FLOW-AF: A Study to Evaluate Electrographic Flow™ (EGF) Mapping Technology (FLOW-AF)

A Randomized Controlled Study to Evaluate the Reliability of Electrographic Flow™ (EGF) Mapping Algorithm Technology to Identify Sources of Atrial Fibrillation and Guide Ablation Therapy in Patients With Persistent Atrial Fibrillation

This study is to evaluate Electrographic Flow™ (EGF) mapping algorithm technology (Ablamap® Software).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation, Persistent
• Intervention / Treatment: Device: Electrographic Flow™ guided ablation

Detailed Description

The objective of this study is to evaluate the reliability of Electrographic Flow™ (EGF) mapping algorithm technology (Ablamap® Software) to identify sources of atrial fibrillation and guide ablation therapy in patients with persistent atrial fibrillation.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Czech Republic
    • Prague, Czech Republic, Czechia, 150 30
      • Nemocnice Na Homolce Hospital
• Germany
  • Hamburg, Germany, 20246
    • University Heart and Vascular Center Hamburg
  • Saxony Land
    • Dresden, Saxony Land, Germany, 01099
      • Practice Clinic Heart And Vessels
• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Suitable candidate for intra-cardiac mapping and ablation of atrial arrhythmias.
2. Above eighteen (18) years of age or of legal age to give informed consent specific to state and national law.
3. Subjects with a history of documented symptomatic, persistent or longstanding persistent atrial fibrillation < 36 months.
4. Subject agrees to comply with study procedures and be available (geographically stable) for follow-up visits for at least 12 months.
5. Treatment of atrial fibrillation with ablation therapy presenting with recurrent symptoms of atrial fibrillation (not applicable to De Novo subjects)

Exclusion Criteria:

1. Left atrial diameter > 5.5 cm.
2. Left ventricular ejection fraction (LVEF) < 35%.
3. Presence of intramural thrombus, tumor or abnormality that precludes vascular access, catheter introduction or manipulation.
4. Coagulopathy, bleeding diathesis or suspected procoagulant state.
5. Known allergies or intolerance to anticoagulant and antiplatelet therapies to be used in conjunction with the study or contrast sensitivity that cannot be adequately pre-treated prior to the ablation procedure.
6. Positive pregnancy test results for female patients of childbearing potential or breast feeding.
7. Acute or chronic medical condition that in the judgment of the investigator would increase risk to the patient or deem the patient inappropriate to participate in the study.
8. Mitral valve stenosis and/or severe mitral regurgitation.
9. Valvular atrial fibrillation.
10. Prosthetic valves.
11. New York Heart Association (NYHA) Class IV.
12. History of myocardial infarction (MI) within 3 months prior to procedure.
13. Atrial septal defect (ASD) or left atrial appendage (LAA) closure device.
14. Atrial fibrillation from a reversible cause (e.g., surgery, hyperthyroidism, sarcoidosis or pericarditis).
15. Life expectancy < 12 months based on medical history or the medical judgement of the investigator.
16. Presence of any transvenous pacing, Implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy (CRT) leads.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized to Treatment: PVI + Electrographic Flow™ (EGF) Guided Ablation Therapy; This arm includes subjects who underwent Electrographic Flow™ (EGF) mapping, and exhibited EGF-identified significant sources with leading source activity above threshold (≥26.5%), qualifying them for randomization. Subjects randomized to the "treatment" group first received pulmonary vein isolation (PVI) or PVI touch-up followed by a 20 minute waiting period and PVI confirmation. After this, EGF mapping in AF was conducted and targeted radiofrequency ablation of EGF-identified source(s) was performed in the left and right atrium. The procedure is considered complete once all EGF-identified sources have been eliminated through ablation. If necessary, the procedure were concluded with cardioversion.	Device: Electrographic Flow™ guided ablation; In addition to standard pulmonary vein isolation (PVI) or PVI touch-up, subjects receive targeted radiofrequency source ablation guided by Electrographic Flow™ (EGF) mapping. EGF mapping enables the full spatiotemporal reconstruction of organized atrial electrical wavefront propagation to identify active sources or origins of excitation that may trigger atrial fibrillation (AF). EGF mapping involves 1 minute recordings of unipolar electrograms from a basket catheter, which are then processed with the EGF software. Several basket catheter positions are acquired in standard positions in both the left and right atria. EGF-identified sources with activity above the threshold (≥ 26.5%) are considered significant and targeted for ablation. The procedure concludes when all EGF-identified sources are eliminated, defined as reducing source activity below the threshold.; Other Names: Electrographic Flow™ Mapping Technology; OptiMap™; Ablamap®
No Intervention: Randomized to Control: PVI Only; This arm includes subjects who underwent Electrographic Flow™ (EGF) mapping, and exhibited EGF-identified significant sources with leading source activity above threshold (≥26.5%), qualifying them for randomization. Subjects randomized to the "control" group received standard pulmonary vein isolation (PVI) or PVI touch-up followed by a 20 minute waiting period and PVI confirmation. Subjects also received EGF mapping while in AF, but no further ablation of the EGF-identified sources. The procedure were concluded with cardioversion.
No Intervention: Not Randomized; This arm includes subjects who underwent Electrographic Flow™ (EGF) mapping, but exhibited no EGF-identified sources with leading source activity above threshold (≥26.5%). Subjects received standard pulmonary vein isolation (PVI) or PVI touch-up followed by a 20 minute waiting period and PVI confirmation. Empiric adjunctive ablation could be performed at operator discretion. If necessary, the procedure were concluded with cardioversion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Acute Procedure Success	Acute Procedure Success is defined as successful elimination of significant sources of electrographic flow (EGF) through targeted radiofrequency ablation. EGF-identified sources are significant when their leading source activity is above threshold. Successful elimination is defined as reduction of the source activity of the leading source below threshold upon post-ablation remapping using EGF mapping.	During the Procedure
Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days	Freedom from Serious Adverse Events (SAE) related to the procedure through 7 days following the index procedure.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Electrographic Flow™ (EGF) Identified Sources With Consistent Location Across Subsequent EGF-Guided Procedures	This measure represents the number of Electrographic Flow™ (EGF) identified sources that remained consistent in anatomical location during subsequent EGF-guided procedures. The number and anatomical locations of EGF-identified sources for each subject were compared between the Index procedure and a subsequent EGF-guided procedure conducted ≥ 3 months later. A source was considered consistent if it was visible in the same anatomical location across both procedures.	Index Procedure until Recurrence Procedure
Number of Participants With 12-month Freedom From AF Recurrence	This measure represents the number of subjects with freedom from documented episodes of atrial fibrillation (AF) recurrence lasting longer than 30 seconds from the 90-day post-procedure blanking period through 12 months of follow-up. Follow-up and electrocardiographic monitoring of AF occurred at 3, 6 and 12 months through 7-day Holter recordings and ECGs.	90 day - 12 months
Average EGF Source Ablations Per Patient	Average number of Electrographic Flow™ (EGF) source ablations per patients, defined as the number of significant EGF-identified sources with a source activity above threshold.	During the procedure
Total Duration of EGF Source Ablation Per Patient	Average total duration of radiofrequency ablation of the significant Electrographic Flow™ (EGF) identified sources per patient. Defined as the number of seconds of radiofrequency ablation spend on EGF-identified source ablation.	During the procedure
Average Fluoroscopy Time Per Patient	Average total fluoroscopy time (in minutes) of the complete electrophysiology procedure per patient.	During the procedure
Total Radiation Dose Per Patient	Average total radiation dose of the complete electrophysiology procedure, expressed in Air Kerma (AK) in mGy	During the procedure
Total Procedure Time	Total procedure time of complete electrophysiology procedure in minutes.	During the procedure

Collaborators and Investigators

• Sponsor: Cortex
• Collaborators: Ablacon, Inc.
• Investigators: Principal Investigator: Petr Neuzil, MD, Principal Investigator - Czech Republic; Principal Investigator: Tamas Szili-Torok, MD, Principal Investigator - The Netherlands; Principal Investigator: Stefan Spitzer, MD, Principal Investigator - Germany

Publications and helpful links

General Publications

• Reddy VY, Langbein A, Petru J, Szili-Torok T, Funasako M, Dinshaw L, Wijchers S, Rillig A, Spitzer SG, Bhagwandien R, Metzner A, Kong MH, Neuzil P. A Randomized Trial of Electrographic Flow-Guided Redo Ablation for Nonparoxysmal Atrial Fibrillation (FLOW-AF). JACC Clin Electrophysiol. 2024 Aug;10(8):1856-1869. doi: 10.1016/j.jacep.2024.03.040. Epub 2024 Jun 5.

Helpful Links

• A Randomized Trial of Electrographic Flow-Guided Redo Ablation for Nonparoxysmal Atrial Fibrillation (FLOW-AF)

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Actual): September 27, 2021
• Study Completion (Actual): September 27, 2021

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 9, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CP-001/002

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