Atrial fibrillation (AF) is the most common arrhythmia with an expected rise in prevalence over the next decade. Catheter ablation is a safe treatment option in eliminating AF however, success rates still remains variable. Existing strategies do not take into account the differences in AF perpetuation mechanisms beyond the pulmonary veins (PVs) due to the underlying substrate. Here, I will investigate the differences in persistent AF mechanisms due to the underlying substrate and utilise these findings to generate AF mechanism specific ablation strategies. I have defined a new metric, rate-dependent conduction velocity (RDCV) slowing that has shown to correlate with sites of re-entry activity in AF. In this study, techniques and methods will be developed to measure RDCV slowing sites. The impact autonomic modulation has on AF mechanisms and CV dynamics will also be assessed. The hypothesis is that a combination of structural, electrical and autonomic remodelling play an important mechanistic role in persistent AF and ablation strategies adapted to target these will result in greater procedural success rate. The study findings have the potential to improve the success rate of catheter ablation in persistent AF thereby improve patient wellbeing and reduce the cost burden of AF treatment.