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Biomedical subjects

E A Espiner

Publications and source records attributed to E A Espiner.

At least 19 recordsLinked to original sources
PubMed2003

Outcome from surgical management of secretory pituitary adenomas in Christchurch, New Zealand.

BACKGROUND: Recent evidence has highlighted the importance of the neurosurgeon in the management of secretory pituitary tumours, but most reports are from major centres. AIMS: To audit the surgical outcome of patients with acromegaly and Cushing's disease treated in a small centre (Christchurch, New Zealand) by a dedicated neurosurgeon with an interest in pituitary disease, and follow-up through an outpatient Department of Endocrinology. METHODS: All cases of acromegaly and Cushing's disease admitted for surgery in Christchurch Hospital between 1984 and 2000 were audited. Data concerning preoperative findings, surgical remission rate, complications and follow-up were obtained from 44 patients (28 acromegaly, 16 Cushing's disease). RESULTS: Of the 28 acromegalic patients, 14 patients (50%) had a mean growth hormone level <2.5 micro g/L within the first postoperative week. Of the 15 Cushing's disease patients in whom the pituitary fossa was explored, 13 patients (87%) entered a postoperative remission, defined as an 08.00 h cortisol <200 nmol/L (normal range 250-800 nmol/L). No perioperative deaths occurred. Two of the 43 patients (4.7%) developed permanent diabetes insipidus, while eight of the 28 patients who were operated on for acromegaly (29%) eventually required some replacement treatment for hypopituitarism during follow-up (one presented with apoplexy and seven were treated with postoperative radiotherapy). CONCLUSION: In a small centre with a dedicated pituitary surgeon, operative remission rates approach those obtained in larger, more specialized centres. However, given New Zealand's small, but geographically spread population, consideration should be given to establishing one or two units for the surgical management of secretory pituitary adenomas.

Acromegaly↗
PubMed2003

An unusual cause of hyperinsulinaemic hypoglycaemia syndrome.

Endogenous hyperinsulinism as a cause for hypoglycaemia can be attributed to a number of different causes including insulinoma, sulphonylurea drugs and the newly described disorder non-insulinoma pancreatogenous hypoglycaemia (NIPH). The calcium stimulation test is increasingly used as a method for not only localizing insulinoma but also for distinguishing the above entities. We describe a case in which felonious sulphonylurea administration was used to mimic either an insulinoma or NIPH. Importantly, this case demonstrates that, contrary to previous reports, the insulin response to calcium stimulation in such cases may be uniformly positive and should alert the physician to possible surreptitious sulphonylurea ingestion.

Calcium↗
PubMed2003

Predicting surgically remedial primary aldosteronism: role of adrenal scanning, posture testing, and adrenal vein sampling.

Distinguishing surgically remedial forms from other causes of primary aldosteronism (PA) may be difficult, and it is made more challenging by the earlier detection of milder disease. The technical demands of bilateral adrenal vein sampling (AVS)-increasingly advocated for localizing a unilateral autonomous lesion (UAL)- and lack of agreed criteria for establishing unilateral autonomy, add further to the diagnostic challenge. This retrospective review of 49 hypokalemic patients with unequivocal PA (41 with surgically proven and remedial UAL, eight patients with bilateral adrenal hyperplasia) analyzes the value of computerized tomography adrenal scanning (n = 32), 4 h erect posture testing (n = 42), and AVS (n = 27) in predicting and lateralizing a surgically remedial lesion. A fall in plasma aldosterone during 4 h erect posture (positive test) occurred in 63% of patients with UAL and in none with bilateral adrenal hyperplasia. A positive posture test or computerized tomography adrenal scan (single focal macroadenoma) both had high positive predictive value (100% and 89% respectively), but low sensitivity for diagnosis of UAL. AVS, undertaken during low dose ACTH stimulation, localized the UAL in all cases (positive predictive value 100%) where the aldosterone/cortisol ratio of blood drawn from the uninvolved gland was less than that of peripheral blood (contralateral ratio <1). Biochemical severity, reflected by overnight supine plasma aldosterone, was strongly correlated with the degree of contralateral gland suppression (n = 16, r = 0.79, P < 0.001). Importantly, the AVS findings show that when bilateral access is not possible, UAL can be successfully lateralized when only one adrenal vein (the contralateral) is accessed, or the ipsilateral vein is sampled in subjects whose posture test was positive. In this series of patients with overt (hypokalemic) PA, preoperative testing successfully identified a surgically remedial lesion in 39 of 41 cases. Confirmation of the recommended diagnostic approach must now await larger prospective studies.

Adenoma↗
PubMed2001

Identification of amino-terminal pro-C-type natriuretic peptide in human plasma.

We report the first identification of a circulating peptide from the amino-terminal end of proCNP. A specific radioimmunoassay was established based on antisera to the synthetic peptide proCNP(1-15). Extracts of plasma, drawn from patients with congestive heart failure or from sheep with experimental heart failure, were subjected to size exclusion and reverse-phase high-pressure liquid chromatography (HPLC) coupled to radioimmunoassay (RIA). These studies revealed the presence of an immunoreactive peptide with a molecular weight (M(r) approximately 5 kDa) similar to that expected for NT-proCNP(1-50), a potential fragment released during processing of pro(CNP). The same material was isolated from extracts of homogenized ovine pituitary, a tissue known to be a relatively enriched source of CNP. Plasma NT-proCNP levels in 22 patients with congestive heart failure (9.7 +/- 0.5 pmol/L, mean +/- SEM, range 5.4-13.7 pmol/L) were raised (P = 0.003) compared to those in 16 healthy volunteers (7.4 +/- 0.3 pmol/L, range 5.7-10.7 pmol/L) and were higher than levels reported for CNP in similar subjects. This first identification of circulating NT-proCNP opens the possibility of studying the factors regulating CNP production and metabolism in vivo.

Animals↗
PubMed2001

Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.

OBJECTIVES: We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo. BACKGROUND: Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported. METHODS: Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients' clinical outcomes, induding mortality and heart failure events, were recorded for 18 months. RESULTS: Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2-10.9] and 3.92 [1.76-8.7], respectively) and hospital admission with heart failure (4.7 [2.2-10.3] and 2.4 [1.3-4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value. CONCLUSIONS: In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.

Adrenergic beta-Antagonists↗
PubMed2001

C-type natriuretic peptide expression in olfactory regions of rat brain is modulated by acute water deprivation, salt loading and central angiotensin II.

To elucidate the central role of c-type natriuretic peptide (CNP), levels of CNP mRNA in control rat brain were compared with levels following acute water deprivation, salt loading and central administration of angiotensin II (AII), using Northern blot and in situ hybridisation. Rats with water deprivation (WD) had no access to water for 48 h, rats with salt loading (SL) had access to 2% saline for 48 h, and control rats had free access to water. Both WD and SL significantly raised plasma sodium (Na). Levels of CNP mRNA in olfactory regions were significantly decreased in WD and increased in SL. In the medulla, WD and SL both increased CNP mRNA, but levels of CNP mRNA elsewhere in the brain were not significantly altered. Intracerebroventricular AII (500 ng) increased water intake, and induced a significant increase in CNP expression at 4 h in olfactory regions, but not in other brain sites. In summary, CNP expression is regulated in olfactory regions of the rat brain in response to acute challenges to water and salt balance and by central AII.

Angiotensin II↗
PubMed2000

Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations.

BACKGROUND: There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen. METHODS: 69 patients with impaired systolic function (left-ventricular ejection fraction <40%) and symptomatic heart failure (New York Heart Association class II-IV) were randomised to receive treatment guided by either plasma N-BNP concentration (BNP group) or standardised clinical assessment (clinical group). FINDINGS: During follow-up (minimum 6-months, median 9.5 months), there were fewer total cardiovascular events (death, hospital admission, or heart failure decompensation) in the BNP group than in the clinical group (19 vs 54, p=0.02). At 6 months, 27% of patients in the BNP group and 53% in the clinical group had experienced a first cardiovascular event (p=0.034). Changes in left-ventricular function, quality of life, renal function, and adverse events were similar in both groups. INTERPRETATION: N-BNP-guided treatment of heart failure reduced total cardiovascular events, and delayed time to first event compared with intensive clinically guided treatment.

Adult↗
PubMed2000

Neurohormones in an ovine model of compensated postinfarction left ventricular dysfunction.

Clinical heart failure, often the result of myocardial infarction, may be preceded by a period of compensated left ventricular impairment. There is substantial need for an experimental model that reflects this human condition. In sheep, coronary artery ligation produced consistent left ventricular anteroapical myocardial infarctions resulting in chronic (5 wk), stable hemodynamic changes compared with sham controls, including reductions in ejection fraction (51 +/- 2 vs. 30 +/- 5%, P < 0.001), cardiac output (6.3 +/- 0.2 vs. 5.1 +/- 0.2 l/min, P < 0.01), and arterial pressure (93 +/- 2 vs. 79 +/- 3 mmHg, P < 0.001), and increases in cardiac preload (left atrial pressure, 3.3 +/- 0.1 vs. 8.3 +/- 1.3 mmHg, P < 0.001). These changes were associated with acute and sustained increases in plasma concentrations of atrial natriuretic peptide (ANP; 5 wk, 11 +/- 2 vs. 27 +/- 5 pmol/l, P < 0.001), brain natriuretic peptide (BNP; 3 +/- 0.2 vs. 11 +/- 2 pmol/l, P < 0.001), and amino-terminal pro-brain natriuretic peptide (NT-BNP; 17 +/- 3 vs. 42 +/- 12 pmol/l, P < 0.001). Significant correlations were observed between plasma levels of the natriuretic peptides (ANP, day 7 to week 5 samples; BNP and NT-BNP, day 1 to week 5 samples) and changes in left ventricular volumes and ejection fraction. In contrast, renin activity, aldosterone, catecholamines, and endothelin were not chronically elevated postinfarction and were not related to indexes of ventricular function. Coronary artery ligation in sheep produces the pathological, hemodynamic, and neurohormonal characteristics of compensated left ventricular impairment secondary to myocardial infarction. Plasma concentrations of the cardiac natriuretic peptides are sensitive markers of left ventricular dysfunction. This is a reproducible model that reflects the clinical condition and should prove suitable for investigating the pathophysiology of, and experimental therapies in, early left ventricular dysfunction.

Aldosterone↗
PubMed2000

Deconvolution analysis of cardiac natriuretic peptides during acute volume overload.

Cardiac natriuretic peptides, especially amino terminal pro-Brain Natriuretic Peptide (NT-proBNP), are emerging as powerful circulating markers of cardiac function. However, the in vivo secretion and elimination (t1/2) of these peptides during acute volume overload have not been studied. We present the first report of the secretion and elimination of cardiac natriuretic peptides, based on deconvolution analysis of endogenous ovine plasma levels measured by specific radioimmunoassay. Four normal, conscious sheep underwent rapid right ventricular pacing (225 bpm) for 1 hour to stimulate acute cardiac natriuretic peptide release. Plasma samples and right atrial pressure measurements were taken at regular intervals 30 minutes before, during, and 4 hours after pacing. Baseline right atrial pressure significantly increased (P:=0.02) during the 1 hour of pacing in association with a prompt increase in plasma BNP (P:=0.03), atrial natriuretic peptide (P:=0.01), and NT-proBNP (P:=0.02). Deconvolution analysis showed that the t1/2 of NT-proBNP (69.6+/-10.8 minutes) was 15-fold longer than BNP (4.8+/-1. 0 minutes). Despite sustained increases in atrial pressure, cardiac secretion of natriuretic peptides (particularly atrial natriuretic peptide) fell during the pacing period, suggesting a finite source of peptide for secretion. Size-exclusion high-performance liquid chromatography revealed NT-proBNP to be a single immunoreactive peak, whereas BNP comprised at least 2 immunoreactive forms. These findings, especially the prompt secretion of BNP and the prolonged t1/2 of NT-proBNP, clarify the metabolism of BNP forms and help to explain the diagnostic value of NT-proBNP measurement as a sensitive marker of ventricular function.

Algorithms↗
PubMed2000

Beneficial renal and hemodynamic effects of omapatrilat in mild and severe heart failure.

Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that may offer benefit in the treatment of heart failure (HF) through simultaneous inhibition of angiotensin-converting enzyme and neutral endopeptidase. We examined the effects of omapatrilat in a placebo-controlled crossover study using a pacing model of HF. Seven sheep were paced sequentially at 180 bpm (mild HF) and then 225 bpm (severe HF) for 7 days each. Omapatrilat (0.005 mg/kg) or vehicle was administered by intravenous bolus on days 4 to 7 of each paced period. Omapatrilat lowered mean arterial and left atrial pressure and increased cardiac output acutely and chronically in both mild and severe HF (P<0.01 for all). Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely (P=NS), while brain natriuretic peptide increased after repeated dosing in severe HF (P<0.05). Plasma renin activity rose, whereas angiotensin II and aldosterone levels fell after acute and repeated dosing in both states (P<0.01 for all). Omapatrilat increased urinary sodium excretion by day 7 in both mild and severe HF (P<0.05). Effective renal plasma flow and glomerular filtration rate increased or were stable after omapatrilat in mild and severe HF after both acute and repeated dosing. Omapatrilat exhibited pronounced acute and sustained beneficial hemodynamic and renal effects in both mild and severe heart failure.

Aldosterone↗
PubMed2000

Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct.

Cardiac gene expression of atrial natriuretic peptide (ANP) and that of brain natriuretic peptide (BNP) are markedly elevated after myocardial infarction. The cellular distribution and temporal responses of ANP and BNP messenger RNA (mRNA) expression were compared by in situ hybridization for 5 weeks after left coronary artery ligation in sheep. Ligation resulted in highly reproducible, transmural, left ventricular infarcts. Within the infarct, ANP mRNA appeared from 7 days after ligation, whereas BNP expression was undetectable in the infarct at any time. The cells synthesizing ANP were shown by in situ hybridization and immunocytochemistry to be fibroblasts invading the infarct. The appearance of ANP expression coincided with the transition of these cells to the myofibroblast phenotype. Treatment of cultured cardiac fibroblasts with transforming growth factor-beta (10 ng/ml) induced the expression of alpha-smooth muscle actin, characteristic of the transformation to myofibroblasts, and raised ANP concentrations in the medium. In the surviving myocardium of the left ventricle, ANP and BNP expression increased in response to ligation, BNP mRNA was particularly strong at the lateral margins of the infarct. In both left and right atria, levels of BNP mRNA increased markedly over the first 18 h, whereas levels of atrial ANP mRNA decreased over 3 days after infarction. This is the first report of ANP expression and synthesis by cardiac fibroblasts invading the fibrotic scar, suggesting that ANP may be involved in regulating fibroblast proliferation during reparative fibrosis.

Animals↗
PubMed2000

Delayed metabolism of human brain natriuretic peptide reflects resistance to neutral endopeptidase.

Metabolism of natriuretic peptides is regulated by two degradative pathways: uptake by the clearance receptor (natriuretic peptide receptor C--NPR-C) and hydrolysis by neutral endopeptidase (NEP). Affinity studies favour a dominant role of NPR-C in hormone degradation in several species but do not account for the efficacy of NEP inhibitors in vivo, nor the uniquely prolonged half life (t((1/2))) of human brain natriuretic peptide (hBNP). Postulating that (1) delayed metabolism of hBNP reflects resistance to NEP and (2) interactions between NPR-C and NEP increase enzyme activity, we have used purified ovine and human NEP, plus ovine lung plasma membranes to study the relative importance of receptor and enzyme pathways. We have also related the findings to hormone metabolism in vivo. Binding affinities of atrial natriuretic peptide (ANP), hBNP and ovine BNP (oBNP) to oNPR-C were similar (K(d)=8-16 pM). In contrast, unlike ANP and oBNP, hBNP was not significantly degraded by purified oNEP or plasma membranes. Despite similar (and high) affinity of oNPR-C for oBNP and hBNP, the t((1/2)) of hBNP (12.7 min) was more than fourfold that of oBNP (2.6 min). Although we found no evidence for receptor-enzyme interaction, our results show that the delayed metabolism of hBNP reflects resistance to NEP. These findings have important implications for future treatment strategies in human disease.

Animals↗
PubMed1999

Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.

BACKGROUND: Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo. METHODS AND RESULTS: Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; P<0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; P<0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4. 0%; P<0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by >90% (P<0.001). CONCLUSIONS: Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of beta-blockade in heart failure.

Arginine Vasopressin↗
PubMed1999

The characterization of ovine genes for atrial, brain, and C-type natriuretic peptides.

The natriuretic peptides (NPs) play an important role in the homeostasis of blood pressure and sodium balance in all mammals studied to date. Their combined actions on the vasculature, kidneys, and adrenals reduce blood pressure and intravascular volume. In order to provide sequence information about the ovine NP genes for our physiological studies in sheep, we have determined the genomic DNA sequence of each of the NPs; atrial NP, brain NP (BNP), and C-type NP using an ovine genomic library. Strong homology with other species was found for ovine peptide and genomic sequences of atrial NP and for C-type NP. Further, despite previous reports of poor conservation of BNP across species, the peptide sequence for ovine BNP was found to be identical to both the 26 amino acid-residue porcine BNP, and the 35 amino acid peptide known as bovine aldosterone secretion-inhibitory factor. This data also revealed strong homology of BNP mature forms in dog, cow, pig, and sheep, thus permitting the use of porcine antisera to study BNP-level changes in sheep models of cardiac failure. This conservation of the BNP gene sequence suggests that BNP, like the other NPs, plays an important role in mammalian physiology.

Amino Acid Sequence↗
PubMed1999

Growth hormone binding protein correlates strongly with leptin and percentage body fat in GH-deficient adults, is increased by GH replacement but does not predict IGF-I response.

GH-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor (GHR) and has been shown to be closely related to body fat. This study aimed to examine the inter-relationship between GHBP, leptin and body fat, and to test the hypothesis that GHBP is modified by GH replacement in GH-deficient adults and predicts IGF-I response. Twenty adults, mean age 47 years (range 20-69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment. Plasma GHBP and leptin were measured at baseline and 2, 4, 8 and 12 weeks after each treatment. Whole body composition was measured at baseline by dual-energy X-ray absorptiometry (DEXA). There was a strong correlation between baseline leptin and GHBP (r = 0.88, P < 0.0001) and between baseline GHBP and percentage body fat, (r = 0.83, P < 0.0001). Mean GHBP levels were higher on GH compared with placebo, 1.53 +/- 0.28 vs 1.41 +/- 0.25nM, P = 0.049. There was no correlation between baseline IGF-I and GHBP (r = -0.049, P = 0.84), and GHBP did not predict IGF-I response to GH replacement. The close inter-relationship between GHBP, leptin and body fat suggests a possible role for GHBP in the regulation of body composition. GHBP is increased by GH replacement in GH-deficient adults, but does not predict biochemical response to GH replacement.

Absorptiometry, Photon↗
PubMed1999

Bioactivity of natriuretic peptide coinfusions; no evidence for unique effects of BNP in conscious sheep.

Few studies have addressed the possibility that brain natriuretic peptide (BNP) possesses a profile of bioactivity that is distinct from that of atrial natriuretic peptide (ANP). Accordingly, we assessed the biologic actions of BNP in the setting of maximal or near-maximal ANP-induced biologic activity. Background ANP infusions (7.5 pmol/kg/min) administered on all study days, increased plasma ANP (approximately 120 pM) and cyclic guanosine monophosphate (GMP) levels (approximately 40 nM), and induced significant decreases in arterial pressure and cardiac output associated with increased heart rate, hematocrit, diuresis, and natriuresis. Increasing the dose twofold after 1 h (experiment 1, n = 5) showed no enhancement of these actions despite a further twofold increase in plasma ANP and cyclic GMP (both p values <0.001). Addition of low-dose BNP (2 pmol/kg/min) after 1 h background infusion (experiment 2, n = 8), increased plasma BNP levels (30 pM, p < 0.001) but caused no significant effects on the hemodynamic, renal, or hormonal indices measured. In conclusion, in the setting of maximal hemodynamic, renal, and endocrine responses to high-dose background infusions of ANP, coinfusion of BNP exhibits no enhancement of, or additional, biologic activity. This study provides no evidence for unique short-term biologic actions of ANP and BNP.

Animals↗
PubMed1999

Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction. The Christchurch Cardioendocrine Research Group.

OBJECTIVE: To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction. DESIGN: Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1-4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3-5 months after infarction. Clinical events were recorded over a mean period of 14 months. RESULTS: Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = -0.60, n = 220, p < 0.001; and r = -0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death. CONCLUSIONS: Plasma BNP measured within 1-4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

Atrial Natriuretic Factor↗