CLOSE to CURE Study

'CLOSE'-Guided Pulmonary Vein Isolation as Cure for Paroxysmal Atrial Fibrillation?

Title: CLOSE-guided pulmonary vein isolation (PVI) as Cure for Paroxysmal Atrial Fibrillation ('CLOSE to CURE' study)

Design: This is a prospective, observational, single-center, unblinded, clinical 3-year study.

Background: In a population of paroxysmal atrial fibrillation (AF) 'CLOSE'-guided PVI, a new approach to obtain single-procedure durable PVI, has been shown to virtually eliminate recurrence of AF at 1 year follow-up with repetitive but discontinuous Holter monitoring.

Objectives: (1) To objectively compare atrial tachyarrhythmia (ATA) burden before and after 'CLOSE'-guided based PVI using continuous monitoring. (2) To assess ATA burden using continuous monitoring up to 3 years after ablation. (3) To identify baseline structural and electrical properties of the atria or procedural characteristics that predict 1-year and 3-year outcome.

Enrollment: Up to 100 subjects will be enrolled in this observational, prospective study.

Clinical Sites: 1 site.

Subject Population: Eligible patients are patients with paroxysmal high-burden AF who are planned for a 'CLOSE'-guided PV isolation. At the time of procedural planning we will ask the patient his/her consent for (1) implantation of a subcutaneous continuous loop recorder (sCLR), (2) a concise electrophysiological study at the time of PVI, (3) a transthoracic echocardiogram at the time of PVI and (4) collection of data during 3 years. Anti-arrhythmic drug treatment (ADT) and oral anticoagulation (OAC) will be given according the updated 2012 European society of Cardiology (ESC) guidelines on AF (Camm et al, European Heart Journal 2012) and the 2012 Heart rhythm society (HRS)/European Heart Rhythm association/European cardiac arrhythmic society Expert Consensus Statement on catheter and surgical ablation of atrial fibrillation (Calkins et al, Heart Rhythm 2012).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Pulmonary vein isolation

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruges, Belgium, 8000
    • AZ Sint-Jan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with symptomatic paroxysmal AF (history of self-terminating AF within 7 days or history of self-terminating AF with 1 or more cardioversions within 48 hours after onset), meeting following criteria at the out-patient clinic:

   • patient has at least 3 AF episodes in the last 3 months prior to the visit
   • AF episodes are symptomatic, and patient is drug-resistant (at least one class IC or III), or drug-intolerant (palpitations, fatigue, dyspnea, cardiomyopathy,…)
   • no advanced structural heart disease
   • patient has a CHA2DS2-VASc score of 0, 1, 2, 3 or 4
2. Signed Patient Informed Consent Form.
3. Age 18 years or older.
4. Able and willing to comply with all follow-up testing and requirements.

Exclusion Criteria:

1. Persistent atrial fibrillation (history of AF>7days or history of cardioversion > 48h of AF)
2. Previous ablation for AF
3. LA antero-posterior diameter > 50 mm (parasternal long axis view , PLAX)
4. LVEF < 35% (ejection fraction)
5. AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause
6. Coronary artery bypass grafting (CABG) procedure within the last three months
7. Awaiting cardiac transplantation or other cardiac surgery
8. Documented left atrial thrombus on imaging
9. Diagnosed atrial myxoma
10. Women who are pregnant or breastfeeding
11. Acute illness or active systemic infection or sepsis
12. Unstable angina
13. Uncontrolled heart failure
14. Myocardial infarction within the previous two months
15. History of blood clotting or bleeding abnormalities
16. Contraindication to anticoagulation therapy (ie, heparin or warfarin)
17. Life expectancy less than 12 months
18. Enrollment in any other study evaluating another device or drug
19. Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLOSE guided PVI and insertable cardiac monitor	Procedure: Pulmonary vein isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Atrial tachyarrhythmia (ATA) burden before and after 'CLOSE'-guided based PVI	Continuous monitoring (24 hours loop recording)
Long-term evaluation of ATA burden after a single 'CLOSE' guided PVI procedure	Continuous monitoring (24 hours loop recording)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating PV re-connection at redo procedure assessed by Lasso catheter	Visual inspection of electrograms on the Lasso catheter will be performed to verify durable PV isolation or re-connection	3 months to 3 years
Evaluating progression of scarring at redo procedure assessed by voltage mapping	Point-by-point bipolar voltage mapping will be performed to quantify the amount of low voltage areas in the left atrium (LA)	3 months to 3 years
Incidence of adverse events related to ablation		Baseline to 3 years
Freedom from stroke/transient ischemic attack (TIA)		Baseline to 3 years
Efficacy of CLOSE protocol ablation assessed by single-procedure freedom from documented atrial tachyarrhythmias (ATA)	ATA include fibrillation, tachycardia, or flutter	1 month to 3 years
Efficacy of CLOSE protocol ablation assessed by incidence of repeat ablation procedures		1 month to 3 years
Efficacy of CLOSE protocol ablation assessed by multiple-procedure freedom from ATA	ATA include fibrillation, tachycardia, or flutter	1 month to 3 years
Health economics and outcomes research assessed by quality of life using Short Form (SF-36v2) Health Survey		Recruitment to 3 years
Health economics and outcomes research assessed by quality of life using Symptomatic Questionnaire V3		Recruitment to 3 years
Health economics and outcomes research assessed by number of hospitalization	Includes total number of hospitalizations and unscheduled arrhythmia-related health care provider visits	Recruitment to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical characteristic assessed by height		At baseline
Clinical characteristic assessed by weight		At baseline
Clinical characteristic assessed by age		At baseline
Clinical characteristic assessed by sex		At baseline
Clinical characteristic assessed by congestive heart failure history		At baseline
Clinical characteristic assessed by hypertension history		At baseline
Clinical characteristic assessed by stroke/TIA/Thromboembolism history		At baseline
Clinical characteristic assessed by vascular disease history		At baseline
Clinical characteristic assessed by diabetes mellitus		At baseline
Clinical characteristic assessed by left ventricle ejection fraction (LVEF)		At baseline
Clinical characteristic assessed by structural heart disease		At baseline
Clinical characteristic assessed by endurance measured by amount of training/cycling per week		At baseline
Clinical characteristic assessed by history of implanted devices		At baseline
Clinical characteristic assessed by LA diameter measured by echocardiography		At baseline
Clinical characteristic assessed by LA volume measured by echocardiography		At baseline
Clinical characteristic assessed by cardiovascular medication history		At baseline
Procedure characteristic assessed by procedure time		At baseline
Procedure characteristic assessed by radiofrequency time		At baseline
Procedure characteristic assessed by fluoroscopy time		At baseline
Electrophysiological characteristic assessed by voltage mapping of the LA	Point-by-point bipolar voltage mapping will be performed to quantify the amount of low voltage areas in the LA	At baseline
Electrophysiological characteristic assessed by atrial refractoriness	This will be done by premature stimulation protocol	At baseline
Electrophysiological characteristic assessed by conduction velocity	This will be done by premature stimulation protocol	At baseline
Electrophysiological characteristic assessed by AF inducibility	This will be done by premature stimulation protocol	At baseline

Collaborators and Investigators

• Sponsor: AZ Sint-Jan AV
• Investigators: Principal Investigator: Mattias Duytschaever, MD, PhD, Department of Cardiology, AZ Sint-Jan Hospital Bruges, Belgium

Publications and helpful links

General Publications

• Duytschaever M, De Pooter J, Demolder A, El Haddad M, Phlips T, Strisciuglio T, Debonnaire P, Wolf M, Vandekerckhove Y, Knecht S, Tavernier R. Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study. Heart Rhythm. 2020 Apr;17(4):535-543. doi: 10.1016/j.hrthm.2019.11.004. Epub 2019 Nov 9.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: September 29, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 4, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: pulmonary vein isolation; ablation index; implantable loop recorder
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 1949