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(Circulation. 1995;92:430-435.)
© 1995 American Heart Association, Inc.

Articles

The Risk of Atrial Fibrillation Following Radiofrequency Catheter Ablation of Atrial Flutter

François Philippon, MD; Vance J. Plumb, MD; Andrew E. Epstein, MD; G. Neal Kay, MD

From the Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham.

Correspondence to G. Neal Kay, MD, Professor of Medicine, Division of Cardiovascular Disease, Department of Medicine, 321J Tinsley Harrison Tower, University of Alabama at Birmingham, Birmingham, AL 35294.

	Abstract

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Background Although radiofrequency catheter ablation of atrial flutter is associated with a high rate of initial success, several clinical issues regarding this therapy remain to be defined. For example, the risks of recurrent atrial flutter and of developing atrial fibrillation after flutter ablation are unknown. In addition, it is not known whether elimination of atrial flutter will modify the natural history of atrial fibrillation in patients who experience both of these arrhythmias. The purpose of the present study was to determine the actuarial freedom from recurrent or new atrial arrhythmias in patients with atrial flutter undergoing catheter ablation.

Methods and Results The study population consisted of 59 consecutive patients (mean age, 61.9±12.6 years) with typical atrial flutter who underwent catheter ablation of the reentrant circuit. Catheter ablation was not advised for patients in whom paroxysmal atrial fibrillation had been a major clinical problem. The inducibility of atrial fibrillation and atrial flutter was assessed after successful atrial flutter ablation with programmed atrial stimulation and rapid atrial pacing to a cycle length of 180 ms or 2:1 atrial capture. Atrial flutter was successfully ablated and rendered noninducible in 53 of 59 patients (90%). Over a mean follow-up period of 13.2±6.6 months, atrial flutter recurred in 5 patients (9.4%). Atrial fibrillation occurred in 14 of 53 patients after successful ablation (26.4%). Four clinical variables were associated by univariate analysis with the late occurrence of atrial fibrillation: (1) the presence of structural heart disease, (2) a history of atrial fibrillation before ablation of atrial flutter, (3) inducible sustained atrial fibrillation after ablation, and (4) a greater number of failed antiarrhythmic drugs. By multivariate analysis, only the persistent inducibility of sustained atrial fibrillation predicted the later development of atrial fibrillation.

Conclusions Although atrial flutter ablation is highly effective and associated with a low risk of recurrent atrial flutter, atrial fibrillation continues to be a long-term risk for individuals undergoing this procedure. The risk of later atrial fibrillation is especially high for patients in whom sustained atrial fibrillation remains inducible after ablation of atrial flutter.

Key Words: atrial flutter • fibrillation • catheter ablation

	Introduction

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Typical atrial flutter is often associated with disabling symptoms and may be resistant to treatment with antiarrhythmic medications.^{1 2 3 4 5} The present concept of atrial flutter is that of a reentrant circuit within the right atrium that is related to the anatomic barriers of the inferior vena cava, coronary sinus ostium, and the tricuspid annulus.^{6 7 8 9 10 11 12 13 14 15} Because the reentrant circuit of atrial flutter may involve reentry around either the tricuspid annulus or within the low right atrium, this arrhythmia can be successfully ablated by the application of direct current or radiofrequency energy in the isthmus of atrial tissue bounded by these structures.^{16 17 18 19 20 21 22 23 24 25 26 27 28}

Although a high initial rate of successful ablation of atrial flutter has been described with the application of radiofrequency current,^{22 24 25 26 28} several clinical issues remain to be settled. Among these, the risk of late recurrence of atrial flutter after successful catheter ablation has not been clearly defined. Second, since many patients experience clinical episodes of both atrial flutter and atrial fibrillation, it is not known whether ablation of atrial flutter will eliminate or reduce the risk of recurrent atrial fibrillation. Third, although patients with atrial flutter who never experienced an episode of atrial fibrillation might be expected to have a low risk of this arrhythmia after ablation of atrial flutter, it is uncertain whether this is true. For example, it is likely that similar anatomic and electrophysiological factors predispose individuals to both arrhythmias.²⁹ Therefore, in order to better understand the role of catheter ablation in the long-term management of patients with atrial flutter, the risk factors for the late development of atrial fibrillation must be identified. To address these questions, we conducted a prospective study of the clinical and electrophysiological factors that predict the late occurrence of atrial fibrillation after successful radiofrequency catheter ablation of atrial flutter.

	Methods

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Study Population
The study population consisted of 59 consecutive patients who underwent catheter ablation of typical (type 1) atrial flutter⁵ at the University of Alabama at Birmingham. Typical atrial flutter was defined as having negative flutter waves in ECG leads II, III, and aVF. The predominant clinical arrhythmia was atrial flutter in all patients. However, in some patients, atrial fibrillation had been documented or suspected before ablation. If paroxysmal atrial fibrillation had been a major clinical problem, atrial flutter ablation was not advised.

Two-dimensional and M-mode echocardiography with color Doppler flow analysis was obtained for all the patients within 3 months of the ablation procedure. The left atrial size was measured in the anteroposterior dimension from the M-mode echocardiogram according to recommendations of the American Society of Echocardiography.³⁰ Left ventricular ejection fraction and qualitative assessment of mitral regurgitation were estimated using two-dimensional echocardiography.³¹ Mitral regurgitation was graded as 0 (no regurgitation), 1 (mild), 2 (moderate), or 3 (severe), using standard criteria.³² The right atrial dimensions were qualitatively assessed from the apical four-chamber view and classified as normal or enlarged.

Electrophysiological Protocol
All patients gave written informed consent to the experimental protocol, which was approved by the Investigational Review Board for Human Subjects of the University of Alabama at Birmingham. Antiarrhythmic medications other than those intended to slow AV nodal conduction were discontinued at least four half-lives before the procedure. No patient had received amiodarone for treatment of atrial flutter for at least 3 months before catheter ablation. Patients were studied in the fasting state and were given sedation with intravenous midazolam and meperidine. A 6F hexapolar catheter with 2-mm interelectrode spacing and 10-mm spacing between the three electrode pairs was inserted into the right internal jugular vein and advanced into the coronary sinus. The proximal pair was positioned under fluoroscopic guidance at the coronary sinus ostium. Quadripolar electrode catheters (6F) were inserted percutaneously into the femoral vein and advanced to the right ventricular apex and across the tricuspid valve for recording of the His bundle activation. Heparin was administered as an intravenous bolus of 5000 IU after catheter placement, followed by an additional 1000 IU each subsequent hour of the procedure.

Technique for Inducing Atrial Flutter and Atrial Fibrillation
For patients with spontaneous and sustained flutter at the beginning of the electrophysiological procedure, atrial mapping and radiofrequency catheter ablation were performed before any programmed atrial stimulation or atrial pacing. For patients in sinus rhythm at the beginning of the procedure, a diagnostic electrophysiological study and induction of sustained atrial flutter were performed before catheter ablation. Programmed atrial stimulation was performed at the high right atrium or from the coronary sinus using an eight-beat S₁ drive at a cycle length of 500 ms with the introduction of single and double extrastimuli. An antegrade AV nodal function curve was constructed as part of the routine electrophysiological study. Incremental atrial pacing was also performed to induce sustained atrial flutter and/or atrial fibrillation.

Catheter Ablation of Atrial Flutter
In 57 procedures, a 7F quadripolar deflectable-tip catheter with a 4- to 5-mm distal electrode (Webster Laboratories or EP Technologies) was used to deliver radiofrequency current from the tip electrode to a cutaneous indifferent dispersive pad (3M) positioned posteriorly on the thorax. A 7F quadripolar deflectable-tip catheter with an 8-mm distal electrode (EP Technologies) was used in five procedures (some patients were treated with both catheters). The power source used for catheter ablation was a commercially available electrosurgical generator (Radionics, model RFG-3C) that delivered continuous, unmodulated radiofrequency current at a frequency of 500 kHz. Ablation of the atrial flutter circuit was performed using an anatomic approach based on landmarks in the low medial and posterior right atrium. The target site was the isthmus bounded by the inferior vena cava and the atrial junction interiorly, the coronary sinus ostium superiorly, and tricuspid annulus anteriorly. In all cases, radiofrequency current was applied during sustained atrial flutter. Radiofrequency current was initially applied using 30 W of power for 30 to 60 seconds at multiple points along the isthmus. When no impedance rise was observed, the power was gradually increased to 50 W. After each application, the atrial cycle length was measured. At the site of successful termination of atrial flutter, one or more additional radiofrequency applications were usually applied for 30 to 60 seconds. In the event of an impedance rise, the ablation catheter was withdrawn and cleaned of any coagulum before further applications of radiofrequency current. After successful catheter ablation, each patient was observed in the clinical electrophysiology laboratory for at least 30 minutes, and electrophysiological testing was repeated to ensure that atrial flutter was no longer inducible and to assess whether sustained atrial fibrillation could be induced.

Postablation Electrophysiological Testing
The inducibility of atrial flutter and atrial fibrillation was assessed with standard electrophysiological techniques after catheter ablation. Programmed atrial stimulation was performed with single and double extrastimuli at a basic drive cycle length of 500 ms with the extrastimulus coupling interval decreased to atrial refractoriness. Incremental atrial pacing was performed by increasing the pacing rate until 2:1 atrial capture or a paced cycle length of 180 ms was reached. Atrial fibrillation was defined as sustained when it lasted longer than 30 seconds.

Follow-up Evaluation
Each patient was evaluated in the clinic 4 to 6 weeks after catheter ablation of atrial flutter with history, physical examination, and a standard 12-lead ECG. Later follow-up visits were performed by the referring cardiologist. All patients were also contacted by telephone at the end of June 1994 to confirm their clinical status.

Variables Analyzed to Predict the Late Occurrence of Atrial Fibrillation
The clinical variables analyzed in relation to the later occurrence of atrial fibrillation were the duration of atrial flutter before ablation, the left ventricular ejection fraction, sex, age, prior history of documented atrial fibrillation, the presence and type of structural heart disease, and the inducibility of sustained atrial fibrillation after ablation of atrial flutter. Follow-up information for all successful procedures was included for statistical analysis.

Statistical Analysis
Continuous variables were expressed as mean±SD. Univariate analysis of factors associated with the late occurrence of atrial fibrillation was performed using the Student's t test for continuous variables and Fisher's Exact test for discrete variables. A value of P.05 was considered to indicate statistical significance. Multivariate logistic regression analysis was performed to determine the independent predictors of the late development of atrial fibrillation, with all variables having a univariate association at a significance level of .1 included in the model.³³ Actuarial freedom from recurrence of atrial flutter or the development of atrial fibrillation after ablation of atrial flutter was determined using the method of Kaplan and Meier.³⁴

	Results

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Study Population
The clinical characteristics of the study population are described in Table 1. There were 43 men and 16 women, with a mean age of 61.9±12.6 years. All patients had previously been treated with at least one class 1 or 3 antiarrhythmic drug (mean, 3.3±1.2 drugs) without control of atrial flutter or had experienced intolerable side effects requiring drug withdrawal. The mean duration of symptoms before referral for ablation was 35±40 months (range, 0.25 to 120 months). The mean atrial flutter cycle length was 233±29 ms.

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics

Radiofrequency Catheter Ablation of Atrial Flutter
The mean follow-up duration for study was 13.2±6.6 months, with a median of 13 months. No complications of the ablation procedure were observed. Radiofrequency catheter ablation was initially successful in terminating and preventing the reinduction of atrial flutter in 53 of 59 patients (90%). Two patients required two separate procedures for successful catheter ablation of atrial flutter. The mean number of radiofrequency applications was 18.3±13 (median, 15), with a mean of 31.1±19.3 W for the successful application. The mean fluoroscopic exposure for the entire procedure (diagnostic and ablation) was 32±16.6 minutes. The ablation procedure was ineffective in eliminating the inducibility of atrial flutter in 6 patients. Among these, 5 had documented structural heart disease. One patient had mitral valve stenosis, 2 had coronary artery disease and previous coronary artery bypass grafting, and 2 had dilated cardiomyopathy. In 1 of these patients, the cycle length of atrial flutter prolonged from 220 to 280 ms and remained inducible at the end of the ablation session, but no clinical recurrence was documented over a follow-up period of 14 months. In another patient considered as a primary failure because nonsustained atrial flutter was still inducible at the end of the procedure, no further treatment was required for control of his clinical arrhythmia during follow-up (15 months). Thus, in 2 of these 6 patients classified as procedural failures, "clinical" success was documented during follow-up (defined as no clinical recurrence of atrial flutter despite its persistent inducibility at the end of the ablation procedure).

Recurrence of Atrial Flutter
Recurrence of atrial flutter was documented in 5 patients (9.4%) during follow-up (Fig 1). Patient sex, left ventricular ejection fraction, number and duration of radiofrequency applications, and symptom duration before ablation were not associated with atrial flutter recurrence. The time to atrial flutter recurrence was 1 day in 1 patient, within 2 months in 3 patients, and at 8 months in 1 patient. In 2 patients with documented atrial flutter recurrence, sustained atrial fibrillation was inducible at the electrophysiological study after successful ablation of the atrial flutter, and spontaneous episodes of sustained atrial fibrillation were documented during follow-up associated with disabling symptoms. These 2 patients subsequently underwent AV nodal ablation and permanent pacemaker implantation. The other 3 patients with clinical recurrence of atrial flutter were successfully ablated in a second session. Thus, at a mean follow-up of 13.2±6.6 months (median, 13) after an initially successful ablation procedure, long-term control of atrial flutter was achieved in 51 of 53 patients (96%). If the 2 patients with persistently inducible atrial flutter who did not have a spontaneous recurrence are included as a clinically successful result, then 53 of the 59 patients (90%) who entered into the study had control of the atrial flutter during follow-up.

View larger version (16K): [in this window] [in a new window]   Figure 1. Actuarial freedom from recurrent atrial flutter after initially successful atrial flutter ablation (Kaplan-Meier analysis).

Presence of Dual AV Node Physiology
In our study population, 9 patients (17%) had evidence of dual antegrade AV nodal conduction pathways during programmed atrial stimulation. Seven of these individuals had inducible AV nodal reentrant tachycardia (AVNRT) and underwent successful slow AV nodal pathway ablation during the same procedure. In the other 2 patients, AVNRT was not inducible despite isoproterenol infusion.

Late Occurrence of Atrial Fibrillation
Atrial fibrillation occurred in 14 of 53 patients (26.4%) after successful catheter ablation of atrial flutter (Fig 2). Four clinical variables were associated with the occurrence of atrial fibrillation after radiofrequency catheter ablation of atrial flutter (Table 2): (1) the presence of identifiable structural heart disease, (2) a history of atrial fibrillation before atrial flutter ablation, (3) inducible sustained atrial fibrillation with electrophysiological testing after ablation of atrial flutter, and (4) failure of a greater number of antiarrhythmic drugs to control atrial arrhythmias before ablation. In addition, there was a trend toward a larger left atrial dimension and more severe mitral regurgitation in patients experiencing atrial fibrillation in follow-up.

View larger version (17K): [in this window] [in a new window]   Figure 2. Actuarial freedom from atrial fibrillation (AFib) after initially successful atrial flutter ablation (Kaplan-Meier analysis).

View this table: [in this window] [in a new window]   Table 2. Predictors of Late Atrial Fibrillation

Structural heart disease was identified before ablation of atrial flutter in 30 of 53 patients (59%). Atrial fibrillation developed during follow-up in 13 of these individuals. In contrast, only 1 developed atrial fibrillation during follow-up among the 23 patients without structural heart disease. Within the group of 14 patients in the study who developed atrial fibrillation, structural heart disease was present in 13 (93%) (P=.004; odds ratio, 17:1 compared with individuals without structural heart disease).

A history of spontaneous atrial fibrillation before successful ablation of atrial flutter was present in 12 patients. Atrial fibrillation recurred after ablation in 6 of these individuals (50%) compared with only 8 of 41 (19.5%) without a prior history of atrial fibrillation (P=.08). Sustained atrial fibrillation was induced by rapid atrial pacing after catheter ablation of atrial flutter in a total of 16 patients, of whom 9 (56%) developed the occurrence of atrial fibrillation during follow-up. In contrast, only 5 of 37 patients without inducible sustained atrial fibrillation had spontaneous development of atrial fibrillation (P=.004; odds ratio, 8.2). When these two variables are considered together, the presence of either spontaneous atrial fibrillation before ablation or inducible atrial fibrillation after ablation of atrial flutter was associated with the late development of atrial fibrillation in 12 of 26 patients (46%) compared with only 2 of 27 patients (14%) without either of these factors (P=.004; odds ratio, 11:1).

Multivariate Analysis
Multivariate analysis demonstrated that only the inducibility of sustained atrial fibrillation after ablation of atrial flutter was independently associated with the late development of atrial fibrillation (P=.04) (Table 2). When this variable was added to the model, neither a clinical history of atrial fibrillation before ablation of atrial flutter, the presence of structural heart disease, age, sex, left ventricular ejection fraction, left atrial size, right atrial enlargement, nor number of failed antiarrhythmic drugs predicted the occurrence of atrial fibrillation during follow-up.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Our findings confirm other studies suggesting that radiofrequency catheter ablation of atrial flutter is both safe and effective.^{22 24 25 26 28} The initial rate of successful ablation of atrial flutter and the risk of atrial flutter recurrence are similar to previous studies.^{22 28} As with other reports, the rate of procedural complications appears to be very low. The risk of recurrent atrial flutter (9.4%) is similar to that observed with catheter ablation of other supraventricular arrhythmias and is probably related to incomplete destruction of the atrial tissue providing the critical isthmus of conduction within the reentrant circuit.²⁶ These encouraging results are tempered, however, by the observation that atrial fibrillation was experienced by 26% of patients over a median follow-up of 13 months.

Factors Predictive of Atrial Fibrillation After Atrial Flutter Ablation
Four factors were found to predict an increased risk for developing atrial fibrillation after successful ablation of atrial flutter: (1) the presence of identifiable structural cardiac disease, (2) a clinical history of spontaneous atrial fibrillation before ablation, (3) the inducibility of sustained atrial fibrillation after atrial flutter ablation, and (4) a greater number of failed antiarrhythmic drugs before ablation. However, only the inducibility of sustained atrial fibrillation after ablation was independently associated with the late occurrence of this arrhythmia.

The development of late atrial fibrillation in this study was higher than previously reported by Feld et al²² (1 of 12 patients) or by Fischer et al²⁸ (5 of 70 patients). In the study by Fischer and colleagues,²⁸ a prior history of atrial fibrillation was not described. Cosio et al²⁴ described atrial fibrillation after radiofrequency catheter ablation of atrial flutter in 2 of 9 patients (22%), including 1 in whom atrial fibrillation had been documented before the ablation procedure. In comparison, Saoudi et al²¹ reported 1 patient with the late development of atrial fibrillation in whom this arrhythmia was inducible at the postablation electrophysiological study and 3 additional patients (37.5%) in whom this was detected with Holter monitoring after ablation. Atrial fibrillation had not been documented before ablation in these individuals. Firm conclusions about the risk of developing atrial fibrillation after ablation of atrial flutter cannot be made from these studies because of the relatively small numbers of patients reported, differences in the study protocols, and the use of different types of ablative energy (DC or radiofrequency).

Clinical Implications
These findings have several important clinical implications. First, although atrial flutter can be successfully ablated with a relatively low risk of recurrence, this procedure should be considered palliative rather than curative for atrial arrhythmias, especially for individuals with identifiable structural heart disease or inducible atrial fibrillation after ablation. These patients must be considered at high risk for the subsequent development of atrial fibrillation, and the implications for anticoagulation strategies should be considered. In contrast, patients without these risk factors are at low risk for developing atrial fibrillation, and anticoagulation is probably unnecessary. Second, relatively infrequent episodes of atrial fibrillation before ablation of atrial flutter are not necessarily an indicator that atrial fibrillation will recur in the first year after the procedure. In this study, 50% of patients with episodes of atrial fibrillation have remained arrhythmia free after ablation of atrial flutter. This is especially significant in view of the fact that all subjects in this study had failed at least one class 1 or class 3 antiarrhythmic drug. However, it must be stressed that the predominant clinical arrhythmia was atrial flutter in all of the study subjects and that patients in whom atrial fibrillation had been the major clinical problem were not advised to undergo an ablation procedure. In light of these considerations, it is our practice to offer catheter ablation to patients with atrial flutter who have also experienced infrequent episodes of atrial fibrillation only if structural heart disease is not present. Another question that can be legitimately raised is whether catheter ablation of atrial flutter is inherently proarrhythmic, increasing the risk of later developing atrial fibrillation. While this possibility cannot be excluded, our observation that late atrial fibrillation occurred in only 2 of 27 patients with neither a clinical history of atrial fibrillation nor inducible atrial fibrillation after ablation suggests that this is unlikely. In addition, the feasibility of using catheter ablation to treat atrial fibrillation by creation of a series of linear zones of conduction block in the right and left atria has been demonstrated by Swartz and colleagues.³⁵ This procedure typically includes the application of radiofrequency current to the same region used to ablate atrial flutter. With further evolution of these techniques, it is likely that patients undergoing ablation of atrial flutter who have persistently inducible atrial fibrillation after elimination of atrial flutter will be considered potential candidates for the more complex ablative procedure used for atrial fibrillation.

Limitations
There are several important limitations of this study. The study population represented a highly selected group of patients with medically refractory atrial flutter. This fact may have increased the risk of late atrial fibrillation. However, it is likely that the true risk of atrial fibrillation is even higher than that observed, especially since this arrhythmia may not be symptomatic in some individuals. For example, Page and colleagues³⁶ have reported that asymptomatic atrial fibrillation may be more frequent than symptomatic episodes. This fact may have caused us to underestimate the frequency of atrial fibrillation before ablation of atrial flutter. In addition, our data do not allow us to determine whether radiofrequency ablation of atrial flutter modifies the natural history of atrial fibrillation. Other studies have suggested that there may be an association between AV nodal reentrant tachycardia and common atrial flutter.³⁷ Since patients with sustained atrial flutter at the time of the procedure did not have electrophysiological testing until after ablation, the frequency of dual AV nodal pathways may have been underestimated by postablation testing. Since our target site for atrial flutter ablation was in close proximity to the usual landmarks for elimination of slow pathway conduction, some slow pathways may have been ablated before their documentation.³⁸ Thus, no conclusions about the frequency of this association should be inferred from our data.

Recent reports suggest that atrial flutter may be more associated with increased right atrial volume than is atrial fibrillation.³⁹ Although there was a trend toward increased anteroposterior left atrial dimension in the patients who later developed atrial fibrillation in the present study, left and right volumes were not quantitated. It is likely that these more precise measures of atrial size would have provided more accurate predictors of the later occurrence of atrial fibrillation after atrial flutter ablation.

Conclusions
Although catheter ablation of atrial flutter is highly effective and associated with a low risk of recurrent atrial flutter, atrial fibrillation continues to be a long-term risk for individuals undergoing this procedure. The risk of developing atrial fibrillation is related to the presence of structural heart disease and prior spontaneous or inducible atrial fibrillation.

	Acknowledgments

 
Dr Philippon is a Scholar of the R.S. McLaughlin Foundation, Québec, Canada.

Received October 25, 1994; revision received January 4, 1995; accepted January 17, 1995.

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