Catheter Ablation of Typical Atrial Flutter. What Are the LongTerm Results and Predictors of Recurrences? P. DELISE, N. SITTA , L. CORO’ , L. SCIARRA, E. MARRAS, M. BOCCHINO, G. BERTON

Introduction Catheter ablation of typical atrial flutter, targeting the cavo-tricuspid (CT) isthmus, is an effective treatment that is frequently used in clinical settings [1–7]. In fact, due to recent technical improvements (e.g. 8-mm catheters, irrigated-tip catheters), the short-term success rate of this approach exceeds 90% with low recurrence rates (no more than 5–10% of cases). However, a major problem in patients with atrial flutter is the possible coexistence of atrial fibrillation (AF). In fact, at least 10–35% of patients with clinically predominant atrial flutter also suffer from AF [8–10] and 5–22% of patients with AF also have atrial flutter, particularly those who are on antiarrhythmic therapy [10–14]. Therefore, there is reasonable risk that ablation of flutter, despite the elimination of arrhythmia, may not resolve the clinical problem owing to the recurrence of AF.

Electrophysiologic Relationships Between Atrial Fibrillation and Atrial Flutter The presence of AF and flutter in the same patient is related to multiple mechanisms. First, the same atrial anatomic substrate can facilitate both multiple wavelet re-entry of AF and right atrial macro re-entry of atrial flutter. Second, AF can trigger atrial flutter [8–14]. In fact, frequently during AF the wave front originating from the left atrium tends to proceed in the right atrium along its anatomic barriers (crista terminalis, inferior vena cava,

Operative Unit of Cardiology, Hospital of Conegliano (Treviso), Italy

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etc.), which constitute the anatomic circuit of atrial flutter. Consequently, in many cases, as AF extinguishes, atrial flutter initiates. Third, atrial flutter, like other supraventricular arrhythmias [15–18], can trigger AF, a phenomenon that was described by Pristowsky [19] as ‘tachycardia-induced tachycardia.’ Finally, the two arrhythmias may have a common trigger, represented by automatic foci of pulmonary veins [18]. Antiarrhythmic drugs may have opposite effects on AF and atrial flutter. More precisely, many drugs (propafenone, flecainide, amiodarone) are able to prevent AF but they have little effect on, or may even facilitate atrial flutter. This observation has been made by several investigators, who demonstrated the occurrence of atrial flutter in 5–22% of patients with AF after treatment with class1 C drugs or amiodarone [10–14]. This phenomenon has been attributed to the slowing of conduction in the potential circuit of flutter.

Factors Influencing Recurrence of Flutter After Radiofrequency Ablation The most important feature which avoids the recurrence of flutter is the creation of a stable and complete block of isthmus conduction [2–7]. In fact when the validation of block was not made in the first ‘90s the recurrence rate of flutter ablation was very high (30% or more) [1]. The validation of block may be reached documenting a clockwise activation of the right atrium stimulating from the inferolateral wall and, respectively, a counterclockwise activation stimulating from the ostium of the coronary sinus. This demontration can be obtained by multielectrode mapping of lateral and septal walls of the right atrium (for example with a Halo catheter) or by non fluoroscopic mapping (CARTO system) or by non contact mapping. In some cases however an incomplete isthmus block with a marked conduction delay can mimick a complete block, thus facilitating the recurrence of the arrhythmia. The differential diagnosis can be obtained using the following additional criteria [5–7]: 1. The demonstration of double potential along the whole line of block 2. Change of unipolar electrograms in the right atrium opposite the pacing site after ablation 3. Maximum delay in the activation of the atrium opposite to the line of block obtained when stimulating close to the lesion in respect to a stimulation 1–2 cm more distant 4. Wider double potentials recorded along the ablation line when stimulating close to the lesion when compared to a stimulation a 1–2 cm more distantThe second factor influencing the possibility of a recurrent atrial flutter, is the resumption of isthmus conduction after a successful block. It

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is important to know that 97% of conduction recovery occurs within 15 minutes [4]. In conclusion after obtaining a complete isthmus block and waiting for at least 15 minutes to confirm the stability of the lesion, the recurrence rate may be less than 5% [2].

Effects of Cavo-Tricuspid Isthmus Ablation of Atrial Fibrillation. Briefand Mid-Term Results At mid-term follow-up, the occurrence of AF in patients who were treated with isthmus ablation for documented atrial flutter is rare: less than 15% of patients, in the absence of antiarrhythmic therapy. In contrast, in patients with both atrial flutter and AF before ablation, the recurrence rate of AF is high (35–74% of patients), despite the use of antiarrhythmic drugs [7, 20–22]. Nevertheless, for the latter group of patients, many authors have recommended CT-isthmus ablation together with antiarrhythmic drugs (hybrid therapy), as this strategy has been shown to eliminate atrial flutter and to prevent or at least significantly reduce AF episodes in 73–90% of patients [13, 14, 21–25], thus significantly improving the quality of life for most patients. For example, Schumacher et al. [13], who performed CT-isthmus ablation in patients with both arrhythmias, observed that during 11 ± 4 months of follow-up 37% of patients remained free from all arrhythmias, and an additional 42% of patients had significantly lower AF recurrence, while only 15% had no clinical benefit. Nabar et al. [24] in another observational study covering a mean followup of 4 months, observed a clinical benefit in 85% of patients (70% disappearance of AF and flutter and 15% less AF recurrence). Lee et al. [26] compared the effect of CT-isthmus ablation on quality of life in two groups of patients, one with only documented atrial flutter and the other with atrial flutter and AF, who had discontinued and continued drug therapy, respectively, after ablation. Quality of life significantly improved in both groups, although the improvement was greater in patients with only atrial flutter before ablation. Finally our group, in a previous study [22] that included a follow-up after CT-isthmus ablation of about 18 months, observed a 13% recurrence rate of AF in patients with only atrial flutter compared to 38% (despite antiarrhythmic prophylaxis) in patients with both atrial flutter and AF before ablation. Two thirds of the latter group, however, had an improvement in quality of life, which was correlated with a significant reduction in the number of episodes of AF.

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Long-Term Results of Atrial Flutter Ablation with Respect to Atrial Fibrillation Recurrence: Personal Experience Methods We studied 141 patients (114 males, 27 females, mean age 63 ± 10) with common atrial flutter who underwent successful CT-isthmus ablation, defined on the basis of short-term electrophysiologic validation at the end of the procedure [5, 27] and on the absence of clinical recurrence of atrial flutter during the first year of follow-up. These strict inclusion criteria were chosen to avoid the possibility that recurrence of atrial flutter played a role in the recurrence of AF. Patients were divided into two groups on the basis of their characteristics before ablation. Group A included 48 patients with only documented common atrial flutter; group B included 93 patients who had both documented atrial flutter and AF. In group A, 40/48 patients consumed 1.5 ± 1 antiarrhythmic drugs, while in group B all patients consumed 2.5 ± 1.2 antiarrhythmic drugs before ablation. The last antiarrhythmic therapy before ablation is reported in Table 1. In group B, 31 patients had only atrial flutter during their last antiarrhythmic therapy (group B1), while 62 patients (group B2) continued to present with atrial flutter and AF during their last antiarrhythmic therapy. Among the latter, the ratio between documented episodes of AF and atrial flutter was about 1 (1 ± 0.1) in 20% of patients, > 1.1 in 60% of patients, and < 0.9 in 20% of patients. After ablation, all group A patients discontinued any antiarrhythmic therapy, while group B patients continued their last (group B1) or best (g roup B2) ant iar rhy thmic dr ug therapy : amiodarone, flecainide, propafenone, or sotalol. Patients at risk of thromboembolic events continued anticoagulant therapy after discharge. Clinical characteristics were similar in both groups, except for the duration of symptoms, which was longer in group B (Table 1). In all patients, CT-isthmus ablation was performed according to standard criteria [2–13]. Electrophysiologic success was defined when a bidirectional isthmus block was obtained, as demonstrated by coronary sinus and right low lateral atrium stimulation [14]. Quality of life was evaluated in the basal state and during follow-up by administering a Specific Symptom Scale (SSS) evaluation, which consisted of six questions concerning symptoms: palpitations, rest and effort dyspnoea, effort intolerance, asthenia, and angina. The SSS is scored from 0 (well) to 10 (unwell).

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Table 1. Characteristics of patients. Group A (atrial flutter alone) and B (atrial flutter and AF) Group A (n = 48)

Group B (n = 93)

P

41/7 64 ± 10

73/20 63 ± 10

NS NS

Heart disease: HHD DCM CAD VHD

31 (64%) 18 (38%) 7 (14%) 6 (12%)

54 (58%) 35 (37%) 9 (9%) 6 (6%) 4 (4%)

NS NS NS NS NS

Last AATx : Amiodarone Flecainide Propaphenon Sotalol

n = 29 17 5 4 3

n = 87 32 26 27 2

26 (54%) 44 ± 10 56 ± 10 3.4 ± 2.4

70 (75%) 44 ± 10 57 ± 10 3.2 ± 1.8 5 ± 4.5

M/F Age

ACT LA EF Mean AFL Mean AF

NS NS NS

HHD Hypertensive heart disease, DCM dilated cardiomyopathy, CAD coronary artery disease, VHD valvular heart disease, AATx antiarrhythmic therapy, ACT anticoagulant therapy, LA left atrium, EF ejection fraction, AFL atrial flutter, AF atrial fibrillation, NS not significant

On discharge, patients were instructed to promptly return to hospital in the event of sustained palpitations or of sustained symptoms possibly related to arrhythmia relapse, in order to undergo electrocardiography. In the case of unsustained symptoms, patients underwent one or more 24-h Holter monitorings. In any case, patients were asked to keep a diary of the number and duration of episodes of recurrent palpitations. Patients were called back 3 months after ablation and at the end of follow-up (44 ± 20 months). During follow-up examinations, an interview focusing particularly on arrhythmia relapses, a clinical evaluation, and an electrocardiogram were carried out. AF recurrence was defined when AF was documented in the standard ECG or in the Holter (> 1 min). For the purposes of this report, the last SSS questionnaire was considered.

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Results During follow-up, no patient had recurrent typical atrial flutter. However, 13/48 (27%) of group A and 57/93 (61%) of group B patients had documented recurrent AF (P< 0.001). Within the latter group, AF recurred in 16/31 (51%) of group B1 and in 41/62 (66%) of group B2 patients (B1 vs B2, P=NS). A comparison of the event-free survival curves (Fig. 1) shows that the three curves (groups A, B1, and B2, respectively) diverge from each other just during the first few months. Subsequently, the B1 and B2 curves tend to furother diverge and overlap with prolonged follow-up. Permanent AF occurred in 3/48 (6%) of group A, in 1/31 (3%) of group B1, and in 13/62 (21%) of group B2 (A vs B1 P = NS, A and B1 vs B2 P < 0.01) . Between patients with heart disease and those without, there was no difference either in the incidence of paroxysmal/persistent AF in groups A (26% vs 18%), B1 (46% vs 50%), and B2 (50% vs 42%) or in the incidence of permanent AF in groups A (7% vs 6%) and B1 (0% vs 5%). In contrast, there was a significant difference in the incidence of permanent AF in group B2 between patients without heart disease (4%) and those with heart disease (33%, P < 0.01) (Table 2). Before ablation, 31/48 (64%) of group A, 18/31 (58%) of group B1, and 36/62 (58%) of group B2 had at least one electrical cardioversion (mean 1.35,

Fig. 1. Event-free survival curves for recurrent atrial fibrillation in groups A (atrial flutter only before ablation), B1, and B2 (both atrial flutter and AF before ablation)

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Table 2. Comparison of recurrence rates of atrial fibrillation in the various patient groups according to the absence or presence of heart disease Group A (n = 48)

Group B1 (n = 31)

Group B2 (n = 62)

13 (27%)

16 (51%)

41 (66%)

Par/Pers AF -Absence of HD -Presence of HD P (Absence vs presence of HD)

10 (21%) 4/15 (26%) 6/13 (46%) NS

15 (48%) 6/33 (18%) 9/18 (50%) NS

28 (45%) 13/26 50%) 15/36 (42%) NS

Permanent AF -Absence of HD -Presence of HD P (Absence vs presence of HD)

3 (6%) 1/15 (7%) 2/33 (6%) NS

1 (3%) 0/13 (0%) 1/18 (5%) NS

13 (21%) 1/26 (4%) 12/36 (33%) < 0.01

Recurrent AF

Par Paroxysmal, pers persistent, HD heart disease

1.03, and 1.37 per patient, respectively). After CT-isthmus ablation 5/48 (10%) of group A, 2/31 (6%) of group B1, and 14/62 (22%) of group B2 had at least one electrical cardioversion (mean 0.12, 0.06, 0.27 per patient, respectively) (groups A, B1, and B2 before ablation vs after ablation P < 0.001 the difference remrined higlity significant also), excluding patients who developed permanent AF (Table 3).

Table 3. Electrical cardioversions before and after ablation PRE RF n. mean

AFTER RF n. mean

P (mean)

All patients Group A (48) Group B1 (31) Group B2 (62)

31 (65%) 18 (58%) 36 (58%)

1.35 1.03 1.37

5 (10%) 0.12 1 (3%) 0.03 14 (22%) 0.27

< 0.0001 < 0.0001 < 0.0001

Permanent AF excluded Group A (45) Group B1 (30) Group B2 (49)

29 (64%) 1.3 18 (60%) 1.04 26 (53%) 1.28

3 (6.6%) 0.06 1 (3%) 0.03 8 (16%) 0.18

< 0.0001 < 0.0001 < 0.0001

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Before ablation, SSS scores were similar in groups A and B. After ablation, at the end of follow-up, SSS scores decreased in all groups: In group A, from 16 ± 5 to 1.2 ± 1 (P < 0.001); in group B1, from 21 ± 10 to 7.8 ± 7 (P < 0.001); in group B2, from 21.3 ± 5 to 10.8 ± 8 (P < 0.001). The improvement in SSS score, however, was significantly higher in group A than in groups B1 and B2 (Table 4).

Table 4. Specific symptom scale (SSS) score. Group A post-ablation vs group B1 postablation, P < 0.001; group A post-ablation vs group B2 post-ablation, P < 0.001; group B1 post-ablation vs group B2 post-ablation, P = 0.09 Before ablation

After ablation

P

Group A

16 ± 5

1.2 ± 1

< 0.0001

Group B1

21 ± 10

7.8 ± 7

< 0.0001

Group B2

21.3 ± 9.4

10.8 ± 8.5

< 0.001

Conclusions and Practical Considerations Atrial flutter and AF have different electrophysiological mechanisms. While the two arrhythmias may coexist in the same patient, in most cases, during long-term follow-up, they have different natural courses. In patients with documented atrial flutter only, isthmus ablation is usually curative. In some patients (less than 30% of cases), despite the elimination of atrial flutter, AF occurs, probably as a result of the previous existence of a non-documented form of this arrhythmia. According to other investigators [28], in patients with both atrial flutter and AF, CT-isthmus ablation (despite the use of antiarrhythmic therapy) prevents AF in less than 40% of patients. In the remaining patients, AF relapses. According to another study (13), group B1 patients (with so-called IC/amiodarone atrial flutter) have a better outcome than group B2 patients (with both atrial flutter and AF during antiarrhythmic therapy). However, longer follow-up showed a tendency of similar recurrence rates compared to group B2 patients. This pattern is not surprising, as it is well-known that the efficacy of antiarrhythmic therapy in preventing AF is inversely proportional to the duration of follow-up. Permanent AF was very rare in group A (6%) while it occurred in about 20% of group B patients. Notably, AF rarely occurred (3%) in the B1 subgroup of patients, whereas there was a particularly high rate of permanent

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AF (33%) in group B2 patients with heart disease. On the basis of our results, CT-isthmus ablation seems mainly indicated in patients with atrial flutter alone. However, it can also be proposed as firstline therapy in symptomatic patients with both atrial flutter and AF, particularly if they have no heart disease and/or if they have only atrial flutter during antiarrhythmic drugs. In fact in such patients, quality of life frequently improves, probably as a result of the abolition of flutter and of the lower number of symptomatic episodes of AF, in particular those needing treatment by electrical cardioversion. CT-isthmus ablation is a questionable form of therapy in patients with heart disease, particularly if they continue to present with AF during antiarrhythmic drug treatment. In patients in whom therapy is unsuccessful (frequent AF relapses and/or compromised quality of life,) pulmonary-vein isolation or an ablate and pace strategy should be proposed only as a second-line therapy. Our opinion derives from the observation that pulmonary-vein isolation, although potentially curative in patients with AF, is a complex and risky procedure, while an ablate and pace strategy is an irreversibly destructive therapy. By contrast, CT-isthmus ablation is simple and safe and provides significant clinical benefit in most patients.

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