Atrial Fibrillation, Persistent
Conditions
Brief summary
This study is to evaluate Electrographic Flow™ (EGF) mapping algorithm technology (Ablamap® Software).
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.
Interventions
DEVICEElectrographic 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.
Sponsors
Ablacon, Inc.
Cortex
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will receive Electrographic Flow™ (EGF) mapping with Ablamap® Software. If EGF mapping identifies a source with a source activity level above threshold (≥26.5%) the subjects will be randomized to treatment or control. If EGF mapping detects no source above threshold the subject will fall into the not randomized arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute Procedure Success | During the Procedure | 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. |
| Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days | 7 days | Freedom from Serious Adverse Events (SAE) related to the procedure through 7 days following the index procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average EGF Source Ablations Per Patient | During the procedure | 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. |
| Total Duration of EGF Source Ablation Per Patient | During the procedure | 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. |
| Number of Electrographic Flow™ (EGF) Identified Sources With Consistent Location Across Subsequent EGF-Guided Procedures | Index Procedure until Recurrence Procedure | 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. |
| Total Radiation Dose Per Patient | During the procedure | Average total radiation dose of the complete electrophysiology procedure, expressed in Air Kerma (AK) in mGy |
| Total Procedure Time | During the procedure | Total procedure time of complete electrophysiology procedure in minutes. |
| Average Fluoroscopy Time Per Patient | During the procedure | Average total fluoroscopy time (in minutes) of the complete electrophysiology procedure per patient. |
| Number of Participants With 12-month Freedom From AF Recurrence | 90 day - 12 months | 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. |
Countries
Czechia, Germany, Netherlands
Participant flow
Pre-assignment details
5 patients from the run-in cohort declined to return for protocol-mandated EGF re-mapping procedure after the initial blanking period.
Participants by arm
| Arm | Count |
|---|---|
| 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, 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. | 22 |
| 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, 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. | 24 |
| Not Randomized This arm includes subjects who underwent Electrographic Flow™ (EGF) mapping, but exhibited no EGF-identified sources with leading source activity above threshold.
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. | 34 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Not inducible in AF | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized to Treatment: PVI + Electrographic Flow™ (EGF) Guided Ablation Therapy | Randomized to Control: PVI Only | Not Randomized | Total |
|---|---|---|---|---|
| Age, Continuous | 67.2 years STANDARD_DEVIATION 9.5 | 69.1 years STANDARD_DEVIATION 10.5 | 62.6 years STANDARD_DEVIATION 7.3 | 65.8 years STANDARD_DEVIATION 9.3 |
| Body Mass Index | 27.2 kg/m2 STANDARD_DEVIATION 4.3 | 29.3 kg/m2 STANDARD_DEVIATION 5.3 | 30.3 kg/m2 STANDARD_DEVIATION 4.2 | 29.1 kg/m2 STANDARD_DEVIATION 4.6 |
| CHA2DS2-VASc score | 2.7 units on a scale [scale range: 0-9] STANDARD_DEVIATION 1.5 | 3.1 units on a scale [scale range: 0-9] STANDARD_DEVIATION 1.4 | 1.8 units on a scale [scale range: 0-9] STANDARD_DEVIATION 1 | 2.4 units on a scale [scale range: 0-9] STANDARD_DEVIATION 1.3 |
| LA Size (cm) | 4.5 cm STANDARD_DEVIATION 0.5 | 4.4 cm STANDARD_DEVIATION 0.7 | 4.4 cm STANDARD_DEVIATION 0.5 | 4.4 cm STANDARD_DEVIATION 0.6 |
| Left Ventricular Ejection Fraction | 56 % STANDARD_DEVIATION 6 | 58 % STANDARD_DEVIATION 6 | 56 % STANDARD_DEVIATION 7 | 57 % STANDARD_DEVIATION 6 |
| Long-Standing Persistent Atrial Fibrillation | 5 Participants | 6 Participants | 6 Participants | 17 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 24 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 24 | 0 / 34 |
| other Total, other adverse events | 3 / 22 | 3 / 24 | 5 / 34 |
| serious Total, serious adverse events | 0 / 22 | 0 / 24 | 2 / 34 |
Outcome results
Primary
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.
Time frame: During the Procedure
Population: Per protocol population. Outcome Measure is only applicable to the group Randomized to Treatment: PVI + EGF-Guided Ablation Therapy, because this outcome assesses the ability to eliminate EGF-identified sources through targeted source ablation. Other groups did not receive EGF-identified source ablation, and are therefore not included in analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Number of Participants With Acute Procedure Success | 19 Participants |
Primary
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.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days | 0 Participants |
| Randomized to Control: PVI Only | Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days | 0 Participants |
| Not Randomized | Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days | 2 Participants |
| Total | Number of Participants With Serious Adverse Events Related to the Procedure Through 7 Days | 2 Participants |
p-value: 0.277Chi-squared
Secondary
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.
Time frame: During the procedure
Population: Intention to Treat of the group Randomized to Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Average EGF Source Ablations Per Patient | 3.05 Source Ablations per Patient | Standard Deviation 1.89 |
Secondary
Average Fluoroscopy Time Per Patient
Average total fluoroscopy time (in minutes) of the complete electrophysiology procedure per patient.
Time frame: During the procedure
Population: Intention to Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Average Fluoroscopy Time Per Patient | 15.1 minutes | Standard Deviation 11.1 |
| Randomized to Control: PVI Only | Average Fluoroscopy Time Per Patient | 10.8 minutes | Standard Deviation 7.2 |
| Not Randomized | Average Fluoroscopy Time Per Patient | 13.8 minutes | Standard Deviation 11.5 |
Secondary
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.
Time frame: Index Procedure until Recurrence Procedure
Population: A subgroup of 12 subjects (with a total of 18 Electrographic Flow™ (EGF) identified sources) from the Randomized to Control, Randomized to Treatment, or Not Randomized groups who returned for a subsequent EGF-guided procedure ≥ 3 months later. Consistency of these sources was evaluated before any randomization/treatment occurred, making inter-group comparisons inappropriate. Groups could be combined as the focus was on source consistency over time, not treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Number of Electrographic Flow™ (EGF) Identified Sources With Consistent Location Across Subsequent EGF-Guided Procedures | 16 EGF-identified Sources |
Secondary
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.
Time frame: 90 day - 12 months
Population: Per protocol population with completed 12 month follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Number of Participants With 12-month Freedom From AF Recurrence | 13 Participants |
| Randomized to Control: PVI Only | Number of Participants With 12-month Freedom From AF Recurrence | 6 Participants |
| Not Randomized | Number of Participants With 12-month Freedom From AF Recurrence | 17 Participants |
p-value: 0.042Kaplan-Meyer Log Rank
Secondary
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.
Time frame: During the procedure
Population: Intention to Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Total Duration of EGF Source Ablation Per Patient | 10.18 minutes | Standard Deviation 6.7 |
Secondary
Total Procedure Time
Total procedure time of complete electrophysiology procedure in minutes.
Time frame: During the procedure
Population: Intention to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Total Procedure Time | 183 minutes | Standard Deviation 57 |
| Randomized to Control: PVI Only | Total Procedure Time | 107 minutes | Standard Deviation 34 |
| Not Randomized | Total Procedure Time | 137.2 minutes | Standard Deviation 47 |
p-value: <0.001t-test, 2 sided
Secondary
Total Radiation Dose Per Patient
Average total radiation dose of the complete electrophysiology procedure, expressed in Air Kerma (AK) in mGy
Time frame: During the procedure
Population: Per Protocol Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Treatment: PVI + EGF Guided Ablation Therapy | Total Radiation Dose Per Patient | 155 mGy | Standard Deviation 113 |
| Randomized to Control: PVI Only | Total Radiation Dose Per Patient | 143 mGy | Standard Deviation 151 |
| Not Randomized | Total Radiation Dose Per Patient | 186 mGy | Standard Deviation 219 |