Dear Colleagues,

Metabolic derangements have long been recognized as playing an important role in the pathophysiology of coronary disease and heart failure. In these conditions, metabolic impairment is not just a feature of the heart, but rather a global issue with important contributions from organs and peripheral tissues. In particular, diabetes mellitus doubles the cardiovascular death rate in patients with coronary artery disease and heart failure, compared to non-diabetic patients. Accelerated atherogenesis mediated by altered cellular metabolism is the likely cause of this association. In fact, ischemic metabolic changes that occur as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the metabolic changes inherent to diabetes itself. Increased utilization of free fatty acid and the reduced utilization of glucose as source of energy during stress and ischemia are responsible for the increased susceptibility of the diabetic heart to myocardial ischemia and to a greater decrease of myocardial performance for given amounts of ischemia compared to non-diabetic hearts. 

From a general point of view, the cardiac ability to oxidize nutrients critical to cardiac contraction is diminished in these pathological conditions, making the heart energy depleted. In this context, therapeutic approaches aimed at improving cardiac metabolism through manipulations of the utilization of metabolic substrates should help offset myocardial ischemia and heart failure. Specific metabolic drugs have been shown to improve global cardiac metabolism and, consequently, to increase cardiac resistance to ischemia and to reduce the decline of left ventricular function due to chronic under-perfusion and repetitive episodes of myocardial ischemia. Therefore, modulation of myocardial metabolism should represent a key target in patients with coronary artery disease and heart failure. 

In this special issue of Reviews in Cardiovascular Medicine, the functional and metabolic correlates of coronary disease and heart failure will be analyzed from different angles. The aim is to disseminate in the cardiological/internal medicine audience the important, but often neglected, concept of metabolic derangement as a major contributing factor to the pathophysiology of these diseases.

Dr. Gabriele Fragasso

Guest Editor