Heart failure with preserved ejection fraction (HFpEF) is an expanding global health challenge, already accounting for ~50% of heart failure cases and projected to reach two-thirds by 2050. This rise parallels increasing rates of obesity, diabetes, and hypertension, which are key drivers of HFpEF through interconnected metabolic, inflammatory, neurohormonal, and haemodynamic pathways that promote myocardial stiffness, endothelial dysfunction, and impaired cardiac metabolism.
While major advances in pharmacotherapy have transformed outcomes in heart failure with reduced ejection fraction, most therapies have not translated to HFpEF, reflecting its complex, multisystem nature and strong influence of extracardiac factors such as insulin resistance, adipose dysfunction, and systemic inflammation. Consequently, management has largely centred on lifestyle and comorbidity optimisation, although newer agents such as sodium–glucose cotransporter-2 inhibitors and, more recently, glucagon-like peptide-1 receptor agonists show emerging promise for improving HFpEF outcomes.
Using knowledge gained from the clinic, alongside cutting-edge technologies and drug discovery platforms, our lab is focused on uncovering novel HFpEF therapies that target the aforementioned pathways contributing to myocardial stiffening, endothelial dysfunction, and impaired cardiac metabolism, with the aim of slowing or reversing HFpEF pathology.
These therapies are subsequently evaluated using a suite of in vitro, ex vivo, and in vivo approaches to determine their effects on:
- cardiac hypertrophy and fibrosis
- cardiac and systemic inflammation
- systemic metabolic dysfunction
- renal and hepatic toxicity
- exercise tolerance
- hypertension
- Cardiac and vascular function.
Ultimately, our aim is to identify novel therapies that prevent, attenuate, or reverse the progression of HFpEF, improving patients’ quality of life and reducing heart failure–related hospitalisations.