BACKGROUND Although heart rate variability (HRV) at 0.1 Hz has been proposed as a noninvasive clinical measure of cardiac sympathetic nerve firing, this premise has not been sufficiently validated by comparison with techniques such as microneurography and the measurement of norepinephrine spillover from the heart that more directly reflect presynaptic sympathetic activity. METHODS AND RESULTS We compared the three techniques under conditions of effective cardiac sympathetic denervation, pure autonomic failure (n = 4), dopamine beta-hydroxylase deficiency (n = 1), and after cardiac transplantation (n = 9) as well as in the context of sympathetic nervous activation in cardiac failure (n = 15) and with aging (n = 10). Age-matched comparisons were made in each case with healthy individuals drawn from a pool of 52 volunteers. In pure autonomic failure and early after transplantation, cardiac norepinephrine spillover was negligible, and HRV was low. Late after transplantation, however, cardiac norepinephrine spillover returned to normal levels, and HRV remained low. In comparison to younger subjects (18 to 35 years old), older individuals (60 to 75 years old) had higher muscle sympathetic nerve activity (young, 22.9 +/- 1.9; old, 31.3 +/- 5.8 bursts per minute; P < .05) and cardiac norepinephrine spillover (young, 14.3 +/- 2.5; old, 20.1 +/- 3.0 ng/min; P < .05). In contrast, total HRV was reduced by 89%, and at 0.1 Hz it was reduced by 93% (P < .05). Cardiac failure was also characterized by elevated cardiac norepinephrine spillover (cardiac failure patients, 59 +/- 4; healthy volunteers, 18 +/- 3 ng/min; P < .01) but reduced 0.1 Hz HRV (cardiac failure patients, 49 +/- 17; healthy volunteers, 243 +/- 4 ms2; P < .05). CONCLUSIONS HRV at 0.1 Hz depends on factors in addition to cardiac sympathetic nerve firing rates, including multiple neural reflexes, cardiac adrenergic receptor sensitivity, postsynaptic signal transduction, and electrochemical coupling, and is not directly related to cardiac norepinephrine spillover, which is a more direct measure of the sympathetic nerve firing rate.

Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder. Epinephrine is released from the heart at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks. Contrary to popular belief, the sympathetic nervous system is not globally activated during panic attacks.

Key Points Question Does a shared decision support intervention for patients considering destination therapy left ventricular assist device (DT LVAD) improve decision quality compared with usual care? Findings In this multicenter randomized stepped-wedgeclinical trial of 248 patients being considered for DT LVAD, compared with patients in the usual care control period, patients enrolled in the intervention period had significantly better knowledge and higher concordance between stated values and patient-reported treatment choice. Meaning An intervention supporting shared decision making for DT LVAD was associated with improved patient decision quality.

Reduced norepinephrine reuptake increases the overflow of the neurotransmitter to plasma from the aging heart during stimulation of the cardiac sympathetic outflow. Failure of transmitter inactivation at postjunctional receptors with aging would amplify the neural signal, and in the presence of myocardial disease could trigger adverse stress-induced cardiovascular events, particularly when accompanied by an age-dependent reduction in vagal tone. Reduction of postsynaptic adrenergic responsiveness with aging, however, might protect against this, as indicated by our finding that in no case was the heart rate increase during stress greater in older men, despite their having larger increases in cardiac norepinephrine spillover.