Quarterly Focus Issue: Heart Failure
State-of-the-Art Paper
Sympathetic Nervous System Activation in Human Heart Failure: Clinical Implications of an Updated Model

https://doi.org/10.1016/j.jacc.2009.03.061Get rights and content
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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.

Key Words

baroreceptor reflex
exercise
heart failure
human
norepinephrine
sleep apnea
sympathetic nervous system

Abbreviations and Acronyms

BP
blood pressure
CNES
cardiac norepinephrine spillover
CPAP
continuous positive airway pressure
CSA
central sleep apnea
HF
heart failure
HR
heart rate
HRV
heart rate variability
LBNP
lower body negative pressure
MSNA
muscle sympathetic nerve activity
NE
norepinephrine
OSA
obstructive sleep apnea
RNES
renal norepinephrine spillover
TNES
total body norepinephrine spillover

Cited by (0)

Dr. Floras holds the Canada Research Chair in Integrative Cardiovascular Biology, is a Career Investigator of the Heart and Stroke Foundation of Ontario, and receives operating grant support from the Canadian Institutes of Health Research (MOP 82731; MOP 85052; MT 9721) and the Heart and Stroke Foundation of Ontario (PRG 5276; T4983; NA 6298; NA 6407) for studies of neural regulation of the circulation in human heart failure. He is a coinvestigator on a recently awarded Canadian Institutes of Health Research University–Industry operating grant to evaluate the treatment of sleep apnea in heart failure. Respironics is the industrial partner.