Metabolic rewiring of the failing heart: unravelling cause and effect

Heart failure (HF) currently affects more than 37 million people globally and is rising in prevalence. The 50% of HF patients who suffer from heart failure with preserved ejection fraction (HFpEF) also commonly present with accompanying diseases associated with the metabolic syndrome, such as obesity or type II diabetes. Changes in the cardiac fuel handling, or metabolism, are increasingly recognized as important in the development of HFpEF. However, their exact contribution remains unclear and therefore successful treatment strategies are lacking. This thesis expands the current knowledge of HF pathophysiology, in particular the contribution of cardiometabolic alterations in HFpEF development. The findings demonstrate that the cardiac metabolism is altered considerably in HFpEF associated with the metabolic syndrome, particularly affecting the mitochondrial metabolism within the heart. Moreover, modulating the metabolism of different cell types present in the heart can alter their functional characteristics, supporting the notion that cardiac metabolism is a target for HFpEF therapy