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ECG-I Targeted Ablation for Persistent AF Not Responding to Pulmonary Vein Isolation Results of a Two Staged Strategy. (TARGET-AF2)

B

Barts & The London NHS Trust

Status

Completed

Conditions

Atrial Fibrillation

Treatments

Device: ECG-I Mapping of Atrial Fibrillation

Study type

Interventional

Funder types

Other

Identifiers

NCT04633265
218367-3

Details and patient eligibility

About

Atrial Fibrillation (AF) is a irregular heart rhythm associated with significant morbidity and mortality. Catheter ablation is a treatment where catheters are passed through the veins in the leg into the left atrium of the heart and lines of scar is delivered to disrupt tissue causing and maintaining atrial fibrillation. Current strategies involve isolating the pulmonary veins which have been shown to trigger and maintain AF. However, success rates for persistent AF lie in the region of 30-60% due to the drivers of AF residing elsewhere to the Pulmonary Veins antra.

The ECG-I is a system which involves wearing a jacket with many ECG electrodes to record electrical activity from the surface of the body. A CT scan then shows where these electrodes are relative to the atria, and computer modelling is used to reconstruct the movements of electricity on the surface of the heart and therefore identifying where the drivers (tissue causing and maintaining AF) are located.

Unfortunately, not all patients respond to PVI due to the drivers of AF being located in areas other than within the Pulmonary Veins. Identifying the drivers of AF is very difficult and the role they play has yet to be proved scientifically.

PHENOTYPE AF is an ongoing clinical trial in which 100 patients with persistent AF are receiving cryoballoon pulmonary vein isolation for persistent AF (NCT03394404). Patients with recurrent AF or atrial tachycardia within 1 year following pulmonary vein isolation for AF within this trial will be recruited into this study. Up to 50 such patients who have failed Pulmonary Vein Isolation will be enrolled. These patients will undergo a second procedure at which time participants will undergo catheter ablation of drivers of AF and will then be followed up for 12 months.

Full description

Atrial Fibrillation (AF) is the commonest heart rhythm disturbance and is associated with significant morbidity and mortality. Catheter ablation (CA) is a procedure where catheters (leads) are passed into the heart and energy is used to disrupt and isolate (by freezing or cauterising) heart tissue causing AF. CA is an established therapy for AF. Success rates for CA for paroxysmal AF lies in the region of 70% or better. However, success rates for persistent AF is much lower and estimates lie in the region of 30-60%.

Current CA protocols for AF centre on isolating the pulmonary veins (the pulmonary veins drain into the left atrium) which have been proven to trigger AF. Pulmonary Vein Isolation (PVI) ablation alone seems sufficient to remove the trigger for the vast majority of patients with paroxysmal AF. However, in patients with persistent AF it is common for AF to continue after the pulmonary veins have been electrically isolated.

The difference in success rates between the paroxysmal and persistent form of AF is thought to be due to changes within the heart atria after AF has been established for some time. In persistent AF the atria dilate and remodel structurally and electrically, and therefore the maintenance of persistent AF differs from paroxysmal AF.

Persistent AF is thought to be maintained by focal sources, whether rotors or sites of radial activation. Currently, targeting other sites within the atria in addition to PVI such as fractionated electrograms (areas of electrical activity) are thought to be imprecise and require extensive ablation. Often AF will persist despite targeting additional sites within the atria.

One particular challenge is to select patients likely to benefit from CA. CA carries an approximate less than 1% risk of life threatening complication. Therefore being able to select suitable patients is desirable in order to prevent unnecessary procedures.

Currently clinical characteristics of patients or structural imaging have limited accuracy in selecting patients likely to benefit from CA. Mapping studies have shown that patients with persistent AF who have higher frequency signals near the pulmonary veins than being distributed in the left atrial body are more likely to terminate to sinus rhythm (normal heart rhythm) with PVI alone and to maintain sinus rhythm.

Studies have suggested that patients undergoing standard PVI ablation procedures for persistent AF who have coincidental interruption of drivers have a far better long term outcome. This suggests that the characteristics of atrial heart tissue and electrical activation patterns maintaining AF are likely to determine the response to ablation therefore it may be possible to determine more directly and accurately the likelihood of success by performing non-invasive mapping of the atria using the ECG-I.

ECG-I is able to localise the drivers of AF and one of the objectives is to study the electrical characteristics of the tissue. ECG-I is currently being used in research into AF. A recently published a study using ECG-I to identify targets of ablation in 103 patients. The on-going multicentre AFACART study has published early data to suggest that ECG-I can identify the drivers of AF and improve CA success rates.

PHENOTYPE AF is an ongoing clinical trial in which 100 patients with persistent AF are receiving cryoballoon pulmonary vein isolation for persistent AF (NCT03394404). Patients with recurrent AF or atrial tachycardia within 1 year following pulmonary vein isolation for AF within this trial will be recruited into this study. Up to 50 such patients who have failed Pulmonary Vein Isolation will be enrolled. These patients will undergo a second procedure at which time participants will undergo catheter ablation of drivers of AF and will then be followed up for 12 months.

Enrollment

150 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Patients with recurrent AF or atrial tachycardia within 1 year of ablation for persistent AF in the PHENOTYPE AF trial (NCT03394404). Original inclusion criteria for PHENOTYPE AF trial:

  • Persistent AF (i.e. episodes of AF that are continuous for > 1 week)
  • Willing for ablation.
  • Age between 18 to 80.

Exclusion Criteria:

  • Exclusions:

    • Continuous persistent AF > 2 years duration
    • Left atrial diameter > 5 cm
    • Severe left ventricular impairment (EF < 40%)
    • New York Heart Association class 3 or 4 heart failure
    • Known hypertrophic cardiomyopathy, cardiac sarcoid or Arrhythmogenic Cardiomyopathy.
    • Known inherited arrhythmia such as Brugada or long QT syndromes
    • Valvular disease that is more than moderate
    • History of valve replacement (metallic or tissue)
    • History of congenital heart disease (other than patent foramen ovale)
    • Previous left atrial ablation (percutaneous or surgical)
    • Cardiac surgery or percutaneous coronary intervention within the last 3 months.
    • Myocardial infarction or unstable angina within the last 3 months.
    • Unwillingness for ablation
    • Unwillingness to be involved in study
    • Suspected reversible cause of AF
    • Any other contraindication to catheter ablation
    • Age < 18 yrs or > 80 years
    • Pregnancy
    • Morbid obesity (defined as body mass index >40)
    • Any other medical problem likely to cause death within the next 18 months

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

150 participants in 1 patient group

ECG-I Mapping and Ablation of drivers
Experimental group
Description:
ECG-I Mapping will be performed and drivers will be ablated as directed by ECG-I.
Treatment:
Device: ECG-I Mapping of Atrial Fibrillation

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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