Should radiofrequency ablation be first-line therapy after a first episode of symptomatic atrial flutter?

Atrial flutter is a macroreentrant atrial arrhythmia characterized by a uniform P-wave morphology, with a characteristic saw-toothed appearance and a regular rate between 240 and 250 beats/min.¹ The prevalence of atrial flutter was difficult to estimate in epidemiological studies¹ until a recent study showed that the incidence was close to 180 new cases/year/100,000 inhabitants.² This arrhythmia is associated with thromboembolic complications in the same way as is atrial fibrillation.² Moreover, atrial flutter can be difficult to manage because it represents a troublesome arrhythmia, often poorly tolerated because of a rapid, difficult-to-control, atrioventricular (AV) conduction rate.^3-5 Restoration of sinus rhythm and the prevention of long-term recurrences are the main treatment objectives.

Although large prospective studies assessing the efficacy of drug therapy only for atrial flutter are lacking in the literature, it is generally recognized that medical management of this arrhythmia can be particularly difficult and may cause a higher risk of morbidity and mortality secondary to bradyproarrhythmia or tachyproarrhythmia.^3-5 This is certainly more common in patients with associated heart disease, which is more frequently encountered in patients with atrial flutter.^4,5

Radiofrequency catheter ablation (RFA) is a different proposition in several aspects. The inferior vena cavatricuspid isthmus has become the universally accepted target for ablation of the typical circuit because of its accessibility and because it is located far from the AV node, even though there is no evidence that this site is the cause of atrial flutter.^6-8 Clinical prospective studies have shown that ablation of the cavotricuspid isthmus (CTI)-dependent atrial flutter is associated with high efficacy and low secondary effects.^6-8 Although it can be extremely technical, developments including better knowledge of the atrial flutter circuit, recognition of the CTI bidirectional conduction block as a reliable end point, and development of ablation technologies that allow creation of both deeper and larger lesions to improve procedural efficacy have improved the CTI RFA technique.^6-8 Consequently, RFA treatment of atrial flutter is associated with an improvement in the quality of life and a decrease of cardiovascular morbidity.^9,10

From a theoretical point of view, atrial flutter RFA could be first-line therapy because of high efficacy, a low rate of long-term recurrences, and few side effects.^6-10 The main weakness of the procedure is that during extended follow-up, atrial fibrillation will emerge in about half of patients, mostly in those with previous atrial fibrillation. Prior to our study, RFA for the treatment of isthmus atrial flutter was indicated for selected patients after the failure of antiarrhythmic drugs.^9-11 Moreover, no data existed comparing medical therapy with RFA in patients with only 1 episode of symptomatic atrial flutter.^9-11 One randomized prospective study compared antiarrhythmic drugs with RFA in subjects with more than 2 symptomatic episodes of atrial flutter.⁹ However, in this study, RFA was not compared with amiodarone (Cordarone, Pacerone), the antiarrhythmic drugs tested were diverse, all patients had 2 episodes of atrial flutter, and the study did not have sufficient power to provide statistical evidence.⁹ These limitations must be taken into consideration when evaluating treatment options for patients with a first episode of atrial flutter.^9-11

According to the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines, a first occurrence of atrial flutter is categorized as a IIa indication with a level of evidence B for RFA therapy.¹¹ We conducted one of the first randomized controlled trials, the Loire-Ardèche-Drôme-Isère-Puy de-Dôme (LADIP) study, to compare RFA treatment with an antiarrhythmic drug in subjects with a first episode of symptomatic atrial flutter.¹²

Subjects and methods

Subjects in the LADIP study had 1 episode of atrial flutter, had not previously taken antiarrhythmic drugs, and were aged 70 years or older (Table). From October 2002 to February 2006, 104 patients were treated with amiodarone therapy or underwent RFA for atrial flutter. Of the 52 subjects treated with amiodarone, a loading dose of 400 mg was given daily for 4 weeks and at least 7 days prior to rhythm restoration. After the loading period, the dose was lowered to 200 mg.

Table. Population characteristics and results of the LADIP study

Results

The mean age of the subjects in the study was 78 years. Atrial flutter recurred in 29.5% of subjects (n = 15) treated with amiodarone over a mean follow-up period of 13 months. Over the same period, atrial flutter recurred in 3.8% of subjects (n = 2) who underwent RFA. An additional RFA procedure was needed for 1 subject, and 1 subject refused a second procedure. Subjects who had a recurrence of atrial flutter in the amiodarone-treatment arm successfully underwent RFA.

At 1 year, symptomatic atrial fibrillation occurred in 8% of amiodarone-treated subjects and in 8% of RFA-treated subjects. The incidence of atrial flutter recurrence or atrial fibrillation occurrence was determined in an identical manner in both treatment groups using a 1-week-long event recorder, with monitoring at regular intervals during follow-up. At the end of the study, 1 subject treated with amiodarone and 2 subjects who underwent ablation were in chronic atrial fibrillation. Another 3 subjects, 2 of whom underwent catheter ablation, were in atrial flutter rhythm. When all episodes of atrial fibrillation were taken into account, including episodes lasting less than 10 minutes and documented by an event recorder, there was no significant difference between the 2 treatment groups, with 20% of amiodarone-treated subjects and 29% of RFA-treated subjects having atrial fibrillation.

Discussion

In our study, RFA treatment was shown to be more effective than amiodarone treatment for the prevention of atrial flutter after a first symptomatic episode. The difference between the 2 forms of therapy is clinically relevant. The proportion of recurrence of atrial flutter in the amiodarone-treated group was similar to that seen in subjects treated with amiodarone for atrial fibrillation (approximately 30%).¹³ However, subjects in the RFA-treated group had the same number of recurrences as that seen following cavotricuspid isthmus bidirectional block validation (< 5%).^3,6-9

It is not known how many patients have a recurrence after the first episode of atrial flutter.^14,15 One study showed that among 50 subjects not receiving prophylactic medication, the proportion in sinus rhythm after a single cardioversion after 1 year was approximately 50%.¹⁴ In our study, the percentage of recurrence among the 29% of subjects receiving medical therapy showed that atrial flutter recurrence is not as high as expected after a first episode. A recent study showed that 63% of subjects in the new-onset atrial flutter group maintained normal sinus rhythm after a 1-year follow-up period.¹⁵ Another study showed that 93% of subjects had a recurrence of atrial flutter while receiving antiarrhythmic therapy after sinus rhythm restoration, but subjects were included after a second episode of atrial flutter, and the variety of medications tested may have affected the results.⁹

According to the results of our study, RFA should be considered as first-line therapy following the first symptomatic episode of atrial flutter. Even among the older population participating in our study, RFA had few serious adverse effects and was well tolerated. The theoretical benefit of amiodarone as a noninvasive treatment is reduced by the increased risk (10%) of long-term side effects from the medication.^12,13

Our findings show for the first time that RFA therapy is more effective than treatment with amiodarone for the prevention of atrial flutter recurrence after a single episode. The risk of atrial fibrillation was not significantly different between the RFA-treated and amiodarone-treated groups. Although the incidence of atrial fibrillation was higher in RFA-treated subjects with a history of atrial fibrillation, the results in subjects with a single episode of atrial flutter were similar. Results of the LADIP study are in accordance with previous studies with regard to the low rate of atrial flutter recurrence and other atrial tachycardia recurrences.^6-9,12 Nevertheless, subjects undergoing earlier ablation did not have as much need for antiarrhythmic drugs or anticoagulants and had fewer episodes of symptomatic atrial arrhythmia.

Conclusions

Radiofrequency ablation is more effective and has fewer secondary effects than traditional amiodarone therapy for the treatment of a first occurrence of symptomatic atrial flutter. For this reason, it should be considered as first-line therapy after the first episode of atrial flutter, especially in older patients.