Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p=9.0001), plasma atrial natriuretic factor (p<0.0001), plasma arginine vasopressin (p=0.006), and plasma renin activity (p=0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p<0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy. (Circulation 1990;82:1724-1729 C ongestive heart failure is a complex clinical syndrome with varying pathophysiology and clinical expression. It is well known that overt heart failure is characterized by activation of several neuroendocrine systems.' Plasma norepinephrine (PNE)2 and plasma atrial natriuretic factor (ANF)3 are increased and known to be prognostic factors in patients with heart failure. Activation of the renin-angiotensin system is common in patients with advanced heart failure. Angiotensin converting enzyme inhibitor therapy improves survival in patients with advanced heart failure,4 suggesting that

In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Nesiritide is useful for the treatment of decompensated congestive heart failure.

These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.