Cryoballoon Ablation as First Line Treatment of Atrial Flutter

Study Overview
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Brief Summary
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Current guidelines recommend radiofrequency catheter ablation of the cavotricuspid isthmus as treatment for symptomatic/drug-refractory atrial flutter, in spite of the fact that recurrences of flutter and incidence of post-ablation atrial fibrillation are common. In this study, the investigators assess the hypothesis that the use of cryoballoon Pulmonary Vein Isolation ('novel' treatment) to achieve the electrical disconnection between the pulmonary veins and the heart will lead to higher rates of freedom from abnormal heart rhythms (atrial flutter, atrial fibrillation, or atrial tachycardia) and more improved quality of life than treatment using heat energy (radiofrequency ablation) directed at the cavotricuspid isthmus ('conventional treatment').

Detailed Description
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Atrial flutter and atrial fibrillation are believed to share the same initiating triggers in the form of pulmonary vein ectopy. Cavo-tricuspid isthmus-dependent atrial flutter almost always results from short bursts of antecedent atrial fibrillation. Radiofrequency (RF) ablation of the cavo-tricuspid isthmus (CTI) is the current accepted first-line treatment for atrial flutter, although post-ablation atrial fibrillation commonly occurs, even in the absence of pre-existing atrial fibrillation. Cryoballoon Pulmonary Vein Isolation (PVI) has become an established treatment for atrial fibrillation. In patients with both atrial flutter and fibrillation, PVI alone has been shown to control both types of atrial arrhythmia, with no benefit derived from supplemental RF CTI ablation. This study aims to demonstrate that standalone cryoballoon PVI for typical atrial flutter without RF CTI ablation will lead to a significant difference in preventing recurrence of atrial arrhythmia compared to radiofrequency ablation of the CTI, and should be offered as first-line therapy.

Official Title
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Cryoballoon Pulmonary Vein Isolation as First Line Treatment for Typical Atrial Flutter

Conditions
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Atrial Flutter Typical

Intervention / Treatment
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* Procedure: Radiofrequency ablation of CTI
* Procedure: Cryoballoon PVI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18-80 years 2. Patients referred for catheter ablation for typical atrial flutter. The atrial flutter may be either persistent or paroxysmal, with at least one episode having been documented on 12-lead ECG. In the view of the treating physician, the ECG morphology should be compatible with a CTI-dependent circuit, either counterclockwise or clockwise. Exclusion Criteria: 1. Any evidence of previously documented atrial fibrillation 2. Previous cavo-tricuspid isthmus ablation or atrial fibrillation ablation 3. Atrial flutter documented solely on Ambulatory monitoring 4. Atrial flutter morphology on ECG suggestive of a left atrial flutter 5. History of atrial flutter with 1:1 atrioventricular conduction and haemodynamic compromise 6. Indwelling atrial-septal defect occluder device, or any anatomical reason that precludes left atrial access 7. Left atrial diameter (PLAX M-mode) >5.5 cm 8. Severe left ventricular dysfunction (LV ejection fraction < 30% on Echocardiography) 9. Recent stroke/transient ischaemic attack within 3 months 10. Inability or unwillingness to take oral anticoagulant treatment 11. Morbid obesity (Body Mass Index ≥40) 12. Extreme frailty (A score of 7,8 or worse on the Clinical Frailty Scale) 13. Implanted metal prosthetic valve(s) in mitral position 14. Indwelling cardiac resynchronisation therapy device, pacemaker or implantable cardioverter defibrillator 15. Advanced Renal dysfunction (eGFR<30 ml/min) 16. Pregnancy 17. Severe valvular heart disease of any kind as assessed by the investigator 18. Previous valve replacement surgery or other prosthetic heart valve

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Participants will be randomised 1:1 into two groups to receive either of the two treatments.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiofrequency ablation of CTI<br>Radiofrequency ablation of CTI (cavo-tricuspid isthmus), which is the 'conventional' treatment of atrial flutter | Procedure: Radiofrequency ablation of CTI<br>* Delivery of radiofrequency energy to the cavotricuspid isthmus (region of right atrial tissue between the tricuspid annulus and the inferior vena cava) until bidirectional block is achieved<br>* Other names: CTI ablation;|
| Active Comparator: Cryoballoon PVI<br>Cryoballoon PVI (Pulmonary Vein Isolation), which is the 'novel treatment' | Procedure: Cryoballoon PVI<br>* Cryoballoon application to the pulmonary veins aiming for Pulmonary Vein Isolation<br>* Other names: Cryoablation Pulmonary Vein Isolation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrence of sustained, symptomatic supraventricular arrhythmia (Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia) following a blanking period of 4 weeks after a single ablation procedure | 'Sustained' is defined as lasting >30 seconds. 'Symptomatic' is defined as acute onset awareness of palpitations, breathlessness, dizziness, fatigue or chest pain associated with patient activation of the loop recorder. | After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first symptomatic or asymptomatic Atrial Fibrillation lasting ≥2 min | How long it takes until first occurrence of atrial fibrillation (associated with symptoms or no symptoms) lasting 2 or more minutes after blanking period. Two minutes is the minimum duration detectable by the loop recorder | After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up | 
| Total Burden of Atrial fibrillation over 12 months | The total occurrence of atrial fibrillation recorded by the loop recorder (symptomatic or asymptomatic) during the follow-up period | After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up | 
| Time to first symptomatic or asymptomatic atrial flutter/atrial tachycardia | Occurrence of atrial flutter/atrial tachycardia with/without symptoms following the blanking period | After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up | 
| Incidence of any significant arrhythmia | Incidence of any arrhythmia requiring medical visit to primary or secondary care, or hospitalisation, or leading to death | After first ablation procedure, through study completion, an average of 12 months | 
| Total burden of abnormal heart rhythm measured by the implantable loop recorder | Total arrhythmic burden up to end of follow up or up to time of intervention (either cardioversion or ablation), whichever comes first. | After first ablation procedure through study completion or time of intervention, whichever comes first, assessed up to 12 months | 
| Incidence of repeat electrophysiological interventional procedure (repeat catheter ablation, or DCCV) over the follow-up period. | Occurrence of repeat ablations/cardioversion | After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up | 
| Incidence of procedural complications | Composite of cardiac tamponade requiring drainage, persistent phrenic nerve palsy lasting >24 hours, serious vascular complications requiring intervention or delaying discharge, stroke/transient ischaemic attack, requirement for a permanent pacemaker, atrio-esophageal fistula, or death | During and after ablation procedure, through study completion, an average of 12 months | 
| Incidence of all-cause hospitalisations | Any hospital admission post-ablation | After first ablation procedure, through study completion, an average of 12 months | 
| Quality of Life questionnaire | Quality of life as assessed by the standard EuroQol Group's 5-dimensional questionnaire. This comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and the visual analogue scale. The single digits for the five dimensions will be combined into a 5-digit number that describes the patient's health state. | At baseline and at 12 months | 
| Procedural duration | Duration of ablation measured in minutes for either treatment | Only during the first ablation procedure | 
| Total Fluoroscopy times | The total time in minutes during which patient will be exposed to radiation under each of the two treatment techniques | Only during the first ablation procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiofrequency ablation, Cavo-tricuspid isthmus, Pulmonary Vein Isolation, Cryoballoon ablation