Cardiac arrhythmia surgery is based on the concept that

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1 From Fisherman to Fibrillation: An Unbroken Line of Progress James L. Cox, MO, John P. Boineau, MO, Richard B. Schuessler, PhD, Kathryn M. Kater, MSN, and Demetrios G. Lappas, MO Division of Cardiothoracic Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis, Missouri The modern era of cardiac arrhythmia surgery was initiated by Dr Will C. Sealy in May 1968, when he performed the first successful surgical division of an accessory pathway for the treatment of the Wolff-Parkinson-White syndrome. During the subsequent 25 years, arrhythmia operations evolved through a series of innovative surgical procedures capable of curing essentially all refractory clinical arrhythmias. The lessons learned during the development of these surgical procedures ultimately led to the refinement and eventual success of less invasive catheter techniques that have now replaced most of these surgical techniques. The surgical experience gained during these years also made possible the current surgical procedure that is used to treat the most complex, and the most common, of all cardiac arrhythmias, atrial fibrillation. Few areas of any speciality are as clearly defined as the unbroken line of progress that extends from Dr Sealy's first procedure in 1968 to the successful surgical treatment of atrial fibrillation in (Ann Thorae Surg ) Cardiac arrhythmia surgery is based on the concept that scar tissue will not conduct electricity, and, therefore, that electrical activity cannot propagate across a surgical incision or through a site of permanent thermal injury created in heart tissue. This basic concept was first confirmed in humans by Dr Will Sealy in 1968, when he successfully divided an invisible accessory atrioventricular connection in a fisherman from the Outer Banks of North Carolina and, in doing so, cured the man's Wolff Parkinson-White syndrome [1]. During the years following that landmark operation, the surgical technique for the Wolff-Parkinson-White syndrome was refined to the point of being uniformly curative [2-4], and specific surgical procedures were developed for the treatment of ischemic ventricular tachycardia [5-9], nonischemic ventricular tachycardia [10], automatic atrial tachycardia [II, 12], atrioventricular (AV) node reentry tachycardia [13-19], and the atrial flutter and fibrillation spectrum of arrhythmias [20-25]. The evolution of each of these surgical procedures can be traced to the principles that were tested and ultimately established during the early years of arrhythmia ablation operations. Indeed, the principles that now allow our cardiologic colleagues to cure the Wolff Parkinson-White syndrome and AV node reentry by catheter techniques [26, 27] were first established in the operating room using intraoperative mapping and direct surgical approaches to treatment. The only remaining group of arrhythmias not yet amenable to nonsurgical ablation is refractory atrial flutter and fibrillation. Despite the excellent results that have been Presented at the Cardiovascular Surgery Symposium Honoring Will Camp Sealy, MD, Macon, GA, March 4,1994. Address reprint requests to Dr Cox, Division of Cardiothoracic Surgery, Washington University School of Medicine, Barnes Hospital, SI. Louis, MO by The Society of Thoracic Surgeons attained by a variety of surgeons using the maze procedure to treat these arrhythmias [28-32], several questions have persisted regarding the specific indications for surgical intervention and the electrophysiologic and functional status of the atria postoperatively. As a part of this festschrift in honor of Dr Sealy's pioneering work in cardiac arrhythmia surgical treatment, this article addresses some of these contemporary questions regarding the maze procedure. Current Surgical Results of the Maze Procedure Between September 25, 1987 and February 25, 1994, 113 patients underwent the maze procedure for the treatment of atrial fibrillation (AF). There were 83 male and 30 female patients with an average age of 54 years (range, 22 to 74 years). The preoperative arrhythmia was paroxysmal (intermittent) in 59 patients and chronic (continuous) in 54 patients. The average duration of the paroxysmal form of AF was 7 years (range, 0.5 to 30 years) and the average duration of the chronic form of AF was 9 years (range, 0.3 to 39 years). The patients had failed an average of six drugs preoperatively, including amiodarone in 36 of the 113 patients (32%). Thirty-three of the 113 patients (29%) had concomitant cardiac surgical procedures in addition to the maze procedure for AF. Three patients (2.7%) died postoperatively, 1 patient after undergoing a combined maze procedure and Morrow procedure for treatment of chronic AF and hypertrophic obstructive cardiomyopathy (HOCM), another of respiratory insufficiency due to black lung disease, and a third of delayed cardiac tamponade. All perioperative morbidity resolved with appropriate treatment. Normal AV synchrony was restored early postoperatively in all 113 patients, including the 3 patients who died, but 48 of the 113 patients (42%) subsequently re /94/$7.00

2 1270 SEALY SYMPOSIUM COX ET AL Ann Thorac Surg quired antiarrhythmia medication for control of temporary atrial flutter or fibrillation that developed within the first 3 months after operation. All of these patients were subsequently taken off the antiarrhythmia medication between 3 and 6 months postoperatively. As of February 25, 1994, 100 patients had been followed for at least 3 months after operation (range, 3 months to 6 years, 5 months). After allowing this 3-month period for complete healing of the atriotomies, AV synchrony was restored in all 100 patients. Spontaneous AF recurred in 5 of the 100 patients (5%) beyond 3 months after operation. Four of these 5 patients have required long-term medical therapy, and only 1 patient has remained in AF despite this therapy. Spontaneous atrial flutter occurred in 10 of the 100 patients (10%) between 4 and 38 months after operation, only 5 of whom required long-term medical therapy. Thus, only 9 of these 100 patients (4 with AF and 5 with atrial flutter) have required long-term antiarrhythmia medication postoperatively (9%), and AV synchrony has been restored long term in 99 of the 100 patients (99%). In summary, by 3 months after operation, the maze procedure had cured AF, restored AV synchrony, and preserved atrial transport function in 99 of the 100 patients (99%). The procedure has been curative without medications in 91 of these 100 patients (91%) and with medications in 8 (8%), medications having failed in only 1 patient (1%). When Is the Maze Procedure Indicated? Although the findings from several recent studies have documented that systemic anticoagulation leads to a decrease in the incidence of stroke associated with AF, these same studies have also shown that anticoagulation does not protect against a second stroke in a person who has already had one stroke while on anticoagulation. Therefore, if a patient is referred to us with a history of having had an AF-related stroke despite anticoagulation, we recommend surgical intervention, assuming there are no specific contraindications to operation. In our series, 28 of the 113 patients (25%) had experienced at least one documented episode of cerebral thromboembolism that resulted in a considerable temporary or permanent neurologic deficit. Although documented recurrent thromboembolism is an absolute surgical indication, we do not consider the threat of thromboembolism to be an indication for operation in patients who have not previously suffered a transient ischemic attack or frank stroke due to AF. In other words, we do not offer this procedure to a patient who is simply afraid of having a stroke in the absence of other indications. The reason for refusing operation for this lone indication is that it is not yet possible to demonstrate that the maze procedure decreases the threat of a stroke in patients with AF even though their AF is abolished. Although intuitively it stands to reason that abolishing the cause should alleviate the threat, it will take several decades to prove that such is the case. Until we know the long-term effects of the maze procedure on atrial transport function, it does not seem prudent to liberalize the indica- tions for this major surgical procedure to the point that it is applied in every patient with AF regardless of the symptoms. Other surgical indications are somewhat more subjective. The most common indication has been intolerance of the arrhythmia. This intolerance may be manifested in one of several ways, however, and the specific symptoms dictate what type of intervention we recommend for each patient. For example, the maze procedure is ideally suited to a patient who has refractory paroxysmal or chronic AF that is associated with fatigue, malaise, substantial apprehension, dyspnea on exertion, shortness of breath, and so on, that precludes the satisfactory performance or enjoyment of his or her job, daily activities, or life-style. On the other hand, if the AF is bothersome only because the patient is aware of the irregularity of the heartbeat and there are no other associated symptoms, we generally recommend catheter ablation of the His bundle and implantation of a permanent ventricular pacemaker. This closed chest procedure is quite capable of relieving the arrhythmia symptoms and it is usually quite incapable of relieving the other symptoms associated with AF. The specific indication for operation in 70 of the 113 patients (62%) was intolerance of the arrhythmia. In many respects, the patients with paroxysmal atrial flutter or fibrillation were more symptomatic than those with chronic AF. 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. They were generally asymptomatic during periods of normal sinus rhythm. It is worth noting that patients with paroxysmal atrial flutter or fibrillation express virtually the same complaints as those with other types of supraventricular arrhythmias, such as those associated with the Wolff-Parkinson-White syndrome and AV node reentry. In the past, patients have been told that they must simply live with these complaints as there was nothing to offer them if their AF could not be controlled. With the advent of catheter ablation of the His bundle, at least the sensation of an irregular heartbeat could be alleviated. Unfortunately, if the patient has failure symptoms associated with the episodes of AF, the simple restoration of a regular heartbeat, in the absence of synchronous AV contraction, would not be expected to alleviate the unpleasantness associated with this arrhythmia. Therefore, in these patients, it is no longer acceptable to ignore their complaints or to temporize by ablating their His bundle. In the absence of specific contraindications, such patients should be offered a surgical cure. Patients with chronic AF seem more resigned and adapted to the sensation of their irregular heartbeat, but most of them complain of exercise limitations, dyspnea on exertion, and easy fatigability. In addition, they frequently express concern about the possibility of having a stroke. In general, however, we use the same indications for operation in these patients as those in patients with paroxysmal AF. All patients who are considered potential candidates for the maze procedure must have received the maximum amount of tolerable drug therapy preoperatively. Unfortu-

3 Ann Thorac Surg SEALY SYMPOSIUM COX ET AL 1271 Table 1. Documented Function in the Right Atrium Early and Late After the Maze Procedure" Table 2. Documented Function in the Left Atrium Early and Late After the Maze Procedure" Examination Early Late 5/5 68/76 24/25 Examination Visualization at operation Transesophageal echocardiography Transthoracic echocardiography Three-dimensional magentic resonance Atrioventricular versus ventricular pacing Total patients with preserved left atrial function Early 55/55 Late 5/5 55/77 22/25 Visualization at operation Transesophageal echocardiography Transthoracic echocardiography Three-dimensional magnetic resonance Atrioventricular versus ventricular pacing 55/55 79/79 64/79 Total patients with preserved right atrial function = not applicable. = not applicable. nately, the drugs are not always tolerated well by the patients. Thus, in 15 of our 113 patients (13%), the specific indication for operation was drug intolerance. Although no patient's arrhythmia was totally abolished by drug therapy, many patients were satisfied with the effect of the drugs in reducing the incidence of their arrhythmia episodes. In the opinion of these 15 patients, however, the effectiveness of the drugs in alleviating the symptoms of the arrhythmia was outweighed by the side effects of the drugs. Finally, three absolute contraindications to operation have been recognized during the course of our nearly 7-year experience with the maze procedure: (1) prohibitively poor left ventricular function; (2) suspicion of cardiomyopathy in the presence of at least moderately depressed ventricular function; and (3) HaCM. The first of these contraindications has been recognized since the initiation of this type of procedure, and has resulted in a selected group of patients who have undergone the maze procedure. The second contraindication stemmed from our experience with operation for the Wolff-Parkinson-White syndrome in which patients with cardiomyopathy constituted the single highest risk category. The third contraindication was recognized soon after our first operative death in a patient with end-stage HaCM, coupled with our learning that the only operative death in the second largest series of maze procedure patients also occurred in a patient with HaCM. We believe that the reason why the mortality rate is high in HaCM patients who undergo the maze procedure is that AF develops late in their disease, and, therefore, that patients with HaCM who are candidates for the maze procedure have more severe HaCM than the usual patients who undergo operation for that problem. Do the Atria Function After the Maze Procedure? Even if the maze procedure were to abolish AF and restore sinus rhythm with normal AV synchrony, the operation would be a failure if atrial transport function were not maintained. Because the preservation of atrial transport function is considered crucial to the success of this procedure, every effort has been made to document its presence or confirm its absence after operation. Postoperative atrial function was evaluated both in the perioperative period and during the late follow-up examination. Five different methods were used to determine the presence or absence of function in the right atrium alone (Table 1), in the left atrium alone (Table 2), and in the two atria as a unit (Table 3): 1. Intraoperative visualization 2. Transesophageal echocardiography 3. Transthoracic echocardiography 4. Magnetic resonance imaging 5. Atrioventricular pacing versus ventricular pacing In assessing postoperative atrial function, it was assumed that any of these tests could give a false-negative result but not a false-positive result. Thus, if any of these techniques documented the presence of atrial contraction, it was considered preserved. Perioperative Assessment of Atrial Transport Function Perhaps the most dramatic way of determining the presence or absence of atrial transport function intraoperatively is to simply look at the atria, as the atrial contractions are in no way subtle. Before intraoperative transesophageal echocardiography was routinely available, the intraoperative assessment of atrial transport function was ac- Table 3. Documented Function in Either Atrium Early and Late After the Maze Procedure" Examination Early Late Visualization at operation Transesophageal echocardiography 55/55 5/5 Transthoracic echocardiography 72/77 Three-dimensional magnetic resonance 25/25 Atrioventricular versus ventricular pacing 51/53 Total patients with preserved atrial function 79/79 = not applicable.

4 1272 SEALY SYMPOSIUM COX ET AL Ann Thorae Surg complished primarily by comparing the hemodynamics observed during AV sequential pacing and ventricular pacing at the same rate. In addition, patients without pacemakers underwent early postoperative dynamic magnetic resonance imaging, but, because of technical difficulties, the studies proved to be of little value in documenting the presence or absence of postoperative atrial transport function. More recently, we have used intraoperative transesophageal echocardiography to assess atrial transport function. Atrial transport function in both the right and left atrium was documented by at least one of these techniques in every patient during the perioperative period (see Tables 1 to 3). Follow-up Assessment of Atrial Transport Function At more than 3 months after operation, patients underwent transthoracic echocardiography (ECHO), magnetic resonance imaging, AV versus same-rate ventricular pacing in the electrophysiology laboratory, transesophageal echocardiography, or various combinations of these studies (see Tables 1 to 3). The fact that all patients did not undergo all four tests has led to a misconception regarding the late status of atrial function after the maze procedure. The majority of the patients have undergone transthoracic ECHO, but this technique has proved to be only moderately sensitive in detecting the presence of atrial transport function after the maze procedure. For example, transthoracic ECHO alone indicated that there was no right atrial function in 8 of 76 patients (11%) after the maze procedure (see Table 1). However, magnetic resonance imaging performed in the same 8 patients clearly documented the presence of right atrial function. In addition, magnetic resonance imaging showed the right atrium to be functioning in the other 3 patients who did not undergo transthoracic ECHO. Therefore, at least one of these tests showed preserved right atrial transport function was still present late in all 79 patients evaluated to date (see Table 1). Likewise, the findings from transthoracic ECHO suggested that there was no left atrial function in 22 of 77 patients (29%) after the maze procedure (see Table 2). The other tests performed in these patients, however, documented the presence of left atrial contraction in 7 of these 22 patients, in addition to the other 2 who did not undergo transthoracic ECHO. Nevertheless, even after accepting the positive results from all tests, 15 of 79 patients (19%) still showed no evidence of postoperative function in the left atrium after the maze procedure. In these patients, the postoperative cardiac hemodynamics are identical to those observed after the left atrial isolation procedure, in that AV synchrony is present on the right side of the heart (right atrium and ventricle) but not on the left side of the heart (left atrium and ventricle) [11]. We have documented in the past, however, that, in terms of the ability to restore overall cardiac hemodynamics, the functional status of the left atrium is irrelevant so long as the right atrium is contracting in synchrony with the right ventricle. This is the exact physiologic state in the 15 patients without documented left atrial function after the maze procedure. Thus, because the maze procedure either restores AV synchrony (with a sinus rhythm) or allows AV synchrony to be restored (by atrial or AV sequential pacing) in all patients postoperatively, it also restores normal cardiac hemodynamics in all patients, including those without detectable left atrial contraction. What Are the Pacemaker Requirements After the Maze Procedure? Preoperative electrophysiologic studies showed 21 of the 100 patients (21%) had an abnormal sinoatrial node preoperatively. As a result, they were told that, although we could abolish their atrial flutter or AF, or both, they would need a permanent pacemaker postoperatively because of the sick sinus syndrome. In addition, 10 of the 100 patients (10%) already had permanent pacemakers in place at the time of operation. Five of the 100 patients (5%) had a normal sinoatrial node preoperatively, but required permanent pacemaker implantation postoperatively before being discharged from the hospital. Two of these patients required a permanent pacemaker because of the need to alter the placement of the maze procedure atriotomies in the region of the sinoatrial node due to previous cardiac operations. Another patient required permanent pacing because of complete heart block that resulted from repair of an anomalous coronary sinus that required extensive operation in the posterior septal space and pericardial patching of the posterior atrial septum and right atrial free wall. Thus, the maze procedure itself has resulted in injury to the sinoatrial node in only 2 of 100 patients (2%). Summary We are now approaching a 7-year follow-up in patients who have undergone the maze procedure for the management of AF. This operation made its debut clinically in a 38-year-old airline captain who refused to remain grounded because of AF and cerebral thromboembolism. It progressed to include a marathon runner who refused to become sedentary, a grandmother who experienced five strokes and one embolic myocardial infarction in the month before operation, and a cardiologist who did not wish to stop practicing. The procedure has proved to be both safe and effective, and is now considered a viable alternative to a lifetime of arrhythmias, pacemaker dependency, recurrent strokes, drug intolerance, or combinations of these. The maze procedure represents the product of the natural evolution of cardiac arrhythmia surgical procedures, from the days when Dr Sealy struggled to initiate the field of such procedures, through the years of experimental and clinical electrophysiologic mapping of all of the arrhythmias, to the years of animal trials of many failed surgical techniques, and finally to the clinical application of a successful surgical procedure for the most common of all cardiac arrhythmias. Indeed, this evolutionary process has been an unbroken line of progress from the Outer Banks fisherman to the cure of AF. The airline captain, the marathon runner, the grandmother, the cardiologist, and the thousands of others who have since been cured of so-called refractory arrhythmias are fortunate that both Dr

5 Ann Thorae Surg SEALY SYMPOSIUM COX ET AL 1273 Sealy and the fisherman had the courage to "collaborate" on the initiation of a form of surgical therapy that for the first time required a surgeon to operate on cardiac structures that he could not see. Supported by NIH grants R01 HL32257 and R01 HL References 1. Cobb FR, Blumenschein SD, Sealy WC, Boineau JP, Wagner GS, Wallace AG. Successful surgical interruption of the bundle of Kent in a patient with Wolff-Parkinson-White syndrome. Circulation 1968;38: COX JL, Gallagher JI, Cain ME. Experience with 118 consecutive patients undergoing surgery for the Wolff-Parkinson White syndrome. J Thorac Cardiovasc Surg 1985;90: Gallagher JJ, Sealy We, Cox JL, et al. Results of surgery for pre-excitation caused by accessory atrioventricular pathways in 267 consecutive cases. In: Josephson ME, Wellens HJI, eds. Tachycardias: mechanisms, diagnosis, and treatment. Philadelphia: Lea & Febiger, 1984: Guiraudon GM, Klein GI, Sharma AD, Milstein S, McLellan DG. Closed-heart technique for Wolff-Parkinson-White syndrome: further experience and potential limitations. Ann Thorac Surg 1986;42: Guiraudon GM, Fontaine G, Frank R, Escande G, Etievent P, Cabrol C. Encircling endocardial ventriculotomy: a new surgical treatment of life-threatening ventricular tachycardias resistant to medical treatment following myocardial infarction. Ann Thorac Surg 1978;26: Josephson ME, Harken AH, Horowitz LN. Endocardial excision-a new surgical technique for the treatment of recurrent ventricular tachycardia. Circulation 1979;60: Boineau JP, COX JL. Rationale for a direct surgical approach to control ventricular arrhythmias. Am J Cardiol 1982;49: Moran JM, Kehoe RF, Loeb JM, Lichtenthal PR, Sanders JH [r, Michaelis LL. Extended endocardial resection for the treatment of ventricular tachycardia and ventricular fibrillation. 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Elective prolongation of atrioventricular conduction by multiple discrete cryolesions: a new technique for the treatment of paroxysmal supraventricular tachycardia. J Thorac Cardiovasc Surg 1982;84: Holman WL, lkeshita M, Lease JG, Ferguson TB [r, Lofland GK, Cox JL. Alteration of antegrade atrioventricular conduction by cryoablation of peri-atrioventricular nodal tissue. J Thorac Cardiovasc Surg 1984;88: Holman WL, Ikeshita M, Lease JG, Smith PK, Lofland GK, Cox JL. Cryosurgical modification of retrograde atrioventricular conduction: implications for the surgical treatment of atrioventricular node reentry tachycardia. J Thorac Cardiovasc Surg 1986;91: COX JL, Holman WL, Cain ME. Cryosurgical treatment of atrioventricular node reentry tachycardia. Circulation 1987;76: COX JL, ed. Surgery for cardiac arrhythmias. Curr Probl Cardiol 1983; vol Ross DL, Johnson De, Denniss AR, Cooper MJ, Richards DA, Uther JB. 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