Disturbances in cardiovascular neural regulation, influencing both disease course
and survival, progress as heart failure worsens. Heart failure due to left ventricular
systolic dysfunction has long been considered a state of generalized sympathetic activation,
itself a reflex response to alterations in cardiac and peripheral hemodynamics that
is initially appropriate, but ultimately pathological. Because arterial baroreceptor
reflex vagal control of heart rate is impaired early in heart failure, a parallel
reduction in its reflex buffering of sympathetic outflow has been assumed. However,
it is now recognized that: 1) the time course and magnitude of sympathetic activation
are target organ-specific, not generalized, and independent of ventricular systolic
function; and 2) human heart failure is characterized by rapidly responsive arterial
baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary
reflex modulation of MSNA, a cardiac sympathoexcitatory reflex related to increased
cardiopulmonary filling pressure, and by individual variation in nonbaroreflex-mediated
sympathoexcitatory mechanisms, including coexisting sleep apnea, myocardial ischemia,
obesity, and reflexes from exercising muscle. Thus, sympathetic activation in the
setting of impaired systolic function reflects the net balance and interaction between
appropriate reflex compensatory responses to impaired systolic function and excitatory
stimuli that elicit adrenergic responses in excess of homeostatic requirements. Recent
observations have been incorporated into an updated model of cardiovascular neural
regulation in chronic heart failure due to ventricular systolic dysfunction, with
implications for the clinical evaluation of patients, application of current treatment,
and development of new therapies.