Various causes of cardiac dysfunction lead to heart failure and they need to be managed differently depending on the cause. Heart failure has a major impact on a patient’s quality of life, resulting in a large health care burden (approximately $2 billion annually in Australia), and is associated with a mortality rate of approximately 50% after 5 years. Ultimately, the only effective treatment for end-stage heart failure is heart transplantation. Our research focusses on the development of new therapeutics to improve heart function and better treatments for patients with heart failure, which can impact people at all stages of life.
Despite substantial improvements in the management of cardiovascular disease over recent decades, heart disease remains the leading cause of death worldwide. Our research has a major focus on understanding heart failure and developing new treatments for this disease.
Heart failure with reduced ejection fraction (HFrEF) is a major event, such as a heart attack, that can cause substantial death of the contractile muscle cells in the heart (cardiomyocytes). Being one of the least regenerative organs in the body, the adult heart is unable to replenish these lost cardiomyocytes. This leads to the placement of these lost cardiomyocytes with non-contractile fibrotic scar tissue, which is stiff and decreases the heart’s performance and also increases the risk of patients having fatal arrhythmia.
Heart failure with preserved ejection fraction (HFpEF) is a form of heart disease that has been steadily increasing in prevalence over the past few decades and has recently become the most prominent form. In HFpEF, the heart still expels what is considered a ‘normal’ fraction of its blood with each contraction, unlike the form of heart failure mentioned above. In HFpEF, relaxation is the issue – the heart relaxes too slowly/not enough and does not fill up with enough blood. There are a variety of risk factors associated with HFpEF, including (but not limited to) ageing, high blood pressure, obesity, diabetes and a sedentary lifestyle. However, the precise molecular mechanisms driving this disease are still being unravelled.
Cardiac injury, damage and dysfunction can be caused by severe inflammatory diseases, such as COVID-19. Improving heart function and limiting damage may be an important therapeutic avenue in improving survival in some of these conditions.
Mutations in some genes (also referred to as genetic heart diseases) can cause a form of heart disease or heart failure in patients known as dilated cardiomyopathy. Genetic analysis has revealed that mutations in some genes such as TITIN or LAMNIN-A can predispose patients to this disease, however, more work is required to ascertain the precise mechanisms driving this disease.
Iron metabolism defects can have widespread health problems and can be caused by iron deficiency or iron overload. Both of these are linked to heart failure. Iron plays a key role in metabolic processes and energy production and due to the high energy demand of the heart, iron disorders have a particularly negative impact on heart function.