Early Restoration of Atrial Contractility After New-Onset Atrial Fibrillation in Off-Pump Coronary Revascularization

Early Restoration of Atrial Contractility After New-Onset Atrial Fibrillation in Off-Pump Coronary Revascularization Ho Young Hwang, MD, PhD, Sungjoon Park, MD, Hyung-Kwan Kim, MD, PhD, Yong-Jin Kim, MD, PhD, and Ki-Bong Kim, MD, PhD Department of Thoracic and Cardiovascular Surgery and Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Background. Duration of anticoagulation therapy is one of the major concerns about management of newonset atrial fibrillation (AF) after myocardial revascularization. We evaluated whether right and left atrial contractility was restored early after electrical sinus conversion in patients who experienced new-onset AF after off-pump coronary artery bypass grafting. Methods. From January 2009 to December 2010, 62 patients who underwent off-pump coronary artery bypass grafting and experienced new-onset AF were prospectively enrolled. Right and left atrial contractility was evaluated with transthoracic echocardiography performed 23 10 hours after restoration of sinus rhythm. Anticoagulation was initiated when the AF continued for more than 24 hours. Results. New-onset AF occurred at 2.3 1.2 postoperative days, and continued or recurred for 26 31 hours (>24 hours in 22 patients). Right and left atrial contractility was demonstrable after sinus conversion in all patients. Mitral inflow E and A wave velocities and the E/A ratio were 0.71 0.21 m/s, 0.68 0.19 m/s, and 1.15 0.57, respectively. Mitral valve A= velocity was 7.9 1.9 cm/s. Tricuspid inflow E and A wave velocities and E/A ratio were 0.52 0.12 m/s, 0.42 0.13 m/s, and 1.30 0.27, respectively. There were no significant differences in echocardiographic data between patients who had AF lasting longer than 24 hours and those with AF lasting 24 hours or less. Anticoagulation was discontinued after demonstration of atrial contractility. No patients experienced bleeding complications during anticoagulation or thromboembolic events after cessation of anticoagulation. Conclusions. Short-term anticoagulation may be sufficient for the prevention of thromboembolic events in patients who underwent off-pump coronary artery bypass grafting and experienced new-onset AF because right and left atrial contractility was restored early after sinus conversion. (Ann Thorac Surg 2013;95:520 4) 2013 by The Society of Thoracic Surgeons New-onset atrial fibrillation (AF) is one of the most common complications after cardiac surgery. The incidence of new-onset AF after cardiac surgery has been reported as 16% to 50%, and AF usually develops in the first 4 postoperative days [1 3]. In spite of its transient nature, postoperative AF is associated with significant mortality and morbidities including higher rates of reintubation, prolonged ventilatory support, renal failure, and stroke [3, 4]. In medical patients with AF, anticoagulation therapy is recommended when AF lasts longer than 48 hours and should be continued for more than 4 weeks even after the restoration of sinus rhythm [5, 6]. Although previous studies have recommended a similar protocol in patients with new-onset AF after cardiac surgery, controversies still exist with regard to optimal timing of initiation and cessation of anticoagulation therapy [6 8]. The aims of this study were to assess the Accepted for publication Sept 13, 2012. Address correspondence to Dr K.-B. Kim, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea; e-mail address: kimkb@snu.ac.kr. restoration of atrial contractility early after sinus conversion and to determine whether long-term anticoagulation therapy is needed in patients who experienced new-onset AF after off-pump coronary artery bypass grafting (off-pump CABG, OPCAB). Material and Methods Patient Characteristics The study protocol was approved by the institutional review board (approval number, H-0811-076-263), and informed consents were obtained in all study patients. Of the 338 consecutive patients who underwent isolated OPCAB between January 2009 and December 2010, 69 patients (20.4%) experienced new-onset AF after surgery. Patient inclusion criteria included (1) patients who underwent isolated OPCAB, (2) patients who experienced new-onset AF after surgery, and (3) patients who returned to sinus rhythm before hospital discharge. Seven patients were excluded from this study owing to the inability to perform adequate echocardiographic evaluation (n 4) and exhibiting sustained AF until discharge 2013 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc http://dx.doi.org/10.1016/j.athoracsur.2012.09.033

Ann Thorac Surg HWANG ET AL 2013;95:520 4 ATRIAL CONTRACTILITY AFTER AF IN OPCAB 521 Table 1. Preoperative Characteristics and Risk Factors of the Study Patients Variables Patients (n 62) Age (y) 67.3 6.8 Male/female 52:10 Unstable/stable angina 42:20 Risk factors, n (%) Smoking 28 (45.2%) Hypertension 48 (77.4%) Diabetes mellitus 37 (59.7%) History of stroke 14 (19.5%) Chronic renal failure 9 (14.5%) Hyperlipidemia 5 (8.1%) Obesity (BMI 30 kg/m 2 ) 3 (4.8%) Angiographic diagnosis, n (%) Left main disease 21 (33.9%) Three-vessel disease 45 (72.6%) Left atrial dimension (mm) 42 7 BMI body mass index. (n 3). Of the 62 patients (male to female ratio, 52:10; 67.3 6.8 years) enrolled in the present study, hypertension (77.4%) and diabetes mellitus (59.6%) were common comorbidities (Table 1). The patients were continuously monitored with postoperative electrocardiography during stays in the intensive care unit, and also in the general ward until the fifth postoperative day at the least or until the chest tubes were removed. Patients who exhibited any short runs of AF received continuous 24-hour telemetry with arrhythmia-detection algorithms during their entire hospital stay. A standard 12-lead electrocardiogram was also checked daily during the hospital stay. The occurrence of any short runs of AF lasting more than 30 seconds during the hospital stay was considered to represent the development of AF. Operative Techniques and Perioperative Management The basic surgical procedures and principles of OPCAB have been previously described [9]. Our surgical strategies during the study period were (1) performing complete revascularization, if possible, using a free right internal thoracic artery or saphenous vein anastomosed to the in situ left internal thoracic artery as a composite graft in most patients, (2) harvesting arterial grafts with a skeletonizing technique, and (3) avoiding aortic manipulation. Patients were anticoagulated with an initial dose of heparin (1.5 mg/kg), and periodically received supplemental doses to maintain an activated clotting time of more than 300 seconds during OPCAB. All patients took aspirin (200 mg/day) and -blocking agents such as bisoprolol and atenolol until the day of surgery and resumed them on the first postoperative day, unless otherwise contraindicated. Ticlopidine hydrochloride (200 mg/day) was used simultaneously with aspirin for 2 months postoperatively. If the patient had a high blood level of low-density lipoprotein cholesterol ( 100 mg/ dl), statin therapy was initiated. Prophylactic amiodarone or other antiarrhythmic medications were not used. Management Protocol for Postoperative Atrial Fibrillation When new-onset AF developed postoperatively, blood gas analysis, serum hemoglobin and potassium levels, and intravascular volume status were evaluated for correction of reversible causes of arrhythmias. After the immediate control of heart rate by intravenous calciumchannel blockers, the patient received a loading dose of intravenous amiodarone (300 mg) for 30 minutes, followed by a continuous intravenous infusion of an additional 300 mg for 12 hours while vital signs were carefully monitored. After the amiodarone infusion was completed, oral amiodarone was initiated at a daily dose of 200 mg. Oral amiodarone therapy was maintained for 7 additional days after restoration of sinus rhythm [10]. Electrical cardioversion was not considered unless the patient was hemodynamically unstable. Full-dose low molecular weight heparin injection therapy was initiated once the duration of AF exceeded 24 hours continuously or recurrently. When the duration of AF continued for longer than 48 hours, oral anticoagulation therapy (warfarin sodium) was added to the antiplatelet medications (aspirin and ticlopidine hydrochloride) until echocardiography demonstrated restoration of atrial activity after cardioversion. If the patient was hemodynamically stable except for AF, the patient s discharge plan was not halted, and medications including anticoagulation (target international normalized ratio, 2.0 to 2.5) and oral amiodarone were continued until sinus rhythm and atrial activities were confirmed at the outpatient clinic follow-up visit. Echocardiographic Evaluation All patients referred for CABG underwent preoperative echocardiography, including measurement of E (peak early diastolic filling velocity) and A wave (peak filling velocity at atrial contraction) velocities on the mitral inflow, and mitral valve A= velocity (peak velocity of mitral annular motion at late diastole), respectively. In patients who experienced new-onset AF postoperatively, echocardiography was performed when sinus rhythm was restored and maintained for more than 12 hours. The E and A wave velocities on the tricuspid and mitral inflows and mitral valve A= velocity were assessed postoperatively. Both E and A wave velocities on the mitral and tricuspid inflows were assessed using pulsed-wave Doppler examination of the apical four-chamber view, with the sample volume placed between the tips of the mitral and tricuspid leaflets. The mean values of five consecutive beats were obtained for quantitative analysis. Atrial mechanical contractility was considered to be restored when a peak A wave velocity at least 0.1 m/s was demonstrated [11]. Mitral valve A= velocity was measured to assess intrinsic atrial longitudinal contraction, with the sample volume placed on the atrial side of the mitral annulus at the basal interatrial septum in the Doppler apical four-chamber view [12].

522 HWANG ET AL Ann Thorac Surg ATRIAL CONTRACTILITY AFTER AF IN OPCAB 2013;95:520 4 Table 2. Early Mortality and Morbidities Variables Patients (n 62) Mortality, n (%) 0 (0%) Morbidities other than AF, n (%) Prolonged ventilation ( 48 h) 3 (4.8%) Pneumonia 1 (1.6%) Bleeding reoperation 1 (1.6%) Thromboembolism 0 (0%) AF atrial fibrillation. Statistical Analysis Statistical analysis was performed using the SPSS software package (version 12.0; SPSS Inc, Chicago, IL). Changes in continuous variables were compared using the paired Student s t test and Mann-Whitney U test. All results were expressed as mean standard deviation or as proportions. A probability value less than 0.05 was considered statistically significant. Results Clinical Results There was no in-hospital mortality, and none of the patients experienced acute renal failure, mediastinitis, or stroke (Table 2). New-onset AF occurred at postoperative 2.3 1.2 days (range, 0 to 6 days), and continued or recurrently occurred for 26 31 hours (range, 1 to 151 hours; 24 hours in 11 and 48 hours in 11; Fig 1). None of the patients underwent electrical cardioversion. Bleeding complications associated with anticoagulation did not occur, and none of the patients experienced thromboembolic events after cessation of anticoagulation therapy. Patients who experienced new-onset AF were discharged at postoperative 8.9 3.1 days. Echocardiographic Data Echocardiographic evaluation was performed 22.6 9.6 hours (range, 5 to 47 hours) after restoration of sinus rhythm. Left atrial contractility was demonstrated in all patients. Mean mitral E and A wave velocities and E/A ratio were 0.71 0.21 m/s, 0.68 0.19 m/s, and 1.15 0.57, respectively. Mitral valve A= velocity was 7.9 1.9 cm/s. Right atrial contractility was documented in 56 patients; it was unable to be confirmed in 6 patients owing to a poor sonic window. Mean tricuspid E and A wave velocities and E/A ratio were 0.52 0.12 m/s, 0.42 0.13 m/s, and 1.30 0.27, respectively. There was no significant difference in mitral valve A= velocity postoperatively when compared with the preoperative value (p 0.168), although postoperative mitral E and A wave velocities and E/A ratio were significantly different from preoperative values (p 0.005, 0.003, and 0.002, respectively). Heart rate was more rapid during postoperative echocardiography when compared with the preoperative examination (p 0.001; Table 3). There were no significant differences in the echocardiographic data between patients who had AF lasting longer than 24 hours and those who exhibited AF lasting 24 hours or less (Table 4). Follow-Up for Recurrent Atrial Fibrillation All patients with new-onset AF underwent postoperative follow-up through the outpatient clinic. The first visit was 16 8 days after discharge, and all study patients remained in sinus rhythm at that time. For the present study, patients were followed up clinically and electrocardiographically at the outpatient clinic until April 30, 2012. Follow-up was complete in 100% (62 of 62) of patients, with a median follow-up duration of 18.0 months (range, 1.6 to 37.4 months). None of the study patients experienced recurrent AF. Of the 3 patients with sustained AF at discharge, 2 patients had resumed sinus rhythm by the first outpatient clinic follow-up visit; their right and left atrial contractilities were demonstrated with transthoracic echocardiography performed 9 and 14 days after the first outpatient clinic visit, respectively. The 2 patients remained in sinus rhythm during follow-up of 24 months and 12 months, respectively. The third patient had resumed sinus rhythm at 8 months postoperatively; right and left atrial contractility was demonstrated with echocardiography performed 3 months after sinus conversion. No patient experienced a thromboembolic event after discharge. Atrial fibrillation is one of the most common morbidities that occur after CABG, with reported incidences ranging from 16% to 50% [1, 2]. Comment The present study demonstrated three main findings. First, normal sinus rhythm was restored in most patients with new-onset AF after OPCAB. Second, right and left atrial contractility was restored early after restoration of normal sinus rhythm in patients with new-onset AF. Fig 1. Distribution of atrial fibrillation duration in the 62 study patients.

Ann Thorac Surg HWANG ET AL 2013;95:520 4 ATRIAL CONTRACTILITY AFTER AF IN OPCAB 523 Table 3. Echocardiographic Evaluation of Right and Left Atrial Activity Variables Preoperative Echocardiogram Postoperative Echocardiogram p Value Left atrial activity E wave velocity (m/s) 0.63 0.21 0.71 0.21 0.005 A wave velocity (m/s) 0.75 0.17 0.68 0.19 0.003 E/A ratio 0.90 0.54 1.15 0.57 0.002 A= velocity (cm/s) 8.2 1.8 7.9 1.9 0.168 Right atrial activity E wave velocity (m/s)... 0.52 0.12... A wave velocity (m/s)... 0.42 0.13... E/A ratio... 1.30 0.27... Heart rate (beats/min) 65 13 79 9 0.001 Third, anticoagulation therapy could be discontinued before hospital discharge if normal sinus rhythm was restored and maintained. Postoperative AF usually develops within the first 4 postoperative days, having a peak incidence on the second postoperative day, and only 6% of patients experience AF after the sixth postoperative day [2, 13]. Most AF episodes end spontaneously even without therapeutic intervention, and resumption of sinus rhythm at the time of discharge has been reported in 93% to 98% of patients who had postoperative AF [3, 10, 14]. In the present study, 66 of 69 patients (95.7%) were discharged in sinus rhythm, and 3 patients with sustained AF at discharge had resumed sinus rhythm during outpatient clinic follow-up. Echocardiographic variables, such as mitral leaflet excursion, peak A wave velocity, and atrial ejection force, have been developed for evaluation of atrial function [15]. The peak A wave velocity, obtained by twodimensional guided pulsed Doppler echocardiography, has commonly been used for the evaluation of atrial mechanical function, although it is influenced by heart rate, ventricular compliance, and loading conditions [16, 17]. However, mitral valve A= velocity, which measures intrinsic atrial longitudinal contraction by Doppler tissue imaging, is a preload-independent marker of atrial function [12]. Restoration of normal sinus rhythm is frequently accompanied by relatively depressed atrial mechanical function [18, 19], and the recovery of atrial contractility has been demonstrated to be related to the duration of AF before cardioversion [16]. Prompt recovery is achieved in patients with short AF duration ( 48 hours) [19]. In the present study, patients underwent echocardiography for evaluation of right and left atrial contractility and postoperative cardiac performance after restoration of sinus rhythm. Atrial contractility was restored early after cardioversion, and both mitral and tricuspid peak A wave velocities were greater than 0.1 m/s in all study patients. There were significant differences in postoperative E and A wave velocities when compared with preoperative velocities; however, the differences seemed to be attributable to different postoperative hemodynamic conditions, including rapid heart rate. However, the preoperative and postoperative A= velocity differences were insignificant because A= velocity reflects intrinsic atrial contraction. When both right and left atrial contractility was compared based on the duration of postoperative AF ( 24 hours versus 24 hours), there were no significant differences in the echocardiographic data between the two groups. One of the complications of postoperative AF is loss of atrial transport function, which increases vulnerability to thromboembolic complications. Hence, it is recommended that patients with postoperative AF start anticoagulation therapy within 48 hours of the onset of AF because of a doubling of the risk of stroke [8]. In addition, the atrial dysfunction remaining after restoration of normal sinus rhythm appears to confer ongoing risk for thrombus formation and thromboembolism in the days after cardioversion, and at least 4 weeks of postcardioversion anticoagulation therapy is recommended [6, 7]. However, there is insufficient evidence of benefit from an additional 4 to 6 weeks of anticoagulation in patients who experience postoperative AF but who recover sinus rhythm spontaneously or pharmacologically. The mechanisms of new-onset AF after cardiac surgery are multi- Table 4. Comparison of Postoperative Echocardiographic Data Based on the Duration of Atrial Fibrillation a Variables AF 24 h (n 40) AF 24 h (n 22) p Value Changes in left atrial activity E wave velocity (%) 118 4 128 57 0.391 A wave velocity (%) 92 28 97 20 0.495 E/A ratio (%) 135 45 140 78 0.747 A= velocity (%) 96 22 99 18 0.715 Right atrial activity E wave velocity (m/s) 0.51 0.11 0.55 0.14 0.342 A wave velocity (m/s) 0.42 0.11 0.44 0.17 0.578 E/A ratio 1.29 0.28 1.32 0.25 0.731 a Variables representing left atrial activity were compared as percent values based on the preoperative data. AF atrial fibrillation.

524 HWANG ET AL Ann Thorac Surg ATRIAL CONTRACTILITY AFTER AF IN OPCAB 2013;95:520 4 factorial and different from those of nonsurgical patients. Some causative mechanisms have been proposed that include pericardial and systemic inflammation, excessive production of catecholamines, autonomic imbalance, and interstitial mobilization of fluid with resultant changes in volume, pressure, and neurohumoral environment during the postoperative period [20]. These factors may cause abnormal, or nonuniform, dispersion of atrial refractoriness, which makes the atria more vulnerable to the development of AF after cardiac surgery. In addition, in surgical patients, an additional several weeks of anticoagulation may increase the risk of bleeding complications such as pericardial tamponade, hemothorax, and graft harvest site hematoma. In the present study, anticoagulation therapy was initiated when AF persisted for more than 24 hours according to the current guidelines of the American College of Cardiology/American Heart Association/European Society of Cardiology [5]. Low molecular weight heparin injection therapy was initiated once the duration of AF exceeded 24 hours continuously or recurrently. When the duration of AF was greater than 48 hours, oral anticoagulation therapy was added to the antiplatelet medications. Anticoagulation therapy was discontinued when echocardiography demonstrated restoration of atrial activity after cardioversion. We did not experience any bleeding or thromboembolic complications such as reoperation for bleeding, pericardial tamponade, hemorrhagic or embolic stroke, or transient ischemic attack. There are limitations to the present study that should be recognized. First, we did not compare these results in patients who underwent on-pump CABG, because almost all CABG procedures at our institution were performed using the off-pump technique during the study period. Second, the number of enrolled patients was too small to reach a definite conclusion, although we demonstrated that atrial contractility was restored early after conversion to sinus rhythm in all study patients. References 1. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmia after cardiothoracic surgery. N Engl J Med 1997;336:1429 34. 2. Maesen B, Nijs J, Allessie M, Schotten U. Post-operative atrial fibrillation: a maze of mechanisms. Europace 2012;14: 159 74. 3. Almassi GH, Pecsi SA, Collins JF, Shroyer AL, Zenati MA, Grover FL. Predictors and impact of postoperative atrial fibrillation on patients outcomes: a report from the Randomized On Versus Off Bypass trial. J Thorac Cardiovasc Surg 2012;143:93 102. 4. Kaw R, Hernandez AV, Masood I, Gillinov M, Saliba W, Blackstone EH. 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