Eur J Cardiothorac Surg 2008;34:67-72. doi:10.1016/j.ejcts.2008.03.054
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Factors predicting the time until atrial fibrillation recurrence after concomitant left atrial ablation
Herko Grubitzscha,*,
Christian Grabowa,
Helmut Orawab,
Wolfgang Konertza
a Department of Cardiovascular Surgery, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
b Department of Biostatistics and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Received 1 December 2007;
received in revised form 29 March 2008;
accepted 31 March 2008.
* Corresponding author. Address: Klinik für Kardiovaskuläre Chirurgie, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Charité-Platz 1, 10117 Berlin, Germany. Tel.: +49 30 450522092; fax: +49 30 450522921. (Email: herko.grubitzsch{at}charite.de).
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Abstract
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Objective: Treatment of atrial fibrillation, a risk factor for morbidity and mortality, by left atrial ablation is a less complex procedure which is increasingly performed in conjunction with surgery for various heart diseases. Although restoration of sinus rhythm is effective initially, atrial fibrillation may recur. We investigated factors predicting the time until its recurrence. Methods: Between January 2003 and December 2005, 162 consecutive patients (52.5% male, age 69 ± 8.7 years) with permanent atrial fibrillation underwent concomitant left atrial ablation and isolated or combined mitral valve surgery (42.6%), isolated or combined aortic valve surgery (32.1%), and isolated or combined coronary artery bypass grafting (24.1%). Ablation was performed by microwave (n
= 93, 57.4%) or radiofrequency (n
= 69, 42.6%) technology. Follow-up was after 3, 6, 12 months and yearly thereafter. Predictive values of variables for postoperative atrial fibrillation were examined using techniques of univariate and multivariate survival analysis (proportional hazards regression). Results: Eight patients died perioperatively and 13 during follow-up (not ablation related). Two patients were lost to follow-up. At last follow-up (19 ± 11.3 months), 86 patients (62%) were in stable sinus rhythm, 73 (52%) without antiarrhythmic drugs, and 43 (31%) were in atrial fibrillation. Predictors for the time until recurrence of atrial fibrillation in a multivariate model were preoperative atrial fibrillation duration (hazard ratio 1.005, 95% confidence interval 1.003–1.007, p
< 0.001) and left atrial diameter (hazard ratio 1.056, 95% confidence interval 1.020–1.093, p
= 0.002). Overall, sinus rhythm conversion rate was 75% when preoperative atrial fibrillation duration was less than 2 years, but 42% in longer lasting atrial fibrillation with left atrial dilatation (>50 mm). Age, gender, primary heart disease, history of thromboembolism or cardioversion, presence of concomitant diseases, EuroScore, left ventricular size and function, aortic cross-clamp time, ablation technology, and treatment with antiarrhythmic drugs did not predict rhythm outcome. Conclusions: Preoperative atrial fibrillation duration and left atrial diameter predict the time until atrial fibrillation recurrence after concomitant left atrial ablation, whereas age, type of primary cardiac surgery, ablation technology and antiarrhythmic therapy do not.
Key Words: Atrial fibrillation • Ablative therapy • Valvular surgery • Coronary artery bypass grafting
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1. Introduction
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Atrial fibrillation (AF) is an arrhythmia that is associated with an increased risk of stroke and premature death [1,2]. Overall, AF incidence increases with age [3] and frequently, AF accompanies structural heart disease. Thus, a significant number of patients referred for cardiac surgery present with AF.
In recent years, surgical AF treatment, classically performed as cut-and-sew maze operation [4], has developed to a less complex procedure by using different energy sources for tissue ablation. Nowadays, ablation is increasingly focused on the left side, because it became clear that AF would not recur if macro re-entry can be prevented by lesions critically placed in the left atrium [5–7]. In fact, this approach allows treatment of AF in combination with surgical interventions for almost all heart diseases.
Although restoration of SR is achieved in the majority of patients, identification of factors determining AF persistence or recurrence may further improve results. So far, for AF treatment mostly in combination with mitral valve surgery (cut-and-sew maze, radiofrequency maze, left atrial ablation), preoperative AF duration, left atrial size, age, rheumatic mitral valve disease, left ventricular ejection fraction (LVEF), and lesion pattern have been described as factors of AF recurrence [8–14].
Our objective was to assess left atrial ablation for treatment of permanent AF routinely performed in all types of cardiac surgery. We focussed on factors predicting the time until AF recurs.
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2. Materials and methods
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2.1 Patients
Between January 2003 and December 2005, a total of 162 consecutive patients (52.5% male) underwent concomitant AF ablation. Their mean age was 69 ± 8.7 years. According to established definitions [6,15], all patients presented with permanent/continuous AF. The median of AF duration was 24 months (interquartile range 6.25–72.0 months). Preoperative diameter of the left atrium was 50 ± 8.2 mm (median 50 mm). After obtaining approval of the local ethics committee and individual informed consent for the study, preoperative, perioperative and follow-up data were prospectively entered into an institutional database.
2.2 Surgical procedure
Procedures for primary cardiac surgery are listed in Table 1
. For all procedures, standard normothermic cardiopulmonary bypass and warm antegrade blood cardioplegia were used. All patients underwent endocardial AF ablation by a strict left atrial approach. According to device's availability, the lesion set (Fig. 1
) was created using microwave (Flex 4®, Guidant Corporation, Santa Clara, CA, USA) or radiofrequency (Cardioblate®, Medtronic Incorporation, Minneapolis, MN, USA) technology in 93 (57.4%) and 69 (42.6%) cases, respectively. The left atrial appendage was oversewn only if thrombi were inside (n
= 3). The transthoracic echocardiographic examination (TEE) probe was removed during ablation to avoid esophageal injury.
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Fig. 1. Lesion set. The lesion pattern consisted of (I) left atrial posterior wall ablation isolating all pulmonary vein ostia, (II) a line into the left atrial appendage, and (III) a line to the mitral valve annulus (P3).
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2.3 Perioperative treatment
All patients were anticoagulated with heparin followed by phenprocoumon. After 3 months and stable sinus or atrial driven pacemaker rhythm in Holter ECG and mechanical atrial function in echocardiogram, anticoagulation was stopped. Patients with mechanical valve substitutes were kept on phenprocoumon permanently. DC shock cardioversion of early recurrent AF was performed if patient was symptomatic or hemodynamically compromised. At the discretion of the surgeon, either patient's preoperative medication was continued or antiarrhythmic treatment with class III antiarrhythmic drugs (sotalol or amiodarone) was initiated. After discharge, patient's general practitioner or cardiologist managed the anticoagulation and antiarrhythmic therapy.
2.4 Follow-up
After 3, 6, 12 months and annually thereafter, patients were interviewed and underwent clinical, electrocardiographic and transthoracic echocardiographic examination. At 3 and 12 months, heart rhythm was monitored by 24 h Holter ECG. In only seven patients (4.3%), who were not able to visit the clinic, interviewing was done by telephone and ECG and echocardiographic data were obtained from the referring cardiologist. Any regular atrial driven rhythm, including atrial (n
= 2), atrioventricular (n
= 2), or atrial triggered ventricular (n
= 4) pacing, was regarded as sinus rhythm (SR).
2.5 Echocardiography
Preoperatively, before discharge and at follow-up, all patients underwent TTE using the HP Sonos 5500 (Hewlett Packard, Andover, Massachusetts, USA). Left atrial and left ventricular diameters were measured using standard techniques. Left ventricular ejection fraction (LVEF) was assessed by the Simpson method. For assessment of left atrial function the pulsed-wave signal of diastolic transmitral flow was used. Maximal flow velocities of early (E) and atrial (A) waves were measured and E/A ratio was calculated.
2.6 Statistical analysis
Overall rhythm outcome was assessed as AF prevalence at each follow-up visit. AF-free intervals were analyzed according to the Kaplan–Meier (K–M) method (definitions see below). The interesting event was persistent AF after surgery, defined as documented AF (ECG) in two sequential follow up visits. The middle of the period between last visit in SR and first visit in AF was assumed as time of occurrence. Data from patients with SR were censored at the time of last follow-up. Patients who died (n
= 21), and patients who were lost to follow up (n
= 2) were censored, too. Patients presenting with heart rhythm other than AF or SR (n
= 3) and patients repeatedly alternating between SR and AF (n
= 7) were excluded from analysis. Since the results of the rhythm examination are grouped into time intervals, the K–M method is as precise as the actuarial method. In order to detect potential risk factors predicting the time until AF recurrence, first durations of freedom from AF of several subgroups of patients were compared using the log-rank test. The fact that the subgroups were samples from the same population regarding freedom from AF was tested as null hypothesis. In order to explore the effects of several potential risk factors at the same time, a second Cox (proportional hazards) regression analysis was performed. The hazard ratio (HR) and 95% confidence interval (CI) of the HR were calculated for each predictor. Trying to obtain the model that predicts the time to AF recurrence best, forward and backward stepwise regression was carried out The cut-off level for statistical significance was taken at 0.05. The distribution of continuous variables in patient groups, was compared using Mann–Whitney's U-test. The distribution of categorical variables was contrasted using the 
2-test or Fisher's exact test. Analysis was performed using a statistical program (SPSS 13.0 for Windows, SPSS Inc., Chicago, IL, USA).
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3. Results
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3.1 Procedural outcome
Ablation time, aortic cross-clamp time, cardiopulmonary bypass time, and operation time were 11 ± 1.9 min, 84 ± 30.0 min, 116 ± 35.9 min, and 209 ± 50.3 min, respectively. Patients were discharged from hospital after 16 ± 14.0 days. Perioperative morbidity was characterized by re-exploration for bleeding (n
= 5), late pericardial effusion (n
= 3), heart failure (n
= 7) requiring intra-aortic balloon pump support (n
= 6) and temporary left ventricular assist device placement (n
= 1), renal failure (n
= 20), pneumonia (n
= 13), mediastinitis (n
= 1), and cerebrovascular accident (n
= 5). Perioperative mortality (30 days) was 4.9% due to cardiac failure (n
= 2), septic multiple organ failure (n
= 5), and rupture of a descending aortic aneurysm (n
= 1). Ablation procedure per se did not cause any injury or death.
The last available follow-up visit was after 19 ± 11.2 months. In total, two patients (1.2%) were lost and 13 patients (8.0%) died during follow-up. Causes of death were heart failure (n
= 4), sudden cardiac death (n
= 1), multiple organ failure following major abdominal surgery (n
= 2), pneumonia (n
= 2), intracerebral hemorrhage (n
= 1), and unknown (n
= 3). Thromboembolic events did not occur.
From 139 patients available for follow-up, 86 (62%) were in stable sinus rhythm, 73 (52%) without antiarrhythmic drugs, and 43 (31%) were in AF at last visit. Remaining patients were alternating between SR and AF (n
= 7), presented atrial flutter (n
= 2) or AV junctional rhythm (n
= 1). AF prevalence at each follow-up visit and the Kaplan–Meier estimates of overall freedom from AF over time are shown in Fig. 2
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Fig. 2. Atrial fibrillation after ablation. The upper graph shows AF prevalence at certain follow-up visits. The lower graph depicts Kaplan–Meier estimates of freedom from AF. Numbers in bars reflect absolute frequency of patients presenting with AF.
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3.2 Predictors for AF recurrence
Table 2
lists preoperative and perioperative characteristics that were analyzed as potential factors for rhythm outcome. Age, gender, body surface area, history of thromboembolism or cardioversion, NYHA functional class, left ventricular size and function, primary heart disease, presence of concomitant diseases, EuroScore, ablation time and technology, and perioperative treatment with antiarrhythmic drugs or DC shock cardioversion did not determine AF recurrence.
The final proportional hazard regression model contains two explanatory variables: preoperative AF duration (hazard ratio [HR] 1.005, 95% confidence interval [CI] 1.003–1.007, p
< 0.001) and preoperative LA size (HR 1.056, 95% CI 1.020–1.093, p
= 0.002) are the best predictors of the time until AF recurrence after operation. Taking the median of AF duration and LA diameter of our cohort as cut-off values, Fig. 3
shows that sinus rhythm conversion rate was superior when preoperative AF duration was 2 years or less. In longer lasting AF, LA dilatation worsened the results if LA diameter was larger than 50 mm.
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Fig. 3. Relationship between predictors of time to AF recurrence and presence of sinus rhythm at last follow-up. According to the median of preoperative LA diameter and AF duration, several patient groups were created (see left-sided legend within bars). Observed sinus rhythm restoration rate at last follow-up is shown. Right-sided numbers within bars reflect absolute frequencies of patients with sinus rhythm. For comparison the
2-test was used.
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3.3 Follow-up results according to heart rhythm
According to transmitral diastolic flow-pattern, 91.1% of patients with SR at latest follow-up presented with normal atrial transport function with an E/A ratio of 2.4 ± 0.82. Compared to patients with AF, more patients with successful SR conversion were in a NYHA class II or less (75 [87.1%] vs 33 [76.7%] patients, p
= 0.023). Based on the number of patients reporting palpitations there was a non-significant trend to fewer episodes with SR (3 [3.5%] vs 5 [11.6%] patients, p
= 0.173). Although left atrial diameter was significantly smaller in SR patients (40 ± 6.8 vs 44 ± 7.1 mm, p
= 0.002), the magnitude of size reduction after operation was comparable in each group (23 ± 12.1 vs 19 ± 11.9%, p
= 0.134). There was no significant difference in dimensions or function of the left ventricle. In patients with AF versus SR, treatment with beta-blocker (32 [74.4%] vs 72 patients [83.7%], p
= 0.376) and class III antiarrhythmic drugs (3 [7.0%] vs 11 patients [12.8%], p
= 0.346) was similar, whereas digitalis was taken more frequently (16 [37.2%] vs 14 patients [16.3%], p
= 0.006). The majority of AF patients (n
= 38, 88.4%) were treated with anticoagulants. However, 37 SR patients (43.0%) were still on phenprocoumon.
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4. Discussion
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With this study we evaluated factors predicting the time until AF recurrence after concomitant left atrial ablation for treatment of permanent AF in patients undergoing cardiac surgery for coronary artery, valvular, or combined heart disease. Out of a huge variety of potential factors examined, only preoperative AF duration and left atrial size were significant determinants for rhythm outcome. Every 1-month increase in AF duration corresponded to an increase in the risk for recurrent AF after surgery of 0.5% and every 1 mm increase in left atrial diameter to a 5.6%-increase in the risk.
Whereas with biatrial maze procedures, performed using either the cut-and-sew technique or ablative technology, preoperative AF duration and left atrial size have been reported to be the most important predictors for AF recurrence [8–11], this has not been demonstrated with left atrial ablation so far (Table 3
) [13,14]. A reason could be that only 67% and 73% of patients from the left atrial ablation studies presented with permanent AF that may have outweighed the influence of AF duration or LA size. Furthermore, Manasse et al. [13] used several different lesion patterns that determined the results rather than did the AF criteria. The importance of left atrial lesions including wide pulmonary vein isolation, at least one connection line between the left and right pulmonary veins, and a connection to the mitral valve annulus when applying alternative energy sources has been proved recently [7]. Pulmonary vein isolation and lesion sets that did not include a lesion to the mitral annulus were less effective for the treatment of permanent AF [7].
In our cohort, SR conversion rate was satisfactory in patients with preoperative AF duration of up to two years (Fig. 3). If AF lasted longer, only 48% of patients were in SR at last follow-up. Left atrial dilatation beyond 50 mm in diameter led to a further reduction of the success rate to 42%. Undoubtedly, from our experience we can conclude that concomitant treatment of permanent AF by left atrial ablation should be undertaken early, if possible before preoperative AF duration exceeds two years. It seems reasonable to consider reduction plasty, if the left atrium is dilated more than 50 mm in diameter. Due to the heterogeneity of our cohort, we may have neither been able to define clear cut-off values of AF predictors nor find out if the magnitude of AF duration and left atrial size, which is associated with satisfactory rhythm results, differs between patients with primary mitral valve disease, aortic valve disease or coronary artery disease.
Whether or not patients with longer lasting AF may benefit from concomitant biatrial ablation or a cut-and-sew Cox-maze III procedure remains a matter of debate. Regarding the excellent SR conversion rates after concomitant Cox-maze or similar procedures [8,10,11], the younger mean age in these cohorts (ranging from 51 to 62 years) has to be considered. AF incidence increases with age in general [3] and older age was shown to be a significant patient-related risk factor for postoperative AF [7]. According to Khargi's meta-analysis that investigated cut-and-sew procedures and ablative techniques, the SR conversion rate was similar when both age and frequency of paroxysmal or lone AF were taken into consideration [16]. Another report claims that biatrial approaches were more effective than left atrial ones, but the patients’ age was completely ignored in this analysis [17]. The mean age of our patients was almost 70 years and increasing age of patients requiring cardiac surgery has to be anticipated for the future. From that point of view, focusing concomitant AF treatment on the left atrium, where the majority of AF is anchored, could be a reasonable way of reducing operative risk, which is higher in older age [18].
In this and other studies [19,20], a beneficial effect of SR conversion on functional status could be demonstrated. This probably results from restored atrial transport function in the majority of patients with SR, as the left ventricular function was comparable to that of patients developing recurrent AF. Obviously, the frequency of palpitations reported by patients was higher when AF recurred.
4.1 Limitations of the study
We used Holter monitoring data and ECGs at follow-up visits for the assessment of heart rhythm results. Hence, asymptomatic AF episodes occurring meanwhile may have been missed. However, continuous monitoring of heart rhythm is currently not feasible, even with 7 days Holter monitoring or event recorders [21]. Certainly, bias was reduced by excluding patients with repeated alternations between SR and AF from analysis.
As time until recurrence of AF was in focus, we used proportional hazards regression as statistical tool for identifying risk factors. The assumption of proportional hazard functions in patients with permanent AF undergoing concomitant ablation seems reasonable. The fact that postoperative AF prevalence has an early peak component and a chronic constant phase [7] suggests that effects of variables influencing the time until AF recurrence are not constant over time. In general, analysis of AF recurrence using survival data methodology is difficult and interpretation must be done with caution [21]. If continuous monitoring of rhythm and its duration becomes available in the near future, the most appropriate method of reporting rhythm outcome will be time-related burden of AF.
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Acknowledgments
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We are thankful to Mrs Doreen Boettner for the excellent work she did in co-ordinating patients’ follow-up.
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Abstract
1. Introduction
