Motivation: The role of sub-cellular spontaneous calcium release events (SCRE) in the development of arrhythmia at the tissue-scale has yet to be investigated in detail. SCRE may underlie the emergence of spontaneous excitation in single cells, resulting in arrhythmic triggers in tissue. However, translation of single-cell data to the tissue scale is non-trivial due to the complex substrate considerations associated with arrhythmic conduction patterns. Computational modelling provides a viable approach to dissect these multi-scale mechanisms, yet there remains a significant challenge in accurately and efficiently modelling this probabilistic behaviour in large-scale tissue models. The aim of this study was to develop an approach to overcome this challenge and investigate the potential organ-scale implications of cellular SCRE. Methods: A computational model of stochastic, spatio-temporal calcium handling [1] was used to investigate the dynamics of SCRE under multiple conditions (pacing rate, beta-stimulation, disease remodelling) in single cells. Analysis of these data allowed the derivation of spontaneous release functions, which capture the variability and properties of SCRE matched to the full cell model [2]. These functions were then integrated with tissue models, comprising idealised 2D sheets as well as full reconstructions of ventricular and atrial anatomy. Mechanisms of synchronisation of independent cellular events into spontaneous focal excitation were investigated under calcium overload conditions; sustained re-entry was implemented to study the potential long-term interactions between re-entry and focal excitation. Results: The developed approach allowed dynamic reproduction of SCRE in efficient single cell models and resulting large-scale tissue models, validated against the behaviour observed in the detailed cell models. In homogeneous tissue, the emergence of a spontaneous beat from a single source was observed and the positive role of electrotonic coupling was demonstrated. Sustained re-entrant excitation promoted calcium overload, and led to the emergence of focal excitations both after termination of re-entry and also during re-entrant excitation. These results demonstrated a purely functional mechanism of re-entry and focal activity localisation, related to the unexcited spiral wave core. Conclusions: A novel approach has been developed to dynamically and accurately model SCRE at the tissue scale, in-line with behaviour observed in detailed single-cell models. Mechanisms of the interaction of cellular SCRE with organ-scale arrhythmia were demonstrated, providing novel insight into the coupling between focal excitation and re-entry.