Ablation of Human Cardiac Fibrillation Based on Models of Hierarchical Organization of Tissue Excitation (TerFib)

San Carlos Clinical Hospital

Status: Enrolling

Conditions: Atrial Fibrillation (AF); Ablation Treatment; TerFib_Hyerarchy

Treatments: Procedure: Active group ablation; Procedure: Control group ablation

Study type: Interventional

Funder types: Other

Identifiers

NCT07390175

80/18 (Other Identifier)

TerFib_Hyerarchy

Details and patient eligibility

About

The mechanisms that maintain persistent atrial fibrillation (AF) in humans remain unknown. In the research project PI18/01268 funded in the previous call for Strategic Action in Health, the group has demonstrated that the hierarchical organization of (i) rotational domains, (ii) frequency domains and (iii) physiological responses to pharmacological provocation with adenosine, allow the identification of domains of high-frequency reentrant activity (hereinafter "DFASI domains") maintainers of AF. As a result, the investigators have developed non-invasive technological models and quantitative indices (currently both subject to patent evaluation; United States Patent and Trademark Office, Application number 63/422,563) for the efficient localization of these domains, whose therapeutic approach through ablation has allowed to improve the clinical results of the patients studied, safely without increase in complications (Calvo D et al. Sci Rep. 2025 Dec 16;15(1):43892). Likewise, and in response to the objectives of the PI18/01268 project, the investigators have identified hierarchical organization patterns in human ventricular fibrillation (VF) that indicate the existence of universal fibrillatory mechanisms, opening the door to new therapeutic opportunities (Europace 2022;24[11]:1788-1799).

Full description

The present research project proposes to characterize the physiology of persistent human AF after therapeutic interaction (ablation) with the "DFASI domains", exploring its impact on the dynamics and maintenance of AF in patients. The investigators propose to reveal the physiological mechanisms by which this interaction improves the clinical outcomes of our patients (Objective 1), which will allow the development of more efficient ablation strategies (Objective 2). Likewise, preclinical models developed by our group in collaboration with the National Center for Cardiovascular Research support the translation of our technological developments to the field of human VF. Therefore, in the present research project the investigators propose to explore the physiological significance of "DFSI domains" in patients with recurrent VF and the eventual development of efficient ablative therapies (Objective 3). With the proposed objectives, the project addresses the challenges posed in the diagnosis and treatment of cardiovascular diseases within the National Health System, in the context of a prevalent pathology (cardiac fibrillation) with high morbidity and mortality.

Enrollment: 78 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients over 18 years of age with persistent AF lasting more than 6 months at the time of the experimental protocol (uninterrupted persistent AF) and clinical indication for an AF ablation procedure.

or

-Patients over 18 years of age with recurrent VF/VT and poor control with conventional pharmacological measures.

Exclusion criteria

• Lack of patient consent to participate in the study.
• In patients with persistent AF, contraindication for the use of adenosine.
• AF/VF/VPT secondary to endocrine-metabolic disorders and/or severe systemic disease (thyrotoxicosis, sepsis, pulmonary thromboembolism, etc.).
• Contraindications for cardiac catheterization (e.g., intracardiac thrombus).
• Impossibility of remote monitoring using an implantable Holter monitor or implantable defibrillator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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78 participants in 2 patient groups

Control group (CPVI only)

Active Comparator group

Description:

Modifications in fibrillation dynamics induced by CPVI will be evaluated. Therefore, an experimental protocol will be carried out in which, once CPVI has been completed, a new acquisition of non-invasive maps will be performed to characterize basal fibrillation dynamics and those under adenosine

Treatment:

Procedure: Control group ablation

Active group (CPVI plus extrapulmonary ablation of DFASI domains)

Experimental group

Description:

Modifications in fibrillation dynamics induced by ablation distributed along the points of singularity of the maintaining reentries (or their inclusion in the CPVI if applicable) will be evaluated, as suggested by our preliminary results (Calvo D et al. Sci Rep. 2025 Dec 16;15(1):43892). Therefore, an experimental protocol will be carried out in which each DFASI reentrant domain will be addressed sequentially. After each ablation set, a new evaluation of noninvasive hierarchical organization patterns will be performed by acquiring new CardioInsight maps in AF

Treatment:

Procedure: Active group ablation