Project summary
Understanding mechanisms underlying a type of “stiff” heart failure common in diabetics.
What is the issue for NSW?
Heart failure is a modern epidemic and carries a similar five-year mortality to many common cancers. We aim to thoroughly understand mechanisms underlying a type of “stiff” heart failure common in diabetics, where the heart doesn’t relax properly. It now accounts for over half of all cases and there is no specific therapy.
However, for the first time, there is promise on the horizon. Recently, three independent clinical trials showed that a new class of type 2 diabetes medication called “SGLT2 inhibitor” improved outcomes for this type of heart failure. We will analyse blood plasma from one of these international clinical trials, the CANVAS study.
These medications raise levels of particular nutrients in the blood that are used by the diabetic heart to provide energy.
What does the research aim to do and how?
Our initial work using human hearts revealed several classes of nutrients that are deprived in heart failure. We will now determine those that are specific to diabetic cardiomyopathy using our diabetic cardiomyopathy clinic, CANVAS trial samples, and mouse and cell models of disease.
Aboriginal Australians are affected disproportionately by this disease. We are collaborating with indigenous researchers in Redfern NSW, and with a leading Australian Aboriginal researcher, Prof Alex Brown, who now has a joint appointment at our Institute, and who will provide plasma samples and relevant imaging and clinical measures.
To determine mechanisms underlying cardiac nutrient changes in this disease, we will use a mouse model established in our lab where the mice develop stiff hearts and the same cardiac nutrient changes as humans. Furthermore, we will use a technique to trace the fate of labelled nutrients in mouse hearts with this disease. Finally, we will deliver candidate nutrients that are depleted in diabetic cardiomyopathy to the mice, and compare effects on heart function with those of SGLT2 inhibitors.
A key aspect of our clinic is patient education. We find that our patients are extremely enthusiastic to join our study, learn more about their disease, and contribute to finding a solution for all. We are launching an awareness campaign to make the public more aware of this condition, which will also help recruit patients. As our project includes pre-clinical work, alongside two clinical cohorts, and has engaged hospital and Local Health District senior administration, we are in a strong position to take forward any potential new therapies into human clinical trials, and to contribute to local policy-making regarding diagnosis and treatment of this condition.