Clinical trial NCT03401099: Cryoballoon Ablation as First Line Treatment of Atrial Flutter
Official title: Cryoballoon Pulmonary Vein Isolation as First Line Treatment for Typical Atrial Flutter
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Flutter Typical
Keywords: Radiofrequency ablation
Cavo-tricuspid isthmus
Pulmonary Vein Isolation
Cryoballoon ablation
Lead sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Medtronic International Trading Sarl
First posted: 2018-01-17
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomised 1:1 into two groups to receive either of the two treatments.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
Secondary outcomes:
measure: Time to first symptomatic or asymptomatic Atrial Fibrillation lasting ≥2 min
timeFrame: After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
measure: Total Burden of Atrial fibrillation over 12 months
timeFrame: After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
measure: Time to first symptomatic or asymptomatic atrial flutter/atrial tachycardia
timeFrame: After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
measure: Incidence of any significant arrhythmia
timeFrame: After first ablation procedure, through study completion, an average of 12 months
measure: Total burden of abnormal heart rhythm measured by the implantable loop recorder
timeFrame: After first ablation procedure through study completion or time of intervention, whichever comes first, assessed up to 12 months
measure: Incidence of repeat electrophysiological interventional procedure (repeat catheter ablation, or DCCV) over the follow-up period.
timeFrame: After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
measure: Incidence of procedural complications
timeFrame: During and after ablation procedure, through study completion, an average of 12 months
measure: Incidence of all-cause hospitalisations
timeFrame: After first ablation procedure, through study completion, an average of 12 months
measure: Quality of Life questionnaire
timeFrame: At baseline and at 12 months
measure: Procedural duration
timeFrame: Only during the first ablation procedure
measure: Total Fluoroscopy times
timeFrame: Only during the first ablation procedure
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: University Hospital Inselspital Bern
city: Papworth Everard
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
state: Cambridge
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust, Wythenshawe Hospital
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust, James Cook University Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospital NHS Foundation Trust, Freeman Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
affiliation: Liverpool Heart and Chest Hospital
name: Dhiraj Gupta, MBBS MD FRCP
role: STUDY_CHAIR
References:
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citation: De Bortoli A, Shi LB, Ohm OJ, Hoff PI, Schuster P, Solheim E, Chen J. Incidence and clinical predictors of subsequent atrial fibrillation requiring additional ablation after cavotricuspid isthmus ablation for typical atrial flutter. Scand Cardiovasc J. 2017 Jun;51(3):123-128. doi: 10.1080/14017431.2017.1304570. Epub 2017 Mar 23.
citation: Gupta D, Ding WY, Calvert P, Williams E, Das M, Tovmassian L, Tayebjee MH, Haywood G, Martin CA, Rajappan K, Bates MGD, Temple IP, Reichlin T, Chen Z, Balasubramaniam RN, Ronayne C, Clarkson N, Morgan M, Barton J, Kemp I, Mahida S, Sticherling C. Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter. Heart. 2023 Feb 14;109(5):364-371. doi: 10.1136/heartjnl-2022-321729.
citation: Ding WY, Williams E, Das M, Tovmassian L, Tayebjee M, Haywood G, Martin C, Rajappan K, Bates M, Temple IP, Reichlin T, Chen Z, Balasubramaniam R, Ronayne C, Clarkson N, Mahida S, Sticherling C, Gupta D. Cryoballoon pulmonary vein isolation as first line treatment for typical atrial flutter (CRAFT): study protocol for a randomised controlled trial. J Interv Card Electrophysiol. 2021 Apr;60(3):427-432. doi: 10.1007/s10840-020-00746-6. Epub 2020 May 8.