The surgical treatment of atrial fibrillation

Volume 101,

April 1991

Number 4

THORACIC AND CARDIOVASCULAR SURGERY The Journal of

J THORAC CARDIOVASC SURG 1991;101:569-83

Original Communications

The surgical treatment of atrial fibrillation III. Development of a definitive surgical procedure On the basis of the known electrophysiologic mechanisms of atrial fibrillation, multiple surgical procedures were designed and tested in dogs to determine the feasibility of developing a surgical cure for human. atrial fibrillation. These experimental studies culminated in a surgical approach that effectively creates an electrical maze in the atrium. The atrial incisiom prevent atrial reentry and allow sinlfi impulses to activate the entire atrial myocardium, thereby preserving atrial transport function postoperatively. Since September 1987, this surgical procedure has been applied in seven patients, five with paroxysmal atrial fibrillation of 2 to 9 years' duration and two with chronic atrial fibrillation of 3 and 10 years' duration. AD seven patients have been cured of atrial fibrillation and none is receiving any postoperative antiarrhythmic medicatiom.

James L. Cox, MD, Richard B. Schuessler, PhD, Harry J. D'Agostino, Jr., MD, Constance M. Stone, MD, Byung-Chul Chang, MD,* Michael E. Cain, MD, Peter B. Corr, PhD, and John P. Boineau, MD, St. Louis, Mo.

From the Division of Cardiothoracic Surgery, Department of Surgery, and the Division of Cardiology, Department of Medicine, Washington University School of Medicine, Barnes Hospital, St. Louis, Mo. Supported by National Institutes of Health Grants ROI HL33722 and ROI HL3225? and an American Heart Association grant, funds contributed in part by the American Heart Association, Missouri Affiliate, Inc. Address for reprints: James L. Cox, MD, Evarts A. Graham Professor of Surgery, Chief, Division of Cardiothoracic Surgery, Suite 3108, Queeny Tower, One Barnes Hospital Plaza, St. Louis, MO 63110. Received for publication May II, 1989. Accepted for publication Oct. I, 1990. *Thirty-seventh Evarts A. Graham Traveling Fellow of The American Association for Thoracic Surgery, 1988. Present address: Department of Surgery, Yonsei University School of Medicine, Seoul, South Korea.

12/1/25818

Atrial fibrillation is one of the most prevalent of all arrhythmias, being present in 0.15% to 1.0% of the general population 1-5 (Table I), 8% to 17% of the population over 60 years of age"? (Table 11), and in up to 79% of patients with mitral valve disease.". When the heart Converts from normal sinus rhythm to atrial fibrillation, three separate sequelae result: (I) a change in the ventricular response, including the onset of an irregular ventricular rhythm and an increase in ventricular rate; (2) detrimental hemodynamic consequences resulting from loss of atrioventricular (AV) synchrony, decreased ventricular filling time, and possible AV valve regurgitation; and (3) an increased likelihood of sustaining a thromboembolic event because of loss of effective contraction and atrial stasis. Pharmacologic treatment of atrial fibrillation is direct569

of

The Journal Thoracic and Cardiovascular Surgery

5 7 0 Cox et al.

Table I. Prevalence of atrial fibrillation in the general population Study Cameron et al.,' 1988 Diamantopoulos et al,,2 1987 Onundarson et al.,3 1987 Hirosawa et al.,4 1987 Savage et al.,5 1983

Country

II

USA (CASS) 18,343 2,000 Greece Iceland 9,067 Japan 31,886 USA (Fram) 5,532 66,828

%

n with AF 0.60 0.15 0.28 0.30 1.00 0.40

CASS, Coronary Artery Surgery Study; Fram, Framingham study; AF, atrial fibrillation.

ed initially at converting the rhythm to normal sinus. When the abnormal rhythm cannot be controlled, pharmacologic therapy is directedat decreasing the ventricular response rate by limiting the numberof atrial impulsesthat can traversethe AV node.Controlofthe heart rate in the presence of continued atrial fibrillation, however, does not alleviate the untoward subjective symptoms associated with an irregular heartbeat, does not restore cardiac hemodynamics to normal, and doesnot decrease the risk of thromboembolism. Most patients are capable of adapting to the irregular heartbeat and compromised hemodynamics associated with the onset of atrial fibrillation eventhough virtually all patients remain symptomatic. However, the threat of thromboembolism is more ominous. At least one million persons in the United States (0.4% of a population of 250 million) have atrial fibrillation. Previous clinical and pathologic studiesindicatethat the prevalence of thromboembolism associated with atrial fibrillation is roughly 33%(330,000U.S. citizens). 10 Approximately 75%of all thromboembolic episodes associated with atrial fibrillation involve the brain (247,500 U.S. citizens). In one series, 60%of cerebroembolic events resultedin death or permanent severe neurologic deficit (148,200 U.S. citizens). 10 From these figures, it is apparent that a more effective form of therapy for atrial fibrillation is needed. Thus it was the purposeof this study to develop a surgicalprocedure capableof curingatrial fibrillation and to applyit to patients with the disease. Limitations of present surgical procedures for atrial fibrillation Left atrial isolation procedure. In 1980well reported the development of a surgical technique capable of isolating the body of the left atrium from the remainder of the heart. Although this procedure was developed primarily for patientswith automatic left atrial tachycardia in whom intraoperativemappingcould not satisfactorily localize the arrhythmogenic focus, it also had potential

Table II. Prevalence of atrial fibrillation in the elderly (>60 years of age) Study

n

% n with AF

Treseder et al.,6 1986 Martin et al.,? 1984 Cobler et al.," 1984 Tammaro et al.,? 1983

4,100 101 316 6,059 10,576

10.1 11-17 8 lOA

10.2

application in the treatment of atrial fibrillation. Our early experimental studiesdocumented that atrial fibrillation could be confined to the left atrium after the left atrial isolation procedure whilethe other three chambers of the heart remained in normal sinus rhythm (Fig. 1). The results of the left atrial isolation procedure are depicted diagrammatically in Fig. 2. The isolated left atrium either remains silent,develops its own asynchronous rhythm, or continues to fibrillate postoperatively. The remainder of the heart, however, is driven by the sinoatrial(SA) node, whichactivates the rightatriumand the ventricles normally. Despiterestoration ofnormalsinusrhythmand normal hemodynamics after the left atrial isolation procedure, thevulnerability ofthe patientto thromboembolism isnot relieved, because the left atrium may continueto fibrillate. Thus, although the left atrial isolation procedure is capable of correcting two of the three detrimental sequelae of atrial fibrillation (the irregular heartbeat and the compromised hemodynamics), it doesnot represent a true cure of atrial fibrillation. Transvenous catheter ablation of the His bundle. In 1982, Scheinmanand associates 12 introduced a technique for ablating the His bundle with a transvenous catheter. A standard recording catheter that is routinely used to record His bundle electrograms was positioned transvenously and 500joules was delivered through the catheter to the His bundle.Because of significant early complications (including one death in the first five cases reported),the electricshockintensity wasdecreased to its presentlevel of 200joules.During the past 8 years,catheter ablationof the His bundle has become the standard procedure for all patientswhorequirenonpharmacologic therapy for atrial fibrillation. Indeed, a review of the International Registry for Catheter Ablationof the His Bundle reveals that 62% of all patients in the registry have had their His bundle ablated because of atrial fibrillation." The effects of His bundle ablation on atrial fibrillation are illustrated diagrammatically in Fig. 3. Corridor procedure. In 1985, Guiraudon and colleagues 14 introduceda surgical technique to treat atri-

Volume 101 Number 4

Surgical treatment of atrial fibrillation, III

April 1991

57 1

RIGHT ATRIUM

LEFT ATRIUM

RIGHT VENTRICLE

LEAD II

I sec Fig. 1. Postoperative leftatrialfibrillation. After the leftatrial isolation procedure, atrial fibrillation isconfined to theleftatrium while therestof theheartremains innormal sinus rhythm. Notethat theright atrium and right ventricle are beating in synchrony and,therefore, the right-sided cardiac output is normal. The leftventricle adapts to this normal right-sided cardiac output immediately, and the result isa normal forward cardiac output despite loss ofsynchronous atrial contraction. The p waves are inconspicuous on the lead II electrocardiogram because of loss ofsynchronous contraction of the leftatrial mass.

al fibrillation in which a strip (or "corridor") of atrial septalmusclebetweenthe SA nodeand the A V nodewas isolated from the rest of the atrial myocardium (Fig. 4). The purposeof isolatingthis strip of atrium was to allow the SA node to drive the ventricles and to prevent the chaotic electricalactivityresponsible for atrial fibrillation from reaching the A V node and ventricles. The corridor procedure has been used clinically and it does restore a regularrhythm to the ventricles. However, because both the left atrium and right atrium are isolated from the ventricles, neither is synchronous with its respective ventricle postoperatively. In addition, because the atria may continue to fibrillate, the vulnerabilityto thromboembolism remains the same postoperatively. This procedure, therefore, results in the same hemodynamiccompromise and in the same thromboembolic vulnerability that the patients experienced preoperatively. Criteria of a satisfactory surgical procedure for atrial fibrillation. The ideal surgical treatment for atrial

fibrillation wouldresult in the abolitionof all three of the detrimental sequelae of the arrhythmia; that is, the procedure would restore a regular ventricular rhythm, restore normal cardiac hemodynamics, and alleviate the patient's vulnerability to thromboembolism (Table III). The only way these criteria of success can be accomplished is by ablating atrial fibrillation, preventing its recurrence, and restoring a sinus or atrial-driven rhythm while preserving enough atrial transport function to prevent stasisof bloodflow in the left atrium. In addition, the procedure must be safe to perform and predictable in its effectiveness. The seriesof experimentalstudiesdescribed herein were performed in an effort to developsuch a surgical procedure.The clinicalefficacy of this procedure is then described. Materials and metbods Experimental protocol. Adult mongrel dogs weighing 25to 35 kg underwent an initial sterile left thoracotomy to create

The Journal of Thoracic and Cardiovascular

5 7 2 Cox et al.

Surgery

Fig. 2. Schematic representation of the results of surgical isolation of the left atrium for the treatment of atrial fibrillation. The thick, heavy black line represents the schematic surgical incision and the stippled area represents that part of the atrial myocardium that has been surgically isolated. Because the isolated left atrium is electrically silent, asynchronous with the left ventricle, or continues to fibrillate, the vulnerability to the development of left atrial thrombi is not alleviated. SAN, Sinoatrial node; RAA, right atrial appendage; LAA, left atrial appendage; PYs, pulmonary veins; AVN, atrioventricular node.

Fig. 3. Schematic representation of the results of catheter ablation ofthe His bundle for the treatment of atrial fibrillation. The induction of complete heart block requires implantation of a permanent pacemaker resulting in a regular heartbeat. However, because the atria are allowed to continue to fibrillate, normal cardiac hemodynamics are not restored and the patients are still vulnerable to thromboembolism. For abbreviations see Fig. 2.

Table III. Surgical procedures designed to treat atrialfibrillation Procedure

Irregular heartbeat

Compromised hemodynamics

Vulnerability to thromboembolism

Cryosurgical ablation of His bundle (1973) Left atrial isolation procedure (1980) Catheter ablation of His bundle (1982) Corridor procedure (1985) Ideal procedure

Corrected Corrected Corrected Corrected Corrected

Unchanged Corrected Unchanged Unchanged Corrected

Unchanged Unchanged Unchanged Unchanged Corrected

Table IV. Patient characteristics Patient No.

Age (yr)

I

5

59 40 52 62 31

6

51

7

38

2 3 4

Sex

Preoperative diagnosis

M M M F M M F

Paroxy.smal AF Paroxysmal AF Paroxysmal AF Chronic AF Chronic AF Paroxysmal AF Paroxysmal AF

Percent of time inAF

Time since onset of AF (yr)

50 95 90 100 100

3 2 3 10 3 3 9

50

50

Associated anomalies None None None

SSS None

SSS None

AF. Atrial fibrillation; SSS, sick sinus syndrome.

mitral regurgitation as described previously.' After at least a 3month interval for the development of left atrial enlargement, the animals underwent a median sternotomy. Control electrograms were recorded during spontaneous sinus rhythm and during pacing of the right and left atrial

appendages, the inferior right atrium, and the right ventricle. The functional refractory period and effective refractory period of the AV node were determined by incrementally pacing both atria at an Sj-S2 interval beginning at 300 msec and progressively decreasing in 10 msec decrements until the ventricles

Volume 101 Number 4 April 1991

failed to capture. Atrial fibrillation was then induced using programmed electrical stimulation by introducing three extrastimuli into either atrium and by burst pacing for 5 seconds at a cycle length of 30 msec and a pulse width of 2.0 msec at twice diastolic threshold. The duration of atrial fibrillation was recorded as the time from the induction of fibrillation to spontaneous termination. If atrial fibrillation did not terminate spontaneously by 5 minutes, the rhythm was electrically cardioverted. For atrial fibrillation to be considered "inducible," we required that three episodes of sustained (>30 seconds) atrial fibrillation be induced in each animal in the control state. Ten-minute periods of stabilization were allowed between each induced episode of sustained atrial fibrillation. Both venae cavae were then cannulated, normothermic cardiopulmonary bypass was instituted, and the ventricles were electivelyfibrillated. The specific surgical procedure to be evaluated was then applied to the atria and, after completion, the ventricles were defibrillated. The animal was then weaned from cardiopulmonary bypass, the cavae were decannulated, and the cardiac hemodynamics were allowed to stabilize for 30 minutes. Electrophysiologic data ~ere recorded exactly as they had been during the control state, and identical programmed electrical stimulation and burst pacing protocols were applied to the atria in an effort to induce atrial fibrillation postoperatively. At the completion of each experiment, the animal was killed and the heart was excised. The body of each atrium and the atrial septum were separated from the remainder of the heart, debrided of fat and connective tissue, and weighed individually. All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National Institutes of Health. The experimental protocol was reviewed and approved by the institutional committee for the care and use of laboratory animals. Initial experimental surgical trials. Our initial attempts at ablating atrial fibrillation were made without the benefit of computerized electrophysiologic mapping capabilities. Although all of the surgical procedures developed and tried during that time eventually failed, several important principles were learned from those initial attempts at managing atrial fibrillation. Thus a brief review of the type of operation that does not cure atrial fibrillation is informative. On the basis of previous studies, we hypothesized that one potential requisite for the development of macroreentry circuits in the atria could be the large areas of "discontinuity" in the free walls of both the right and left atria. The orifices ofthe superior vena cava (SVC) and inferior vena cava (lVC) essentially represent "holes" in the otherwise relatively smooth wall of the right atrium; therefore electrical wave fronts traversing the free wall of the right atrium must circumvent them. Likewise, the smooth continuity of the posterior wall of the left atrium is interrupted by the four orifices of the pulmonary veins and the lateral wall by the large, circular introit of the left atrial appendage. Thus, in the absence of the ability to map atrial fibrillation effectively, it seemed logical to attempt to interrupt the potential "pathways" of conduction between these areas of discontinuity in the left and right atria as an initial step in the development of a surgical procedure to ablate atrial fibrillation. Since the studies by Boineau and colleagues 15 had document-

Surgical treatment of atrialfibrillation, III 5 7 3

Fig. 4. Schematic representation of the results of the corridor procedure for the surgical treatment of atrial fibrillation. Technically speaking, a sinus rhythm may follow this procedure in that the sinus node impulse drives the ventricles. However, because ofloss of both right atrial and left atrial synchrony with the respective ventricles, the hemodynamic abnormalities associated with atrial fibrillation are not improved. In addition, the vulnerability to the development of left atrial thrombi is not alleviated. For abbreviations see Fig. 2.

ed macroreentry around the SVC and IVC orifices during atrial flutter and the studies by Allessie's group'P- 17 had suggested multiple macroreentrant circuits in the left and right atria during atrial fibrillation, our initial attempts at surgical ablation of atrial fibrillation were directed at the left atrium. It was our hypothesis that if the left atrial reentrant circuits could be ablated, atrial fibrillation should not occur but atrial flutter would still be possible because of reentrant circuits in the right atrium. The first procedure used was simple isolation of the pulmonary veins from the left atrium (Fig. 5, A), but it had no effect on the ability to induce or maintain atrial fibrillation. Isolation of the pulmonary veins combined with a lateral incision to the level of the mitral valve anulus was likewise unsuccessful in ablating atrial fibrillation. Isolation of the pulmonary veins combined with a lateral incision to the mitral anulus and a medial incision to the posterosuperior atrial septum and extending down the septum to divide the anterior limbus of the fossa ovalis (Fig. 5, B) resulted in ablation of atrial fibrillation, but atrial flutter immediately ensued. This suggested that the atrial flutter was originating, as suspected, in the right atrium. Therefore the medial incision between the pulmonary veins and the atrial septum was extended between the SVC and IVC orifices, across the body of the right atrium, to the lateral tricuspid valve anulus (Fig. 5, C). Extending this incision in this manner divided the crista terminalis. This combination of incisions invariably ablated both atrial fibrillation and atrial flutter. Subsequent trials were directed at determining how many of these incisions could be deleted without losing the effectiveness of the procedure. We learned that the same results could be obtained without actually isolating the pulmonary veins so long as they were separated from the orifice of the left atrial append-

The Journal' 0/' Thoracic and Cardiovascular

5 7 4 Cox et al.

Surgery

A

B RA

LA

LA

RA

LA

RA

,---- ..

:I ~~PV j):'\ ,' '\!l-\~ " \

~\

\

'--'

c

o LA

RA

,-----

,'~PV ff))'.... J

- ,il \

.. ,'

I

"'~-"""

~

..fY',,,----__

'~' \

\

SVC

~

-- .

" 'i ..

pv}f) t

'"

~~c

I~

_

Fig. 5. Development of the atrial transection procedure. The atria are represented schematically as seen from a posterior view. A, A circumferential incision around the insertion of the pulmonary veins into the left atrium is performed. B, The incision is extended laterally to the mitral anulus and medially to the interatrial septum. C, The incision is extended through the anterior limbus of the fossa ovalis to the tendon of Todaro (not shown) and across the right atrial free wall to the tricuspid anulus. D, The atrial transection procedure (septal incision not shown). The inferior portion of the pulmonary vein incision is eliminated without altering the antiarrhythmic effect. LA, Left atrium; RA, right atrium; SVC, superior vena cava; IVC, inferior vena cava; PV, pulmonary valve. age by the left atrial portion of the incision (Fig. 5, D). This observation greatly simplified the final procedure (Fig. 6), because the incision could be started in the right atrium, carried across the crista terminalis between the SvC and IVe, down the atrial septum across the anterior limbus of the fossa ovalis, and across the top of the left atrium between the pulmonary veins and the left atrial appendage, to the lateral mitral valve anulus. This incision thus precluded contiguous conduction around the most prominent areas of discontinuity in both atria and also divided the most common suspected routes for reentrant circuits in the atria. Moreover, all areas of both atria remained in continuity with the SA node via the lower atrial septum between the tendon of Todaro and the level of the mitral and tricuspid valve anuli medially, thereby preventing the actual isolation of any portion of either atrium. It was believed that this aspect of the procedure, combined with the fact that normal antegrade conduction through the AV node should not be impaired, would

result in the preservation of synchronous contraction of both atria with the ventricles during normal sinus rhythm. This preservation of synchronous AV conduction should, in turn, preserve normal cardiac hemodynamics. This single surgical incision involving both atria proved to be effective in preventing the induction of atrial fibrillation in our canine model (Fig. 7), and it was initially effective in the only patient in whom it was attempted in September 1986. Unfortunately, approximately 5 months postoperatively atrial fibrillation again developed, and the procedure has not been performed again clinically. However, it may remain a viable option in patients in whom intraoperative mapping shows atrial fibrillation to be due to two macroreentrant circuits, one in the right atrium and one in the left atrium (Fig. 8). Development of the present surgical procedure. With the development of computerized intraoperative mapping systems capable of mapping atrial flutter and atrial fibrillation, it was our

Volume 101 Number 4 April 1991

Surgical treatment ofatrialfibrillation. III

575

Cut edges of Atr ial Septum

Fig. 6. Diagrammatic sketch of the atrial transection procedure. Note the bridge of inferior atrial septum near the AV node beneath the lower extent of the septal incision.

Table V. Surgical results Pati ent

.No .

2 3 4

5 6 7

Date of operation

Operative death

Early « 30 days ) complications

Late (>30 days) complications

POSlOp. medications

D,Q,V

9/ 25/8 7

No

None

None

Am,F, F,I, N,P, V Am,D,E

1/ 26/ 88

No

Atrial flutter, drug-induced lupus Atrial flutter

None

None

11 / 22/8 8

No

None

None

9/6 /89 11 /8 /89 11 / 30/ 89 1/19 /90

No No No No

Postop. bleeding, delerium tremens, LLL pneumonia None None Fluid retention Cholestasis

None None None None

None None None None

Failed preop. medi cations*

D,I,Q D, Q,V D,F, P,Q, V AC, Am,D,E, F,N, P, Q, V

LLL. Left lower lobe. 'Drug names: D, Digoxin; Q, quinidine: Y, vera pam il; Am, amiodarone; F. flecainide; I, Inderal; N, Norpace; P. procain am ide; Ac, acebutolol; E, encainide.

hope that a map-guided surgical procedure could be developed for the treatment of the entire spectrum of these arrhythmias. The electrophysiologic data suggested that atrial fibrillation might have the same relationship to atrial flutter that ventricular fibrillation has to ventricular tachycardia, that is, that many types of atrial fibrillation might be preceded by a short period during which the entire atrium is driven by a single "flutterwave" that degenerates into the multiple wavelets characteristic of atrial fibrillation. Much as ventricular fibrillation can be prevented by surgical procedures directed at treating ventricular tachycardia, we thought it possible that atrial fibrillation might be prevented by surgical procedures directed at treating atrial flutter. We still are not certain whether or not this relationship exists between atrial flutter and atrial fibrillation. However, if this hypothesis proves to be true in the future, intraoperative mapping of atrial flutter might eventually be used

to guide surgical intervention. However, our present studies indicate that once complex atrial fibrillation caused by multiple reentrant flutter waves has developed, the changing patterns of atrial activation are so complex that even if detailed on-line atrial fibrillation maps were available to the surgeon, they would be helpful only in guiding the placement of incisions to interrupt specific reentrant circuits that existed at the time a particular map was recorded. Our data indicate that these reentrant circuits are so fleeting and unstable in atrial fibrillation that at the present time map-guided incisions would have no effect on the arrhythmia. It is apparent that perhaps the only way to prevent the atrium from fibrillating is to interrupt all of the potential pathways for atrial macroreentrant circuits that have been identified by intraoperative mapping either experiinentally or clinically, and our eventual surgical approach was based on this principle . The

The Journal' of' Thoracic and Cardiovascular

Cox et al.

576

Surgery

ATRIAL FIBRILLATION 2 Macro-Reentrant Circuits

300 280 260

oQ) 240 In

~

W

~

~

Z 0

!;i

220 200 180 160

...J 140 ...J

c:: CD

RAA

120

Li: 100 ...J

e::(

0::

l-

e::(

A.

80 60

ATRIAL TRANSECTION PROCEDURE FOR ATRIAL FIBRILLATION

40 20 0

PRE-OP

POST-OP

Fig. 7. Effect of the atrial transection procedure on the duration of atrial fibrillation. Preoperatively, sustained atrial fibrillation was induced in all 12 dogs. Postoperatively, the atrial transection procedure prevented the induction of sustained atrial fibrillation in II of 12 dogs. In one dog, the procedure was performed incorrectly and sustained atrial fibrillation could be induced postoperatively. Four dogs (designated by the dashed lines) underwent an intermediate sham procedure after which sustained atrial fibrillation was easily induced. These dogs then underwent the atrial transection procedure which eliminated the ability to induce sustained atrial fibrillation thereafter. surgical incisions are placed on all but one side of the SA node (care being taken to spare its blood supply), dictating that wave-front propagation from the SA node can exit in only one direction. Subsequent surgical incisionsare then placed to direct the wave front to all regions of both atria and finally to the AV node, so that the impulse can then activate the ventricles. Otherwise, the portions of the atria not activated will not contract and atrial transport function will be impaired or lost entirely. Postoperatively, the electrical wave fronts emanating from the sinus node are incapable of turning back on themselves to establish a reentrant circuit because of the electrical refractoriness that immediately trails the activating wave front. Thus these electrical wave fronts are simply extinguished at the final suture lines after completing atrial activation just as they are normally extinguished at the valve anuli between the atria and ventricles. In essence, the principle of this surgical procedure is based on that of a maze (Fig. 9). Although it was recognized that this theoretical surgical approach should be successful, the next task was to decide exactly where to place the various atrial incisions anatomically to create such an electrical maze. To solve this problem, we initially placed colored lines (representing potential surgical incisions) on formaldehyde-preserved canine atria. The lines were

B. Fig. 8. A, The original concept of atrial fibrillation in which two macroreentrant circuits were present, one in the right atrium centered around the orifices of the sve and Iv'C and the second in the left atrium centered around the orifices of the left atrial appendage and pulmonary veins. B, The initial operation that was designed for the treatment of atrial fibrillation caused by the type of reentrant circuits depicted in the upper panel. The atrial transection procedure preserved a bridge of atrial septum across which the sinus impulse could travel to reach all portions of the atria and the AV node. This procedure was characterized by uniform success in our experimental model, but its one clinical application resulted in early success and late failure. For abbreviations see Fig. 2.

placed in such a manner that a sinus node impulse would be "directed" to the AV node while allowing the entire atrial myocardium to be activated by the electrical activity traveling along confined paths throughout the atria. In addition, these colored lines were placed so that it would be impossible for a mac-

Volume 101 Number 4 April 1991

roreentrant circuit, such as those recorded experimentally and clinically during atrial flutter and atrial fibrillation, to exist without crossing one ofthe colored lines. Experiments were then performed on our animal model of atrial fibrillation, and surgical incisions were placed on the dogs' atria in vivo that corresponded to the colored lines drawn on the formaldehydefixed atria. Surgical technique. The initial portion of the procedure (Fig. 10) is performed in the beating heart, the second portion during cardioplegic arrest, and the third portion in the beating heart during systemic rewarming and reperfusion. Standard aortic cannulation is performed in preparation for cardiopulmonary bypass, but both the SVC and IVC are cannulated directly to leave as much room as possible for exposure of both atria. Both the SVC and IVC are dissected free of all surrounding connective tissue, and the roof of the atrium between the aorta and SVC is exposed. Cardiopulmonary bypass is established and the heart is retracted out of the pericardium to expose the pulmonary veins as they enter the left atrium posteriorly. Minimum dissection of the pulmonary veins from the posterior pericardium is performed to make accurate identification easier later. The interatrial groove is developed as completely as possible. The right atrial appendage is excised (A-A') and a perpendicular incision (B-B') is placed from the base of the excised appendage down the posterolateral right atrium, stopping short of the SA node artery. The transverse incision is continued from the medial base of the excised right atrial appendage (A ') across the top of the right atrium to the interatrial septum (C). The heart is then arrested with cold cardioplegic solution and the transverse incision is continued across the septum onto the top of the left atrium to the medial base of the left atrial appendage (C'). The septal portion of the incision (C-D) is carried down the atrial septum, across the anterior limbus of the fossaovalis,and across the fossa ovalisitself, stopping at the level ofthe tendon of Todaro. A 3-0 pledget-supported monofilament suture is placed at the base of the septal incision (D) to prevent tearing during later retraction. Before the left atrial appendage is excised, attention is directed toward isolation of the pulmonary veins. The initial incision for pulmonary vein isolation is a standard left atriotomy performed in the interatrial groove (F). This incision (F) is carried cranially between the right superior pulmonary vein and the SVC until it joins the previously placed transverse atriotomy (C-C'). A marking suture is then placed at this junction to maintain alignment for later closure. The left atriotomy (F) is then extended inferiorly behind the IVC onto the posterior free wall of the left atrium (F-H). Exposure of the inside of the left atrium is regained across the septal incision. At this point in the procedure, before excision of the left atrial appendage, an Army-Navy retractor is inserted into the orifice of the left atrial appendage and lifted upward. This maneuver has proved to be one of the most helpful innovations to improve the exposure for completion of the pulmonary vein isolation. Exposure of this area can be difficult because the entire procedure is performed from the right side looking underneath the aortic root through the transverse sinus. Of course, some of the left atrial incisions can be performed from a posterior approach by retracting the ventricles out of the pericardium and in a cephalad direction, but we have found that approach to be more difficult.

Surgical treatment of atrialfibrillation, III 5 7 7

Fig. 9. Maze procedure for atrial fibrillation. Because atrial fibrillation is characterized by the presence of multiple macroreentrant circuits that are fleeting in nature and can occur anywhere in the atria, a surgical procedure based on the principle of a maze was developed. Both atrial appendages are excised and the pulmonary veins are isolated. Appropriately placed atrial incisions not only interrupt the conduction routes of the most common reentrant circuits, but they also direct the sinus impulse from the SA node to the AV node along a specified route. The entire atrial myocardium (except for the atrial appendages and pulmonary veins) is electrically activated by providing for multiple blind alleys off the main conduction route between the SA node and the AV node, thereby preserving atrial transport function postoperatively. For abbreviations see Fig. 2.

Once the left atrial appendage is put on traction, the pulmonary vein isolation is completed by continuing the posteroinferior left atriotomy from H to G and back up to the transverse atriotomy (C-C'). The pulmonary vein isolation incision is then immediately closed with continuous 3-0 monofilament suture to a point just inferior to the right and left inferior pulmonary veins (between G and H). A vertical incision (H) is placed from the bottom of the pulmonary vein isolation incision to the levelof the mitral valve anulus. While this incision is open, the coronary sinus is dissected free of the AV groove fat pad and encircled with vessel loops at the level of incision H. The coronary sinus is then subjected to circumferential cryoablation at -60 C for 2 minutes. This inferior vertical incision (H) is then closed, beginning at the level of the posterior mitral valve anulus. A separate suture is then placed at the junction of this vertical incision (H) with the incision isolating the pulmonary veins (FG). The pulmonary vein isolation incision (F-G) is then closed in both directions back to the transverse atriotomy (C-C'). The left atrial appendage is then excised (C' -E). with a single transverse incision left extending from the lateral base of the right atrial appendage across the top of both atria to the lateral base of the left atrial appendage (A-A'-C-C' -E). The base of the left atrial appendage is then closed with a continuous 3-0 monofilament suture, starting at the lateral base (E) and working medially to the top of the interatrial septum (C). The septal 0

5 7 8 Cox et al.

The Journal of Thoracic and Cardiovascular Surgery

Fig. 10. Two-dimensional (upper panel)and three-dimensional (lower panel)depiction of the incisions used for the maze procedure.See text for further discussion. incision (C-D) is then closed, air is evacuatedfrom the left side of the heart, and the aortic crossclamp is released. During the rewarming phase,a small perpendicular incision (I) is made from the right atrial transverseincision to the anterior portionof the SVC. A counterincision (J) isthen made from the posterolateral SVC down the posterolateral right atrium to the level of the tricuspidvalveanulus just posteriorto the os of the coronarysinus. This incision is then promptlyclosed with a continuous3-0monofilament suture.The shortanteriorvertical incision (I) is closed with a small pericardial patch to prevent narrowingof the orifice of the SVC by the twoverticalincisions. The remaining portion of the transverse incision extending across the top of the right atrium (C-A '). including the base of the right atrial appendage (A I -A), is then closed, followed by closureof the initialperpendicular incision (B'-B) on the posterolateral right wall,whichcompletes the procedure. Two of the three primary pathways of conduction between the SA and AV nodes, the crista terminalis and the anterior limbusof the fossaovalis, are divided as a result of this surgical procedure. Assuming a normal location of the SA node, an

electrical impulseemanating from that location can propagate inonlyonedirection, namelyposteriorly and inferiorly (Fig. 10). The impulsethen travelsanteriorlyaroundthe lateralbaseofthe right atrium onto the anterior surface of the right atrium. It continues its propagation in a right-to-Ieft directionto the left atrium and enters the atrial septum anteriorly (closed circle on anterioratrial surface,Fig. 10, left upperpanel). The epicardial wavefront continues around the base of the lateral left atrium onto the posteriorsurfaceof the left atrium, whereit is blocked superiorly and inferiorly. The electrical activitythat entersthe atrial septumanteriorly travelsinan anteroposterior directionbeneaththe septalportion of the incision (D) to break through on the epicardial surface posteriorly (closedcircle on posterioratrial surface,Fig. 10, left upperpanel). It thenspreadsto the posteroinferior rightatrium, posteroinferior left atrium, and posterosuperior left atrium between the right superiorpulmonaryveinand the SVC. After this posterior surfaceof the atria has beenactivated,the electrical impulseisblocked fromfurther propagation inanydirection. This procedure accomplishes the goal of allowing a normally

Volume 101 Number 4

Surgical treatment ofatrial fibrillation, III

April 1991

A-V SEQUENTIAL PACING

r----

AEG

VENTRICULAR PACING

579

A-V SEQUENTIAL PACING

ECG

LEAD II

r'"'"';

! Ll.-J~L---l.--LII

V

ECG

V

200

r

AEG

,"-' ! li!~~'-v-'l~~"~l'-vV

V

AP

ImmHg)

~

o 20

I sec Fig. 11. Atrial electrogram (AEG) recorded 4 days after the maze procedure for atrial fibrillation in patient 7. The atrial electrograms were recorded from temporary atrial wires placed at the time of operation and clearly show the presence of atrial (A) activity preceding each ventricular (V) complex.

I

LAP

(mmHg)

~

o 20

r

CVP

(mmHg)

generated impulse to propagate from the SA node and to activate the entire atrial myocardium except for the excised atrial appendages and the pulmonary veins while making it impossible for a large macroreentrant circuit to exist. Thus, regardless of the number of macroreentrant circuits responsible for the development and perpetuation of atrial fibrillation, they cannot occur postoperatively unless the refractory period of the atrial myocardium is so short that microreentrant circuits occur within the relatively small zones of tissue between the various incisions. Such microreentrant circuits may theoretically exist in some patients with so-called "fine" atrial fibrillation. If so, antiarrhythmic medications that prolong atrial refractoriness should convert these microreentrant circuits into macroreentrant ones that would then be precluded by the surgical incisions, thereby resulting in a cure of the arrhythmia. The results of our experimental studies on this surgical procedure have been published elsewhere. 18 In summary, the procedure was extremely successful in ablating atrial fibrillation in our canine model of mitral regurgitation and also in chemically induced atrial fibrillation, which was a much finer and more rapid atrial fibrillation. Chronic animal studies documented preservation of normal atrial transport function, and histologic studies confirmed that the atrial incisions did not result in atrial myocardial ischemia.

Clinical experience Patient characteristics. Seven patients have undergone surgery for atrial fibrillation since Sept. 25, 1987 (Table IV). The

+ o Fig. 12. Hemodynamic data recorded after the maze procedure in patient 5 immediately after being weaned from cardiopulmonary bypass. The patient's underlying sinus rhythm was 65 beats/min. AV sequential pacing was instituted at 85 beats/min (left third of the panel). The atrial wires were then abruptly disconnected, which resulted in ventricular pacing at the same rate (middle third of the panel). The atrial wires were then reconnected, which resulted in a return to AV sequential pacing at the same rate (right third of the panel). Note that with the loss of synchronous atrioventricular contraction, the central venous pressure (CVP) abruptly increased, the left atrial pressure (LAP) abruptly decreased, and the arterial blood pressure (AP) decreased. All three of these parameters immediately returned to normal with the institution of synchronous AV contraction. This confirms preservation of atrial transport function immediately after the maze procedure in this patient who had had chronic atrial fibrillation for 3 years preoperatively. ECG. Electrocardiogram.

five men and two women had an average age of 41 years (range 31 to 62 years). In six patients the indication for operation was failure of medical therapy to control the symptoms (arrhythmias, shortness of breath, and dyspnea on exertion) associated with the atrial fibrillation. Patient 2, a commercial airline cap-

The Journal of . Thoracic and Cardiovascular Surgery

5 8 0 Cox et af.

PATIENT NUMBER

MITRAL VALVE

TRICUSPID VALVE

2

age of time that each patient was in atrial fibrillation and the duration of the problem are listed in Table IV. Two patients had continuous chronic atrial fibrillation, one for 3 years and one for 10 years before the operation. Patients 4 and 6 were known to have the sick sinus syndrome preoperatively and therefore were informed preoperatively that they would need a dual-chamber, rate-responsive pacemaker (DDD-R) postoperatively. All of the patients had normal ventricular function preoperatively and all had slight enlargement of the left atrium as determined by preoperative echocardiography. Only patient 2 had had a previous cardiac operation. He was the one patient in whom the original procedure developed for atrial fibrillation (Fig . 6) had been applied in September 1986.

Surgical results

3

4

5

6

7

Fig. 13. Doppler flow velocity spectra across the mitral and tricuspid valves in each of the seven patients showing the rapid inflow (E) and the corresponding atrial contribution (A) to filling of the ventricles. The presence of A waves documents the preservation of atrial transport function after the surgical treatment of atrial fibrillation (Tracings provided by courtesy of Dr. Julio E. Perez, Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri) . tain, had had a severe transient ischemic attack at the age of 38 years during which he temporarily lost the use of his right upper extremity. He was prescribed anticoagulants and grounded. Five patients had paroxysmal atrial fibrillation. The percent-

There were no operative deaths (Table V).An average of 4.6 drugs had been unsuccessful before the operation. Early complications included temporary intermittent atrial flutter and a drug-induced lupus syndrome in patient 1 (he had been placed on a regimen of procainamide for 2 months because of an undetermined type of postoperative arrhythmia on the fifth postoperative day); postoperative bleeding necessitating reexploration and delirium tremens complicated by pneumonia, both in patient 3; excessive fluid retention in patient 6; and postoperative cholestasis that resolved without treatment in patient 7. In addition, atrial flutter developed on the eighth postoperative day in patient 2 because the coronary sinus cryolesion failed to ablate all of the atrial fibers coursing through the wall of the coronary sinus. The atrial flutter was permanently ablated on Sept. 7, 1988, by delivering an electric shock to the atrial septum via a transvenous catheter and a normal sinus rhythm has been present since that day. Another observation that was made in these patients related to their propensity to retain fluid postoperatively. We believe this to be due to a temporary depletion of the stores of atrial natriuretic peptide during the first 2 to 3 weeks after the operation, probably as a result of the multiple atrial incisions. We have not measured serum atrial natriuretic peptide levels in these patients, however, because the assay technique in humans is not sensitive enough to detect a significant decrease in normal levels.• This problem is much less significant since we have instituted postoperative aldactone therapy routinely. Moreover, it should also be mentioned that an osmotic diuretic, such as mannitol, is much more effective than other types of diuretics for the management of fluid and electrolyte balance in these patients during the early postoperative period. All early complications resolved complete• Personal communication with PhillipNeedleman. PhD,formerly Professor and Chairman, Department of Pharmacology, Washington University Schoolof Medicine, St. Louis, Missouri, and co-discoverer of atrial natriuretic peptide.

Volume 101 Number 4 April 1991

Surgical treatmentof atrialfibrillation, III 5 8 1

Table VI. Postoperative electrophysiologic evaluation Time operation (mo)

24-Hour Holter monitor

Resting sinus rate (beats/min)

3/26/90 4/23/90 3/9/90 2/20/90

30 27 16 5.5

NSR NSR NSR A paced

78 82 50 57

136 185 119 100

5 6

4/11/90 2/7/90

5.0 2.2

NSR A paced

76 51

124 (61%) 100 (A paced)

7

4/7/90

2.6

NSR

88

125 (69%)

Patient No.

Date of study

I 2 3 4

since

Stressed sinus rate (beats/min)

A-H interval (msec) (normal: 60-125)

H-V interval (msec) (normal: 35-55)

65 100 65 60 (63%) 70 75 (60%) 90

55 50 55 70

Not Not Not Not

55 48

Not inducible Not inducible

51

Not inducible

(86%) (104%) (71%) (A paced)

Inducibility ofAF inducible inducible inducible inducible

AF. Atrial fibrillation; NSR, normal sinus rhythm; A, atrium.

Table VII. Assessmentofpostoperative atrial transport function Patient No.

Cardiac output with AV pacing (L/min)

Cardiac output with V pacing (Lfmin)

Atrial contraction on dynamic M RI scan

LA contraction on Doppler

RA contraction on Doppler

Subjective symptoms

I 2 3 4 5 6 7

6.2 6.1 6.5 6.6 6.2 10.2 5.8

5.8 6.9 6.3 5.2 5.8 10.1 4.8

Present Present Present but diminished Not performed Present Not performed Present

Present Present Absent Questionable Present Present Present

Present Present Present Present Present Present Present

Dyspnea on heavy exertion None None None None None None

AV. Atr~oventricular; Y, ventricular; MRI, magnetic resonance imaging; LA, left atrial; RA. right atrial.

ly and there have been no late complications in any of the patients. All seven patients were cured of atrial fibrillation after the operation and none of them are receiving postoperative antiarrhythmia medications. The predominant rhythm in the early postoperative period was junctional, with sinus rhythm resuming as early as 4 days in patient 7 and as late as 3 weeks in patient 3 (Fig. II). However, 24-hour Holter monitoring performed from 2 months to 2V2 years postoperatively (all between Feb. 7, 1990, and April 23, 1990) has demonstrated sinus rhythm or an atrially generated rhythm to be present in all seven patients, although, as expected, the two patients with the sick sinus syndrome preoperatively are not in sinus rhythm continuously (Table VI). Patient 4 is atrially paced (DDD-R) approximately 5% of the time because of intermittent slowing of the sinus rhythm, usually during sleep. Patient 6 is atrially paced approximately 50% of the time for the same reason. A formal endocardial catheter electrophysiologic study was performed in all seven patients from 2 months to 2.5 years postoperatively. High-dose epinephrine infusions were combined with programmed electrical stimulation and high-energy, rapid burst pacing of the atria in an

attempt to induce atrial fibrillation. Despite these aggressive maneuvers, atrial fibrillation could not be induced in any patient postoperatively; Atrial flutter was inducible in patient I but it has not occurred clinically despite the lack of antiarrhythmic drug therapy. He receives no medications. The effects of the operation on the specialized conduction tissues of the heart were also evaluated during the postoperative electrophysiologic studies. Surgery seemed to have the effect of limiting the maximum attainable sinus rate during exercise to 120 to 130 beats/min in some patients and not in others. However, the AV conduction time (A-H interval) and the His bundle-to-ventricle conduction time (H-V interval) were normal in all patients postoperatively with the exception of slight H -V prolongation in patient 4. Every effort was made to document preservation of atrial transport function postoperatively. AV sequential pacing was compared with ventricular pacing alone immediately after the patients were weaned from cardiopulmonary bypass. These studies usually demonstrated significant atrial transport function immediately postoperatively even in the patients with chronic atrial fibrillation (Fig. 12). During the late postoperative elec-

The Journal of Thoracic and Cardiovascular Surgery

5 8 2 Cox et al.

trophysiologic study, both atrial and ventricular temporary pacing catheters were inserted in the five patients who did not already have permanent dual-chamber pacemakers in place (Table VII). Thus in all seven patients it was possible to compare the cardiac output during AV sequential (DVI) pacing with the cardiac output during ventricular (VOO) pacing at the same rate. In this manner, the contribution of atrial contraction to forward cardiac output could be evaluated, albeit in a somewhat gross fashion. Six of seven patients had an increase in the cardiac output with synchronous atrial contraction. The ability of this test to detect significant atrial transport is paradoxically limited because of the presence of normal ventricular function, which minimizes the importance of atrial contraction to forward cardiac output. Dynamic magnetic resonance imaging scans were also performed in the five patients without permanent pacemakers (which preclude the ability to perform these scans). Four of the fivescans (all except patient 3) clearly documented that the atria contracted forcefully postoperatively. Most important, echocardiography and Doppler color flow studies in all seven patients confirmed the preservation of atrial transport function in all seven patients from 2 months to 2 $ years postoperatively (Fig. 13). This is considered to be the most crucial evidence documenting preservation of atrial transport function. Not only is this generally recognized to be the most reliable noninvasive test of atrial function, but one only needs to document the presence of a synchronous atrial contraction wave on the study to rule out the problem of stasis in the atria, the prerequisite of mural thrombus formation, and the precursor ofthromboemboli.associated with atrial fibrillation. Finally, all patients have experienced remarkable subjective improvement and each claims to feel the same now that he or she did before the problem of atrial fibrillation developed. Although the follow-up period is still relatively short, there have been no long-term complications of the operation and no recurrences of atrial fibrillation or of other atrial arrhythmias. The patients were routinely given warfarin sodium for 3 months and then all anticoagulation was stopped. No thromboembolic events have occurred postoperatively in any of the patients. Comment

These preliminary clinical results of surgery for the treatment of atrial fibrillation are most encouraging. One of the attractive characteristics of this particular surgical procedure is that, unlike most antiarrhythmia procedures, it does not depend on intraoperative mapping because it is performed in exactly the same manner in all patients with atrial fibrillation. This characteristic provides the potential for widespread application. Therefore it is not

necessary for this procedure to beconfined to institutions that have sophisticated intraoperative mapping capabilities. Only in this manner can such a procedure be offered to all the patients who might benefit from it. Addendum A total of 14 patients have now received the operation, and it has been successful in all. REFERENCES I. Cameron A, Schwartz MJ, Kronmal RA, Kosinski AS. Prevalence and significanceof atrial fibrillation in coronary artery disease (CASS Registry). Am J Cardiol 1988;61: 714-7. 2. Diamantopoulos EJ, Anthopoulos L, Nanas S, Maliaras G, Chrisos D, Moulopoulos SD. Detection of arrhythmias in a representative sample of the Athens population. Eur Heart J 1987;8(suppl D): 17-9. 3. Onundarson PT, Thorgeirsson G, Jonmundsson E, Sigfusson N, Hardarson T. Chronic atrial fibrillation. Epidemiologic features and 14 year follow-up: a case control study. Eur Heart J 1987;8:521-7. 4. Hirosawa K, Sekiguchi M, Kasanuki H, et al. Natural history of atrial fibrillation. Heart Vessels 1987;suppl. 2:14-23. 5. Savage DD, Garrison RJ, Castelli WP, et al. Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham study). Am J Cardiol 1983;51:1375-8. 6. Treseder AS, Sastry BS, Thomas TP, Yates MA, Pathy MS. Atrial fibrillation and stroke in elderly hospitalized patients. Age Aging 1986;15:89-92. 7. Martin A, Benbow LJ, Butrous GS, Leach C, Camm AJ. Five-year follow-up of 101 elderly subjects by means of long-term ambulatory cardiac monitoring. Eur Heart J 1984;5:592-6. 8. Cobler JL, Williams ME, Greenland P. Thyrotoxicosis in institutionalized elderly patients with atrial fibrillation. Arch Intern Med 1984;144:1758-60. 9. Tammaro AE, Ronzoni D, Bonaccorso 0, et al. Le aritmie nell'anziano. Minerva Med 1983;74:1313-8. 10. Fisher CM. Embolism in atrial fibrillation. In: Kulbertus HE, Olsson SB, Schlepper M, eds. Atrial fibrillation. Molndal, Sweden: AB Hassle, 1982;192-210. II. WilliamsJM, Ungerleider RM, Lofland GK, CoxJL. Left atrial isolation: a new technique for the treatment of supraventricular arrhythmias. J THORAC CARDIOVASC SURG 1980;80:373-80. 12. Scheinman MM, Morady F, Hess DS, et al. Catheter-induced ablation of the atrioventricular junction to control refractory supraventricular arrhythmias. JAMA 1982;248: 851-5. 13. Scheinman MM, Evans-Bell T. Catheter ablation of the atrioventricular junction: a report of the percutaneous mapping and ablation registry. Circulation 1984;70: 1024-9. 14. Guiraudon GM, Campbell CS, Jones DL, McLellan JL,

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MacDonald 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(Pt 2):III220. 15. Boineau JP, Schuessler RB, Mooney CR, et al. Natural and evoked atrial flutter due to circus movement in dogs: role of abnormal atrial pathways, slow conduction, nonuniform refractory period distribution and premature beats. Am J CardioI1980;45:1167-81. 16. Allessie MA, Bonke FIM, Schopman FJG. Circus movement in rabbit atrial muscle as a mechanism of tachycar-

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dia. III. The "leading circle" concept: a new mode of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res 1977;41:9-18. 17. Alessie MA, Lammers WJEP, Bonke FIM, Hollen JM. Experimental evaluation of Moe's multiple wavelet hypothesis of atrial fibrillation. In: Zipes DP, Jalife J, eds. Cardiac electrophysiology and arrhythmias. Orlando, Florida: Grune & Stratton, 1985:265-75. 18. Stone CM, Chang BC, TweddelJ JS, et al. Ablation of atrial fibrillation by the maze procedure. Surg Forum 1989; 40:213-5.