Single Versus Double Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Atrial Fibrillation (SD-CRYO-AF)

Efficacy of Single Versus Double Cryoballoon Ablation for Pulmonary Vein Isolation in Patients With Atrial Fibrillation (SD-Cryo-AF): A Randomized Study

This is a clinical study where the investigators will assess the efficacy of a single cryoballoon application per vein guided by a multipolar recording catheter as compared with a conventional technique with 2 cryoballoon applications for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: PVI by single cryoballoon application guided by Achieve Mapping Catheter; Device: PVI by 2 routine cryoballoon applications

Detailed Description

This is a prospective, randomized clinical study performed at one centre. The objective is to assess the efficacy of a single cryoballoon application per vein guided by a multipolar recording catheter as compared with a conventional technique with 2 cryoballoon applications for pulmonary vein isolation in patients with atrial fibrillation (AF).

140 subjects with paroxysmal or persistent atrial fibrillation referred for their first AF ablation procedures will be enrolled.

Recruitment, ablation and follow-up will be performed at Dep of Cardiology in Uppsala University Hospital, Uppsala, Sweden.

Study duration is 2 years with 12--months enrolment period and 1 year follow-up per subject.

Pulmonary vein isolation (PVI) will be performed using the Arctic Front Advance cryoballoon ablation catheter. Patients will be randomized to a single cryoballoon application guided by a multipolar recording catheter or to a conventional technique with 2 cryoballoon applications. After cryoballoon ablation of all pulmonary veins, PV conduction block will be assessed by a separate circular mapping catheter. Acute procedural success is defined as complete electrical isolation of a pulmonary vein assessed by entrance and exit block, including 20 minutes waiting time. Complications and duration of the procedure will be assessed.

Patients will be followed at three, six and 12 months after the ablation procedure. A 12 lead ECG, a 7 day Holter monitoring, quality of life (EQ5D) and EHRA score, will be performed at baseline, 6 and 12 months. as well as Biomarkers including nTproBNP and troponin I, will be performed at baseline, and at 6 and 12 months (only nTproBNP). Predictive variables for successful outcome/AF recurrence will be analysed.

The frequency of symptomatic recurrence of AF and number of reablations will be compared at 6 and 12 months, and in those requiring a redo ablation procedure the status of PV reconduction will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Department of Cardiology, University Hospital in Uppsala

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with paroxysmal or persistent AF verified by ECG
• Patients with symptoms corresponding to at least Europe Heart Rhythm Association (EHRA) score 2.

Exclusion Criteria:

• Sinus rhythm cannot be maintained for at least one hour after an electrical cardioversion.
• Congestive heart failure with New York Heart Association (NYHA) class 3 or more.
• Left ventricular ejection fraction < 35% not secondary to AF with inadequate rate control, according to the judgement of the investigator.
• Left atrial diameter ≥ 55 mm judged by transthoracic echocardiography.
• Prior AF ablation procedure.
• Longstanding persistent AF
• AF secondary to a transient or correctable abnormality including electrolyte imbalance, trauma, recent surgery, infection, toxic ingestion, and uncontrolled thyroid disease as well as AF triggered by other uniform supraventricular tachycardia.
• Contraindication to treatment with anticoagulants.
• Significant valvular disease or planned cardiac intervention.
• Hypertrophic cardiomyopathy.
• Recent cardiac disease states within the last 6 months; unstable angina, acute myocardial infarction, revascularisation procedures, valve disease
• Implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT) device.
• Dual chamber- and single chamber-pacemaker when the patient is pacemaker dependent on ventricular level
• Patients with contraindications for transseptal catheterization or appropriate vascular access is precluded.
• Renal failure requiring dialysis or abnormalities of liver function tests.
• Participant in investigational clinical or device trial.
• Unwilling or unable to give informed consent or inaccessible for follow-up and psychological problem that might limit compliance.
• Active abuse of alcohol or other substance which may be causative of AF and/or might affect compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PVI by single cryoballoon application; A single cryoballoon application for pulmonary vein isolation will be guided by a Multipolar Recording Catheter (Achieve Mapping Catheter), passed through the inner lumen of the cryoablation catheter. A single application of 4 minutes will be used per vein guided by recording of loss of electrograms and by a defined drop of temperature within 2 minutes application. If a stable position with adequate occlusion of the vein the Achieve catheter should be located proximally for evaluation of entrance block during application, but can be advanced deeper for stability and then retracted to the ostium to evaluate vein isolation (entrance block). If the vein then is isolated after a single application, the operator can move on to the next vein.	Device: PVI by single cryoballoon application guided by Achieve Mapping Catheter; Pulmonary vein isolation by single cryoballoon application guided by recorded electrogram signals from an internal Mapping Catheter and by temperature drop if mapping of signals is not possible (temperature cutoff < or = -40 degrees C); Other Names: Arctic Front™ Advance Cardiac CryoAblation Catheter; Achieve Mapping Catheter
Active Comparator: PVI by 2 cryo applications; Cryoballoon ablation with a conventional guidewire passed through the inner lumen of the catheter for stability will be used. Ablation will be performed with 2 consecutive applications for 4 minutes each in each vein guided by degree of occlusion and temperature drop at the discretion of the physician.	Device: PVI by 2 routine cryoballoon applications; Pulmonary vein isolation by 2 cryoballoon applications guided by degree of occlusion and by temperature drop according to discretion of physician; Other Names: Arctic Front™ Advance Cardiac CryoAblation Catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of acute pulmonary vein isolation after first ablation.	Frequency of complete pulmonary vein isolation after first pass of ablation as per protocol	Acute during ablation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure time	Procedure time of AF ablation (from initial puncture to removal of sheaths)	During ablation procedure
Fluoroscopy exposure	Total time of fluoroscopy for AF ablation	During ablation procedure
Freedom from atrial fibrillation	No atrial fibrillation after first ablation	Evaluated after 12 months
Adverse/Serious Adverse events	Complications during and after ablation	Evaluated after 12 months
Quality of Life after ablation	Quality of life assessed by EQ5D after ablation compared to baseline	Evaluated after 12 months
Reduction of symptom severity score after ablation	Symptoms Severity Questionnaire, score reduction after ablation	Evaluated after 12 months
Reduction of overall symptoms of atrial fibrillation after ablation	Symptom assessed by EHRA Symptom Classification score reduction after ablation	Evaluated after 12 months
Cost of ablation procedure	Assessed by time for procedure, used resources and equipment during/after ablation	Evaluated after initial ablation (within 24 h after ablation)
Quality of life after ablation (measured as EQ5D score)	EQ5D measured before ablation and after 12 months	Evaluated after 12 months
Hospitalisation after ablation	hospitalisation (no of days)	Evaluated after 12 months
Maximum troponin I (ng/L) levels after ablation as a predictor of clinical success	Maximum troponin I (ng/L) levels as a predictor of freedom from AF after 12 months	Evaluated after 12 months
Nt-proBNP levels before ablation as a predictor of clinical success	Nt-proBNP levels as a predictor of freedom from AF after 12 months	Evaluated after 12 months
Left atrial diameter (mm) before ablation as a predictor of clinical success	Left atrial diameter in mm (LAX view) as a predictor of freedom from AF after 12 months	Evaluated after 12 months
Left atrial volume (ml/m2) before ablation as a predictor of clinical success	Left atrial volume (ml/m2) as a predictor of freedom from AF after 12 months	Evaluated after 12 months
Age (years) as a predictor of clinical success	Age at ablation (years) as a predictor of freedom from AF after 12 months; 2 groups; < 70 and >70 years old	Evaluated after 12 months
Sex as a predictor of clinical success	Sex as a predictor of freedom from AF after 12 months. 2 groups; male vs females	Evaluated after 12 months
CHADsVASc score as a predictor of clinical success	CHADsVASc score as a predictor of freedom from AF after 12 months	Evaluated after 12 months
BMI (kg/m2) as a predictor of clinical success	BMI (kg/m2) as a predictor of freedom from AF after 12 months	Evaluated after 12 months
Atrial conduction time as a predictor of clinical success	Mean conduction time over left atrium as a predictor of freedom from AF after 12 months	Evaluated after 12 months

Collaborators and Investigators

• Sponsor: Uppsala University Hospital
• Investigators: Principal Investigator: Carina Blomström Lundqvist, Professor, Uppsala University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: December 9, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 7, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Ablation; Cryoballoon; Achieve
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: SD-CRYO-AF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO