GAP-AF study helps to define optimal approach to ablation/ SARA study shows ablation superior to drugs for patients with persistent AF
- Gap-AF -AFNET 1 Trial. K Kuck
- Catheter Ablation for the Treatment of Persistent Atrial Fibrillation: A Prospective, Multicentric, Randomized Controlled Trial of Ablation Versus Antiarrhythmic Drugs in Persistent Atrial Fibrillation. SARA trial. L Mont
- Clinical Evaluation of the PhD function in the PARADYM CRT device trial. CLEPSYDRA trial. A Auricchio.
- Incidence and Risk Factors for Thromboembolic Events After Catheter Ablation of Atrial Fibrillation: The Leipzig Heart Center AF Ablation Registry. G Hindricks, A Bollmann
- PainFree SmartShock technology: trial primary results: inappropriate shock rates in patients with single chamber ICD’s using a novel suite of detection algorithms. A. Meijer.
Using catheter ablation to create complete linear lesions around pulmonary veins, proved more effective than the creation of incomplete lesions in preventing recurrence of atrial fibrillation (AF), reports the GAP-AF study. The study, presented today in the Late Breaking Clinical Trials session I at the EHRA EUROPACE 2013 meeting in Athens, Greece, represents the first time that a randomized controlled study has been undertaken comparing the two different ablation strategies for patients with paroxysmal AF.
Identification of triggers initiating AF within the pulmonary veins led to prevention of AF recurrence by catheter ablation at the site of origin of the trigger. The Heart Rhythm Society /European Heart Rhythm Association/European Society of Cardiology Expert Consensus Document on Catheter and Surgical Ablation of Atrial Fibrillation (published in 2007 and updated in 2012) states that patients undergoing catheter ablation for AF should have complete isolation of the pulmonary veins, which involves a complete circumferential lesion being created around the pulmonary vein.
“This recommendation was based on observational studies, not on a prospective randomized trial. But some electrophysiologists (EPs) continue to believe that it’s sufficient to create incomplete linear lesions where conduction sites still exist between the pulmonary veins and left atrium,” explained Professor Karl Kuck, from Asklepios Klinik St George, Hamburg ,Germany, presenter of the GAP-AF study.
Part of their reasoning is that 95% of patients with AF recurrence after complete PV isolation procedures are found to have conduction gaps between the pulmonary veins and left atrium, he said. “Since they can’t isolate the pulmonary veins permanently, they reason that incomplete isolation is sufficient and has the advantage of being a shorter procedure that has a potentially lower complication rate and costs less,” said Prof Kuck.
In the GAP-AF (AFNET1) study between February 2006 and August 2010, 233 patients with drug refractory paroxysmal AF were randomized to have either a complete procedure (n=117) or an incomplete procedure (n=116). For the incomplete procedure the EPs stopped the radiofrequency application at one site to permit reconduction from the circumference. The study, which was performed in seven German centres, was funded by the German Atrial Fibrillation Network (AFNET). The inclusion criteria for the study were that patients had to be aged over 55 years and to have been treated with one anti arrhythmic drug before they entered the trial. Patients with poor left ventricular function were excluded from the study.
The primary endpoint of the study was the time to first recurrence of symptomatic AF with duration of more than 30 seconds on trans-telephonic ECG monitoring, or detection of asymptomatic AF defined as two consecutive recordings of AF during a minimum of 72 hours. The study made use of the RhythmCard™ technology, a small credit card sized device that patients can place on their chest wall to record an ECG whenever they experienced symptoms of AF and transmit the data via the telephone. Additionally, patients were asked to record and transmit an ECG every day regardless of their symptoms.
Results showed that at the three month follow-up, sinus rhythm (normal beating of the heart) had been achieved in 37.8% (46)of patients who had complete ablation, versus 20.8% (26) with incomplete ablation (P<0.001). Furthermore, the mean number of days in sinus rhythm was 60 days for the complete group versus 16 days for the incomplete group (P<0.001).
At three months, when patients were taken back to the EP lab for a repeat investigation, 70 % of those randomised to complete PVI had gaps versus 89% randomised to incomplete PVI.
No significant differences were found for serious adverse events (including syncope, stroke, major bleeding, tamponade) between the complete and incomplete groups.
“The study shows us for the first time that complete isolation of the pulmonary veins is more effective than incomplete isolation. It suggests that the level of evidence for complete ablation should be upgraded from class Ic to class Ia, where it is supported by a multicentre randomized trial,” said Prof. Kuck.
However, the study also highlighted that recurrence rates were high even for patients who had undergone complete isolation procedures. “Research is urgently needed to improve ablation techniques to make the complete lines more durable. There is a need to explore other energy sources and tools for catheter ablation,” he said.
The Fire and Ice trial, for example, is currently underway, to see whether a thermocool catheter might be more effect than cryo ablation for patients with paroxysmal AF.
The SARA study, also presented in the Late Breaking Clinical Trials session today, found that catheter ablation therapy was superior to medical therapy for maintenance of sinus rhythm in patients with persistent AF.
While a number of previous studies have showed the superiority of catheter ablation (CA) over antiarrhythmic drug therapy (ADT) for patients with paroxysmal AF, no previous studies have been undertaken specifically comparing ablation to drugs in patients with persistent AF. “Patients with persistent AF have in general been considered bad candidates for ablation, due to poor results, and the need for prolonged and aggressive procedures,” explained principal investigator Professor Lluis Mont, from the Atrial Fibrillation Unit, University of Barcelona, Spain.
Between May 2009 and November 2011 in the open parallel Study of Ablation vs AntiaRrhythmic Drugs in Persistent Atrial Fibrillation (SARA) study Prof. Mont and colleagues, from eight ablation centres in Spain, randomly assigned a total of 146 patients with persistent AF 2:1 to CA (n=98) or ADT (n=48). ADT was given according to current guidelines, with class III drugs (amiodarone) recommended for patients with structural heart disease and class Ic (flecainide) plus dilitiazem or beta blockers for patients without structural heart disease. The inclusion criteria were that patients should have experienced symptomatic persistent AF (> seven days or <seven days requiring electrical or pharmacological cardioversion) that was refractory to at least one class I or class III antiarrhythmic drug. Additionally, the study excluded patients with long standing persistent AF (continuous for more than one year) since this represents ‘a bad scenario for ablation’, and also patients with extremely dilated atriums (>50mm anterioposterior diameters).
In an intention-to-treat analysis, the proportion of patients free of prolonged (>12 hours) AF at 12 months (the primary end-point) was 70.4% in the CA group versus 43.7% in the ADT group (p=0.002); implying an absolute risk difference of 26.6% (95% CI: 10.0-43.3) favouring ablation group.
The proportion of patients free of any recurrence of AF or flutter (lasting >30 seconds) was 60.2% in the CA group compared to 29.2% in the ADT group (p<0.001).
“Our study shows that, if proper selection criteria are applied, ablation can achieve good results for patients with persistent AF,” said Mont. “It’s likely to have an impact on guidelines and may contribute to an upgrade of ablation in persistent AF to category 1B.” Results would not apply to patients with very dilated atrium and long standing persistent AF.
A challenge for increasing the number of ablation procedures taking place was likely to be the shortage of highly trained physicians. “But as happened years ago with coronary angioplasty, the demand is likely to increase the numbers of physicians and centres prepared to perform such procedures,” said Prof. Mont.
Further studies, he added, are now needed looking at outcomes according to ‘shape remodelling’ and levels of fibrosis.”This should help to further stratify patients and select good candidates for ablation,” he concluded.
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About the European Society of Cardiology
The European Society of Cardiology (ESC) represents more than 80,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.
About the European Heart Rhythm Association
The European Heart Rhythm Association (EHRA) is a registered branch of the ESC. Its aim is to improve the quality of life of the European population by reducing the impact of cardiac arrhythmias and reducing sudden cardiac death.
The German competence Network on Atrial Fibrillation Network (AFNET), which celebrated its 10 year anniversary in March this year, was set up to investigate the reasons and mechanism behind atrial fibrillation. The initiative has been funded by the German Federal Ministry of Research and Education (BMBF) with € 17 million.
Between 2004 and 2006 AFNET enrolled 10,000 patients coming from all levels of care (university hospitals, non-university hospitals, cardiologists in private practice and GPs) into a registry. The follow up data, currently being analysed, promises to provide insights into the long term complications of AF.
In addition to GAP-AF- AFNET1, large multicentre trials that have been undertaken by AFNET include the ANTIPAF-AFNET2 trial testing the efficacy of Angiotensin receptor blockers in paroxysmal atrial fibrillation and the Flec-SL AFNET3 which assessed the benefits of a short term antiarrhythmic drug treatment for four weeks after cardioversion.
Since 2007 AFNET and the European Heart Rhythm Association (EHRA) have organized joint consensus conferences in which AF specialists from Europe and North America pool their knowledge and define recommendations.