Plasma Norepinephrine as a Guide to Prognosis in Patients with Chronic Congestive Heart Failure

Abstract

Hemodynamics, plasma norepinephrine, and plasma renin activity were measured at supine rest in 106 patients (83 men and 23 women) with moderate to severe congestive heart failure. During follow-up lasting 1 to 62 months, 60 patients died (57 per cent); 47 per cent of the deaths were sudden, and 45 per cent were related to progressive heart failure. Statistically unrelated to the risk of mortality were cause of disease (60 patients had coronary disease, and 46 had cardiomyopathy), age (mean, 54.8 years), cardiac index (mean, 2.11 liters per minute per square meter of body-surface area), pulmonary wedge pressure (mean, 24.5 mm Hg), and mean arterial pressure (mean, 83.2 mm Hg). A multivariate analysis of the five significant univariate prognosticators--heart rate (mean, 84.4 beats per minute), plasma renin activity (mean, 15.4 ng per milliliter per hour), plasma norepinephrine (mean, 700 pg per milliliter), serum sodium (mean, 135.7 mmol per liter), and stroke-work index (mean, 21.0 g-meters per square meter)--found only plasma norepinephrine to be independently (P = 0.002) related to the subsequent risk of mortality. Norepinephrine was also higher in patients who died from progressive heart failure than in those who died suddenly. These data suggest that a single resting venous blood sample showing the plasma norepinephrine concentration provides a better guide to prognosis than other commonly measured indexes of cardiac performance.

β-adrenoceptor blocker treatment and the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure

“…Thus, numerous studies have shown that plasma noradrenaline levels are elevated in CHF patients (Cohn 1990). The increase in plasma noradrenaline levels, that has been taken as a guide to prognosis for these patients (Cohn et al 1984), is caused by an enhanced cardiac noradrenaline spillover due to the increased sympathetic drive to the heart (for review, see Esler et al 1997) and a decreased activity and density of the neuronal noradrenaline re-uptake transporter (uptake 1 ; Böhm et al 1995;Eisenhofer et al 1996). Accordingly, myocardial catecholamine stores are depleted in CHF patients (Chidsey and Braunwald 1966).…”

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance

“…Plasma norepinephrine is a potent prognostic factor in HF,4, 5 and the increase in plasma norepinephrine is one of the reasons for the use of beta blockers in HF. However, norepinephrine spillover is a stronger predictor of outcome than plasma norepinephrine 7…”

“…Plasma norepinephrine is a systemic prognostic marker,4, 5 but cardiac uptake of the norepinephrine analogue iodine‐123–labelled meta ‐iodobenzylguanidine ( 123 I‐ m IBG) allows more direct assessment of cardiac denervation which has a greater prognostic value in HF patients 6, 7…”

Targeting GRK2 by gene therapy for heart failure: benefits above β-blockade

“…7 Indeed, plasma norepinephrine levels are known to be significantly correlated to HF mortality. 8 In addition to the AR changes seen in the SNS, the density and signaling of ARs in myocardium are significantly altered in HF because of chronic catecholamine exposure and the actions of GRK2. [1][2][3] In cardiac myocytes, b 1 -and b 2 -ARs are desensitized and b 1 ARs additionally downregulated, leading to an overall loss in contractile stimulatory capacity of compromised myocardium through defective cyclic AMP signaling and Ca 2+ handling.…”