Atrial Fibrillation After Ablation of Atrial Flutter: Who Is at Risk?

Who Is at Risk?

E. B

Radiofrequency catheter ablation targeting the isthmus between the tricuspid anulus and the inferior vena cava is an established therapy for typical atrial flutter (AFL). It is successful in more than 90% of patients [1–7]. However, in the clinical setting, AFL and atrial fibrillation (AF) often coexist, and the fol- low-up of patients successfully treated with transisthmus ablation is compli- cated by the occurrence of AF in 10–47% of patients [2, 5, 8–15]. Indeed, although caused by different electrophysiological mechanisms, AFL and AF may share the same arrhythmogenic substrate [12, 16, 17]. Identifying patients at higher risk of post-ablation AF occurrence after ablation was a major issue until the introduction of transisthmus catheter ablation.

Occurrence of Atrial Fibrillation After Transisthmus Ablation

As reported in several papers, AF frequently occurs after transisthmus abla- tion of AFL: its occurrence ranges from 12% to 54% [8–15, 18–23]. In the study that enrolled the largest cohort, AF was observed in 42% of patients after a mean of 20.5 months from ablation of AFL [23]. The occurrence of AF increased progressively as time passed (Fig. 1): at 4 years, the cumulative probability of AF occurrence rose to 62%. The progression of AF behaved differently in patients with and patients without AF before ablation (Fig. 2).

While in the former group almost all of the recurrences of AF appeared dur- ing the first 2 years (66%), in patients without pre-ablation AF the rate of AF occurrence was quite low during the first 2 years (12%), and increased sig- nificantly later (52% at 4 years).

Dipartimento di Cardiologia, Ospedale Civile, Mirano (Venice), Italy

However, not all patients with pre-ablation AF present the same risk of post-ablation AF. Some authors have already suggested that patients with drug-induced AFL [those with paroxysmal or persistent AF in whom persis- tent or paroxysmal AFL appeared only after the beginning of treatment with class IC drugs (so-called IC-AFL) or only after the beginning of treatment with amiodarone (so-called amio-AFL)] present an incidence of post-ablation AF occurrence as low as the incidence in patients with pre-ablation lone AFL [14, 20, 24]. More recently, we directly compared the long-term outcome

Fig. 1. Kaplan–Meier estimate of the t ime to at r ial fibr illat ion occurrence in the general popula- tion after atrial flutter ablation.

From [23], with permission

Fig. 2. Kaplan–Meier estimates of the time to occurrence of atrial fibrillation after atrial flutter abla- tion in patients without pre-abla- tion atrial fibrillation (dashed

ablation atrial fibrillation (unbro-

sion

Months following ablation

Months following ablation

Atrial fibrillation free survivalAtrial fibrillation free survival

of four subgroups of patients after transisthmus ablation: patients with AFL in whom AF had never been documented prior to transisthmus ablation;

patients with AFL in whom AF had been documented prior to transisthmus ablation; patients with IC-AFL; and patients with amio-AFL [25].

The clinical courses after transisthmus ablation were significantly differ- ent among the four subgroups of patients (Fig. 3). In the patients with amio- AFL the cumulative probability of post-ablation AF occurrence was signifi- cantly lower than in the patients with pre-ablation coexistent AF, and similar to that seen in the patients with pre-ablation lone AFL. By contrast, a similar cumulative probability of post-ablation AF to that recorded among patients with pre-ablation coexistent AF was observed in the patients with IC-AFL.

Thus, a significant difference emerges between class IC anti-arrhythmic drugs and amiodarone in respect of the possibility of preventing AF relapses after transisthmus ablation [25]. The protective effect of amiodarone on AF recurrences could be related to the great reduction in intra-atrial conduction velocity exerted by this drug [20]. In this way, amiodarone prevents the simultaneous occurrence of the reentrant circuits which might trigger and perpetuate AF despite the block of the cavo-tricuspid isthmus.

Some interesting differences can also be observed regarding the time of onset of AF recurrences after transisthmus ablation (Fig. 3). Post-ablation AF began later in the patients without pre-ablation AF than in patients with pre- ablation AF. At least in some patients, AFL, rather than triggering AF, seems to be a different clinical expression of the same electrical disease, which is able, as time passes, to induce AF once the preferential route through the flutter circuit is blocked.

Fig. 3. Kaplan–Meier estimates of

the time to occurrence of atrial

fibrillation in patients with lone

atrial flutter (unbroken line), with

pre-ablation coexistent atrial fib-

rillation (dashed and dotted line),

with class IC drug-induced atrial

flutter (dotted line), and w ith

amiodarone-induced flutter

(dashed line). From [25], with per-

mission

Predictors of Atrial Fibrillation Occurrence

Predictors of post-ablation AF are: pre-ablation AF, left atrial size, left ven- tricular ejection fraction, inducibility of sustained AF after transisthmus ablation, and age [8, 10–12, 14–16, 21–23, 26, 27].

Left atrial size is closely correlated with AF: this arrhythmia is likely to occur in a more diseased, and thus enlarged, atrium [10]. Patients with low left ventricular ejection fraction are more prone to develop AF [8, 11, 12, 15, 21]. AF inducibility to programmed electrical stimulation is associated with high spatial atrial refractoriness and with the development of AF before and after the ablation [27]. A surprising result is the inverse correlation of age with occurrence of post-ablation AF [23]. According to our knowledge about the prevalence of AF in the general population [28], it would be expected that post-ablation AF would occur more frequently in the elderly. On the contrary, however, it was found that patients younger than 65 years experi- enced post-ablation AF more frequently than patients aged over 65 years despite similar rates of pre-ablation AF, predominant pre-ablation AF, and of anti-arrhythmic drug use [23].

A pre-ablation history of AF remains the most common predictor of post-ablation AF occurrence [8, 11, 12, 15, 16, 22, 23, 26, 27]. Pre-ablation AF identifies patients in whom there is a structural and electrophysiological substrate that allows multiple reentrant circuits favouring AF [11, 12, 27].

However, among patients with pre-ablation AF different variables predict the occurrence of AF after transisthmus ablation in different subgroups of patients [25]. In patients with pre-ablation AF and not drug-induced AFL, post-ablation AF relapses correlated significantly with an enlarged left atri- um. In contrast to this, among patients with IC-AFL, the presence of struc- tural heart disease correlated significantly with post-ablation AF recur- rences. Treatment with class IC anti-arrhythmic drugs is not the first choice for patients with structural heart disease. Treatment of patients with struc- tural heart disease with a class IC anti-arrhythmic drug generally stems from failure of other anti-arrhythmic drugs. Patients with structural heart disease receiving treatment with a class IC anti-arrhythmic drug are there- fore at very high risk of AF occurrence [25].

Clinical Implications

AF occurs frequently after ablation, and its occurrence increases during the

follow-up period. This is true both for patients with AF before the ablation

and for those without. After 4 years, the probability of post-ablation AF was

68% for patients with pre-ablation AF and 52% for patients without pre-

ablation AF. This means that even patients with pre-ablation lone AFL are at high risk of developing AF as time passes. Hence, they must be advised of the risk of recurrent symptoms and late AF, and closely followed up even if tran- sisthmus ablation was successful. ECG Holter monitoring must be advised too, because up to 34% of AF episodes are asymptomatic.

Patients w ith pre-ablation AF and not drug-induced AFL w ith an enlarged left atrium, and patients with IC-AFL with structural heart disease, are at high risk of developing AF despite continuation of anti-arrhythmic drug treatment, and anticoagulation therapy should be continued during the follow-up due to the risk of stroke.

Patients with AFL induced by amiodarone run a significantly lower risk of post-ablation AF than patients with spontaneous AFL and those with IC- AFL.

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