Diabetes mellitus is among the top 10 causes of death worldwide with an increasing incidence.
Patients with diabetes are at risk of developing heart failure which is characterised by
significant changes in the heart muscle including scarring and thickening. Contraction of the
heart involves movement of calcium across the heart muscle and disruption of this process is
an early change seen in heart failure. Recently, a drug therapy (SGLT2 inhibitor therapy) in
patients with diabetes was shown to benefit patients with heart failure but the mechanisms of
benefit are unknown.
Our hypothesis is that calcium handling is altered in patients with either type 2 diabetes
mellitus (T2DM) or heart failure and that SGLT2 inhibitors can improve this in heart failure
irrespective of the presence of T2DM.
Scanning the heart using magnetic resonance imaging (MRI) enables detailed assessment of its
structure and function by using a new contrast 'dye' containing manganese that has shown
advantages over traditional contrast. We plan to further test this new dye as it has the
potential to track and quantify improvements in heart function over time and detect changes
in calcium handling in the heart muscle, making it an ideal measure to identify the
mechanisms of benefit from SGLT2 inhibitor therapy.
The study population will comprise patients with heart failure with and without type 2
diabetes, patients with type 2 diabetes without heart failure and healthy volunteers.
Baseline comparisons will be made between the four groups before progressing to the
randomised controlled trial with heart failure patients only. Patients will have a clinical
assessment and blood tests, electrocardiogram, echocardiogram and MRI of the heart at each
visit.
If successful, this study will give us significant insights into mechanisms of action of
SGLT2 inhibitors in heart failure and will enable us to tailor specific treatments in heart
failure patients.