ADVERSE CONSEQUENCES OF HIGH SYMPATHETIC NERVOUS ACTIVITY IN THE FAILING HUMAN HEART

Objectives. In view of previous experimental evidence relating sympath etic nervous overactivity in the heart to myocardial necrosis and vent ricular arrhythmias, we prospectively examined the hypothesis that hei ghtened cardiac sympathetic nervous activity is associated with an adv erse outcome in patients with moderate to severe heart failure. Backgr ound. Despite recent therapeutic advances, patients with heart failure continue to have high mortality from progressive hemodynamic decompen sation and lethal ventricular arrhythmias. It is believed that initial ly compensatory increases in sympathetic nervous system activity may u ltimately be maladaptive, potentially contributing to subsequent adver se events. Methods. Sixty patients with moderate to severe heart failu re (left ventricular ejection fraction 18.9 +/- 0.9% [mean +/- SEI]) w ere studied prospectively. In addition to the compilation of a hemodyn amic, biochemical and electrocardiographic profile for each patient, w hole-body and cardiac sympathetic activity were determined by isotope dilution. The relation of these variables to outcome was determined by Cox proportional hazards analysis. Results. The mean follow-up period of the study group was 7 +/- 1 months (range 1 to 24) with a 12-month actuarial survival of 75%. Deaths (14 in all) were accounted for eith er by sudden death or progressive heart failure in equal numbers. The rate of release of norepinephrine from the heart was significantly hig her in patients with heart failure than in healthy subjects (402 +/- 3 7 vs. 105 +/- 19 pmol/min, p < 0.01), although the values for heart fa ilure ranged widely from normal to 10 times normal. By univariate Cox proportional hazards analysis, pulmonary capillary wedge pressure (p < 0.01), mean pulmonary artery pressure (p < 0.001), serum sodium level s (p < 0.01) and cardiac norepinephrine spill-over rate (p < 0.001) we re identified as significant prognostic markers. In a multivariate ana lysis, cardiac norepinephrine spillover rate was identified as the mos t powerful prognostic marker (p = 0.0006) of those evaluated in this s tudy. Conclusions. These results suggest that activation of the sympat hetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis assoc iated with severe heart failure. The data therefore provide a rational e for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure.