Incidence and Predictors of Pacemaker Placement After Surgical Ablation for Atrial Fibrillation

Incidence and Predictors of Pacemaker Placement After Surgical Ablation for Atrial Fibrillation Berhane Worku, MD, Sang-Woo Pak, MD, Faisal Cheema, MD, Mark Russo, MD, Brian Housman, BA, Danielle Van Patten, BA, Jessica Harris, and Michael Argenziano, MD Columbia University College of Physicians and Surgeons/New York Presbyterian Hospital Department of Cardiothoracic Surgery, New York, New York Background. Bradyarrhythmia requiring pacemaker placement is a relatively common complication after surgical ablation for atrial fibrillation (AF). We report our experience with surgical ablation procedures using various energy modalities and lesion sets in an attempt to identify the risk factors associated with postoperative pacemaker requirement. Methods. Intraoperative data were collected prospectively, and preoperative and postoperative data were collected retrospectively. Energy modality and lesion sets used were dependent on availability on the date of the procedure and surgeon preference. Results. From October 1999 to October 2009, 701 patients underwent surgical ablation for AF at our institution. Forty-five patients (7.6%) required early postoperative pacemaker placement. There were no significant differences in baseline characteristics or associated procedures between patients who required pacemaker placement and those who did not. Ninety-day mortality was greater in patients requiring pacemaker placement (15.6% versus 6.6%; p 0.025). In multivariable analysis, a pacemaker requirement was more likely with the use of microwave energy (odds ratio [OR] 2.87; confidence interval [CI], 1.41 to 5.84; p 0.004) and a right atrial lesion set (OR, 2.82; CI, 1.07 to 7.45; p 0.036). Conclusions. In conclusion, over our 10-year experience with surgical AF ablations, the incidence of pacemaker requirement was much lower than that reported in series of classic cut and sew Maze procedures, even among patients undergoing full biatrial ablations. Although biatrial ablation is currently our favored approach to patients with long-standing or persistent AF, right atrial lesion sets increase the risk of this complication and should be used judiciously. (Ann Thorac Surg 2011;92:2085 90) 2011 by The Society of Thoracic Surgeons Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting up to 1% of the general population, and 8% of those older than 80 years of age [1]. With the increasing age of our society, the incidence of this disease is on the rise. AF has been shown to be an independent predictor of stroke and death [2, 3]. Heart rate control strategies are effective in treating AF, but in susceptible patients the persistent loss of coordinated atrial contraction can still compromise cardiac output, and the risk of thromboembolism is not eliminated. Although conversion to sinus rhythm is the optimal outcome, antiarrhythmic medications have had limited success and are associated with significant side effects that negate these benefits [4]. In 1987, the Cox-Maze procedure was introduced. A series of surgical incisions in the heart ( cut and sew ) are created that interrupt the various abnormal reentrant circuits that result in AF. Cardiopulmonary bypass support and a full sternotomy are required. The procedure was modified twice to what is now known as the Cox- Maze III. These procedures have resulted in a 90% to 99% long-term freedom from AF [5,6]. However they are Accepted for publication July 19, 2011. Address correspondence to Dr Worku, 1330 1st Ave, Apt 607, New York, NY, 10021; e-mail: bmworku@hotmail.com. cumbersome and infrequently performed by most cardiac surgeons because of their invasiveness. More recently technology has been developed to perform the Cox-Maze lesions using various energy modalities. Laser, microwave, ultrasound, radiofrequency, and cryoablation have all been used in the surgical treatment of AF, eliminating the need for incisions. Although the goal of these procedures is to create transmural lesions that will block abnormal proarrhythmic circuits, an occasional consequence is postoperative bradyarrhythmia requiring pacemaker placement. The initial Cox-Maze procedures resulted in rates of postoperative pacemaker requirement as high as 6% to 56% [5 8]. With the advent of minimally invasive approaches and the replacement of various incisions with ablation techniques, the procedure has been simplified. Although efficacy may be slightly compromised, the incidence of various complications such as bleeding and bradyarrhythmia are also reduced. Minimally invasive approaches using radiofrequency, microwave, and cryoablation technologies have reported pacemaker placement rates of 0% to 10% [9 13]. Although various studies compare pacemaker requirement rates between the various surgical procedures for AF, few assess for specific variables that may contribute to this complication after 2011 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2011.07.058

2086 WORKU ET AL Ann Thorac Surg ATRIAL FIBRILLATION ABLATION AND PACEMAKERS 2011;92:2085 90 ablation [14, 15]. We report our experience with the Maze procedure using various energy modalities and lesion sets, with the goal of identifying risk factors associated with postoperative pacemaker requirement. Patients and Methods Patient Population From October 1999 to October 2009, 701 patients underwent surgical ablation for AF at our institution. Radiofrequency, microwave, laser, or cryoablation energy sources were used, depending on surgeon preference and availability of the energy source on the date of the procedure. Eligibility criteria for surgical ablation for AF were either the presence of AF for at least 6 months or a history of at least 2 unsuccessful cardioversion attempts. Paroxysmal AF was defined as intermittent AF and persistent AF was defined as continuous AF. Intraoperative data were collected prospectively and preoperative and postoperative data were collected retrospectively. The study was approved by the Columbia University Institutional Review Board. Surgical Approach The left atrial lesions are performed via either an epicardial or endocardial approach. Epicardial approaches may be performed with or without cardiopulmonary bypass and usually consist of pulmonary vein isolation of the right and left veins independently, with the use of a bipolar clamp device, or a box lesion encircling all 4 veins simultaneously, with the use of a unipolar device. The left atrial appendage may be amputated with the use of a stapling device. Endocardial approaches are usually performed with cardiopulmonary bypass on an arrested heart. The left atrium is entered through the interatrial groove. The right and left pulmonary veins are encircled independently (with a connecting lesion between the 2 sides) or all 4 veins are encircled simultaneously as in a box lesion. Additional lesions to the mitral valve annulus and the left atrial appendage may also be created. The left atrial appendage is sewn closed by an endocardial approach or amputated and closed with a stapling device or suture. The right atrial lesions are generally created with the heart beating. The superior and inferior venae cavae are snared. A small incision is made in the right atrial appendage and a right atrial free-wall lesion is created from this incision. Two centimeters from this lesion, a vertical atriotomy is performed and a lesion is created from this incision to the tricuspid valve annulus. Additional lesions are created from the inferior aspect of this incision to the superior and inferior venae cavae. Demographics, Risk Factors, and Outcomes Preoperative variables examined included age, gender, chronicity of AF, duration of AF, preoperative left ventricular ejection fraction, and left atrial size, as well as comorbidities. Intraoperative variables included energy source, lesions created, site of lesions (epicardial versus endocardial), approach (minimally invasive versus open), operative times, and concomitant procedures. Postoperative variables included need for pacemaker placement, length of hospital stay, and survival. Statistical Methods Continuous variables are represented as mean standard deviation and categorical variables are represented as frequency and percentage. Continuous variables were compared using the Student s t test and categorical variables were compared using the 2 test or Fischer s exact test as appropriate. A p value of less than 0.05 was considered statistically significant. All reported p values are 2-sided. Kaplan-Meier analysis was used to calculate survival rates and the log-rank test was used to determine statistical significance. Multivariable analysis was used to determine independent predictors of pacemaker requirement. All data were analyzed using STATA (StataCorp LP, College Station, TX) or Excel (Microsoft Corporation, Seattle, WA). Results Baseline Characteristics From October 1999 to October 2009, 701 patients underwent surgical ablation for AF at our institution. Preoperative pacemakers were present in 13% (89) of patients. Early postoperative pacemaker placement (within the first 30 postoperative days) was required in 7.6% (45) of patients for bradyarrhythmia. Indications for pacemaker placement are listed in Table 1. There was a trend toward increasing age in patients requiring early postoperative pacemaker placement (69.2 versus 65.4 years; p 0.082). There were no other differences between groups in baseline characteristics (Table 2). Intraoperative Details Of those patients requiring early postoperative pacemaker placement, 26.7% (12 patients) underwent minimally invasive approaches. Endocardial lesions were used in 80% (36 patients). Mean bypass time was 2 hours and 35 minutes, and mean cross-clamp time was 1 hour and 47 minutes. A mitral valve repair/replacement was the most common concomitant procedure, and 6.7% (3 patients) had an isolated Maze procedure for lone AF. All patients underwent pulmonary vein isolation, and 55.6% (25 patients) underwent creation of additional right or left atrial lesions as well. There were no significant differences between groups in the previously mentioned in- Table 1. Indications for Pacemaker Placement Sick sinus syndrome (12 cases) Symptomatic sinus bradycardia (2 cases) Tachycardia-bradycardia syndrome (2 cases) Pauses (3 cases) Bradycardia limiting medical rate control (3 cases) Sinus arrest (2 cases) Atrioventricular block (33 cases)

Ann Thorac Surg WORKU ET AL 2011;92:2085 90 ATRIAL FIBRILLATION ABLATION AND PACEMAKERS 2087 Table 2. Baseline Characteristics Table 4. Lesion Sets PPM No PPM p (%, n) a (%, n) a Value Lesion PPM (%, n) NO PPM (%, N) p Value Age (years) 69.2 65.4 0.082 Female 44.4 (20) 44.9 (246) 0.954 Duration of AF (years) 6.1 6.1 0.959 Paroxysmal AF 44.2 (19) 38.5 (212) 0.8 Preoperative ejection 48 47 0.605 fraction (%) Preoperative left atrial size 5.69 5.76 0.774 (cm) Reoperation 17.8 (8) 14.2 (78) 0.513 Preoperative sinus rhythm 25.6 (10) 26.4 (137) 0.815 Previous ablation 2.2 (1) 4.7 (26) 0.435 Diabetes 15.6 (7) 17 (93) 0.807 Congestive heart failure 17.8 (8) 28 (153) 0.14 Renal insufficiency 15.6 (7) 8.9 (49) 0.145 Hyperlipidemia 35.6 (16) 32.5 (178) 0.673 Hypertension 55.6 (25) 54.0 (296) 0.842 COPD 4.4 (2) 6.0 (33) 0.666 a Unless otherwise stated. AF atrial fibrillation; COPD chronic obstructive pulmonary disease; traoperative details, including concomitant procedures (Table 3) or lesion sets (Table 4). Early postoperative pacemaker placement was seen least frequently in patients undergoing radiofrequency ablation. Compared with these patients, those undergoing microwave ablation had a significantly higher risk of requiring early postoperative pacemaker placement (OR, 3.44; CI, 1.38 to 8.58; p 0.008) (Table 5). Postoperative Outcomes Length of hospital stay was similar between groups (14.5 days versus 12.4 days; p 0.341). Ninety-day mortality Table 3. Operative Details Operation PPM No PPM p (%, n) a (%, n) a Value Coronary artery bypass 28.9 (13) 22.8 (125) 0.354 grafting Aortic valve procedure 24.4 (11) 24.5 (134) 0.999 Mitral valve procedure 71.1 (32) 67.2 (368) 0.586 Tricuspid valve procedure 13.3 (6) 10.9 (60) 0.625 Isolated Maze procedure 6.7 (3) 5.3 (29) 0.695 Minimally invasive approach 26.7 (12) 21.9 (120) 0.638 Bypass time (minutes) 155 148.4 0.413 Cross-clamp time (minutes) 107.3 103 0.675 Beating-heart ablation 22.2 (10) 19.6 (106) 0.666 Off-pump ablation 9 (4) 10.8 (58) 0.730 Endocardial ( epicardial) lesions 80 (36) 78.8 (431) 0.850 a Unless otherwise stated. Pulmonary vein isolation 100 (44) 97.5 (515) 0.333 Mitral valve annulus lesion 52.5 (23) 45.5 (238) 0.387 Left atrial appendage lesion 25.0 (11) 25.3 (131) 0.966 Right atrial lesion set 20.9 (9) 14.9 (78) 0.297 was significantly greater in patients requiring early postoperative pacemaker placement (15.6% versus 6.6%; p 0.025). Kaplan-Meier analysis revealed no difference in overall survival between groups (log-rank test, p 0.51) (Fig 1). Multivariable Analysis Multivariable analysis demonstrated that microwave ablation was associated with an increased risk of early postoperative pacemaker requirement at 30 days (OR, 2.87; CI, 1.41 to 5.84; p 0.004), as was performance of a right atrial lesion set (OR, 2.82; CI, 1.07 to 7.45; p 0.036). Renal insufficiency and creation of a mitral valve annulus lesion were associated with a trend toward an increased likelihood of early postoperative pacemaker requirement, whereas a history of congestive heart failure was associated with a trend toward a decreased likelihood of early postoperative pacemaker requirement (Table 6). Comment In recent years the majority of patients with AF undergoing open heart procedures have been offered simultaneous surgical ablation. With simplification of the procedure and the use of various energy sources to replace the incisions of the original Maze procedure, surgical treatment for AF has become more widespread. Increasingly, minimally invasive approaches are used and patients with lone AF who meet certain criteria such as intractable symptoms, failure of medical management, and contraindications to anticoagulation are offered isolated Maze procedures. Several studies have demonstrated the safety and efficacy of the procedure, with rare complications such as atrioesophageal fistula and coronary artery or coronary sinus injury rates of less than 1% to 2% [9 12]. The rate of pacemaker requirement, however, has remained at 5% to 10%. Few studies have analyzed the factors responsible for this, partly because of the small number powered to so. In our series, microwave energy and performance of a right atrial lesion set were found to correlate with pacemaker placement. Right atrial lesion sets were not used more extensively in patients undergoing microwave ablation versus ablation with other energy modalities (laser, 4%; microwave, 6%; cryoablation, 50%; radiofrequency, 22%), hence both factors demonstrated independent correlation with pacemaker requirement on multivariate analysis. Thus there is no clear explanation for the finding regarding microwave energy use. However the

2088 WORKU ET AL Ann Thorac Surg ATRIAL FIBRILLATION ABLATION AND PACEMAKERS 2011;92:2085 90 Table 5. Energy Sources Source PPM (%, n) NO PPM (%, N) Odds Ratio a Microwave 55.6 (25) 35.4 (194) 3.44; CI 1.38 8.58; p 0.008 Cryoablation 15.6 (7) 11.5 (63) 2.96; CI, 0.96 9.16; p 0.059 Laser 15.6 (7) 23.9 (131) 1.42; CI, 0.467 4.34; p 0.533 a Other energy modalities compared with radiofrequency (PPM, 13.3%, n 6; no PPM, 29.2%, n 160). CI confidence interval; correlation between the use of a right atrial lesion set and pacemaker requirement suggests a possible iatrogenic mechanism for bradyarrhythmia. The Cox-Maze I procedure resulted in an inability to generate an appropriate sinus tachycardia (ie, to exercise) and left atrial dysfunction in some patients. An area overlying the right atrial superior vena cava junction in the vicinity of the sinoatrial node, known as the atrial pacemaker complex, was found to be responsible for mediating sinus tachycardia, and one of the Cox-Maze I lesions traverses this area. This lesion was modified to create the Cox-Maze II procedure. Although generation of an appropriate sinus tachycardia was preserved, this procedure was more cumbersome than its predecessor and still resulted in some incidence of left atrial dysfunction. An additional modification to alter the lesion traversing Bachmann s bundle, responsible for propagation of the sinus impulse from the right atrium to the left atrium, solved the problem of left atrial dysfunction and coincidentally resulted in a lesion set that was technically easier to perform than the previous procedures [7]. Thus the actual locations of the Cox-Maze lesions and their relation to relevant cardiac circuitry were responsible for various aberrations in postoperative conduction. Similarly, one may expect that lesion set may correlate with the incidence of bradyarrhythmia and pacemaker requirement postoperatively. The initial cut and sew lesions of the Cox-Maze procedure have for the most part been replaced with various energy sources in what is known as the Cox- Maze IV. The lesion sets involve a set of left atrial ablations used either in isolation or in combination with a set of right atrial ablations. It has been demonstrated that paroxysmal AF originates from the pulmonary veins [16] and thus in patients with this condition, a left atrial lesion set incorporating pulmonary vein isolation with or without additional lesions (including those to the mitral valve annulus and left atrial appendage) is generally sufficient. The left atrial appendage is closed or amputated to reduce the risk of stroke. In those with more persistent forms of AF, triggers and reentrant circuits originating in the right atrium are thought to be responsible, and in these patients a right atrial lesion set is generally added [17]. It is the portion of the lesion to the superior vena cava that is most likely to injure either the sinoatrial node or its blood supply, and it is generally kept as lateral as possible to avoid this complication [18, 20]. In addition, the tricuspid annulus lesion courses near the atrioventricular node and puts this structure at risk for injury and subsequent heartblock. Our results are consistent with this hypothesis, as all surgeons performed a caval and tricuspid annulus lesion as part of any right atrial lesion set. Several studies have demonstrated the incidence of postoperative pacemaker requirement to be between 0% and 10% [9 13] after surgical ablation for AF. However few studies have attempted to analyze the factors associated with this complication. Gillinov and associates [15] Table 6. Multivariable Analysis Variable Odds Ratio CI p Value Age 1.02 0.992 1.05 0.156 Female 0.857 0.438 1.67 0.651 Beating heart 2.39 0.851 6.74 0.098 Microwave 2.87 1.41 5.84 0.004 Minimally invasive 1.91 0.786 4.65 0.153 Mitral valve annulus 2.05 0.922 4.56 0.078 lesion Left atrial appendage 0.769 0.297 1.99 0.588 lesion Right atrial lesion set 2.82 1.07 7.45 0.036 Congestive heart failure 0.473 0.202 1.11 0.084 Renal insufficiency 2.5 0.956 6.52 0.062 Preoperative ablation 0.515 0.057 4.65 0.554 CABG 1.25 0.527 2.96 0.613 Mitral valve procedure 1.54 0.594 4.00 0.374 Aortic valve procedure 1 0.404 2.48 0.998 Fig 1. Survival. () CABG coronary artery bypass grafting; CI confidence interval.

Ann Thorac Surg WORKU ET AL 2011;92:2085 90 ATRIAL FIBRILLATION ABLATION AND PACEMAKERS 2089 analyzed 575 patients undergoing surgical treatment for AF with either pulmonary vein isolation alone (n 68), pulmonary vein isolation with additional left- or rightsided lesion sets (n 265; 53% of patients in this group had right atrial lesions), or a Cox-Maze II or III procedure (n 242). New permanent pacemakers were required in 50 patients (8.7%), and there were no differences between the 3 groups. However if there was a direct iatrogenic cause of bradyarrhythmia related to the creation of right atrial lesions, it may not have been detected in the previously mentioned study because those patients receiving such lesions were grouped with a roughly equal number of patients who received left-sided lesions only. Surprisingly the incidence of pacemaker requirement was the same between patients undergoing a full Cox- Maze procedure and those undergoing limited ablation [15]. A metaanalysis of 48 studies comparing 2279 patients undergoing surgical ablation for AF with various energy sources to 1553 patients undergoing a cut and sew Cox-Maze procedure similarly found no difference between groups with regard to pacemaker requirement [14]. These findings are in contrast to other studies documenting much higher pacemaker requirement rates in patients undergoing cut and sew procedures for AF [7]. Nonetheless, to our knowledge, the current study is the first in which various specific lesions were tested independently for their association with pacemaker requirement. No clear explanation for the correlation between energy modality and postoperative pacemaker requirement is readily available. In a series of 42 patients undergoing valve surgery and ablation for AF with a biatrial lesion set using either microwave (n 23) or radiofrequency (n 19) energy, the pacemaker requirement rate was similar between groups (22% versus 21%). The authors comment that this complication was definitely due to lesion lines, which may have been too close to the atrioventricular node, and that after the first few cases extra attention was paid during ablation in this area to prevent future cases of atrioventricular block [19]. In the current study, the association between microwave energy and pacemaker requirement is unlikely to be explained by the learning curve, as radiofrequency energy was used most extensively in the first 2 years of our experience. Radiofrequency energy demonstrated the lowest incidence of pacemaker placement. The association between energy modality and pacemaker requirement warrants further analysis. Limitations of this study include those inherent to a retrospective analysis using chart review and include incomplete data, potential inaccuracies in data, and potential for selection bias. In addition, because of differences in clinical practice across centers, extrapolation of results may be of limited value. In conclusion, over our 10-year experience with surgical AF ablations, the incidence of pacemaker requirement was much lower than that reported in series of classic cut and sew Maze procedures, even among patients undergoing full biatrial ablations. Although biatrial ablation is currently our favored approach in pa tients with long-standing or persistent AF, right atrial lesion sets increased the risk of this complication and should be used judiciously. References 1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation. Circulation 2006;114:e257 354. 2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983 88. 3. Benjamin EJ, Wolf PA, D Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946 52. 4. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825 33. 5. Cox JL, Ad N, Palazzo T, et al. Current status of the Maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg 2000;21:15 9. 6. McCarthy PM, Gillinov AM, Castle L, Chung M, Cosgrove D 3rd. The Cox-Maze Procedure: The Cleveland Clinic Experience. Semin Thorac Cardiovasc Surg 2000;21:25 9. 7. Cox JL, Boineau JP, Schuessler RB, Jaquiss RD, Lappas D. Modification of the Maze procedure for atrial flutter and atrial fibrillation. Rationale and surgical results. J Thorac Cardiovasc Surg 1995;110:473 84. 8. Ad N. The Cox-Maze procedure: History, results, and predictors for failure. J Interv Card Electrophysiol 2007;20:65 71. 9. Mohr FW, Fabricus AM, Falk V, et al. Curative treatment of atrial fbrillation with intraoperative radiofrequency ablation: short-term and midterm results. J Thorac Cardiovasc Surg 2002;123:919 27. 10. Moten SC, Rodriguez E, Cook RC, Nifong LW, Chitwood WR Jr. New ablation techniques for atrial fibrillation and the minimally invasive cryo-maze procedure in patients with lone atrial fibrillation. Heart Lung Circulation 2007;16:S88 93. 11. Beyer E, Lee R, Lam BK. Point: minimally invasive bipolar radiofrequency ablation of lone atrial fibrillation: early multicenter results. J Thorac Cardiovasc Surg, 2009;137: 521 6. 12. Sagbas E, Akpinar B, Sanisoglu I, et al. Video-assisted bilateral epicardial pulmonary vein isolation for the treatment of lone atrial fibrillation. Ann Thorac Surg 2007;83: 1724 30. 13. Pruitt JC, Lazzara RR, Ebra G. Minimally invasive surgical ablation of atrial fibrillation: the thoracoscopic box lesion approach. J Interv Card Electrophysiol 2007;20:83 7. 14. Khargi K, Keyhan-Falsafi A, Hutten BA, Ramanna H, Lemke B, Deneke T. Surgical treatment of atrial fibrillation: a systematic review. Herzschr Elektrophys 2007;18:68 76. 15. Gillinov AM, Bhavani S, Blackstone EH, et al. Surgery for permanent atrial fibrillation: impact of patient factors and lesion set. Ann Thorac Surg 2006;82:502 14. 16. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659 66. 17. Li H, Li Y, Sun L, et al. Minimally invasive surgical pulmonary vein isolation alone for persistent atrial fibrillation: preliminary results of epicardial atrial electrogram analysis. Ann Thorac Surg 2008;86:1219 26. 18. Damiano RJ Jr, Voeller RK. Biatrial lesion sets. J Interv Card Electrophysiol 2007;20:95 9. 19. Wisser W, Khazen C, Deviatko E, et al. Microwave and radiofrequency ablation yield similar success rates for treatment of chronic atrial fibrillation. Eur J Cardiothorac Surg 2004;25:1011 7. 20. Chen MC, Chang JP, Chen CJ, et al. Atrial pacemaker complex preserved radiofrequency Maze procedure reducing the incidence of sick sinus syndrome in patients with atrial fibrillation. Chest 2005;128:2571 5.