A arrhythmias. It is associated with significant morbidity

Transcription

1 ORIGINAL ARTICLES Five-Year Experience With the Maze Procedure for Atrial Fibrillation James L. Cox, MD, John P. Boineau, MD, Richard B. Schuessler, PhD, Kathryn M. Kater, MSN, and Demetrios G. Lappas, MD Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis, Missouri Between September 25,1987, and December 31,1992, 75 patients (53 men, 22 women; average age, 52 years) underwent the maze procedure for the treatment of atrial fibrillation. Six patients had undergone a previous cardiac operation and 28% underwent concomitant cardiac procedures in addition to the maze procedure. One patient (1.3%) died 10 days after undergoing a combined maze procedure and Morrow procedure for the management of chronic atrial fibrillation and hypertrophic obstructive cardiomyopathy. Postoperative atrial pacemakers were required in 40%: 26% for preoperative sick sinus syndrome and 6% for iatrogenic injury of the sinus node, and 8% had pacemakers in place preoperatively. As of December 31,1992,65 patients had been followed up for at least 3 months after operation (range, 3 to 63 months). The maze procedure cured atrial fibrillation, restored atrioventricular synchrony, and preserved atrial transport function in 64 of 65 patients (98%). The procedure has been curative without the need for medications in 58 of 65 patients (89%) and with the need for medications in 6 of 65 (9%), with medications failing in only 1 of the 65 patients (2%). The results support the maze procedure as the treatment of choice in patients with medically refractory symptomatic atrial fibrillation. (Ann Thorac Surg 1993;56:81&24) trial fibrillation is the most common of all cardiac A arrhythmias. It is associated with significant morbidity and mortality and is frequently resistant to medical therapy. As a result, during the past decade, several nonmedical techniques have been designed to either ablate the arrhythmia or ameliorate its attendant detrimental sequelae. In 1980, we described the left atrial isolation procedure, which was capable of confining atrial fibrillation to the left atrium while leaving the remainder of the heart in normal sinus rhythm [l]. In 1982, Scheinman and colleagues [2] introduced catheter fulguration of the His bundle as a means of controlling the irregular cardiac rhythm associated with atrial fibrillation and other refractory supraventricular arrhythmias. In 1985, Guiraudon and associates [3] described the corridor procedure for the treatment of atrial fibrillation, an open heart technique that accomplishes the same physiologic state as that associated with the closed-chest His bundle ablation of Scheinman, except that a permanent pacemaker is not always required [4, 51. Each of these nonpharmacologic approaches to the treatment of atrial fibrillation confers some benefit that is an advantage over allowing the patient to continue with the arrhythmia, but none of them alleviates all three of the detrimental sequelae of atrial fibrillation: (1) the irregular heartbeat, (2) the compromise in hemodynamics secondary to the absence of synchronous atrioventricular con- Resented at the Twenty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 2527, Address reprint requests to Dr Cox, Division of Cardiothoracic Surgery, Washington University School of Medicine, Suite 3108, Queeny Tower, One Barnes Hospital Plaza, St. Louis, MO traction, and (3) the vulnerability to systemic thromboembolism. Only a procedure capable of actually ablating atrial fibrillation, per se, can alleviate all three of these untoward side effects of the arrhythmia, and, to accomplish this goal, we believed that a clearer understanding of the basis of atrial fibrillation was required. Thus, in 1980, we initiated a systematic program of study into the electrophysiologic basis of atrial flutter and atrial fibrillation utilizing several different animal models of these arrhythmias [6-81 and incorporating the use of specially designed multipoint electrodes [ 71 and a computerized mapping system. In 1986, these intraoperative studies were extended to human patients with atrial fibrillation and other supraventricular arrhythmias [ This program culminated in the development of an operative procedure specifically designed to accomplish three goals: (1) the permanent ablation of atrial fibrillation, (2) the restoration of atrioventricular synchrony, and (3) the preservation of atrial transport function. The safety, efficacy, and long-term effects of the surgical technique that was conceived [ were evaluated extensively in the experimental laboratory [15], and the technique was then first applied clinically on September 25, 1987 [12]. Our 5-year experience with this technique, the maze procedure, forms the basis of this report. Material and Methods Patient Characteristics Between September 25, 1987, and December 31, 1992, 75 patients underwent the maze procedure for the treatment of atrial flutter or atrial fibrillation, or both. There were 53 men (71%) and 22 women (29%) with an average age of by The Society of Thoracic Surgeons /93/$6.00

2 Ann Thorac Surg 1993; COXETAL 815 NUMBER OF PATIENTS v-- FEMALE Fig 1. Age and sex distribution of the 75 patients undergoing the maze procedure. years (range, 22 to 74 years) (Fig 1). The presenting arrhythmia was paroxysmal atrial flutter in 5 patients (7%), paroxysmal atrial fibrillation in 34 patients (45%), and chronic atrial fibrillation in 36 patients (48%). All patients had failed to respond to extensive medical therapy consisting of an average of five drugs per patient. Amiodarone treatment had also failed preoperatively in 28 of the patients (37%). In the interest of clarity, the 5 patients with paroxysmal (intermittent) atrial flutter and the 36 with paroxysmal (intermittent) atrial fibrillation are considered as a single treatment group, separate from the group of patients with chronic (continuous) atrial fibrillation. None of the patients suffered from chronic atrial flutter. Therefore, the patient population consisted of 39 patients with paroxysmal atrial flutter or fibrillation (52%) and 36 patients with chronic atrial fibrillation (48%). The average duration of paroxysmal atrial flutter or fibrillation in the 39 patients before operation was 8 years, with 1 year being the shortest duration and 30 years the longest. There were two subgroups of patients who presented for operation in a state of chronic atrial fibrillation (n = 36). Twenty-one of these patients had first had paroxysmal atrial fibrillation for several years before chronic atrial fibrillation developed. The average time that these patients had experienced paroxysmal atrial fibrillation before converting to chronic fibrillation was 10 years, and they had been in a state of chronic fibrillation for an average of 2 years before operation. The duration of the total arrhythmia in these patients ranged from 4 months to 46 years. The second subgroup (n = 15) of chronic atrial fibrillation patients consisted of those who had never experienced intermittent arrhythmias before the sudden onset of continuous atrial fibrillation. The average duration of chronic atrial fibrillation in these patients before operation was 9 years. In 1 patient in this group, the electrocardiogram documented the atrial fibrillation to have been continuous for 39 years. Indications for Operation The specific indication for operation in 47 of the 75 patients (63%) was intolerance of the arrhythmia. In many respects, the patients with paroxysmal atrial flutter or fibrillation were more symptomatic than those with chronic atrial fibrillation. At the very least, they seemed to be less accepting of the fact that they must live with a recurrent arrhythmia that could not be prevented or cured. The major symptoms in the paroxysmal group included dyspnea on exertion, easy fatigability, lethargy, malaise, and a general sense of impending doom during the periods of atrial flutter or fibrillation. All of these patients also complained of the unpleasant sensation of feeling either a rapid heartbeat or a frequently described "floppy heartbeat." They were generally asymptomatic during the periods of normal sinus rhythm. The patients with paroxysmal atrial flutter or fibrillation expressed virtually the same complaints as those patients with other types of supraventricular arrhythmias, such as those associated with the Wolff-Parkinson-White syndrome [16] and atrioventricular node reentry [17]. The patients with chronic atrial fibrillation seemed more resigned and adapted to the sensation of their irregular heartbeat, but all of them complained of exercise limitations, dypsnea on exertion, and easy fatigability. In addition, they frequently expressed concern over the possibility of having a stroke. As already mentioned, all patients had received the maximum amount of tolerable drug therapy preoperatively. In 13 of the 75 patients (17%), the major indication for operation was drug intolerance. Although no patient's arrhythmia was totally abolished by drug therapy, many patients expressed satisfaction with the effect of the drugs in reducing the incidence of their arrhythmia episodes. In the opinion of these 13 patients, however, the effectiveness of the drugs in alleviating the symptoms of the arrhythmia was outweighed by the adverse side effects of the drugs. Fifteen of the 75 patients (20%) had experienced at least one documented episode of cerebral thromboembolism that resulted in a pronounced temporary or permanent neurologic deficit. A documented cerebral thromboembolism in a patient with paroxysmal or chronic atrial fibrillation, in the absence of other demonstrable causes, was considered an absolute indication for operation. This indication was considered absolute because recent studies have demonstrated that, although systemic anticoagulation is effective in reducing the incidence of stroke associated with atrial fibrillation, once a person has had a thromboembolic episode due to atrial fibrillation, systemic anticoagulation does not protect that patient from a subsequent thromboembolic episode [ 18-20]. Despite this fact, we have not considered the threat of thromboembolism to be an indication for operation in patients who have not previously experienced a transient ischemic attack or frank stroke due to atrial fibrillation. Thirty-seven patients (49%) were on sodium warfarin treatment preoperatively. Surgical Procedures The first 33 patients in this series underwent the standard maze procedure as previously described [ For reasons that cannot be elucidated within the scope of this report, the surgical technique was modified slightly in

3 816 COXETAL Ann Thorac Surg 1993; Table 1. Summa y of 7 Patients Who Had Undergone Thoracic Surgical Procedures Before the Maze Procedure Patient Age No. (y) Sex Previous Surgical Procedure 1 38 M Atrial transection procedure ( M Secundum ASD closure 3 39 F Secundum ASD closure 4 40 F Left free-wall accessory pathway division (endocardial approach) and perinodal cryosurgery for AV node reentry tachycardia 5 56 M Pectus excavatum repair 6 74 M CABG X M Aortic valve replacement and CABG X 1 ASD = atrial septal defect; nary artery bypass grafting. AV = atrioventricular; CABG = coro- patients 34 through 48 and again in patients 49 through 75. Despite these technical modifications, no significant differences in the intermediate-term postoperative results (3 to 63 months) attributable to these modifications have yet become apparent. Seven of the 75 patients (9%) had undergone previous thoracic surgical procedures that had a potential impact on exactly how the maze procedure could be performed and on the potential operative risk of the procedure (Table 1). Because the atriotomies comprising the maze procedure must be placed in precise locations to prevent atrial macro-reentry and to preserve atrioventricular synchrony and atrial transport function postoperatively, any previous atriotomy, which necessarily alters the specific placement of the maze atriotomies, has the potential to defeat the effectiveness of the maze procedure. For example, 1 patient had undergone division of a left free-wall accessory atrioventricular connection by the endocardial approach and a concomitant perinodal cryosurgical procedure for the treatment of atrioventricular node reentry tachycardia at another institution. Thus, this patient already had a left atriotomy, a supraannular incision above the mitral valve, a right atriotomy, and cryoablation of the tissues around the atrioventricular node that are normally spared in the maze procedure. The altered positioning required for the maze procedure atriotomies was determined in advance of the operation in this patient, as well as in the other patients who had undergone previous cardiac operations. However, a description of the specific manner in which the atriotomies were altered to accomplish the goals of the maze procedure in each of these patients is not within the scope of this report. Twenty-one of the 75 patients (28%) underwent concomitant cardiac surgical procedures in addition to the maze procedure for the treatment of atrial fibrillation (Table 2). In performing the maze procedure, we have routinely employed moderate systemic hypothermia (28 C) and antegrade and retrograde crystalloid (and, occasionally, blood) cardioplegia, with topical hypothermia accomplished by a cooling jacket. In patients undergoing only the maze procedure who had not had previous surgical treatment (n = 49), the cardiopulmonary bypass time averaged 184 minutes (range, 130 to 256 minutes) Table 2. Cardiac Surgical Procedures Performed in Addition to Maze Procedure in 21 Patients Patient Age No. (Y) Sex Date of Operation Concomitant Surgical Procedure 1 68 M 11/1/90 CABG X F 3/22/91 Mitral valve repair 3 68 M 9/17/91 CABG x M 10/16/91 Patch closure of secundum ASD 5 61 M 11/7/91 CABG x M 12/4/91 Morrow procedure 7 65 M 2/7/92 CABG X M 3/15/92 CABG x M 4/23/92 CABG X M 6/24/92 CABG x M 7/7/92 CABG x M 7/8/92 Mitral valve repair and redo CABG X F 8/5/92 Mitral valve repair M 9/9/92 Repair of anomalous coronary artery F 11/4/92 Mitral valve repair M 11/10/92 CABG x M 11/23/92 LV septal aneurysm and redo CABG x F 11/24/92 Atrial septal aneurysm resection M 12/3/92 CABG x F 12/8/92 Tricuspid valve repair F 12/28/92 Mitral valve repair ASD = atrial septal defect; CABG = coronary artery bypass grafting; LV = left ventricular.

4 Ann Thorac Surg 1993;56: COXETAL 817 and the aortic cross-clamping time averaged 69 minutes (range, 50 to 102 minutes). The first 25 patients in this series were anticoagulated with sodium warfarin for 3 to 6 months after the operation, but this is no longer routinely done. However, all patients with a history of preoperative thromboembolic episodes and those who experience a perioperative transient ischemic attack undergo a 3-month course of warfarin treatment postoperatively. In the absence of specific indications for systemic anticoagulation, patients who undergo the maze procedure alone and those who undergo other concomitant cardiac procedures, including mitral valve repair, are treated with aspirin for 3 months postoperatively. Other routine postoperative medications include spironolactone (Aldactone) for 6 weeks and flecainide for 3 months. In the absence of specific complications, all medications are discontinued at 3 months. Results Mortality and Early Morbidity (Less Than 3 Months) There was one operative death in this series of 75 patients (1.3%), and this occurred in a 44-year-old man with severe hypertrophic obstructive cardiomyopathy (HOCM) in whom atrial fibrillation had developed, resulting in heart failure several months before operation. Medical therapy for both the atrial fibrillation and HOCM had failed in this patient, including two experimental drugs for the control of the HOCM administered at the National Institutes of Health. Pacemaker therapy initiated at that institution specifically for the treatment of severe HOCM had also failed. He underwent the maze procedure concomitant with a Morrow procedure (myotomy and myectomy) for the HOCM and initially did well, being extubated on the first postoperative day. However, he suffered persistent systolic anterior motion of the mitral valve, which caused such a sudden and rapid deterioration in his condition postoperatively that mitral valve replacement was precluded by the presence of severe acute respiratory failure. He died on the tenth postoperative day in normal sinus rhythm. There were no other early or late deaths in this series. The major perioperative morbidity in this series affected the patients who had undergone previous cardiac procedures, especially if they required a concomitant redo cardiac surgical procedure in addition to the maze procedure. Although all of these patients survived, the complexity of their cases is informative in terms of identifying the possible limitations to the applicability of the maze procedure. The three most demanding of these cases involved performing (1) a repeat quadruple coronary artery bypass grafting (redo CABG x 4), mitral valve repair (for severe mitral regurgitation), and the maze procedure (for chronic atrial fibrillation of 4 years duration) in a 74-year-old male cardiologist; (2) a redo CABG x 1, left ventricular septal aneurysm repair, and the maze procedure (for chronic atrial fibrillation of 1 year s duration) in a 67-year-old obese man who had undergone a previous CABG x 1 and aortic valve replacement for calcific aortic stenosis; and (3) the maze procedure alone in a 39-year-old woman who had suffered chronic atrial fibrillation since birth (documented by electrocardiography) and who had undergone pericardial patch closure of a secundum atrial septal defect 27 years previously. Upon entering the old median sternotomy and removing a broken sternal wire from the previous operation in this patient, the right coronary artery was completely severed by the end of the fractured sternal wire before the sternum itself had been opened. Emergency measures were successful in saving the patient, but she ultimately required biventricular assist devices for the first 2 postoperative days, the intraaortic balloon pump for 5 days, and inotropic support for 10 days postoperatively, and she suffered three cardiac arrests during this time. She subsequently completely recovered, but 1 year after operation, recurrent atrial fibrillation developed, representing the only long-term failure of the maze procedure in this series. One of the earliest postoperative complications recognized in these patients was the propensity to conserve large amounts of fluid in the immediate postoperative period. Pulmonary edema developed within the first 7 postoperative days in 5 of the first 7 patients (71%) to undergo the maze procedure. Although not yet documented, we believe the cause to be a dramatic postoperative decrease in the atrial naturietic peptide level triggered by the multiple atriotomies. As a result, we have begun to routinely administer spironolactone to all patients postoperatively. Subsequently, mild pulmonary edema has developed postoperatively in only 4 of 68 patients (6%). Several other early problems have occurred in these patients, all of which have completely resolved with proper therapy and the passage of time. Five of the 75 patients (7%) have required reexploration for postoperative bleeding, 3 have experienced mild pancreatitis, and 2 have suffered serious pneumonia postoperatively. Two patients had postoperative transient ischemic attacks, and 1 patient, a 69 year-old woman who had had chronic atrial fibrillation for 12 years, suffered an intraoperative stroke (1.3%). Although the effects of the stroke have completely resolved, our concern about precipitating the embolization of left atrial mural thrombi by manipulation of the heart has prompted us to avoid contact with the left atrium until the heart has been cardioplegically arrested. Finally, 2 patients had low output syndrome postoperatively, both of which resolved. Early Electrophysiologic Results (Less Than 3 Months) All 75 patients left the operating room either being atrially paced or in sinus rhythm. Perhaps the major early postoperative complication, however, is the development of atrial flutter or atrial fibrillation. Atrial arrhythmias developed in 35 of the 74 survivors (47%) at some time during the first 3 months postoperatively, most of them occurring within the first 10 postoperative days. These postoperative arrhythmias are treated in the same manner as the postoperative atrial fibrillation that occurs after other types of cardiac procedures. We prefer a combination of intravenously administered procainamide and

5 818 COXETAL Ann Thorac Surg 1993;56: digoxin, both of which are converted to the oral route after control of the arrhythmia, and this is continued for 6 weeks to 3 months postoperatively. Fortunately, like other types of postoperative atrial fibrillation, these arrhythmias disappear after the atrium has healed and they do not require long-term medical therapy. Documentation of Early Atrial Transport Function (Perioperative Period) Atrial transport function was documented early in each patient. Before the routine availability of intraoperative transesophageal echocardiography (TEE), the intraoperative assessment of atrial transport function was accomplished primarily by comparing the hemodynamics during atrioventricular sequential pacing with those during ventricular pacing at the same rate [12]. In addition, patients without pacemakers underwent early postoperative dynamic magnetic resonance imaging (MRI) but, because of technical difficulties, these studies proved to be of little value in documenting the presence or absence of postoperative atrial transport function. In the last 45 patients, we have used intraoperative TEE to assess atrial transport function (Figs 2, 3). By analyzing the characteristics of the A wave on the TEE tracings, the effectiveness of atrial contraction can be calculated [21]. Finally, perhaps the most dramatic way of determining the pre, cence or absence of atrial transport function intraoperatively is Fig 3. Documentation of early postoperative right atrial transport function. This intraoperative transesophageal echocardiogram shows the Doppler flow velocity spectra across the tricuspid valve immediately after the maze procedure for the treatment of paroxysmal atrial fibrillation of 7 years' duration. The E wave represents the passive flow of blood across the tricuspid valve during early ventricular diastole due to rapid right ventricular (RV) relaxation. The A wave represents the right atrial contribution to right ventricular filling and is present only if the right atrial contraction is functional. to simply look at the atria, because the atrial contractions are in no way subtle. Permanent Pacemaker Requirements (More Than 3 Months) As of December 31, 1992, 65 patients had been observed for at least 3 months after operation (range of follow-up, 3 to 63 months; mean follow-up, months). Preoperative electrophysiologic studies showed that 17 of these 65 patients (26%) had an abnormal sinoatrial node. As a result, they were told that, although we could abolish their atrial flutter or fibrillation, they would need a permanent pacemaker postoperatively because of the sick sinus syndrome. Five of these 65 patients (8%) had permanent pacemakers in place at the time of operation. Four of the 65 patients (6%) had a normal sinoatrial node preoperatively but required permanent pacemaker implantation postoperatively before discharge from the hospital. One of the patients (the 74-year-old cardiologist) required a permanent pacemaker because of the need to alter the placement of the maze procedure atriotomies in the region of the sinoatrial node. ~ 1 pacemakers 1 im- Fig 2. Documentation of early postoperative left atrial (LA) transport function. This intraoperative transesophageal echocardiogram shows the Doppler flow velocity spectra across the mitral valve immediately after the procedure for the treatment Of paroxysmal fibrilla- planted postoperatively were dual-chamber, rate-responsive (DDD-R) devices. tion of 7 years' duration that had deteriorated to chronic atrial fibrillation for 1 year before operation. The E wave represents the passive flow of blood across the mitral valve during early ventricular diastole due to rapid left ventricular (LV) relaxation. The A wave represents the left atrial contribution to left ventricular filling and is present only if the left atrial contraction is functional. The first two beats are atrially paced (AP) and the next three beats are normal sinus rhythm. Follow-up Evaluations (More Than 3 ~ ~ ~ ~ All 65 Patients were contacted every to months during the first year and approximately yearly thereafter. In addition, all patients were rehospitalized

6 Ann Thorac Surg >993;56;81&24 COXETAL 819 and underwent extensive reevaluation between 3 and 30 months after operation. A routine battery of studies was performed and included the following. Endocardia1 catheter electrophysiology study. Programmed electrical stimulation and high-energy, highfrequency burst pacing of the atria was used in an effort to induce atrial flutter or atrial fibrillation. It was impossible to induce atrial fibrillation in any of the 65 patients. Atrial flutter was induced in 4 patients (6%), but it was considered to be clinically insignificant. Therefore, none of the patients have been treated medically and there have been no subsequent spontaneous recurrences in these patients. 24-hour Holter monitor. Atrial fibrillation was documented in the 1 patient (2%) known to have a recurrence. This patient had also had a pacemaker implanted in advance of the maze procedure. Besides this patient with atrial fibrillation, the predominant rhythm was normal sinus rhythm in 39 patients (60%) and atrial paced rhythm in 25 patients (38%). Exercise stress test. These studies were among the most revealing and important late examinations performed. All of the first 33 patients, except patient 2 who had a modified maze procedure similar to the one we now perform, failed to reach their maximum targeted heart rate during treadmill exercise. The average maximum sinus node response to exercise was 115 beatslmin, with a range of 86 to 142 beatdmin. Patient 2, however, reached a rate of 185 beatslmin during treadmill exercise. We belatedly recognized that one of the incisions in the original maze procedure transected the sinus tachycardia region of the atrial pacemaker complex [22, 231, and therefore the procedure was modified to eliminate that particular incision. Color-flow Doppler evaluation of transmitral and transtricuspid valve flow. These studies proved to be the most accurate way to determine the presence or absence of postoperative atrial transport function (Figs 4, 5). In selected patients without permanent pacemakers, dynamic MRI scans were also obtained to assess atrial function. In addition, during the endocardia1 electrophysiology studies, cardiac output was determined in 42 patients during both atrial and ventricular pacing at the same heart rate to assess the atrial contribution to cardiac hemodynamic performance. The cardiac output increased from 6.1 * 1.24 L/min during ventricular pacing to Llmin during atrial pacing (p < 0.001), confirming the atrial contribution to cardiac output postoperatively. Thus, by means of one or all of these tests, all 64 patients with atrioventricular synchrony were shown to have preserved atrial transport function after the maze procedure. After the first 3 months had passed and the atrial incisions had healed, only 1 patieni (2%) had a recurrence of atrial fibrillation, and this occurred 1 year after operation. The patient was treated with appropriate medical Fig 4. Documentation of late postoperative left atrial transport function. This transthoracic echocardiogram shows the Doppler flow velocity spectra across the mitral valve 6 months after the maze procedure for the treatment of paroxysmal atrial fibrillation of 4.5 years duration followed by chronic atrial fibrillation for 6 months before operation. The patient is in normal sinus rhythm despite the fact that the p wave cannot be discerned on this particular electrocardiographic lead. The presence of the A wave confirms preservation of left atrial transport function. therapy by the referring physician but remains in atrial fibrillation. Eight of 65 patients (12%), all receiving no antiarrhythmia medications at the time, experienced an isolated episode of spontaneous atrial flutter between 4 and 38 months postoperatively. In 2 of these patients, the episode was so brief and clinically insignificant that we elected not to treat the patients medically. Neither patient has had a subsequent recurrence of atrial flutter. The remaining 6 patients (9%) are receiving a single antiarrhythmia drug and none has had a recurrence of atrial flutter. In summary, atrial flutter and atrial fibrillation have been abolished in 64 of the 65 patients (98%) observed for at least 3 months after operation. The arrhythmias have been controlled by operation alone in 58 of the 65 patients (89%) and by operation plus one medication in 6 of the 65 patients (9%). Atrioventricular synchrony has been restored in 64 of the 65 patients (98%). This has been accomplished by restoring a sinus rhythm in 39 (60%) and by atrial pacing in 25 (38%) with abnormal sinoatrial nodes. Finally, atrial transport function has been preserved in all 64 patients with restored atrioventricular synchrony. Comment When the maze procedure was initially conceived, we believed that it would likely be effective in controlling atrial flutter and atrial fibrillation only with the assistance

7 820 COXETAL Ann Thorac Surg 1993;56: of continued medical therapy. We thought that by preventing the development of large macro-reentrant circuits involving virtually the entire atria, the procedure would allow the drugs to be more effective postoperatively, but that all patients would still require some type of medical therapy postoperatively. Thus, it has been a pleasant surprise to find that only 11% of the patients have required postoperative medical therapy (9% effective, 2% failure) and that 89% of the patients have been cured by the operation alone. Nevertheless, we were also surprised at the high incidence of atrial flutter and fibrillation in the immediate postoperative period. Atrial fibrillation developed on the tenth postoperative day in the first patient to undergo the maze procedure in This caused substantial consternation because our prior experimental studies had indicated that the atrium was incapable of fibrillating after the maze procedure. Only after observing this patient s course for several months postoperatively, while simultaneously gaining more insight into the basic electrophysiologic mechanisms involved in atrial flutter and atrial fibrillation through continued animal experimentation, did we come to realize how postoperative atrial fibrillation could occur in patients after undergoing the maze procedure. The ability of the atrium to fibrillate preoperatively or postoperatively is determined by the relationship between the effective refractory period of atrial myocardium and the area of atrium available for the development of a macro-reentrant circuit. As a wave front of depolarization passes across the 0 Rfpolorizatiq: Wavef ront Depolarizatton Wavefront Depolarized Myocardium 0 EFFECTIVE REFRACTORY 0 Fig 6. Representation of the duration of the efective refractory period US the length of an arrow (see text for further discussion). (Reprinted with permission from The Society of Thoracic Surgeons [Ann Thorac S~rg 1993;56:405-9].) atrium, a similar wave front of repolarization trails behind it at a specific distance. This specific distance is the effective refractory period of the atrium in that particular region. This distance can be represented as an arrow, the length of which corresponds to the duration of the atrial refractory period (Fig 6). If one imagines that the arrow is bent such that the tip of the arrow almost (but not quite) touches the tail of the arrow, the size of the circle made with the bent arrow is the smallest that a reentrant circuit in that region can be (Fig 7). Thus, the minimum size of a reentrant circuit is determined by the duration of the local atrial refractory period-the longer the refractory period, the larger the reentrant circuit, and the shorter the refractory period, the smaller the reentrant circuit. Fortunately, the effective refractory period of atrial myocardium is relatively long (in comparison to the size of the atria) in both normal and diseased atria, and 0 Fig 5. Documentation of late postoperative right atrial transport function. This transthoracic echocardiogram shows the Doppler flow velocity spectra across the tricuspid valve (TV) 6 months after the maze procedure for the treatment of paroxysmal atrial fibrillation of 45 years duration, followed by chronic atrial fibrillation for I year before operation. The patient is in normal sinus rhythm despite the fact that the p wave cannot be discerned on this particular electrocardiographic lead. The presence of the A wave confirms preservation of right atrial transport function. - Long Refractory Period - Shorter Refractory Period - Large Reentrant Circuit - Smaller Reentrant Circuit Fig 7. Demonstration of the relationship between the duration of the local atrial refractory period (straight arrow) and the size of a macroreentrant circuit (bent arrow) in the atrium. The duration of the refractory period determines the minimum size that a reentrant circuit can be. The longer the refractory period, the larger the reentrant circuit; the shorter the refractory period, the smaller the reentrant circuit. (See text for further discussion.)

8 Ann Thorac Surg 1993:56:81424 COXETAL 821 rl MAZE PROCEDURE INCISIONS 7 Long Refractory Period -Large macro-reentrant circuit cannot occur after maze procedure Temporarily Shorter Refractory Period Early After Surgery -Smaller macro-reentrant circuit can occur between suture lines of maze procedure fact that, during the perioperative period, the effective refractory period of the atrium shortens, probably because of a combination of factors, including local tissue edema, pericarditis, surgical trauma, and elevated levels of circulating catecholamines. This allows smaller-than-normal reentrant circuits to form in the atrium, circuits that are small enough to form between the suture lines of the maze procedure (Fig 8, lower panel). The result is postoperative atrial flutter with a shorter atrial cycle length (Fig 9) and a more rapid ventricular response (Fig 10) than occurs with "standard" atrial flutter. Medical treatment of this rapid atrial flutter or fibrillation is directed at lengthening the refractory period, which dictates that the reentrant circuit be larger, resulting in its "bumping into" one of the maze procedure suture lines and thereby extinguishing itself (see Fig 8, upper panel). Interestingly, refractory period prolongation (ie, lengthening) is the goal of most antiarrhythmia drug therapy and it was for this reason that we initially believed all maze procedure recipients would probably require drug therapy postoperatively. Fortuitously, the critical area required for the development'of atrial fibrillation in the Fig 8. Electrophysiologic basis for the recurrence of atrial fibrillation in the early postoperative period and for the disappearance of atrial fibrillation after the atria have healed following the maze procedure. In both normal and diseased atria, the refractory period is relatively long, thus limiting the minimum size that a macro-reentrant circuit can be. The maze procedure abolishes atrial fibrillation by positioning atriotomies close enough together to prevent the development of such large macro-reentrant circuits (upper panel). However, in the early postoperative period, the refractory period of the atrium is decreased, allowing the formation of macro-reentrant circuits that are small enough to occur between the suture lines of the maze procedure (lower panel) and resulting in perioperative atrial flutter or fibrillation. Once the atria have healed postoperatively (more than 3 months), the refractory period returns to preoperative ranges and the atria can no longer fibrillate. Lead A EG therefore a relatively large electrically contiguous area of atrium is necessary for a reentrant circuit to form. The maze procedure cures atrial fibrillation for two reasons: (1) the atriotomies are positioned so that it is impossible for an electrical wave front to originate in any one area of the atrium, propagate around major orifices (or regions of functional conduction block) in the left atrium, right atrium, or both, and then return to (reenter) the site of origin (thereby establishing a complete reentrant circuit) without crossing one of the incisions; and (2) the atriotomies are placed close enough together so that there is not normally enough room for a large reentrant circuit to form between them. If a reentrant circuit cannot form, atrial fibrillation cannot occur. How is it possible, then, for atrial flutter or fibrillation to develop in 47% of the patients in the early postoperative period after the maze procedure? The answer lies in the Lead v6 Fig 9. Postoperative atrial electrocardiogram (AEG) demonstrating that the perioperative atrial flutter that may recur early (within 3 months) after the maze procedure has a shorter cycle length, in this case 180 ms, than standard atrial putter, which has a cycle length of 200 ms. This phenomenon results from the formation of smaller-thannormal macro-reentrant circuits between the suture lines of the maze procedure in the early postoperative period (see Fig 8).

9 822 COXETAL Ann Thorac Surg 1993; Fig 10. The shorter-than-normal atrial cycle length characteristic of atrial arrhythmias that occur in the perioperative period after the maze 260 procedure (see Fig 9) result in a faster-than-normal ventricular response rate during these arrhythmias. This 200 graph compares the ventricular response rates during atrial flutter before and soon after the maze procedure in 9 patients. Note that the 160 ventricular rate is faster in the early postoperative period than in the preoperative period in each patient. 100 = PREOP POSTOP 50 PREOP RATE POSTOP RATE Pt.1 Pt.2 Pt.3 Pt.4 Pt Pt.6 Pt.7 Pt.8 Pt atria of most patients is greater than the area between the suture lines of the maze procedure. An obvious exception to this fortunate circumstance would seem to be a very large dilated atria. Because the maze procedure incisions are theoretically positioned in the same places in the large and small atria, it is possible for there to be enough distance between the incisions in the large atria for relatively large reentrant circuits to form. Surprisingly, we have not noticed a difference in the incidence of early postoperative atrial flutter or fibrillation in patients with large atria as compared to those with smaller ones, except in the 1 patient in this series in whom the maze procedure failed. Her atria were the largest of any of the 75 patients yet operated on. However, virtually all the atria in the other 74 patients were at the upper limits of normal in size and most were grossly enlarged. Nevertheless, the maze procedure remained effective in these patients with large atria. There are at least two potential explanations for this: (1) the large dilated atria may also have relatively prolonged refractory periods and, if so, the larger area available for reentry to develop between the suture lines may be effectively counterbalanced by the requirement of a larger reentrant circuit dictated by the prolonged refractory period; and (2) we routinely encompass more of the left atrium within the pulmonary vein-encircling incision in large atria and we also frequently trim portions of a large right atrium along the incision lines before suturing them closed. Finally, we should comment on the terminology employed to describe the success in this study and in other reports of the surgical treatment of atrial fibrillation. When speaking of a cure for atrial fibrillation, one should take into account all of the detrimental sequelae of the arrhythmia and the status of the heart once the arrhythmia has been abolished. Previous nonpharmacologic therapies for atrial fibrillation have been deemed successful, but they have been so only in terms of their limited goals. For example, the success rate of catheter ablation of the His bundle for atrial fibrillation is reported to exceed 90% [24). However, this simply means that permanent heart block can be accomplished by the catheter technique in more than 90% of the cases. The atrial fibrillation in those patients is nmer cured, although the ventricular response rate can be controlled by a permanent pacemaker. Likewise, the corridor procedure has been promoted as a successful treatment for atrial fibrillation. Again, however, the only goal of this procedure is to reestablish a regular heartbeat without a pacemaker in patients with atrial fibrillation. In terms of that limited goal, the corridor procedure is quite successful. However, the atria may continue to fibrillate postoperatively and, even if they do not, they are prevented from contracting in synchrony with their respective ventricle by the effects of the surgical procedure. In contrast to these previously developed procedures, the maze procedure was designed with three specific goals in mind: (1) the permanent ablation of atrial fibrillation, (2) the restoration of atrioventricular synchrony, and (3) the preservation of atrial transport function. Only by realizing all three of these goals can atrial fibrillation be considered cured. Ninety-eight percent of the patients in the present series who have undergone the maze procedure are currently free of atrial fibrillation and have atrioventricular synchrony with preservation of atrial transport function. Therefore, we consider the maze procedure to represent a surgical cure for medically refractory atrial fibrillation. Supported by NIH grants R01 HL32257 and R01 HL References 1. Williams JM, Ungerleider RM, Lofland GK, Cox JL. Left atrial isolation: new technique for the treatment of supraventncular arrhythmias. J Thorac Cardiovasc Surg 1980;80:

10 Ann Thorac Surg 1993; COXETAL Scheinman MM, Morady F, Hess DS, Gonzalez R. Catheterinduced ablation of the atrioventricular junction to control refractory supraventricular arrhythmias. JAMA 1982; Guiraudon GM, Campbell CS, Jones DL, McLellan JL, Mac- Donald JL. Combined sino-atrial node atrio-ventricular node isolation: a surgical alternative to His bundle ablation in patients with atrial fibrillation [Abstract]. Circulation 1985; 72(Suppl 3): Cox JL. Discussion of Defauw JJAMT, Guiraudon GM, van Heme1 NM, Vermeulen FEE, Kingma JH, de Bakker JMT. Surgical therapy of paroxysmal atrial fibrillation with the corridor operation. Ann Thorac Surg 1992;53: Cox JL. Surgical treatment of atrial fibrillation (reply). J Thorac Cardiovasc Surg 1992; Smith PK, Holman WL, Cox JL. Surgical treatment of supraventricular tachyarrhythmias. Surg Clin North Am 1985; 65: DAgostino HJ Jr, Harada A, Schuessler RB, Boineau JP, Cox JL. Global epicardial mapping of atrial fibrillation in a canine model of chronic mitral regurgitation. Circulation 1987; 76(Suppl 4): Yamauchi S, Sat0 S, Schuessler RB, Boineau JP, Matsunaga Y, Cox JL. Induced atrial arrhythmias in a canine model of left atrial enlargement. PACE 990;13: Canavan TE, Schuessler RB, Boineau JP, Corr PB, Cain ME, Cox JL. Computerized global electrophysiological mapping of the atrium in patients with Wolff-Parkinson-White syndrome. Ann Thorac Surg 1988;46: Canavan TE, Schuessler RB, Cain ME, et al. Computerized global electrophysiological mapping of the atrium in a patient with multiple supraventricular tachyarrhythmias. Ann Thorac Surg 1988;46: Cox JL, Canavan TE, Schuessler RB, et al. The surgical treatment of atrial fibrillation: 11. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg 1991;101: Cox JL, Schuessler RB, DAgostino HJ Jr, et al. The surgical treatment of atrial fibrillation: 111. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg 1991;lOl: Cox JL. The surgical treatment of atrial fibrillation: IV. Surgical technique. J Thorac Cardiovasc Surg 1991;lOl: Cox JL, Boineau JP, Schuessler RB, et al. Successful surgical treatment of atrial fibrillation. JAMA 1991;266: Stone CM, Chang BC, Tweddell JS, et al. Ablation of atrial fibrillation by the maze procedure. Surg Forum 1989;40: 21S Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing surgery for the Wolff-Parkinson- White syndrome. J Thorac Cardiovasc Surg 1985;90: Cox JL, Ferguson TB Jr, Lindsay BD, Cain ME. Pen-nodal cryosurgery for AV node reentry tachycardia in 23 patients. J Thorac Cardiovasc Surg 1990;99:44& Petersen P, Boysen G, Godtfredsen J, et al. Placebocontrolled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet 1989;l: Stroke Prevention in Atrial Fibrillation Study Group Investigators. Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med 1990;322: Boston Area Anticoagulation Trial in Atrial Fibrillation Investigators. The effect of low dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323: Hand DE, Lappas DG, Hogue CW Jr, Cox JL. Perioperative transesophageal Doppler echocardiographic verification of atrial transport function following the maze procedure for atrial fibrillation. Surg Forum 1992;43: Boineau JP, Canavan TE, Schuessler RB, Cain ME, Corr PB, Cox JL. Demonstration of a widely distributed atrial pacemaker complex in the human heart. Circulation 1988;77: Boineau JP, Schuessler RB, Canavan TE, Corr PB, Cain ME, Cox JL. The human atrial pacemaker complex. J Electrocardiol 1989;22(Suppl): Scheinman MM, Evans-Bell T. Catheter ablation of the atrioventricular junction: a report of the percutaneous mapping and ablation registry. Circulation 1984;70: DISCUSSION DR VINCENT L. GOTT (Baltimore, MD): Doctor Cox, this is an exciting new procedure with really outstanding results. I wonder if you would take just 1 minute and update us on the current surgical approach. DR COX In the original maze procedure, we placed a straight incision across the top of the atrium, encircled the pulmonary veins, and added several other incisions that allowed the entire atrium to be activated, except for the pulmonary veins and the excised atrial appendages. When we examined these patients several months later and exercised them on a treadmill, they frequently could not attain an optimal rate response with maximal exercise. We had learned about this time that sinus tachycardia always originates at the anterior junction of the superior vena cava (SVC) with the right atrium. Unfortunately, in the original maze procedure, we were placing one incision right through that area, and therefore injuring the sinus tachycardia area. As a result, we modified the maze procedure first by altering the incision around the sinoatrial node slightly, but it then became necessary to divide the SVC for exposure of the left side of the heart. Therefore, we further modified the incisions such that the septa1 incision was placed posterior to the SVC, as diagramed. This operation is considerably easier to perform than the original one, and we have seen some improvement in the later sinus node response to exercise. DR FRED A. CRAWFORD, JR (Charleston, SC): I appreciate very much the opportunity to discuss this nice presentation by Dr Cox and associates, and also the opportunity to review the manuscript in advance. A number of years ago, Dr Cox and I were walking across a bridge in Geneva, Switzerland, where the outflow from Lake Geneva empties into the Rhone River. That day, the current was particularly strong and numerous swirls and eddies were visible on the surface of the water, testifying to the rather chaotic flow of the river. Doctor Cox looked down and said, You know, that s just like atrial fibrillation, and we can cure that surgically. Based on logical thinking and meticulous study in the experimental laboratoly, he was well along at that time into developing the ingenious operation, the 5-year results of which have been described today. Unfortunately, I am unable to discuss this presentation from the perspective of a large personal experience, although I have visited Dr Cox several times, taken part in several maze procedures with him, and recently performed the first such operation

11 824 COXETAL Ann Thorac Surg 1993;56:81424 at our institution. I do, however, have several comments and a few questions. First, this is a beautifully reported series. I was particularly impressed by the careful long-term follow-up of these patients and by the meticulous studies performed, documenting that these patients remain in sinus rhythm not only at rest but also with exercise and despite efforts to induce atrial fibrillation in the electrophysiology laboratory. The data documenting preservation of atrial transport were also impressive. The maze operation is not simple, despite the low operative risk that has been cited. However, it is repeatable and can be learned and applied by other surgeons, as evidenced by Jatene s series and also by the current series from the Cleveland Clinic. Clearly, in good hands, the operation, though difficult, is safe and the outcome superb. Nevertheless, many of us spent some time learning to do operations for the Wolff-Parkinson-White syndrome, only to see them disappear from use literally overnight because of the advent of radiofrequency catheter ablation techniques. My first question then for Dr Cox is: realistically, what is the possibility of some modification of these radiofrequency techniques coming available that can cure atrial fibrillation in the same sense that the maze operation now does? Next, you have described patient intolerance, drug intolerance, and a history of previous cerebral vascular accidents as indications for the procedure. Although the latter two are fairly clear-cut, what is the level of patient intolerance that now serves as an indication? Is this based on the duration of atrial fibrillation or the number of drug failures, or do you now believe that, insofar as safety is concerned, the operation is at the point where it should be offered to any patient who just does not like to be in atrial fibrillation? Are there specific contraindications? Do you perform preoperative electrophysiologic studies on all of these patients, and, if not, do you catheterize them to assess the coronary artery anatomy? Finally, in your manuscript, you speculate on possible mechanisms for the early postoperative atrial fibrillation seen in about half of the patients and on the reasons why the operation could fail in some patients. An example of a potential failure might be a patient with a markedly enlarged left atrium in whom the incisions for the standard maze procedure are simply too far apart to prevent the reentry circuit from recurring or propagating. At the same time, others have proposed that the operation is a useful adjunct to mitral valve procedures when the patient has been in chronic atrial fibrillation preoperatively. These, however, are exactly the same patients who would have markedly dilated left atria. In your series, you had 5 such patients who underwent concomitant mitral valve procedures, and Jatene has reported on 14 others. What do you think the role of the maze procedure is in such patients with mitral valve disease and chronic atrial fibrillation? If performed, does it add significantly to the operative risk or should it be considered routinely? I enjoyed this presentation very much and commend Dr Cox and associates for their ingenious and innovative approach to the treatment of this disabling cardiac problem. I thank The Society for the privilege of discussing the report. DR COX: I would like to thank Dr Crawford for his nice and kind comments. We were once interns together and it is always a privilege and pleasure to have Dr Crawford s thoughts on any subject. In terms of the possibility of catheter ablation for atrial fibril- lation, if you had asked me that question 5 years ago, I would have answered, Absolutely not. I am not so sure I would be quite that confident now, as virtually all the other types of procedures have been taken away from us by catheter ablation. However, I think that catheter ablation for atrial fibrillation will never be as simple as it is now for the Wolff-Parkinson-White syndrome. On the other hand, if you are asking whether 10 years from now we may be able to do this with a closed chest procedure, I think the answer is probably yes. Fortunately, I think that such an approach will require visualization through angioscopes and interpericardial scopes, which hopefully will keep the procedure in the hands of surgeons rather than cardiologists. The patient intolerance issue was raised with regard to surgical indications. It is interesting that, as we have seen more of these patients, one of the things that has impressed us is that patients with atrial fibrillation complain of exactly the same symptoms as patients with supraventricular tachycardia due to the Wolff- Parkinson-White syndrome or atrioventricular node reentry. Thus, once we demonstrated that the maze procedure was safe and effective, we liberalized the indications, just as we had earlier for the Wolff-Parkinson-White syndrome and atrioventricular node reentry. If a patient s life-style is substantially altered and he or she is a young, otherwise healthy person, the same indications that we have used in the past would be in effect. The only specific contraindication we have used is poor left ventricular function preoperatively. In terms of preoperative electrophysiology studies, we perform them in every patient who is in intermittent atrial fibrillation, because we can study them during normal sinus rhythm. In patients with continuous atrial fibrillation, we do not do these studies because we do not think it is worth the risk of cardioverting these patients. We catheterize all patients over the age of 40, male or female, or anyone in whom there is any suspicion of some other type of cardiac disease. The issue of the large atrium is a concern. The patient in our study who represents the one failure had atrial fibrillation for 39 years and had undergone repair of her atrial septa1 defect 27 years before the maze operation. She also had the biggest heart I have ever seen. I think the reason the maze procedure did not work in her is that there was enough room between the incisions for reentry circuits to develop. In the case of large atria, therefore, we make a wider incision around the pulmonary veins to encompass and isolate more of the left atrium and the pulmonary veins, thereby leaving less of the left atrium available for fibrillation. On the right side, before closing the incisions, we frequently trim the edges of the incisions to make the right atrium smaller. We try to keep the distance between the incisions no more than 4 to 5 cm. Whether the maze procedure should be used routinely in patients in chronic atrial fibrillation is difficult to say with complete confidence. There are certainly some patients who can benefit from it. However, patients who have had atrial fibrillation for less than a year before operation for mitral valve disease probably do not need the maze procedure because most of these patients are destined to convert back to sinus rhythm. Patients who have had long-term atrial fibrillation and who are undergoing mitral valve repair or replacement should be considered for the maze procedure if there are no specific contraindications to performing it concomitantly. Again, I appreciate the invitation to present this paper and I appreciate the comments of Drs Gott and Crawford.