The Maze III procedure was introduced in 1995 as a

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1 Long-Term Effects of the Maze Procedure on Atrial Size and Mechanical Function Stefan Lönnerholm, MD, Per Blomström, MD, Leif Nilsson, MD, and Carina Blomström-Lundqvist, MD Departments of Cardiology and Thoracic Surgery, University Hospital, Uppsala, Sweden Background. The Maze procedure is effective in restoring sinus rhythm, but the extensive procedure may have negative effects on atrial mechanical function. Decreased atrial contractility has been observed early after the Maze procedure. The purpose of this study was to determine the long-term effect of the Maze procedure on atrial size and mechanical function. Methods. Fifty-two patients with symptomatic atrial fibrillation, without structural heart or valvular disease, underwent the Cox Maze III procedure. Atrial size and mechanical function were assessed by echocardiographic examination at baseline and postoperatively at a mean SD of 6 1 and months. Results. The left atrial area was decreased 6 months after the procedure compared with baseline (mean, vs cm 2, p < 0.01). By 56 months, however, the left atrial area had increased compared with the 6-month follow-up ( vs cm 2, p < 0.001), resulting in no difference in left atrial size compared with the baseline values. The left atrial contractility, measured as fractional area change, was significantly reduced at 6 and 56 months of follow-up ( and vs baseline ), as was the transmitral A-wave velocity (30 12 and 28 8 cm/s vs baseline 40 15). The same pattern was seen for the right atrium. Conclusions. This study shows that the Maze procedure results in a sustained decrease in atrial contractility. The initial reduction in atrial size is later reversed. These findings contradict late improvements in atrial mechanical function after Maze surgery and may have important implications for the risk of thromboembolic complications. (Ann Thorac Surg 2008;85:916 20) 2008 by The Society of Thoracic Surgeons The Maze III procedure was introduced in 1995 as a curative therapy for atrial fibrillation (AF) [1]. Despite the described high efficacy rate of 75% to 98% [2 11], the cost and complexity of the Maze III procedure, as well as concerns about atrial mechanical function, have been arguments against the operation. With the advent of transvenous catheter ablation for AF, the Cox Maze procedure has mainly been reserved for combined surgical procedures where the primary indication has been other than AF. Return of atrial contraction after the Maze operation has been observed in several studies including patients with permanent AF [12 14]. Reduced atrial mechanical function was, however, seen in a group of patients with paroxysmal lone AF after the Maze procedure compared with preoperatively, and there were indications of further deterioration of left atrial mechanical function late after surgery [15]. Catheter-based procedures were initially confined to the ostium of the pulmonary veins [16], but have gradually changed with the addition of extensive ablation lines in the left atrium [17] resembling the lesion sets of the Maze III procedure. Recently, reduced atrial contractility was reported 5 months after circumferential pulmonary vein isolation for AF [18]. Reduced atrial contractility has Accepted for publication Oct 29, Address correspondence to Dr Lönnerholm, Department of Cardiology, University Hospital, Uppsala, S , Sweden; stefan. lonnerholm@akademiska.se. implications for the atrial contribution to ventricular myocardial performance and may also promote thromboembolic complications. This fact emphasizes the importance of assessing the long-term effect of atrial mechanical function after both surgical and catheter-ablation procedures for AF. In this prospective study, we assessed atrial size and mechanical function by echocardiography before the Maze III operation, early postoperatively (mean 6 1 months), and at a long-term follow-up (mean months). Material and Methods Study Population Between February 1996 and February 2000, 75 patients with AF underwent the Maze III procedure at the University Hospital of Uppsala, Sweden. The primary indication for surgery was severely symptomatic, drugrefractory AF in all patients. Excluded from the study were 14 patients who underwent additional cardiac procedures. The exceptions were a patient who underwent coronary artery bypass grafting (CABG) and another patient who underwent aortic root grafting (both pathologies found at preoperative routine evaluation) because no procedures were done inside the heart. None of the patients had undergone any previous cardiac operations or catheter ablation for AF. We performed a long-term follow-up of all living patients, with a minimum obser by The Society of Thoracic Surgeons /08/$34.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg LÖNNERHOLM ET AL 2008;85: ATRIAL SIZE AND FUNCTION AFTER MAZE SURGERY Table 1. Clinical Characteristics All Patients (n 52) Longitudinally Followed Up (n 17) Age, mean SD years Sex, No. Male Female 11 5 Permanent AF, No (%) 15 (29) 0 AF duration, mean SD years Structural heart disease, No. (%) 7 (13) 3 (18) Hypertension, No. (%) 6 (12) 2 (12) AF atrial fibrillation; SD standard deviation. vation period of 38 months after the Maze surgery. Nine patients were excluded for this follow-up: 4 were living abroad, 3 were unwilling to participate, and 2 had incomplete recordings of the echocardiographic examination. The study population consisted of 52 patients with a mean age of 55 years (range, 32 to 72 years). Clinical characteristics are summarized in Table 1. The mean duration after Maze surgery to the end of long-term follow-up was months. Most patients (35 of 52) were in AF during the preoperative echocardiographic evaluation. In the remaining 17 patients who were in sinus rhythm, complete echocardiographic evaluations, including measurements of atrial mechanical function, were performed serially before the operation and postoperatively at 6 1 and months. One patient with sinus rhythm at baseline evaluation had died by the end of long-term follow-up, but had an echocardiographic examination 29 months after the Maze operation and was included in this subgroup. The study complies with the Declaration of Helsinki, and the Regional Ethics Review Board approved the research protocol. All patients provided oral and written informed consent to participate in the study. Surgical Procedure The standard Maze III procedure, described by Cox [1], was completed in all patients without any modification. The cut and sew technique was used for all lesions. Cryolesions were used to secure electric isolation where the incision lines ended at the tricuspid and mitral annulus. Clinical Follow-Up All patients received warfarin for 6 months. Antiarrhythmic drugs were not routinely prescribed after the procedure but were given to patients with early AF recurrences. If the patients were free of AF at 6 months, the warfarin and antiarrhythmic drugs were stopped unless the patient had another indication for warfarin. Echocardiographic Examination Echocardiographic examinations were made according to a standard study protocol by experienced technicians supervised by a clinical physiologist. A commercially available Hewlett-Packard Sonos 1500, 2500, or 5500 instrument (Hewlett-Packard Co, Medical Products Group, Andover, MA) with a 2.5-MHz transducer was used, and the results were recorded on video home system (VHS) videotapes. The recordings were later reviewed by one experienced cardiologist who measured the right and left atrial dimensions and transmitral inflow velocities. Maximal right and left atrial cavity areas were obtained by planimetry in the apical 4-chamber view at the end of systole, defined as the last frame before mitral valve opening. Minimal left and right atrial cavity areas were obtained at end diastole at the time of the R wave on the electrocardiogram (ECG). The mean values were calculated from 3 consecutive beats. The atrial fractional area change (maximum area-minimum area/maximum area 100) of the right and left atria was then calculated. Pulsed-Doppler echocardiography was used to assess the transmitral flow velocities from an apical 4-chamber view with a sample volume from the tip of the mitral leaflets during diastole. Peak velocities of the early filling (E) wave and atrial filling (A) wave, as well as the deceleration time of the E wave, were measured and averaged over 3 beats and the E/A ratios were calculated. Statistical Analysis All values are expressed as the mean SD. The Student two-tailed paired t test was used for comparison of data for each patient at different time periods. Statistical significance was set at p Results 917 At long-term follow-up, months after the procedure, 45 of 52 patients (86.5%) were in sinus rhythm, 3 (5.8%) were paced in AAI mode, and 4 (7.7%) paced in DDD mode. No patient had experienced a symptomatic recurrence of AF, and no AF was found on ECG at follow-up. In the group with sinus rhythm postoperatively, all 17 patients were in sinus rhythm both at 6 months and at long-term follow-up. No patient had had any thromboembolic event. Atrial Area Dimensions At long-term follow-up, the maximal and minimal left atrial area was and cm 2, respectively. The corresponding figures for the right atrial area were and cm 2, respectively. Group mean values of the maximum area of the left and right atrium were not significantly different at long-term follow-up compared with baseline ( vs cm 2 and vs cm 2, respectively). In 17 patients with paroxysmal AF, significant changes were found in the left and right atrial areas compared with baseline (Table 2). Six months after the Maze procedure, the maximum area of both the left and right atria had decreased significantly, whereas both dimensions of the left and right atria increased significantly when measured at 56 months. The minimal areas of both atria at long-term follow-up were larger than before the procedure. CARDIOVASCULAR

3 918 LÖNNERHOLM ET AL Ann Thorac Surg ATRIAL SIZE AND FUNCTION AFTER MAZE SURGERY 2008;85: Table 2. Atrial Measurements and Fractional Area Change at and at Follow-Up After Cox Maze Procedure a Post-Maze Follow-Up 6 Months p Value b 56 Months p Value b Left atrium Max area, cm c 0.09 Min area, cm c FAC Right atrium d Max area, cm c 0.08 Min area, cm c FAC a Values are for the 17 patients with sinus rhythm at baseline evaluation. b Values for p vs baseline. c p months vs 56 months post-maze. d The right atrial wall could not be clearly delineated in 1 patient at 6 months post-maze and in 3 patients at 56 months post-maze. FAC fractional area change. Atrial Mechanical Function At long-term follow-up, 10 of 52 patients (19%) had no measurable left atrial contraction based on the absence of a transmitral A wave. In the remaining 42 patients, the mean transmitral A-wave velocity was cm/s and the mean transmitral E-wave velocity was cm/s, resulting in a mean E/A ratio of at a mean months after the Maze procedure. The longitudinal measurements of the transmitral E wave and A wave in the 17 patients with sinus rhythm preoperatively are shown in Table 3, and the corresponding E/A ratios are shown in Figure 1. A significant increase in the transmitral E wave (p 0.01) and a decrease in the transmitral A wave (p 0.03) were seen at 6 months after the Maze operation compared with baseline values. The transmitral E wave continued to increase between 6 and 56 months postoperatively, but no significant change was measured for the transmitral A wave. Correspondingly, the E/A ratio measured at 56 months was higher than the ratio at baseline ( vs , p ). The fractional area changes at baseline and follow-ups after the Maze procedure, in the group of patients with sinus rhythm at baseline, are shown in Figure 2. The fractional area change was significantly decreased at 6 months after the Maze procedure and remained unchanged at 56 months in both the left and the right atria compared with baseline (Table 2). Comment Main Findings We describe the long-term effects on atrial size and mechanical function after the Maze III surgical procedure in a population with AF without structural heart disease. All patients were successfully treated, with 100% freedom from symptomatic AF recurrences at 56 months. Despite the effective rhythm control, a sustained decline in the atrial mechanical function was found in the population with paroxysmal AF. Atrial mechanical function could be measured in most patients with chronic AF before the operation, but the level was far from normal. Several groups have previously reported reduced atrial mechanical function after Maze III surgery as well as after modified Maze procedures [12 19]. Most of these patients had concomitant valvular disease, however, and it is therefore unclear if the reduced contractility was related to the valvular disease per se or the surgical procedure. We have previously reported results from a small patient population with paroxysmal AF followed up longitudinally for 24 months after Maze III operations in which a trend towards a gradual decline in the atrial mechanical function was seen [15]. The present study supports our previous findings in that there are no late improvements in atrial contractility after surgical therapy for AF in this population. Reports on the atrial mechanical function after pulmonary vein isolation by transvenous catheter ablation Table 3. The Transmitral Pulsed Doppler Velocities a Post-Maze Follow-up Wave 6 Months p Value vs 56 Months p Value vs 6 Months E-wave (cm/s) b A-wave (cm/s) b a Values are for the 17 patients with sinus rhythm at the baseline evaluation. b Value of p 0.01 for baseline vs 56 months.

4 Ann Thorac Surg LÖNNERHOLM ET AL 2008;85: ATRIAL SIZE AND FUNCTION AFTER MAZE SURGERY Fig 1. Transmitral pulsed Doppler measurements of E/A wave ratio before and at short- and long-term follow-up after the Maze procedure in the 17 patients with sinus rhythm at baseline evaluation. Data are presented as mean, and the vertical bars denote 95% confidence intervals. techniques have been conflicting. In a study by Lemola and colleagues [18], who used contrast-enhanced computed tomography imaging, the left atrial ejection fraction was reduced by 30% after surgery in a patient population with paroxysmal AF, whereas in another echocardiographic study by Reant and colleagues [20], the mechanical function was unchanged in patients with paroxysmal AF. The conflicting results may be explained by the different ablation technique used. In the study by Reant and colleagues [20], only the pulmonary veins were electrically isolated in most of the patients, whereas in the study by Lemola and colleagues [18], a more extensive approach was used that isolated a larger area of the left atrium. Another important finding in our study is that both the systolic and diastolic sizes of the left and right atria increased late postoperatively compared with 6 months postoperatively. The reduced atrial size observed 6 to 12 months after both surgical and catheter-based procedures for AF has been proposed as a key factor for maintaining sinus rhythm [21]. Maintenance of sinus rhythm and scarring due to extensive procedures, whether surgical or catheter-based, have been proposed as explanations for the reduction in atrial size. Our finding of a late increase in both the systolic and diastolic atrial sizes despite almost 5 years of sinus rhythm was unexpected. The pathophysiologic mechanisms for this atrial enlargement are unknown. One may speculate whether an ongoing myocardial process could be the reason for and not the consequence of AF, or whether an irreversible mechanical remodelling with fibrosis and compensated dilatation related to longstanding AF may be an explanation. Another tentative explanation may be a late deterioration of atrial myocardial function due to the surgical procedure and subsequent scarring. Clinical Implications The goal of most therapies for AF is to restore sinus rhythm, which thereby is expected to improve quality of 919 life, restore the mechanical function, and reduce the risk of thromboembolic complications. Sinus rhythm can be restored most patients with both the Maze procedure and different catheter ablation procedures. It has been established for both techniques that they improve quality of life [22 24]. For patients with permanent AF, atrial mechanical function is improved after any AF therapy that restores sinus rhythm. For patients with paroxysmal AF, however, the Maze III procedure, different modified Maze procedures, and at least the more extensive catheter-ablation procedures seem to reduce atrial mechanical function. The clinical significance of this reduction is yet unclear. The risk of thromboembolic complications is related to stasis of blood within the left atrium and left atrial appendage. It has been presumed that restoration of sinus rhythm prevents the risk for thromboembolic complications. Despite this presumption, the left atrial appendage is removed in many surgical procedures to minimize the risk of future formation of thrombi. The level of atrial mechanical function needed to prevent thromboembolic complications is presently not known. In this long-term study, reduced or even absent atrial contractility was noted both early and late after cut and sew Maze procedure. If similar changes occur after catheter ablation procedures performed without excision of the left atrial appendage, the risk of thromboembolic complications might increase despite resumption of sinus rhythm. The finding in this study, together with reports of reduced atrial contraction after commonly used catheter ablation procedures, stress the need for long-term studies assessing the risk of thromboembolic complications after nonpharmacologic therapies for AF. Fig 2. Echocardiographic measurement of the fractional change in the right (squares) and left atrial (circles) area before and at 6 and 56 months after the Cox Maze procedure in the 17 patients with sinus rhythm at baseline evaluation. The vertical bars denote 95% confidence intervals; p 0.05 for 6 and 56 months measurements vs baseline. CARDIOVASCULAR

5 920 LÖNNERHOLM ET AL Ann Thorac Surg ATRIAL SIZE AND FUNCTION AFTER MAZE SURGERY 2008;85: Study Limitation One limitation of this study is the small number of patients in sinus rhythm at baseline evaluation, permitting evaluation of changes in atrial mechanical function after the procedure compared to before in only 17 patients. This was because patients accepted for Maze surgery had long-standing AF and had to have tried and failed most available antiarrhythmic drugs and thus often developed persistent or permanent AF. Although a small number of patients were studied, they were homogenous and without any concomitant valvular disease. It was therefore possible to evaluate the effects of the surgical procedure per se on atrial size and transport function. References 1. Cox JL, Boineau JP, Schuessler RB, Jaquiss RDB, Lappas DG. Modification of the Maze procedure for atrial flutter and fibrillation: rational and surgical results. J Thorac Cardiovasc Surg 1995;110: Raanani E, Albåge A, David TE, Yau TM, Armstrong S. The efficacy of the Cox/maze procedure combined with mitral valve surgery: a matched control study. Eur J Cardiothorac Surg 2001;19: Izumoto H, Kawase T, Ishihara K, et al. Survival and sinus rhythm maintenance after modifiead Cox/Maze procedure and mitral valve operation in patients with chronic atrial fibrillation. Jpn J Thorac Cardiovasc Surg 2001;49: Kosakai Y. Treatment of atrial fibrillation using the Maze procedure: the Japanese experience. Semin Thorac Cardiovasc Surg 2000;12: Cox J, Ad N, Palazzo T, Fitzpatrick S, et al. The Maze-III procedure combined with valve surgery. Semin Thorac Cardiovasc Surg 2000;12: Arcidi JM, Doty DB, Millar RC. The Maze procedure: The LDS Hospital experience. Semin Thorac Cardiovasc Surg 2000;12: Kalil RAK, Albrecht A, Lima GG, et al. Results of the surgical treatment of chronic atrial fibrillation. Arq Bras Cardiol 1999;73: Kim K-B, Cho KR, Sohn D-W, Ahn H, Rho JRR. The Cox-Maze procedure for atrial fibrillation associated with rheumatic mitral valve disease. Ann Thorac Surg 1999;68: Schaff HV, Dearani JA, Daly RC, Orszulak TA, Danielson GK. Semin Thoracic Cardiovasc Surg 2000;12: McCarthy PM, Gillinov AM, Castle L, Chung M, Cosgrove D 3rd. The Cox-Maze procedure: the Cleveland Clinic experience. Semin Thoracic Cardiovasc Surg 2000;12: Jessurun ER, van Hemel NM, Defauw JAMT, et al. Results of Maze surgery for lone paroxysmal atrial fibrillation. Circulation 2000;101: Feinberg MS, Waggoner AD, Kater KM, Cox JL, Lindsay BD, Perez JE. Restoration of atrial function after the Maze procedure for patients with atrial fibrillation. Circulation 1994; 90:II-285 II Albrini A, Scalia GM, Murray D, et al. Left and right atrial transport function after the Maze procedure for atrial fibrillation: an echocardiographic Doppler follow-up study. J Am Soc Echocardiogr 1997;10: Isobe F, Kawashima Y. The outcome and indication of the Cox Maze III procedure for chronic atrial fibrillation with mitral valve disease. J Thorac Cardiovasc Surg 1998;116: Lonnerholm S, Blomstrom P, Nilsson L, Blomstrom- Lundqvist C. Atrial size and transport function after the Maze III procedure for paroxysmal atrial fibrillation. Ann Thorac Surg 2002;73: Haissaguerre M, Jais P, Shah DC, et al. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000;101: Pappone C, Oreto G, Rosanio S, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 2001; 104: Lemola K, Desjardins B, Sneider M, et al. Effect of left circumferential ablation for atrial fibrillation on left atrial transport function. Heart Rhythm 2005;2: Bauer EP, Szaly ZA, Brandt RR, et al. Predictors for atrial transport function after mini-maze operation. Ann Thorac Surg 2001;72: Reant P, Lafitte S, Jais P, et al. Reverse remodeling of the left cardiac chambers after catheter ablation after1 year in a series of patients with isolated atrial fibrillation. Circulation 2005;112: Beukema W, Elvan A, Sie H, Ramdat A, Misier R, Wellens H. Successful radiofrequency ablation in patients with previous atrial fibrillation results in a significant decrease in left atrial size. Circulation 2005;112: Lonnerholm S, Blomstrom P, Nilsson L, Oxelbark S, Jideus L, Blomstrom-Lundqvist C. Effects of the Maze operation on health-related quality of life in patients with atrial fibrillation. Circulation 2000;101: Weerasooriya R, Jais P, Hocini M, et al. Effect of catheter ablation on quality of life of patients with paroxysmal atrial fibrillation. Heart Rhythm 2005;2: Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42: