Restoring healthy heart energy use with new treatments to improve health outcomes for people with stiff heart failure (HFpEF).
The growing burden of stiff heart failure in NSW
Stiff heart failure, also called heart failure with preserved ejection fraction (HFpEF), is now the most common type of heart failure, especially in older adults and people living with obesity, diabetes, or high blood pressure. In NSW, stiff heart failure is a major cause of hospitalisation and rising healthcare costs. Unlike other forms of heart failure, there are no effective treatments that directly target the processes driving the disease. One important factor is the heart’s reduced ability to generate and use energy, which contributes to fatigue, breathlessness, and poor quality of life. Our research will investigate a newly identified enzyme in the heart, called HMGCS2 Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2. This controls a key energy pathway. By targeting this pathway, we aim to discover new treatment strategies that could restore heart energy, improve patient outcomes, and reduce the growing impact of this condition on the NSW health system.
Enhancing a key energy pathway to restore cardiac function
We aim to test whether enhancing a key energy pathway in the heart can restore function and improve outcomes in stiff heart failure (HFpEF), which is a major cause of hospitalisation in NSW. Our research focuses on the HMGCS2 enzyme as research has recently shown it plays an important role in the heart by supporting energy production and clearing excess fat. Using well-established heart failure models and human heart samples, we will test if activating this enzyme improves heart function and reduces inflammation. We will also develop and test new drug candidates, aiming to guide future treatments for preserved ejection fraction.