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Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Napoli, Italy
Accepted for publication July 19, 2007.
* Address correspondence to Dr Onorati, Viale dei Pini, 28, Napoli, 80131, Italy (Email: frankono{at}libero.it).
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Abstract |
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Methods: Eighty-seven patients undergoing radiofrequency left mini-Maze without (group A) or with (group B) concomitant cavotricuspid isthmus ablation underwent serial electrocardiography and echocardiography to assess sinus rhythm recovery and atrioventricular remodelling. Recurrence of AF, incidence of atrial flutter, hospital readmission, and episodes of congestive heart failure were recorded. Predictors of AF recurrence were evaluated.
Results: Follow-up of 33.4 ± 11.2 months demonstrated 88.5% had sinus rhythm recovery, with normalized E/A velocity in 90.9%. Freedom from AF recurrence, congestive heart failure, and hospital readmission was 72.6% ± 7.8%, 93.3% ± 5.5%, and 79.9% ± 8.2%, respectively, without differences between the two groups. Atrial flutter developed in group A more frequently during hospitalization (19.5% versus 2.2%; p = 0.009) and follow-up (12.2% versus 0%; p = 0.02); freedom from atrial flutter was thus lower (79.6% ± 7.8% versus 100%; p = 0.024). Although no differences were recorded in postoperative and follow-up New York Heart Association (NYHA) functional class or in postoperative or follow-up echocardiographic indicators between the two groups, AF patients displayed a worse NYHA than did sinus rhythm patients (discharge p = 0.009; follow-up p = 0.0002). Accordingly, only sinus rhythm patients showed reverse remodelling of longitudinal (discharge p = 0.002; follow-up p = 0.0001) and transverse diameter (discharge p = 0.0001; follow-up p = 0.001), and of follow-up left ventricular diastolic diameter (p = 0.0001). Mitral valve disease and high postoperative and follow-up echocardiographic pulmonary pressures were independent predictors of AF recurrence. Left + right ablation was the only protective factor against AF recurrence.
Conclusions: Concomitant cavotricuspid isthmus ablation should be routinely considered in AF surgery, given the shorter hospitalization, low incidence of atrial flutter onset, and beneficial effect on AF recurrences.
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Introduction |
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These innovations, however, carry the risk of failing to achieve a transmural effect and impairing efficacy. These factors, together with the more frequent adoption of the surgical approach, have led to the appearance of various supraventricular tachycardias, chiefly atrial flutter [4–8], in a considerable percentage of patients treated for AF. Although the nature of atrial flutter is still unclear, some authors have shown that the right isthmus plays a key role in its appearance, which further demonstrates the efficacy of right isthmus ablation in treating this postoperative complication [5–8].
Accordingly, we recently reported the preliminary results of a simple technique in which bipolar irrigated radiofrequency (RF) energy is used to ablate the cavotricuspid isthmus to reduce the incidence of postoperative atrial flutter [9]. Since then, we have routinely adopted this strategy to ablate the left and right atria simultaneously in patients with AF who undergo cardiac procedures.
The aim of the present study was to compare the clinical, electrocardiographic (ECG), echocardiographic, and follow-up results of two different strategies—isolated left mini-Maze versus left + right mini-Maze—used in the last 4 years to contemporary treat AF in patients undergoing cardiac operations.
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Material and Methods |
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Aortic valve repair was performed through an oblique aortotomy: aortic valve prostheses were implanted in supraannular position with pledgeted interrupted Tevdek 2-0 stitches (Genzyme Biosurgery, Cambridge, MA). The mitral valve procedure was performed through a longitudinal atriotomy, with prostheses always being implanted in the intraannular position. When tricuspid disease was encountered, longitudinal inter-caval right atriotomy was used as the surgical access. Intraoperative data are summarized in Table 1.
Two surgical strategies were adopted for arrhythmia: 41 patients underwent isolated left mini-Maze (group A), mostly during the first phase of the study (January 2003 to December 2004); 46 patients underwent combined "left + right mini-Maze" (group B), mostly during the second surgical phase (December 2004 to December 2006). Left-sided lesions are reported in Figure 1. A total of 19 patients (46.3%) in group A and 14 patients in group B (30.4%; p = 0.096) underwent left mini-Maze using isolated endocardial irrigated monopolar RF ablation (RFA) with the Cardioblate surgical pen and Cardioblate surgical ablation generator (both Medtronic, Minneapolis, MN) as the power source. The remaining 22 patients (53.7%) in group A and 32 (69.6%; p = 0.096) in group B underwent combined endocardial irrigated monopolar RFA with the Cardioblate pen plus bipolar RFA with the bipolar clamp (Medtronic).
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Right-sided ablation lines were created as previously reported [9]. Owing to the risk of incomplete septal isthmus ablation, patients with 7.0 cm or more right atrium undergoing tricuspid valvuloplasty also underwent monopolar RFA septal isthmus ablation. However, except for the surgical AF ablation technique, preoperative, intraoperative, and postoperative management were the standard during the study.
Postoperative Care
Inotropic support was defined as low-dose when enoximone was administered at a dosage of 5 µg/kg/min, medium-dose between 6 and 10 µg/kg/min or when dobutamine was added between 5 and 10 µg/kg/min, and high-dose when enoximone or dobutamine exceeded 10 µg/kg/min or epinephrine at any dose was added.
An intravenous amiodarone bolus (150 mg), followed by continuous intravenous infusion at 1 mg/kg/h for 12 hours and then 0.5 mg/kg/h until patients tolerated oral intake, was routinely administered intraoperatively. Patients then received oral amiodarone (200 mg twice daily for 1 week, then 200 mg daily) until postoperative month 6. Those with postoperative persistence of AF, as well as those with new-onset AF or atrial flutter, did not undergo electrical cardioversion but were treated with intravenous and oral amiodarone. The international normalized ratio was maintained between 2.5 and 3.5 for the first 6 months in all patients and life-long in patients who received mechanical valves or who had AF persistence, or both.
Cardiac Rhythm Assessment and Follow-up
Twelve-lead ECG recordings were performed preoperatively, on admission to the intensive therapy unit, and daily thereafter until hospital discharge or whenever necessary. All patients underwent continuous ECG monitoring for the first 72 hours postoperatively. The incidence of dysrhythmias, both atrial and ventricular, was recorded during hospitalization and follow-up.
Mean follow-up time was 33.4 ± 11.2 months (range, 6 to 49 months), and no patient was lost during follow-up (100% complete). Postoperative follow-up data were collected by routine examination in our outpatient clinic at 7 and 14 days, 1, 3 and 6 months, and 1 year, and then yearly or whenever requested by the patient. Phone contacts with patients and cardiologists were made when necessary. One month after operation, patients underwent 24-hour Holter ECG, which was repeated at least once during the first 6 months of follow-up. Six months of follow-up was recorded. Follow-up was closed on the June 30, 2007.
End Points
AF recurrence and atrial flutter onset were the primary end points. AF recurrence was defined as any symptomatic episode of AF, or AF requiring hospital admission or specific therapy, as well as any AF episode registered at Holter or occasional ECG. Independent predictors of AF recurrence were analyzed.
Secondary end points were episodes of congestive heart failure (CHF) and hospital readmission, which were monitored during follow-up. CHF was defined as any episode of cardiac decompensation during follow-up requiring adjustment of the therapy or hospitalization. Hospital readmission was defined as any hospital admission due to cardiac causes that required more than a 6-hour stay.
Echocardiography
The echocardiographic examinations were performed preoperatively, postoperatively, and at the 6-month follow-up using a VIVID 7 Pro ultrasound machine (GE Technologies, Milwaukee, WI).
Statistical Analysis
Continuous variables are expressed as mean ± SD, and categoric data as proportions. Comparisons of continuous variables were made with Student unpaired t test, and categoric variables were compared with the 
2 test or Fisher exact test. Comparison between and within groups was made using two-way analysis of variance for repeated measures. Univariate analyses of risk factors were performed. Variables with a p < 0.05 were consecutively subjected to a multivariate logistic regression model to assess the independent impact of each risk factor on AF recurrence. A stepwise procedure (backward Wald) was used with a p < 0.05 to enter and eliminate variables.
Freedom from AF, atrial flutter, CHF, and hospital readmission was determined by means of the Kaplan-Meier life-table analysis. The log-rank test was performed to ascertain differences during follow-up between patients with isolated left mini-Maze and those with combined left + right mini-Maze, as well as between patients maintaining sinus rhythm and those experiencing AF recurrence/atrial flutter onset. All statistical analyses were considered significant at p < 0.05 and were performed with SPSS 10.1 software (SPSS Inc, Chicago, IL).
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Results |
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During hospitalization, 29 patients (33.3%) required low doses of inotropic drugs, 56 (64.4%) had medium doses, and 2 (2.3%) needed high doses. Again, no differences in perioperative inotropic support were detected between the two groups (high doses—group A: 0 of 41 [0%] versus group B: 2 of 46 [4.3%]; medium doses—group A: 29 of 41 [70.7%] versus group B: 27 of 46 [58.7%]; low doses—group A: 12 of 41 [29.3%] versus group B: 17 of 46 [37.0%]; p = 0.265).
Finally, although the group A and B had similar lengths of stay in the intensive therapy unit, at 2.17 ± 0.44 days versus 2.15 ± 0.41, respectively (p = 0.702), hospitalization was slightly shorter in group B (6.82 ± 0.67 days) compared with group A (7.60 ± 1.11 days; p = 0.018), generally due to rhythm issues.
When long-term amiodarone therapy was considered, only 1 patient, who was in group B (2.2%; p = 0.529), experienced optic neuropathy at 4 months after surgery, with partial improvement after drug discontinuation.
Cardiac Rhythm
On aortic declamping, 64 patients (73.6%) recovered sinus rhythm, 17 (19.5%) were in junctional rhythm, and 6 (6.9%) displayed persistence of AF. Group B showed a lower rate of AF persistence at 2.2% (1 of 46) versus group A at 12.2% (5 of 41; p = 0.077), but had a higher rate of junctional rhythm requiring temporary pacemaker stimulation at 26.1% (12 of 46) versus 12.2% (5 of 41; p = 0.086), although these differences were not significant. However, a comparable restoration of sinus rhythm was detected (group A: 31 of 41 [75.6%] versus group B: 33 of 46 [71.7%]; p = 0.435). All patients were treated with amiodarone postoperatively, as mentioned, and 79 (90.8%) recovered and were discharged in sinus rhythm. One patient in group A (2.4%) and 2 in group B (4.3%; p = 0.544) needed definitive ventricle-paced, ventricle-sensed, inhibited (VVI) pacemaker implantation; 8 (9.2%) were discharged in AF. On discharge, no differences were recorded between the groups A and B in either AF (5 patients [12.2%] versus 3 patients [6.5%], respectively; p = 0.294) or sinus rhythm (35 of 41 [85.4%] versus 41 of 46 [89.1%], respectively; p = 0.418).
At the 6-month follow-up, a higher proportion of patients in group A demonstrated AF persistence compared with group B (6 of 41 [14.6%] versus 2 of 46 [4.3%]; p = 0.099), even though a comparable proportion of patients in the two groups experienced episodes of AF during the first 6 month of follow-up (2 of 41 [4.9%] versus 4 of 46 [8.7%]; p = 0.395).
On follow-up examination after a mean 33.4 ± 11.2 (SE) months (range, 6 to 49 months), 77 patients (88.5%) were in sinus rhythm. Of the 10 patients in whom AF persisted at the closure of follow-up, 8 belonged to group A (19.5%) and 2 to group B (4.3%; p = 0.041). Actuarial freedom from AF recurrence after 40.7 ± 1.9 months was 72.6% ± 7.8% (Fig 2A). Although follow-up proved shorter in patients undergoing combined left + right Maze (29.9 ± 1.9 months versus group A: 39.1 ± 2.6), no differences were recorded when actuarial freedom from AF recurrence was compared between the two groups (Fig 2B).
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The rate of postoperative atrial flutter was significantly higher in group A patients during hospitalization (8 of 41 [19.5%]) compared with group B (1 of 46 [2.2%]; p = 0.009) and during follow-up (5 of 41 [12.2%] versus 0 of 46; p = 0.02). However, no episodes of atrial flutter were registered during the first 6 months of follow-up. Because the cumulative actuarial freedom from atrial flutter after 45.7 ± 1.3 SE months was 87.1% ± 5.9% (Fig 2C), group B displayed significantly greater freedom from atrial flutter during follow-up (Fig 2D). Finally, when the subgroup of patients who had undergone tricuspid valve operations (with longitudinal right atriotomy scar) was considered, no cases of atrial flutter were registered in those who had undergone combined left + right RFA, with a significantly higher incidence of atrial flutter in group A during hospital stay (8 of 15 [53.3%]; p = 0.001) and during follow-up (5 of 15 [33.3%]; p = 0.018).
New York Heart Association Functional Class
In all patients NYHA class improved significantly after surgery, from 3.42 ± 0.52 preoperatively versus 1.45 ± 0.56 at discharge (p = 0.0001), and further ameliorated during follow-up at 1.10 ± 0.30 (p = 0.0001 versus preoperative [p = 0.001] versus discharge). No differences were recorded between the two groups in terms of NYHA improvements on discharge (group A preoperative NYHA: 3.36 ± 0.48 versus postoperative NYHA: 1.41 ± 0.54, p = 0.0001; group B preoperative NYHA: 3.47 ± 0.54 versus postoperative: 1.50 ± 0.58, p = 0.0001; statistical significance between groups, p = 0.486) or during follow-up (group A follow-up NYHA: 1.09 ± 0.30 [p = 0.0001] versus postoperative NYHA; group B follow-up NYHA: 1.10 ± 0.31 [p = 0.0001] versus postoperative NYHA; statistical significance between groups, p = 0.867).
However, patients discharged in AF displayed less improvement in NYHA class than those discharged in sinus rhythm (AF patients’ preoperative NYHA: 3.45 ± 0.52 versus NYHA on discharge: 1.72 ± 0.46, p = 0.0001; sinus rhythm patients’ preoperative NYHA: 3.42 ± 0.52 versus NYHA on discharge: 1.42 ± 0.57 [p = 0.0001] versus preoperative [p = 0.009 versus AF patients]); a similar trend was seen during follow-up (AF patients’ follow-up NYHA: 1.36 ± 0.50 [p = 0.033] versus discharge NYHA; sinus rhythm patients’ follow-up NYHA: 1.08 ± 0.28 [p = 0.0001] versus discharge NYHA, p = 0.0002 versus AF patients).
Two patients, both from group A, had episodes of CHF during follow-up. The global actuarial freedom from CHF after 42.5 ± 1.2 SE months was therefore 93.3% ± 5.5% (Fig 3A). No differences were recorded between the two groups in follow-up freedom from CHF (Fig 3B). On the other hand, 7 patients were readmitted to the hospital during follow-up, meaning that actuarial freedom from hospital readmission was 79.9% ± 8.2% after 39.4 ± 1.6 SE months (Fig 3C). Again, no differences were detected between groups A and B in follow-up freedom from hospital readmission (Fig 3D).
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Predictors of Atrial Fibrillation Recurrence
Univariate analysis revealed that 16 of 57 recorded variables were significantly (p < 0.05) associated with AF recurrence at the end of follow-up (Appendix). However, multivariate logistic regression analysis demonstrated that the only independent predictors of AF recurrence were mitral valve disease and high (
45 mm Hg) postoperative and follow-up echocardiographic PAPs. By contrast, combined left + right RFA was the only protective factor against AF recurrence (Table 3).
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Comment |
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It is well known that although the left-sided partial Maze procedures can eliminate AF, they carry an estimated 5% to 10% increased risk of atrial flutter, which is usually of right atrial origin [5–8, 15]. This is of particular relevance for the scientific community, given that in most studies it is difficult to determine whether coronary sinus ablation has been performed [2]. Since Cox and Ad [16] emphasized the importance of right-sided ablation, various studies in the literature have shown the beneficial role of right isthmus ablation, although performed postoperatively by interventional procedures [5, 6, 17]. Nakagawa and colleagues [17] emphasized the importance of the isthmic line between the coronary sinus and the tricuspid valve in preventing atrial flutter onset. Accordingly, in explanted hearts, Chauvin and colleagues [18] observed striated muscle around the coronary sinus, connecting the inferior right atrium to the left atrium, which may account for the inconsistent results reported for the isolated left atrial ablation procedures.
Our finding that combined left + right ablation yielded better results can be further explained by the observation that our patients were referred for surgical treatment in the presence of advanced biatrial enlargement. Indeed, according to Lammers and colleagues [19], who first showed that the left atrial refractory period is shorter than the right and given that AF can be maintained in the right atrium only if the atrium is enlarged [2], it can be hypothesized that in patients with normal atria, isolated left-sided AF ablation is sufficient to avoid AF and atrial flutter recurrence owing to the shorter refractory periods of the left atrium, whereas additional right atrial ablation lines will be required in patients with large right atria [19].
Our original technique of right isthmus ablation has been shown to be safe and effective in lowering the postoperative risk of atrial flutter onset by achieving both septal and inferior isthmus ablation [9]. Our results are consistent with those obtained by means of postoperative interventional procedures [5, 6, 17]; however, our technique has the great advantage of being a single-stage procedure. It can be suggested that the single-stage nature of the procedure may yield somewhat of a reduction in hospital costs (as shown by the slightly lower hospital stay observed in group B), which is further enhanced by the possibility to perform a full right + left ablation off-pump [9]. Moreover, the success rate of cardiologic interventional procedures is reported to be higher after ablation of the posterior isthmus than after septal isthmus ablation alone, owing to the ease of achieving a stable catheter position at the posterior isthmus [6]. In our procedure, the bipolar RF forceps can be positioned easily and stably on both the septal and posterior isthmus.
The incidence of definitive pacemaker implantation that we recorded was significantly lower than the 5% to 25% reported for the Cox-Maze III [1, 8, 20], nor was there a significant difference between our two groups. This is because our right lesion set is critically targeted on the cavotricuspid isthmus, thus avoiding the risk of transecting the sinus node arteries, irrespective of their origin. Furthermore, it is well known that alternative energy sources carry a still lower risk of this complication than the cut-and-sew method [8].
It is well known that transmurality plays a key role in the success of ablation procedures [1–4, 6, 12, 14]. Recent animal studies have shown that bipolar RF induces complete and permanent transmural lesions [21], and clinical experiences with such devices are promising [12, 14, 22]. It can therefore be argued that the extensive use of the RF bipolar clamp to ablate the cavotricuspid isthmus in our experience may be responsible for permanent transmural isthmic lesions, which would explain the very low incidence of atrial flutter in our group B. Indeed, the only postoperative atrial flutter detected in group B was seen in a patient with a huge right atrium (8.5 cm) who had undergone concomitant monopolar RF septal isthmus ablation, which carries the risk of incomplete, nontransmural, ablation. On the other hand, we did not find significant differences in freedom from AF recurrence in patients undergoing monopolar versus monopolar + bipolar ablation. It can be hypothesized that the comparable cross-clamp time may account for a similar efficacy of the lesions in terms of transmurality.
In the subgroup of patients who underwent concomitant tricuspid procedures, we found a further significant difference in atrial flutter onset and freedom from atrial flutter in the two groups; indeed, it is well known that incisional atrial flutter may easily develop around a right atriotomy [8]. Usui and colleagues [8] recommend additional cryoablation between the right atriotomy ridge and the inferior vena cava. Furthermore, Chan and coworkers [5] first demonstrated that the right isthmus is part of the reentrant circuit and can be targeted for ablation with a good rate of success; by contrast, when the cavotricuspid isthmus is not part of the reentrant circuit and other areas of the right atrium are targeted for ablation, the results of ablation are not as good. We suggest routine right ablation in patients undergoing tricuspid surgery [5]. Our results can therefore be attributed to a high success rate of cavotricuspid isthmus ablation in preventing postoperative incisional flutter.
It is well known that AF impairs cardiac function; therefore, it can be expected that restoring sinus rhythm will positively influence ventricular function. Accordingly, we found a significant recovery of functional status in all patients undergoing this procedure, confirming previous reports by Stulak and colleagues [23] and Gillinov and colleagues [3]. However, our results showed that although all patients recovered their functional status because of the relief of the underlying heart disease, only those who also recovered sinus rhythm displayed a further improvement in their symptoms; this improvement was significantly greater than in patients in whom AF persisted following surgery.
Previous studies have demonstrated that sinus rhythm restoration induces reverse remodelling of atrial geometry [24]. Establishing whether the magnitude of this remodelling is due to sinus rhythm restoration or to the relief of the underlying heart disease is challenging. Our results demonstrated that only sinus rhythm patients showed reverse remodelling of both longitudinal and transverse atrial diameters, in addition to improved PAPs and LVMi. Furthermore, a high percentage of these patients (90.9%) displayed a normalized E/A ratio with restoration of the atrial kick. Reverse atrial remodelling therefore does not take place in AF patients, despite the relief of the underlying heart pathology.
Finally, multivariate analysis showed that four variables independently correlated with AF recurrence, and that the combination of left-sided + right-sided ablation was the only protective factor towards recurrences. The growing number of CHF patients referred to surgery has led to the frequent observation of biatrial enlargement in the operating theater. It has also been demonstrated that the left atrial refractory period is shorter than the right [19], and that AF persists in enlarged right atria [2]. In this scenario, associated right lesions may be helpful in reducing AF recurrence [19]. Of the other three variables selected by multivariate analysis, mitral valve disease is the principal underlying heart disease associated with AF because it creates all the conditions that trigger AF (atrial enlargement and structural abnormality, inflammation or fibrosis, electrical dysfunction, among others) [3]. It is not surprising that in a mixed population, like that of our study, mitral disease significantly favors AF recurrence more than other cardiac diseases. High postoperative and follow-up PAPs, on the other hand, indicate a persistent state of cardiac failure despite operation: complex neuroendocrine mechanisms activated by a CHF state are responsible for hyperexcitability of the atria [25], which poorly respond to surgical procedures. AF ablation will not be successful in these patients unless the heart failure is relieved.
We conclude that RFA of the right isthmus should be routinely considered in patients undergoing AF ablation during heart surgery, given the shorter hospital stay, low incidence of atrial flutter onset and beneficial effect on AF recurrences.
The main limitation of the study is the limited number of patients enrolled; the lack of randomization to treatment is another. Moreover, different associated cardiac diseases affected the study population, and the type and duration of AF were heterogeneous. All these limitations stem from the single-center design of the study, which, on the other hand, guaranteed uniformity of the perioperative management of the patient population. The use of a historical control means that follow-up is shorter in the group with concomitant cavotricuspid isthmus ablation. This is another limitation of the study. Further randomized study would be required to confirm the necessity of concomitant cavotricuspid isthmus ablation during AF operations.
At the same time, the strengths of our study include its prospective design and the sequential echocardiographic assessment of both atrial and ventricular size and function before and after operation. Furthermore, few data are available in the literature with which to compare isolated left-sided with combined right-sided + left-sided ablation, especially in the heart operations.
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