Swapping the heart’s energy source to treat heart failure

Altering substrate selection as a potential therapeutic target in heart failure (Dr William Watson)

Regardless of cause, most heart diseases ultimately result in the heart being unable to pump out as much blood as a normal heart can, because it can’t contract as forcefully. To contract, the heart needs an energy source called ATP, and it’s thought that a reduction in levels of ATP could be the final route to heart failure. ATP is produced in the heart by an enzyme called creatine kinase, which breaks down a source material called phosphocreatine. However, the heart has a flexible metabolism, and will alter its preferred choice of energy source under different conditions. This prompted Dr Oliver Rider to see whether altering the heart’s energy source could be a viable treatment option for people with heart failure. He is now supervising a BHF Clinical Research Training Fellowship to conduct a study in healthy volunteers and people with heart failure. They will use cardiac magnetic resonance imaging (MRI) and spectroscopy techniques (which measure heart metabolism) to compare heart function in participants when the levels of fatty acids and glucose in the heart are altered. Dr Rider has previously shown that different energy sources can alter metabolism in the hearts of mice, and has identified a potential molecule that could be central to the process. This study will build on these results and could lead to new treatments for people with heart failure.