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Right arrow Electrophysiology - arrhythmias

Ann Thorac Surg 2006;81:1773-1779
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Favorable Long-Term Outcome of Maze Surgery in Patients With Lone Atrial Fibrillation

Martin E.W. Hemels, MD a , Youlan L. Gu, MS b , Anton E. Tuinenburg, MD, PhD a , Piet W. Boonstra, MD, PhD b , Ans C.P. Wiesfeld, MD, PhD a , Maarten P. van den Berg, MD, PhD a , Dirk J. Van Veldhuisen, MD, PhD a , Isabelle C. Van Gelder, MD, PhD a , *

a Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
b Department of Thoracic Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Accepted for publication October 10, 2005.

* Address correspondence to Dr Van Gelder, Department of Cardiology, Thoraxcenter, University Medical Center Groningen, PO Box 30.001, Groningen 9700 RB, the Netherlands (Email: i.c.van.gelder{at}thorax.umcg.nl).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: Rhythm control is indicated for patients suffering from symptomatic atrial fibrillation (AF), but remains difficult to establish. We investigated the long-term outcome of Cox maze III surgery in patients with symptomatic lone AF refractory to antiarrhythmic drug therapy.

METHODS: Patients with a history of symptomatic paroxysmal or persistent AF refractory for at least two class I or III antiarrhythmic drugs and without structural heart disease or bradyarrhythmias were included. All patients underwent Cox maze III surgery. Complete success was defined as the absence of AF without antiarrhythmic drugs beyond 3 months after the procedure, and partial success as the absence of AF with antiarrhythmic drug use.

RESULTS: A total of 29 patients were included (27 male), with a mean age of 48 ± 6 years. At the time of surgery, 11 patients (38%) had persistent AF. After a mean follow-up of 4.8 ± 2.4 years, 79% of patients had complete success, and 2 patients (7%) were free of AF with antiarrhythmic drugs. At the end of follow-up, left ventricular fractional shortening was significantly improved (from 31% ± 10% to 39% ± 8%, p = 0.002), left atrial size was unchanged, exercise capacity was within normal ranges, and quality of life was comparable with that of healthy controls. Severe complications included reoperations for postoperative bleeding (n = 3), pericardial effusion (n = 1), and mediastinitis (n = 1). In 2 patients, a pacemaker was implanted postoperatively because of sinus node dysfunction.

CONCLUSIONS: Cox maze III surgery is a highly effective therapy for drug-refractory lone AF, and therefore remains an alternative to transvenous pulmonary vein ablation.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
A trial fibrillation (AF) is an important cardiac arrhythmia [1–5]. Recent trials have demonstrated that rate control is an acceptable alternative to rhythm control [6, 7]. Highly symptomatic patients were not included in these trials, however, and in these patients, rhythm control remains the treatment of choice. Rhythm control with serial antiarrhythmic drugs and cardioversions is unsuccessful in almost half of the patients [8]. If patients remain highly symptomatic, a nonpharmacologic approach may be considered. Such an approach includes preventive atrial pacing, permanent pacing after His bundle ablation, catheter ablation including pulmonary vein isolation, and the Cox maze III procedure [9–12]. The latter alternative was the most frequently tested option a decade ago, and many patients with intractable AF were offered the Cox maze III procedure. Success percentages between 75% and 97% have been reported [13, 14].

Cox maze III surgery for patients with intractable lone AF has been performed for many years in our institution, and there has been a comprehensive, prospective data collection. During long-term follow-up, we investigated the efficacy of Cox maze III surgery, and collected functional data including echocardiographic studies, exercise capacity, and ambulatory electrocardiographic recordings, quality of life, and complications of the procedure.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients with paroxysmal or persistent AF were considered eligible for Cox maze III surgery when they (a) were below 60 years of age; (b) had no underlying heart diseases (these were excluded by performing echocardiography, exercise testing, ambulatory electrocardiographic recording, and coronary angiography in all patients); (c) had no signs of sinus node dysfunction; (d) were refractory or intolerant to at least two class I or III antiarrhythmic drugs; and (e) remained highly symptomatic from AF, which interfered with their functionality or daily life. The Institutional Review Board approved the study in September 1994. Informed consent was obtained from all patients.

All patients underwent Cox maze III atrial arrhythmia surgery as described by Cox [15]. This procedure was strictly followed in all patients. In-hospital perioperative management is detailed elsewhere [16].

The first objective of the present study was to investigate the long-term success of the Cox maze III procedure. Complete success was defined as permanent absence of AF and other atrial arrhythmias (atrial flutter and tachycardia) beyond 3 months of surgery and no prophylactic antiarrhythmic drug use. Partial success was defined as the absence of AF with class I or III antiarrhythmic drug use (instituted because of recurrent AF, atrial flutter, or tachycardia beyond 3 months after surgery).

Secondary study objectives included (a) medication use at the end of follow-up; (b) changes in left ventricular function and recovery of atrial function; (c) occurrence of sustained atrial arrhythmias (other than AF), ventricular arrhythmias, sinus node dysfunction, or atrioventricular conduction disturbances; (d) changes in exercise tolerance; (e) quality of life; and (f) perioperative complications, namely, redo surgery, bleeding, infection, and bradycardia necessitating pacemaker therapy.

Follow-Up
After hospital discharge, all patients visited the outpatient clinic at 1, 3, 6, and 12 months, and yearly thereafter. These visits also included echocardiography, 24-hour Holter monitoring, and exercise testing. Quality of life and an additional survey were assessed at the end of follow-up.

Medication
Antiarrhythmic drugs were stopped at the day of surgery and restarted in case of repeated symptomatic AF or other atrial arrhythmias. Oral anticoagulation therapy was prescribed by the treating physician (I.C.V.G or A.C.P.W.) for at least 6 months postoperatively, and replaced by aspirin, unless there was an other reason to continue.

Echocardiographic measurements
During follow-up, routine transthoracic echocardiography was performed to evaluate left and right atrial diameters and function, and left ventricular diameters and function. Baseline measurements were compared with measurements at the end of follow-up. Presence of an A wave representing normal atrial contraction was defined as peak A wave velocity greater than 0.4 m/s [17, 18].

Holter monitoring
At every follow-up visit, a 24-hour electrocardiogram was performed to detect sinus node dysfunction, the occurrence of AF or other sustained atrial arrhythmias, ventricular arrhythmias, and atrioventricular conduction disturbances.

Exercise testing
At every follow-up visit, a symptom-limited bicycle exercise test was performed, starting at 50 W during the first minute, and increasing with 10 W every 30 seconds (modified Bruce protocol). Heart rate was measured at rest, at peak exercise (maximal attained workload), and after 3 minutes of recovery.

Quality of life
Quality of life was assessed using the Medical Outcomes Study Short-Form Health Survey (SF-36) questionnaire [19]. The SF-36 is a standardized, validated, generic health survey that has been frequently used in arrhythmia studies. It contains items to assess physical health (general health perception, physical functioning, role limitations due to physical problems, and bodily pain) and mental health (social functioning, role limitations due to emotional problems, and mental health and vitality). The SF-36 data at the end of follow-up were compared to a control population of 120 healthy subjects with a comparable age and sex distribution.

Statistical Analysis
Descriptive statistics are the mean ± SD or median (range) for continuous variables and counts with percentages for categorical variables. The Student t test was used in case of normally distributed variables and a Mann-Whitney U test in case of skewed variables. A paired t test was used for comparison of measurements at different time point. Survival analysis was performed according to Kaplan-Meier (percent of patients free of AF recurrence). Analyses were performed using the statistical package SPSS 11.0 (SPSS, Chicago, Illinois).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Patient Demographics
A total of 29 patients were included between February 1995 and February 2004. The characteristics of the study patients are shown in Table 1. All patients had a history of paroxysmal AF. At the time of surgery, 11 patients (38%) were classified as having persistent AF, and these patients were in AF for a median of 12 (4 to 18) months at the moment of surgery. Of the patients with paroxysmal AF, 67% (12 of 18 patients) were in sinus rhythm at the moment of surgery. Six patients (21%) underwent an unsuccessful transvenous pulmonary vein ablation before, segmentally according to Haissaguerre and associates [20] in 5 patients, and circumferentially according to Pappone and colleagues [11] in 1 patient.


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  		Table 1. Characteristics of Study Patients
 
Perioperative Outcome
Total surgery duration was 253 ± 43 minutes, and the average aortic cross-clamp duration was 71 ± 19 minutes with a mean cardiopulmonary bypass time of 150 ± 29 minutes. Total in-hospital stay was a median 17 (8 to 78) days, with a thoracic intensive care unit stay of 1 day (range, 1 to 26). There were no perioperative deaths.

Long-Term Outcome
The mean follow-up duration was 4.8 ± 2.4 years. One patient died 5 years after surgery as a result of a colon tumor. No patients were lost to follow-up.

At the end of follow-up, 79% (n = 23) of the patients were free from AF and antiarrhythmic drugs (complete success), and 2 patients (7%) were free of AF, but still used class I or III antiarrhythmic drug therapy (partial success). Figure 1 shows long-term outcome. Maze surgery was unsuccessful in 4 patients (14%). Two patients still suffered from paroxysmal AF, permanent AF developed in 1 patient with preoperative paroxysmal AF, and 1 patient with preoperative persistent AF (duration of 5 months) underwent atrioventricular node ablation and pacemaker implantation owing to recurrent episodes of AF during the first months after surgery. No patients suffered from AF recurrences after 2 years of follow-up.


Figure 1
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  		Fig 1. Survival free of atrial fibrillation (AF) after Cox maze III surgery. (AAD = antiarrhythmic drugs.)

 
Medication use
Medication use before surgery and at the end of follow-up is shown in Table 2. At the end of follow-up, only the 2 partial successfully treated patients (and 1 unsuccessfully treated patient) used class I or III antiarrhythmic drugs (in total 10% of patients versus 52% of patients before surgery). More patients were on ß-blocker therapy (38% at follow-up versus 17% before surgery), mainly because of high mean heart rate early after surgery or frequent premature supraventricular complexes, or both. One successfully and 3 unsuccessfully treated patients (in total 14%) were still using oral anticoagulation (acenocoumarol) at the end of follow-up because of the presence of stroke risk factors or the necessity to use oral anticoagulation perielectrical cardioversion. Eighteen patients (59%) used aspirin at the end follow-up (Table 2). No patient suffered from systemic thromboembolism.


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  		Table 2. Medication Used Before Surgery and at End of Follow-Up
 
Pacemaker therapy
Four of the 29 patients (14%) received a cardiac pacemaker. The indication was sinus node dysfunction in two patients (7%). During follow-up, sinus rhythm was maintained in these patients. In the other 2 patients, recurrent AF was the reason for pacemaker implantation. One patient underwent atrioventricular node ablation for persistent symptoms of paroxysmal AF during the first months after surgery. Later, he was in permanent sinus rhythm. The other patient received a pacemaker for prevention of AF but still had paroxysmal AF at the end of follow-up (AF burden of 40%).

Echocardiography
No significant differences in atrial diameters were found between baseline and end of follow-up (Table 3). There was a significant improvement of left ventricular function (fractional shortening at baseline 31% ± 10% versus 39% ± 8% at the end of follow-up, respectively; p = 0.002). According to the definition, atrial contraction was considered to be normal in both atria in 41% of patients at the end of follow-up (Table 4).


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  		Table 3. Echocardiographic Variables Before Surgery and at End of Follow-Up
 

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  		Table 4. Atrial Contraction at End of Follow-Up
 
Holter monitoring
Twenty-four hours of ambulatory Holter monitoring at the end of follow-up showed a mean heart rate of 76 ± 15 beats per minute with a minimum of 56 ± 11 beats per minute and a maximum of 125 ± 24 beats per minute. Mean longest RR-interval (range) was 1.4 s (0.9 to 1.9 s). Symptomatic short episodes of atrial arrhythmias were experienced by only 2 patients still suffering from paroxysmal AF at the end of follow-up (failures). Short asymptomatic atrial tachycardias (without AF) were observed in 14 patients (median number of 4 [1 to 20] runs, median length 3 [3 to 45] beats). In 2 patients, frequent, asymptomatic, premature ventricular beats were observed, 1,000 and 1,807 in 24 hours, respectively.

Exercise tolerance testing
No AF occurred during exercise testing in the successfully treated patients. Mean maximum workload at the end of follow-up was comparable with baseline, 190 ± 64 W (range, 50 to 300 W) versus 196 ± 43 W (range, 90 to 250 W), respectively (p = not significant). At the end of follow-up, 4 patients (including 2 failures of Maze surgery) had a reduced exercise capacity in comparison with baseline, whereas in 3 patients (all successfully treated patients), exercise tolerance was increased in comparison with before surgery. Heart rate increased from 77 ± 12 beats per minute at rest to 137 ± 30 beats per minute at maximal exercise, and was 101 ± 19 after 3 minutes of recovery.

Quality of life
Twenty-seven of 28 surviving patients completed the SF-36 questionnaire (Fig 2) and our survey (Table 5) at the end of follow-up. There were no differences in quality of life scores between the Maze patients and healthy control subjects. Seventy-eight percent of the patients concluded that Maze surgery was worthwhile and would recommend it to other patients.


Figure 2
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  		Fig 2. Comparison of the Short-Form Health Survey (SF-36) quality of life scores between patients who underwent Cox maze III surgery (black bars; n = 27) and a control group of 120 healthy subjects (gray bars) in our database (with age- and sex-matched distribution). Data are shown as scores (maximum value = 100) on the eight scales of the SF-36. No statistical difference could be demonstrated on any scale.

 

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  		Table 5. Results of Cox Maze III Specific Questionnaire With Concise Questions on the Topic (n = 27)
 
Perioperative complications
Severe complications included 3 reoperations for postoperative bleeding (10%), clinically significant pericardial effusion in 1 case (3%), and mediastinitis in 1 patient (3%). The bleeding sites were the atriotomy closure-line on the left side (n = 1) and on the right side (n = 1), and the appendage closure-line of the left atrium (n = 1). No postoperative stroke or myocardial infarction was diagnosed, there was no renal failure, no intra-aortic balloon pump placement was necessary, and no excessive fluid retention was observed in the postoperative phase. Two patients (7%) received a cardiac pacemaker for sinus node dysfunction, 1 patient immediately postoperatively and 1 patient during the postoperative in-hospital phase.


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
This study shows an excellent outcome of Cox maze III surgery for the treatment of intractable lone AF. After a mean follow-up of 4.8 years, 86% of patients were free of AF, with only 2 of them (7%) on antiarrhythmic drugs. No AF recurrences were observed after 2 years of follow-up. Perioperative complication rate was acceptable without surgery related mortality.

Comparison With Other Surgical Maze III and Transvenous Catheter Ablation Studies for Lone AF
The outcome of our study compares favorably with other studies investigating the outcome of maze III surgery for lone AF. These studies showed a complete success rate between 76% and 80% after a mean follow-up of 2.6 to 5.8 years [13, 14, 21]. At present, however, transvenous radiofrequency catheter ablation performing segmental or circumferential isolation of the pulmonary veins has become the preferred strategy to cure patients from symptomatic lone AF. Short-term and midterm results indeed are promising [20, 22]. In a study performed by Haissaguerre and colleagues [20] in 90 patients, mainly without structural underlying heart disease, segmental isolation of the pulmonary veins was reported to be successful in 71% without the use of antiarrhythmic drugs; but follow-up was only 8 ± 5 months, and in more than half of the study group, a second or third procedure was needed to attain the final results [20]. The complication rate was approximately 10%, being mainly asymptomatic pulmonary vein stenosis.

Circumferential isolation of the pulmonary veins, as developed by Pappone and coworkers [22], seems even more effective. They compared 589 patients (34% lone AF) who underwent circumferential pulmonary vein ablation with 582 patients who received antiarrhythmic drugs for rhythm control [22]. After a median follow-up of 900 days (range, 161 to 1,508), 120 ablated patients (20%) versus 340 pharmacologically treated patients (58%) had a recurrence of AF. All 120 unsuccessfully ablated patients underwent a second ablation procedure, but afterward, 31 patients (26%) had recurrent persistent AF again. Since then, many studies have been performed investigating the efficacy of transvenous catheter ablation to cure patients of AF. Complete success percentages (ie, without antiarrhythmic drugs) range from 50% to 80% [23–28]. In contrast to the surgical data, however, follow-up in all these studies was relatively short, ranging from 0.5 to 2.5 years.

Also, surgical treatment of AF has evolved rapidly [21]. New energy sources with either an endocardial or epicardial, or a combined, approach have been successfully used concomitantly with additional surgical procedures, and short-term follow-up is encouraging [29–32]. These minimally invasive procedures using various epicardial, off-pump, beating-heart ablation techniques may also become an alternative for patients with lone AF.

The complications observed in our study compare favorably with other maze III studies. Prasad and colleagues [14] and Gaynor and associates [21] reported surgery-related major complications occurring in 11% to 13% of the patients and 1.5% perioperative deaths. In our study, surgery-related complications occurred in 16%, but we observed no perioperative deaths. A worldwide survey on catheter ablation for AF performed by Cappato and colleagues [28] revealed a major complication rate of 6%. The main complications included tamponade in 1.2%, significant pulmonary vein stenosis in 1.3%, stroke in 0.2%, and perioperative death in 0.05%.

In general, the outcome of maze III surgery is favorable. However, transvenous catheter ablation has a preference predominantly, as it is easier to perform, excludes a large surgical procedure, and severe complications probably occur less often. Until now, however, only in experienced hands are success percentages of transvenous catheter pulmonary vein ablation comparable with maze III surgery. Furthermore, long-term efficacy and morbidity remain at present unclear. Finally, various epicardial, off-pump, beating-heart ablation techniques may become alternatives for the transvenous ablation techniques.

Objective and Subjective Improvement
In our study, atrial sizes did not change significantly after surgery, which has been described before in lone AF patients after maze III surgery [33]. Although at baseline left ventricular function was considered to be normal and all patients were without signs of heart failure, a significant improvement occurred afterward. Earlier studies found an improvement in cardiac function in patients with lone AF after atrioventricular node ablation, but most of these patients already had a depressed systolic function [34, 35]. Although our studied group was small, it is important to recognize that a concealed cardiomyopathy may be present, even in patients who are considered to have normal cardiac function. Restoration of atrial contractile function occurred in almost all patients, although complete recovery was found in only half of the patients, which is comparable with data of other studies [33, 36, 37].

Exercise capacity after surgery was within normal ranges in the majority of patients. This finding implies that despite extensive cardiac surgery, the function remains intact. In particular, chronotropic response to exercise was appropriate, although maximal heart rate was lower than normal. That can partly be explained by almost half of the patients being on ß-blocker therapy after surgery. At the end of follow-up, quality of life scores were comparable with those of healthy control subjects, similar to the results of Jessurun and coworkers [13]. In addition, most patients affirmed, in retrospect, their initial choice for surgical intervention of AF and would recommend maze surgery to patients with equal complaints. That is, in our view, a very important finding.

Thromboembolism and Anticoagulation Therapy
No thromboembolic complications occurred during follow-up. That indicates that in these patients, predominantly without stroke risk factors and without atrial appendages, it seems safe to discontinue oral anticoagulation despite incomplete recovery of atrial function in many patients.

Study Limitations
The number of patients was relatively small. However, the number was large enough to show long-term efficacy of Cox maze III surgery. Owing to the small number of unsuccessfully treated patients, analysis of variables related to the success or failure of the procedure was not possible. No preoperative quality of life assessment was obtained, so at the end of follow-up, no comparison with baseline values was possible.

In conclusion, Cox maze III surgery is a highly effective rhythm control strategy for severely symptomatic AF patients. It therefore remains an alternative for transvenous pulmonary vein isolation in the management of patients with drug-refractory symptomatic lone atrial fibrillation. Severe complications may occur, but patients almost always recover without sequelae. New surgical beating-heart epicardial procedures are promising, however, and may in future replace the Cox maze III technique, including for patients with lone AF.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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