The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study

Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.

The outcome of ablation for non-paroxysmal atrial fibrillation targeting spatiotemporal electrogram dispersion compared with ganglionated plexi ablation

Background Although catheter ablation targeting ganglionated plexi (GP) playing an important role in formation of triggers and substrates of atrial fibrillation (AF) has been reported as one of the effective ablation strategies in non-paroxysmal AF (non-PAF) patients, its effectiveness varies among the study groups. More recently, ablation targeting spatiotemporal electrogram dispersion (STED) areas, assumed to contain AF drivers in forms of rotational activation is proposed. However, the optimal ablation strategy for non-PAF is still controversial since the exact mechanisms of non-PAF are not well understood. Purpose To investigate the effectiveness of GP ablation for autonomic modification and STED ablation for modulation of AF drivers. Methods Consecutive 149 non-PAF patients who underwent STED ablation in our center were enrolled. We detected STED areas within the whole left and right atrium during AF using PentaRay®, and ablated them. If AF was terminated during STED ablation, we finished the procedure without burning the remaining STED areas. If not, electrical cardioversion was applied. The outcome was compared with that in consecutive 156 non-PAF patients undergoing GP ablation previously in our center. Results (1) The clinical characteristics were comparable between two groups (see Table). (2) A Kaplan-Meier curve showed that there was no significant difference between the freedom rates from non-PAF/non-paroxysmal atrial tachycardia (non-PAT) after single procedure in STED group and GP group (Figure, left). (3) However, the freedom rates from non-PAT in STED group was significantly lower than that GP group (Figure, right). Conclusions The recurrence type of atrial arrhythmia after ablation was remarkably different between ablation of STED and GP. STED ablation might eliminate fibrillatory conduction and control AF driver in patients with non-PAF. Freedom from atrial arrhythmia Funding Acknowledgement Type of funding source: None

Ivabradine as a stabilising anti-arrhythmic agent for multifocal atrial tachycardia

Multifocal atrial tachycardia has certain electrocardiographic similarities to atrial fibrillation. The mechanism of atrial fibrillation is heterogenous but in some cases may arise from a single ectopic driver with fibrillatory conduction to the rest of the atria. This has led to the speculation that multifocal atrial tachycardia may have a similar mechanistic unifocal site that disperses through the atrium in a fibrillatory pattern. Ivabradine has been reported to be efficacious in an adult with paroxysmal atrial fibrillation as well as in children with junctional or ectopic atrial tachycardias. This is the first report of successfully using ivabradine, a novel anti-arrhythmic If blocking agent, to convert multifocal atrial tachycardia in a 5-month-old critically ill infant to a pattern indicating a single ectopic atrial focus. This allowed the patient’s single atrial focus to be ablated with return to sinus rhythm and decannulation from ventriculoarterial extracorporeal membrane oxygenation. This case suggests that multifocal atrial tachycardia may arise from a single automatic focus with downstream fibrillatory conduction to the atria.

Abstract 18492: Phase Analysis Detects Human Atrial Fibrillation Sources While Classical Activation Mapping May Not: Reconciling Classical and Computational Mapping

Introduction: The mechanisms maintaining human persistent AF are elusive. It is striking how most optical mapping studies in animal and recently human AF show rotors and focal sources, while most classical activation mapping studies of electrograms do not. We tested the hypothesis that sites in human persistent AF showing rotors by phase analysis may, due to precession (‘wobble’) and fibrillatory collision, rarely reveal sources in activation maps. Methods: We studied 25 patients with persistent AF (LA 47 mm, CHADS2=1.9), in whom phase-mapping of electrograms from 64 pole baskets revealed rotors/focal sources where ablation terminated AF. Electrograms (fig A) were annotated (Matlab) using minimum dV/dt (unipoles, fig B) and peak amplitude criteria (bipoles) to create contours (isochrones), that were classified into a) complete, b) partial or c) unresolvable sources. Results: In each case, ablation at phase-identified rotors/sources (4.0±5.7 mins) terminated persistent AF to sinus rhythm (fig C, 64%) or atrial tachycardia. Notably, isochrones detected sources in only 5/25 (20%) of cases (fig D), more easily in unipolar than bipolar signals. Isochrones revealed partial sources in 11 (44%) and were unresolvable in 9 (36%). Source detection in classical maps was obscured by low signal: noise, varying sequence (rotor precession), or electrode noise that phase analysis resolved by analyzing neighboring sites (fig E). The figure summarizes these steps for a case with perfect agreement between activation and phase maps. Conclusions: Rotors and focal sources for human persistent AF detected by phase analysis were mostly undetected in activation maps, due to rotor precession and fibrillatory conduction. These data may inform approaches to revise classical criteria to better map AF.

Role of Rotors in the Ablative Therapy of Persistent Atrial Fibrillation

Atrial fibrillation (AF) ablation is increasingly used to maintain sinus rhythm yet its results are sub-optimal, especially in patients with persistent AF or prior unsuccessful procedures. Attempts at improvement have often targeted substrates that sustain AF after it is triggered, yet those mechanisms are debated. Many studies now challenge the concept that AF is driven by self-sustaining disordered wavelets, showing instead that localised drivers (rotors) may drive disorder via a process known as fibrillatory conduction. Novel mapping using wide-area recordings, physiological filtering and phase analysis demonstrates rotors in human AF. Contact mapping with focal impulse and rotor modulation (FIRM) shows that localised ablation at sources can improve procedural success in many populations on long-term follow up and some newer approaches to rotor mapping are qualitatively similar. This review critically evaluates the data on rotor mapping and ablation, which advances our conceptual understanding of AF and holds the promise of substantially improving ablative outcomes in patients with persistent AF.