[Pathophysiology of chronic heart failure]

Heart failure is a progressive and often fatal disease process. In general, the pathophysiologic mechanisms responsible for progressive myocyte dysfunction and cell loss, cardiac remodeling and arrhythmias involve signaling mechanisms that alter myocardial gene expression. These changes in gene expression are complex and involve contractile proteins, ion channels, Ca(++) handling, apoptosis, cell metabolism, the extracellular matrix, signal transduction pathways and growth factors. In the failing heart, several changes occur in cardiac adrenergic receptor-signal transduction pathways. The most striking of these changes occur in beta-adrenergic receptors, and of the changes in beta-adrenergic receptors beta1-receptor down-regulation is the most prominent. Other changes include uncoupling of beta2-adrenergic receptors and increased activity of the inhibitory G-protein. Most of these changes appear to be related to increased activity of the adrenergic nervous system, i.e. increased exposure to norepinephrine. Antagonists of the adrenergic nervous system may improve left ventricular function and outcome in patients with heart failure. This fact supports the notion that activation of these neurohormonal systems exerts a net long-term detrimental effect on the natural history of chronic heart failure and that myocardial adrenergic desensitization phenomena are at least partially maladaptive in the setting of left ventricular dysfunction. In addition to functional alterations structural remodeling plays a major role in the progression of various heart diseases to congestive heart failure. Major contributors to this remodeling process in the heart include alterations in myocyte shape, myocyte number and extracellular matrix. However, it is unclear as to which of these changes is most critical in the development of congestive heart failure, and this may vary by etiology.