The progression of atrial fibrillation (AF) is marked by profound subcellular remodeling, yet previous studies have primarily focused on Ca²⁺-release heterogeneity driven by RyR2 cluster reorganization and T-tubule degradation. Spatial patterns of myolysis driven by mitochondrial encroachment into myofibrillar space and intracellular distribution of the myofilament Ca²⁺ buffer troponin C (cTnC), a key determinant of Ca²⁺–contraction coupling, remain underexplored. Whether these spatial remodeling independently modulate Ca²⁺ dynamics and downstream contractile regulation—specifically through Ca²⁺ binding to cTnC, competitive cTnI release from actin, and consequent thin-filament unblocking—remains unclear. Constructing a subcellular Ca²⁺-handling model that integrates both types of spatial heterogeneity through imaging-based techniques within a unified computational framework allows us to explore the remodeling mechanisms of AF. For myolysis, we contrast dispersed versus block-wise clustered structural patterns and evaluate their effects on intracellular Ca²⁺ dynamics. For Ca²⁺ buffering, we maintain total cTnC per domain while independently varying the spatial aggregation of high-cTnC regions, assessing their impact on systolic Ca²⁺ peaks and signal morphology. Spatiotemporal simulations reveal that dispersed myolysis largely preserves near-baseline Ca²⁺ behavior, whereas block-wise myolysis more readily induces fragmented spontaneous Ca²⁺ activity and increased Ca²⁺ signal instability. In certain remodeled settings, block-wise patterns are also associated with an elevated action-potential plateau, consistent with enhanced Ca²⁺-dependent depolarizing drive. Independently, altering cTnC aggregation alone significantly elevates systolic Ca²⁺ loading, potentially facilitating AF-promoting conditions, with downstream consequences for myofilament activation via cTnC–cTnI–regulated thin-filament availability and contractile regulation. Overall, myolysis spatial patterning and cTnC buffering distribution constitute two independent classes of spatial regulators that jointly shape Ca²⁺ stability and arrhythmogenic susceptibility. These findings motivate explicit incorporation of spatial heterogeneity in Ca²⁺-handling models and support future integration of histology-derived subcellular structure into multiscale computational studies.