated and revealed a prolonged P-wave duration in patients with atrial fibrillation [14, 15]. Frost and colleagues [16], however, have shown that signal-averaged P-wave duration did not provide significant information on the risk of atrial fibrillation after coronary artery bypass grafting surgery. Therefore, the predictive value of postoperative atrial arrhythmias is still controversial in cardiac surgical patients.

In the present study, prolonged P-wave duration measured by P wave–triggered signal-averaged system was a potent and independent predictor of atrial arrhythmias after cardiac surgery, whereas type of cardiac surgical procedures, ie, bypass surgery or valve surgery, was not. The incidence of this complication was 3.3-fold if its duration was 135 ms or greater. These results are in accord with the findings of Steinberg and associates [14]. Delayed atrial conduction, as manifested by the prolonged P-wave duration, has been shown to be a major predisposing factor of the onset and maintenance of atrial reentry [6, 7]. We therefore believe that the increased incidence of postoperative atrial arrhythmias in the present study is strongly associated with atrial conduction abnormalities that already exist preoperatively. Left atrial dimension measured by echocardiography was also a potent and accurate predictor of the development of postoperative atrial arrhythmias. Klein and associates [17] and Aytemir and colleagues [18] also have shown that left atrial enlargement was associated with an increased risk of postoperative atrial arrhythmias. Its sensitivity, however, was weak for prediction, perhaps because their studies applied standard electrocardiography to detect left atrial enlargement, whereas we used echocardiography. Although our study excluded patients with significant mitral or tricuspid valve disease, an involvement of patients with aortic valve disease who are prone to have elevated left ventricular end-diastolic pressure, which creates atrial overload, may also contribute to the differences between the results in our study and those of previous studies [17, 18].

In patients undergoing cardiac surgery, numerous intraoperative factors, such as anesthetic drugs, atrial injury by surgical handling and ischemia, pericarditis, and alterations in the sympathetic nervous system, may influence atrial conduction substantially [1, 2]. These factors, together with preoperative predisposing factors, may work synergistically to cause development of postoperative atrial arrhythmias. Therefore, it is very likely that the cause of atrial arrhythmia is multifactorial, especially in the postoperative setting. In the present study, signal-averaged P-wave duration was measured preoperatively because of a difficulty in isolating patients in the electrically shielded room immediately after surgery. Because our results regarding P-wave duration did not reflect the influences of the intraoperative factors, immediate postoperative abnormalities in atrial conduction might have been more prominent. Accordingly, further studies that examine the postoperative signal-averaged P-wave duration, along with the preoperative value, are of enormous value so as to elucidate the additional influences associated with the operation.

In summary, the present study demonstrated that although a prolonged P-wave duration recorded with P-wave signal-averaged electrocardiography is the most potent predictor of atrial arrhythmias after cardiac surgery, advanced age and left atrial enlargement should also be entertained as important risk factors of this complication. Patients with these risk factors may benefit most from prophylactic antiarrhythmic treatment.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
This work was supported in part by the Grant-in-Aid for Encouragement of Young Scientists, Japan Society for the Promotion of Science (grant A-14770696) and Grant-in-Aid for Scientific Research (grants C-15591505 and C-14571290), Japan.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Hogue CW, Hyder ML. Atrial fibrillation after cardiac operation: risks, mechanisms, and treatment Ann Thorac Surg 2000;69:300-306.[Abstract/Free Full Text]
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  3. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias Ann Thorac Surg 1993;56:539-549.[Abstract]
  4. Breithardt G, Cain ME, El-Sherif N, et al. Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiographyA statement by a task force committee of the European Society of cardiology, the American Heart Association, and the American College of Cardiology. Circulation 1991;83:1481-1488.[Abstract/Free Full Text]
  5. Can L, Kayikçioglu M, Halil H, et al. The effect of myocardial surgical revascularization on left ventricular late potentials Ann Noninvasive Electrocard 2001;6:84-91.
  6. Fukunami M, Yamada T, Ohmori M, et al. Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram Circulation 1991;83:162-169.[Abstract/Free Full Text]
  7. Guidera SA, Steinberg JS. The signal-averaged P wave duration: a rapid and noninvasive marker of risk of atrial fibrillation J Am Coll Cardiol 1993;21:1645-1651.[Abstract]
  8. Lietch JW, Thomson D, Baird DK, Harris PJ. The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting J Thorac Cardiovasc Surg 1990;100:338-342.[Abstract]
  9. Mendes LA, Connelly GP, McKenney PA, et al. Right coronary artery stenosis: an independent predictor of atrial fibrillation after coronary artery bypass surgery J Am Coll Cardiol 1995;25:198-202.[Abstract]
  10. Andrew TC, Reomold SC, Berlin JA, Antman EM. Prevention of supraventricular arrhythmias after coronary artery bypass surgery: a meta-analysis of randomized control trials Circulation 1991;84(Suppl 3):III-236-III-244.
  11. Fanning WJ, Thomas CS, Roach A, Tomichek R, Alford WC, Stoney WS. Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass grafting Ann Thorac Surg 1991;52:529-533.[Abstract]
  12. Paull DL, Tidwell SL, Guyton SW, et al. Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery Am J Surg 1997;173:419-421.[Medline]
  13. Buxton AE, Josephson ME. The role of P wave duration as a predictor of postoperative atrial arrhythmias Chest 1981;80:68-73.[Abstract/Free Full Text]
  14. Steinberg JS, Zelenkofske S, Wong SC, Gelernt M, Sciacca R, Menchavez E. Value of the P-wave signal-averaged ECG for predicting atrial fibrillation after cardiac surgery Circulation 1993;88:2618-2622.[Abstract/Free Full Text]
  15. Stafford PJ, Kolvekar S, Cooper J, et al. Signal averaged P wave with standard electrocardiography or echocardiography for prediction of atrial fibrillation after coronary artery bypass grafting Heart 1997;77:417-422.[Abstract/Free Full Text]
  16. Frost L, Lund H, Pilegaard H, Christiansen EH. Re-evaluation of the role of P-wave duration and morphology as predictors of atrial fibrillation and flutter after coronary artery bypass surgery Eur Heart J 1996;17:1065-1071.[Abstract/Free Full Text]
  17. Klein M, Evans SJL, Blumberg S, Cataldo L, Bodenheimer MM. Use of P-wave-triggered, P-wave signal-averaged electrocardiogram to predict atrial fibrillation after coronary artery bypass surgery Am Heart J 1995;129:895-901.[Medline]
  18. Aytemir K, Aksoyek S, Ozer N, Aslamaci S, Oto A. Atrial fibrillation after coronary bypass surgery: P wave signal averaged ECG, clinical and angiographic variables in risk assessment Int J Cardiol 1998;69:49-56.



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