The symptoms of heart failure (HF) can result broadly either from reduced systolic function, an inability to effectively pump blood around the body (Heart Failure with preserved Ejection Fraction, HFrEF) or from abnormal diastolic function in the presence of a preserved ejection fraction (termed HF with Preserved Ejection Fraction, HFpEF). This is the inability of the heart muscle to relax and adequately fill with blood prior to the pumping action. While proven therapy is available for HFrEF, no effective treatments have been developed for HFpEF, in which increased heart muscle stiffness is the key feature. Importantly, it is projected that HFpEF will become the most common form of heart failure in the next 5 years and as such there is an urgent need to develop effective treatments.
A. A stiff heart causes higher pressures in the ventricle during diastole. B. Patients with HFpEF have high pressures in the heart and lungs during exercise due to increased cardiac stiffness.
Our group is investigating the physiological and molecular mechanisms involved in the development of HFpEF, determining targets with therapeutic potential and developing new and effective, clinically applicable therapies for the prevention and treatment of this form of cardiac dysfunction. Apart from cardiac fibrosis we are investigating other targets that can potentially improve cardiac function.
- Inhibition of phosphodiesterases
Studies performed in heart cells and animals are investigating the effects of various treatments on heart function. Some of these studies have already extended to the clinic.
- Effects of exercise training
Extensive evidence shows that exercise can improve heart function in HF. We are investigating the mechanisms responsible for this in animal studies of various forms of HF.