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 subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.

Background. Endothelial cells produce a number of substances, collectively termed endothelium-derived relaxing factor (EDRF), that promote local relaxation of vascular smooth muscle. Although studies have demonstrated defects in endothelium-dependent vasodilation in animal models of hypertension, atherosclerosis, and heart failure, there are only limited data from human subjects because of the difficulty in obtaining fresh vascular segments.Methods and Results. To address the hypothesis that endothelium-dependent vasodilation is attenuated in patients with heart failure, we measured forearm blood flow responses to the intra-arterial administration of methacholine, a known stimulus of EDRF release through muscarinic receptors. In 14 normal subjects, a dosage range of methacholine increased forearm blood flow by 5.26±+0.63, 10.50±0.63, and 13.22±0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98+±0.46, 5.48±0.79, and 8.50±+1.53 ml/min/100 ml FAV in 14 patients with heart failure. When pooled over all doses, the responses were strikingly less in the patients with heart failure (5.32+±0.31 versus 9.52+±0.60 ml/min/100 ml FAV; p=0.0003). In a second study, the average difference in forearm blood flow responses between patients with heart failure and normal subjects with methacholine was significantly greater than the average difference between the groups with nitroprusside (4.04±1.10 versus 2.20±0.71 ml/min/100 ml FAV; p=0.04). The decreased methacholine responses in the patients with heart failure were not related to age (r= 0.39; p=NS) or etiology because there was no difference in the responses between patients with ischemic heart disease and those with idiopathic cardiomyopathy.Conclusions. These data suggest that endothelium-dependent vasodilation is attenuated in patients with heart failure. Although the mechanisms of the decreased endothelium-dependent responses in heart failure are not known, this impaired local vasodilation may contribute to characteristic of heart failure. (Circulation

No abstract

This study describes a technique for determining arterial elastic properties and a model that can be used to estimate a number of mechanical parameters of the human brachial artery in vivo. This technique may be useful in studies of the arterial elastic properties of arteries in patients with vascular pathology.

VNS does not reduce the rate of death or HF events in chronic HF patients. (INcrease Of VAgal TonE in CHF [INOVATE-HF]; NCT01303718).

We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11±0.9 fmol/ml in NL and 71±9.9 in CHF (P < 0.01); the latter with twofold night ventricular increment (P < 0.05). In NL, ANF infusion of 0.10 ig/ kg per min (40 pmol/kg per min) induced increases (P < 0.05) of absolute (from 160±23 to 725±198 iseq/min) and fractional(1-4%) sodium excretion, urine flow rate (from 10±1.6 to 20±2.6 ml/min), osmolar (from 3.2±0.6 to 6.8±1.2 ml/min) and free water (from 6.8±1.6 to 13.6±1.6 ml/min) clearances, and filtration fraction (from 20±1 to 26±2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P < 0.01). Systolic blood pressure fell (from 112±3 to 104±5 mmHg, P < 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11±1 to 7±1 mmHg, P < 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P < 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P < 0.05) but not in CHF.

Supplemental oral L-arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral L-arginine and to identify mechanisms of action in patients with heart failure.