He has made important contributions to translational physiology in man, linking basic mechanisms and whole body physiology and leading to novel therapies in heart failure and the cardiomyopathies. He demonstrated both the mechanism and prognostic significance of the paradoxical fall in blood pressure that is seen during upright exercise in patients with hypertrophic cardiomyopathy. This has had a lasting impact on the care of patients with this common and serious disease worldwide leading to improved risk factor stratification and clinical guidelines. The greatest impact of his work is in the pathophysiology of heart failure. By assessing the complex inter-dynamics between the chambers of the heart, preload and afterload, he has explained the descending limb of the Frank-Starling curve, brought understanding to the complex and clinically important topic of ventricular dys-synchrony, explored the impact of changes in endothelial function in the circulation and provided some of the first clinical evidence that metabolic manipulation in heart failure really works.