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Eur J Cardiothorac Surg 2007;31:586-591. doi:10.1016/j.ejcts.2006.12.039
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

The effect of preoperative atrial fibrillation on survival following mitral valve repair for degenerative mitral regurgitation

Christos Alexioua, George Doukasa, Mehmet Oca, Bahar Ocb, Justiaan Swanevelderb, Nilesh J. Samanic, Tomasz J. Spyta,*

a Department of Cardiac Surgery, Glenfield Hospital, University Hospitals of Leicester, Groby Rd, Leicester LE3 9QP, UK
b Department of Cardiac Anaesthesia, Glenfield Hospital, University Hospitals of Leicester, UK
c Department of Cardiology, Glenfield Hospital, University Hospitals of Leicester, UK

Received 20 September 2006; received in revised form 11 December 2006; accepted 12 December 2006.

* Corresponding author. Tel.: +44 116 2563991; fax: +44 116 2563077. (Email: tom.spyt{at}uhl-tr.nhs.uk).


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A
 References
 
Objective: There is conflicting evidence with regard to the impact of preoperative atrial fibrillation (AF) on the post mitral valve (MV) repair on the early and late outcome. Methods: A total of 349 patients undergoing various MV repair procedures for degenerative mitral regurgitation (MR) between 1997 and 2003 were studied. Preoperatively, 152 (44%) of these patients were in AF and 197 (56%) patients were in sinus rhythm (SR). The clinical features and the outcome in these two cohorts of patients were compared. Results: The patients in the AF group were older than their counterparts in the SR group (66 ± 7 vs 62 ± 9 years) (p = 0.01), had a higher mean NYHA class score (2.4 ± 0.6 vs 2.2 ± 0.7) (p = 0.04) and were more likely to have impaired left ventricular function (60% vs 36%) (p < 0.0001). A similar proportion of patients in the AF (38%) and SR (30%) groups had additional cardiac surgical procedures (p = 0.12). Operative mortality was 3.9% in AF group versus 0.5% in SR group (p = 0.04), and operative morbidity was 27% versus 17%, respectively (p = 0.03). At latest follow up, 4% of patients that were in SR preoperatively developed AF; conversely, 2% of the patients in the AF group converted to SR. The rates of recurrent grade II or III MR (4% vs 5%) (p = 0.8) and MV re-operation (2.6% vs 2.5%) (p = 1.0) were similar in the AF and SR groups. Kaplan–Meier survival at 7 years was 75 ± 6% versus 90 ± 3% (p = 0.005). On Cox proportional hazards regression model, impaired LV function [(p = 0.02), hazard ratio 0.25 (95% confidence intervals (C.I.) 0.078–0.84)] and AF [(p = 0.03), hazard ratio 2.70 (95% C.I. 1.09–6.68)] were significant adverse predictors of survival. Conclusions: This study shows that in patients undergoing MV repair for degenerative MR, preoperative AF has a major negative impact on the early and late survival.

Key Words: Atrial fibrillation • Mitral valve repair • Survival


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A
 References
 
Atrial fibrillation (AF) is present in 3% of patients above 60 years of age and is associated with higher stroke rates, poorer quality of life and reduced survival [1]. The prevalence of degenerative mitral regurgitation (MR) it also increases with advancing age, and left untreated has serious implications [2]. There is a tendency therefore to perform an earlier surgical intervention to avoid the complications of chronic MR [3]. The onset of AF in patients with pre-existing degenerative MR denotes disease progression and is, on its own right, one of the indications for MV surgery [3].

Whilst the adverse effects of AF (lone or compounding pre-existing MR) in general population studies are well documented [1,4], its impact on the outcome following MV surgery is less clear [4–11].

There is now type I evidence that application of radiofrequency ablation (RFA) during MV surgery in patients having permanent AF significantly reduces the prevalence of this arrhythmia postoperatively [12]. Given the widespread use of various ablation procedures during MV surgery, we feel that more information is needed on the clinical significance of AF in this patient group.

This aim of this study was to ascertain the effect of AF on the early and late outcome of patients undergoing MV repair for degenerative MR.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 5. Conclusions
 Appendix A
 References
 
A total of 349 patients undergoing various MV repair procedures for degenerative MR between 1997 and 2003 were studied. Preoperatively, 152 (44%) of these patients were in AF (31 paroxysmal AF and 121 persistent or permanent AF) and 197 (56%) patients were in sinus rhythm (SR). The clinical features and the early and late outcome in these two cohorts of patients were compared.

Patients undergoing repeat cardiac surgery, MV repair with left ventricular remodelling procedures and AF ablation procedures (mainly in the context of a prospective randomised clinical trial) [12] were not included in this study.

2.1 Surgery
The reconstructive techniques used in our center have been previously described [12–16]. In brief, the MV was accessed through the left atrium or the interatrial septum if concomitant tricuspid valve surgery was performed. Posterior leaflet prolapse was managed with quadrangular resection, anterior leaflet prolapse with insertion of artificial chordae and bileaflet prolapse with combination of the two techniques. An edge-to-edge repair [15] was used for correction of MR in the setting of Barlow disease. A Cosgrove-Edwards annuloplasty band was implanted to support the repair and prevent further annular dilatation. Tricuspid valve repair was also accomplished with the insertion of a Cosgrove-Edwards annuloplasty band. Patients in atrial fibrillation had their left atrial appendage obliterated from within. Transoesophageal echocardiography (TOE) was used routinely in the perioperative period.

2.2 Follow up and data collection
Postoperatively, patients that were in AF were anti-coagulated with Warfarin, aiming to achieve an INR level between 2.0 and 3.0. Patients that were in sinus rhythm were kept on Aspirin, unless this was contraindicated. The patients were seen regularly in the outpatient clinics. In each visit they had a clinical examination, a 12-lead ECG and a chest radiograph. Echocardiograms were performed approximately yearly as part of the follow up or more frequently if clinically indicated. Data were collected from the departmental database, the medical notes and from the family doctors of the patients. The mean follow-up was 54 ± 19 months for the AF group and 63 ± 18 months for the SR group (p = 0.002).

2.3 Statistical analysis
Statistical analysis was performed using the SPSS software package (SPSS version 11, Chicago, Illinois). Means were compared with t-test and proportions with Chi-square or Fishers exact test as appropriate. Survival was calculated with the Kaplan–Meier method and the resulting curves compared with the log-rank test. Cox proportional hazards regression models were used to identify predictors of survival between the following variables: age, gender, NYHA class, cardiac rhythm, left ventricular function, history of neurological event, hypertension, diabetes mellitus, chronic obstructive airways disease, renal impairment, type of mitral valve pathology, coronary artery disease, additional valvular disease, concomitant procedures, cardiopulmonary bypass time and ischaemic time. A p-value <0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 5. Conclusions
 Appendix A
 References
 
3.1 Preoperative clinical profile
The patient demographics and preoperative clinical features are shown on Table 1 . The patients in the AF group were older (p = 0.01), had a higher mean NYHA functional class score (p = 0.04) and were more likely to have impaired left ventricular function (defined as an ejection fraction < 60%) (p < 0.0001) and moderate to severe tricuspid regurgitation (p = 0.001). Associated risk factors such as hypertension, hypercholesterolaemia, diabetes mellitus, chronic obstructive airways disease, renal impairment, cerebrovascular disorders and concomitant aortic valve disease were evenly distributed in the two groups (Table 1).


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  		Table 1 Preoperative clinical profile
 
3.2 Mitral valve lesions and operative data
The types of MV lesions and the additional procedures performed (other than MV repair) are shown in Table 2 . Overall, posterior leaflet prolapse was the most common lesion in both groups. However, the patients in AF were more likely to have bi-leaflet prolapse (p = 0.01) and annular dilatation (p < 0.0001) requiring larger annuloplasty bands (p < 0.0001).


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  		Table 2 Mitral valve lesions and additional procedures (other than MV repair)
 
Although coronary artery bypass grafting and aortic valve replacement procedures were carried out at similar rates, a significantly higher proportion of AF patients had tricuspid valve repair (0.007). There were no statistically differences in the operative urgency, duration of cardiopulmonary bypass and ischaemic times between the two groups (Table 2).

3.3 Operative mortality and complications
Operative (30-day) mortality was 0.5% (1 death) in the SR group versus 3.9% (6 deaths) in the AF group (p = 0.04). The only death in the SR group was due to the low cardiac output syndrome, chest infection and renal failure in a patient who underwent MV repair and CABG. The main causes of death in the AF group were low cardiac output syndrome [3], pneumonia [1], stroke [1], and adult respiratory distress syndrome [1].

A significantly higher proportion of patients in the AF group sustained postoperative complications (27% vs 17%) (p = 0.03), the most common of these complications being cardiac (p = 0.02), respiratory, renal (p = 0.06) and heart block requiring insertion of a permanent pacemaker (Table 3 ).


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  		Table 3 Postoperative complications
 
3.4 Late outcome
There were 13 late deaths in the AF group and 10 late deaths in the SR group. Kaplan–Meier survival at 5, 6 and 7 years in the AF versus SR groups was 91 ± 2% versus 96 ± 1.5%, 87 ± 3% versus 94 ± 2% and 75 ± 6% versus 90 ± 3%, respectively (p = 0.005). It is seen, therefore, that survival tended to be better in the SR group at 5 and 6 years after surgery with a further increase in the observed difference at 7 years (Fig. 1 ). On Cox proportional hazards regression model, impaired LV function [(p = 0.02), hazard ratio 0.25 (95% C.I. 0.078–0.84)] and AF [(p = 0.03), hazard ratio 2.70 (95% C.I. 1.09–6.68)] were significant adverse predictors of survival. The variable ‘need for concomitant procedures’ has also demonstrated a trend towards (but without reaching) statistical significance [(p = 0.09), hazard ratio 0.76 (95% C.I. 0.15–3.76)].


Figure 1
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  		Fig. 1. Kaplan–Meier survival at 7 years for the patients with sinus rhythm (continuous line) was 90 ± 3% and for those in atrial fibrillation it was 75 ± 6% (Log rank, p = 0.005).

 
At follow up, 4% of patients that were in SR preoperatively developed AF; conversely, 2% of patients in the AF group converted to sinus rhythm. The mean NYHA functional class score in patients with preoperative SR was 1.2 ± 0.3 versus 1.4 ± 0.5 in those that were in AF (p = 0.01). When compared to preoperative status, NYHA functional class score was significantly improved within each of the two groups (p < 0.0001).

Neurological events (TIA or stroke) were recorded in 5 patients in the SR group (2.5%) and 8 patients in the AF group (5.2%) (p = 0. 42).

Recurrent grade II or III MR was recorded in 10 patients (5%) of the SR group and 6 patients (4%) of the AF group (p = 0.80) whereas a re-operation to the MV was undertaken in 5 (2.5%) (SR group) and 4 patients (2.6%) (AF), respectively (p = 1.0).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
5. Conclusions
 Appendix A
 References
 
General population studies have previously shown that ‘lone’ AF or AF co-existing with MR has a strong negative effect on morbidity and mortality [1,2], and it therefore is treated aggressively with medications, cardioversion and interventional catheter based therapies [17,18].

Cardiac surgeons initially used the maze procedure and currently employ a variety of ablation techniques aiming to abolish AF [19–22]. The efficacy of this approach has been shown in several observational studies that were summarized in a recent meta-analysis [23], and has been confirmed in a prospective randomized controlled trial involving the use of RFA in the demanding group of patients with permanent AF [12].

The addition of an AF ablation procedure during MV surgery is based on the knowledge of the proven adverse effects of AF [1,2] and the expectation that restoration of SR would improve haemodynamics, quality of life and the long-term patient outcome, notably survival. Non-withstanding the proven success of surgical ablation in restoring SR in a significant proportion of patients, however, the published evidence on the impact of AF on survival following MV surgery is conflicting [5–11].

In our study, patients with preoperative AF had higher operative mortality than their counterparts in SR group (0.5% vs 3.9%). This is not surprising given the differing clinical profile of the two groups, with the AF patients being older, having poorer left ventricular function and undergoing more tricuspid valve repair procedures. Previous studies have described operative morality rates ranging between 0.6% and 2.1% for patients in SR and 2%–3.1% for those in AF preoperatively [5–8].

An important finding of our study was that patients with preoperative AF had significantly reduced survival than the patients in the SR group, with AF and LV impairment being independent negative predictors of survival on multivariate analysis. Previous publications on this subject produced inconsistent results that merit a detailed description. Lim et al. found that patients with preoperative AF had a significantly lower survival than those that were in SR at 5 years (73% vs 88%) (p = 0.002); on multivariate analysis, though, poor preoperative LV function was the only independent adverse predictor [5]. In the study of Jessurun et al., the 4-year survival did not differ between patients with preoperative SR (95%), paroxysmal AF (89%) and chronic AF (82%) (p = 0.12) but AF persisting after surgery tended to influence survival (p = 0.052) [10]. Obadia et al. also described similar 5-year survival between the patients with preoperative AF and SR (86% in both groups) [6]. Chua et al. again found no difference in the 5-year survival between the patients with preoperative AF (74%) and SR (76%) on univariate analysis, identifying advanced age, concomitant CABG and low ejection fraction as independent predictors of late death [8]. Chaput et al. reported on 5200 patients undergoing valvular procedures, of which 52% had isolated aortic valve replacement and only 4% had MV repair [11]; after excluding operative mortality from the analysis, patients with preoperative AF had poorer survival (p < 0.0001); AF was not an independent risk factor of long-term mortality (p = 0.6) [11]. Enriquez-Sarano et al. identified AF as a significant adverse factor for survival on a multivariate analysis including only clinical variables (p = 0.027); after including a series of echocardiographic variables on the multivariate analysis model, preoperative AF became a factor of borderline significance (p = 0.057) [9]. In a recent study involving only patients with degenerative MR, Eguchi et al. showed that patients with pre-op SR had better survival compared to those in AF (96% vs 87%, p = 0.002) and higher cardiac event free rates (96% vs 75%, p = 0.001) at 5 years. Moreover, on multivariate regression analysis AF and age were independent predictors of survival [7].

The reasons for the lack of consistency in the results of the above mentioned studies are not entirely clear, and may partly reflect the complex nature of MR, which is often compounded by additional disease processes. It is, nevertheless, likely that heterogeneity in the clinical and pathological features of the patient populations included in these studies, variation in the treatment modalities offered to these patients at various institutions over long time periods, lack of uniformity in the variables forming the statistical analysis models and uneven lengths of follow up, may all contribute.

Recognizing these problems, we tried to create a homogenous group for analysis by including only patients with degenerative MR. Furthermore, in order to delineate the impact of preoperative AF alone on the outcome we have excluded patients who underwent surgical ablation procedures.

Encouragingly, the incidence of recurrent MR and need for re-operation were similar between the two populations in our study, which suggests that preoperative AF is not compromising the functional outcome of the repair. Lim et al. have previously reported repair failure of 5.4% in AF patients versus 3.6% in those with SR (p = 0.41) [5].

We feel that our study, despite the inherent limitations and pitfalls arising from its retrospective nature, has two potential clinical implications. First, surgery to correct MR should be undertaken before the occurrence of AF; secondly, considering the very low SR conversion rate in the AF group (only 2%), an attempt should be made to restore SR by adding a surgical ablation procedure to MV surgery.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
Appendix A
 References
 
This study shows that in patients undergoing MV repair for degenerative MR, preoperative AF has a major negative impact on the early and late survival. Preoperative AF, however, does not appear to affect the functional outcome of the repair.


   Appendix A
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A
References
 
Conference discussion

Dr I. Tzanavaros (Cottbus, Germany): There was no difference in the cerebrovascular events between the two groups, the sinus rhythm group and the atrial fibrillation group. What kind of anticoagulation did you use for the patients?

Dr Doukas: The patients who were in AF were on Warfarin. It may appear somewhat surprising. It was probably the combination of left atrial appendage ligation together with anticoagulation which prevented a higher incidence of thromboembolic events.

Dr H. Najm (Riyadh, Saudi Arabia): I wonder why you excluded your patients with ablation, because this would be supporting your second conclusion on the slide, your recommending that you want to actually ablate the AF so you can get sinus rhythm and you can improve survival. You would have actually proven that by just putting in an extra survival curve showing that those who are ablated actually do better than those who are not ablated.

Dr Doukas: We have shown that in the context of a randomized trial in a previous study published, but on this occasion we wanted to keep homogeneity. If we were introducing those who were ablated as well, then we would have to perform the analysis both on the basis of preop rhythm as well as postop rhythm, and we thought that this might complicate things. We wanted to keep the message clear, because, as we’ve noticed in similar studies that have been previously published, the main problem is that they don’t compare apples with apples.

Dr J. Melo (Lisbon, Portugal): I would like to go deeper on this previous question. There are selected groups of patients with AF you have ablated. So how much bias may have been in your assessment? Some of your AF patients were excluded from the study. You were selecting for ablation the good patients or the bad patients. So I don’t know if you have operated the high-risk group patients in the AF group or the low-risk. The decision to do the ablation was based on what?

Dr Doukas: This was a retrospective study. The vast majority of the patients who were ablated were selected through randomization. These patients were excluded from the study as I pointed out earlier. However they did not differ from those who were in AF and were not ablated and therefore included in the study. As a result there could not be a case of selection bias.

Dr U. von Oppell (Wales, United Kingdom): You have shown that preoperatively there were more patients in atrial fibrillation with poorer left ventricular function by NYHA class. We also know that in patients undergoing mitral valve surgery, regardless of atrial fibrillation, patients with higher NYHA class, or lower left ventricular function have a poorer late survival. So the only message to take home is that patients with mitral disease should be operated early before they go into atrial fibrillation.

Dr Doukas: Yes, that is true. Ideally we would like to have two identical populations to compare. I think that what you point out is an inherent problem with most AF studies. For this reason we performed multivariate analysis.


   Acknowledgments
 
The authors would like to thank the Consultant Cardiac Surgeons Mr A.W. Sosnowski, Mr M.St.J. Hickey, Mr G.J. Peek, Mr J.N. Leverment, Professor M. Galinanes and Mr R.K. Firmin for operating on some of the patients described in this paper. Thanks are also due to the cardiologists, anesthetists and the staff of the Echocardiographic Department at Glenfield Hospital, University Hospitals of Leicester for their invaluable contribution in the management of these patients.


   Footnotes
 
\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 Appendix A
 References
 

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