Fibrosis and Atrial Fibrillation: Computerized and Optical Mapping

Abstract

Recent studies strongly suggest that the majority of atrial fibrillation (AF) patients with diagnosed or subclinical cardiac diseases have established or even pre-existing fibrotic structural remodeling, which may lead to conduction abnormalities and reentrant activity that sustain AF. As conventional treatments fail to treat AF in far too many cases, an urgent need exists to identify specific structural arrhythmogenic fibrosis patterns, which may maintain AF, in order to identify effective ablation targets for AF treatment. However, the existing challenge is to define what exact structural remodeling within the complex 3D human atrial wall is arrhythmogenic, as well as linking arrhythmogenic fibrosis to an underlying mechanism of AF maintenance in the clinical setting. This review is focused on the role of 3D fibrosis architecture in the mechanisms of AF maintenance revealed by submillimeter, high-resolution ex-vivo imaging modalities directly of human atria, as well as from in-silico 3D computational techniques that can be able to overcome in-vivo clinical limitations. The systematic integration of functional and structural imaging ex-vivo may inform the necessary integration of electrode and structural mapping in-vivo. A holistic view of AF driver mechanisms may begin to identify the defining characteristics or “fingerprints” of reentrant AF drivers, such as 3D fibrotic architecture, in order to design optimal patient-specific ablation strategies.

Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells

“…Many studies over the past several decades have demonstrated that transcription factors, e.g., TBX5 and PITX2, can directly or indirectly influence atrial rhythm by regulating the expression of membrane effector genes 5 , 13 . However, the exact mechanisms, particularly how electrical remodeling induced by these transcription factors contribute to the increased susceptibility to AF, remain unclear due to its nature of complexity and limitation of clinical/experimental studies 39 . To our knowledge, this is the first study in silico to show that TBX5 insufficiency-induced electrical remodeling predicts the incidence of triggered activity in human atrial cells and lends support to the concept of a crucial pathophysiological role of TBX5 insufficiency in the development of AF.…”

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion

“…Electrophysiological models were used for understanding the start-up and the perpetuation of rotors, since this task is not easy to develop in experimental terms. The proposed computational descriptions of rotors propagating in a structurally remodeled atrial tissue, provided insight of how rotors evolve under such circumstances (Trayanova et al, 2014 ; Zhao et al, 2015 ; Hansen et al, 2017 ). Structural heterogeneities are modeled through non-conducting elements, reduced conductivity elements and boundary conditions.…”

Iterative navigation of multipole diagnostic catheters to locate repeating‐pattern atrial fibrillation drivers

“…Given that the main principle of ICAN, which is finding the direction towards the wave source and making a step in this direction, can be preserved, we anticipate that the ICAN algorithm can be expanded to detect focal activity [38] by identifying additional stopping criteria (Section 7 of the Supplement Content) for the focal source (see Supplement Figure 7). Focal sources can be produced by 3D scroll waves whose filaments do not intersect the surface and manifest themselves as breakthroughs as well as other types of intramural reentry [7] [39]. …”

“…Previous studies have shown that such additional sources are often functional reentry circuits that manifest themselves on the endocardium as repeating-pattern reentry, macroreentry, or focal AF drivers [6] [7]. Such AF drivers are usually localized with the help of the excitation phase maps of the entire atria [8] constructed using 64-electrode bi-atrial basket catheters.…”