This thesis aimed to determine the mechanisms that sustain ventricular fibrillation (VF) and their modulation by two important electroarchitectural components, the pattern and degree of fibrosis and gap junction (GJ) coupling. The mechanisms that maintain myocardial fibrillation remain debated. Conflicting data exists supporting critical areas sustaining rotational drivers (RDs) and disorganised multiple wavelet driven activation. Abnormal GJ coupling and ventricular fibrosis are implicated in VF initiation and maintenance. VF mechanisms were studied with optical mapping of the transmembrane potentials in ex vivo perfused rat hearts that underwent pharmacological modulation of GJ coupling and separately in hearts that had differing patterns of chronic myocardial fibrosis induced. Enhanced GJ coupling progressively organised VF in a concentration-dependent manner and stabilised RDs, whilst GJ uncoupling progressively disorganised VF. Disorganised multiple wavelet activity sustained VF in compact fibrosis, whilst VF in patchy fibrosis was organised and harboured long duration spatially stable RDs, with diffuse fibrosis exhibiting an intermediate VF phenotype. By utilising ex vivo rat VF optical mapping data, Granger causality (GC), an econometric tool for quantifying causal relationships between complex time-series, was developed as a novel fibrillation mapping tool. GC-based mapping tools were validated, adapted for low spatial resolution multisite-mapping and tested in human VF optical mapping of left ventricular wedge preparations and in vivo human persistent AF mapping, where they showed a similar range of fibrillatory organisation and mechanisms as in rat VF. These findings support the existence of differing fibrillation electrophenotypes, along a continuous spectrum between globally organised fibrillation driven by stable RDs and disorganised fibrillation driven by multiple wavelets, influenced by fibrosis and GJ coupling. This work provides a unifying explanation for hitherto conflicting reports on mechanisms sustaining myocardial fibrillation and suggests that mechanism-directed treatment strategies based on the fibrillation electrophenotype may be more effective than standard empirical treatment approaches.