Influence of spatial resolution and scar extent on stretch-activated mechano-electric feedback in post-infarction...

Sudden cardiac death after myocardial infarction (MI) remains a major clinical problem, partly driven by complex electromechanical feedback mechanisms that are not fully understood. In particular, the interplay between scar stiffness, border zone (BZ) remodeling, mechano-electric feedback (MEF) through stretch-activated channels (SACs), and cross-bridge formation, can strongly influence ventricular function and arrhythmogenic risk. In this study, we developed a 3D finite element model of human ventricular electromechanics coupled with a closed-loop circulation model to investigate the impact of scar size on cardiac function. Before addressing scar effects, we first analyzed the spatial resolution of the mesh to ensure reliable electromechanical predictions. Within the present electromechanical framework and mechanical discretization, spatial resolutions of approximately 1.0-1.3 mm were required to capture SAC-driven depolarizations in the BZ. Using this confirmed to be suitable resolution, we examined infarct volume fractions (IVFs) from 5-20% of the left ventricle (LV). Increasing IVF progressively impaired contractility and ejection fraction, with a nonlinear threshold emerging between 10% and 15% IVF in the primary models studied here, above which SACs elicited premature activations which disrupted sinus-driven dynamics, and produced irregular multi-beat PV-loop patterns. These findings highlight two key insights: spatial resolution is critical for capturing SAC-mediated feedback accurately, and scar extent strongly influences the severity of this feedback, with larger scars significantly altering ventricular dynamics. Together, this work provides mechanistic understanding of how scar enlargement can accelerate heart failure progression and arrhythmic risk through nonlinear MEF.