Original Cardiovascular
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Long-Term Outcomes after Mitral Valve Repair for Degenerative Mitral Regurgitation with Persistent Atrial Fibrillation Hideo Kanemitsu1
1 Department of Cardiovascular Surgery, Kobe City Medical Center
General Hospital, Kobe, Hyogo, Japan Thorac Cardiovasc Surg 2015;63:243–249.
Abstract
Keywords
► warfarin therapy ► mitral valve surgery ► outcomes
Yasunobu Konishi1
Address for correspondence Takashi Murashita, MD, Department of Cardiovascular Surgery, Kobe City Medical Center General Hospital, 21-1 Minatozimaminami, Chuo, Kobe, Hyogo 650-0047, Japan (e-mail: [email protected]).
Background Atrial fibrillation (AF) adversely affects surgical outcomes of mitral valve surgery. However, the long-term impact of Maze procedure has not been clear yet. Patients and Methods We retrospectively investigated 159 patients who underwent mitral valve repair for degenerative mitral regurgitation with persistent AF between 1991 and 2010. The mean age of patients was 63.1 10.5 years. After we started performing Maze procedure in 2002, 65 patients underwent concomitant Maze procedure. The median follow-up time was 7.5 years. Results There was one operative death (0.63%). The overall survival rate was 91.0 2.6% at 5 years and 79.1 4.7% at 10 years. Survival was significantly better in patients who underwent Maze procedure than those who did not. The rate of freedom from AF in patients who underwent Maze procedure was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years. The freedom rate from stroke was higher in patients who underwent Maze procedure than those who did not. Patients with postoperative AF had larger left ventricular systolic and diastolic diameters at follow-up and higher New York Heart Association functional class than patients without postoperative AF (1.4 0.5 vs. 1.1 0.3, p < 0.001). Conclusion Maze procedure can have a positive effect on long-term survival, freedom from stroke, and cardiac function.
Introduction Mitral valve repair is a standard surgical treatment for patients with degenerative mitral regurgitation, and excellent long-term outcomes have been reported.1,2 However, patients with degenerative mitral regurgitation are often associated with atrial fibrillation (AF), which affects the rates of late stroke and long-term survival after mitral valve surgery.3 Bando et al4 reported a Japanese multicenter study which found that a concomitant Maze procedure with mitral valve
received February 6, 2014 accepted after revision May 15, 2014 published online July 15, 2014
Naoto Fukunaga1
repair can improve long-term survival, freedom from stroke, and late cardiac function. A recent study showed that a combination of mitral valve repair and Maze procedure can provide long-term survival and quality of life benefits for patients with nonrheumatic mitral regurgitation and persistent AF.5 However, there have not been many reports that showed the long-term positive impact of Maze procedure. Previous studies have enrolled patients with various causes of mitral regurgitation. It is estimated that Carpentier type III mitral regurgitation, which is characterized by restricted leaflet motion,6 tends to have a longer duration of AF
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DOI http://dx.doi.org/ 10.1055/s-0034-1383719. ISSN 0171-6425.
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Takashi Murashita1 Yukikatsu Okada1 Ken Nakamura1 Tadaaki Koyama1
Long-Term Outcomes after Mitral Valve Repair
Murashita et al.
and poorer surgical outcome than type II (degenerative) mitral regurgitation. There have been few studies comparing the long-term outcomes of patients with degenerative mitral regurgitation who underwent Maze procedure and those who did not. The aims of this study were to investigate the long-term outcomes after mitral valve repair for degenerative mitral regurgitation with persistent AF, and to determine the impact of performing a concomitant Maze procedure on long-term survival, cardiac events, stroke, and cardiac function, by comparing the outcomes of patients who underwent Maze procedure with those who did not.
Statistical Analysis The continuous data in this study are expressed as mean standard deviation and range. Categorical variables were compared with the χ2 or Fisher exact tests, and continuous variables were compared with unpaired t or Wilcoxon tests. Survival and freedom from events were calculated with the Kaplan–Meier method. Statistical analysis was performed with StatView (SAS Institute, Cary, North Carolina, United States).
Results Patient Characteristics
Patients and Methods The data analysis for this retrospective study was approved by the Institutional Review Board of Kobe City Medical Center General Hospital. The Board waived the need for patient consent.
Patient characteristics and preoperative echocardiographic data are shown in ►Table 1. We divided the patients into two groups according to whether they underwent Maze procedure (Maze [þ] group: 65 patients) or not (Maze [] group: 94 patients). Of note, patients in Maze () group had lower body surface area, higher New York Heart Association (NYHA) class, and larger left ventricular diameter.
Patient Population From January 1991 to December 2010, 1,138 patients underwent mitral valve surgery (949 mitral valve repair and 169 mitral valve replacement) at Kobe City Medical Center General Hospital. Persistent AF is defined when AF continues more than 7 days and does not end spontaneously. Of those who underwent mitral valve repair, 268 (28.2%) patients had persistent AF preoperatively. Patients with ischemic, congenital, type III, or rheumatic mitral regurgitation, or who underwent concomitant aortic valve or thoracic aorta procedures, were also excluded. The remaining 159 patients with degenerative mitral regurgitation and persistent AF were retrospectively analyzed.
Follow-Up Examination and Management We basically administer warfarin to all patients postoperatively. If patients stay in sinus rhythm (SR), we discontinue warfarin approximately 3 months postoperatively. If AF remains or recurs, we continue or restart warfarin treatment, with a target international normalized ratio of 1.5 to 2.5. Patient follow-up was done at the outpatient clinic or by telephone survey, and was completed in 156 patients (98.1%). The median follow-up time was 7.5 years (range, 1 month–21 years). Postoperative cardiac rhythm was checked at the outpatient clinic by 12-lead electrocardiography. If patients complained of palpitation or some irregular pulse, we performed further investigation with 24hour Holter monitoring even if 12-lead electrocardiography showed SR. Postoperative echocardiographic follow-up was generally performed before discharge and at the outpatient clinic at 1, 5, and 10 years postoperatively. The median echocardiographic follow-up time was 5.5 years (range, 1 month–21 years). Follow-up echocardiographic data were obtained in 129 patients at 1 year, 88 patients at 5 years, and 57 patients at 10 years postoperatively.
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Surgical Techniques Surgery was performed via median sternotomy in all patients. Standard cardiopulmonary bypass techniques were used, including bicaval cannulation. Myocardial protection was achieved with antegrade and retrograde intermittent cold blood cardioplegia. A left atrial incision was used in most patients. We used the techniques of mitral valve repair described by Carpentier7 and David et al.8 Prolapse of the posterior leaflet was usually corrected by resection and suture of the mitral leaflets. Prolapse of the anterior leaflet was usually corrected by chordal replacement with polytetrafluoroethylene sutures (Gore-Tex; W.L. Gore and Associates Inc., Flagstaff, Arizona, United States). In May 2002, we started performing Maze procedure in patients with persistent AF. The indications for performing Maze procedure were discussed in each case, considering factors such as the patient’s age, duration of AF, and f-wave in lead V1. We used radiofrequency and/or cryoablation intraoperatively. The right and left pulmonary veins were encircled in a box lesion, and additional lesions to the mitral valve annulus and left atrial appendage were also created. In August 2004, we started closing the orifice of the left atrial appendage using a running suture, to prevent late stroke. The right atrial appendage was partially incised and a right atrial free wall lesion was created from this incision. A vertical incision was made in the wall of the right atrium and a lesion was created from this incision to the tricuspid valve annulus. Additional lesions were created from the inferior aspect of this incision to the superior and inferior vena cavae. Concomitant procedures were performed in 124 patients (78.0%). The details of surgical procedures are shown in ►Table 2. In terms of the surgical procedures, folding plasty for posterior leaflet and concomitant tricuspid annuloplasty were more frequently performed in Maze (þ) group. The mean cardiopulmonary bypass time and aortic cross-clamp time were longer in Maze (þ) group.
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Table 1 Preoperative clinical characteristics Variables
Maze (þ) (n ¼ 65)
Maze () (n ¼ 94)
p value
Mean age, y
63.2 11.4
63.0 9.9
0.924
Male, n (%)
44 (67.6)
54 (57.4)
0.192
BSA, m2
1.64 0.21
1.57 0.18
0.029
NYHA functional class
2.3 0.5
2.7 0.6
< 0.001
Anterior, n (%)
24 (36.9)
28 (29.8)
0.346
Posterior, n (%)
28 (43.1)
46 (48.9)
0.467
Both, n (%)
13 (20.0)
20 (21.3)
0.845
AF duration, y
4.8 5.9
6.2 8.4
0.317
f-wave in V1, mV
0.17 0.17
0.15 0.09
0.457
LVDd, mm
54.5 6.5
57.6 7.1
0.007
LVDs, mm
34.0 7.1
37.2 7.2
0.006
LVEF, %
63.3 8.0
64.7 8.1
0.327
LAD, mm
54.3 9.8
56.2 10.8
0.255
Systolic PA pressure, mm Hg
42.2 11.2
43.1 15.8
0.680
Mild or less, n (%)
28 (43.1)
44 (46.8)
0.642
Moderate or severe, n (%)
37 (56.9)
50 (53.2)
TR grade
Abbreviations: AF, atrial fibrillation; BSA, body surface area; LAD, left atrial diameter; LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PA, pulmonary artery; TR, tricuspid regurgitation.
Survival There was one operative death (0.63%) due to intraoperative left ventricular rupture, which was found in Maze () group. There were 24 late deaths (12 due to stroke, 3 cardiac, 8 noncardiac, and 1 unknown). There were no operative or late deaths in Maze (þ) group. The overall survival rate was 91.0 2.6% at 5 years, 79.1 4.7% at 10 years, and
57.8 9.7% at 15 years. The survival rate was better in Maze (þ) group than in Maze () group (5-year survival: 100 vs. 85.2 4.0%, p < 0.001) (►Fig. 1).
Postoperative Cardiac Events and Rhythms In Maze (þ) group, 43 patients (66.2%) were in SR at discharge and 3 (4.6%) required permanent pacemaker implantation
Table 2 Details of surgical procedures Variables
Maze (þ) (n ¼ 65)
Maze () (n ¼ 94)
p value
Operative procedure for mitral valve Leaflet resection and suture, n (%)
38 (58.5)
66 (70.2)
0.126
Artificial chordal reconstruction, n (%)
36 (55.4)
49 (52.1)
0.686
Folding plasty, n (%)
10 (15.4)
1 (1.1)
0.001
Ring annuloplasty, n (%)
62 (95.4)
82 (87.2)
0.146
Tricuspid annuloplasty, n (%)
48 (73.8)
52 (55.3)
0.017
Left atrial appendage closure, n (%)
32 (49.2)
22 (23.4)
0.310
Concomitant procedures
Coronary artery bypass grafting, n (%)
3 (4.6)
7 (7.4)
0.696
Closure of atrial septal defect, n (%)
7 (10.8)
3 (3.2)
0.109
Cardiopulmonary bypass time, min
202 42
164 40
< 0.001
Aortic cross-clamp time, min
150 33
115 31
< 0.001
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Prolapse region
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Fig. 2 Freedom rate from atrial fibrillation in Maze (þ) group. Fig. 1 Survival rates of Maze (þ) and Maze () groups.
due to bradycardia. The differences in baseline characteristics between patients who converted to SR and those who did not are shown in ►Table 3. Longer duration of AF was a risk factor for lack of conversion to SR (p ¼ 0.012). There were eight cardiac-related readmissions in Maze (þ) group. The reasons for readmission were permanent pacemaker implantation for symptomatic bradycardia in five patients, congestive heart failure in two patients, and catheter ablation for recurrent AF in one patient. There were no reoperations or recurrences of severe mitral regurgitation. The rate of freedom from AF was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years (►Fig. 2). In Maze () group, 15 patients (16.1%) were in SR at discharge and 1 (1.1%) required permanent pacemaker implantation. There were 18 cardiac-related readmissions in this group. The reasons for readmission were reoperation for mitral valve disease in seven patients, congestive heart failure in four patients, permanent pacemaker implantation in three patients, heart rate control for fast AF in two patients, vasospastic angina pectoris in one patient, and catheter ablation for AF in one patient. We performed seven reopera-
tions for mitral valve disease: five were for recurrence of severe mitral regurgitation and two were for massive thrombus in the left atrium. The overall rate of freedom from reoperation for mitral valve disease was 96.4 1.6% at 5 years and 94.6 2.3% at 10 years. There was no difference in the rate of freedom from cardiac events (cardiac death, cardiac-related readmission, or reoperation) between Maze (þ) and Maze () groups (5-year freedom rate: 81.6 5.9 vs. 88.9 3.5%, p ¼ 0.113) (►Fig. 3).
Postoperative Stroke In Maze (þ) group, four patients developed postoperative stroke. All of these were patients who did not convert to SR postoperatively. All of them had undergone left atrial appendage closure during Maze procedure. In Maze () group, 28 patients developed postoperative stroke. Four of them had undergone left atrial appendage closure during surgery. The rate of freedom from stroke at 5 years postoperatively was 92.1 3.9% in Maze (þ) group and 82.6 4.2% in Maze ()
Table 3 Baseline characteristics of patients who underwent the Maze procedure, who were in SR or AF at the time of discharge SR (n ¼ 43)
AF (n ¼ 22)
p value
Age, y
62.4 12.8
64.6 8.2
0.459
Male, n (%)
27 (62.8)
17 (77.3)
0.368
Hypertension, n (%)
20 (46.5)
11 (50.0)
0.790
Preoperative NYHA functional class
2.3 0.5
2.3 0.6
0.910
Anterior region, n (%)
26 (60.5)
11 (50.0)
0.420
AF duration, y
3.5 4.7
7.6 7.1
0.012
f-wave in V1, mV
0.14 0.12
0.22 0.23
0.081
LVDd, mm
54.9 5.7
53.8 7.8
0.526
LVDs, mm
34.0 6.6
33.8 8.1
0.942
LVEF, %
62.7 7.9
64.5 8.5
0.421
LAD, mm
53.8 8.9
55.1 11.4
0.609
Systolic PA pressure, mm Hg
40.9 8.6
44.7 15.2
0.211
Preoperative TR grade
1.7 0.8
1.9 0.9
0.204
Abbreviations: AF, atrial fibrillation; LAD, left atrial diameter; LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PA, pulmonary artery; SR, sinus rhythm; TR, tricuspid regurgitation. Thoracic and Cardiovascular Surgeon
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Fig. 3 Freedom rate from cardiac events in Maze (þ) and Maze () groups.
group, which was better in Maze (þ) group (log-rank p ¼ 0.047) (►Fig. 4).
Echocardiographic Data We compared serial echocardiographic data between patients who maintained SR during follow-up (SR group) and those who did not convert to SR and who had recurrent AF (AF group). Left ventricular diastolic diameter and left ventricular systolic diameter were similar between these groups at discharge, but then increased gradually in the AF group, resulting in a significant difference between groups in the long term. Left atrial diameter was larger in the AF group at discharge, and this difference continued during the follow-up period. There were no differences in left ventricular ejection fraction, right ventricular pressure, residual mitral regurgitation grade, or tricuspid regurgita-
Murashita et al.
Fig. 4 Freedom rate from stroke in Maze (þ) and Maze () groups.
tion grade between the two groups at discharge or during the follow-up period. The latest NYHA functional class was higher in the AF group than the SR group (1.4 0.5 vs. 1.1 0.3, p < 0.001). The serial echocardiographic data are shown in ►Fig. 5a–d.
Discussion AF is associated with lower rates of survival and freedom from late stroke after surgery.3,9 Some articles have reported the efficacy of the cryoMaze procedure for conversion to SR in patients with AF who underwent mitral valve surgery or other disease.5,10–13 Previous studies included patients with various causes of mitral regurgitation. In this study, we focused on patients with degenerative mitral regurgitation with persistent AF. The overall survival rate was 91.0 2.6%
Fig. 5 Serial echocardiographic data in the sinus rhythm (SR) and atrial fibrillation (AF) groups. (a) Serial changes in left ventricular diastolic diameter (LVDd). (b) Serial changes in left systolic diastolic diameter (LVDs). (c) Serial changes in left ventricular ejection fraction (LVEF). (d) Serial changes in right ventricular pressure (RVP). Thoracic and Cardiovascular Surgeon
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Long-Term Outcomes after Mitral Valve Repair
Long-Term Outcomes after Mitral Valve Repair
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at 5 years and 79.1 4.7% at 10 years, which was similar or better than previous reports. We started performing Maze procedure in 2002, and the results of this study show that the survival rate was higher in Maze (þ) group than in Maze () group. There were some differences in background characteristics between Maze (þ) and Maze () groups. Patients in Maze () group were more symptomatic and had larger left ventricular diameter. In the early period, early surgical intervention was not as strongly recommended as it is currently. Patients therefore tended to wait a long time before surgery, and tended to have worse symptoms and larger left ventricular diameter at the time of surgery. Although there was no difference in preoperative age between the two groups, the preoperative NYHA functional class was higher in Maze () group than in Maze (þ) group, which reflects the difference in time between the onset of disease and surgery. The timing of surgery is likely to affect long-term survival. Moreover, the follow-up period was shorter in Maze (þ) group than in Maze () group. However, our results show that Maze procedure can have a positive impact on survival in patients with degenerative mitral regurgitation with persistent AF even though cardiopulmonary bypass time and aortic cross-clamp time become longer. In this study, patients were operated in a different period. Maze (þ) patients were operated through 2002 to 2010 and Maze () patients were operated through 1991 to 2010. However, we had one operator during the whole time (Y.O.) and there were little changes in surgical approach and postoperative management. We usually performed both right- and left-side Maze procedures in patients with persistent AF. Our technique is based on the Cox Maze IV technique. The primary success rate of Maze procedure was 66.2%. Some patients converted to SR during the follow-up period. As a result, the rate of freedom from AF in Maze (þ) group was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years, which is similar or even better than the rates reported in other studies.5,14 Some articles have reported that the risk factors for AF recurrence include a long history of AF, a small f-wave voltage, and a large left atrial diameter.5,15 In our study, the only risk factor for nonconversion to SR was a long duration of AF. Mitral valve repair before the development of AF has been recommended.4 Our results suggest that early surgical intervention for severe mitral regurgitation should also be advocated, even after patients develop AF. The rate of freedom from AF is affected by how we detect postoperative paroxysmal AF. It is true we could not rule out all paroxysmal AF with our follow-up method. However, it is not practical to do a Holter monitoring to all patients who underwent Maze procedure. Moreover, we cannot detect all paroxysmal AF even with a 24-hour Holter monitoring. Worku et al16 reported on the incidence of pacemaker placement after surgical ablation for AF. They found that 7.6% of patients required early postoperative pacemaker placement, and that the 90-day mortality rate was higher in patients who required pacemakers than those who did not. In our study, 4.6% of patients required permanent pacemaker implantation for bradycardia at discharge, and 7.6% of paThoracic and Cardiovascular Surgeon
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tients required pacemaker implantation during the followup period. However, pacemaker implantation did not lead to increased mortality, and there were no early or late deaths in patients who required pacemaker implantation. We believe that the positive effects of Maze procedure outweigh the risk of bradycardia requiring permanent pacemaker implantation. The leading cause of late death was stroke, which occurred in 28 of 78 patients (35.9%) who had AF at discharge. Some patients suffered from stroke even though they were under adequate warfarin control at outpatient clinic. Ten patients developed bleeding during adequate warfarin therapy. Of these, six had bowel bleeding and four had intracerebral bleeding, all of which resulted in severe deterioration of their quality of life. These outcomes reflect the difficulty of treating patients with warfarin without increasing the complication rate. The effect of concomitant left atrial appendage closure during Maze is still controversial. Lee et al compared the rate of stroke after Maze procedure in the patients who underwent left atrial appendage resection and patients whose left atrial appendage was preserved, and they did not find any difference.17 In our study, all of the patients who suffered from stroke in Maze (þ) group had undergone left atrial appendage closure; nevertheless, stroke could not be prevented. Bando et al4 reported that Maze procedure can have a positive impact on cardiac function. In our study, we found that patients with residual postoperative AF developed gradual enlargement of the left ventricle. The differences in left ventricular systolic and diastolic diameters between the AF and SR groups became larger over time, but this was not associated with a difference in left ventricular ejection fraction between groups. However, the differences may be the cause of lower survival rates and higher rates of readmission for cardiac failure in Maze () group. These findings indicate the importance of conversion to SR for the improvement of long-term outcome. Some limitations exist in this study. First, this is a singleinstitution, retrospective study. Second, the patient population is small. Third, clinical and echocardiographic follow-up were not obtained in all patients and the follow-up period was not long enough. Fourth, we did not perform 24-hour Holter monitoring for all patients. Some recurrent AF might not be detected. Finally, both cohorts were operated along separated periods. Some improvements in surgical techniques and perioperative care might influence the clinical outcomes. In conclusion, our study showed that Maze procedure can improve long-term survival and cardiac function, and can improve the rate of freedom from stroke, in patients with degenerative mitral regurgitation with persistent AF. Early surgical intervention before the development of AF should be advocated, and surgical intervention is also indicated after the development of AF.
Conflict of Interest The authors have no conflict of interest to disclose.
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9 Ling LH, Enriquez-Sarano M, Seward JB, et al. Clinical outcome of
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Sarano M. Very long-term survival and durability of mitral valve repair for mitral valve prolapse. Circulation 2001;104(12, Suppl 1): I1–I7 Braunberger E, Deloche A, Berrebi A, et al. Very long-term results (more than 20 years) of valve repair with carpentier’s techniques in nonrheumatic mitral valve insufficiency. Circulation 2001; 104(12, Suppl 1):I8–I11 Ngaage DL, Schaff HV, Mullany CJ, et al. Influence of preoperative atrial fibrillation on late results of mitral repair: is concomitant ablation justified? Ann Thorac Surg 2007;84(2):434–442, discussion 442–443 Bando K, Kasegawa H, Okada Y, et al. Impact of preoperative and postoperative atrial fibrillation on outcome after mitral valvuloplasty for nonischemic mitral regurgitation. J Thorac Cardiovasc Surg 2005;129(5):1032–1040 Fujita T, Kobayashi J, Toda K, et al. Long-term outcome of combined valve repair and maze procedure for nonrheumatic mitral regurgitation. J Thorac Cardiovasc Surg 2010;140(6):1332–1337 Carpentier A, Chauvaud S, Mihaileanu S. Classification of congenital malformations of the mitral valve and their surgical management. . In: Crupi G, Parenzan L, Anderson RG, eds. Perspectives in Pediatric Cardiology. Part 3: Pediatric Cardiac Surgery. Mt Kisco (NY): Futura Publishing Company; 1990:97–102 Carpentier A. Cardiac valve surgery—the “French correction”. J Thorac Cardiovasc Surg 1983;86(3):323–337 David TE, Bos J, Rakowski H. Mitral valve repair by replacement of chordae tendineae with polytetrafluoroethylene sutures. J Thorac Cardiovasc Surg 1991;101(3):495–501
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mitral regurgitation due to flail leaflet. N Engl J Med 1996;335(19): 1417–1423 Funatsu T, Kobayashi J, Nakajima H, Iba Y, Shimahara Y, Yagihara T. Long-term results and reliability of cryothermic ablation based maze procedure for atrial fibrillation concomitant with mitral valve surgery. Eur J Cardiothorac Surg 2009;36(2):267–271, discussion 271 Nakajima H, Kobayashi J, Bando K, et al. The effect of cryo-maze procedure on early and intermediate term outcome in mitral valve disease: case matched study. Circulation 2002;106(12, Suppl 1): I46–I50 Lim E, Barlow CW, Hosseinpour AR, et al. Influence of atrial fibrillation on outcome following mitral valve repair. Circulation 2001;104(12, Suppl 1):I59–I63 Wi J, Choi JY, Shim JM, et al. Fate of preoperative atrial fibrillation after correction of atrial septal defect. Circ J 2013;77(1):109–115 Khargi K, Hutten BA, Lemke B, Deneke T. Surgical treatment of atrial fibrillation; a systematic review. Eur J Cardiothorac Surg 2005;27(2):258–265 Itoh A, Kobayashi J, Bando K, et al. The impact of mitral valve surgery combined with maze procedure. Eur J Cardiothorac Surg 2006;29(6):1030–1035 Worku B, Pak SW, Cheema F, et al. Incidence and predictors of pacemaker placement after surgical ablation for atrial fibrillation. Ann Thorac Surg 2011;92(6):2085–2089 Lee CH, Kim JB, Jung SH, Choo SJ, Chung CH, Lee JW. Left atrial appendage resection versus preservation during the surgical ablation of atrial fibrillation. Ann Thorac Surg 2014;97(1): 124–132
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References
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Long-Term Outcomes after Mitral Valve Repair for Degenerative Mitral Regurgitation with Persistent Atrial Fibrillation Hideo Kanemitsu1
1 Department of Cardiovascular Surgery, Kobe City Medical Center
General Hospital, Kobe, Hyogo, Japan Thorac Cardiovasc Surg 2015;63:243–249.
Abstract
Keywords
► warfarin therapy ► mitral valve surgery ► outcomes
Yasunobu Konishi1
Address for correspondence Takashi Murashita, MD, Department of Cardiovascular Surgery, Kobe City Medical Center General Hospital, 21-1 Minatozimaminami, Chuo, Kobe, Hyogo 650-0047, Japan (e-mail: [email protected]).
Background Atrial fibrillation (AF) adversely affects surgical outcomes of mitral valve surgery. However, the long-term impact of Maze procedure has not been clear yet. Patients and Methods We retrospectively investigated 159 patients who underwent mitral valve repair for degenerative mitral regurgitation with persistent AF between 1991 and 2010. The mean age of patients was 63.1 10.5 years. After we started performing Maze procedure in 2002, 65 patients underwent concomitant Maze procedure. The median follow-up time was 7.5 years. Results There was one operative death (0.63%). The overall survival rate was 91.0 2.6% at 5 years and 79.1 4.7% at 10 years. Survival was significantly better in patients who underwent Maze procedure than those who did not. The rate of freedom from AF in patients who underwent Maze procedure was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years. The freedom rate from stroke was higher in patients who underwent Maze procedure than those who did not. Patients with postoperative AF had larger left ventricular systolic and diastolic diameters at follow-up and higher New York Heart Association functional class than patients without postoperative AF (1.4 0.5 vs. 1.1 0.3, p < 0.001). Conclusion Maze procedure can have a positive effect on long-term survival, freedom from stroke, and cardiac function.
Introduction Mitral valve repair is a standard surgical treatment for patients with degenerative mitral regurgitation, and excellent long-term outcomes have been reported.1,2 However, patients with degenerative mitral regurgitation are often associated with atrial fibrillation (AF), which affects the rates of late stroke and long-term survival after mitral valve surgery.3 Bando et al4 reported a Japanese multicenter study which found that a concomitant Maze procedure with mitral valve
received February 6, 2014 accepted after revision May 15, 2014 published online July 15, 2014
Naoto Fukunaga1
repair can improve long-term survival, freedom from stroke, and late cardiac function. A recent study showed that a combination of mitral valve repair and Maze procedure can provide long-term survival and quality of life benefits for patients with nonrheumatic mitral regurgitation and persistent AF.5 However, there have not been many reports that showed the long-term positive impact of Maze procedure. Previous studies have enrolled patients with various causes of mitral regurgitation. It is estimated that Carpentier type III mitral regurgitation, which is characterized by restricted leaflet motion,6 tends to have a longer duration of AF
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DOI http://dx.doi.org/ 10.1055/s-0034-1383719. ISSN 0171-6425.
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Takashi Murashita1 Yukikatsu Okada1 Ken Nakamura1 Tadaaki Koyama1
Long-Term Outcomes after Mitral Valve Repair
Murashita et al.
and poorer surgical outcome than type II (degenerative) mitral regurgitation. There have been few studies comparing the long-term outcomes of patients with degenerative mitral regurgitation who underwent Maze procedure and those who did not. The aims of this study were to investigate the long-term outcomes after mitral valve repair for degenerative mitral regurgitation with persistent AF, and to determine the impact of performing a concomitant Maze procedure on long-term survival, cardiac events, stroke, and cardiac function, by comparing the outcomes of patients who underwent Maze procedure with those who did not.
Statistical Analysis The continuous data in this study are expressed as mean standard deviation and range. Categorical variables were compared with the χ2 or Fisher exact tests, and continuous variables were compared with unpaired t or Wilcoxon tests. Survival and freedom from events were calculated with the Kaplan–Meier method. Statistical analysis was performed with StatView (SAS Institute, Cary, North Carolina, United States).
Results Patient Characteristics
Patients and Methods The data analysis for this retrospective study was approved by the Institutional Review Board of Kobe City Medical Center General Hospital. The Board waived the need for patient consent.
Patient characteristics and preoperative echocardiographic data are shown in ►Table 1. We divided the patients into two groups according to whether they underwent Maze procedure (Maze [þ] group: 65 patients) or not (Maze [] group: 94 patients). Of note, patients in Maze () group had lower body surface area, higher New York Heart Association (NYHA) class, and larger left ventricular diameter.
Patient Population From January 1991 to December 2010, 1,138 patients underwent mitral valve surgery (949 mitral valve repair and 169 mitral valve replacement) at Kobe City Medical Center General Hospital. Persistent AF is defined when AF continues more than 7 days and does not end spontaneously. Of those who underwent mitral valve repair, 268 (28.2%) patients had persistent AF preoperatively. Patients with ischemic, congenital, type III, or rheumatic mitral regurgitation, or who underwent concomitant aortic valve or thoracic aorta procedures, were also excluded. The remaining 159 patients with degenerative mitral regurgitation and persistent AF were retrospectively analyzed.
Follow-Up Examination and Management We basically administer warfarin to all patients postoperatively. If patients stay in sinus rhythm (SR), we discontinue warfarin approximately 3 months postoperatively. If AF remains or recurs, we continue or restart warfarin treatment, with a target international normalized ratio of 1.5 to 2.5. Patient follow-up was done at the outpatient clinic or by telephone survey, and was completed in 156 patients (98.1%). The median follow-up time was 7.5 years (range, 1 month–21 years). Postoperative cardiac rhythm was checked at the outpatient clinic by 12-lead electrocardiography. If patients complained of palpitation or some irregular pulse, we performed further investigation with 24hour Holter monitoring even if 12-lead electrocardiography showed SR. Postoperative echocardiographic follow-up was generally performed before discharge and at the outpatient clinic at 1, 5, and 10 years postoperatively. The median echocardiographic follow-up time was 5.5 years (range, 1 month–21 years). Follow-up echocardiographic data were obtained in 129 patients at 1 year, 88 patients at 5 years, and 57 patients at 10 years postoperatively.
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Surgical Techniques Surgery was performed via median sternotomy in all patients. Standard cardiopulmonary bypass techniques were used, including bicaval cannulation. Myocardial protection was achieved with antegrade and retrograde intermittent cold blood cardioplegia. A left atrial incision was used in most patients. We used the techniques of mitral valve repair described by Carpentier7 and David et al.8 Prolapse of the posterior leaflet was usually corrected by resection and suture of the mitral leaflets. Prolapse of the anterior leaflet was usually corrected by chordal replacement with polytetrafluoroethylene sutures (Gore-Tex; W.L. Gore and Associates Inc., Flagstaff, Arizona, United States). In May 2002, we started performing Maze procedure in patients with persistent AF. The indications for performing Maze procedure were discussed in each case, considering factors such as the patient’s age, duration of AF, and f-wave in lead V1. We used radiofrequency and/or cryoablation intraoperatively. The right and left pulmonary veins were encircled in a box lesion, and additional lesions to the mitral valve annulus and left atrial appendage were also created. In August 2004, we started closing the orifice of the left atrial appendage using a running suture, to prevent late stroke. The right atrial appendage was partially incised and a right atrial free wall lesion was created from this incision. A vertical incision was made in the wall of the right atrium and a lesion was created from this incision to the tricuspid valve annulus. Additional lesions were created from the inferior aspect of this incision to the superior and inferior vena cavae. Concomitant procedures were performed in 124 patients (78.0%). The details of surgical procedures are shown in ►Table 2. In terms of the surgical procedures, folding plasty for posterior leaflet and concomitant tricuspid annuloplasty were more frequently performed in Maze (þ) group. The mean cardiopulmonary bypass time and aortic cross-clamp time were longer in Maze (þ) group.
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Table 1 Preoperative clinical characteristics Variables
Maze (þ) (n ¼ 65)
Maze () (n ¼ 94)
p value
Mean age, y
63.2 11.4
63.0 9.9
0.924
Male, n (%)
44 (67.6)
54 (57.4)
0.192
BSA, m2
1.64 0.21
1.57 0.18
0.029
NYHA functional class
2.3 0.5
2.7 0.6
< 0.001
Anterior, n (%)
24 (36.9)
28 (29.8)
0.346
Posterior, n (%)
28 (43.1)
46 (48.9)
0.467
Both, n (%)
13 (20.0)
20 (21.3)
0.845
AF duration, y
4.8 5.9
6.2 8.4
0.317
f-wave in V1, mV
0.17 0.17
0.15 0.09
0.457
LVDd, mm
54.5 6.5
57.6 7.1
0.007
LVDs, mm
34.0 7.1
37.2 7.2
0.006
LVEF, %
63.3 8.0
64.7 8.1
0.327
LAD, mm
54.3 9.8
56.2 10.8
0.255
Systolic PA pressure, mm Hg
42.2 11.2
43.1 15.8
0.680
Mild or less, n (%)
28 (43.1)
44 (46.8)
0.642
Moderate or severe, n (%)
37 (56.9)
50 (53.2)
TR grade
Abbreviations: AF, atrial fibrillation; BSA, body surface area; LAD, left atrial diameter; LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PA, pulmonary artery; TR, tricuspid regurgitation.
Survival There was one operative death (0.63%) due to intraoperative left ventricular rupture, which was found in Maze () group. There were 24 late deaths (12 due to stroke, 3 cardiac, 8 noncardiac, and 1 unknown). There were no operative or late deaths in Maze (þ) group. The overall survival rate was 91.0 2.6% at 5 years, 79.1 4.7% at 10 years, and
57.8 9.7% at 15 years. The survival rate was better in Maze (þ) group than in Maze () group (5-year survival: 100 vs. 85.2 4.0%, p < 0.001) (►Fig. 1).
Postoperative Cardiac Events and Rhythms In Maze (þ) group, 43 patients (66.2%) were in SR at discharge and 3 (4.6%) required permanent pacemaker implantation
Table 2 Details of surgical procedures Variables
Maze (þ) (n ¼ 65)
Maze () (n ¼ 94)
p value
Operative procedure for mitral valve Leaflet resection and suture, n (%)
38 (58.5)
66 (70.2)
0.126
Artificial chordal reconstruction, n (%)
36 (55.4)
49 (52.1)
0.686
Folding plasty, n (%)
10 (15.4)
1 (1.1)
0.001
Ring annuloplasty, n (%)
62 (95.4)
82 (87.2)
0.146
Tricuspid annuloplasty, n (%)
48 (73.8)
52 (55.3)
0.017
Left atrial appendage closure, n (%)
32 (49.2)
22 (23.4)
0.310
Concomitant procedures
Coronary artery bypass grafting, n (%)
3 (4.6)
7 (7.4)
0.696
Closure of atrial septal defect, n (%)
7 (10.8)
3 (3.2)
0.109
Cardiopulmonary bypass time, min
202 42
164 40
< 0.001
Aortic cross-clamp time, min
150 33
115 31
< 0.001
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Prolapse region
Long-Term Outcomes after Mitral Valve Repair
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Fig. 2 Freedom rate from atrial fibrillation in Maze (þ) group. Fig. 1 Survival rates of Maze (þ) and Maze () groups.
due to bradycardia. The differences in baseline characteristics between patients who converted to SR and those who did not are shown in ►Table 3. Longer duration of AF was a risk factor for lack of conversion to SR (p ¼ 0.012). There were eight cardiac-related readmissions in Maze (þ) group. The reasons for readmission were permanent pacemaker implantation for symptomatic bradycardia in five patients, congestive heart failure in two patients, and catheter ablation for recurrent AF in one patient. There were no reoperations or recurrences of severe mitral regurgitation. The rate of freedom from AF was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years (►Fig. 2). In Maze () group, 15 patients (16.1%) were in SR at discharge and 1 (1.1%) required permanent pacemaker implantation. There were 18 cardiac-related readmissions in this group. The reasons for readmission were reoperation for mitral valve disease in seven patients, congestive heart failure in four patients, permanent pacemaker implantation in three patients, heart rate control for fast AF in two patients, vasospastic angina pectoris in one patient, and catheter ablation for AF in one patient. We performed seven reopera-
tions for mitral valve disease: five were for recurrence of severe mitral regurgitation and two were for massive thrombus in the left atrium. The overall rate of freedom from reoperation for mitral valve disease was 96.4 1.6% at 5 years and 94.6 2.3% at 10 years. There was no difference in the rate of freedom from cardiac events (cardiac death, cardiac-related readmission, or reoperation) between Maze (þ) and Maze () groups (5-year freedom rate: 81.6 5.9 vs. 88.9 3.5%, p ¼ 0.113) (►Fig. 3).
Postoperative Stroke In Maze (þ) group, four patients developed postoperative stroke. All of these were patients who did not convert to SR postoperatively. All of them had undergone left atrial appendage closure during Maze procedure. In Maze () group, 28 patients developed postoperative stroke. Four of them had undergone left atrial appendage closure during surgery. The rate of freedom from stroke at 5 years postoperatively was 92.1 3.9% in Maze (þ) group and 82.6 4.2% in Maze ()
Table 3 Baseline characteristics of patients who underwent the Maze procedure, who were in SR or AF at the time of discharge SR (n ¼ 43)
AF (n ¼ 22)
p value
Age, y
62.4 12.8
64.6 8.2
0.459
Male, n (%)
27 (62.8)
17 (77.3)
0.368
Hypertension, n (%)
20 (46.5)
11 (50.0)
0.790
Preoperative NYHA functional class
2.3 0.5
2.3 0.6
0.910
Anterior region, n (%)
26 (60.5)
11 (50.0)
0.420
AF duration, y
3.5 4.7
7.6 7.1
0.012
f-wave in V1, mV
0.14 0.12
0.22 0.23
0.081
LVDd, mm
54.9 5.7
53.8 7.8
0.526
LVDs, mm
34.0 6.6
33.8 8.1
0.942
LVEF, %
62.7 7.9
64.5 8.5
0.421
LAD, mm
53.8 8.9
55.1 11.4
0.609
Systolic PA pressure, mm Hg
40.9 8.6
44.7 15.2
0.211
Preoperative TR grade
1.7 0.8
1.9 0.9
0.204
Abbreviations: AF, atrial fibrillation; LAD, left atrial diameter; LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PA, pulmonary artery; SR, sinus rhythm; TR, tricuspid regurgitation. Thoracic and Cardiovascular Surgeon
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Fig. 3 Freedom rate from cardiac events in Maze (þ) and Maze () groups.
group, which was better in Maze (þ) group (log-rank p ¼ 0.047) (►Fig. 4).
Echocardiographic Data We compared serial echocardiographic data between patients who maintained SR during follow-up (SR group) and those who did not convert to SR and who had recurrent AF (AF group). Left ventricular diastolic diameter and left ventricular systolic diameter were similar between these groups at discharge, but then increased gradually in the AF group, resulting in a significant difference between groups in the long term. Left atrial diameter was larger in the AF group at discharge, and this difference continued during the follow-up period. There were no differences in left ventricular ejection fraction, right ventricular pressure, residual mitral regurgitation grade, or tricuspid regurgita-
Murashita et al.
Fig. 4 Freedom rate from stroke in Maze (þ) and Maze () groups.
tion grade between the two groups at discharge or during the follow-up period. The latest NYHA functional class was higher in the AF group than the SR group (1.4 0.5 vs. 1.1 0.3, p < 0.001). The serial echocardiographic data are shown in ►Fig. 5a–d.
Discussion AF is associated with lower rates of survival and freedom from late stroke after surgery.3,9 Some articles have reported the efficacy of the cryoMaze procedure for conversion to SR in patients with AF who underwent mitral valve surgery or other disease.5,10–13 Previous studies included patients with various causes of mitral regurgitation. In this study, we focused on patients with degenerative mitral regurgitation with persistent AF. The overall survival rate was 91.0 2.6%
Fig. 5 Serial echocardiographic data in the sinus rhythm (SR) and atrial fibrillation (AF) groups. (a) Serial changes in left ventricular diastolic diameter (LVDd). (b) Serial changes in left systolic diastolic diameter (LVDs). (c) Serial changes in left ventricular ejection fraction (LVEF). (d) Serial changes in right ventricular pressure (RVP). Thoracic and Cardiovascular Surgeon
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Long-Term Outcomes after Mitral Valve Repair
Long-Term Outcomes after Mitral Valve Repair
Murashita et al.
at 5 years and 79.1 4.7% at 10 years, which was similar or better than previous reports. We started performing Maze procedure in 2002, and the results of this study show that the survival rate was higher in Maze (þ) group than in Maze () group. There were some differences in background characteristics between Maze (þ) and Maze () groups. Patients in Maze () group were more symptomatic and had larger left ventricular diameter. In the early period, early surgical intervention was not as strongly recommended as it is currently. Patients therefore tended to wait a long time before surgery, and tended to have worse symptoms and larger left ventricular diameter at the time of surgery. Although there was no difference in preoperative age between the two groups, the preoperative NYHA functional class was higher in Maze () group than in Maze (þ) group, which reflects the difference in time between the onset of disease and surgery. The timing of surgery is likely to affect long-term survival. Moreover, the follow-up period was shorter in Maze (þ) group than in Maze () group. However, our results show that Maze procedure can have a positive impact on survival in patients with degenerative mitral regurgitation with persistent AF even though cardiopulmonary bypass time and aortic cross-clamp time become longer. In this study, patients were operated in a different period. Maze (þ) patients were operated through 2002 to 2010 and Maze () patients were operated through 1991 to 2010. However, we had one operator during the whole time (Y.O.) and there were little changes in surgical approach and postoperative management. We usually performed both right- and left-side Maze procedures in patients with persistent AF. Our technique is based on the Cox Maze IV technique. The primary success rate of Maze procedure was 66.2%. Some patients converted to SR during the follow-up period. As a result, the rate of freedom from AF in Maze (þ) group was 86.4 4.5% at 1 year and 81.1 5.6% at 5 years, which is similar or even better than the rates reported in other studies.5,14 Some articles have reported that the risk factors for AF recurrence include a long history of AF, a small f-wave voltage, and a large left atrial diameter.5,15 In our study, the only risk factor for nonconversion to SR was a long duration of AF. Mitral valve repair before the development of AF has been recommended.4 Our results suggest that early surgical intervention for severe mitral regurgitation should also be advocated, even after patients develop AF. The rate of freedom from AF is affected by how we detect postoperative paroxysmal AF. It is true we could not rule out all paroxysmal AF with our follow-up method. However, it is not practical to do a Holter monitoring to all patients who underwent Maze procedure. Moreover, we cannot detect all paroxysmal AF even with a 24-hour Holter monitoring. Worku et al16 reported on the incidence of pacemaker placement after surgical ablation for AF. They found that 7.6% of patients required early postoperative pacemaker placement, and that the 90-day mortality rate was higher in patients who required pacemakers than those who did not. In our study, 4.6% of patients required permanent pacemaker implantation for bradycardia at discharge, and 7.6% of paThoracic and Cardiovascular Surgeon
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tients required pacemaker implantation during the followup period. However, pacemaker implantation did not lead to increased mortality, and there were no early or late deaths in patients who required pacemaker implantation. We believe that the positive effects of Maze procedure outweigh the risk of bradycardia requiring permanent pacemaker implantation. The leading cause of late death was stroke, which occurred in 28 of 78 patients (35.9%) who had AF at discharge. Some patients suffered from stroke even though they were under adequate warfarin control at outpatient clinic. Ten patients developed bleeding during adequate warfarin therapy. Of these, six had bowel bleeding and four had intracerebral bleeding, all of which resulted in severe deterioration of their quality of life. These outcomes reflect the difficulty of treating patients with warfarin without increasing the complication rate. The effect of concomitant left atrial appendage closure during Maze is still controversial. Lee et al compared the rate of stroke after Maze procedure in the patients who underwent left atrial appendage resection and patients whose left atrial appendage was preserved, and they did not find any difference.17 In our study, all of the patients who suffered from stroke in Maze (þ) group had undergone left atrial appendage closure; nevertheless, stroke could not be prevented. Bando et al4 reported that Maze procedure can have a positive impact on cardiac function. In our study, we found that patients with residual postoperative AF developed gradual enlargement of the left ventricle. The differences in left ventricular systolic and diastolic diameters between the AF and SR groups became larger over time, but this was not associated with a difference in left ventricular ejection fraction between groups. However, the differences may be the cause of lower survival rates and higher rates of readmission for cardiac failure in Maze () group. These findings indicate the importance of conversion to SR for the improvement of long-term outcome. Some limitations exist in this study. First, this is a singleinstitution, retrospective study. Second, the patient population is small. Third, clinical and echocardiographic follow-up were not obtained in all patients and the follow-up period was not long enough. Fourth, we did not perform 24-hour Holter monitoring for all patients. Some recurrent AF might not be detected. Finally, both cohorts were operated along separated periods. Some improvements in surgical techniques and perioperative care might influence the clinical outcomes. In conclusion, our study showed that Maze procedure can improve long-term survival and cardiac function, and can improve the rate of freedom from stroke, in patients with degenerative mitral regurgitation with persistent AF. Early surgical intervention before the development of AF should be advocated, and surgical intervention is also indicated after the development of AF.
Conflict of Interest The authors have no conflict of interest to disclose.
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mitral regurgitation due to flail leaflet. N Engl J Med 1996;335(19): 1417–1423 Funatsu T, Kobayashi J, Nakajima H, Iba Y, Shimahara Y, Yagihara T. Long-term results and reliability of cryothermic ablation based maze procedure for atrial fibrillation concomitant with mitral valve surgery. Eur J Cardiothorac Surg 2009;36(2):267–271, discussion 271 Nakajima H, Kobayashi J, Bando K, et al. The effect of cryo-maze procedure on early and intermediate term outcome in mitral valve disease: case matched study. Circulation 2002;106(12, Suppl 1): I46–I50 Lim E, Barlow CW, Hosseinpour AR, et al. Influence of atrial fibrillation on outcome following mitral valve repair. Circulation 2001;104(12, Suppl 1):I59–I63 Wi J, Choi JY, Shim JM, et al. Fate of preoperative atrial fibrillation after correction of atrial septal defect. Circ J 2013;77(1):109–115 Khargi K, Hutten BA, Lemke B, Deneke T. Surgical treatment of atrial fibrillation; a systematic review. Eur J Cardiothorac Surg 2005;27(2):258–265 Itoh A, Kobayashi J, Bando K, et al. The impact of mitral valve surgery combined with maze procedure. Eur J Cardiothorac Surg 2006;29(6):1030–1035 Worku B, Pak SW, Cheema F, et al. Incidence and predictors of pacemaker placement after surgical ablation for atrial fibrillation. Ann Thorac Surg 2011;92(6):2085–2089 Lee CH, Kim JB, Jung SH, Choo SJ, Chung CH, Lee JW. Left atrial appendage resection versus preservation during the surgical ablation of atrial fibrillation. Ann Thorac Surg 2014;97(1): 124–132
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References
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