From the Emergency Department Directly to Ablation of Atrial Fibrillation Study

Study Overview
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Brief Summary
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The study is a prospective, two-arm, randomized, open-label, blinded endpoint, multi-center study to investigate the impact of first line ablation in patients presenting at the emergency room with recent-onset paroxysmal or persistent atrial fibrillation.

Detailed Description
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As stated in the current guidelines, the prevalence of AF tripled over the last 30 years and further progress is expected. AF is associated with increased mortality and morbidity. Approximately 70% of the patients who are hospitalized for AF are admitted through the emergency department. The steady increase of AF-related visits at the emergency departments therefore lead to a high number of hospitalizations. The direct costs of AF already amount to approximately 1% of total healthcare spending, driven by AF-related complications (e.g. stroke) and treatment costs (e.g. hospitalizations). These costs will increase dramatically unless AF is prevented and treated in a timely and effective manner. Catheter ablation therapy has been proven to be safe and effective for the treatment of paroxysmal and persistent AF and is now standard in AF therapy. Several trials have shown that catheter ablation of AF is superior to antiarrhythmic drug therapy. As evidenced by the FIRE & ICE trial, cryoballoon ablation is non-inferior to the former goldstandard of radiofrequency current (RFC) energy. Importantly, it has been reported that cryoballoon ablation was associated with a reduction in resource use and costs as compared to RFC ablation of AF. These cost savings persisted over multiple healthcare systems. However, data on the optimal timing of AF ablation is scarce. While there is evidence that catheter ablation is highly efficient in delaying progression from paroxysmal to persistent AF, there are only few trials evaluating a strategy of early treatment of AF, regarding the patients' medical history (CRYO-FIRST, EARLY-AF). Another trial investigated the utilization of a multidisciplinary AF treatment pathway in patients presenting to the emergency department, which resulted in reduction of admission rate and hospital stays but did not include catheter ablation of AF. However, there is no scientific evidence on a strategy of early treatment of atrial fibrillation comparing anti-arrhythmic drug therapy to catheter ablation in the large number of patients presenting to the emergency departments. A well-known limitation of many trials investigating catheter ablation of AF, can be found during the trials follow up after ablation, as detection of AF recurrences can be challenging. The sensitivity of detecting asymptomatic episodes with intermittent 24-hours ECG-monitoring is low. The Heart Rhythm Society and the European Heart Rhythm Society encourage continuous arrhythmia monitoring due to the greater sensitivity in detecting symptomatic and asymptomatic AF recurrences but also when assessing the overall AF burden. Additionally, in an era of digital revolution, the AFNET incorporated the use of wearables, smartphones, hand held-devices and health-related apps to new approaches of AF management. To evaluate the efficacy and safety of an early rhythm control treatment of AF by catheter ablation with the cryoballoon with particular respect to arrhythmia recurrence, rehospitalisation, heart failure and health care costs in patients presenting to the emergency department due to AF, a prospective randomized study is necessary.

Official Title
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From the Emergency Department Directly to Ablation of Atrial Fibrillation - Study - The EMERGE Cryo Study

Conditions
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Atrial Fibrillation (AF)

Intervention / Treatment
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* Procedure: Ablation of atrial fibrillation (AF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented, paroxysmal or persistent AF (longest AF episode < 6-month duration). Any ECG documentation of AF (12 lead ECG, Holter ECG or mobile ECG monitoring) needs to be presented. Recent-onset AF (≤ 1 year prior to enrolment) Presenting at the emergency department or outpatient clinic within the last 2 weeks because of AF, including patients with spontaneous conversion in sinus rhythm (with prior AF documentation) Age ≥ 18 years Subject is able and willing to give informed consent Exclusion Criteria Pers. AF > 6 Mon (one episode) LA-Diameter > 60mm Severe mitral stenosis or regurgitation, prior mitral valve reconstruction or replacement Any previous left atrial ablation Ongoing continuous AAD therapy with Amiodarone at baseline History of failed continuous AAD therapy with > 1 agent. Exceptions are Beta blocker, Verapamil or pill in the pocket-therapy. Any condition or disease, which is contraindication for AF ablation, up to the assessment of the investigator Any condition or disease, which is a contraindication for antiarrhythmic drug treatment, up to the assessment of the investigator Known intra-cardiac thrombus formation under continuous oral anticoagulation (defined as intake >4 weeks) Any contraindication for oral anticoagulation Any untreated or uncontrolled hyperthyroidism or other reversible causes for AF like alcoholism Pregnant or breastfeeding woman or woman of childbearing potential not on adequate birth control Active systemic infection Co-Existence of non PV-dependent atrial Tachycardia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective, two-arm, randomized, open-label, blinded endpoint, multi-center study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group1: Cryo-AF-Ablation<br>Patients randomized in the Cryo-AF-Ablation group should receive the cryo AF ablation within 21 days from baseline. | Procedure: Ablation of atrial fibrillation (AF)<br>* Cryo-AF-ablation of pulmonary vein (pulmonary vein isolation = PVI)<br>|
| No Intervention: Group 2: Usual care<br>Patients randomized in the usual care group should start or maintain on AAD therapy within 21 days from baseline, based on decision of the investigator according to current ESC Guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from any atrial tachyarrhythmia | Freedom from any atrial tachyarrhythmia, including atrial fibrillation (AF), atrial flutter and atrial tachycardias (>30 s) through 3 to 12 months follow-up on ILR monitoring or any 12 lead ECG on visits, ECG Holter monitoring, or on symptom driven event monitoring | within 3 to 12 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AF burden (1) | AF burden between 3 to 12 months after randomization. AF burden is defined as overall percentage of AF during the observed time | within 3 to 12 months follow up | 
| AF burden (2) | AF burden between 0 to 3, 3 to 6 and 6 to 12 months after randomization | within 0 to 12 months follow up | 
| Freedom from atrial fibrillation | Freedom from atrial fibrillation (AF) (>30 s) | within 3 to 12 months follow up | 
| Freedom from atrial tachycardia and atrial flutter | Freedom from atrial tachycardia and atrial flutter (AFl) | within 3 to 12 months follow up | 
| symptomatic versus asymptomatic atrial tachyarrhythmia | Analysis of amount of symptomatic versus asymptomatic atrial tachyarrhythmia recurrences | within 3 to 12 months follow up | 
| Re-hospitalization rate | Re-hospitalization rate due to cardiovascular disease (AF, worsening of heart failure, cardiovascular disease) | up to 12 months follow up | 
| Progression of heart failure | Progression of heart failure defined as trend in LV-EF and trend in BNP | up to 12 months follow up | 
| Quality of life (AFEQT and EQ-5D-5L) | Improvement of quality of life at 12 months compared to baseline (AFEQT and EQ-5D-5L Questionnaire) | within 0 to 12 months follow up | 
| Safety / Complications | Safety / Complications | within 0 to 12 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ablation