Heart failure is conventionally attributed to direct alterations in cardiac myocyte contractile function. However, therapeutic attempts to improve pump function appear to have little effect on the long-term outcome of the disease. Attention is now focusing on a possible role of the coronary microcirculation, impairment of which would result in alterations in extravascular compressive forces that could limit dilation of intramural coronary resistance vessels. This hypothesis is borne out by findings of marked reduction of endocardial-epicardial distribution of myocardial perfusion in the failing heart, and, in various models of heart failure, of blunted endothelium-dependent vasodilator responses and augmented constriction in coronary arterioles. This could result in impaired or even insufficient vasodilation at the microvascular level and, in turn, in myocyte death and patchy fibrosis, both of which are frequently observed in heart failure...