Hybrid Therapy and Heart Team for Atrial Fibrillation

Study Overview
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Brief Summary
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Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence ranging from 5% over 60 years old to 17% after 85 years old. Besides hemodynamical compromises and occurrence of heart failure, stroke remains the most feared complication related to AF with a risk increased by 5-fold. Catheter ablation with the aim of pulmonary veins isolation (PVI) has evolved as a standardized treatment option in paroxysmal AF (PAF), supported by the current guidelines. However, due to advanced electrical and structural remodeling, catheter ablation for persistent AF is rather disappointing with a limited success rate, at least after a single procedure. Due to these shortcomings, minimally invasive thoracoscopic surgical techniques have gained attention with good results in persistent AF patients. Comparison between thoracoscopic surgical ablation and catheter ablation have shown that surgical ablation was associated with higher success rates, less redo procedures but also with higher complication rates. The main issue with surgical ablation is the difficulty to check the ablation lines and pulmonary vein isolation, which are the cornerstones for achieving good long-term results. Hybrid therapy, combining both epicardial surgical and endocardial catheter ablation is expected to be the most effective technique. It would avoid incomplete lesions or incomplete pulmonary vein isolation, and would provide complete lesion set. Hybrid therapy of AF has been compared with mini-invasive surgical ablation of AF, showing a significant higher rate of sinus rhythm achievement in the hybrid therapy group. However, no comparative clinical trials data are currently available in the setting of persistent AF comparing hybrid ablation and conventional catheter ablation.

Official Title
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Comparison of the Efficacy of Hybrid Ablative Therapy for Patients With Persistent Atrial Fibrillation Versus Conventional Catheter Ablation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Hybrid ablation
* Procedure: Percutaneous catheter ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To have a history of symptomatic persistent atrial fibrillation (AF) (continuous AF lasting 7 days or more) or long-standing persistent AF (continuous AF lasting for more than 12 months) To be refractory to or intolerant to at least one class I (flecainide / propafenone) or III (sotalol / amiodarone) antiarrhythmic drug, To be at least 18 years of age, To agree to participate (signature of the informed consent) Exclusion Criteria: A previous AF ablation procedure, A longstanding persistent AF > 3 years, A paroxysmal AF AF consecutive to electrolyte imbalance, thyroid disease, or other reversible non-cardiovascular cause, Presence of left atrial appendage (LAA) thrombus, Left atrial size ≥ 70ml/m² on transthoracic echocardiogram (TTE), Left ventricular ejection fraction < 35%, Cardiac surgery (other than AF treatment) planned within 12 months, Contra-indication to heparin and/or oral anticoagulation Contra-indication to transoesophageal echocardiogram (TEE) Carotid stenosis > 80%, Active infection or sepsis Pleural adhesions, Elevated hemi diaphragm Proven and untreated sleep apnoea syndrome, Occurrence of a cerebrovascular accident (CVA) or a transient ischemic attack (TIA) during the past 6 months, History of blood clotting abnormalities Indication for a permanent dual antiplatelet therapy History of thoracic radiation, History of myocarditis or pericarditisHistory of cardiac tamponade, History of thoracotomy or cardiac surgery, Body-mass-index > 40 kg/m2, Significant lung dysfunction Contra-indication to anesthesia Patient with chronic obstructive pulmonary disease (COPD) Pregnancy, Life expectancy less than 12 months, Adults protected by the law

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hybrid ablation procedure<br>In the hybrid ablation procedure, the epicardial surgical ablation procedure will be combined with percutaneous endocardial catheter ablation procedure in a single step procedure. | Procedure: Hybrid ablation<br>* In the hybrid ablation arm, the epicardial surgical ablation procedure will be combined with percutaneous endocardial catheter ablation procedure in a single step procedure (same operative time). During the endocardial approach, the isolation of the pulmonary veins and the posterior box will be checked and completed if necessary. Then additional ablation will be performed for atrial tachycardia or ongoing persisting atrial fibrillation (AF) according the same lesions setup or stepwise protocol than the conventional arm<br>|
| Active Comparator: Percutaneous endocardial catheter ablation procedure<br>In the percutaneous catheter ablation arm, the procedure will be performed according to the current guidelines (pulmonary vein isolation, linear ablation and fragmented potentials ablation if needed, with the achievement of sinus rhythm during the procedure being the optimal endpoint). | Procedure: Percutaneous catheter ablation<br>* In the percutaneous catheter ablation arm, the procedure will be performed according to the current guidelines (pulmonary vein isolation, linear ablation and fragmented potentials ablation if needed, with the achievement of sinus rhythm during the procedure being the optimal endpoint. Any atrial tachycardia will be mapped and ablated as well (DC shock performed otherwise).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation (AF)/Atrial tachycardia (AT) recurrence | occurrence of at least one episode of AF/AT > 30 seconds in any ECG or Holter tracing (absence or presence) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AF/AT recurrence or major complication | Percentage of patients developing a recurrence of AF/AT or a major complication (related to the procedure or related to AF/AT) | 12 months | 
| Major complication related to the procedure | Percentage of patients developing a major complication related to the procedure | 12 months | 
| Major complication related to AF/AT | Percentage of patients developing a major complication related to AF/AT | 12 months | 
| Any complication (major or minor) | Percentage of patients developing any complication (major or minor) related to the procedure or related to AF/AT | 12 months | 
| Redo-procedure | Percentage of patients requiring a redo-procedure (new ablation in left atrium) | 12 months | 
| Cardioversion | Percentage of patients requiring a cardioversion | 12 months | 
| Number of hospitalizations | Number of hospitalizations for AF/AT recurrence or complications related to AF/AT or to the procedure | 12 months | 
| Duration of the hospitalization | Mean duration of the hospitalization for AF ablation | 1 month | 
| Radiation exposure time | Radiation exposure time (expressed in minutes) per patient. In case of redo-ablation during the follow-up, the total exposure time of the two first and the redo procedure will be totalized. | 12 months | 
| Radiation exposure dosage | Radiation exposure dosage per patient. In case of redo-ablation during the follow-up, the total exposure dosage of the two first and the redo procedure will be totalized. | 12 months | 
| Antiarrhythmic drugs | Percentage of patients requiring class I (flecainide ou propafenone) or III (sotalol ou amiodarone) antiarrhythmic drugs | 12 months | 
| Electrophysiological success | Percentage of patients considered as reaching electrophysiological success, i.e. isolation of pulmonary veins and posterior box after epicardial surgical ablation. The validation will be performed during catheter ablation: isolation will be validated if there an entrance block in the posterior wall and in the pulmonary veins. | Day 0 | 
| Evolution of quality of life | Evolution of quality of life using the Canadian Cardiovascular Society Severity in Atrial Fibrillation (CCS-SAF) scale. Symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF are evaluated by this scale. The scale ranges from 0 to 4, corresponding to 0=no effect on functional quality of life to 4=a severe effect on life quality. | Between baseline to 12 months | 
| ICER | The incremental cost-effectiveness ratio (ICER) of hybrid ablation versus catheter ablation, including long term evaluation with MARKOV modelling | 12 months | 
| ICUR | The incremental Cost-Utility Ratio (ICUR) of hybrid ablation versus catheter ablation, including long term evaluation with MARKOV modelling | 12 months | 
| Production costs | Production costs of the two strategies using the micro-costing approach | during the surgical procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epicardial surgical ablation, Percutaneous endocardial catheter ablation