AF Recurs Despite Strategies Added to AF Ablation in EAST-AF, UNDER-ATP Trials

August 30, 2015

LONDON, UK — Two new studies testing different treatment strategies in patients undergoing radiofrequency catheter ablation of atrial fibrillation (AF) disappointed today here at the European Society of Cardiology (ESC) 2015 Congress.

The studies, part of the 2x2 factorial Kansai Plus Atrial Fibrillation (KPAF) randomized trial, tested the addition of antiarrhythmic drug therapy for 90 days following AF ablation and the use of adenosine-triphosphate (ATP) to guide pulmonary-vein isolation in more than 2000 patients. Both studies failed to show a reduction in AF/atrial tachyarrhythmias (AT) at 1 year following the ablation.

The trials are known as the Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation of AF Trial (EAST-AF) and Unmasking Dormant Electrical Reconduction by Adenosine Triphosphate Trial (UNDER-ATP).

In UNDER-ATP, led by Dr Atsushi Kobori (Kobe City Medical Center General Hospital, Japan), 1113 patients undergoing a first catheter-ablation procedure were randomized to ablation with pulmonary-vein isolation guided by ATP and 1007 patients randomized to conventional pulmonary-vein isolation[1].

Speaking with heartwire from Medscape, Kobori said ATP is used in some centers by electrophysiologists looking to find dormant electrical-conduction pathways between the atria and pulmonary veins. The hope is that by identifying the dormant pathways, physicians would then further ablate to completely isolate the veins from the atria and prevent AF/AT recurrence in the long term.

Dr Atsushi Kobori

For patients in the ATP-guided arm, dormant pulmonary-vein–conduction activity was detected by ATP in nearly 28% of patients, roughly split between the left- and right-sided pulmonary veins. After additional applications of radiofrequency ablation, the elimination of all dormant conduction was achieved in 98.4% of patients.

Despite the elimination of virtually all of the dormant conduction pathways, there was no significant reduction in AF/AT at 1 year. Event-free survival at 1 year was 68.7% in the ATP-guided pulmonary-vein–isolation group and 67.1% in the conventional-treatment arm, a nonsignificant difference. There was no difference in event-free survival when investigators stratified patients by AF subtype.

Speaking with heartwire , Dr Luigi Di Biase (Albert Einstein College of Medicine, New York) pointed to the recent ADVICE study in the Lancet, one led by Dr Laurent Macle (Montreal Heart Institute, QC), showing that adenosine testing to identify and target dormant pulmonary-vein–conduction pathways improved arrhythmia-free survival in patients with paroxysmal AF. Overall, Di Biase, who was not part of the KPAF studies, is not convinced of adenosine's benefits in ablation.

"I personally believe there is enough technology and experience out there to achieve a durable pulmonary-vein isolation," said Di Biase, notably referencing the use of contact force-sensing catheters in ablation procedures. "When patients have a recurrence of atrial fibrillation nowadays, the majority of the time the vein is isolated. The reason the patient has atrial fibrillation is because it's coming from non–pulmonary-vein areas, one area being the left atrial appendage."

Other cardiologists were also at a loss to explain the lack of benefit with isolating the pulmonary veins with adenosine. Dr John Camm (University of London, UK), the scheduled discussant during the late-breaking trial, noted the Japanese study contradicts a previous meta-analysis suggesting a benefit with adenosine-guided pulmonary-vein isolation and the ADVICE trial. He notes the studies all differed in patient population, AF types, and the type of ablation performed (pulmonary-vein isolation alone or with other ablation "lines").

Dr Jagmeet Singh (Massachusetts General Hospital, Boston) said he routinely uses adenosine to check whether the pulmonary veins have been electrically isolated from atria but notes that not every physician will do so. Singh, who not involved in the trial, called the results "very surprising," telling heartwire he expected that ensuring a complete isolation of pulmonary veins would translate into lower rates of AF/AT recurrence.

Back on Antiarrhythmic Drugs but No Long-Term Benefit

Dr Kazuaki Kaitani

EAST-AF, led by Dr Kazuaki Kaitani (Tenri Hospital, Nara, Japan), included 2044 patients who underwent catheter ablation following the completion of the UNDER-ATP trial[2]. Of these, 1018 were randomized to antiarrhythmic drug therapy for 90 days postablation (approximately 75% of patients received a class I antiarrhythmic medication) and 1022 randomized to a control group. Patients in the trial were slightly older in the drug-therapy arm (66 years vs 61 years; P<0.001) but approximately two-thirds in both arms had paroxysmal AF, 23% had persistent AF, and 10% long-standing AF.

Speaking during the ESC media briefing, Kaitani said transient atrial arrhythmias occur frequently in the first few months following AF ablation, likely attributable to atrial irritability from the procedure. These early events are a strong predictor of late recurrence of atrial arrhythmias, he said.

In the 90-day blanking period, 59.0% of patients in the antiarrhythmic-drug-therapy arm were free from AF/AT vs 52.1% in the controls, a statistically significant difference. Despite the benefit observed in this early period, the EAST-AF investigators did not observe a significant reduction in AF/AT at 1 year.

To heartwire , Di Biase said physicians typically will use the antiarrhythmic drug therapy in the 90-day blanking period in patients who have undergone catheter ablation of AF. His personal strategy is to stop drug therapy 3 days prior to the ablation—4 months in the case of amiodarone because of the long half-life—and to restart the drugs immediately after the procedure for 90 days.

"After 90 days, the real clock starts," he said about assessing AF/AT recurrence postablation.

Despite the negative results, Di Biase said he will continue to use antiarrhythmic medication in the 90-day blanking period—not to reduce AF/AT recurrence at 1 year but to offset events resulting from myocardial irritability following ablation.

"I still believe the heart may be irritated in this time, and I hope it would avoid the need for hospitalization or any problem with the patient in the first 90 days," he said. "Although many patients are refractory to antiarrhythmic drugs, and that's why they go for the ablation. They have tried them and they have side effects. The failure of a drug is because it's ineffective or because the patient has side effects. If a patient has discontinued a drug because of a side effect, of course, we don't routinely give these drugs. Like everything in medicine, it requires a tailored approach based on the patient."

Kobori and Kaitani have no relevant financial relationships. Di Biase is a consultant for Biosense Webster, Stereotaxis, and St Jude Medical. He has received speaker fees and travel reimbursement from Medtronic, Atricure, EPiEP, Boston Scientific, and Biotronik.

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