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

NCT07390175 | Recruiting DMC

• 2 other identifiers: TerFib_Hyerarchy80/18
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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 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).

Conditions

Atrial Fibrillation (AF); Ablation Treatment; TerFib_Hyerarchy

Keywords

Hierarchical organization of tissue excitation; Atrial Fibrillation (AF); Ablation; TerFib_Hyerarchy

Outcome Measures

Primary Outcomes (4)

• Mapping for the identification of stable reentrant domains with high activation frequency in persistent AF.

  After performing cardiac CT, non-invasive mapping will be performed using ECGi non-invasive map system. The signals will be analyzed for real-time inverse solution calculations using proprietary spectral fingerprint identification algorithms (Calvo D et al. Sci Rep. 2025 Dec 16;15(1):43892). In particular, non-invasive mapping will provide the fibrillation signal from both atria for the implementation of the calculations necessary for the spectral fingerprint study. The instantaneous phase will be computed by two methods: (i) by Hilbert transformation of the signal; and (ii) by phase calculation on the discrete frequencies identified in the power spectrogram. On the other hand, invasive mapping will be used to process bipolar and unipolar cardiac signals in order to analyze hierarchically organized patterns.

  During procedure

• Effects of ablation of DFSAI > 0.8 domains on fibrillation dynamics and sustainability

  * In patients in the active group, changes in fibrillation dynamics induced by CPVI and ablation of DFASI domains 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, after CPVI, each DFASI domain will be addressed sequentially. The following will be determined: a) changes in hierarchical organization levels, b) the formation of new DFASI domains; c) if AF ends after ablation, the termination mechanisms will be described. Once all ablation sets on the identified DFASI reentrant domains have been completed, noninvasive maps will be acquired under the effect of adenosine in order to compare fibrillatory dynamics under basal adenosine vs. post-ablation. * In patients in the control group, once CPVI is completed new noninvasive maps will be acquired to characterize basal and adenosine-induced fibrillatory dynamics.

  During procedure

• Effects of ablation of reentrat domains of human ventricular fibrillation on arrhythmia inducibility.

  Adapt the model to patients with ventricular arrhythmias such as polymorphic ventricular tachycardia and/or VF. After performing a cardiac CT scan, non-invasive mapping will be performed using ECGi non-invasive map system. The signals will be analyzed for real-time inverse solution calculations using algorithms for identifying reentrant domains and their correlation with hierarchical organization patterns (Calvo D et al. Sci Rep. 2025 Dec 16;15(1):43892). To this end, VF will be induced by programmed stimulation on two occasions in order to identify the hierarchical organization of the stability of rotational activity in terms of frequency. Ablation will follow and inducibility tested as measurement of efficacy.

  Procedure

• Arrhythmia burden during Follow-up

  A subcutaneous Holter monitor will be implanted one month prior to the ablation procedure to mesure arrhythmia burden (Atrial fibrillation; number of recurrences and hours per day). Patients will be monitored continuously after the ablation procedure using remote subcutaneous Holter monitoring platforms and in person at cardiology consultations at 3, 6, and 12 months, at a minimum. Patients with VF ablation will be followed up after the ablation procedure on an ongoing basis using implantable defibrillator remote monitoring platforms and in person at cardiology consultations at least 3, 6, and 12 months after the procedure. The arrhythmia burden will be measure as a function of number of recurrences per follow-up time.

  3, 6 and 12 months follow-up visits

Study Arms (2)

Control group (CPVI only)

ACTIVE COMPARATOR

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

Procedure: Control group ablation

Active group (CPVI plus extrapulmonary ablation of DFASI domains)

EXPERIMENTAL

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 non-invasive maps in AF

Procedure: Active group ablation

Interventions

Active group ablation PROCEDURE

In patients in the active group, changes in fibrillation dynamics induced by CPVI and ablation of DFASI domains 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, after CPVI, each DFASI domain will be addressed sequentially. The following will be determined: a) changes in hierarchical organization levels, b) the formation of new DFASI domains; c) if AF ends after ablation, the termination mechanisms will be described. Once all ablation sets on the identified DFASI reentrant domains have been completed, noninvasive maps will be acquired under the effect of adenosine in order to compare fibrillatory dynamics under basal adenosine vs. post-ablation.

Active group (CPVI plus extrapulmonary ablation of DFASI domains)

Control group ablation PROCEDURE

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

Control group (CPVI only)

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital San Carlos, Madrid: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist electrophysiologist

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: February 5, 2026
• Study Start: January 20, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

ES (1)