N-terminal Pro-brain Natriuretic Peptide Assay Research Articles

Performance of the Abbott Architect Immuno-Chemiluminometric NT-proBNP Assay.

Background: We evaluated the performance of the Abbott N-terminal pro-brain natriuretic peptide (NT-proBNP) assay against the Roche NT-proBNP immunoassay across two sites. Methods: Precision, linearity, and sensitivity studies were performed. A combined method of comparison and regression analysis was performed between the Roche and Abbott assays using samples from both sites (n = 494). To verify biotin interference, lyophilised biotin powder was reconstituted and spiked into serum samples at two medical decision levels (final concentration 500/4250 ng/mL) and compared to controls. NT-proBNP was also measured in anonymised leftover sera (n = 388) in a cardio-renal healthy population and stratified into three age bands—<50 (n = 145), 50–75 (n = 183) and >75 (n = 60). Results: Between-run precision (CV%) for NT-proBNP was 4.17/4.50 (139.5/142.0 pg/mL), 3.83/2.17 (521.6/506.3), and 4.60/2.51 (5053/4973), respectively. The assay was linear from 0.7–41,501 pg/mL. The limit of blank/quantitation was 1.2/7.9 pg/mL. The assay showed no interference from biotin up to 4250 ng/mL. Passing–Bablok regression analysis showed excellent agreement between the two assays (r = 0.999, 95% CI 0.999 to 0.999, p < 0.0001). The Roche assay had a slightly persistent, negative bias across different levels of NT-proBNP. ESC age cut-offs for diagnosing acute heart failure are applicable for the Abbott assay, with the median NT-proBNP of subjects < 50 years old at 43.0 pg/mL (range 4.9–456 pg/mL), 50–75 years old at 95.1 pg/mL (range 10.5–1079 pg/mL), and >75 years old at 173.1 pg/mL (range 23.2–1948 pg/mL). Conclusions: The Abbott Architect NT-proBNP assay has good performance that agrees with the manufacturer’s specifications. ESC/AHA recommended NT-proBNP age groups for acute heart failure diagnosis are applicable to this assay.

Analytical validation of a novel point-of-care immunoassay for canine N-terminal pro-brain natriuretic peptide analysis.

BackgroundN‐terminal pro‐brain natriuretic peptide (NT‐proBNP) is a widely used point‐of‐care (POC) cardiac biomarker in human medicine. Canine NT‐proBNP is used less in veterinary medicine, possibly due to the lack of a POC canine NT‐proBNP assay resulting in temporal delay, increased degradation in transport, and high reported variability in the available assay. A new quantitative POC analyzer allows fast, onsite measurement of NT‐proBNP, minimizing preanalytical error and reducing variability.ObjectiveWe aimed to analytically validate an NT‐proBNP assay (Vcheck) according to American Society of Veterinary Clinical Pathology (ASVCP) and Clinical Laboratory Improvement Amendments (CLIA) specifications.MethodsArchived and prospective plasma and serum samples were collected from male and female, client‐owned dogs of various breeds with cardiac abnormalities (n = 81) and a healthy control population (n = 225). Precision, accuracy, analytical sensitivity, and specificity, and other statistical analyses were performed.ResultsImprecision was considered acceptable with a coefficient of variation ranging from 9% at 4000 pmol/L to 20% at 600 pmol/L. The lower limit of quantitation was 650 pmol/L based on repetitive measures evaluation. Comparison of the Vcheck assay with the Cardiopet NT‐proBNP assay revealed an excellent correlation with minimal bias when preanalytical factors were controlled. Significant degradation of NT‐proBNP occurred when current methods were used at refrigerated and room temperatures, which could change diagnostic and prognostic decision‐making. Age‐partitioned reference intervals have high reference values of 750 pmol/L and 1280 pmol/L for juvenile and adult dogs, respectively.ConclusionsThe Vcheck NT‐ProBNP assay provides analytically acceptable results. Onsite testing can minimize variability related to preanalytical error and provide clinically useful contemporaneous results. Samples should be centrifuged immediately and analyzed within 2 hours of collection.

Diagnostic accuracy of N-terminal pro-brain natriuretic peptide for Kawasaki disease: An updated systematic review and meta-analysis.

This study aimed to investigate the diagnostic accuracy of circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) for Kawasaki disease (KD). We searched the PubMed, Web of Science and EMBASE databases to identify the eligible studies investigating the diagnostic accuracy of NT-proBNP for KD. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to evaluate the eligible studies' quality. A meta-analysis was performed with the bivariate model and summary receiver operating characteristic (sROC) curve. We also performed subgroup, publication bias and sensitivity analyses. We included 12 studies with 2173 KDs and 1909 control. The pooled sensitivity and specificity of eligible studies were 0.80 (95%CI: 0.72-0.86) and 0.81 (95%CI: 0.73-0.88), respectively. The area under sROC curve was 0.88 (95%CI: 0.84-0.90). Patient selection bias and partial verification bias were the major design weakness of the eligible studies. Sensitivity analysis revealed that the results of this meta-analysis were robust. Subgroup analysis revealed that study design, NT-proBNP assay and participants' body temperature were not the source of heterogeneity across all eligible studies. No publication bias was observed. NT-proBNP has moderate diagnostic accuracy for KD. It cannot be used for ruling in or ruling out KD when used alone.

Role of Stress Echocardiography in Operated Fallot: Feasibility and Detection of Right Ventricular Response

Patients with repaired tetralogy of Fallot often present residual hemodynamic abnormalities leading to right ventricular (RV) burden. Semisupine exercise echocardiography (Ex-Echo) is a validated method for diagnosis and prognosis in ischemic and valvular heart diseases and has potential for the evaluation of RV burden, pressure, and function. The aims of this study were to assess the effect of exercise on the right ventricle in adults with repaired tetralogy of Fallot and to identify factors associated with decreased RV function at peak exercise in an observational study. A total of 128 patients with repaired tetralogy of Fallot referred to an outpatient congenital heart disease unit were evaluated by Ex-Echo and conventional clinical and diagnostic examinations (i.e., electrocardiography, transthoracic echocardiography, cardiovascular magnetic resonance, cardiopulmonary exercise testing, and N-terminal pro-brain natriuretic peptide assay). The following Ex-Echo parameters were measured at rest and at peak exercise: tricuspid annular plane systolic excursion, RV pressure, and RV fractional area change (FAC). Interpretable images for RV FAC analysis were obtained in 123 of 128 patients. In 91 of 128 with detectable tricuspid valve regurgitation, RV systolic pressure during exercise was evaluated. According to positive or negative RV FAC variation during exercise, 74 patients were respectively defined as "responders" on stress echocardiography and 49 as "nonresponders"; the median percentage change between rest and stress was 13.8% (interquartile range, 5.9% to 26.9%) in responders and -13.5% (interquartile range, -25.4% to -7.4%) in nonresponders. Systolic RV systolic pressure increased in a similar manner in the two groups (65±36% in responders vs 59±39% in nonresponders, P=.45). Tricuspid annular plane systolic excursion increased significantly during peak exercise in responders from 17.2±3.4 mm at rest to 19.7±4.3 mm (P<.0001) but did not in nonresponders (from 16.9±4.7 to 18.1±4.6mm, P=.20). Left ventricular end-diastolic volume at rest and left ventricular ejection fraction < 50% were related to the lack of increased RV FAC on exercise. Ex-Echo is feasible in patients with repaired tetralogy of Fallot and allows the integrated assessment of variation in RV systolic pressure, area, and function during exercise, which usefully complement more conventional indices of hemodynamic burden in these patients. Longitudinal follow-up is needed to better delineate the prognostic value of the results of Ex-Echo.

Biohumoral markers as predictor of right ventricular dysfunction in AL Amyloidosis

Aim: In AL amyloidosis, the importance of right ventricle (RV) involvement has recently been underlined and its role in predicting prognosis has been emphasized. Little is known about the relationship between RV involvement, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin levels. Aim of our study was to clarify the relationship between NT-proBNP and troponin and RV involvement and analyze their independent value as predictors of RV dysfunction.Methods and Results: We examined 76 consecutive patients with biopsy-proven AL amyloidosis. Each patient received complete clinical evaluation, troponin I, NT-proBNP assay and comprehensive echocardiographic evaluation. Considering a tricuspidal annulus plane systolic excursion (TAPSE) value <16 mm, 23 patients (30%) presented RV systolic dysfunction, whereas 53 (70%) did not. Patient with reduced TAPSE had thicker left ventricle (LV) walls and RV free walls, reduced LV fractional shortening, impaired LV diastolic function and worse LV and RV myocardial performance index. For RV dysfunction the best predictive value for NT-proBNP was identified as 2977 ng/l with sensitivity and specificity of 87% and 84%, respectively; best cut-off for troponin I was identified as 0.085 ng/l, with sensitivity and specificity of 85% and 90% respectively.At multivariable logistic regression analysis, both NT-proBNP and troponin I emerged as independent predictors of RV dysfunction presence but troponin appears to have a higher predictive power.Conclusion: Our study demonstrated that cut-off values of 2977 ng/ml for NT-proBNP and 0.085 ng/l for troponin were able to identify a subgroup of AL patients with RV dysfunction. Troponin I is more accurate and seems to be the best biohumoral marker of RV dysfunction.

The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with heart failure caused by various acquired and congenital heart diseases (CHD). In January 2013, we performed a computerized literature search in the National Library of Medicine (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included a mix of Medical Subject Headings and free-text terms for the key concepts, starting from BNP assay and 'NT-proBNP assay', children, CHD. The search was further refined by adding the keywords neonate/s, newborn/s, heart failure, cardiomyopathy, screening, prognosis, follow-up, and management. BNP values are age and method dependent, even in pediatric populations. Regardless of age, there is great variability in BNP/NT-proBNP values within CHD characterized by different hemodynamic and clinical conditions. There is enough evidence to support the use of BNP/NT-proBNP as an adjunctive marker in the integrated evaluation of patients with congenital and acquired heart disease to help define severity and progression of heart failure as well in the monitoring of response to treatment. BNP/NT-proBNP can also be used for the screening of heart failure and as a prognostic marker in children undergoing cardiac surgery; however, to date, there are studies with heterogeneous patient groups, and diverse outcome measures selected are still few. BNP/NT-proBNP can be used as adjunctive markers in the integrated screening, diagnosis, management, and follow-up of children with heart failure caused by various acquired and congenital heart disease.

Signal-enhancer molecules encapsulated liposome as a valuable sensing and amplification platform combining the aptasensor for ultrasensitive ECL immunoassay

An innovatory ECL immunoassay strategy was proposed to detect the newly developing heart failure biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). Firstly, this strategy used small molecules encapsulated liposome as immune label to construct a sandwich immune sensing platform for NT-proBNP. Then the ECL aptasensor was prepared to collect and detect the small molecules released from the liposome. Finally, based on the ECL signal changes caused by the small molecules, the ECL signal indirectly reflected the level of NT-proBNP antigen. In this experiment, the cocaine was chosen as the proper small molecule that can act as signal-enhancer to enhance the ECL of Ru(bpy) 3 2+. The cocaine-encapsulated liposomes were successfully characterized by TEM. The quantificational calculation proved the ∼5.3 × 10 3 cocaine molecules per liposome enough to perform the assignment of signal amplification. The cocaine-binding ECL aptasensor further promoted the work aimed at amplifying signal. The performance of NT-proBNP assay by the proposed strategy exhibited high sensitivity and high specificities with a linear relationship over 0.01–500 ng mL −1 range, and a detection limit down to 0.77 pg mL −1.

Diagnostic, prognostic and therapeutic relevance of B-type natriuretic hormone and related peptides in children with congenital heart diseases

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with congenital cardiac diseases (CHD). A computerized literature search in the National Library of Medicine using the keywords "BNP assay" and "NT-proBNP assay"+neonate/s and newborn/s was performed. Next, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP measurements in children with CHD. Several authors suggested that BNP/NT-proBNP is clinically helpful as a diagnostic and prognostic marker for children with suspected CHD. BNP values are age dependent, even in paediatric populations. Unfortunately, accurate reference values for BNP and NT-proBNP for neonatal ages have only recently become available. As a result, the lack of homogenous and accurate decisional levels in the neonatal period greatly limits the clinical impact of the BNP assay, and also contributed to the production of conflicting results. Regardless of age, there is great variability in BNP/NT-proBNP values among CHD characterized by different hemodynamic and clinical conditions. In particular, cardiac defects characterized by left ventricular volume and pressure overload usually show a higher BNP response than CHD which is characterized by right ventricular volume or pressure overload. BNP and NT-proBNP may be considered helpful markers in the integral clinical approach for patients with CHD. Measurement of BNP cannot replace cardiac imaging (including echocardiography, angiography and magnetic resonance), but provide independent, low cost and complementary information for the evaluation of cardiac function and clinical status.

A multiplexed point-of-care assay for C-reactive protein and N-terminal pro-brain natriuretic peptide

Several new plasma protein biomarkers have been associated with increased risk of cardiovascular events. It would be of great value if sets of these markers could be measured in a multiplexed format at point-of-care settings. A major challenge is the extremely wide concentration range in which different plasma biomarkers are present. Two promising biomarkers for cardiac risk prediction are C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NTproBNP). The concentrations of these markers can differ by more than six orders of magnitude. Here we present a chip-based multiplexed assay for CRP and NTproBNP. The high-concentration analyte, CRP, is analyzed in a competitive format, whereas the low-concentration analyte, NTproBNP, is analyzed in a sandwich format. This allows concurrent measurement of the two analytes in a single multiplexed assay. The dynamic ranges for the two assays were optimized to match the relevant serum concentration ranges; thus, no dilutions were needed. Both assays exhibit good precision (5–15% in the clinically relevant concentration ranges), and the limit of detection for the NTproBNP assay was 5 ng/L. Patient plasma samples were used for comparison with clinical methods, resulting in coefficients of determination ( R 2) of 0.9762 and 0.9606 for NTproBNP and CRP, respectively.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide

To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Neurohormonal activation in patients with systemic sclerosis-related pulmonary arterial hypertension

Systemic sclerosis (SSc) is a connective tissue disease, which may lead to pulmonary artery hypertension (PAH). N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biologic marker for the diagnosis and treatment of congestive heart failure. The aim of our study was to investigate the potential role of the plasma NT-proBNP assay in the assessment of functional status and right heart performance in systemic sclerosis-related pulmonary hypertension (SScPAH). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, six-minute walk test (SMWT) and plasma NT-proBNP levels were recorded from 45 SSc patients. Mean value of NT-proBNP for SSc patients with PAH ( n = 14) was 691.7 ± 325.7 fmol/L compared to 417.4 ± 167.1 fmol/L for patients without PAH ( n = 31) ( p = 0.0007). In SSc patients we found a statistically significant correlation between NT-proBNP values and sPAP ( r = 0.32, p = 0.03). Amongst SScPAH patients, NT-proBNP values were significantly correlated with sPAP ( r = 0.73, p = 0.003) and inversely correlated with the SMWT ( r = − 0.60, p = 0.02). These results suggest NT-proBNP as a useful additional biological tool in the evaluation and management of SScPAH patients.

Utility of N terminal pro brain natriuretic peptide in elderly patients

Objective: To evaluate the utility of N terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic marker for diastolic dysfunction or failure, systolic dysfunction, and significant valve disorders in patients...

Comparison of BNP and NT-proBNP assays in the approach to the emergency diagnosis of acute dyspnea

N-terminal pro-brain natriuretic peptide (NT-proBNP) and BNP measurement could have a significant role in differentiating dyspnea between cardiac or pulmonary origin in the emergency room. The development of new and different commercial assays for these B-type natriuretic peptides offers the possibility of improving and simplifying their measurements but this could be defaulted due to the differences in methodology and the lack of assay standardization. We compared four available methods of measuring NT-proBNP and BNP and evaluated their usefulness in diagnosing the causes of breathlessness in the emergency room. The correlation of BNP with different assays was strong with r>0.98 (P<0.0001). Comparison studies between NT-proBNP and BNP procedures were in good agreement with r>0.87. The area under the receiver-operating characteristic curve (ROC) for BNP or NT-proBNP for detecting any cardiac dysfunction was higher than 0.96 (95% CI). A BNP value of 116 pg/mL measurement with the Access BNP assay (Beckman Coulter Inc., Fullerton, CA), a BNP value of 79 pg/mL with Advia Centaur BNP assay (Bayer Diagnostics, Tarrytown, NY), and an NT-proBNP level of 817 pg/mL in Elecsys NT-proBNP assay (Roche Diagnostic, Mannheim, Germany), showed both high sensitivity (>92%) and high specificity (>93%). We have found that NT-proBNP and BNP present similar diagnostic accuracies for the differential diagnosis of dyspnea.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations

Objective: To investigate the performance of a novel assay for N-terminal pro-brain natriuretic peptide (NT-proBNP) in diagnosing heart failure in various randomly selected general and high risk community populations.Design: Community...