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Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease
IJCA-17845; No of Pages 6 International Journal of Cardiology xxx (2014) xxx–xxx
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease Xu Wang 1, Xin Wang 1, Yunhu Song, Shengshou Hu, Wei Wang ⁎ Cardiovascular Surgery Department, Fuwai Hospital, Peking Union Medical College & Chinese Academy Of Medical Sciences, Beijing, 100037, China
a r t i c l e
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Article history: Received 12 November 2013 Received in revised form 12 February 2014 Accepted 22 March 2014 Available online xxxx Keywords: Atrial fibrillation Rheumatic heart valve disease Ablation
a b s t r a c t Background: It remains unclear whether concomitant radiofrequency ablation procedure in valvular surgery could offer additional benefits to patients with rheumatic valvular disease. We designed a prospective and randomized control study to evaluate the efficacy of surgical radiofrequency ablation in patients with rheumatic heart disease. Methods: From June 2008 to July 2011, 210 patients with chronic atrial fibrillation and rheumatic heart disease were randomized: (1) control group, patients underwent only valve replacement followed by amiodarone for rhythm control, (2) left atrial group (LA group), patients underwent valve replacement and left atrial mono-polar radiofrequency ablation, (3) bi-atrial group (BA group), patients underwent valve replacement and bi-atrial mono-polar radiofrequency ablation. The primary endpoints included: cardiac death, stroke, and recurrent AF after discharge. Results: There was no perioperative death. One patient died 4 months after MVR in BA group. In univariate Cox analysis, the two ablation groups were associated with less AF (BA group vs control group: P b 0.001; LA group vs control group: P b 0.001) as well as atrial tachycardia arrhythmia (AF/AT/AFL) recurrent (BA group vs control group: P b 0.001; LA group vs control group: P = 0.02). The comparison between BA and LA groups revealed no differences in terms of AF (P = 0.06) or AF/AT/AFL (P = 0.09). Atrial transport function restoration rate 12 months after operation was 31.4% in LA group, 32.9% in BA group, and 8.6% in control group respectively (P b 0.01). Conclusions: Radiofrequency ablation concurring with valvular surgery can bring a higher sinus rhythm restoration rate when compared with medical anti-arrhythmic drug therapy in low-medium risk rheumatic heart disease. The trial was registered on Clinicaltrials.gov (registry number NCT01013688). © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Atrial fibrillation (AF) is the most common arrhythmia in clinical practice [1], especially for patients with valve heart diseases. Up to 30%–40% of patients about to receive mitral valve surgery are with preoperative chronic AF, and in most cases the arrhythmia still exists after the operation [2,3]. In recent decades, the clinical application of radiofrequency ablation for AF has achieved satisfactory results [4–6]. However, the reports were largely limited to non-rheumatic mitral valve diseases and little is known about surgical ablation outcomes for AF with rheumatic heart diseases. But in consideration of its distinctive pathogenesis and poorer
Abbreviations: AF, Atrial Fibrillation; LA, Left Atrial; BA, Bi-Atrial; AF/AT/AFL, Atrial Tachycardia. ⁎ Corresponding author at: 167A, Bei Li Shi Road, Xi Cheng District, Beijing 100037, China. E-mail address: [email protected] (W. Wang). 1 The first two authors contributed equally to this paper.
clinical outcomes [7–9], we hypothesize that rheumatic AF might respond differently to surgical ablation therapy. Although there were few studies focusing on AF ablation outcomes among patients receiving concomitant rheumatic mitral valve operations, those studies were generally small-sized or retrospectivelydesigned with controversy outcomes [10–15]. Up till now, there is no randomized controlled trial designed on this topic. The current RCT study aims to evaluate the clinical effectiveness of radiofrequency ablation for chronic AF combined with rheumatic mitral lesion. 2. Methods 2.1. Study design Candidates were those diagnosed as rheumatic mitral valve diseases complicated with AF. The AF definition in the current study was consistent with that defined by ACC/ AHA/ESC [16]. Inclusion criteria were as follows: AF duration N six months, age ≥ eighteen years, left atrial dimension ≤ 70 mm and without left atrial thrombus. Exclusion standards were as follows: AF duration ≤ six months, age b eighteen years old, emergency operation, left atrial dimension N 70 mm, left ventricular ejection fraction b 30%, left atrial thrombus, onset of acute myocardial infarction b six weeks, time of apoplexy b six months.
http://dx.doi.org/10.1016/j.ijcard.2014.03.153 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx
From June 2008 to July 2011, 432 consecutive patients with rheumatic mitral valve disease and AF required surgical intervention. As is shown in Fig. 1, there were 432 consecutive patients that require surgical intervention, among which 186 patients were not eligible. Among the remaining 246 patients, 36 candidates declined to enter the study. Finally, we got 210 subjects with written consents. Patients were randomly assigned, in 1:1:1 ratio, into three groups: (1) control group, patients underwent only valve replacement followed by amiodarone, (2) left atrial group (LA), patients underwent valve replacement and left atrial mono-polar radiofrequency ablation, and (3) bi-atrial group (BA), patients underwent valve replacement and bi-atrial mono-polar radiofrequency ablation. The random table was generated by the SAS software. After randomization, the study processes were blinded to the patients, coordinators and the investigators who were responsible for the patient assessment but were not blinded to participant surgeons. The study was approved by the ethics committee of Fuwai Hospital, Peking Union Medical College (ID: 875). 2.2. Endpoints Primary endpoints relate to one-year outcomes that included cardiac death, stroke, and recurrent AF after discharge; secondary endpoints include recurrent atrial tachycardia (a combination of atrial fibrillation, atrial flutter, and other types of atrial tachycardia), prosthetic dysfunction, and pacemaker implantation. Cardiac death was defined as deaths from cardiovascular causes or unknown causes; stroke was defined as newly occurred stroke after discharge; recurrent AF after discharge was defined as AF recurrence among converted individuals; and prosthetic dysfunction was defined as a prosthetic valve failure requiring surgical interventions. Blinded adjudication board includes two senior cardiologists involved in assessment and classification of endpoints. If difference in opinions occurred in the assessment, a third cardiologist will be invited to help solve the disagreement. 2.3. Surgical procedures A median sternotomy approach and conventional ascending aorta and bicaval cannulation were used for all patients. A standard right atrial free wall incision was made and atrial septum approach was used to expose left atrial cavity. The left-sided MAZE procedure was performed with the same technique in both experimental groups. Left auricle was removed with Marshall ligament disconnection. In general, the ablation procedure included encirclement of the pulmonary veins with extension to the mitral valve annulus as well as extension to the appendage amputation site (Supplemental Fig. 1). An additional ablation line between the pulmonary vein encirclements was made at the left atrial dome. After ablation, patients received mitral valve replacement or other procedures. In BA group, the patients received additional ablation procedures on right atrium: a free wall incision, a line from coronary sinus to orifice of the inferior vena cava, and a line from coronary sinus to tricuspid annulus (Supplemental Fig. 1). 2.4. Peri-operative care The baseline characteristics were evaluated and all patients routinely received echocardiography, 12-lead electrocardiography and Holter monitoring preoperatively. For all but those with heart rate b60 bpm postoperatively, amiodarone was intravenously infused in a loading dose of 150 mg over 10–15 min right after the procedures,
then at a maintenance dose of 1 mg/min for 6 h, and then 0.5 mg/min. All the patients were submitted to the examination of chest X-ray, a 12-lead surface electrocardiogram (ECG), echocardiogram, and Holter monitoring before discharge. For those still in AF after surgery, cardioversion was attempted during hospital stay. Those still in AF at discharge were planned to have electrical cardioversion one month later. For patients remaining in AF three months postoperatively, further conversion attempts were at physicians' judgment. 2.5. Follow-up All patients were followed up in outpatient clinic at three months, six months and one year after discharge. The follow-up information were obtained mainly from regular outpatient clinic visits. If the patients didn't come back as scheduled, phone calls were made to obtain required information. If unscheduled visits occurred, hospital cards were used to retrieve the information. If necessary, the attending physicians were contacted for those patients not going to the outpatient clinic of our institute. In this study, the follow-up completion rate was 100%. During follow-up period, all patients took warfarin and adjusted the dose according to standard anticoagulation protocols. Oral amiodarone, in a dose of 200 mg/day, was maintained for 3 months and then withdrawn when the AF recurrence was absent. In case of recurrent AF, β-blockers would be administered. The patients of control group needed to take oral amiodarone for one year. Patients in control group required to monitor their heart rates at home (to count heart rate three times per day). If the heart rate was lower than 50 bpm, the patients should report to our researching staff. The chest X ray, liver function, and thyroid function were also routinely monitored (at three months, six months, and one year postoperatively). There were three patients who withdrew from amiodarone for reported low heart rate (b50 bpm), two patients for abnormal liver functions (three months postoperatively), and one patient for abnormal thyroid functions. Patients with abnormal liver or thyroid function would be switched from amiodarone to β-blockers while for withdrawal for heart rate reasons, amiodarone protocol was discontinued and resumed when the heart rate was over 50 bpm. While reexamined, the patients had to undergo Holter and echocardiography. In the current study, we adhered to a pre-defined three-month blanking protocol. We didn't document tachyarrhythmia events during this period. Three months after ablation, discontinuation of amiodarone was recommended. ECG, 24-hour Holter recording and transthoracic echocardiogram were obtained at our outpatient clinic in three, six, and twelve months following surgery. Any documented episode of AF or atrial tachyarrhythmia (AF/AT/AFL) lasting more than 30 s (by ECG or Holter) was considered a recurrent arrhythmic event. In the event of symptoms suggestive of ATs, patients were required to undergo additional ECG and Holter in the referring hospital. 2.6. Echocardiography assessment The echocardiography was evaluated by experienced cardiologist. During the followup visit, we focused on evaluating the size and function of the left atrium. The changes of left atrium diameter (δLAD) were obtained by the following formula:
δLAD6m ¼ LAD6m –LAD0
Fig. 1. The flow chart of the current trial. LA: left atrial group. BA: Bi-atrial group.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx δLAD6m: change of left atrium diameter six months after surgery; LAD6m = left atrium diameter six months after surgery; and LAD0 = left atrium diameter before operation. δLAD12m ¼ LAD12m –LAD0 δLAD12m: change of left atrium diameter one year after surgery; LAD12m = left atrium diameter twelve months after surgery; and LAD0 = left atrium diameter before operation. Furthermore, left atrial transportation function was evaluated through color Doppler echocardiography in one year. The peak A and peak E are indicative of the mitral valve function. When peak A of mitral valve was above 10 cm/s, we considered that the left atrium contraction is effective. 2.7. Statistical analysis According to findings in prior studies, the anticipated elimination rate of AF is 60% in surgery group, and 30% in medication group. A total sample of 189 patients (63 in each group) was computed to achieve 90% power at a 2-sided 0.05 significance level to detect the difference in effectiveness. Considering a drop-out rate of 10%, and the block size during randomization, 210 patients should be enrolled. Continuous variables are presented as means (±SD), unless otherwise specified. Categorical variables were compared among three treatment groups using chi-square test or Fisher's exact test. Nonparametric Mann–Whitney U tests and Kruskal–Wallis tests were used to compare continuous variables. The outcomes were compared using survival analysis (Kaplan–Meier and Cox analysis). Risk factors for recurrent AF and AF/AT/AFL were then estimated by a Cox proportional-hazards model, with surgical types (BA, LA or control) as the exposure variable, variables listed in Table 1 as covariate. All the statistical analyses were performed using SAS version 9.13 (SAS Inc.).
3. Results 3.1. Baseline characteristics Among the 210 patients undergoing mitral valve replacement, 67 of them received aortic valve replacement, 115 of them received tricuspid valvuloplasty and 15 received coronary artery bypass graft (CABG). After the MAZE procedure, other cardiac procedures were performed. The baseline characteristics were of no significant difference among the three groups (Table 1). The mean age of all patients was 53.0 ± 9.8 years, with 61.9% women patients. Patients with NYHA
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classification N II accounted for 41.4%. The overall median AF duration was 24 months (quartile: 12, 60). The median AF duration in BA, LA, and control group was 36 months (quartile: 12, 60), 24 months (quartile: 8, 60), and 36 months (quartile: 12, 60) respectively. The mean left atrial diameter was 52.9 ± 7.8 mm, the left ventricular end-diastolic dimension (LVEDD) was 50.1 ± 7.7 mm, and the mean left ventricular ejection fraction (LVEF) was 61.3 ± 6.6%. 10% of the patients had a history of preoperative cerebral embolism before surgery. In addition, 6.2% of the patients had coronary heart disease, 4.8% of the patients had diabetes mellitus, and 6.7% of the patients had hypertension.
3.2. Surgical data The cardiopulmonary bypass (CPB) time in LA, BA and control groups were 101.0 ± 34.0 min, 138.2 ± 46.0 min and 85.3 ± 34.7 min, respectively (P b 0.001). The aortic cross-clamp time in LA, BA and control groups were 72.1 ± 28.3 min, 101.2 ± 38.6 min and 61.9 ± 29.3 min, respectively (P b 0.001). All the patients received mitral valve replacement (MVR), while 31.9% of the patients received aortic valve replacement (AVR) and 54.8% of the patients received tricuspid valvuloplasty (TVP) during the same procedure. Moreover, 7.1% of the patients received CABG. The CPB time in LA group was 16 min longer than that in control group, and the CPB time of BA group was 37 min longer than that in control group.
3.3. In-hospital outcomes There was no perioperative death. AF conversion was considered in patients with distinguishable, sinus P waves. Before discharge, the BA group had the highest conversion rate (64.3%), while the single atrium group had a rate of 62.9%, and control group was only 22.9% (P b 0.01).
Table 1 Clinical characteristics.
Age (y) Female, n (%) BSA (m2) Duration of AF (mo) NYHA N II, n (%) Echocardiography LAD (mm) LVEDd (mm) LVEF (%) Diabetes, n (%) History of stroke, n (%) Hypertension, n (%) Hyperlipidemia, n (%) CAD, n (%)a Aortic valve diseases, n (%)a Mitral valve diseases, n (%)a Tricuspid valve diseases, n (%)a Medical therapy ß-blockers Statins ACE inhibitors Amiodarones Digoxin EuroSCORE
LA group
BA group
Control group
Total
(n = 70)
(n = 70)
(n = 70)
(n = 210)
P
52.3 ± 10.3 42 (60.0) 1.68 ± 0.18 34.5 ± 20.6 30 (42.9)
53.1 ± 9.3 47 (67.1) 1.68 ± 0.19 31.4 ± 27.2 29 (41.4)
53.6 ± 10.0 41 (58.6) 1.62 ± 0.18 33.7 ± 20.9 28 (40.0)
53.0 ± 9.8 130 (61.9) 1.66 ± 0.18 33.2 ± 23.0 87 (41.4)
0.721 0.676 0.168 0.705 0.694
54.0 ± 7.0 50.7 ± 6.9 61.2 ± 6.9 2 (2.9) 8 (11.4) 5 (7.1) 0 (0) 6 (8.6) 19 (27.1) 70 (100) 31 (44.3)
53.4 ± 6.5 50.4 ± 7.9 61.4 ± 6.5 4 (5.7) 5 (7.1) 5 (7.1) 2 (2.9) 8 (11.4) 26 (37.1) 70 (100) 44 (62.9)
51.4 ± 9.3 49.3 ± 8.2 61.2 ± 6.4 4 (5.7) 8 (11.4) 4 (5.7) 1 (1.4) 5 (7.1) 22 (31.4) 70 (100) 40 (57.1)
52.9 ± 7.8 50.1 ± 7.7 61.3 ± 6.6 10 (4.8) 21 (10.0) 14 (6.7) 3 (1.4) 19 (9.0) 67 (31.9) 210 (100) 115 (54.8)
0.111 0.501 0.964 0.678 0.220 0.223 0.486 0.397 0.469 1.00 0.497
4 (5.7) 0 (0) 3 (4.3) 2 (2.9) 58 (82.9) 2.40 ± 1.16
6 (8.6) 1 (1.4) 5 (7.1) 1 (1.4) 61 (87.1) 2.17 ± 1.31
3 (4.3) 0 (0) 3 (4.3) 3 (4.3) 62 (88.6) 2.14 ± 1.39
13 (6.2) 1 (0.5) 11 (5.2) 6 (2.9) 181 (86.2) 2.23 ± 1.29
0.298 0.995 0.451 0.321 0.807 0.434
Continuous variables were analyzed using analysis of variance. Categorical variables were analyzed using χ2 test. LA, left atrial; BA, bi-atrial; BSA, body surface area; NYHA, New York Heart Association; CAD, coronary artery disease; CTR, cardiothoracic ratio; LAD, left atrial dimension; LVEDd, left ventricular end diastolic dimension; and LVEF, left ventricular ejection fraction. a The diagnosis refers to those requiring surgical intervention.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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3.4. One-year outcomes All patients were discharged alive and finished a one-year follow-up. One patient died four months after surgery in BA group. There were no strokes, or prosthetic dysfunctions. Five cases required pacemakers subsequently, three in BA group and two in LA group. One patient received a pacemaker for a third degree atrial-ventricular block, the other four patients received pacemaker because of symptomatic bradycardia. The comparative results in terms of recurrent AF and recurrent AF/ AT/AFL were shown in Fig. 2. At six months during follow-up, the proportions of patients in sinus rhythm were 61.4%, 51.4%, and 18.6% in BA, LA, and control group, respectively; at 12 months during follow up, the proportions of patients in sinus rhythm were 57.1%, 37.1%, and
10.0% in BA, LA, and control group, respectively (Fig. 2B). For BA patients who didn't stay in sinus rhythm at one year follow-up, 21.4% (15/70) were in AF, 2.9% (2/70) in AFL, and 18.6% (13/70) in other types of AT; for those in L group, 35.7% (25/70) were in AF, 4.3% (3/70) in AFL, and 22.9% (16/70) in other types of AT; for those in control group, 77.1% (54/70) were in AF, 4.3% (3/70) in AFL, and 8.6% (6/70) in other types of AT (Fig. 2A, B). Of patients discharged in sinus rhythm, there were 8 eventually degenerating to AF during follow-up. Among the 8 patients, two were in BA group and one in LA group, all of which were paroxysmal AF. While among the 5 remaining patients in control group, 3 were paroxysmal and 2 were persistent in AF. During follow-up, both BA and LA groups showed less AF and AF/AT/AFL events than control group did (Log Rank: AF, P b 0.001; Log Rank: AF/AT/AFL, P b 0.001). In univariate Cox analysis, the two ablation groups were associated
Fig. 2. Recurrent AF and AF/AT/AFL among BA, LA, and control groups. AF = atrial fibrillation, AF/AT/AFL = atrial tachycardia, BA = bi-atrial group, and LA = left atrial group.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx
with less AF (BA group vs control group: HR = 0.210, 95% CI 0.118– 0.374, P b 0.001; LA group vs control group: HR = 0.396, 95% CI 0.247–0.635, P b 0.001) as well as AF/AT/AFL recurrent (BA group vs control group: HR = 0.367, 95% CI 0.239–0.562, P b 0.001; LA group vs control group: HR = 0.542, 95% CI 0.366–0.803, P = 0.02). The comparison between BA and LA groups revealed no differences in terms of AF (HR = 0.536, 95% CI 0.284–1.013, P = 0.06) or AF/AT/AFL (HR = 0.683, 95% CI 0.436–1.068, P = 0.09). After adjustment, BA and LA ablation were associated with less AF recurrent (BA group vs control group: HR = 0.320, 95% CI 0.181– 0.567, P b 0.001; LA group: HR = 0.532, 95% CI 0.329–0.863, P = 0.010). Higher BMI (HR = 1.104, 95% CI 1.017–1.200; P = 0.018), history of smoking (HR = 3.195, 95% CI 1.100–9.259; P = 0.033), and duration of AF (HR = 1.081, 95% CI 1.020–1.144; P = 0.008) were associated with more AF recurrence. 3.5. Echocardiographic outcomes during follow-up In six months and one year after operation, the size of the left atrium in three groups significantly reduced when compared with that before operation. All sinus-converted patients' left atrial diameter reduction was greater than that of non-sinus-converted patients (P b 0.01, Table 2). The left atrial function recovery rate was 32.9% in BA group, 31.4% in LA group, and 8.6% in control group (P b 0.01). The results revealed that the left atrial function of the ablation groups was obviously improved in contrast to that of the control group (Table 3). 4. Discussion 60% to 80% of AF patients, in need of mitral valve surgery, require ablation intervention [17,18], because postoperative sinus rhythm restoration rate would be as low as 15%–20% without specific treatments [2,19]. Although surgical ablation has been proven to be effective, it is still a concern as for whether surgical ablation concomitant with mitral valve surgery would increase the incidence of complications and mortality. What's more, it was still under debate as for whether sinus rhythm restoration can improve long-term survival [20], especially for patients with rheumatic mitral valve diseases. In the current prospectively designed, randomized controlled study involving 210 individuals, we found that patients receiving concomitant surgical ablation during valve surgery have a favorable one-year outcome when compared to those that didn't have an ablation. Substantial proportion of patients in surgical ablation group restored sinus rhythm as well as atrial transport function. Previous studies demonstrated that rheumatic AF features in inflammation, platelet activation, and increased sympathetic nerve density [7,9,12]. The vicious circle between rheumatic heart diseases and AF contributes to adverse prognosis. Kim and colleagues showed that patients with rheumatic AF receiving classic Cox-MAZE III presented a progressively decreased cure rate in long term [10]. Other authors also demonstrated that rheumatic heart disease is a strong predictor for MAZE procedure failure, and close follow-up with antiarrhythmic drugs or cardioversion is needed to improve the success rate [11]. Furthermore, after reviewing a series of 29 patients, Fukada and colleagues
Table 3 Atrial transport function restoration at 12 months postoperatively.
Left atrial transport restoration P value
LA group
BA group
control group
31.40% 0.001a
32.90% 0.000a
8.60%
LA, left atrial; BA, Bi-atrial a χ2 test.
[13] suggested a second thought for the MAZE procedure for rheumatic AF, because of poor prognosis of cut-and-sew MAZE. However, several more recent reports, in contrast to the above studies, showed that MAZE procedure provides satisfactory results. In a retrospective study, Sternik and colleagues found that the outcomes of AF ablation were similar in rheumatic and non-rheumatic patients with similar preoperative AF type and duration [14]. Another retrospective study involving 53 patients also demonstrated that radiofrequency ablation was effective in converting AF to sinus rhythm in patients with rheumatic mitral valve diseases [15]. Our results were consistent with previous studies [14,15,21], showing that concomitant AF ablation during valve surgeries had satisfactory sinus rhythm conversion rates (68.6% in LA group and 70.0% in BA group). These results might be due to advances in ablation techniques and radical surgical strategies in our center. In the current study, we found that BMI, history of smoking, and duration of AF were negatively related to sinus conversion in one year after surgery. Previous studies were in support of our findings, suggesting the association between these risk factors and the onset of AF or refractory AF [1,22,23]. A radical control of these factors is plausible to get more satisfactory surgical ablative outcomes. Aside from sinus rhythm restoration, long term prognosis involving the heart function and thrombo-embolism is also of big concern. However, in our study, the incidence rates of stroke and heart failure were quite low. Actually, there was only 1 stroke in LA group and there were no patients re-admitted for heart failure. This might be due to the low-medium risk profile of the current study. For example, in the current study the average EF was 61.28 ± 6.56% and the diameter of average left atrium was 52.92 ± 7.76, which were lower than other reports [8,23]. It is also possible that those entering RCT are more adherent to anti-coagulation and anti-heart failure therapies during follow-up period. Classic Cox-MAZE procedure is demonstrated to be highly effective in AF treatment [24,25]. But the inherent defects of the severe injury and massive bleeding can hardly be overcame [26]. Recent evidence shows that focal activation in the left atrium close to the pulmonary veins plays an important role in patients with chronic AF and mitral valve disease [27]. Therefore, less extensive lesion sets with alternative ablation techniques, to be specific, left-sided procedures, became more and more preferred. In our study, we found no significant difference in terms of one-year outcomes between LA and BA groups. Our results echoed those of another study demonstrating that the therapeutic effects seem to be equal between a left atrial MAZE procedure and biatrial procedure [28]. However, in our study five patients in BA group needed permanent pacemaker implantation during follow-up. So the more extensive bi-atrial ablation should be carefully evaluated before surgery lest adverse arrhythmic complications.
4.1. Limitation
Table 2 δLAD (millimeter). SR 6 months 12 months
5
8.87 ± 6.63 (n = 115) 10.09 ± 7.34 (n = 116)
δLAD = reduction in left atrium diameter. SR = Sinus rhythm. AF = Atrial fibrillation. a T-test.
AF 5.86 ± 6.92 (n = 94) 5.47 ± 6.89 (n = 93)
p value a
.002 .000a
This study is, however, not without its limitation. The number of patients involved is still small with somewhat low-medium risk profiles. However, it is hard to maneuver a sample with various risk stratifications, especially when candidates are not quite easy to be recruited. During the study, we do have strict inclusion criteria to guarantee a complete randomization. Another setback is that part of the patients enrolled were complicated cases instead of isolated mitral valve diseases.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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So the influence of other surgical procedures was unable to be excluded and the sample could not be considered representative of population with rheumatic mitral valve and AF. But in the current study, proportions of patients requiring combined CABG or AVR were evenly distributed throughout three groups. So the results were not likely to be confounded. In the current study, we found that BA/LA groups, which saw more patients staying in sinus rhythm, have significantly greater LAD reduction than in control group (Table 1). However, by randomizing 65 patients to cryoablation + mitral replacement or isolated mitral replacement group and using atrial volume as substitute for atrial function, a recent study demonstrated that left atrial volume reduced significantly six months after surgery, irrespective of sinus or AF rhythm [29]. Different indexes used might underlie the different findings. Although atrial volume is demonstrated to be a better predictor for cardiovascular prognosis [30,31], due to our institute echocardiographic protocol, the atrial volume data could not be obtained in clinical scenario. So we have to use atrial diameter. In our ongoing work, we might take atrial volume as the substitute for functional as well as thromboembolic risk evaluation. In summary, valve surgery with radiofrequency ablation could bring a higher sinus rhythm restoration rate when compared with antiarrhythmic drug therapy in low-medium risk rheumatic heart disease. What's more, left-sided atrial ablation and bi-atrial ablation provide equal one-year outcomes. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.03.153. Acknowledgments Dr. Xu Wang and Xin Wang wrote the paper; Dr. Yunhu Song and Shengshou Hu help design the protocol; Dr. Wei Wang was the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article. References [1] Go AS, Hylek EM, Phillips KA. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (atria) study. JAMA 2001;285:2370–5. [2] Chua YL, Schaff HV, Orszulak TA, Morris JJ. Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty? J Thorac Cardiovasc Surg 1994;107:408–15. [3] Handa N, Schaff HV, Morris JJ, Anderson BJ, Kopecky SL, Enriquez-Sarano M. Outcome of valve repair and the cox maze procedure for mitral regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 1999;118:628–35. [4] Guden M, Akpinar B, Sanisoglu I, Sagbas E, Bayindir O. Intraoperative saline-irrigated radiofrequency modified maze procedure for atrial fibrillation. Ann Thorac Surg 2002;74:S1301–6. [5] Sie HT, Beukema WP, Misier AR, et al. Radiofrequency modified maze in patients with atrial fibrillation undergoing concomitant cardiac surgery. J Thorac Cardiovasc Surg 2001;122:249–56. [6] Pasic M, Bergs P, Muller P, et al. Intraoperative radiofrequency maze ablation for atrial fibrillation: the Berlin modification. Ann Thorac Surg 2001;72:1484–90 [discussion 1490–1481]. [7] Azzam H, Abousamra NK, Wafa AA, Hafez MM, El-Gilany AH. Upregulation of cd40/ cd40l system in rheumatic mitral stenosis with or without atrial fibrillation. Platelets 2013;24(7):516–20. [8] Wang B, Xu ZY, Han L, Zhang GX, Lu FL, Song ZG. Impact of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mechanical mitral valve replacement for rheumatic mitral valve disease. Eur J Cardiothorac Surg 2013;43:513–9.
[9] Li Y, Lu Z, Tang Q, et al. The increase in sympathetic nerve density in the atrium facilitates atrial fibrillation in patients with rheumatic heart disease. Int J Cardiol 2013;165:174–8. [10] Kim KC, Cho KR, Kim YJ, Sohn DW, Kim KB. Long-term results of the Cox-Maze III procedure for persistent atrial fibrillation associated with rheumatic mitral valve disease: 10-year experience. Eur J Cardiothorac Surg 2007;31:261–6. [11] Ad N, Barnett S, Lefrak EA, et al. Impact of follow-up on the success rate of the cryosurgical maze procedure in patients with rheumatic heart disease and enlarged atria. J Thorac Cardiovasc Surg 2006;131:1073–9. [12] Ishii Y, Nitta T. Atrial fibrillation surgery for patients with rheumatic valve disease. J Interv Card Electrophysiol 2007;20:109–12. [13] Fukada J, Morishita K, Komatsu K, et al. Is atrial fibrillation resulting from rheumatic mitral valve disease a proper indication for the maze procedure? Ann Thorac Surg 1998;65:1566–9 [discussion 1569–1570]. [14] Sternik L, Luria D, Glikson M, Malachy A, First M, Raanani E. Efficacy of surgical ablation of atrial fibrillation in patients with rheumatic heart disease. Ann Thorac Surg 2010;89:1437–42. [15] Canale LS, Colafranceschi AS, Monteiro AJ, et al. Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation in rheumatic mitral disease. Rev Bras Cir Cardiovasc 2011;26:565–72. [16] Fuster V, Ryden LE, Cannom DS, et al. Acc/aha/esc 2006 guidelines for the management of patients with atrial fibrillation: full text: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006;8:651–745. [17] Abreu Filho CA, Lisboa LA, Dallan LA, et al. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with permanent atrial fibrillation and rheumatic mitral valve disease. Circulation 2005;112:I20–5. [18] Deneke T, Khargi K, Grewe PH, et al. Efficacy of an additional maze procedure using cooled-tip radiofrequency ablation in patients with chronic atrial fibrillation and mitral valve disease. A randomized, prospective trial. Eur Heart J 2002;23:558–66. [19] Jessurun ER, van Hemel NM, Kelder JC, et al. Mitral valve surgery and atrial fibrillation: is atrial fibrillation surgery also needed? Eur J Cardiothorac Surg 2000;17:530–7. [20] Chaput M, Bouchard D, Demers P, et al. Conversion to sinus rhythm does not improve long-term survival after valve surgery: insights from a 20-year follow-up study. Eur J Cardiothorac Surg 2005;28:206–10 [discussion 210]. [21] Khargi K, Lemke B, Deneke T. Concomitant anti-arrhythmic procedures to treat permanent atrial fibrillation in CABG and AVR patients are as effective as in mitral valve patients. Eur J Cardiothorac Surg 2005;27:841–6. [22] Heeringa J, Kors JA, Hofman A, van Rooij FJ, Witteman JC. Cigarette smoking and risk of atrial fibrillation: the Rotterdam study. Am Heart J 2008;156:1163–9. [23] Tinetti M, Costello R, Cardenas C, Piazza A, Iglesias R, Baranchuk A. Persistent atrial fibrillation is associated with inability to recover atrial contractility after maze iv surgery in rheumatic disease. Pacing Clin Electrophysiol 2012;35:999–1004. [24] Cox JL, Ad N, Palazzo T, et al. Current status of the maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg 2000;12:15–9. [25] Izumoto H, Kawazoe K, Kitahara H, Kamata J. Operative results after the cox/maze procedure combined with a mitral valve operation. Ann Thorac Surg 1998;66:800–4. [26] Ballaux PK, Geuzebroek GS, van Hemel NM, et al. Freedom from atrial arrhythmias after classic maze III surgery: a 10-year experience. J Thorac Cardiovasc Surg 2006;132:1433–40. [27] Nitta T, Ishii Y, Miyagi Y, Ohmori H, Sakamoto S, Tanaka S. Concurrent multiple left atrial focal activations with fibrillatory conduction and right atrial focal or reentrant activation as the mechanism in atrial fibrillation. J Thorac Cardiovasc Surg 2004;127:770–8. [28] Deneke T, Khargi K, Grewe PH, et al. Left atrial versus bi-atrial maze operation using intraoperatively cooled-tip radiofrequency ablation in patients undergoing openheart surgery: safety and efficacy. J Am Coll Cardiol 2002;39:1644–50. [29] Johansson B, Bech-Hanssen O, Berglin E, et al. Atrial function after left atrial epicardial cryoablation for atrial fibrillation in patients undergoing mitral valve surgery. J Interv Card Electrophysiol 2012;33:85–91. [30] Tsang TS, Abhayaratna WP, Barnes ME, et al. Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? J Am Coll Cardiol 2006;47:1018–23. [31] Keenan NG, Cueff C, Cimadevilla C, et al. Usefulness of left atrial volume versus diameter to assess thromboembolic risk in mitral stenosis. Am J Cardiol 2010;106:1152–6.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease Xu Wang 1, Xin Wang 1, Yunhu Song, Shengshou Hu, Wei Wang ⁎ Cardiovascular Surgery Department, Fuwai Hospital, Peking Union Medical College & Chinese Academy Of Medical Sciences, Beijing, 100037, China
a r t i c l e
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Article history: Received 12 November 2013 Received in revised form 12 February 2014 Accepted 22 March 2014 Available online xxxx Keywords: Atrial fibrillation Rheumatic heart valve disease Ablation
a b s t r a c t Background: It remains unclear whether concomitant radiofrequency ablation procedure in valvular surgery could offer additional benefits to patients with rheumatic valvular disease. We designed a prospective and randomized control study to evaluate the efficacy of surgical radiofrequency ablation in patients with rheumatic heart disease. Methods: From June 2008 to July 2011, 210 patients with chronic atrial fibrillation and rheumatic heart disease were randomized: (1) control group, patients underwent only valve replacement followed by amiodarone for rhythm control, (2) left atrial group (LA group), patients underwent valve replacement and left atrial mono-polar radiofrequency ablation, (3) bi-atrial group (BA group), patients underwent valve replacement and bi-atrial mono-polar radiofrequency ablation. The primary endpoints included: cardiac death, stroke, and recurrent AF after discharge. Results: There was no perioperative death. One patient died 4 months after MVR in BA group. In univariate Cox analysis, the two ablation groups were associated with less AF (BA group vs control group: P b 0.001; LA group vs control group: P b 0.001) as well as atrial tachycardia arrhythmia (AF/AT/AFL) recurrent (BA group vs control group: P b 0.001; LA group vs control group: P = 0.02). The comparison between BA and LA groups revealed no differences in terms of AF (P = 0.06) or AF/AT/AFL (P = 0.09). Atrial transport function restoration rate 12 months after operation was 31.4% in LA group, 32.9% in BA group, and 8.6% in control group respectively (P b 0.01). Conclusions: Radiofrequency ablation concurring with valvular surgery can bring a higher sinus rhythm restoration rate when compared with medical anti-arrhythmic drug therapy in low-medium risk rheumatic heart disease. The trial was registered on Clinicaltrials.gov (registry number NCT01013688). © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Atrial fibrillation (AF) is the most common arrhythmia in clinical practice [1], especially for patients with valve heart diseases. Up to 30%–40% of patients about to receive mitral valve surgery are with preoperative chronic AF, and in most cases the arrhythmia still exists after the operation [2,3]. In recent decades, the clinical application of radiofrequency ablation for AF has achieved satisfactory results [4–6]. However, the reports were largely limited to non-rheumatic mitral valve diseases and little is known about surgical ablation outcomes for AF with rheumatic heart diseases. But in consideration of its distinctive pathogenesis and poorer
Abbreviations: AF, Atrial Fibrillation; LA, Left Atrial; BA, Bi-Atrial; AF/AT/AFL, Atrial Tachycardia. ⁎ Corresponding author at: 167A, Bei Li Shi Road, Xi Cheng District, Beijing 100037, China. E-mail address: [email protected] (W. Wang). 1 The first two authors contributed equally to this paper.
clinical outcomes [7–9], we hypothesize that rheumatic AF might respond differently to surgical ablation therapy. Although there were few studies focusing on AF ablation outcomes among patients receiving concomitant rheumatic mitral valve operations, those studies were generally small-sized or retrospectivelydesigned with controversy outcomes [10–15]. Up till now, there is no randomized controlled trial designed on this topic. The current RCT study aims to evaluate the clinical effectiveness of radiofrequency ablation for chronic AF combined with rheumatic mitral lesion. 2. Methods 2.1. Study design Candidates were those diagnosed as rheumatic mitral valve diseases complicated with AF. The AF definition in the current study was consistent with that defined by ACC/ AHA/ESC [16]. Inclusion criteria were as follows: AF duration N six months, age ≥ eighteen years, left atrial dimension ≤ 70 mm and without left atrial thrombus. Exclusion standards were as follows: AF duration ≤ six months, age b eighteen years old, emergency operation, left atrial dimension N 70 mm, left ventricular ejection fraction b 30%, left atrial thrombus, onset of acute myocardial infarction b six weeks, time of apoplexy b six months.
http://dx.doi.org/10.1016/j.ijcard.2014.03.153 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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From June 2008 to July 2011, 432 consecutive patients with rheumatic mitral valve disease and AF required surgical intervention. As is shown in Fig. 1, there were 432 consecutive patients that require surgical intervention, among which 186 patients were not eligible. Among the remaining 246 patients, 36 candidates declined to enter the study. Finally, we got 210 subjects with written consents. Patients were randomly assigned, in 1:1:1 ratio, into three groups: (1) control group, patients underwent only valve replacement followed by amiodarone, (2) left atrial group (LA), patients underwent valve replacement and left atrial mono-polar radiofrequency ablation, and (3) bi-atrial group (BA), patients underwent valve replacement and bi-atrial mono-polar radiofrequency ablation. The random table was generated by the SAS software. After randomization, the study processes were blinded to the patients, coordinators and the investigators who were responsible for the patient assessment but were not blinded to participant surgeons. The study was approved by the ethics committee of Fuwai Hospital, Peking Union Medical College (ID: 875). 2.2. Endpoints Primary endpoints relate to one-year outcomes that included cardiac death, stroke, and recurrent AF after discharge; secondary endpoints include recurrent atrial tachycardia (a combination of atrial fibrillation, atrial flutter, and other types of atrial tachycardia), prosthetic dysfunction, and pacemaker implantation. Cardiac death was defined as deaths from cardiovascular causes or unknown causes; stroke was defined as newly occurred stroke after discharge; recurrent AF after discharge was defined as AF recurrence among converted individuals; and prosthetic dysfunction was defined as a prosthetic valve failure requiring surgical interventions. Blinded adjudication board includes two senior cardiologists involved in assessment and classification of endpoints. If difference in opinions occurred in the assessment, a third cardiologist will be invited to help solve the disagreement. 2.3. Surgical procedures A median sternotomy approach and conventional ascending aorta and bicaval cannulation were used for all patients. A standard right atrial free wall incision was made and atrial septum approach was used to expose left atrial cavity. The left-sided MAZE procedure was performed with the same technique in both experimental groups. Left auricle was removed with Marshall ligament disconnection. In general, the ablation procedure included encirclement of the pulmonary veins with extension to the mitral valve annulus as well as extension to the appendage amputation site (Supplemental Fig. 1). An additional ablation line between the pulmonary vein encirclements was made at the left atrial dome. After ablation, patients received mitral valve replacement or other procedures. In BA group, the patients received additional ablation procedures on right atrium: a free wall incision, a line from coronary sinus to orifice of the inferior vena cava, and a line from coronary sinus to tricuspid annulus (Supplemental Fig. 1). 2.4. Peri-operative care The baseline characteristics were evaluated and all patients routinely received echocardiography, 12-lead electrocardiography and Holter monitoring preoperatively. For all but those with heart rate b60 bpm postoperatively, amiodarone was intravenously infused in a loading dose of 150 mg over 10–15 min right after the procedures,
then at a maintenance dose of 1 mg/min for 6 h, and then 0.5 mg/min. All the patients were submitted to the examination of chest X-ray, a 12-lead surface electrocardiogram (ECG), echocardiogram, and Holter monitoring before discharge. For those still in AF after surgery, cardioversion was attempted during hospital stay. Those still in AF at discharge were planned to have electrical cardioversion one month later. For patients remaining in AF three months postoperatively, further conversion attempts were at physicians' judgment. 2.5. Follow-up All patients were followed up in outpatient clinic at three months, six months and one year after discharge. The follow-up information were obtained mainly from regular outpatient clinic visits. If the patients didn't come back as scheduled, phone calls were made to obtain required information. If unscheduled visits occurred, hospital cards were used to retrieve the information. If necessary, the attending physicians were contacted for those patients not going to the outpatient clinic of our institute. In this study, the follow-up completion rate was 100%. During follow-up period, all patients took warfarin and adjusted the dose according to standard anticoagulation protocols. Oral amiodarone, in a dose of 200 mg/day, was maintained for 3 months and then withdrawn when the AF recurrence was absent. In case of recurrent AF, β-blockers would be administered. The patients of control group needed to take oral amiodarone for one year. Patients in control group required to monitor their heart rates at home (to count heart rate three times per day). If the heart rate was lower than 50 bpm, the patients should report to our researching staff. The chest X ray, liver function, and thyroid function were also routinely monitored (at three months, six months, and one year postoperatively). There were three patients who withdrew from amiodarone for reported low heart rate (b50 bpm), two patients for abnormal liver functions (three months postoperatively), and one patient for abnormal thyroid functions. Patients with abnormal liver or thyroid function would be switched from amiodarone to β-blockers while for withdrawal for heart rate reasons, amiodarone protocol was discontinued and resumed when the heart rate was over 50 bpm. While reexamined, the patients had to undergo Holter and echocardiography. In the current study, we adhered to a pre-defined three-month blanking protocol. We didn't document tachyarrhythmia events during this period. Three months after ablation, discontinuation of amiodarone was recommended. ECG, 24-hour Holter recording and transthoracic echocardiogram were obtained at our outpatient clinic in three, six, and twelve months following surgery. Any documented episode of AF or atrial tachyarrhythmia (AF/AT/AFL) lasting more than 30 s (by ECG or Holter) was considered a recurrent arrhythmic event. In the event of symptoms suggestive of ATs, patients were required to undergo additional ECG and Holter in the referring hospital. 2.6. Echocardiography assessment The echocardiography was evaluated by experienced cardiologist. During the followup visit, we focused on evaluating the size and function of the left atrium. The changes of left atrium diameter (δLAD) were obtained by the following formula:
δLAD6m ¼ LAD6m –LAD0
Fig. 1. The flow chart of the current trial. LA: left atrial group. BA: Bi-atrial group.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx δLAD6m: change of left atrium diameter six months after surgery; LAD6m = left atrium diameter six months after surgery; and LAD0 = left atrium diameter before operation. δLAD12m ¼ LAD12m –LAD0 δLAD12m: change of left atrium diameter one year after surgery; LAD12m = left atrium diameter twelve months after surgery; and LAD0 = left atrium diameter before operation. Furthermore, left atrial transportation function was evaluated through color Doppler echocardiography in one year. The peak A and peak E are indicative of the mitral valve function. When peak A of mitral valve was above 10 cm/s, we considered that the left atrium contraction is effective. 2.7. Statistical analysis According to findings in prior studies, the anticipated elimination rate of AF is 60% in surgery group, and 30% in medication group. A total sample of 189 patients (63 in each group) was computed to achieve 90% power at a 2-sided 0.05 significance level to detect the difference in effectiveness. Considering a drop-out rate of 10%, and the block size during randomization, 210 patients should be enrolled. Continuous variables are presented as means (±SD), unless otherwise specified. Categorical variables were compared among three treatment groups using chi-square test or Fisher's exact test. Nonparametric Mann–Whitney U tests and Kruskal–Wallis tests were used to compare continuous variables. The outcomes were compared using survival analysis (Kaplan–Meier and Cox analysis). Risk factors for recurrent AF and AF/AT/AFL were then estimated by a Cox proportional-hazards model, with surgical types (BA, LA or control) as the exposure variable, variables listed in Table 1 as covariate. All the statistical analyses were performed using SAS version 9.13 (SAS Inc.).
3. Results 3.1. Baseline characteristics Among the 210 patients undergoing mitral valve replacement, 67 of them received aortic valve replacement, 115 of them received tricuspid valvuloplasty and 15 received coronary artery bypass graft (CABG). After the MAZE procedure, other cardiac procedures were performed. The baseline characteristics were of no significant difference among the three groups (Table 1). The mean age of all patients was 53.0 ± 9.8 years, with 61.9% women patients. Patients with NYHA
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classification N II accounted for 41.4%. The overall median AF duration was 24 months (quartile: 12, 60). The median AF duration in BA, LA, and control group was 36 months (quartile: 12, 60), 24 months (quartile: 8, 60), and 36 months (quartile: 12, 60) respectively. The mean left atrial diameter was 52.9 ± 7.8 mm, the left ventricular end-diastolic dimension (LVEDD) was 50.1 ± 7.7 mm, and the mean left ventricular ejection fraction (LVEF) was 61.3 ± 6.6%. 10% of the patients had a history of preoperative cerebral embolism before surgery. In addition, 6.2% of the patients had coronary heart disease, 4.8% of the patients had diabetes mellitus, and 6.7% of the patients had hypertension.
3.2. Surgical data The cardiopulmonary bypass (CPB) time in LA, BA and control groups were 101.0 ± 34.0 min, 138.2 ± 46.0 min and 85.3 ± 34.7 min, respectively (P b 0.001). The aortic cross-clamp time in LA, BA and control groups were 72.1 ± 28.3 min, 101.2 ± 38.6 min and 61.9 ± 29.3 min, respectively (P b 0.001). All the patients received mitral valve replacement (MVR), while 31.9% of the patients received aortic valve replacement (AVR) and 54.8% of the patients received tricuspid valvuloplasty (TVP) during the same procedure. Moreover, 7.1% of the patients received CABG. The CPB time in LA group was 16 min longer than that in control group, and the CPB time of BA group was 37 min longer than that in control group.
3.3. In-hospital outcomes There was no perioperative death. AF conversion was considered in patients with distinguishable, sinus P waves. Before discharge, the BA group had the highest conversion rate (64.3%), while the single atrium group had a rate of 62.9%, and control group was only 22.9% (P b 0.01).
Table 1 Clinical characteristics.
Age (y) Female, n (%) BSA (m2) Duration of AF (mo) NYHA N II, n (%) Echocardiography LAD (mm) LVEDd (mm) LVEF (%) Diabetes, n (%) History of stroke, n (%) Hypertension, n (%) Hyperlipidemia, n (%) CAD, n (%)a Aortic valve diseases, n (%)a Mitral valve diseases, n (%)a Tricuspid valve diseases, n (%)a Medical therapy ß-blockers Statins ACE inhibitors Amiodarones Digoxin EuroSCORE
LA group
BA group
Control group
Total
(n = 70)
(n = 70)
(n = 70)
(n = 210)
P
52.3 ± 10.3 42 (60.0) 1.68 ± 0.18 34.5 ± 20.6 30 (42.9)
53.1 ± 9.3 47 (67.1) 1.68 ± 0.19 31.4 ± 27.2 29 (41.4)
53.6 ± 10.0 41 (58.6) 1.62 ± 0.18 33.7 ± 20.9 28 (40.0)
53.0 ± 9.8 130 (61.9) 1.66 ± 0.18 33.2 ± 23.0 87 (41.4)
0.721 0.676 0.168 0.705 0.694
54.0 ± 7.0 50.7 ± 6.9 61.2 ± 6.9 2 (2.9) 8 (11.4) 5 (7.1) 0 (0) 6 (8.6) 19 (27.1) 70 (100) 31 (44.3)
53.4 ± 6.5 50.4 ± 7.9 61.4 ± 6.5 4 (5.7) 5 (7.1) 5 (7.1) 2 (2.9) 8 (11.4) 26 (37.1) 70 (100) 44 (62.9)
51.4 ± 9.3 49.3 ± 8.2 61.2 ± 6.4 4 (5.7) 8 (11.4) 4 (5.7) 1 (1.4) 5 (7.1) 22 (31.4) 70 (100) 40 (57.1)
52.9 ± 7.8 50.1 ± 7.7 61.3 ± 6.6 10 (4.8) 21 (10.0) 14 (6.7) 3 (1.4) 19 (9.0) 67 (31.9) 210 (100) 115 (54.8)
0.111 0.501 0.964 0.678 0.220 0.223 0.486 0.397 0.469 1.00 0.497
4 (5.7) 0 (0) 3 (4.3) 2 (2.9) 58 (82.9) 2.40 ± 1.16
6 (8.6) 1 (1.4) 5 (7.1) 1 (1.4) 61 (87.1) 2.17 ± 1.31
3 (4.3) 0 (0) 3 (4.3) 3 (4.3) 62 (88.6) 2.14 ± 1.39
13 (6.2) 1 (0.5) 11 (5.2) 6 (2.9) 181 (86.2) 2.23 ± 1.29
0.298 0.995 0.451 0.321 0.807 0.434
Continuous variables were analyzed using analysis of variance. Categorical variables were analyzed using χ2 test. LA, left atrial; BA, bi-atrial; BSA, body surface area; NYHA, New York Heart Association; CAD, coronary artery disease; CTR, cardiothoracic ratio; LAD, left atrial dimension; LVEDd, left ventricular end diastolic dimension; and LVEF, left ventricular ejection fraction. a The diagnosis refers to those requiring surgical intervention.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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3.4. One-year outcomes All patients were discharged alive and finished a one-year follow-up. One patient died four months after surgery in BA group. There were no strokes, or prosthetic dysfunctions. Five cases required pacemakers subsequently, three in BA group and two in LA group. One patient received a pacemaker for a third degree atrial-ventricular block, the other four patients received pacemaker because of symptomatic bradycardia. The comparative results in terms of recurrent AF and recurrent AF/ AT/AFL were shown in Fig. 2. At six months during follow-up, the proportions of patients in sinus rhythm were 61.4%, 51.4%, and 18.6% in BA, LA, and control group, respectively; at 12 months during follow up, the proportions of patients in sinus rhythm were 57.1%, 37.1%, and
10.0% in BA, LA, and control group, respectively (Fig. 2B). For BA patients who didn't stay in sinus rhythm at one year follow-up, 21.4% (15/70) were in AF, 2.9% (2/70) in AFL, and 18.6% (13/70) in other types of AT; for those in L group, 35.7% (25/70) were in AF, 4.3% (3/70) in AFL, and 22.9% (16/70) in other types of AT; for those in control group, 77.1% (54/70) were in AF, 4.3% (3/70) in AFL, and 8.6% (6/70) in other types of AT (Fig. 2A, B). Of patients discharged in sinus rhythm, there were 8 eventually degenerating to AF during follow-up. Among the 8 patients, two were in BA group and one in LA group, all of which were paroxysmal AF. While among the 5 remaining patients in control group, 3 were paroxysmal and 2 were persistent in AF. During follow-up, both BA and LA groups showed less AF and AF/AT/AFL events than control group did (Log Rank: AF, P b 0.001; Log Rank: AF/AT/AFL, P b 0.001). In univariate Cox analysis, the two ablation groups were associated
Fig. 2. Recurrent AF and AF/AT/AFL among BA, LA, and control groups. AF = atrial fibrillation, AF/AT/AFL = atrial tachycardia, BA = bi-atrial group, and LA = left atrial group.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx
with less AF (BA group vs control group: HR = 0.210, 95% CI 0.118– 0.374, P b 0.001; LA group vs control group: HR = 0.396, 95% CI 0.247–0.635, P b 0.001) as well as AF/AT/AFL recurrent (BA group vs control group: HR = 0.367, 95% CI 0.239–0.562, P b 0.001; LA group vs control group: HR = 0.542, 95% CI 0.366–0.803, P = 0.02). The comparison between BA and LA groups revealed no differences in terms of AF (HR = 0.536, 95% CI 0.284–1.013, P = 0.06) or AF/AT/AFL (HR = 0.683, 95% CI 0.436–1.068, P = 0.09). After adjustment, BA and LA ablation were associated with less AF recurrent (BA group vs control group: HR = 0.320, 95% CI 0.181– 0.567, P b 0.001; LA group: HR = 0.532, 95% CI 0.329–0.863, P = 0.010). Higher BMI (HR = 1.104, 95% CI 1.017–1.200; P = 0.018), history of smoking (HR = 3.195, 95% CI 1.100–9.259; P = 0.033), and duration of AF (HR = 1.081, 95% CI 1.020–1.144; P = 0.008) were associated with more AF recurrence. 3.5. Echocardiographic outcomes during follow-up In six months and one year after operation, the size of the left atrium in three groups significantly reduced when compared with that before operation. All sinus-converted patients' left atrial diameter reduction was greater than that of non-sinus-converted patients (P b 0.01, Table 2). The left atrial function recovery rate was 32.9% in BA group, 31.4% in LA group, and 8.6% in control group (P b 0.01). The results revealed that the left atrial function of the ablation groups was obviously improved in contrast to that of the control group (Table 3). 4. Discussion 60% to 80% of AF patients, in need of mitral valve surgery, require ablation intervention [17,18], because postoperative sinus rhythm restoration rate would be as low as 15%–20% without specific treatments [2,19]. Although surgical ablation has been proven to be effective, it is still a concern as for whether surgical ablation concomitant with mitral valve surgery would increase the incidence of complications and mortality. What's more, it was still under debate as for whether sinus rhythm restoration can improve long-term survival [20], especially for patients with rheumatic mitral valve diseases. In the current prospectively designed, randomized controlled study involving 210 individuals, we found that patients receiving concomitant surgical ablation during valve surgery have a favorable one-year outcome when compared to those that didn't have an ablation. Substantial proportion of patients in surgical ablation group restored sinus rhythm as well as atrial transport function. Previous studies demonstrated that rheumatic AF features in inflammation, platelet activation, and increased sympathetic nerve density [7,9,12]. The vicious circle between rheumatic heart diseases and AF contributes to adverse prognosis. Kim and colleagues showed that patients with rheumatic AF receiving classic Cox-MAZE III presented a progressively decreased cure rate in long term [10]. Other authors also demonstrated that rheumatic heart disease is a strong predictor for MAZE procedure failure, and close follow-up with antiarrhythmic drugs or cardioversion is needed to improve the success rate [11]. Furthermore, after reviewing a series of 29 patients, Fukada and colleagues
Table 3 Atrial transport function restoration at 12 months postoperatively.
Left atrial transport restoration P value
LA group
BA group
control group
31.40% 0.001a
32.90% 0.000a
8.60%
LA, left atrial; BA, Bi-atrial a χ2 test.
[13] suggested a second thought for the MAZE procedure for rheumatic AF, because of poor prognosis of cut-and-sew MAZE. However, several more recent reports, in contrast to the above studies, showed that MAZE procedure provides satisfactory results. In a retrospective study, Sternik and colleagues found that the outcomes of AF ablation were similar in rheumatic and non-rheumatic patients with similar preoperative AF type and duration [14]. Another retrospective study involving 53 patients also demonstrated that radiofrequency ablation was effective in converting AF to sinus rhythm in patients with rheumatic mitral valve diseases [15]. Our results were consistent with previous studies [14,15,21], showing that concomitant AF ablation during valve surgeries had satisfactory sinus rhythm conversion rates (68.6% in LA group and 70.0% in BA group). These results might be due to advances in ablation techniques and radical surgical strategies in our center. In the current study, we found that BMI, history of smoking, and duration of AF were negatively related to sinus conversion in one year after surgery. Previous studies were in support of our findings, suggesting the association between these risk factors and the onset of AF or refractory AF [1,22,23]. A radical control of these factors is plausible to get more satisfactory surgical ablative outcomes. Aside from sinus rhythm restoration, long term prognosis involving the heart function and thrombo-embolism is also of big concern. However, in our study, the incidence rates of stroke and heart failure were quite low. Actually, there was only 1 stroke in LA group and there were no patients re-admitted for heart failure. This might be due to the low-medium risk profile of the current study. For example, in the current study the average EF was 61.28 ± 6.56% and the diameter of average left atrium was 52.92 ± 7.76, which were lower than other reports [8,23]. It is also possible that those entering RCT are more adherent to anti-coagulation and anti-heart failure therapies during follow-up period. Classic Cox-MAZE procedure is demonstrated to be highly effective in AF treatment [24,25]. But the inherent defects of the severe injury and massive bleeding can hardly be overcame [26]. Recent evidence shows that focal activation in the left atrium close to the pulmonary veins plays an important role in patients with chronic AF and mitral valve disease [27]. Therefore, less extensive lesion sets with alternative ablation techniques, to be specific, left-sided procedures, became more and more preferred. In our study, we found no significant difference in terms of one-year outcomes between LA and BA groups. Our results echoed those of another study demonstrating that the therapeutic effects seem to be equal between a left atrial MAZE procedure and biatrial procedure [28]. However, in our study five patients in BA group needed permanent pacemaker implantation during follow-up. So the more extensive bi-atrial ablation should be carefully evaluated before surgery lest adverse arrhythmic complications.
4.1. Limitation
Table 2 δLAD (millimeter). SR 6 months 12 months
5
8.87 ± 6.63 (n = 115) 10.09 ± 7.34 (n = 116)
δLAD = reduction in left atrium diameter. SR = Sinus rhythm. AF = Atrial fibrillation. a T-test.
AF 5.86 ± 6.92 (n = 94) 5.47 ± 6.89 (n = 93)
p value a
.002 .000a
This study is, however, not without its limitation. The number of patients involved is still small with somewhat low-medium risk profiles. However, it is hard to maneuver a sample with various risk stratifications, especially when candidates are not quite easy to be recruited. During the study, we do have strict inclusion criteria to guarantee a complete randomization. Another setback is that part of the patients enrolled were complicated cases instead of isolated mitral valve diseases.
Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153
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X. Wang et al. / International Journal of Cardiology xxx (2014) xxx–xxx
So the influence of other surgical procedures was unable to be excluded and the sample could not be considered representative of population with rheumatic mitral valve and AF. But in the current study, proportions of patients requiring combined CABG or AVR were evenly distributed throughout three groups. So the results were not likely to be confounded. In the current study, we found that BA/LA groups, which saw more patients staying in sinus rhythm, have significantly greater LAD reduction than in control group (Table 1). However, by randomizing 65 patients to cryoablation + mitral replacement or isolated mitral replacement group and using atrial volume as substitute for atrial function, a recent study demonstrated that left atrial volume reduced significantly six months after surgery, irrespective of sinus or AF rhythm [29]. Different indexes used might underlie the different findings. Although atrial volume is demonstrated to be a better predictor for cardiovascular prognosis [30,31], due to our institute echocardiographic protocol, the atrial volume data could not be obtained in clinical scenario. So we have to use atrial diameter. In our ongoing work, we might take atrial volume as the substitute for functional as well as thromboembolic risk evaluation. In summary, valve surgery with radiofrequency ablation could bring a higher sinus rhythm restoration rate when compared with antiarrhythmic drug therapy in low-medium risk rheumatic heart disease. What's more, left-sided atrial ablation and bi-atrial ablation provide equal one-year outcomes. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.03.153. Acknowledgments Dr. Xu Wang and Xin Wang wrote the paper; Dr. Yunhu Song and Shengshou Hu help design the protocol; Dr. Wei Wang was the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article. References [1] Go AS, Hylek EM, Phillips KA. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (atria) study. JAMA 2001;285:2370–5. [2] Chua YL, Schaff HV, Orszulak TA, Morris JJ. Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty? J Thorac Cardiovasc Surg 1994;107:408–15. [3] Handa N, Schaff HV, Morris JJ, Anderson BJ, Kopecky SL, Enriquez-Sarano M. Outcome of valve repair and the cox maze procedure for mitral regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 1999;118:628–35. [4] Guden M, Akpinar B, Sanisoglu I, Sagbas E, Bayindir O. Intraoperative saline-irrigated radiofrequency modified maze procedure for atrial fibrillation. Ann Thorac Surg 2002;74:S1301–6. [5] Sie HT, Beukema WP, Misier AR, et al. Radiofrequency modified maze in patients with atrial fibrillation undergoing concomitant cardiac surgery. J Thorac Cardiovasc Surg 2001;122:249–56. [6] Pasic M, Bergs P, Muller P, et al. Intraoperative radiofrequency maze ablation for atrial fibrillation: the Berlin modification. Ann Thorac Surg 2001;72:1484–90 [discussion 1490–1481]. [7] Azzam H, Abousamra NK, Wafa AA, Hafez MM, El-Gilany AH. Upregulation of cd40/ cd40l system in rheumatic mitral stenosis with or without atrial fibrillation. Platelets 2013;24(7):516–20. [8] Wang B, Xu ZY, Han L, Zhang GX, Lu FL, Song ZG. Impact of preoperative atrial fibrillation on mortality and cardiovascular outcomes of mechanical mitral valve replacement for rheumatic mitral valve disease. Eur J Cardiothorac Surg 2013;43:513–9.
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Please cite this article as: Wang X, et al, Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.03.153