Stochastic Termination of Spiral Wave Dynamics in Cardiac Tissue

Abstract

Rotating spiral waves are self-organized features in spatially extended excitable media and may play an important role in cardiac arrhythmias including atrial fibrillation (AF). In homogeneous media, spiral wave dynamics are perpetuated through spiral wave breakup, leading to the continuous birth and death of spiral waves, but have a finite probability of termination. In non-homogeneous media, however, heterogeneities can act as anchoring sources that result in sustained spiral wave activity. It is thus unclear how and if AF may terminate following the removal of putative spiral wave sources in patients. Here, we address this question using computer simulations in which a stable spiral wave is trapped by an heterogeneity and is surrounded by spiral wave breakup. We show that, following ablation of spatial heterogeneity to render that region of the medium unexcitable, termination of spiral wave dynamics is stochastic and Poisson-distributed. Furthermore, we show that the dynamics can be accurately described by a master equation using birth and death rates. To validate these predictions in vivo, we mapped spiral wave activity in patients with AF and targeted the locations of spiral wave sources using radiofrequency ablation. Targeted ablation was indeed able to terminate AF, but only after a variable delay of up to several minutes. Furthermore, and consistent with numerical simulations, termination was not accompanied by gradual temporal or spatial organization. Our results suggest that spiral wave sources and tissue heterogeneities play a critical role in the maintenance of AF and that the removal of sources results in spiral wave dynamics with a finite termination time, which could have important clinical implications.

The role of the Cx43/Cx45 gap junction voltage gating on wave propagation and arrhythmogenic activity in cardiac tissue

“…This process is associated with the reduction of re-entrant activity and, thus, the reduced arrhythmogenicity of the cardiac tissue. For example, the disruption of re-entry by a drift of a spiral wave tip and its subsequent collision with a non-conductive boundary has been reported in multiple studies 28 – 30 . We wanted to test whether the drift of the spiral waves may affect the formation of chaotic fibrillation-like processes, which exhibit a multiplication of the spiral waves.…”

Spatially Conserved Spiral Wave Activity During Human Atrial Fibrillation

“…31 In patients in whom pulmonary vein isolation does not eliminate AF, spatially conserved spiral waves could be targets for ablation to destroy tissue close to the spiral wave tip, as demonstrated in computational analyses, 32,33 in explanted hearts, 34 and in some clinical studies. 11,12 In such cases, removing spatially conserved spiral waves can result in wave dynamics with a finite termination time 22,35,36 as shown in subsets of patients. 12,37 In addition, our finding that a spiral wave come back in step and are thus manifestations of a temporally stable, spatially conserved wave may also explain why a recording interval that is much shorter than 60 s can be sufficient to determine the location of AF drivers.…”

The role of pulse timing in cardiac defibrillation

“…Future studies may also consider more realistic geometries of the (human) heart Fenton et al (2005) including fiber orientation Doste et al (2019) influencing the excitation propagation. Heterogeneities, such as blood vessels and collagen, may not only act as virtual electrodes but also have an impact on the spatio-temporal dynamics Bittihn et al (2017); Rappel et al (2022). Modelling this impact in detail requires the use of bidomain models differentiating between intra-and extracellular space.…”