Aortic stenosis (AS) is characterised by left ventricular (LV) hypertrophy and altered
myocardial substrate metabolism. Peroxisome proliferator-activated receptor (PPARα), a
regulator of lipid metabolism is deactivated in pressure overload hypertrophy such as in AS
and can lead to dysregulation of fatty acid oxidation, myocardial triglyceride accumulation
(steatosis) and lipotoxicity. The investigators propose a proof-of-concept study to
investigate the effect of altering myocardial triglyceride (MTG) using a PPARα agonist,
fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. The
primary endpoint is a change in MTG assessed by magnetic resonance spectroscopy at baseline
and after 6 months of treatment. Exploratory endpoints are changes in cardiac physiology
including myocardial deformation (strain) as assessed by cardiac magnetic resonance imaging.
The investigators hypothesise that pharmacological reduction of MTG with a PPARα agonist will
result in steatosis regression and changes in cardiac physiology.