BNP Assay Research Articles

Cord Blood (UCB) and 24 Hours Postnatal (PN-24) Reference Values of B-Type Natriuretic Peptide (BNP) among Elective CS (ECS) Born Healthy Full Term (FT) Neonates

Background: The fetal to neonatal transition is accompanied by lung expansion and lung fluid clearance soon after birth. BNP reference values are available mostly for preterm infants. BNP synthesized predominantly in the cardiac ventricle play an important role in the regulation of ECF volume and postnatal circulatory adaptation. Neonates born via ECS are at higher risk for postnatal transitional failure states like TTN. Reference values of BNPs among healthy FT born via ECS (not in labor) have not been reported. Aims: To determine the reference values of BNP from UCB and PN-24 plasma samples among ECS born FTs. Methods: IRB approved prospective study, n=66 Eligibility: FTs born via ECS. BNP assay was done using commercial kit (Triage BNP test) on UCB and PN-24 samples. Maternal and infant birth characteristics collected. Results: Shapiro Wilk's test was used to test the normal distribution of quantitative variable. Median and interquartile range of BNP values are shown below UCB levels are not related to BW and gender. Gender difference was significant in PN-24 levels. Table Conclusions: Our preliminary data for the reference value range of UCB and PN-24 BNP levels in healthy FTs born via ECS showed expected increase after birth. These reference values are essential to facilitate the use of these markers in neonatal transition failure states.

The clinical significance of urinary B-type natriuretic peptide assay for the diagnosis of chronic heart failure

Objective To investigate the value of urinary BNP for diagnosis of chronic heart failure (CHF). Methods The levels of Urinary BNP and plasma BNP were measured by microparticle enzyme immunoassay (MEIA) in 83 patients with CHF and 30 control subjects. The heart function was classified according to the NYHA criteria. Left ventricular ejection fractions (LVEF) were measured by echocardiology. Results The level of urinary BNP in patients with CHF was[90. 0(38. 3 -209. 5 )]ng/L and the level of plasma BNP was[680. 0 ( 289. 7 - 1543.5)]ng/L, both of them were much higher than those in healthy subjects,[17. 0 ( 13.0 - 33. 0)]ng/L and[84. 5 ( 56. 0 - 158.0 )]ng/L, respectively (P＜0. 01 ). The concentrations of urinary BNP increased gradually with more severe symptoms ( NYHA cl ass Ⅰ -ⅣV ). The level of urinary BNP was positively correlated with NYHA class ( r = 0. 742, P ＜ 0. 01 )and the level of plasma BNP (r =0. 842,P ＜0. 01 ) while negatively related with LVEF (r = -0. 801 ,P ＜0. 01 ). The level of urinary BNP in patients with LVEF ＜ 40％ was[143.0 ( 85. 0 - 258.0)]ng/L , which was much higher than that in patients with LVEF≥40％ ,[31.5( 17.3 -38. 8)]ng/L, (P ＜0. 01 ). At a decision threshold of 36. 5 ng/L, the urine BNP assay demonstrated a clinical sensitivity and specificity of 84％ and 80％ ,respectively. In this study,the area under the curve(AUC) was 0. 905. Conclusion Urinary BNP is a new candidate marker for the diagnosis of CHF,it provides a similar accuracy with plasma BNP. Key words: Heart failure; Natriuretic peptide, brain; Urinalysis

Clinical relevance of time course of BNP levels in neonates with congenital heart diseases

IntroductionThe aim of this study is to better characterize the time courses of BNP levels throughout the first days of life in larger populations of neonate and infant with or without congenital heart diseases (CHD) in order to increase the diagnostic accuracy of BNP assay in pediatric patients with CHD. Materials and methodsBNP was measured by an automated platform (Triage BNP reagents, ACCESS Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA 92835) in 218 neonates and infants with different CHD; 222 healthy children, matched for age, served as controls. ResultsBNP values were significantly higher (P<0.001) in the whole group of CHD patients (median 1029.8ng/L, range 25–20,152ng/L) than in controls (median 149.5ng/L, range 9–866ng/L). A different trend between BNP values and age was observed in healthy subjects and CHD patients. After an initial increase within the first 4days of life, BNP values in CHD patients tend to stabilize to high values in the following days. On the contrary, in control subjects a peak of BNP levels was observed in the second or third day, followed by a progressive decrease. Therefore, the diagnostic accuracy of BNP assay, calculated in the samples collected in the first four days of life (AUC of ROC analysis 0.86, 95% CI 0.83–0.90) was significantly lower (P<0.0001) compared to samples collected from 5days to 30days of life (AUC 0.97, 95% CI 0.95–0.99). Optimal cut-off values for BNP assay, as calculated by ROC analysis, were also age-dependent (cutoff for the first 4days of life: 363.5ng/L; cutoff values from 5 to 30days of life: 109.5ng/L). ConclusionsOur study demonstrates that differences in time-courses of BNP values between newborns with and without CHD throughout the first days of life clearly affect the diagnostic accuracy of BNP assay. Indeed, the diagnostic accuracy of BNP assay in discriminating between healthy newborns and CHD patients progressively increases after the 4th day of life. As a result, also cutoff values of BNP assay greatly change throughout the first days of life. However, decision values of BNP assay are strongly method-dependent, consequently clinicians should give great care to compare results obtained by different laboratories, especially when different methods are used.

Validez y utilidad del péptido ventricular natriurético tipo B (BNP) en la detección de disfunción ventricular izquierda en pacientes de alto riesgo en atención primaria

Objective The aim of this study was to determine the accuracy of BNP test for early diagnosis of left ventricular dysfunction in patients at high-risk for heart failure. Design Cross-sectional descriptive study. Setting 7 Primary Care Centres in Madrid (Spain). Participants A consecutive sample of 204 consecutive asymptomatic patients with high risk for heart failure (Stages A-B, AHA/ACC Classification). Main measurements BNP plasma levels were measured in the clinical setting using Triage BNP Test ® (Biosite ®) and an echocardiography was performed in the following 3 days in a single hospital unit as a reference standard. Plasma BNP levels were compared depending on the presence/absence of left ventricular dysfunction (LVD), type and severity degree. Sensitivity, specificity, positive and negative predictive values, and Área under the receiver operating characteristic curve (ROC) for BNP assay were calculated. Results BNP values were significantly higher ( P<.001) in patients with left ventricular systolic dysfunction (LVSD). No significant differences were found for diastolic dysfunction. The best cut-off value to discriminate the patients with LVSD was 71.00 pg/ml, with an Área under the ROC curve of 0.757 (95% CI 0.64-0.87). Sensitivity for LVD diagnosis was 75% (95% CI 50.66-99.34), specificity 70.19% (95% CI 62.81-77.57), positive predictive value (PPV) 20% (95% CI 9.05-30.95), and negative predictive value (NPV) 96.58% (95% CI 92.86-100), with LVSD prevalence of 9.04% in this population. Conclusions BNP determinations are of value in diagnosing LVSD in a primary care setting, with similar sensitivities and specificities. Due to the high NPV is useful to rule-out patients for echocardiography.

313 Levosimendan in dilated cardiomyopathy and refractory cardiogenic shock in children

Levosimendan (Lev) is a new calcium sensitizer and K-ATP channel opener. The documentation regarding this drug is one of the largest ever on the safety and efficacy of a new pharmacological agent in acute heart failure syndromes in adult population. Its use in paediatric is limited to successful weaning from biventricular mechanical support in case reports or small trials conducted in the immediate postoperative period. We report our experience of using (Lev) during refractory cardiogenic shock (RCS) in infants. Four infants aged 2–24 months and suffering from hypokinetic dilated cardiomyopathy) were included in this study. All presented with uncontrolled RCS (LVEF < 20%) despite conventional inotropes treatment. Lev was intended as a last resort before ECMO. The effectiveness of treatment was monitored by measuring the echocardiographic left ventricular ejection fraction (LVEF) and plasma BNP assay before and 8 days after administration. A total of 15 injections of Lev were realized and studied. Mean LVEF before and 8 days after administration of Lev significantly increase from 19.75% +/− 1.7 to 33 +/− 2.95 (p < 0.01) and mean BNP level decrease from 2267 pg/ml +/− 518 to 1673 +/− 372 (p < 0.08). These children could benefit from additional treatments of Lev in order to wean amines and defer the circulatory support. In one of these, a total of 6 cycles was necessary without the use of circulatory support for an improvement. In the 4 patients studied, the outcome was favorable. Figure 1 illustrates the individual changes in LVEF and BNP after each Lev injection. During the refractory cardiogenic shock of the child with hypokinetic dilated cardiomyopathy, levosimendan may improve myocardial function allowing weaning of conventional inotropes and circulatory support. Re-injection may also be necessary. Randomized studies with larger number of patients are needed to confirm these very encouraging results.

Characterization of Molecular Forms of N-Terminal B-Type Natriuretic Peptide In Vitro

The heterogeneity of circulating peptides may influence the interpretation of results from N-terminal profragment of BNP (NT-proBNP) assays. Our objective was to characterize the heterogeneity for better usability of the assays. Endogenous proBNP was purified from patient samples and treated with trifluoromethanesulfonic acid (chemical deglycosylation). The human proBNP gene was introduced into rat hearts by adenoviral transfer. Cell lysates and plasma samples containing proBNP-derived peptides were analyzed by chromatography. The fate of exogenous recombinant NT-proBNP added to fresh whole blood samples was followed by immunoassays and chromatography. The main NT-proBNP components were isolated and identified by mass spectrometry. Immunoreactive NT-proBNP in human plasma comprised several molecular forms, as did circulating immunoreactive human NT-proBNP after adenoviral transfer of human proBNP cDNA into rat ventricular myocardium. Incubation of recombinant NT-proBNP(1-76) in human plasma or serum resulted in multiple components with the 2 major components identified as NT-proBNP(1-36) and NT-proBNP(1-62/64). Profiling by different antisera and chromatography indicated masking of the non-mid-region epitopes likely due to formation of oligomers. More than 75% of the original immunoreactivity in the mid-region epitope was retained after 3-week storage of plasma samples at room temperature. There is marked heterogeneity in immunoreactive NT-proBNP in plasma not related to glycosylation. The mid-region epitope of NT-proBNP is stable even in harsh storage conditions. Careful choice of antibody epitopes can yield extraordinarily robust assays.

Measurement of B-type natriuretic peptide by two assays utilizing antibodies with different epitope specificity

Objectives To compare plasma BNP values determined by a conventional-type and a novel-type of BNP assays. Design and Methods Plasma samples (n = 94) from HF patients were analyzed by the novel-type “Single Epitope Sandwich” (SES assay prototype) and the conventional-type Siemens ADVIA Centaur BNP assays. Both assays were calibrated using recombinant proBNP (expressed in E. coli). Results The SES assay measured 1.2- to 7.2-fold (2.1 ± 0.9; mean, SD) greater BNP concentrations compared to the Siemens assay. A subset of six samples (6.4%) demonstrated the largest (3- to 7.2-fold higher) difference. Conclusions The SES prototype assay appears to more accurately measure the absolute concentrations of BNP immunoreactive forms.

Diagnostic accuracy of B-type natriuretic hormone for congenital heart disease in the first month of life

The goal of the present study was to evaluate the diagnostic accuracy of B-type natriuretic hormone (BNP) assay in children with congenital heart disease (CHD) in the first month of life. BNP was measured in 152 neonates with CHD; 154 healthy children matched for age were used as controls. BNP was measured with a fully automated platform (Triage BNP reagents, Access Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA, USA). BNP values were significantly higher (p<0.0001) in newborns and infants with CHD compared with control (CHD patients: median 1167.5 ng/L, range 25-54,447 ng/L; healthy children: median 150.5 ng/L, range 5-866 ng/L). The diagnostic accuracy of BNP was assessed using the receiver operating characteristic (ROC) analysis, taking into account the three different groups divided according to age. Group 1: all CHD patients and healthy newborns and infants as a whole (i.e., from birth to the 30th day of life); Group 2: from the 1st to 3rd day of life; Group 3: from the 4th to 30th day of life. The area under the curve (AUC) of the ROC curve for Group 3 (0.935) was significantly higher than that for Group 1 (0.843, p=0.009) and Group 2 (0.769, p=0.0003), while the AUC values of Group 1 and Group 2 were not significantly different (p=0.191). BNP may be considered a useful marker for screening in the integrated approach of newborns, infants and children with suspected CHD. However, the accuracy of the BNP assay varies greatly during the first month of extra-uterine life, showing the lowest diagnostic accuracy in the first 3 days after birth. After the second week of life, the biomarker becomes more accurate in ruling in CHD.

A Comparison of Transcutaneous Doppler Corrected Flow Time, B-Type Natriuretic Peptide and Central venous Pressure as Predictors of Fluid Responsiveness in Septic Shock: A Preliminary Evaluation.

Aortic corrected flow time (FTc) is easily measured by Doppler techniques. Recent data using transoesophageal Doppler suggest that it may predict fluid responsiveness in critical care. This use of FTc has not previously been evaluated in septic shock, nor have any studies incorporated transcutaneously measured FTc. Furthermore, no comparison has been made between FTc, plasma B-type natriuretic peptide concentration (BNP) or central venous pressure. The aim of this preliminary study was to compare FTc, BNP and central venous pressure as predictors of fluid responsiveness in septic shock patients without cardiac dysrhythmia. This was a prospective study of 10 consecutive adult septic shock patients (in sinus rhythm; 60% mechanically ventilated) treated with intravenous fluid challenge (4% albumin 250 ml over 15 minutes) in a mixed medical/ surgical tertiary intensive care unit. Mean + SD Acute Physiological and Chronic Health Evaluation II score was 21.8 +/- 12.7. Haemodynamic assessment incorporating transcutaneous aortic Doppler (USCOM) occurred before and five minutes after fluid challenge. Concurrent with initial assessment, blood samples were collected for BNP assay (ADIVA Centaur). Four patients demonstrated an increase in stroke volume > or = 15% (responders). Percent change in stroke volume strongly correlated with baseline FTc (r = -0.81, P = 0.004) but not BNP (r = -0.3, P = 0.4) or central venous pressure (r = -0.4, P = 0.2). Baseline FTc < 350 ms discriminated responders from non-responders (P = 0.047). Our data support FTc as a better predictor of fluid responsiveness than either BNP or central venous pressure in septic shock. Transcutaneous aortic Doppler FTc offers promise as a simple, completely non-invasive predictor of fluid responsiveness and should be evaluated further

067 Releasing of unprocessed natriuretic peptides in heart failure

Both biologically active BNP1-32 and inactive NT-proBNP1-76 are released in circulation from prohormone, proBNP1-108. Recent data suggest that proBNP is detected in blood of heart failure (HF) patients. Blood levels, kinetics as well as determinants of proBNP1-108 secretion are unknown as compared to processed forms. We sought to measure and to compare blood levels of BNP and proBNP in HF and non HF patients. Plasma natriuretic peptides were assessed in 131 HF patients and in 36 non-HF patients using both Triage BNP assay and BioRad proBNP assay. BioRad assay is highly specific of proBNP when the Triage BNP assay may be influenced by proBNP. Among HF patients, 33 were admitted because of acute HF and blood samples were analyzed on admission and at discharge. In order to compare BNP and proBNP levels, results are expressed as nmole/l. ProBNP was detected in all patients (104 ± 145 nmol/l) and demonstrated a high degree of correlation with BNP in non-HF patients (r = 0.95 [95% IC 0.90 – 0.97], p<0.0001) as well as in HF patients (r = 0.97, [0.95 - 0.98], p<0.0001). The proBNP/BNP ratio was higher in HF patients as compared to non-HF patients (0.82 ± 0.23 versus 0.62 ± 0.18, p < 0.0001). In patients with decompensated HF, proBNP/BNP ratio were similar on admission and at discharge, and changes in both BNP and proBNP were similar (0.91, [0.82-0.95], p < 0.0001). Interestingly, proBNP/BNP ratio was lower in the most severe HF patients according to discharge BNP and proBNP/BNP ratio was negatively correlated with discharge BNP (r = -0.40, [-0.65 – -0.06], p 0.02). The intact precursor – proBNP- to both BNP and NT-proBNP circulates in both HF and non-HF patients and is an important part of the pool of circulating natriuretic peptides. HF seems to be characterized by a decrease in proBNP processing but, unexpectedely, at a lesser level in acute and/or severe HF as compared with less severe HF. Biological and physiological meanings of our results deserves further studies.

Prevalence and Predictors of Pulmonary Arterial Hypertension in Hemoglobin E/ β-Thalassemia Patients.

Abstract 2015Poster Board I-1037 Introduction:Pulmonary arterial hypertension (PAH) associated with thalassemia (Thal) hemoglobinopathy is now an accepted clinical entity. Most of the reports are in sickle cell disease and splenectomized β-Thal patients. Once manifested, it connotes poor prognosis. We herein present its prevalence and predictors in hemoglobin E/β-Thal (E/β-Thal) patients. Patients and Methods:One hundred and ten clinically stable E/β-Thal outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). PAH was defined as an estimated SPAP ≥36 mmHg. Clinical features and laboratory data were stratified according to the presence or absence of PAH, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value <0.05 as statistically significant. Predictors of PAH were considered in univariate analysis. Results:There were 110 patients, 56 of whom were female and 61 were asplenic. PAH was present in 41 patients (37.3%), all of whom had normal left ventricular ejection fraction. There was no gender difference between the 2 groups (p=0.055). Selected statistically significant results are shown in the table.ResultsWith PAH (41 Patients)Without PAH (69 Patients)P valueAge at 1st transfusion (median)6 years11.25 years0.03Total transfusions (median)37 units PRBC15 units PRBC0.04Splenectomy78%42%<0.001Cardiomegaly52.5%32.3%0.042Extramedullary hematopoiesis56.4%30.6%0.01RBC count3.24 +/- 0.93 × 106/μL3.65 +/- 0.9 × 106/μL0.034Corrected reticulocyte count (median)4%1.7%0.02Nucleated RBC (median)530/100 WBCs15.5/100 WBCs<0.001Corrected WBC count9.34 +/- 4 × 103/μL7.8 +/- 3.5 × 103/μL0.036Platelet count627.7 +/- 313.2 × 103/μL436 +/- 267.4 × 103/μL0.001Globulin4.4 +/- 1.2 g/dL3.8 +/-0.8 g/dL0.002LDH323.3 +/- 117.2 u/L243.3 +/- 85.6 u/L<0.001Free hemoglobin (median)4.42 mg/dL2.7 mg/dL0.001C-reactive protein (high sens) (median)2.9 mg/L1.3 mg/L0.008Soluble VCAM-11,896.1 +/- 553.5 ng/mL1,463 +/- 622 ng/mL0.004NT pro BNP11.7 pmol/L6.2 pmol/L0.026 Conclusions:Prevalence of PAH in E/β-Thal patients is 37.3% without gender preponderance. Predictors are asplenia, more severe hemolysis, higher number of circulating (activated) platelets and nucleated RBCs, increased chronic low grade inflammation and increased cellular adhesion between blood and endothelial cells. These changes could facilitate development of thrombotic pulmonary arteriopathy, the underlying basis of PAH. Serum NT pro BNP assay can be utilized as a predictor or a screener of PAH in these patients. Disclosures:No relevant conflicts of interest to declare.

Abstract 5265: Alternatively Spliced B-Type Natriuretic Peptide (ASBNP) is a Renal Selective Natriuretic and Diuretic Peptide Without Hypotensive Properties

Background: B-type natriuretic peptide (BNP1–32) is a 32- amino acid cardiac peptide secreted in response to cardiac stress and plays an important compensatory role in cardiorenal homeostasis. Studies have recently reported that a mRNA encoding an alternatively spliced variant of BNP (ASBNP) exists in the human heart and like BNP1–32 is increased in the failing heart. While ASBNP and BNP1–32 have identical ring structures and amino termini, ASBNP and BNP1–32 differ in their carboxy terminus (34 vs. 6 amino acids, respectively). Studies have also reported that ASBNP activates cGMP, the second messenger of BNP1–32, in isolated glomeruli but not in endothelial cells. Also, unlike BNP1–32 ASBNP does not vasorelax isolated arteries or veins. The cardiorenal actions in vivo of ASBNP are unknown. We hypothesized that ASBNP in vivo would have selective renal actions yet as suggested by studies in isolated vessels would be devoid of blood pressure effects. Methods: We therefore determined for the first time the cardiorenal actions of three subsequent intravenous doses of ASBNP (10, 50, and 150 pmol/kg/min) in 5 healthy canines in an acute study under anesthesia in 30-minute clearances at baseline, during, and following infusion. Values provided are mean±SEM for baseline vs. 150 pmol/kg/min. *p&lt;0.05. Results: ASBNP dose-dependently increased plasma levels of cGMP (8.6±1.0 vs. 11.5±1.3* pmol/mL), and the same was true for urinary cGMP excretion (878±191 vs. 2028±551* pmol/min). Mean arterial pressure (p=0.83) and heart rate (p=0.43) remained unchanged. Urine flow increased (0.38±0.05 vs. 1.32±0.20* mL/min) as did urinary sodium excretion (38±15 vs. 133±38* μ Eq/min). Renal blood flow (p=0.51) and glomerular filtration rate (p=0.99) remained unchanged. BNP-immunoreactivity as measured by the Biosite BNP assay increased (5±4 vs. 3807±573* pg/mL). Conclusion: ASBNP, an alternatively spliced form of BNP produced in the human heart, activates cGMP and has diuretic and natriuretic actions but is without blood pressure lowering actions. Thus, ASBNP represents a novel renal selective, non-hypotensive, natriuretic, and diuretic peptide.

Chronic Renal Insufficiency: Prevalence in the General Population and Improved Detection of Cardiac Disease in Combination with BNP Assays

Chronic renal insufficiency (CRI) is predictor of increased mortality in congestive heart failure (CHF) and its prevalence has been increasing in the US. We evaluated the prevalence of CRI in adult population and addressed whether glomerular filtration rate (GFR, CockroftGault) adds value to the biomarkers BNP and NT-proBNP in detecting early cardiac-structural and functional impairments in the general population. From 1997-1999 medical history, physical examination, echocardiography, BNP (Biosite) and NT-proBNP (Roche) and serum creatinine were obtained in 1,982 randomly selected residents of Olmsted County, MN >= 45 years (range 45-96).

B-Type Natriuretic Peptide Single Nucleotide Polymorphism rs198389 Impacts Test Characteristics of Common Assays

Background: BNP assays are widely used in the diagnosis and prognosis of left ventricular (LV) dysfunction and heart failure. The functional single nucleotide polymorphism (SNP) rs198389 in the promoter region of the BNP gene is common in the US and has been associated with higher BNP levels. Its impact on common assay test characteristics for the detection of LV systolic dysfunction is unknown. Objective: To determine the impact of rs198389 on the diagnostic test characteristics of two commonly used BNP assays for the detection of LV systolic dysfunction.

Multimarker panel in patients admitted to emergency department: A comparison with reference methods

Objectives Point of care testing and multimarker panels are rapidly expanding in emergency departments. We determined the reliability of Short-of-Breath SOB® panel in patients admitted for acute dyspnea and/or chest pain. Design and methods SOB® d-dimer, BNP, cTnI, CK-MB and myoglobin assays were compared with references in 97 outpatients. Results The correlation between SOB® and references methods was acceptable, but with limited precision and accuracy. Conclusions Diagnostic performances and cut-off values should be further validated before clinicians replace traditional cardio-respiratory biomarkers by the new SOB® panel.

Evaluation of NT‐Pro BNP and CT‐ANP as Markers of Concentric Hypertrophy in Dogs with a Model of Compensated Aortic Stenosis

Serum C-terminal atrial natriuretic peptide (CT-ANP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) concentrations have not been measured serially in dogs with chronic pressure overload of the heart. We investigated whether serial evaluation of CT-ANP and NT-pro BNP concentrations is a useful guide to the risk of cardiac remodeling in dogs with a model of aortic stenosis. Six male Beagles. After anesthesia, the aorta was constricted with a polyester band and mean left ventricular systolic pressure (LVPs) was 50 mmHg above baseline. Echocardiographic and intracardiac catheter examinations and blood sampling were performed before surgery and 3 and 6 months after surgery. LVP and left ventricular end-diastolic pressure (LVEDP) were significantly higher at 6 months. Compared with baseline, end-diastolic intraventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), and relative wall thickness (RWT) were significantly increased 3 and 6 months after aortic constriction. Serum CT-ANP concentrations were increased significantly at 3 months and serum NT-pro BNP concentrations were significantly higher 3 and 6 months after aortic constriction. Serum NT-pro BNP concentration was significantly correlated with LVEDP and IVSd whereas serum CT-ANP concentration was not correlated with any measurement. Stepwise regression analysis showed that LVEDP, IVSd, and RWT could predict serum NT-pro BNP. This study indicated the differential regulation of NT-pro BNP and CT-ANP concentrations during pressure overload. NT-pro BNP assay may be used as an additional screening method to stratify early-stage ventricular remodeling because of aortic constriction.

Performance characteristics of the Architect® brain natriuretic peptide (BNP) assay: A two site study

IntroductionBrain natriuretic peptide (BNP) is produced by the ventricles of the heart and is a biomarker for heart failure. Several commercial assays are now available. We evaluated the performance characteristics of the ARCHITECT® BNP assay. MethodsWe evaluated the limit of blank, limit of detection, linearity and imprecision. Method comparison studies were performed with 3 other automated BNP assays including the ADVIA Centaur®, AxSYM®, and UniCel DxI® 800 methods. ResultsThe mean LOB and LOD of the Architect assay were 3.5 and 5.8 ng/L, respectively. Imprecision studies yielded within run CVs of 1.1 to 5.1% and total CVs of 2.3 to 5.3% using human plasma based multi-constituent controls at concentrations of 92, 500, and 3500 ng/L. The maximum deviation from the target recovery for dilution linearity was 9.6%. Concordance with other BNP assays at a 100 ng/l cutoff was 91 to 98% and κ statistics were 0.78 to 0.96. The mean difference between the Architect and Advia Centaur methods was positive. For the other methods, the mean difference with the Architect was negative. ConclusionsThe Architect BNP assay shows good performance characteristics with total imprecision ≤5.3%. It agrees well with the Advia Centaur, AxSYM, and UniCel DxI BNP assays.

Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis.

BackgroundCardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study.Materials and methodsThe pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE).ResultsPatients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205).ConclusionIn cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden.

The Effect of Impaired Renal Function on BNP and NT-proBNP Determinations

Introduction: Co-existing diseases contribute to false positive and negative test results. The value of a laboratory test increases with pre-test knowledge of the predictive value for a negative and positive test result. BNP and NT-proBNP have different pharmacokinetics and modes of clearance. We attempted to further clarify the effect of chronic kidney disease (CKD) on the BNP and NT-proBNP assays in patients observed in our emergency room who presented with signs and symptoms suspicious of HF.

THE RELEVANCE OF BRAIN NATRIURETIC PEPTIDES INVESTIGATION IN VARIOUS CARDIOVASCULAR DISEASES

Brain natriuretic peptides are relevant markers of heart impairment. We investigated the relevance of investiging brain natriuretic peptides (NT-proBNP, BNP) in monitoring different types of cardiovascular disease (chronic heart failure due to coronary artery disease, cardiomyopathy, acquired valve disease, congenital heart diseases). The NT-proBNP assay (Roche) was performed on 280 patients (mean age 49 years; range 20-89 years) and 48 healthy controls (mean age 43 years; range 13-65 years) and BNP assay (Bayer Shionoria) was performed in a subgroup of 42 patients (mean age 50 years; range 20-79 years). Patients were divided into four groups characterized by severity of heart failure according to the New York Heart Association classification. NT-proBNP concentrations differed in patients with cardiovascular diseases from controls (median 371 ng/l versus 41.5 ng/l, p < 0.0001). The cut off value of NT-proBNP determined in 280 patients with cardiovascular diseases was at 130 ng/l (AUC-area under curve = 0.93; sensitivity 98 %; specificity 79 %). Comparison of NT-proBNP and BNP values in patients showed significant correlation (r = 0.93; p < 0.0001). NT-proBNP showed significant differences between groups. Measurement of brain natriuretic peptides is useful and relevant in various types of heart diseases including congenital.