Increased Cardiac Adrenergic Drive Precedes Generalized Sympathetic Activation in Human Heart Failure

Abstract

Background Previous studies with radiotracer methods have indicated increases in cardiac norepinephrine (NE) and renal NE spillover in patients with severe congestive heart failure (CHF). However, data on the regional sympathetic profile in early stages of CHF are limited. In this study, sympathetic function in the heart, kidneys, and skeletal muscle was evaluated in patients with mild-to-moderate CHF and compared with 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 [ 3 H]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n=21) was increased threefold versus that in healthy 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 NE spillover and MSA were high compared with both mild-to-moderate CHF subjects and healthy subjects ( P <.05 for both). Fractional extraction of [ 3 H]NE across the heart was reduced by ≈40% in both CHF groups versus control subjects ( P <.05). Conclusions These results indicate a selective increase in cardiac adrenergic drive (increased amounts of transmitter available at neuroeffector junctions) in patients with mild-to-moderate CHF. This increase appears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF.