Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure

AbstractProposed reflex mechanisms for generalized neurohumoral activation in heart failure include decreased input from inhibitory baroreceptor afferent vessels and increased input from excitatory afferent vessels arising from arterial chemoreceptors, skeletal muscle metaboreceptors or the lungs. Not all subjects with left ventricular dysfunction have increased sympathetic nerve activity, but the magnitude of sympathoneural activation appears to independently predict survival. This association suggests both a causative mechanism linking sympathetic activation with adverse outcome and a therapeutic opportunity to improve the prognosis of such patients by inhibiting central sympathetic outflow.Generalized sympathetic activation is not unique to heart failure, and its functional consequences appear to be both organand condition-specific. Sympathetic activation is present in other disorders such as mild hypertension, cirrhosis and aging that do not share the dim prognosis of congestive heart failure. The adverse effects of adrenergic activation on the diseased myocardium may be a function of the magnitude and time course of increases in cardiac sympathetic nerve activity, the mechanical and electrophysiologic consequences of nonuniform abnormalities of sympathetic innervation in the failing heart and the absence of specific countervailing mechanisms present in other conditions also characterized by increased sympathetic traffic. The hypotheses that activation of adrenergic drive to the diseased myocardium is the causative mechanism linking sympathoexcitation to adverse outcome and that interventions that inhibit sympathetic outflow to the heart will improve the prognosis of patients with congestive heart failure have not been specifically tested. Greater understanding of the mechanisms responsible for the heterogeneity of sympathetic activation in response to ventricular dysfunction, for cardiac-specific and generalized activation of the sympathetic nervous system and for the stimulation or suppression of countervailing mechanisms capable of resisting its adverse effects is fundamental to the development of better therapies for congestive heart failure