INCREASED CARDIAC ADRENERGIC DRIVE PRECEDES GENERALIZED SYMPATHETIC ACTIVATION IN HUMAN HEART-FAILURE

Background Previous studies with radiotracer methods have indicated in creases in cardiac norepinephrine (NE) and renal NE spillover in patie nts with severe congestive heart failure (CHF). However, data on the r egional sympathetic profile in early stages of CHF are limited. In thi s study, sympathetic function in the heart, kidneys, and skeletal musc le was evaluated in patients with mild-to-moderate CHF and compared wi th that in patients with severe CHF and healthy subjects. Methods and Results Total body and regional NE spillover from the heart and kidney was assessed with isotope dilution with steady state infusions of [H- 3]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (M SA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n=21) was increased threefold versus that in hea lthy subjects (n=12, P<.05), whereas total body and renal NE spillover and MSA did not differ from those in healthy subjects. In the severe CHF group (n=12), cardiac NE spillover was increased fourfold (P<.05), and total body and renal ME spillover and MSA were high compared with both mild-to-moderate CHF subjects and healthy subjects (P<.05 for bo th). Fractional extraction of [3H]NE across the heart was reduced by a pproximate to 40% in both CHF groups versus control subjects (P<.05). Conclusions These results indicate a selective increase in cardiac adr energic drive (increased amounts of transmitter available at neuroeffe ctor junctions) in patients with mild-to-moderate CHF. This increase a ppears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF.