Multi-Parametric Cardiovascular Magnetic Resonance Assessment of Hypertrophic Cardiomyopathy - Therapeutic Metformin sub-study

HCM is the most common cardiovascular genetic disorder and can cause significant morbidity and mortality, including the most serious complications of heart failure and sudden death. At present, there are no proven pharmacological therapies that either prevent or cause regression of clinical features. This is largely due to a lack of knowledge in our understanding of the molecular and functional consequences of the disease-causing gene mutations leading to the clinical disease. The proposed study will aim to test whether cardiac energetic compromise is a central pathophysiological mechanism in HCM. We will investigate potentially beneficial treatments based on our hypothesis, by trialling the use of metformin in an HCM group. If the results from this ‘proof of concept study’ are confirmatory, it could pave the way for larger multi-centre randomised studies (with longer duration of treatment) with either metformin or facilitators of fatty acid oxidation such as ranolazine. If realised, these treatments could prevent the vicious cycle of cardiac hypertrophy and myocardial dysfunction seen in hypertrophic cardiomyopathy, leading to improved morbidity and mortality. These investigations will establish early phenotype changes in HCM patients and provide insights into potential therapeutic interventions for a condition that currently has little therapeutic evidence base. This therapeutic sub-study is linked to the main study ACTRN12611000479909.