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

Ablación de la fibrilación Cardiaca Humana Basada en Modelos de organización jerárquica de la excitación Tisular.

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).

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.

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.