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

INTERVENTION: From the main study criteria (ACTRN12611000479909), patients with reduced PCR/ATP ratio of < 1.7 will be eligible to participate in the therapeutic metformin sub‐study. They will have a baseline 10ml blood sample before having 12 weeks treatment of either metformin 1g orally 3 x daily or placebo orally 3 x daily before crossing over to the other treatment after a 4 week drug wash‐out period. At the end of each 12 week treatment phase they will have another 10ml blood sample, cardiac magnetic resonance imaging with gadolinium contrast (0.025mmol/kg body weight), cardiac magnetic resonance spectroscopy with adenosine intravenously (140mcg/kg/min) for 3‐6 mins and echocardiography. CONDITION: Hypertrophic Cardiomopathy PRIMARY OUTCOME: Phosphocreatine (PCr)/Adenosinetriphosphate (ATP) ratio. Method: Cardiac magnetic resonance spectroscopy will be used to measure cardiac high energy phosphate metabolism in‐vivo. The novel SLOOP method (spatial localisation with optimum pointspread function) allows accurate measurement of absolute concentrations of high‐energy phosphates. SECONDARY OUTCOME: AMPK activity as measured by peripheral blood test Absolute concentration of high‐energy phosphates as measured by cardiac magnetic spectroscopy. LV diastolic function as measured by cardiac magnetic resonance imaging and doppler echocardiography LV systolic function as measured by cardiac magnetic resonance imaging Regional function as measured by cardiac magnetic resonance imaging INCLUSION CRITERIA: Hypertrophic cardiomyopathy patients aged between 18 and 75; phenotype positive (established by echocardiography or cardiac magnetic resonance scan); genotype positive for cardiac myosin binding protein‐C gene mutations or cardiac beta‐myosin heavy chain gene mutations; patients with reduced baseline PCR/ATP ratio of <1.7