B-type Natriuretic Peptide Concentrations Research Articles

Prognostic Role of NT-proBNP for in-Hospital and 1-Year Mortality in Patients with Acute Exacerbations of COPD.

Background and objectiveThe association between N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and in-hospital and 1-year mortality in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is largely unknown. Our objective was to explore the usefulness of NT-proBNP concentrations in AECOPD patients as a prognostic marker for in-hospital and 1-year mortality.MethodsNT-proBNP levels were measured in patients upon admission and laboratory and clinical data were also recorded. The cut-point for the NT-proBNP concentration level for in-hospital death was obtained using the receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression and Cox regression were used in the analyses of factors of in-hospital and 1-year mortality.ResultsA total of 429 patients were enrolled. Twenty-nine patients died during hospitalization and 59 patients died during the 1-year follow-up. Patients who died in-hospital compared with those in-hospital survivors were older (80.14±6.56 vs 75.93±9.45 years, p=0.003), had a higher percentage of congestive heart failure (65.52% vs 33.75%, p<0.001), had higher NT-proBNP levels (5767.00 (1372.50–12,887.00) vs 236.25 (80.03–1074.75) ng/L, p<0.001), higher neutrophil counts (10.52±5.82 vs 7.70±4.31, p=0.016), higher D-dimer levels (1231.62±1921.29 vs 490.11±830.19, p=0.048), higher blood urea nitrogen levels (9.91±6.33 vs 6.51±4.01 mmol/L, p=0.001), a lower body mass index (19.49±3.57 vs 22.19±4.76, p=0.003), and higher hemoglobin levels (122.34±25.36 vs 130.57±19.63, p=0.034). The area under the ROC curve (AUC) for NT-proBNP concentration was 0.88 (95% confidence interval [CI], 0.84–0.93). NT-proBNP concentrations ≥551.35 ng/L were an independent prognostic factor for both in-hospital and 1-year mortality after adjustment for relative risk (RR) (RR=29.54, 95% CI 3.04–286.63, p=0.004 for the multivariate logistic regression analysis) and hazard ratio (HR) (HR=4.47, 95% CI, 2.38–8.41, p <0.001 for the multivariate cox regression analysis).ConclusionNT-proBNP was a strong and independent predictor of in-hospital and 1-year mortality in AECOPD patients.

Association of Estimated Insulin Resistance with N-Terminal B-Type Natriuretic Peptide Concentration in Men with Metabolic Syndrome.

Background The diagnostic and prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure is well established. However, additional factors may influence its concentration. One of them is obesity, which in general is accompanied by reduced NT-proBNP levels. However, specific data concerning metabolic syndrome (MS) are equivocal. The aim of the present study was to evaluate the association of NT-proBNP with estimated insulin resistance (eIR) in men with MS. Methods In 86 male patients with MS (78 of them hypertensive), blood pressure, anthropometric measures, NT-proBNP, creatinine, glucose, and insulin were assessed and eIR was calculated using homeostatic model assessment (HOMA-IR). Results Both eIR and age were independently associated with NT-proBNP concentrations (b = 0.2248, p=0.019; b = 0.0102, p=0.049, respectively). Blood pressure, anthropometric measures, and eGFR were not correlated with NT-proBNP. Patients without eIR had higher NT-proBNP than those with eIR (32.2 ± 26.4 vs 21.4 ± 25.4 pg/mL, p=0.014). The difference was even higher in the younger subgroup of patients reaching nearly 50%. Conclusions Insulin resistance and, to a lesser degree, age were associated with NT-proBNP levels in men with MS. In younger subjects with eIR, mean NT-proBNP level was lower than in corresponding healthy age males.

P5673Combination of high-sensitivity cardiac troponin and B-Type natriuretic peptide (BNP) for diagnosis and risk-stratification of syncope

Abstract Background While high-sensitivity cardiac troponin (hs-cTn) and B-Type natriuretic peptide (BNP) have been assessed separately for the diagnosis and risk-stratification of patients with syncope, their combined accuracy is unknown. Methods We assessed the diagnostic and prognostic accuracy of the combination of hs-cTnI and BNP in a prospective international multicenter study enrolling patients 40 years and older presenting with syncope to the emergency department (ED). Hs-cTnI (Architect) and BNP (Architect) concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two independent physicians using all available clinical information including one year follow-up, was the diagnostic endpoint. MACE were defined as death, resuscitation, life-threatening arrhythmia, implantation of a pacemaker or implantable cardioverter defibrillator (ICD), acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack (TIA), intracranial bleeding or valvular intervention. Patients were classified in three risk groups (low (&lt;10%), medium (10–30%), high (&gt;30%)) for cardiac syncope based on hs-cTnI and BNP levels. Results Among 1533 patients, cardiac syncope was the adjudicated final diagnosis in 233 (15.2%). Hs-cTnI and BNP concentrations both remained independent predictors of cardiac syncope in multivariable models. The diagnostic accuracy of the combination hs-cTnI/BNP for cardiac syncope was good with an area under the curve (AUC) of 0.81 (95%-CI 0.78–0.84) and significantly better than each biomarker separately or a set of clinical variables (each p&lt;0.001). The classification of patients in three risk groups, depending on the probability for cardiac syncope based on their hs-cTnI and BNP values, translated well in predictions for MACE (AUC 0.79, 95%-CI 0.77–0.82) and death (AUC 0.78, 95%-CI 0.74–0.82) at 2 years follow-up. Based on these results, we designed a visual tool allowing convenient patient-specific diagnostic and prognostic risk evaluation based solely on hs-cTnI and BNP concentrations (Figure). Risk stratification based on hs-cTnI/BNP Conclusion The combination hs-cTnI/BNP may have clinical utility in patients presenting to the ED with syncope as it allows good diagnostic as well as prognostic discrimination. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University Basel

P3532Quantifying hemodynamic cardiac stress and cardiomyocyte injury in hypertensive and normotensive acute heart failure

Abstract Background Better characterization of the different pathophysiological mechanisms involved in normotensive and hypertensive acute heart failure (AHF) might help to develop novel individualized treatment strategies. Methods The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring B-type natriuretic peptide (BNP) as well as high-sensitive cardiac troponin T (hs-cTnT) in 1,152 unselected patients presenting with AHF to the emergency department (derivation cohort). Systolic blood pressure (SBP) of 90 - 140 mmHg at presentation was used to define normotensive AHF. Findings regarding hemodynamic cardiac stress and cardiomyocyte injury were validated in a second independent AHF cohort (validation cohort; n=324). Results In the derivation cohort 667 (58%) patients had hypertensive AHF. Hemodynamic cardiac stress, as quantified by BNP levels, was significantly higher in normotensive AHF as compared to hypertensive AHF (1,105 pg/mL versus 827 pg/mL, p&lt;0.001). In addition, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF (41 ng/L versus 33 ng/L, p&lt;0.001). These findings were confirmed in the validation cohort. Table 1. Cardiac stress and myocardial necrosis as quantified by BNP and hs-cTnT plasma concentrations Overall Hypertensive AHF Normotensive AHF p-value BNP in pg/ml, median (IQR) 974 (536–1,712) 827 (448–1,419) 1,105 (611–1,956) &lt;0.001 hs-cTnT in ng/L, median (IQR) 37 (22–67) 33 (19–59) 41 (24–71) &lt;0.001 BNP = B-type natriuretic peptide; hs-cTnT = high-sensitivity cardiac Troponin T; IQR = inter-quartile range. Figure 1 Conclusion Biomarker profiling revealed that the extent of hemodynamic stress and cardiomyocyte injury is different in patients with normotensive and hypertensive AHF. This characterization could help to understand AHF phenotypes better, which in turn may lead to more specific management in future, thus improving the dismal prognosis in these patients. Acknowledgement/Funding European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel

Detection of Neprilysin-Derived BNP Fragments in the Circulation: Possible Insights for Targeted Neprilysin Inhibition Therapy for Heart Failure.

Entresto™ is a new heart failure (HF) therapy that includes the neprilysin (NEP) inhibitor sacubitril. One of the NEP substrates is B-type natriuretic peptide (BNP); its augmentation by NEP inhibition is considered as a possible mechanism for the positive effects of Entresto. We hypothesized that the circulating products of BNP proteolysis by NEP might reflect NEP impact on the metabolism of active BNP. We suggest that NEP-based BNP cleavage at position 17-18 results in BNP ring opening and formation of a novel epitope with C-terminal Arg-17 (BNP-neo17 form). In this study, we use a specific immunoassay to explore BNP-neo17 in a rat model and HF patient plasma. We injected BNP into rats, with or without NEP inhibition with sacubitril. BNP-neo17 in plasma samples at different time points was measured with a specific immunoassay with neglectable cross-reactivity to intact forms. BNP-neo17 and total BNP were measured in EDTA plasma samples of HF patients. BNP-neo17 generation in rat circulation was prevented by NEP inhibition. The maximum 13.2-fold difference in BNP-neo17 concentrations with and without sacubitril was observed at 2 min after injection. BNP-neo17 concentrations in 32 HF patient EDTA plasma samples ranged from 0 to 37 pg/mL (median, 5.4; interquartile range, 0-9.1). BNP-neo17/total BNP had no correlation with total BNP concentration (with r = -0.175, P = 0.680) and showed variability among individuals. BNP-neo17 formation is NEP dependent. Considering that BNP-neo17 is generated from the active form of BNP by NEP, we speculate that BNP-neo17 may reflect both the NEP activity and natriuretic potential and serve for HF therapy guidance.

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP

ObjectivesThis study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF. BackgroundThe endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload. MethodsANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study’s goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3′,5′cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects. ResultsIn cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003). ConclusionsAmong a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

ProBNP That Is Not Glycosylated at Threonine 71 Is Decreased with Obesity in Patients with Heart Failure.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients. Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were <15%; limits of detection were <21 ng/L; and samples diluted in parallel. Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44-664), 114 (18-254), and 179 (880-3459) ng/L vs 36 (18-229), 36 (18-175), and 40 (17-68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI <30 kg/m2. Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

Carvedilol Among Patients With Heart Failure With a Cocaine-Use Disorder

ObjectivesThis study sought to assess the safety of carvedilol therapy among heart failure (HF) patients with a cocaine-use disorder (CUD). BackgroundAlthough carvedilol therapy is recommended among certain patients with HF, the safety and efficacy of carvedilol among HF patients with a CUD is unknown. MethodsThis was a single-center study of hospitalized patients with HF. Cocaine use was self-reported or defined as having a positive urine toxicology. Patients were divided by carvedilol prescription. Subgroup analyses were performed by strata of ejection fraction (EF) ≤40%, 41% to 49%, or ≥50%. Major adverse cardiovascular events (MACE) were defined as cardiovascular mortality and 30-day HF readmission. ResultsFrom a cohort of 2,578 patients hospitalized with HF in 2011, 503 patients with a CUD were identified, among whom 404 (80%) were prescribed carvedilol, and 99 (20%) were not. Both groups had similar characteristics; however, those prescribed carvedilol had a lower LVEF, heart rate, and N-terminal pro–B-type natriuretic peptide concentrations at admission and on discharge, and more coronary artery disease. Over a median follow-up of 19 months, there were 169 MACEs. The MACE rates were similar between the carvedilol and the non-carvedilol groups (32% vs. 38%, respectively; p = 0.16) and between those with a preserved EF (30% vs. 33%, respectively; p = 0.48) and were lower in patients with a reduced EF taking carvedilol (34% vs. 58%, respectively; p = 0.02). In a multivariate model, carvedilol therapy was associated with lower MACE among patients with HF with a CUD (hazard ratio: 0.67; 95% confidence interval; 0.481 to 0.863). ConclusionsOur findings suggest that carvedilol therapy is safe for patients with HF with a CUD and may be effective among those with a reduced EF.

HeartLogic Performs as Well as NT-proBNP to Rule out Acute Heart Failure at Point of Care

Background The ESC Guidelines recommend the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration in all patients who present to emergency rooms with acute dyspnoea and suspected acute decompensated heart failure (HF), with a decision cut-off (NT-proBNP Purpose The purpose of this analysis was to compare the diagnostic accuracy of NT-proBNP and HeartLogic to rule out ADHF in acute settings. Methods The MultiSENSE study followed 900 HF patients with implanted CRT-Ds for up to 1 year. All hospitalizations were adjudicated by an independent panel of clinicians, and classified as HF or non-HF based on the presenting cause. Optional NT-proBNP tests were conducted when patients were hospitalized. The composite HeartLogic index of the day before each of the hospitalization dates were extracted to differentiate HF and non-HF hospitalizations. By varying the HeartLogic index decision cutoff, a ROC curve was generated to assess the prediction accuracy of HeartLogic and compared to the counterpart performance of NT-proBNP using Hanley and McNeil's method. Results Of the total 603 hospitalizations, 76 hospitalizations (52 HF, 24 non-HF) had both valid NT-proBNP measures within 48 hours of admission (71 within 24 hours), and valid HeartLogic for the day before the hospitalization date. Figure 1 illustrates that the HeartLogic -based ROC was similar to the ROC of NT-proBNP (AUC of 0.809 and 0.803, respectively, p=0.932). An exclusion criterion of HeartLogic index Conclusion HeartLogic showed similar accuracy for differentiating HF and non-HF hospitalizations in the MultiSENSE dataset as NT-proBNP. HeartLogic may be used in the acute setting to exclude acute decompensated heart failure.

Fetal cardiac remodeling and dysfunction is associated with both preeclampsia and fetal growth restriction

Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus. To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies. This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted. Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies. Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidatethe mechanism(s) underlying fetal cardiac adaptation in these conditions.

Maternal and cord blood homocysteine, vitamin B12, folate, and B-type natriuretic peptide levels at term for predicting congenital heart disease of the neonate: A case-control study

Objective: To investigate the effectiveness of the metabolic markers homocysteine, vitamin B12, folate, and B-type natriuretic peptide in maternal and cord blood for detecting congenital heart disease.Methods: Homocysteine, vitamin B12, folate, and B-type natriuretic peptide concentrations in maternal and cord blood samples at term were measured in the case (n = 42) and control (n = 43) groups with and without fetal congenital heart disease, respectively. Additionally, newborns with congenital heart disease were divided into two subgroups: those with (n = 30) and without (n = 8) 6-month infant survival. The case and control groups and case subgroups were compared with each other with respect to maternal age, gravidity, parity, gestational age at delivery, birth weight, maternal and cord blood levels of homocysteine, vitamin B12, folate, and B-type natriuretic peptide, and arterial cord blood pH and base excess values. Statistical analyses were performed using SPSS for Windows, version 22.0. The Student’s t-test, the Mann–Whitney U test, and the χ2 test were used where appropriate. A p value of < .05 was considered statistically significant.Results: Mean maternal age, birth weight and median gravidity, parity and gestational age at delivery were not significantly different between the case and control groups, as well as between the case subgroups (all p > .05). Concentrations of metabolic markers in maternal blood were not significantly different between the two groups (p > .05). Homocysteine and B-type natriuretic peptide levels in cord blood samples were significantly higher, whereas folate levels were significantly lower in the case group compared with the control group (all p < .05). Cord blood B-type natriuretic peptide levels were significantly higher (p < .05) and arterial cord blood pH values were significantly lower (p < .05) in the case subgroup without 6-month infant survival compared with the case subgroup with 6-month infant survival.Conclusion: High cord blood B-type natriuretic peptide and homocysteine levels and low cord blood folate levels at term may be useful for predicting congenital heart disease in the neonate. Neonates with congenital heart disease who have high cord blood B-type natriuretic peptide and low pH values may have adverse outcomes.

In vitro stability of B-type natriuretic peptide (BNP) in plasma stored under different conditions when measured with the Lumipulse® assay

Natriuretic peptides are a laboratory tool with significant implications for the diagnosis and prognosis of heart failure (HF). The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that assays must be examined for sample stability because there appears to be assay dependent. We aimed to evaluate the in vitro stability of B-type natriuretic peptide (BNP) under different handling conditions and using a BNP assay from Fujirebio Diagnostics (Tokyo, Japan). BNP concentrations were measured in plasma EDTA samples from 11 subjects to evaluate the in vitro stability at room temperature and at 4 °C and in 10 subjects to check the in vitro stability of samples stored at –20 °C during 1 and 3 months. Stability limit was defined according to Spanish Society of Laboratory Medicine (SEQC-ML) recommendations. At room temperature and 4 °C, BNP concentrations decreased progressively in samples collected in both groups, remaining stable within four hours from collection. BNP concentrations also were stable within four hours from collection in whole blood at room temperature. Finally, at –20 °C, BNP concentrations remained stable in both groups at 1 and 3 months, respectively. According to our results, BNP, stored at room temperature or at 4 °C, should be assayed in the first four hours after collection. Besides, BNP was shown to be stable in whole blood for at least four hours at room temperature. If the testing cannot be performed within the first four hours, the plasma should be frozen and kept at –20 °C for up to 3 months.

Analyte-resolved magnetoplasmonic nanocomposite to enhance SPR signals and dual recognition strategy for detection of BNP in serum samples

B-type natriuretic peptide (BNP) is a short peptide that is considered to be an important heart failure (HF)-related biomarker. Due to its low concentration in the blood and short half-life, the sensitive detection of BNP is a bottleneck for diagnosing patients at early stages of HF. In this paper, we report a facile surface plasmon resonance (SPR) sensor to measure BNP; the sensor is based on aptamer-functionalized Au nanoparticles (GNPs-Apt) and antibody-modified magnetoplasmonic nanoparticles (MNPs-Ab) to enable dual screening of BNP in complex environments. During sensing, BNP forms MNP-Ab/BNP/GNP-Apt nanoconjugates that can be rapidly separated from the complex sample by a magnet to avoid degradation within the analyte's half-life. The developed SPR biosensor shows high selectivity, a wide dynamic response range of BNP concentrations from 100 fg/mL to 10 ng/mL, and a low detection limit of 28.2 fg/mL (S/N = 3). Using the proposed sensor, BNP was successfully detected in clinical samples. Thus, the designed SPR biosensor provides a novel and sensitive sensing platform for BNP detection with potential applications in clinical practice.

Analytical performance of a single epitope B-type natriuretic peptide sandwich immunoassay on the Minicare platform for point-of-care diagnostics

Point-of-care B-type natriuretic peptide (BNP) testing with adequate analytical performance has the potential to improve patient flow and provide primary care givers with easy-to-use advanced diagnostic tools in the management of heart failure. We present the analytical evaluation of the Minicare BNP immunoassay under development on the Minicare I-20 platform for point-of-care testing. Analytical performance was evaluated using EDTA venous whole blood, EDTA plasma and capillary whole blood. Method comparison with a lab-testing system was performed using samples from 187 patients. Normal values were determined based on 160 healthy adults, aging from 19 to 70 years. Limit of blank (LoB), limit of detection (LoD) were determined to be 3.3 ng/L, 5.8 ng/L. Limit of quantitation (LoQ) in whole blood at 20% and 10% coefficient of variation (CV) was found < 9 ng/L and <30 ng/L respectively without significant differences between EDTA whole blood and EDTA plasma. Total CV was found to be from 6.7% to 9.7% for BNP concentrations between 92.6 and 3984 ng/L. The sample type comparison study demonstrated correlation coefficients between 0.97 and 0.99 with slopes between 1.03 and 1.09 between the different samples. Method comparison between Minicare BNP and Siemens ADVIA Centaur BNP demonstrated a correlation coefficient of 0.92 with a slope of 1.06. The 97.5% URL of a healthy population was calculated to be 72.6 ng/L. The Minicare BNP assay is a robust, easy-to-use and sensitive test for rapid determination of BNP concentrations that can be used in a near-patient setting.

B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial

BackgroundNatriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro–B-type natriuretic peptides (NT-proBNP) has been preferred and recommended. ObjectivesThe purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan. MethodsBNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF. ResultsMedian BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively). ConclusionsCirculating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)

Effect of Neprilysin Inhibition on VariousNatriuretic Peptide Assays.

With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP1-108, or C-type natriuretic peptide (CNP) is not well understood. This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP1-108, and CNP were measured over 3 visits. Average time to 3 follow-up visits was 22, 46, and 84days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.

B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope.

The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding, or valvular surgery. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) served as the prognostic comparators. Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope versus other causes (P<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74-0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 0.68 [95%-CI 0.65-0.71], P<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an area under the curve of 0.81 (P<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75-0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS. BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope. URL: https://www. gov. Unique identifier: NCT01548352.

Elevated Level of Plasma B-Type Natriuretic Peptide (BNP) as a Prognostic Marker in Patients with Acute Coronary Syndrome

Acute coronary syndrome (ACS), a life-threatening manifestation of coronary artery disease, ranges from unstable angina (UA) to acute myocardial infarction (AMI). To reduce the morbidity and mortality resulting from acute coronary syndrome, we should have to find out some predictor or prognostic indicator. A prognostic indicator should be available at the time of initial patient’s evaluation, in order to maximize the potential benefits of early risk assessment. This study designed to evaluate plasma BNP as a prognostic tool in patients with acute coronary syndrome. A prognostic cohort study was carried out with 90 (ninety) acute coronary syndrome patients on the basis of their clinical and laboratory criteria with age range of 30 to 90 years in the department of biochemistry, BSMMU, in collaboration with department of cardiology, NICVD, BSMMU and BIRDEM. Plasma BNP concentrations were measured on enrollment and then grouping of the study subjects were done on the basis of their empirical cut off value of plasma BNP concentration. All the patients were free from heart failure, renal disease, thyroid disease and hepatic disorder. Main outcomes were mortality, morbidity and survival after hospital discharge with or without any disability. All the subjects were categorized into two and to see the significance between two groups in relation to age and sex Unpaired –t test and Chi square test were done. Finally, Binary logistic regression was done. Among 90 acute coronary syndromes patients, there were 74(82.2%) male and 16(17.8%) female with mean age of the study population 51.8 years and the age range of 30 t0 90 years. Among enrolled patients, 24 (26.7%) were NSTEMI and 66 (73.3%) were STEMI that includes 29 (32.2%) anterior MI, 21 (23.3%) inferior MI, 16 (17.8%) other varieties of MI. All the study subjects were grouped into two on the basis of empirical cut off value of plasma BNP 640pg/ml on enrollment. Group I with plasma BNP level less than 640pg/ml includes 57 (63.3%) subjects and group II with plasma BNP more than 640pg/ml includes 33 (36.7%) subjects. Among group I (n=57) good recovery, morbidity and mortality found to be in 41(71.9%), 15(26.3%) and 1(1.8%) patients and those in group II (n=33) found in 6(18.2%), 19(57.6%) and 8(24.2%) patients respectively. Keeping the group I in reference category binary logistic regression analysis done, showing odds ratio 11.5 with p- value 0.000. The odds ratio 11.5 indicates that there is 11.5 times higher chance of getting bad outcome in ACS patients having higher plasma BNP concentrations.&#x0D; Bangladesh Med J. 2017 May; 46 (2): 32-37

Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure

BackgroundAcute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril–valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown.MethodsWe enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.ResultsOf the 881 patients who underwent randomization, 440 were assigned to receive sacubitril–valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril–valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril–valsartan group as compared with 0.75 in the enalapril group (percent change, −46.7% vs. −25.3%; ratio of change with sacubitril–valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril–valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.ConclusionsAmong patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890.)

Sex-related risks of recurrence of atrial fibrillation after ablation: Insights from the Guangzhou Atrial Fibrillation Ablation Registry

Female sex has been linked with worse prognosis in patients with atrial fibrillation (AF). Clinical risk stratification of women with AF may help decision-making before catheter ablation (CA). To evaluate arrhythmia outcomes and the predictive value of clinical scores for arrhythmia recurrence in a large cohort of Chinese patients with AF undergoing CA. A total 1410 of patients (68.1% men) who underwent AF ablation with scheduled follow-up were analysed retrospectively. Baseline characteristics and ablation outcome were compared between men and women. The predictive values of risk scoring systems for AF recurrence were assessed in women. Recurrence, early recurrence and complications after CA were similar in women and men over similar follow-up periods (20.7±8.0 vs 20.7±9.1 months; P>0.05). Compared with men, women with AF recurrence were older and had a larger left atrial diameter (LAD), less paroxysmal AF, lower left ventricular ejection fraction, lower estimated glomerular filtration rate (eGFR) and higher serum concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) (all P<0.01). Multivariable analysis showed that age, non-paroxysmal AF, body mass index, coronary artery disease, LAD, early recurrence, eGFR, BNP and CRP were independent risk factors with sex differences (all P<0.05) in the whole cohort. In women, only non-paroxysmal AF, early recurrence, BNP, CRP (all P<0.01) and history of stroke/transient ischaemic attack (P=0.016) were independent risk factors. Of the clinical scoring systems tested, MB-LATER, APPLE, CAAP-AF and BASE-AF2 scores (C-indexes 0.73, 0.72, 0.68 and 0.72, respectively; all P<0.01) had a modest predictive value for AF recurrence after CA in women. CA for AF has similar recurrence risks in women and men, but there are sex differences in the clinical characteristics and risk factors associated with AF recurrence.