Datasheet1_The circle of reentry: Characteristics of trigger-substrate interaction leading to sudden cardiac arrest.docx

Sudden cardiac death is often caused by ventricular arrhythmias driven by reentry. Comprehensive characterization of the potential triggers and substrate in survivors of sudden cardiac arrest has provided insights into the trigger-substrate interaction leading to reentry. Previously, a “Triangle of Arrhythmogenesis”, reflecting interactions between substrate, trigger and modulating factors, has been proposed to reason about arrhythmia initiation. Here, we expand upon this concept by separating the trigger and substrate characteristics in their spatial and temporal components. This yields four key elements that are required for the initiation of reentry: local dispersion of excitability (e.g., the presence of steep repolarization time gradients), a critical relative size of the region of excitability and the region of inexcitability (e.g., a sufficiently large region with early repolarization), a trigger that originates at a time when some tissue is excitable and other tissue is inexcitable (e.g., an early premature complex), and which occurs from an excitable region (e.g., from a region with early repolarization). We discuss how these findings yield a new mechanistic framework for reasoning about reentry initiation, the “Circle of Reentry.” In a patient case of unexplained ventricular fibrillation, we then illustrate how a comprehensive clinical investigation of these trigger-substrate characteristics may help to understand the associated arrhythmia mechanism. We will also discuss how this reentry initiation concept may help to identify patients at risk, and how similar reasoning may apply to other reentrant arrhythmias.</p

DataSheet1_Strain-controlled electrophysiological wave propagation alters in silico scar-based substrate for ventricular tachycardia.docx

Introduction: Assessing a patient’s risk of scar-based ventricular tachycardia (VT) after myocardial infarction is a challenging task. It can take months to years after infarction for VT to occur. Also, if selected for ablation therapy, success rates are low.Methods: Computational ventricular models have been presented previously to support VT risk assessment and to provide ablation guidance. In this study, an extension to such virtual-heart models is proposed to phenomenologically incorporate tissue remodeling driven by mechanical load. Strain amplitudes in the heart muscle are obtained from simulations of mechanics and are used to adjust the electrical conductivity. Results: The mechanics-driven adaptation of electrophysiology resulted in a more heterogeneous distribution of propagation velocities than that of standard models, which adapt electrophysiology in the structural substrate from medical images only. Moreover, conduction slowing was not only present in such a structural substrate, but extended in the adjacent functional border zone with impaired mechanics. This enlarged the volumes with high repolarization time gradients (≥10 ms/mm). However, maximum gradient values were not significantly affected. The enlarged volumes were localized along the structural substrate border, which lengthened the line of conduction block. The prolonged reentry pathways together with conduction slowing in functional regions increased VT cycle time, such that VT was easier to induce, and the number of recommended ablation sites increased from 3 to 5 locations.Discussion: Sensitivity testing showed an accurate model of strain-dependency to be critical for low ranges of conductivity. The model extension with mechanics-driven tissue remodeling is a potential approach to capture the evolution of the functional substrate and may offer insight into the progression of VT risk over time.</p