William Bayliss and Ernest Starling are famous as pioneers in cardiovascular physiology but are also responsible the discovery of the first hormone (from the Greek “setting in motion”), the intestinal signalling molecule and neuropeptide secretin in 1902¹. My research group focuses on neuropeptides and neuromodulators that influence cardiovascular autonomic control as potential biomarkers in disease and tractable targets for therapeutic intervention. Acute myocardial infarction (AMI) and chronic systolic heart failure (CHF) result in high levels of cardiac sympathetic stimulation, which is a poor prognostic indicator. Whilst beta-blockers improve mortality in these conditions by preventing the action of the neurotransmitter noradrenaline, a substantial residual risk remains. Recently, we have identified the sympathetic co-transmitter neuropeptide-Y (NPY) as being released during AMI, leading to larger infarcts² and life-threatening arrhythmia³ in both animal models and patients. Moreover, in patients with severe CHF, local cardiac NPY levels correlate with mortality⁴. I will present recently published and unpublished data demonstrating that peripheral venous NPY levels are associated with heart failure hospitalisation and mortality after AMI⁵, and all cause and cardiovascular mortality in CHF, even when adjusting for known risk factors (including BNP). We have investigated NPY expression in human and rat stellate ganglion and cardiac tissue and used human induced pluripotent stem cell (hiPSC) cardiomyocytes to manipulate NPY neurochemistry using state-of-the-art imaging techniques, establishing the receptor pathways responsible for NPY signalling. We propose NPY as a new mechanistic biomarker in AMI and CHF patients and aim to determine whether specific NPY receptor blockers can attenuate the development of heart failure.