Ablation of Fibrotic Areas in Patients With Persistent Atrial Fibrillation. (IDEAL-AF)

Individually DEsigned Ablation of Low Voltage Areas in Patients With Persistent Atrial Fibrillation, a Randomized Controlled Multicenter Trial

Brief summary: The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to pulmonary vein isolation or pulmonary vein isolation plus ablation of fibrotic areas.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Radio frequency ablation

Detailed Description

Background:

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with a prevalence of 2-3 percent in the population. Catheter ablation performing pulmonary vein isolation (PVI) is an established treatment, which aim to eliminate triggers from the pulmonary veins. This treatment is successful in most patients with paroxysmal AF. In many patients, especially the patients with persistent AF, this treatment is not sufficiently to achieve freedom from arrhythmia and symptoms.

There are several studies showing that fibrosis in the left atrium (LA) is an independent factor to relapse in AF after PVI. The fibrotic areas can be detected by measuring the voltage in the left atrium and creating a voltage map. There are non-randomized studies that suggest better results regarding reduction of arrhythmia burden after ablating the low voltage areas (LVAs). This ablation strategy is commonly used in clinical praxis although there are no randomized studies in this field.

Aim:

The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to PVI versus PVI plus ablation of LVAs.

The primary endpoint is freedom of atrial arrhythmias after 1 to 2 ablation procedures within 6 months measured at 12 months after the first ablation procedure without antiarrhythmic drugs. Secondary endpoints will be atrial arrhythmia burden, health related quality of life measured by AFEQT score, and RAND 36 and periprocedural complications; death, stroke/ TIA, tamponade, atrio-esophageal fistula, and atrioventricular block.

Study design:

Randomized controlled multicenter trial. The study will be single blinded. All the participants will undergo PVI and the substrate map will be collected during atrial pacing. The patients with LVA will be randomized in a 1:1 fashion to; PVI plus ablation of LVA or PVI alone. Follow up visits will be at 3, 6, 12, 18 and 24 months. Before ablation and at every follow up visit the participants will fill in arrhythmia symptom specific questionnaires (AFEQT and ASTA) and questionnaire about quality of life (RAND 36). The participants will register arrhythmia with a heart monitoring system if symptoms of arrhythmia and two times daily during two weeks before every follow up visit.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nikola Drca, MD; Phone Number: +46858580000; Email: nikola.drca@sll.se
• Study Contact Backup: Name: Astrid Paul Nordin, MD; Phone Number: +46858580000; Email: astrid.paul-nordin@sll.se

Study Locations

• Sweden
  • Stockholm, Sweden, SE-14186
    • Recruiting
    • Karolinska University Hospital
    • Contact: Mats Jensen-Urstad, Professor; Phone Number: 0046-8-58580000; Email: mats.jensen-urstad@sll.se
    • Principal Investigator: Mats Jensen-Urstad, Professor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ECG-documented persistent or long-standing persistent atrial fibrillation according to European Society of Cardiology (ESC) definition
2. Symptoms e. g. palpitations, dyspnea, tiredness that is due to the atrial fibrillation.
3. Suitable candidate for catheter ablation.
4. Tried one or more antiarrhythmic drugs or unwilling to try antiarrhythmic drugs
5. Age ≥18 years.

Exclusion Criteria:

1. LA dimension >55 mm as determined by an echocardiography within the previous year
2. Acute coronary syndrome or coronary artery bypass surgery within 12 weeks
3. Severe aortic or mitral valvular heart disease using the ESC guidelines
4. Congenital heart disease
5. Prior surgical or percutaneous AF ablation procedure or atrioventricular-nodal ablation
6. Medical condition likely to limit survival to < 1 year
7. New York Heart Association (NYHA) class IV heart failure symptoms
8. Contraindication to oral anticoagulation
9. Renal failure requiring dialysis
10. AF due to reversible cause
11. Pregnant and fertile women without anticonception
12. History of non-compliance to medical therapy
13. Unable or unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pulmonary vein isolation plus substrate modification; Pulmonary vein isolation plus ablation of low voltage areas in the left atrium	Procedure: Radio frequency ablation; Two different radio frequency ablation procedures
Active Comparator: Pulmonary vein isolation	Procedure: Radio frequency ablation; Two different radio frequency ablation procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Freedom from Atrial Arrhythmia	Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures within 6 months without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure without Antiarrhythmic Drugs (AAD)	Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 ablation procedure without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure
Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure with/ without AAD	Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 ablation procedure with or without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure
Number of Participants with Freedom from Atrial Arrhythmia after 1 or 2 Ablation Procedures with/ without AAD	Freedom from documented atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures with or without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure
Number of Participants with Freedom from Atrial Fibrillation	Freedom from documented atrial fibrillation >30 seconds at 12 months after 1 or 2 ablation procedures without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure
Number of Participants with Freedom from Symptomatic Atrial Arrhythmias	Freedom from documented symptomatic atrial arrhythmias >30 seconds at 12 months after 1 or 2 ablation procedures with or without antiarrhythmic drugs	From 3 months (blanking period) to 12 months after the first ablation procedure
Number of Participants with Freedom from Atrial Arrhythmias without AAD	Freedom from documented atrial arrhythmias >30 seconds at 24 months after 1 or several ablation procedures without antiarrhythmic drugs	From 3 months (blanking period) to 24 months after the first ablation procedure
Number of Participants with Freedom from Atrial Arrhythmias with or without AAD	Freedom from documented symptomatic atrial arrhythmias >30 seconds at 24 months after 1 or several ablation procedures with or without antiarrhythmic drugs	From 3 months (blanking period) to 24 months after the first ablation procedure
Arrhythmia Burden	Number of Registrations with Remote Heart Monitor / Number of Registrations with Atrial Arrhythmia with Remote Heart Monitor	From 3 months (blanking period) to 12 months and 24 months after the first ablation procedure
Time to First Recurrens	Time from first ablation procedure to first documented recurrens of atrial arrhythmias	From first ablation procedure to 24 months
Number of Repeat Procedures	Number of repeat procedures	12 and 24 months after the first ablation procedure
Changes in Quality of Life Measures: Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Overall Score and Subscale Scores	AFEQT is a 21 questions atrial fibrillation specific health related quality of life questionnaire. Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Score ranges from 0 to 100 points. Higher scores mean a better outcome.	Baseline, 12 and 24 months after the first ablation procedure
Changes in Quality of Life Measures: RAND 36 (Research ANd Development) 36 All Domains	RAND 36 (developed by RAND corporation) is a 36 questions health related quality of life questionnaire. The RAND 36 is divided into 8 domains: Physical functioning, role physical, role emotional, bodily pain, vitality, general health, social functioning and mental health. Score range from 0 to 100 points. Higher scores mean a better outcome.	Baseline,12 and 24 months after the first ablation procedure
Number of Participants with Adverse Events/ Complications	Complications related to the ablation procedure: Cardiac perforation, stroke, transitory ischemic attack (TIA), systemic embolic events, atrio-esophageal fistula, major bleeding, atrioventricular block, groin hematoma requiring vascular surgery or extended hospitalization.	12 and 24 months after the first ablation procedure
Number of Participants With All-cause Mortality	Number of Participants With All-cause Mortality	12 and 24 months after the first ablation procedure
Procedure time	Time from start of groin punction to withdrawal of the catheters	Immediately after the procedure
Fluoroscopy time	Total fluoroscopy time during the procedure	Immediately after the procedure

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Investigators: Study Director: Mats Jensen-Urstad, MD, Karolinska University Hospital

Publications and helpful links

General Publications

• Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available.
• Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110(9):1042-6. doi: 10.1161/01.CIR.0000140263.20897.42. Epub 2004 Aug 16.
• Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, Blauer JJ, Rao SN, DiBella EV, Segerson NM, Daccarett M, Windfelder J, McGann CJ, Parker D, MacLeod RS, Marrouche NF. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation. 2009 Apr 7;119(13):1758-67. doi: 10.1161/CIRCULATIONAHA.108.811877. Epub 2009 Mar 23.
• Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Cosedis Nielsen J, Curtis AB, Davies DW, Day JD, d'Avila A, Natasja de Groot NMS, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T; Document Reviewers:. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2018 Jan 1;20(1):e1-e160. doi: 10.1093/europace/eux274. No abstract available.
• Phlips T, Taghji P, El Haddad M, Wolf M, Knecht S, Vandekerckhove Y, Tavernier R, Duytschaever M. Improving procedural and one-year outcome after contact force-guided pulmonary vein isolation: the role of interlesion distance, ablation index, and contact force variability in the 'CLOSE'-protocol. Europace. 2018 Nov 1;20(FI_3):f419-f427. doi: 10.1093/europace/eux376.
• El Haddad M, Taghji P, Phlips T, Wolf M, Demolder A, Choudhury R, Knecht S, Vandekerckhove Y, Tavernier R, Nakagawa H, Duytschaever M. Determinants of Acute and Late Pulmonary Vein Reconnection in Contact Force-Guided Pulmonary Vein Isolation: Identifying the Weakest Link in the Ablation Chain. Circ Arrhythm Electrophysiol. 2017 Apr;10(4):e004867. doi: 10.1161/CIRCEP.116.004867.
• Tilz RR, Rillig A, Thum AM, Arya A, Wohlmuth P, Metzner A, Mathew S, Yoshiga Y, Wissner E, Kuck KH, Ouyang F. Catheter ablation of long-standing persistent atrial fibrillation: 5-year outcomes of the Hamburg Sequential Ablation Strategy. J Am Coll Cardiol. 2012 Nov 6;60(19):1921-9. doi: 10.1016/j.jacc.2012.04.060. Epub 2012 Oct 10.
• Scherr D, Khairy P, Miyazaki S, Aurillac-Lavignolle V, Pascale P, Wilton SB, Ramoul K, Komatsu Y, Roten L, Jadidi A, Linton N, Pedersen M, Daly M, O'Neill M, Knecht S, Weerasooriya R, Rostock T, Manninger M, Cochet H, Shah AJ, Yeim S, Denis A, Derval N, Hocini M, Sacher F, Haissaguerre M, Jais P. Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint. Circ Arrhythm Electrophysiol. 2015 Feb;8(1):18-24. doi: 10.1161/CIRCEP.114.001943. Epub 2014 Dec 20.
• Verma A, Wazni OM, Marrouche NF, Martin DO, Kilicaslan F, Minor S, Schweikert RA, Saliba W, Cummings J, Burkhardt JD, Bhargava M, Belden WA, Abdul-Karim A, Natale A. Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure. J Am Coll Cardiol. 2005 Jan 18;45(2):285-92. doi: 10.1016/j.jacc.2004.10.035.
• Rolf S, Kircher S, Arya A, Eitel C, Sommer P, Richter S, Gaspar T, Bollmann A, Altmann D, Piedra C, Hindricks G, Piorkowski C. Tailored atrial substrate modification based on low-voltage areas in catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 2014 Oct;7(5):825-33. doi: 10.1161/CIRCEP.113.001251. Epub 2014 Aug 23.
• Yagishita A, Sparano D, Cakulev I, Gimbel JR, Phelan T, Mustafa H, De Oliveira S, Mackall J, Arruda M. Identification and electrophysiological characterization of early left atrial structural remodeling as a predictor for atrial fibrillation recurrence after pulmonary vein isolation. J Cardiovasc Electrophysiol. 2017 Jun;28(6):642-650. doi: 10.1111/jce.13211. Epub 2017 May 29.
• Schreiber D, Rieger A, Moser F, Kottkamp H. Catheter ablation of atrial fibrillation with box isolation of fibrotic areas: Lessons on fibrosis distribution and extent, clinical characteristics, and their impact on long-term outcome. J Cardiovasc Electrophysiol. 2017 Sep;28(9):971-983. doi: 10.1111/jce.13278. Epub 2017 Jul 5.
• Kottkamp H, Bender R, Berg J. Catheter ablation of atrial fibrillation: how to modify the substrate? J Am Coll Cardiol. 2015 Jan 20;65(2):196-206. doi: 10.1016/j.jacc.2014.10.034.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Catheter ablation; Low voltage
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 200212IDEALAF

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No