Heart failure (HF) is a leading cause of morbidity and mortality that is up to five times more prevalent in Māori compared to non-Māori. Effective diagnosis and treatment are hampered by the lack of mechanistic knowledge of the pathophysiological processes underlying HF. We will investigate the mechanical basis of HF using a novel combination of biophysical modelling, microstructural and clinical imaging, and access to a diverse range of patient data through clinical collaborations with Oxford, New York, London, Christchurch and Auckland. We will develop new bioengineering methods to integrate structural and functional information from cardiac images of HF patients and animal models. Personalised biophysical simulations will reveal the relative roles of ventricular filling, contraction and relaxation to provide a mechanistic understanding of the different forms of HF, and to assess the applicability of animal models for studying human HF. This will aid development of targeted therapeutic strategies for HF.