Personalised Ablation Strategies in AF

NCT05633303 | Recruiting

• 1 other identifier: 22/PR/0961
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is the most common arrhythmia with an expected rise in prevalence over the next decade. Catheter ablation is a safe treatment option in eliminating AF however, success rates still remains variable. Existing strategies do not take into account the differences in AF perpetuation mechanisms beyond the pulmonary veins (PVs) due to the underlying substrate. Here, I will investigate the differences in persistent AF mechanisms due to the underlying substrate and utilise these findings to generate AF mechanism specific ablation strategies. I have defined a new metric, rate-dependent conduction velocity (RDCV) slowing that has shown to correlate with sites of re-entry activity in AF. In this study, techniques and methods will be developed to measure RDCV slowing sites. The impact autonomic modulation has on AF mechanisms and CV dynamics will also be assessed. The hypothesis is that a combination of structural, electrical and autonomic remodelling play an important mechanistic role in persistent AF and ablation strategies adapted to target these will result in greater procedural success rate. The study findings have the potential to improve the success rate of catheter ablation in persistent AF thereby improve patient wellbeing and reduce the cost burden of AF treatment.

Conditions

Atrium; Fibrillation

Keywords

Atrial fibrillation; Autonomic remodelling; Conduction velocity; Novel ablation strategies

Outcome Measures

Primary Outcomes (7)

• Sequential rate dependent conduction velocity (RDCV) assessment

  RDCV slowing sites can be effectively identified prospectively using pacing protocols and multipolar catheters that are applicable to those routinely used in conventional ablation procedures.

  6 months

• Ablation of RDCV slowing results in an positive ablation response.

  RDCV slowing sites are mechanistically important in driving AF in patients with underlying LVZs. This will be measured through the impact ablation of RDCV slowing sites has on electrophysiological endpoints. RDCV slowing sites will be ablated and the proportion of these sites that results in a positive ablation response i.e. termination of AF into sinus rhythm or slowing of AF cycle length will be measured.

  6 months

• Autonomic modulation impacts on conduction velocity measurements.

  Autonomic modulation impacts conduction velocity (CV) measurements in patients with underlying LVZs. This will be measured through the impact autonomic modulation with Isoprenaline has on CV by comparing CVs measurements obtained post autonomic modulation to CVs measurements pre autonomic modulation.

  6 months

• Autonomic modulation impacts on conduction velocity measurements.

  Autonomic modulation impacts conduction velocity (CV) measurements in patients with underlying LVZs. This will be measured through the impact autonomic modulation by ganglionated plexi stimulation has on CV by comparing CVs measurements obtained post autonomic modulation to CVs measurements pre autonomic modulation.

  6 months

• Substrate guided ablation in patients with LVZs impacts freedom from AF/AT during follow-up.

  GP site ablation and substrate modification guided by RDCV slowing sites in addition to PV isolation impacts freedom from AF and atrial tachycardia (AT) rates during 12 months follow-up in patients with underlying LVZs. This will be measured through the impact this ablation strategy (GP site ablation, substrate modification guided by RDCV slowing sites and PV isolation) has on the number of patients that are free from AF and AT during 12 months follow-up.

  12 months

• Ablation of GP sites results in an positive ablation response.

  GP sites are mechanistically important in driving AF in patients without underlying LVZs whereby ablation of GP sites will have an impact on electrophysiological endpoints and electrical parameters (spectral analysis parameters and CS electrogram characteristics). This will be measured through the impact ablation of GP sites has on electrophysiological endpoints. GP sites will be ablated and the proportion of these sites that results in a positive ablation response i.e. termination of AF into sinus rhythm or slowing of AF cycle length will be measured.

  6 months

• Substrate guided ablation in patients without LVZs impacts freedom from AF/AT during follow-up.

  GP site ablation in addition to PV isolation results impact freedom from AF and atrial tachycardia (AT) rates during follow-up in patients without underlying LVZs. This will be measured through the impact this ablation strategy (GP site ablation, substrate modification guided by RDCV slowing sites and PV isolation) has on the number of patients that are free from AF and AT during 12 months follow-up.

  12 months

Secondary Outcomes (1)

• RDCV slowing sites and GP sites identification on cardiac MRI

  12 months

Study Arms (2)

Patients with underlying LVZs (≥30% of LVZs in the LA body)

EXPERIMENTAL

Study 1- Developing a methodology and technique for sequential CV assessment. Twenty patients. Study 2- Assess the mechanistic importance of RDCV slowing sites in AF. Twenty patients. Study 3- Assess the impact autonomic modulation has on CV dynamics and RDCV slowing sites. Twenty patients. Study 4- GP site ablation and substrate modification guided by RDCV slowing sites whereby substrate ablation is limited to substrate with these electrical properties and the impact on freedom from AF/AT during 12 months follow-up. Forty patients. . Study 5- RDCV slowing sites and GP site identification on cardiac MRI. Twenty patients.

Other: Substrate guided ablation

Patients without underlying LVZs (<30% of LVZs in the LA body)

EXPERIMENTAL

Study 1- Mechanistic importance of GP site ablation. Twenty patients. Study 2- GP site ablation in addition to PV isolation and the impact on freedom from AF/AT during 12 months follow-up. Forty patients. Study 3- RDCV slowing sites and GP site identification on cardiac MRI. Twenty patients.

Other: Substrate guided ablation

Interventions

Substrate guided ablation OTHER

Ablation strategy implemented will be dependent on the Arm the patient has been allocated to based on the presence of underlying LVZs.

Patients with underlying LVZs (≥30% of LVZs in the LA body); Patients without underlying LVZs (<30% of LVZs in the LA body)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing catheter ablation for persistent AF (\<24 months AF duration and no previous left atrial ablation).
• Able to provide informed consent

You may not qualify if:

• Unwillingness to sign consent
• Age \<18 years
• Contraindications for catheter ablation procedure

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

Barts Heart Centre, Barts Health NHS trust

London, EC1A 7BE, United Kingdom

RECRUITING

Related Publications (1)

• Honarbakhsh S, Roney C, Wharmby A, Vidal Horrach C, Hunter RJ. Spatial and temporal relationship between focal and rotational activations and their relationship to structural remodeling in patients with persistent atrial fibrillation. Heart Rhythm. 2024 Jun;21(6):752-761. doi: 10.1016/j.hrthm.2024.01.039. Epub 2024 Jan 28.

  PMID: 38286244 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Shohreh Honarbakhsh, MRCP, BSc, PhD

CONTACT

020 3765 8682; shohreh.honarbakhsh@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: For all the studies performed all patients will have a bipolar voltage map created in sinus rhythm. If patients are not in sinus rhythm at the start of the procedure, they will undergo DC cardioversion (DCCV) to achieve sinus rhythm. Low voltage zones (LVZs) will be defined as sites with a voltage \<0.5mV on bipolar voltage map. If patients have ≥30% of LVZs in the LA body excluding the PVs and mitral valve annulus, they will be classified as patients with underlying LVZs whilst those with a proportion of LVZs of \<30% will be defined as those without LVZs. The study protocol undertaken will be decided based on whether the patient has underlying LVZs or not.

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: December 1, 2022
• Study Start: October 14, 2022
• Primary Completion (Estimated): October 10, 2027
• Study Completion (Estimated): October 10, 2027
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)