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J Thorac Cardiovasc Surg 1999;118:628-635
© 1999 Mosby, Inc.
SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE |
From the Divisions of Thoracic and Cardiovascular Surgerya and Cardiovascular Diseases and Internal Medicine,b Mayo Clinic and Mayo Foundation, Rochester, Minn.
Address for reprints: Hartzell V. Schaff, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
| Abstract |
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| Introduction |
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In patients with severe mitral valve regurgitation and atrial fibrillation, the Cox maze procedure
6-10 has not been used routinely by most surgeons because of the generally low risk of postoperative thromboembolism and because of the potential of this additional procedure to increase the mortality of valve repair. Although several authors have reported that atrial fibrillation was successfully ablated with the Cox maze procedure in patients undergoing mitral valve procedures,
7-10 no data demonstrate a long-term benefit of reduced late morbidity and mortality associated with the elimination of atrial fibrillation. We have used the Cox maze procedure in conjunction with valve repair in patients with severe mitral regurgitation and atrial fibrillation, anticipating a low risk of thromboemboli when sinus rhythm is maintained and the long-term benefit of avoiding anticoagulation with warfarin. The purpose of this study was to assess the early- and intermediate-term results of this combined procedure.
| Patients and methods |
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For this study, we retrospectively reviewed and collected data from operative notes, anesthesia records, clinical case histories, and laboratory investigations, including electrocardiograms, echocardiograms, and cardiac catheterization reports. Follow-up data were collected from Mayo Clinic records of outpatient visits and correspondence with patients and referring physicians. A total of 204 clinical, hemodynamic, electrocardiographic, and echocardiographic variables were entered into a computerized database and analyzed. Follow-up data more than 6 months after the operations were available for all patients.
Patients.
Demographic data and pertinent cardiac information are given in Table I. Groups were similar in age, gender distribution, and New York Heart Association (NYHA) functional class. Similar proportions of patients in each group had previous myocardial infarction, stroke, rheumatic fever, or cardioversion. The decision to add the Cox maze procedure was made by the surgeon; these patients represent the first group to have combined procedures at our clinic. Eight patients in the control group had previous heart surgery, but no patient in the maze group had previous heart surgery (P = .02). Also, associated coronary artery disease was more frequent in the control group than in the maze group (P = .01).
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Surgical procedure.
Methods of mitral valve repair varied according to the pathologic findings; an annuloplasty ring was used in almost all patients. The maze III procedure described by Cox and associates
11,12 was used.
Statistical methods.
Comparisons of the characteristics between the 2 patient groups were carried out with
2 tests or Fishers exact tests for nominal variables, with 2-sample t tests or Wilcoxon rank sum tests for continuous variables, and with Wilcoxon rank sum tests for ordinal variables. Survival and survivorship free of atrial fibrillation, bleeding, and stroke were estimated by means of the Kaplan-Meier method. Survivorship curves were compared with the log-rank test. The relationships of continuous variables to survivorship and the multivariate relationship of multiple risk factors to survival were evaluated with the Cox proportional hazards model.
| Results |
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Associated procedures included coronary artery bypass grafting (n = 28), repair of atrial septal defects or patent foramen ovale (n = 14), tricuspid valve repair (n = 6), pericardiectomy (n = 1), and aortic valve replacement with tissue valve (n = 1). There was no difference between the 2 groups in terms of incidence of associated procedures except that concomitant coronary artery bypass grafting was performed in 7 patients in the maze group (18%) and 21 patients in the control group (36%) (P = .05).
Postoperative morbidity and mortality.
No in-hospital deaths occurred in either group. Hospital stay in the maze group was prolonged compared with that in the control group (12.6 ± 6.4 days vs 9.3 ± 3.4 days, P = .003). Postoperative complications included bleeding (n = 5), respiratory failure (intubation > 72 hours) (n = 2), intra-aortic balloon pump insertion (n = 2), pneumonitis (n = 2), pneumothorax (n = 1), and gastrointestinal bleeding (n = 1). One patient in each group required postoperative pacemaker implantation for junctional bradycardia. There was no difference between the 2 groups in the incidence of complications.
Survival and late events.
All patients were observed for a minimum of 6 months after the operation. Overall 2-year survival was similar for the 2 groups (maze group, 92% ± 5%; control group, 96% ± 3%; Fig 1). There were 7 late deaths. In the maze group, 1 patient died of congestive heart failure, 1 had ventricular tachycardia, and another died of an unknown cause. In the control group, 4 late deaths were due to pulmonary embolism, intracerebral hemorrhage, cerebral infarction, and myocardial infarction. Three patients (1 in the control group, 2 in the maze group) required reoperation for recurrent mitral valve regurgitation (2 patients) or hemolysis.
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Freedom from stroke and bleeding at 2 years was 95% ± 5% in the maze group and 86% ± 6% in the control group ( P = .08). If we consider only bleeding associated with warfarin treatment, freedom from combined stroke and bleeding at 2 years was 100% in the maze group and 90% ± 8% in the control group ( P = .04; Fig 3).
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The relationship between return of sinus rhythm and duration of preoperative atrial fibrillation is shown in Table IV. Only 18.5% of patients in the control group who had chronic atrial fibrillation more than 3 months regained normal sinus rhythm. In the maze group, 76% of patients who had chronic atrial fibrillation longer than 3 months regained normal sinus rhythm (Table IV
).
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The spectrum and intensity of preoperative antiarrhythmic therapy were comparable for the 2 groups, but after operation, the number of antiarrhythmic drugs decreased over time in the maze group from 1.31 ± 0.69 to 0.71 ± 0.76 at follow-up, compared with 1.26 ± 0.78 to 1.16 ± 0.79 for the control group (P = .01). In the maze group, 45% of patients were free of all antiarrhythmic agents at most recent follow-up, compared with 22% in the control group ( P = .02).
With respect to warfarin, 63% of patients in the maze group were not taking warfarin compared with 50% in the control group, but this difference did not reach statistical significance. However, 9 patients (23%) who had no episodes of atrial fibrillation after surgery are still taking warfarin, and the drug presumably may be safely discontinued. In addition, 5 patients in the control group who had a permanent pacemaker for profound bradycardia with underlying atrial fibrillation stopped taking warfarin.
| Discussion |
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Atrial fibrillation is prevalent among patients referred for operations on the mitral valve; previous studies have shown that approximately 30% to 40% of patients were in chronic atrial fibrillation when mitral valve repair was scheduled.
1-5 In our experience, approximately 80% of the patients who had preoperative chronic atrial fibrillation more than 3 months before the operation remained in atrial fibrillation after successful mitral valve repair.
5 In the present investigation, the adjunctive Cox maze procedure increased the restoration of normal sinus rhythm to 82% of patients, a finding similar to that of other studies.
8-10 Furthermore, our data suggest that concomitant Cox maze procedure reduced the combined risks of stroke and anticoagulant-related bleeding, as well as decreased the need for antiarrhythmic drugs.
Risks of stroke in nonrheumatic atrial fibrillation have been studied extensively in regard to primary prevention
15-18 and secondary prevention.
19,20 Recent prospective studies have shown that the risk of stroke in placebo-treated patients with atrial fibrillation is 5% to 8% per year.
15,16,18 The reduction in risk of stroke by anticoagulation with warfarin ranges from 37% to 86%, but chronic anticoagulation with warfarin carries a risk of bleeding from 0.5% to 2.8% per year.
21,22 Furthermore, anticoagulation with warfarin requires careful follow-up and adjustment of dosage; use of a low dose of warfarin and aspirin without monitoring the international normalized ratio is not as effective as conventional anticoagulation with warfarin.
23
Maintenance of sinus rhythm and avoidance of anticoagulation with warfarin may reduce medical expenses; long-term anticoagulation with warfarin is estimated to cost about $800 per person annually in the United States.
24 Medical expenditures for care of patients with stroke or bleeding also are substantial.
24 In the early results of the present study with 21 months of mean follow-up, about 36% of patients in the maze group (50% in the control group) were still taking warfarin. We expect that the majority of patients in the maze group who are in sinus rhythm eventually will discontinue taking warfarin.
An additional benefit of concomitant Cox maze procedure for restoration of sinus rhythm is reduced need for antiarrhythmic agents. The results of the Cardiac Arrhythmia Suppression Test (CAST) study and other clinical trials suggested that antiarrhythmic agents commonly used for atrial fibrillation, such as quinidine and amiodarone, have proarrhythmic effects.
25-27 After the Cox maze procedure, the number of antiarrhythmic drugs was decreased, and 44% of patients were free of antiarrhythmic therapy.
The major limitation of our study is that it was not randomized, and there were some differences in the baseline characteristics of patients in the 2 groups. The decision for or against an adjunctive Cox maze procedure reflected the surgeons experience with the procedure, as well as the anticipated difficulty with mitral valve repair. With experience, however, we rarely decided against a concomitant Cox maze procedure on the basis of the planned operation; more often, local factors such as extreme fragility of tissue, unusual bleeding, or poor exposure militated against a concomitant maze procedure. Selection bias is reflected by the absence of patients with previous cardiac operations and coronary artery disease in the maze group. However, we do not consider previous heart surgery alone to be a contraindication to the procedure and have successfully performed the Cox maze procedure in several patients having second or third procedures.
Of interest, the duration of preoperative atrial fibrillation was longer in the maze group than in the control group, and the proportion of patients in chronic atrial fibrillation was also greater; these factors would be expected to increase the risk of late atrial fibrillation. Among patients in the control group who had chronic atrial fibrillation more than 3 months, only 18.5% had a return of sinus rhythm (Table IV
). In the maze group, 76% of patients who had chronic atrial fibrillation longer than 3 months regained normal sinus rhythm. Thus the addition of the Cox maze procedure appears to be particularly useful in patients with chronic atrial fibrillation of more than 3 months duration. Of note, survival free of recurrent atrial fibrillation in a control group with paroxysmal atrial fibrillation was only 49% ± 1% at 2 years (Fig 4
). The complete suppression of paroxysmal atrial fibrillation with the Cox maze procedure in this study suggests that the combined operation may be of benefit for patients who have multiple episodes of paroxysmal atrial fibrillation necessitating long-term anticoagulation before mitral valve repair.
Some groups have advocated only the left-sided incisions to ablate atrial fibrillation in patients having mitral valve repair or replacement to reduce morbidity and mortality.
28 In our series, there was little difference in either survival or perioperative morbidity between patients having valve repair with and those having valve repair without concomitant maze procedure, and it is unlikely that limiting the incisions to the left atrium would have influenced the clinical results.
Reduction of left atrial size by resection of atrial muscle at the time of the Cox maze procedure has been described.
7 However, multivariable analysis of our data did not confirm that preoperative left atrial size was predictive of recurrence of atrial fibrillation. Therefore the role of additional resection to reduce atrial size during the Cox maze procedure is questionable.
Although 9 patients who had the Cox maze procedure were in junctional rhythm at the time of hospital dismissal, only 1 required a permanent pacemaker and 4 of the 9 had return of sinus rhythm. In the experience at Barnes Hospital, 25% of patients who had the Cox maze procedure required permanent pacemaker placement.
29 Persistent junctional rhythm may indicate long-standing sinus node dysfunction and, certainly, this predisposes patients to reentrant atrial arrhythmias and stroke.
30 Among the other 4 patients with junctional rhythm at dismissal, recurrent atrial fibrillation developed in 2 and atrial flutter in 2. It has been reported that up to 50 weeks are required until normal sinus rhythm is restored.
7 Theophylline therapy was proposed for early sinus node dysfunction with slow junctional rhythm after the Cox maze procedure,
7 but we have not used this.
Our experience suggests that the Cox maze operation is a safe and reliable adjunctive procedure for selected patients with atrial fibrillation undergoing mitral valve repair. It seems particularly useful for patients with chronic atrial fibrillation of more than 3 months duration before the operation. Perioperative morbidity and mortality are very low. Early follow-up documents restoration of sinus rhythm in more than 75% of patients and reduced risks of thromboembolism and bleeding due to warfarin. Although the addition of the Cox maze procedure lengthens hospital stay in patients having mitral valve repair, overall medical costs may be decreased by reducing the need for long-term anticoagulation, as well as costs associated with stroke and bleeding complications.
| Footnotes |
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| References |
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