N-terminal pro-atrial natriuretic peptide as a biochemical marker of long-term interventional success after radiofrequency catheter ablation of paroxysmal supraventricular tachyarrhythmias.

Radiofrequency (RF) catheter ablation has been shown to be highly effective in the treatment of supraventricular tachycardias. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart mainly in response to myocardial stretch induced by volume load. The aim of the present study was to determine the time course of the N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) in patients undergoing radiofrequency (RF) catheter ablation for paroxysmal supraventricular tachycardias. Serial blood samples were taken from 13 patients with symptomatic paroxysmal supraventricular tachycardias undergoing RF ablation and from 13 age- and gender-matched healthy controls. Blood was taken before ablation (day 0, baseline), and at day one and day 120 after ablation. Levels of NT-proANP were significantly higher before RF ablation (4862+/-726 pmol/l) as compared to day one (2021+/-220 pmol/l) and day 120 after RF ablation (2470+/-349 pmol/l) (with p<0.01 on day one and p<0.05 on day 120; n=13). The size of the left atrium decreased from 41.0+/-5.5 mm before ablation to 34.9+/-5.9 mm (n=13; p<0.05) on day 120 as measured by M-mode echocardiography. Levels of NT-proBNP showed comparable values before and on day one and day 120 after ablation and were not significantly elevated as compared to healthy controls. NT-proANP levels are increased in patients presenting with paroxysmal supraventricular tachycardias and decrease one day after radiofrequency catheter ablation, possibly reflecting a transient reduction of ANP secretion from injured myocardial cells. Lower NT-proANP levels in the long-term time course may result from reduction of atrial volume load and reconstitution of atrial architecture after successful treatment of supraventricular tachycardias. NT-proANP may serve as a useful laboratory marker to describe the long-term interventional success after RF ablation.     

Analytical performance and diagnostic accuracy of a fully-automated electrochemiluminescent assay for the N-terminal fragment of the pro-peptide of brain natriuretic peptide in patients with cardiomyopathy: comparison with immunoradiometric assay methods for brain natriuretic peptide and atrial natriuretic peptide.

We evaluated the analytical performance of a fully-automated electrochemiluminescence "sandwich" immunoassay method for the N-terminal fragment of the pro-peptide of brain natriuretic peptide (BNP). We then compared the diagnostic accuracy of this method in discriminating between normal subjects and patients with cardiomyopathy with that found with two previously described immunoradiometric assay methods for the assay of atrial natriuretic peptide (ANP) and BNP. We studied 193 consecutive patients (mean age 64.4 +/- 12.3 years, range 20-89 years, including 56 women and 137 men) with chronic cardiomyopathy and a group of 85 healthy subjects (mean age 52.3 +/- 12.0 years, 42 women and 43 men, range 20-79 years). N-terminal fragment of proBNP1-76 (NT-proBNP) was measured with a fully-automated "sandwich" electrochemiluminescence method using an Elecsys 2010 analyzer, while ANP and BNP were measured with immunoradiometric assay methods. The low detection limit of the NT-proBNP assay was 4.2 pg/ml (0.50 pmol/l), while the functional sensitivity was 22 pg/ml (2.60 pmol/l) with a working range (imprecision profile < or = 10% coefficient of variation) extended up to about 30 000 pg/ml (3540 pmol/l). Healthy women (64.3 +/- 41.6 pg/ml, 7.59 +/- 4.91 pmol/l) showed significantly higher values than men (46.9 +/- 30.9 pg/ml, 5.53 +/- 3.64 pmol/l, p = 0.0118). Moreover, age and sex were significantly and independently related to the NT-proBNP values in healthy subjects, as assessed by a multiple linear regression analysis (R = 0.389, F-value = 7.316, P-value = 0.0012). As expected, the NT-proBNP values of patients with cardiomyopathy were significantly higher than those of normal subjects and progressively increased with the severity of heart failure. The respective diagnostic accuracy of the ANP, BNP and NT-proBNP assays in discriminating between the group of normal subjects and that of patients with cardiomyopathy was tested by the response operating characteristic curve analysis. Our data indicated that the NT-proBNP assay is significantly better than either of the ANP or BNP immunoradiometric assays in discriminating affected patients from healthy subjects, especially when only patients with mild disease severity (New York Heart Association class I and II) are considered.     

Single assay for amino-terminal fragments of cardiac A- and B-type natriuretic peptides

BACKGROUND: High circulating concentrations of N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) identify patients with impaired cardiac function. ProANP-derived peptides are particularly sensitive to increased preload of the heart and proBNP-derived peptides to increased afterload; therefore, combining the information from the ANP and BNP systems into a single analyte could produce an assay with increased diagnostic and prognostic power. METHODS: We prepared a hybrid peptide containing peptide sequences from both NT-proBNP and NT-proANP (referred to as NT-proXNP) by recombinant techniques and used it to develop a RIA combining weighed concentrations of NT-proANP and NT-proBNP into a new virtual analyte, NT-proXNP. We used the novel method to measure the circulating concentrations in healthy persons and in patients with cardiac disorders. We also characterized the assay by HPLC analysis of the immunoreactive molecular forms in human plasma and serum. RESULTS: The results from the novel assay correlated well with independent home-made NT-proANP and NT-proBNP assays (r2 = 0.75-0.85) as well with the arithmetic sum of NT-proANP and NT-proBNP (r2 = 0.92). Patients with valvular heart disease (VHD) and coronary artery disease (CAD) had significantly increased NT-proXNP concentrations. The areas under the curve (AUC) of the NT-proXNP assay in detecting VHD and CAD (0.961 and 0.924, respectively) were significantly larger than the AUC of either NT-proANP (0.947 and 0.872) or NT-proBNP (0.913 and 0.782) assays. HPLC analysis showed that the novel NT-proXNP assay detects two major classes of circulating immunoreactivity corresponding to peptides derived from NT-proANP and NT-proBNP. CONCLUSIONS: Our novel immunoassay mimics the physiologic signaling system working in the body by converging the information obtained from the activation of ANP and BNP into a single virtual analyte, NT-proXNP. It appears to have a diagnostic efficiency equal to or slightly better than that of individual NT-proANP or NT-proBNP assays.     

Plasma atrial natriuretic peptide (ANP) fragments proANP (1-30) and proANP (31-67) measurements in chronic heart failure: a useful index for heart transplantation?

The family of the atrial natriuretic peptides, proANP fragments and the active alphaANP, is strongly related to heart disease. The aim was to study in CHF subjects the relation of mdANP and NtANP with brain natriuretic peptide (BNP) and with other traditional medical parameters. Sixteen CHF patients (aged 51.9+/-13.7 years) and 16 healthy subjects age matched (50.8+/-5.9 years) were selected. Both NtANP and mdANP were higher in CHF patients than in healthy subjects (1436+/-288 vs. 288+/-22 pmol/l p<0.001 and 2305+/-383 vs. 423+/-65 pmol/l p<0.0001, respectively). BNP in CHF patients was 28.0+/-9 pmol/l (reference values 1.7+/-1.8 pmol/l). Both NtANP and mdANP demonstrated positive correlation with BNP, p<0.0001 and with left atrial end-systolic volume, p<0.05. BNP correlated with left ventricular mass, p<0.03. In conclusion, plasma NtANP and mdANP analyses are useful laboratory markers in CHF patient investigation and follow up. In particular, they could be employed as non-invasive parameters to follow up worsening of systolic dysfunction until heart transplantation is required.     

Effects of thyroid hormone withdrawal on natriuretic peptides during radioactive iodine therapy in female patients with differentiated thyroid cancer

Objective: We aimed to investigate the effects of thyroid hormone withdrawal on N-terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC).

Methods: Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT-proBNP were measured in 51 female patients with DTC (48.7?±?4.2 years) at three time-points: day of radioiodine therapy (t1 – under acute hypothyroidism), 5 days after radioiodine (t2 – under acute hypothyroidism) and 3 months after radioiodine (t3 – under TSH suppression). Thirty healthy euthyroid women served as controls (42.8?±?5.6 years).

Results: At t1/t2/t3, median NT-proANP was 5.2/1.7/487?pmol/L vs. 297.7?pmol/L in control group (p?p?p?r?=?0.38, p?=?0.005), NT-proANP/NT-proBNP ratios (r?=?0.47, p?=?0.001), heart rate (r?=?0.39, p?=?0.005), and negatively with mean arterial blood pressure (r?=??0.58, p?Conclusions: Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes.     

The circulating levels of cardiac natriuretic hormones in healthy adults: effects of age and sex.

In order to study the relationships between sex hormones, aging, and circulating levels of cardiac natriuretic peptides and to define reference values for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) assays, we measured the plasma levels of cardiac natriuretic peptides in a large group of healthy adults divided according to age and sex. We studied 216 healthy subjects of both sexes (109 men and 107 women) with age ranging from 20 to 77 years (mean 43.2+/-14.8 years). All subjects were non-obese and had normal arterial blood pressure; they were free from acute diseases, including asymptomatic heart disease. Highly sensitive and specific IRMA methods were used to measure plasma ANP and BNP. The mean ANP value in healthy adult subjects of both sexes was 17.8+/-10.9 pg/ml with no significant difference between men (16.7+/-10.0 pg/ml) and women (18.8+/-11.7 pg/ml). The mean BNP value in healthy adult subjects of both sexes was 9.9+/-9.0 pg/ml with a significant difference (p<0.0001) between men (7.7+/-7.1 pg/ml) and women (12.2+/-10.2 pg/ml). There was a weak linear relationship between age and either ANP (r=0.350, p<0.0001) or BNP (r=0.254, p=0.0002) values. When the circulating levels of cardiac natriuretic hormones, and age and sex were analyzed by multiple stepwise regression analysis, both age and sex significantly and independently contributed to the regression. Our study indicates independent positive effects of aging and female sex hormones on ANP and BNP levels in healthy adult subjects. These effects should be taken into account in the calculation of appropriate reference values for cardiac natriuretic hormones.     

Natriuretic peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers

BACKGROUND: We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers. METHODS: We measured BNP (Triage BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28-83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively). RESULTS: For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63-0.89) and 0.75 (0.58-0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48-0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56-0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34-0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD. CONCLUSIONS: The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.     

Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75±0.06. However, NT-proBNP (AUC: 0.67±0.07) and NT-proANP (AUC: 0.69±0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83±0.06. NT-proBNP showed only a slightly smaller AUC (0.79±0.07). The AUC for NT-proANP was significantly smaller (0.65±0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: −0.472, p<0.001; NT-proBNP: −0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.     

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in chronic renal failure

Secretion of ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) is pulsatile in healthy humans. However, the patterns of secretion of ANP and BNP have not been studied in chronic renal failure. The aim of the present study was to test the hypotheses that ANP and BNP are secreted in pulses in dialysis patients, and that pulsatile secretion is regulated by prostaglandins. Blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 1-2 h in 13 dialysis patients and 13 healthy control subjects (Study 1), and in 15 healthy control subjects, who participated in a randomized placebo-controlled cross-over study after treatment with indomethacin and placebo (Study 2). Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. The results from Study 1 showed that the secretion of ANP and BNP was pulsatile in nine patients with chronic renal failure. The maximum amplitude was significantly higher in chronic renal failure compared with control subjects for both ANP and BNP (ANP, 4.3 compared with 0.7 pmol/l; BNP, 2.0 compared with 0.3 pmol/l; values are medians) and correlated positively with the mean plasma level of ANP (rho=0.900, P=0.001; n=9) and BNP (rho=0.983, P=0.000; n=9). The frequency was the same for patients and controls. The results from Study 2 demonstrated pulsatile secretion in all subjects, but both the amplitude and frequency were unaffected by indomethacin. The maximum amplitude correlated positively with the mean plasma level of ANP and BNP during both placebo and indomethacin treatment. It can be concluded that the secretion of ANP and BNP is pulsatile with abnormally high amplitude in chronic renal failure, that prostaglandins apparently are not involved in the secretion of these peptides in healthy subjects and that the high secretion rate in chronic renal failure results in higher ANP and BNP in plasma.     

Measurement of brain natriuretic peptide in plasma samples and cardiac tissue extracts by means of an immunoradiometric assay method

We evaluated the analytical characteristics and clinical usefulness of a commercial immunoradiometric assay (IRMA) kit for brain natriuretic peptide (BNP). Mean (+/-SD) plasma BNP concentrations measured in 129 normal subjects were 2.9+/-2.7 pmol/l (median 2.2 pmol/l; range 0.1-12.4 pmol/l). The mean (+/- SD) value observed in healthy men (2.1 +/- 2.0 pmol/l, n = 49) was significantly (p=0.0009) different to that found in women (3.4 +/- 2.9 pmol/l, n=80). A positive relationship (R=0.214, p=0.0174) was found between BNP values and age. In 65 patients with cardiac diseases, BNP levels increased with the progression of clinical severity of disease; patients with more severe disease [NYHA functional class III-IV, mean (+/- SD) BNP +/- 254 +/- 408 pmol/l, n=22] showed significantly (p<0.0001) increased values compared to patients with mild symptoms of disease (NYHA functional class I-II, mean (+/- SD) BNP=19.6 +/- 17.2 pmol/l, n=43). Furthermore, in 32 patients with chronic renal failure, greatly increased (p<0.0001) BNP values were found both before (mean +/- SD=88. 1+/- 111.1 pmol/l) and after haemodialysis (mean +/- SD=65.6 +/- 76.7 pmol/l), with a significant reduction after haemodialysis (p=0.0004) compared to pre-haemodialysis. The mean (+/- SD) BNP value found in atrial extracts collected during aorto-coronary bypass operations in 15 patients was 14.5 +/- 51.9 pmol/g of cardiac tissue. Moreover, the mean (+/- SD) tissue levels of BNP in 7 heart transplant recipients were 128.4 +/- 117.2 pmol/g of cardiac tissue in atrium, 68.4 +/- 76.7 pmol/g in ventricle, and 10.9 +/- 8.5 pmol/g in interventricular septum. Finally, BNP values found in cardiac tissues of two subjects collected at autopsy were considerably lower (on average 1/1000) than those observed in cardiac tissues of patients with cardiac diseases. The IRMA method for BNP determination evaluated in this study showed a good degree of sensitivity, precision and practicability. Therefore, this method should be a reliable tool for the measurement of plasma BNP levels for both experimental studies and routine assay.     

Radioimmunoassay for N-terminal probrain natriuretic peptide in human plasma

Measurement of plasma levels of natriuretic peptides has been used to assess left ventricular dysfunction and prognosis. Recently levels of the N-terminal peptide fragment of the precursor of brain natriuretic peptide have been reported to be present in peripheral plasma and to be increased in chronic heart failure patients. Our aim in this study was to develop a radioimmunoassay for N-terminal proBNP, to compare its plasma concentrations in control subjects and in patients with end-stage heart failure and to define its relation to brain natriuretic peptide (BNP). A polyclonal antibody was raised in rabbits against human N-terminal proBNP fragment (amino acid 1-21). The plasma N-terminal proBNP concentrations were assayed directly without extraction. No detectable cross-reactivity existed with other natriuretic peptides: BNP, ANP or N-terminal proANP. The assay had a detection limit (2 SD from zero) of 9.7 pmol/L. Plasma N-terminal proBNP was 29 (13-75) (median (range)) pmol/L in the control group. There were no gender difference, male: 28 (13-61) vs. female 33 (13-75) pmol/L, p= NS, but there was a positive correlation to age (r=0.52, p<0.0001). In patients with end-stage heart failure the median N-terminal proBNP levels were increased significantly 616 (114-2781) pmol/L (p<0.001) and in pooled data N-terminal proBNP showed a close correlation to BNP (r=0.96, p<0.0001). Size exclusion of plasma extracts indicated that proBNP (1-108) may circulate both as intact prohormone and as split products, N-terminal proBNP (1-76) and BNP (77-108). Our results support the concept that N-terminal proBNP measurement could be a valuable tool in the biochemical indication of increased cardiac wall stress.     

Direct comparison of serial B-type natriuretic peptide and NT-proBNP levels for prediction of short- and long-term outcome in acute decompensated heart failure

Introduction

Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome.

Methods

This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission.

Results

During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions.

Conclusions

BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP.

Trial registration

ClinicalTrials.gov identifier: NCT00514384.     

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF ( n =12) and controls ( n =12) were investigated. Plasma ANP and BNP levels were determined every 2 min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76 pmol/l; controls, 0.75 pmol/l; P <0.01. BNP: CHF, 3.24 pmol/l; controls, 0.23 pmol/l; P <0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.     

Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.     

Prognostic value of increased plasma levels of brain natriuretic peptide in patients with septic shock

Our objective was to investigate the plasma levels of brain and atrial natriuretic peptides (BNP and ANP, respectively) in patients with septic shock/severe sepsis and to study the association of BNP and ANP levels with hemodynamic parameters, severity of the disease, and prognosis of those patients. This is a prospective case series study of 22 patients with septic shock, 11 patients with severe sepsis, and 20 healthy volunteers at the Department of Emergency and Critical Care Medicine, Nara Medical University Hospital, Japan. Blood collection was performed on admission and on days 1, 2, and 4. Plasma BNP and ANP levels were measured by radioimmunoassay. Right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, and left ventricular stroke work index were determined using a thermodilution catheter. Acute Physiological and Chronic Health Evaluation II scores were calculated. Plasma levels of BNP and ANP were markedly elevated in patients with septic shock/severe sepsis compared with controls (BNP, 7 +/- 0.3 pg mL; ANP, 13 +/- 1 pg mL). In patients with septic shock, both BNP and ANP peaked on day 2 (BNP, 987 +/- 160 pg mL; ANP, 103 +/- 17 pg mL). Plasma levels of BNP on day 2 in patients with septic shock significantly correlated with right atrial pressure (r = 0.744, P < 0.01), mean pulmonary arterial pressure (r = 0.670, P < 0.01), pulmonary arterial wedge pressure (r = 0.709, P < 0.01), left ventricular stroke work index (r = -0.552, P < 0.05), Acute Physiological and Chronic Health Evaluation II score (r = 0.581, P < 0.01), and poor prognosis (P < 0.05). The optimal cutoff point for predicting mortality in patients with septic shock was a BNP level of 650 pg mL on day 2, in which sensitivity and specificity were 92% and 80%, respectively. Increased plasma levels of BNP may reflect not only the severity of myocardial depression but also the disease severity and could be of prognostic value in patients with septic shock.     

Copeptin and risk stratification in patients with acute dyspnea

Introduction

The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea.

Methods

We conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea.

Results

Copeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk.

Conclusions

Copeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.     

Midregional pro-A-type natriuretic peptide measurements for diagnosis of acute destabilized heart failure in short-of-breath patients: comparison with B-type natriuretic peptide (BNP) and amino-terminal proBNP

BACKGROUND: The aim of the present study was to assess the utility of amino-terminal pro-A-type natriuretic peptide (NT-proANP) measurements for the emergency diagnosis of acute destabilized heart failure (HF), using a novel sandwich immunoassay covering midregional epitopes (MR-proANP). METHODS: The retrospective analysis comprised 251 consecutive patients presenting to the emergency department of a tertiary care hospital with dyspnea as a chief complaint. The diagnosis of acute destabilized HF was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction. A commercially available immunoluminometric assay was used for measurement of MR-proANP plasma concentrations. RESULTS: Median MR-proANP plasma concentrations were significantly higher in patients with dyspnea attributable to acute destabilized HF (338 pmol/L; n = 137) than in patients with dyspnea attributable to other reasons (98 pmol/L; n = 114; P <0.001). The area under the curve for MR-proANP was 0.876 (SE = 0.022; 95% confidence interval, 0.829-0.914), and the cutoff concentration with the highest diagnostic accuracy was 169 pmol/L (sensitivity, 89%; specificity, 76%; diagnostic accuracy, 83%). In the setting evaluated, diagnostic information obtained by MR-proANP measurements was similar to that obtained with B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) measurements. CONCLUSIONS: MR-proANP measurements may be useful as an aid in the diagnosis of acute destabilized HF in short-of-breath patients presenting to an emergency department. The diagnostic value of MR-proANP appears to be comparable to that of BNP and NT-proBNP.     

Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man

The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli. We infused human alpha-ANP (1-28) at a calculated rate of 1.2 pmol min-1 kg-1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 +/- 1.5 to 20.9 +/- 1.9 pmol/l. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 +/- 18 to 182 +/- 30 mumol/min (P less than 0.001) and a 28% increase of mean water excretion from 10.8 +/- 0.8 to 13.8 +/- 1.6 ml/min (P less than 0.01). The infusion suppressed mean plasma renin activity from 1.55 +/- 0.10 to 1.17 +/- 0.06 pmol of ANG I h-1 ml-1 (P less than 0.001). Mean plasma aldosterone concentration (242 +/- 16 basally and 215 +/- 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive Peptide Release in Relation to Hemodynamic and Metabolic Changes During Rapid Ventricular Pacing

Plasma atrial natriuretic peptide (ANP) concentration increases during ventricular arrhythmias and rapid ventricular pacing but less is known about plasma brain natriuretic peptide (BNP) and endothelin (ET-1). In the present study concentrations of ANP, the amino terminal part of the proANP (NT-proANP), BNP, and ET-1 were measured in the coronary sinus and femoral artery before and at the end of rapid ventricular pacing in 15 patients with coronary arterial disease. The changes were compared with the changes in mean arterial blood pressure, pulmonary capillary wedge pressure (PCWP), transcardiac differences in pH, pCO2, lactate, and norepinephrine. There was an increase in PCWP and a transient decrease in blood pressure after initiation of pacing. Pacing caused a decrease in ST-segment, transcardiac difference of norepinephrine, lactate extraction, pCO2 difference, and an increase in pH difference. Concentration of ANP in the coronary sinus and femoral artery and its transcardiac difference increased during pacing (P < 0.001), whereas changes in NT-proANP were small and BNP and ET-1 levels remained unchanged. The change in transcardiac ANP difference correlated with the change in lactate (r = 0.53, P < 0.05) but not that of norepinephrine, PCWP, or blood pressure. The results show that the plasma concentration of ANP increases more than that of NT-proANP during rapid ventricular pacing. Ischemia-induced release of ANP and its diminished elimination may contribute to the increased plasma ANP level.     

Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes: relation to coronary artery narrowing and plaques number

BACKGROUND: To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells. METHODS: 178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in patients respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p<0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p<0.001). CONCLUSIONS: Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.