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Eur J Cardiothorac Surg 2007;31:414-422. doi:10.1016/j.ejcts.2006.11.045
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
a Cardiac Surgery Unit Magna Graecia University of Catanzaro, Catanzaro, Italy
b Cardiovascular and Diseases Unit Magna Graecia University of Catanzaro, Catanzaro, Italy
Received 5 September 2006; received in revised form 27 November 2006; accepted 28 November 2006.
* Corresponding author. Address: Viale dei Pini, 28, 80131 Napoli, Italy. Tel.: +39 081 7441531; fax: +39 0961 712405. (Email: frankono{at}libero.it).
| Abstract |
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Key Words: Atrial fibrillation ablation Arrhythmia surgery Electrophysiology Tissue Doppler imaging Mini-Maze
| 1. Introduction |
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AF ablation with these simplified procedures has recently become the focus a rapidly increasing amount of research, also fuelled by technological advances [6,8,9]. Ablation technologies, such as monopolar and bipolar radiofrequency devices (RF), allow a complete isolation of the pulmonary veins, by a rapid and safe creation of atrial lesions [8,9]. However, results of these new procedures required scrutiny, being the results of the different experiences variable [4,6,810]. Moreover, together with the improvement of technology, surgical skill, and of the amount of studies, the interest of the researchers have moved from the recovery and maintenance of the sinus rhythm, to the recovery of the atrial function, to the reverse remodelling of the cardiac chambers [110]. In particular, although SR restoration has been proven to reduce atrial volumes and diameters secondary to the recovery of the atrial kicking [11,12], little is known about the effect of a successful AF ablation on the ventricular function and structure.
Therefore, it was the aim of our study to evaluate clinical and echocardiographic results of patients undergoing AF ablation during MV surgery, either postoperatively or at mid-term follow-up. Tissue Doppler imaging echocardiography was used to study perioperative systolic and diastolic function of the left ventricle. Finally, independent predictors of AF recurrence at follow-up were evaluated.
| 2. Materials and methods |
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Due to the impact of the underlying ventricular disease on prognosis, no cases of chronic ischemic mitral regurgitation were enrolled in the study. All patients undergoing concomitant CABG suffered of primary mitral valve disease with incidental or associated coronary heart disease.
Demographic data were expressed in Table 1 .
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Operations were performed by three surgeons through a median sternotomy, under cardiopulmonary bypass with standard aortic and bicaval cannulation. A standard cardiopulmonary bypass circuit was used: a Dideco (Mirandola Modena) tubing set, which included a 40 µm filter, a Stockert roller pump (Stockert Instrumente, Munich, Germany) and a hollow fibre membrane oxygenator (Dideco D903 Avant, Mirandola (MO), Italy). Non-pulsatile flow with an output of 2.4 l/m2 per min was used. Systemic temperature was kept between 32 and 34 °C. Cardiac arrest was achieved and maintained with intermittent warm blood cardioplegia. Blood recovery with autotransfusion device (Autotrans Dideco, Mirandola, Modena) was performed intraoperatively and routinely in all cases. A level of haemoglobin lower than 8 g/dl was used as an indication for blood transfusion.
The left atrium was entered through a longitudinal atriotomy in all cases after Waterston's groove dissection. MV surgery and concomitant surgical procedures are reported in Table 2 .
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The left-sided lesions were shown in Fig. 1 . Isolation of the left and right pulmonary veins was done with the monopolar RF pen in all patients, as well as the lesion connecting the left pulmonary veins with the left appendage, the upper and lower lesions connecting the right and left pulmonary veins, and the left isthmic lesion. Isolation of the left appendage was performed with bipolar RF in 18 patients (34.6%), with unipolar RF in all other cases (65.4%). Left and right appendages were always excluded by either external ligation or internal stitch. Of 21 patients undergoing left bipolar RF ablation (seven of whom 13.4% underwent concomitant tricupid valve repair), right atrial RF ablation was achieved with bipolar clamp, as previously published [14]. Protective devices to the adjacent structures were never used.
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An intravenous amiodarone bolus (150 mg), followed by a continuous intravenous infusion at 1 mg/kg per hour for 12 h and then 0.5 mg/kg per hour until patients were tolerating oral intake, was routinely started intraoperatively. Patients then underwent oral amiodarone (200 mg twice/day for 1 week, then 200 mg daily) until the 6th postoperative month. All SR-patients discontinued oral amiodarone following the 6th postopertive month. Those with postoperative persistence of AF, as well as those with new onset of AF or atrial flutter did not undergo electric cardioversion, but were treated with i.v. and oral amiodarone as above mentioned.
2.3 Anticoagulation
Oral warfarin was administered to maintain international normalized ratio between 2.5 and 3.5, starting on the 2nd postoperative day. Warfarin was then continued for the first 6 months in all, life-long in patients receiving mechanical valves and/or with AF persistence. Following the 6th postoperative month, all patients undergoing mitral plasty or mitral valve replacement with a bioprosthesis demonstrating normalized E/A ratio at echocardiography discontinued oral warfarin intake.
2.4 Assessment of cardiac rhythm and follow-up
Twelve-lead electrocardiographic recordings were performed preoperatively, on admission in Intensive Therapy Unit postoperatively, and then daily thereafter until hospital discharge or whenever judged necessary. All patients had continuous electrocardiogram monitoring for the first 72 h postoperatively. The incidence of dysrhythmias, both atrial and ventricular, were recorded during hospital stay and follow-up.
Mean follow-up time was 29.5 ± 8.6 months (range 2.237.5 months), and no patient was lost during follow-up. Follow-up data were collected prospectively, by routinely examination in our outpatient clinic (7 days, 14 days, 1 month, 3 months, 6 months, 1 year following surgery, then once/year or whenever asked from the patient). Phone contacts with patients and cardiologists were used whenever necessary.
Patients underwent a 24-h Holter ECG 1 month following surgery, and repeated at least once during the first 6 months of follow-up. Follow-up was closed on the 28th February 2006.
AF recurrence was the primary end-point of the study. AF was defined when there was no consistent P waves before each QRS complex and ventricular rate was irregular. AF episodes lasting longer than 5 min were recognized. The occurrence of the first AF was considered as recurrence (i.e. the endpoint of our study). Episodes of congestive heart failure and hospital re-admission were considered as secondary end-points, and therefore monitored during follow-up. Congestive heart failure was defined as any episode of cardiac decompensation during follow-up requiring adjustment of the therapy or hospitalization; hospital re-admission as any hospital admission requiring more than 6 h of stay, during the follow-up time, due to cardiac causes.
2.5 Echocardiography
The echocardiographic examinations were performed preoperatively, postoperatively and at 3 months follow-up in all patients, using a VIVID 7 Pro ultrasound machine (GE Technologies, Milwaukee, WI, USA). According to the early remodelling of cardiac chambers following SR restoration, 3-months echocardiographic follow-up was chosen to assess definitive results, so to consider the procedure to be a success or a failure.
Tissue Doppler echocardiography (TDI) was performed with transducer frequencies of 1.83.6 MHz, using minimum optimal gain as possible to obtain the best signal to noise ratio. In the apical four chamber view, a 5 mm pulsed Doppler sample volume was placed at the level of the septal and lateral sites of the mitral annulus. The incident angle between the interrogating Doppler beam and longitudinal motion of the ventricle was kept as small as possible. Myocardial systolic wave (Sm), myocardial early (Em) contraction peak velocity, ratio of early diastolic mitral inflow velocity (E) to Em (E/Em) were measured [15].
2.6 Statistical analysis
Continuous variables are expressed as mean ± SD, and categorical data as proportions. Comparisons of continuous variables were made with Student's unpaired t-test and categorical variables were compared with the
2 test or Fisher exact test. Comparison between and within groups was made using two-way analysis of variance for repeated measures.
Univariate analyses of risk factors were performed. Variables with a p value less than 0.05 were consecutively subjected to a multivariate logistic regression model to assess the independent impact of each risk factor on AF recurrence. A stepwise procedure (backward Wald) was used with a p value of less than 0.05 to enter and eliminate variables.
Freedom from AF, CHF, and hospital re-admission were determined with the method of KaplanMeier life table analysis. Log-rank test was performed to ascertain differences between patients with AF-recurrence or SR-maintenance during follow-up.
All statistical analyses were considered significant if p < 0.05 and performed using the SPSS statistical package 10.1 (SPSS Inc., Chicago, IL).
| 3. Results |
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3.2 Cardiac rhythm
At aortic declamping 40 patients (76.9%) recovered sinus rhythm, seven (13.4%) were on junctional rhythm, five (9.6%) demonstrated persistence of atrial fibrillation. Of these, three underwent mitral valve replacement + tricuspid annuloplasty, two received mitral valve surgery (one replacement, one plasty) + CABG.
All patients were treated with amiodarone postoperatively, as above mentioned, so that 46 (88.5%) patients recovered and were discharged home on sinus rhythm; one patient (1.9%) needed definitive VVI pace-maker implantation, five (9.6%) were discharged home on AF. The patient experiencing VVI pace-maker implantation suffered of permanent AF, and underwent mitral valve plasty + tricuspid anuloplasty + left internal mammary artery on the left anterior descending, showing junctional rhythm (40 bpm) at aortic declamping, which did not recover during the hospital stay: according to that, we think pace-maker implantation can be attributed to the AF ablation procedure itself.
At a mean 29.5 ± 8.6 months follow-up 41 (78.8%) patients were on SR. 24.6 ± 1.8 months actuarial freedom from AF-recurrence was 64.6 ± 0.76%, as shown in Fig. 2 .
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Moreover, two patients developed episodes of congestive heart failure during the follow-up, so that actuarial freedom from CHF was 91.6 ± 0.63% (Fig. 2). On the other side, five patients needed hospital re-admission during the follow-up (two because of CHF, two because of high-rate AF recurrence, one because of high-rate atrial flutter), giving an actuarial freedom from hospital readmission of 88.9 ± 0.47% (Fig. 2).
When recovery of the SR at follow-up is considered, SR-patients demonstrated better freedom from CHF compared to AF-patients (100 vs 72.7%; p = 0.008); similarly, follow-up freedom from hospital readmission was higher in SR-patients than AF-patients (97.4 vs 60.6%; p = 0.0003) (Fig. 3 ).
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3.5 Predictors of AF-recurrence
Univariate analysis revealed that 11 of 53 recorded variables had a significant (p
< 0.05) association with AF recurrence at the end of follow-up (Appendix B); however, multivariate logistic regression analysis demonstrated that only four of these were independent predictors of AF recurrence: in particular, large (
55 mm) preoperative atrial diameter, preoperative NYHA-IV, high diuretics (furosemide
50 mg) at discharge, grade
2 tricuspid insufficiency at follow-up echocardiogrphy were all independent predictors of AF-recurrence (Table 4
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| 4. Discussion |
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When symptoms are considered, a recent report from the Mayo clinic [16] demonstrated that conversion to SR in patients with AF plus tachycardia-induced cardiomyopathy improved systolic function and functional status at follow-up, contrary to the results of the atrial fibrillation follow-up investigation of Rhythm Management and Rate Control versus Electrical cardioversion trials, which demonstrated a trend toward rate control versus rhythm control for the composite end points of death, stroke, and recurrent hospitalization [17,18]. It is well known that AF impairs cardiac function by several mechanisms, such as the loss of atrio-ventricular synchrony and atrial contraction, the reduction of the diastolic filling, the induction of a tachycardia-induced cardiomyopathy. It can be therefore expected that the restoration of an adequate rhythm or at least of the rate, will positively influence the ventricular function. Accordingly, we have found a significant recovery of the functional status in all patients undergoing surgery, confirming previous reports by Stulak and co-workers [16] and Gillinov and co-workers [6]; furthermore Forlani and co-workers [19] evidenced in a retrospective study that the recovery of the SR in patients undergoing mitral valve surgery improved the quality of life assessed by the Short Form 36 (SF-36) Health Survey, despite the Authors did not found any difference in ejection fraction, left atrial diameter, mitral dysfunction, tricuspidal regurgitation, and New York Heart Association functional class; on the other side, Jessurun and colleagues [20] reported in a prospective randomized study that patients with AF and mitral pathology had a quality of life that was markedly improved after valve surgery, but was not different between patients with or without maze surgery. Our study showed that despite all patients recovered their functional status because of the relief of the valve pathology, only those who parallel recovered the heart rhythm demonstrated a further improvement in their symptoms; moreover, patients with AF-persistence demonstrated only an initial amelioration of their NYHA, whereas SR-patients further improved during the folllow-up time-course, together with a better freedom from hospital admission and episodes of acute decompensation; all these data seems to indicate a first recovery of the haemodynamic due to the correction of the valve disease, further progressive during follow-up only in those who recovered also the cardiac rhythm.
When echocardiographic findings are considered, previous literature studies have demonstrated that restoration of the sinus rhythm is consistent with a reverse remodelling of the atrial diameters, volumes and function [11,12]; again, the evaluation if the entity of such remodelling is due to the restoration of the rhythm or to the restoration of the underlying valve disease is still challenging. As for the functional class, we similarly demonstrated that only in SR-patients a reverse remodelling of either longitudinal and transverse atrial diameters could be detected at pre-discharge echocardiography, further improving during follow-up; furthermore, a high percentage of these patients (92.7%) demonstrated a normalized E/A ratio with a restoration of the atrial kick. Therefore, patients with persistence of AF do not undergo to a reverse atrial remodelling, despite the relief of the underlying valve pathology.
However, if SR restoration, functional status and the recovery of the atrial function have been the matter of debate of the majority of the literature published data, little is known on the ventricular response to AF ablation. To the best of our knowledge, the only published paper addressing such topic [16] referred to a very selected subgroup of patients (lone high-rate atrial flutter/fibrillation with tachycardia-induced cardiomyopathy), and investigated only the systolic aspect of the ventricular function, demonstrating a recovery of the left ventricular ejection fraction in patients who recovered SR. Moreover, according to Stulak and co-workers [16], we found a statistically significant reverse remodelling of either systolic and diastolic diameters only in patients undergoing AFAMVS who recovered a stable SR, whereas only a trend toward a reverse remodelling could be detected in those in whom AF persisted following surgery, suggesting a key-role of SR in structural remodelling of the ventricle following surgery. Furthermore, TDI results confirmed a clear benefit from the restoration of the SR not only on the systolic but also on the diastolic ventricular function, showing a significant left ventricular improvement in patients undergoing contemporary relief of the valve disease and of the heart rhythm. This may have an impact on the prognosis of patients undergoing AFAMVS, as suggested by the higher freedom from hospital readmission and freedom from CHF, although larger randomized controlled trials are needed to confirm these findings and evaluate outcomes [21].
Multivariate analysis showed that 4 of 53 analysed variables were independent predictors of AF recurrence in patients undergoing AFAMVS: in particular
55 mm preoperative atrial diameter, preoperative NYHA-IV,
50 mg daily of furosemide at hospital discharge, and
2 tricuspid insufficiency at follow-up echocardiography predict recurrence of AF. Interestingly, in our series of patients nor the type of AF (permanent, persistent), nor duration (months, years), nor surgical technique (left Maze, left + right Maze), nor associated cardiac procedures prolonging cross-clamp time and cardiopulmonary bypass time had an impact on the outcome of AF ablation. According to previous studies, which firstly demonstrated the low rate of SR-conversion in patients with preoperative large atrial diameters [22], either irrespective of concomitant surgical procedures [23], we also found preoperative advanced atrial dilation to poorly correlate with SR conversion; on the other hand, the other three predictive variables were all whiteness of a cardiac failure state, either preoperatively (NYHA IV) or postoperatively (high diuretics and grade
2 tricuspid insufficiency); it can be argued that more complex neuro-endocrine mechanisms activated by a CHF state were responsible of an hyperexcitability of the atria [24], which poorly respond to the surgical procedures, regardless of the lesion set, and are independent from the type or duration of AF; thus, AF ablation will not be successful if the recovery of an heart failure state is not previously achieved in these patients.
Finally, some controversy exists as to whether certain patients with AF and mitral valve disease should receive a maze procedure to reduce the risk of stroke: surgeons who perform Maze consider it is useful only in patients undergoing valve repair, thus eliminating the warfarin-related risk of stroke; others do not believe that the maze procedure is justified in patients undergoing valve replacement, as these patients will require lifelong anticoagulation; others routinely perform AF ablation also in patients undergoing valve replacement because they believe that refractory AF poses an increased risk of stroke even in the presence of anticoagulation [25]. We did not found stroke in our series, maybe because we routinely excluded left appendages in all patients, thus limiting a main factor for perioperative thrombo-embolisms [23]; therefore we can not have conclusions on this topic, although the clear benefit of AF ablation on the ventricular function and remodelling seems to suggest an expanded indication for arrhythmia surgery in all patients undergoing valve surgery, irrespective of the valve repair or replacement.
4.1 Limitations of the study
The main limitation of the study is related to the limited number of patients enrolled. The lack of a comparative group and of randomization are other limitations of this study. Moreover, despite mitral valve surgery with AF ablation was performed in all patients, some of them underwent associated cardiac procedures; moreover, heterogeneity exist on type of AF and its duration. Moreover, either unipolar or bipolar technologies were employed, with the limitation of a not-definitely proven transmurality (although highly suspected with the irrigation) of the unipolar ablation. All these limitations are however the result of the single-center design of the study itself, which, on the other hand, guarantees uniformity of the perioperative management of the patient population throughout the experimentation. On the other side, the strength of our study includes the prospective design and the sequential echocardiographic assessment, either with TDI technology, of both atrial and ventricular size and function before and after surgery. Moreover, these results open discussion to the feasibility for the surgeon to discuss with cardiologist about the possibility to treat with a minimally invasive approach chronic lone AF. Certainly, meta-analyses on larger number of patients - to make subgroups with specific statistical analysis and conclusions reliable for each group of patients with specific and independent predictors of AF recurrence - should validate these findings.
| Appendix A |
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Dr U. von Oppell (Wales, United Kingdom): You stated regardless of technique. Could you summarize the different techniques you used in terms of ablation pattern?
Dr Renzulli: Regardless of the technique, I mean whether we performed the right isthmus ablation or whether we isolated with the bipolar the left atrial appendage, but the basic technique was the box in the mini-Maze procedure in the left atrium, pulmonary vein isolation and left appendage isolation, plus left isthmus isolation.
Dr von Oppell: Was ablation confined to only the left atrium?
Dr Renzulli: Yes.
Dr N. Moat (London, United Kingdom): I would just like to ask you about your postoperative management in terms of cardioverting patients. I think you said that you didnt cardiovert any patients. With the patients that you see 3 months postoperatively who are on amiodarone but are still in atrial fibrillation, could you clarify that you dont cardiovert them, and in that group, how many of those patients do you see spontaneously revert to sinus rhythm between 3 and 6 months?
Dr Renzulli: This is a policy of reality, because patients go to the rehabilitation program after 7 days. Sometimes they come back and they might be in atrial fibrillation. Moreover, to do cardioversion, we have to do transesophageal echo before, and then in our hospital, hospital admission is required. Therefore, we believe that those patients who didnt regain sinus rhythm on amiodarone, even if they have a successful cardioversion, AF might occur later on. So if we have a patient at follow-up with AF on amiodarone after our procedure, we do not try to do a DC shock again. How many patients are in this group, I do not have the exact figure, but I believe that patients who had recurrence of AF might be, let's say, 5%, 10% of the group of AF recurrence.
Dr Moat: I understand your logistic difficulties, but do you think your results might be better if you did adopt a cardioversion policy? Certainly our practice and experience is that there are patients who remain in atrial fibrillation who can be cardioverted and then sustain sinus rhythm for some considerable time after that.
Dr Renzulli: I take your point. We think that we could get some patients out of AF with cardioversion, but, again, as a practical, a financial restrictive problem, we didnt embark on such a program, so we cannot say anything on such an event.
Dr J. Melo (Lisbon, Portugal): If I may, you have shown a significant reduction in your volumes, either from the left atrium or in the left ventricle, but you were not very clear in saying that in all your patients there were not mechanical problems that might even justify remaining in atrial fibrillation, so that your mitral procedure was without mechanical problems. So Im assuming that all your patients had a perfect either repair or replacement.
Dr Renzulli: Nobody is perfect in life. Therefore, when we did mitral repair, that was more than 70% of this group, because replacement was in about 30, we have a postoperative echo, and we cannot accept regurgitation above a grade II, so this is already intraoperative, and postoperatively we are very aggressive on regurgitation above a grade II.
Dr Melo: Yes, I understand that, but you know we have two factors forming the same result. So if we have regurgitant volume, then the likelihood of getting AF is higher, and that may affect and may be a confounding factor for your results. Maybe it's not the technique. Maybe it's because you have a hemodynamic problem that is increasing your volumes. That is only my comment. So I would like to know exactly in each group, those patients who were in sinus and those patients who were in atrial fibrillation, how many in each group there were with hemodynamic residual problems of regurgitation.
Dr Renzulli: Our protocol was the following one. Patients who had recurrence of AF were equally distributed between patients with replacement and repair. I mean we didnt go further with analysis because the numbers are getting smaller and smaller, but we couldnt see differences on the type of repair, and then multivariate analysis didnt show any differences at the end.
| Appendix B |
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| Footnotes |
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| References |
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