BNP Detection Research Articles

Calycosin alleviates ferroptosis and attenuates doxorubicin-induced myocardial injury via the Nrf2/SLC7A11/GPX4 signaling pathway

BackgroundHeart failure is primarily characterized by damage to the structure and function of the heart. Ferroptosis represents a form of programmed cell death, and studies indicate that it constitutes one of the primary mechanisms underlying cardiomyocyte death in heart failure. Calycosin, a natural compound derived from astragalus, exhibits various pharmacological properties, including anti-ferroptosis, antioxidant effects, and cardiovascular protection. Nonetheless, the specific role of Calycosin in the treatment of ferroptosis in heart failure remains poorly understood.ObjectiveThis study aims to elucidate the regulatory effect of Calycosin on ferroptosis and its influence on the treatment mechanisms of heart failure through in vivo and in vitro experiments.MethodsA rat model of heart failure was induced using doxorubicin, and the cardiac function was evaluated through cardiac ultrasound examination and NT-Pro BNP detection. Myocardial injury was assessed using H&E staining and Masson staining. The extent of mitochondrial damage was evaluated through transmission electron microscopy. Concurrently, the level of ferroptosis was analyzed by measuring ferroptosis markers, including MDA, ferrous ions, the GSH/GSSG ratio, and GPX4 activity. Subsequently, the molecular mechanism by which Calycosin exerts its therapeutic effects in heart failure was investigated through immunofluorescence and Western blotting. Finally, H9c2 cardiomyocytes were treated with doxorubicin to simulate myocardial injury, and the mechanism by which Calycosin mediates its effects in the treatment of heart failure was further verified through Nrf2 gene silencing.ResultsCalycosin significantly improves cardiac function in rats, reduces serum NT-Pro BNP levels, and alleviates myocardial cell damage. Additionally, it significantly decreases the levels of ferroptosis in myocardial tissue, as confirmed through transmission electron microscopy and the assessment of ferroptosis markers, including MDA, ferrous ions, GSH, and GPX4 activity. At the molecular level, Calycosin exerts its effects by activating the Nrf2/SLC7A11/GPX4 signaling pathway, evidenced by the upregulation of Nrf2, SLC7A11, GPX4, GSS, and GCL protein expression. This process substantially enhances the antioxidant capacity of rat myocardial tissue and effectively suppresses ferroptosis in myocardial cells. The results obtained from both in vivo and in vitro experiments are consistent. Notably, when Nrf2 is silenced, the protective effect of Calycosin on the myocardium is markedly diminished.ConclusionCalycosin effectively treats doxorubicin-induced cardiac injury, and its therapeutic effect is likely closely associated with the activation of the Nrf2/SLC7A11/GPX4 signaling pathway and the inhibition of ferroptosis in myocardial cells. Consequently, Calycosin, as a promising compound against doxorubicin-induced cardiotoxicity, warrants further investigation.

The Effects of Different Blood Sample and Anticoagulant Types on Quantitative Tests of B-Type Natriuretic Peptide.

BNP is a sensitive and widely used biomarker for an early diagnosis of heart failure. Currently, most commercial BNP detection products use EDTA plasma samples. The aim of this study was to evaluate the clinical performance of the BNP test by using whole blood samples compared to plasma samples, and to evaluate the effect of the anticoagulant type on the BNP test result. In total, 106 patients with different BNP levels from the Dahua Hospital volunteered for this study. Clinically homogenous samples, including EDTA anticoagulant plasma, EDTA whole blood, and heparin anticoagulant plasma, were collected and analyzed by using i-Reader S automatic immuno-analyzer and its supporting reagent kits. Pearson's correlation and weighted least squares linear regression analysis, Bland-Altman plotting, and Kappa test were used for statistical analysis. Correlation analysis showed that BNP concentrations, measured from EDTA anticoagulated plasma samples, had a good linear regression relationship with BNP from whole blood samples, with a slope of 0.9477, r = 0.9978, p < 0.05. A similar correlation was observed between EDTA anticoagulated plasma samples and heparin anticoagulant plasma, with a slope of 0.8413, r = 0.9793, p < 0.05. The BNP concentration measured from the heparin plasma samples were lower than of the EDTA plasma samples. Bland-Altman analysis for assessing BNP concentration agreement showed there was no outlier ratio between EDTA whole blood and EDTA plasma within the range of the detection system, as well as no outlier between EDTA anticoagulated and heparin anticoagulant plasma. Kappa coefficient of BNP concentration between homologous EDTA anticoagulated and heparin anticoagulant plasma was 0.8553 (p < 0.001), and for EDTA anticoagulated plasma and homologous whole blood it was 0.8941 (p < 0.001). The diagnostic performance of EDTA anticoagulated whole blood samples did not differ significantly from EDTA anticoagulated plasma samples for the BNP test. This study showed no big significant difference between EDTA anticoagulated and heparin anticoagulated plasma measurements within 2 hours. The type of anticoagulant should be carefully chosen when performing the BNP test if BNP samples were in vitro for a long time.

Retracted: Early Diagnosis and Prediction of Death Risk in Patients with Sepsis by Combined Detection of Serum PCT, BNP, Lactic Acid, and Apache II Score.

[This retracts the article DOI: 10.1155/2022/8522842.].

The predictive value of eGFR combined with BNP detection in acute kidney injury after acute myocardial infarction.

The combined detection of eGFR and BNP may provide some value in predicting the occurrence of AKI after AMI, and the study is designed to propose and validate this hypothesis. In retrospective research, AMI patients hospitalized at Weifang People's Hospital from January to December 2020 were included. Whether AKI occurred within a week of admission, patients were divided into two groups. Clinical data from two groups of patients were collected, and the Logistic regression model analysed the risk factors for AKI after AMI. The association between eGFR and BNP was analysed using Pearson linear correlation. The predictive value of eGFR and BNP alone and combined detection on AKI after AMI was analysed using the receiver operating characteristic (ROC) curve. Multivariate logistic regression showed that eGFR, BNP, HDLC, UA, and K ions were AKI risk factors (P < 0.05). The eGFR correlates negatively with BNP (R = -0.324, P < 0.05). The area under the curve (AUC) of eGFR and BNP alone and combined prediction for post-AMI AKI were 0.793, 0.826, and 0.831, respectively. The combined detection of eGFR and BNP has a high predictive value for AKI development in AMI patients.

Hydrogel Encapsulated Core–Shell Photonic Barcodes for Multiplex Biomarker Quantification

Acute myocardial infarction (AMI) is one of the most fatal diseases in the world in recent decades. Because rapid and accurate determination of AMI has the potential to save millions of lives globally, the development of new diagnostic method is of great significance. Here, we designed a magnetic responsive structural color core-shell hydrogel microcarrier as a novel platform for a high-throughput detection of a variety of cardiovascular biomarkers. The composite hydrogel shell was formed from methacrylated gelatin, acrylic acid, and poly(ethylene glycol diacrylate), and the core silica photonic crystals acted as a detector. Fe3O4 nanoparticles were infused into the void of the core-shell structure to impart magnetic response properties to the encoded carrier. The findings indicated that our method possessed high sensitivity and reliable specificity in the high-throughput detection of AMI-related biomarkers Myo, cTnI, and BNP. In addition, the developed method not only showed good specificity and high sensitivity in clinical samples but also was comparable to the clinical gold standard method. Therefore, the magnetic response structural color core-shell hydrogel carriers were regarded as a potential approach to detect some AMI disease-related biomarkers.

Dual‐signal immuno‐competitive determination of brain natriuretic peptide based on magnetic nanozyme

AbstractBrain natriuretic peptide (BNP) has been a disease marker in the diagnosis of heart failure. In this study, gold nanoparticles modified with Hemin (H‐AuNPs) as nanozymes were used to oxidize ABST and MB to amplified colorimetric and electrochemical redox signals respectively. BNP was combined with H‐AuNPs (BNP‐H‐AuNPs) through electrostatic adsorption to construct competitive nanozyme probes. Target BNP in the sample compete with BNP‐H‐AuNPs to bind the antibody‐modified magnetic nanoparticles (AntiBNP‐MNPs). Due to the excellent catalytic performance of the nanozyme, BNP can be observed well by colorimetric and electrochemical assays. Electrochemical method ensured more accurate detection of BNP with a wide detection range (1–200 pg/mL) and a low detection of limit (0.03 pg/mL). Meanwhile, the results of the experiment can be easily observed with the naked eye by simple colorimetric method with a range from 5 ng/mL to 25 ng/mL and a limit of detection down to 80.3 pg/mL. Thus, based on the important role of H‐AuNPs, this assay has exhibited potential value of detection the other small proteins through this competitive nanozyme method.

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.

Low limit of detection of the AlGaN/GaN-based sensor by the Kelvin connection detection technique

The AlGaN/GaN-based sensor is a promising POCT (point-of-care-testing) device featuring miniaturization, low cost, and high sensitivity. BNP is an effective protein biomarker for the early diagnosis of HF (heart failure). In this work, a novel AlGaN/GaN device with the Kelvin connection structure and the corresponding detection technique was proposed. This technique can effectively suppress the background noise and improve the SNR (signal-to-noise ratio). A BNP detection experiment was carried out to verify the effectiveness of this technique. It is shown that compared with that of the traditional detection method, the LOD (limit of detection) was improved from 0.47 ng/mL to 1.29 pg/mL. The BNP detection experiment was also carried out with a traditional electrochemical Au-electrode sensor with the same surface functionalization steps. The AlGaN/GaN sensor showed a better LOD than the Au-electrode sensor. Moreover, the influence of AlGaN/GaN sensor package on background noise was investigated with the mechanism of the noise source revealed. Finally, based on the optimized package, the optimal SNR quiescent operating point of the AlGaN/GaN sensor was determined. By biasing the sensor at the optimal quiescent operating point and immobilizing the magnetic beads with anti-BNP on the gate of the AlGaN/GaN sensor, the LOD for BNP detection was further improved to 0.097 pg/mL.

Induced bioresistance via BNP detection for machine learning-based risk assessment

Machine Learning (ML) is a powerful tool for big data analysis that shows substantial potential in the field of healthcare. Individual patient data can be inundative, but its value can be extracted by ML's predictive power and ability to find trends. A great area of interest is early diagnosis and disease management strategies for cardiovascular disease (CVD), the leading cause of death in the world. Treatment is often inhibited by analysis delays, but rapid testing and determination can help improve frequency for real time monitoring. In this research, an ML algorithm was developed in conjunction with a flexible BNP sensor to create a quick diagnostic tool. The sensor was fabricated as an ion-selective field effect transistor (ISFET) in order to be able to quickly gather large amounts of electrical data from a sample. Artifical samples were tested to characterize the sensors using linear sweep voltammetry, and the resulting data was utilized as the initial training set for the ML algorithm, an implementation of quadratic discriminant analysis (QDA) written in MATLAB. Human blood serum samples from 30 University of Pittsburgh Medical Center (UPMC) patients were tested to evaluate the effective sorting power of the algorithm, yielding 95% power in addition to ultra fast data collection and determination.

Implications of Cardiac Markers in Risk-Stratification and Management for COVID-19 Patients

Background: Coronavirus disease (COVID-19) has resulted in high mortality worldwide. However, information regarding cardiac markers for precise risk-stratification is limited. We aimed to discover a sensitive and reliable early-warning biomarker for optimizing management and improving COVID-19 patients’ prognosis. Methods: This single-center case series was conducted between February 4 and April 10, 2020. In total, 2,954 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included in the retrospectively selected cohort. All patients were diagnosed with COVID-19 and treated at the study site. Data of serum levels of cardiac markers, coronary artery disease (CAD) diagnosis, and survival were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression.Findings: Median patient age was 60 years (range, 50-68 years); 1,461 (49.5%) were female, and 1,515 (51.3%) patients were in a severe/critical condition. Compared to mild/moderate patients (1,439, 48.7%), severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. Among severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide had a significantly higher mortality rate than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide levels than those without CAD. Enhanced SARS-CoV-2 receptor expression was observed in patients with CAD. Regression analysis revealed that patients with elevated brain natriuretic peptide levels were at a higher risk of death (hazards ratio, 1.001 [95% confidence interval, 1.0003-1.002]).Interpretation: Brain natriuretic peptide is an effective biomarker for risk assessment in COVID-19 patients with or without pre-existing CAD. The detection of BNP is widely used in clinical practice and can be easily implemented in hospitals at all levels.Funding Statement: This research was supported by grants from National Nature Science Foundation of China (Grant No. 31771334, 81970428, 91959113, 81972358, 81572893), the Key Research Plan of the National Natural Science Foundation of China (Grant No. 81820108002), the Major Research Plan of the National Natural Science Foundation of China (Grant No. 91649125, 91639204), Key Foundation of Wuhan Huoshenshan Hospital (Grant No. 2020[18]), Key Research & Development Program of Jiangsu Province (Grant Nos. BE2017733, BE2018713), Medical Innovation Project of Logistics Service (Grant No. 18JS005), Basic Research Program of Jiangsu Province (Grant No. BK20180036), and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No.18KJB180014).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study design was approved by the institutional ethics board. Written informed consent was waived due to the urgency of the COVID-19 pandemic.

Clinical value of hs-CRP and BNP detection in the diagnosis and treatment of COPD patients with pulmonary heart disease

Objective To investigate the application value of hs-CRP and BNP detection in COPD patients with pulmonary heart disease. Methods From January 2016 to January 2018, 80 patients with COPD in the Fifth People's Hospital of Datong were selected.Forty-two COPD patients complicated with pulmonary heart disease were selected as COPD and cor pulmonale group, 38 COPD patients without pulmonary heart disease were selected as COPD group, and 30 healthy volunteers were selected as control group.The differences of hs-CRP and BNP levels were compared, and the diagnostic value of hs-CRP and BNP for COPD combined with pulmonary heart disease was analyzed. Results There were statistically significant differences in hs-CRP[(72.5±20.4) mg/L vs.(37.5±9.8) mg/L vs.(3.7±1.2)mg/L], BNP[(362.8±86.9) ng/L vs.(125.9±34.8) ng/L vs.(28.5±9.9)ng/L] among the COPD and cor pulmonale group, COPD group and control group (F=9.245, 14.668, all P<0.05). The hs-CRP and BNP levels in the COPD and cor pulmonale group were significantly higher than those in the other two groups(t=19.294, 11.576, 21.385, 9.258, 9.258, all P<0.05), which of the COPD group were significantly higher than those of the control group (t=8.912, 12.567, all P<0.05). The best boundary value of BNP in diagnosis of COPD with cor pulmonale was 261.8ng/L, and its diagnostic sensitivity and specificity were 96.2% and 85.4%, respectively, the area under the line was 0.834, which were all higher than those of hs-CRP.With the increase of cardiac function, the levels of hs-CRP[(38.5±10.3) mg/L vs.(51.4±14.8) mg/L vs.(75.1±21.5) mg/L vs.(93.7±31.8)mg/L], BNP[(142.8±56.5) ng/L vs.(285.9±94.8) ng/L vs.(352.5±118.2) ng/L vs.(478.5±130.3)ng/L] increased, the differences were statistically significant (F=13.577, 16.776, all P<0.05). There were significant correlation between hs-CRP, BNP levels and COPD patients complicated with cor pulmonale (r=0.675, 0.766, all P<0.05). Conclusion hs-CRP and BNP have high diagnostic potency for COPD patients combined with cor pulmonale, and are positively correlated with cardiac function classification. Key words: Pulmonary disease, chronic obstructive; C-reactive protein; Natriuretic peptide, brain; Pulmonary heart disease; Ventricular function; Heart failure

Magnetic electrode-based electrochemical immunosensor using amorphous bimetallic sulfides of CoSnSx as signal amplifier for the NT[sbnd]pro BNP detection

In this work, by using amorphous bimetallic sulfides of CoSnSxPd as signal amplifier and magnetic material of Fe3O4 @PPyAu as the substrate, we fabricated an electrochemical immunoassay for Nterminal prohormone of brain natriuretic peptide (NTpro BNP). CoSnSx was used as the signal amplifier of the immunosensor for the first time, which was synthesized by fast stoichiometric co-precipitation method. The binary sulfide was identified as an amorphous structure and performed apparent electrochemical behavior. The excellent performance of signal marker was induced by the synergistic effect between SnS2 and cobalt, as well as the loaded Pd nanoparticles (NPs). Both CoSnSx and Pd NPs presented excellent electrocatalytic activity toward H2O2 oxidation. Moreover, the magnetic nanocomposite of Fe3O4 @PPyAu was firmly immobilized on the magnetic glassy carbon electrode (MGCE) by the magnetic force. The magnetic substrate not only performed good electron conductivity, but also improved the stability of the fabricated electrochemical immunosensor. The developed immunosensor for the NTpro BNP detection exhibited a wide linear response (0.1 pg/mL to 50 ng/mL), and low detection limit of 31.5 fg/mL. In addition, the immunosensor held an excellent analysis capability and broad fascinating application for the detection of other biomarkers in medical diagnosis and treatment.

A sandwich-type photoelectrochemical immunosensor for NT-pro BNP detection based on F-Bi2WO6/Ag2S and GO/PDA for signal amplification

A sandwich-type photoelectrochemical (PEC) immunosensing platform was designed for detection of amino-terminal pro-B-type natriuretic peptide (NT-pro BNP). Thereinto, flower-like Bi2WO6/Ag2S nanoparticles (F-Bi2WO6/Ag2S) were employed as photoelectrochemical matrix, and graphene oxide and polydopamine composite (GO/PDA) were prepared as signal labels. In this proposal, Ag2S was in-situ growth on the surface of F-Bi2WO6 modified with thioglycolic acid (TGA). Specially, a cascade-like band-edge level between F-Bi2WO6 and Ag2S effectively improved the photocurrent conversion efficiency and enhanced the photocurrent response. Then, the conjugated GO/PDA aimed to further amplify signal because PDA as electron donor could sweep the holes and inhibit the recombination of photogenerated electron-hole pairs, while GO owned brilliant conductivity speeding up the electrons transfer. The photocurrent increased with the amount of GO/PDA conjugates which had positive correlation with the NT-pro BNP. Under optimal experimental conditions, the proposed sandwich-type PEC immunosensor presented a desirable linear relationship ranged from 0.1 pg/mL to 100 ng/mL for NT-pro BNP with the detection limit of 0.03 pg/mL (S/N = 3). The prepared PEC immunosensor exhibited high stability and selectivity, which offered an innovative idea for the detection of other biomolecules.

Improved LFIAs for highly sensitive detection of BNP at point-of-care.

Heart failure (HF) has become a major cause of morbidity and mortality with a significant global economic burden. Although well-established clinical tests could provide early diagnosis, access to these tests is limited in developing countries, where a relatively higher incidence of HF is present. This has prompted an urgent need for developing a cost-effective, rapid and robust diagnostic tool for point-of-care (POC) detection of HF. Lateral flow immunoassay (LFIA) has found widespread applications in POC diagnostics. However, the low sensitivity of LFIA limits its ability to detect important HF biomarkers (e.g., brain natriuretic peptide [BNP]) that are normally present in low concentration in blood. To address this issue, we developed an improved LFIA by optimizing the gold nanoparticle (GNP)–antibody conjugate conditions (e.g., the conjugate pH and the amount of added antibody), the diameter of GNP and the concentration of antibody embedded on the test line and modifying the structure of test strip. Through these improvements, the proposed test strip enabled the detection of BNP down to 0.1 ng/mL within 10–15 min, presenting ~15-fold sensitivity enhancement over conventional lateral flow assay. We also successfully applied our LFIA in the analysis of BNP in human serum samples, highlighting its potential use for clinical assessment of HF. The developed LFIA for BNP could rapidly rule out HF with the naked eye, offering tremendous potential for POC test and personalized medicine.

Rapid loop-mediated isothermal amplification assays for grapevine yellows phytoplasmas on crude leaf-vein homogenate has the same performance as qPCR

A fluorescence-based real-time loop-mediated isothermal amplification (LAMP) assay for ‘Candidatus Phytoplasama solani’ (Bois noir phytoplasma; BNp) detection was developed and optimised for rapid laboratory and on-site BNp detection. This assay is highly specific, rapid and as sensitive as qPCR. It was validated according to European and Mediterranean Plant Protection Organisation recommendations. In addition, 286 grapevine leaf samples from the 2015 growing season were tested with this new real-time LAMP assay and an assay previously developed for detection of Flavescence dorée phytoplasma (FDp). These LAMP assays for detection of both BNp and FDp used without any DNA extraction step, which is a required step for qPCR analysis, were comparably effective to qPCR, and positive results were obtained in less than 35 min.

Diagnosis value of CRP combined with BNP detection in elderly patients with myocardial infarction heart failure

Objective To explore the diagnosis value of CRP combined with BNP detection in elderly patients with myocardial infarction heart failure. Methods 360 patients with myocardial infarction were selected as subjects.And they were divided into non-heart failure group(n=187) and heart failure group(n=173). The heart failure group was divided into three groups according to the NHYA heart function.To observe and compare the contents of BNP and CRP of patients in different groups. Results CRP in the non-heart failure group was (6.24±3.01)mg/L, which was significantly lower than (16.77±2.67)mg/L in the heart failure group (t=1 754.892, P<0.05). BNP in the non-heart failure group was (521.91±29.11)pg/L, which was significantly lower than (2 995.39±496.48)pg/L in the heart failure group (t=1 754.892, P<0.05). And the contents of BNP and CRP in high NHYA patients were more higher than those in low NHYA patients.The positive rate of CRP combined with BNP detection was 93.64%, which was higher than 69.44% in single CRP detection (χ2=32.622, P<0.05), and 79.44% in the single BNP detection (χ2=14.442, P<0.05). Conclusion The plasma BNP and CRP can help diagnose heart failure with old myocardial infarction and heart failure degree classification. Key words: C reactive protein; Natriuretic peptide, brain; Myocardial infarction; Heart failure

GW25-e4295 Efficacy of microRNA423-5p and BNP detection on evaluation of cardiac dysfunction after cardiac pacing

GW25-e4295 Efficacy of microRNA423-5p and BNP detection on evaluation of cardiac dysfunction after cardiac pacing

Changes and significance of plasma cardiotrophin-1 in children with heart failure

Objective To explore the changes and significance of plasma cardiotrophin-1(CT-1) in children with heart failure. Methods Forty children with heart failure(NYHA II, n=14; NYHA Ⅲ, n=16; NYHA Ⅳ, n=10) were chosen as observation group, and 20 healthy children without heart failure were taken as healthy control group.Plasma CT-1 was measured by a double antibody sandwich enzyme-linked immunosorbent assay(ELISA). N terminal probrain natriuretic peptide(NT-pro BNP) concentration was tested by Pu Rui fluorescent dry quantitative analyzer.Left ventricular ejection fraction(LVEF) was evaluated by GE Vivid 7 doppler echocardiography and cardiac function assessed by modified ROSS score.Plasma CT-1 level, NT-pro BNP and LVEF were compared between the 2 groups.The correlation of plasma CT-1 level with NT-pro BNP and LVEF were analyzed in patients with different degrees of heart failure. Results Plasma levels of CT-1 and NT-pro BNP were significantly higher in children with heart failure than those in healthy control group(P<0.01), and with progression of heart failure, the levels of CT-1 and NT-pro BNP progressively increased in heart failure children.Plasma CT-1 level in different NYHA had statistical significance(F=55.5, P<0.01). Plasma CT-1 level was positive correlated with NT-pro BNP and modified ROSS score(r=0.787, 0.848, all P<0.01), and negative associated with LVEF(r=-0.66, P<0.01), respectively, in heart failure children. Conclusions Plasma CT-1 level is significantly elevated in heart failure children.There are good correlation among CT-1, NT-pro BNP and LVEF.Plasma CT-1 is a reliable marker of reflecting the severity of heart failure, combined with NT-pro BNP detection helps to improve the diagnostic accuracy of heart failure in children. Key words: Cardiotrophin-1; N terminal probrain natriuretic peptide; Heart failure; Child

Detection of Subclinical Trastuzumab-Induced Cardiotoxicity in Patients with Breast Cancer

In recent decades, the treatment of cancer has shown great development in the fields of surgery, radiation therapy and the emergence of cytotoxic chemotherapy and targeted cancer therapies (including monoclonal antibodies, tyrosine-kinase inhibitors and angiogenesis inhibitors). Consequently, there has been an increase in survival of patients with cancer, making cardiovascular complications related to chemotherapy be more carefully taken into consideration by cardiologists and oncologists. The most frequent clinical manifestation of cardiotoxicity is symptomatic or asymptomatic ventricular dysfunction that can progress to heart failure1. Ventricular dysfunction can occur not only after conventional chemotherapy with anthracyclines, but with the new antitumor agents, such as trastuzumab. Several studies have shown that screening for cardiotoxicity by assessing the ejection fraction may be inadequate to detect subclinical disease2. It is known that the time of implementation of cardiovascular therapy is an important prognostic factor in heart function recovery and to prevent heart failure development3. Thus, several biomarkers have been studied in an attempt at early detection of cardiotoxicity, particularly troponin, BNP and microRNAs4,5. However, the optimal time of collection, or an ideal population to be submitted to this screening is yet to be determined. In addition, more sensitive methods for the assessment of cardiac structure and function, such as magnetic resonance imaging and strain echocardiography seem to detect the subclinical forms of the disease2. Some medications commonly used in the management of heart failure have shown a beneficial effect on chemotherapy-related cardiotoxicity. The use of angiotensin-converting enzyme inhibitors in patients with troponin increase during chemotherapy can be an effective tool to prevent left ventricular dysfunction and late cardiovascular events6. However, there are no large studies that evaluated the effect of these medications on anticancer therapy efficacy. In the treatment of cardiotoxicity associated with the use of chemotherapeutic agents, beta-blockers, enzyme inhibitors and angiotensin-converting enzyme inhibitors seem to be effective. However, early treatment of ventricular dysfunction is important, considering the correlation between the time of start of ventricular dysfunction treatment and cardiac function recovery1. The HER2 gene amplification and/or overexpression of its protein occurs in approximately 20% of breast cancers and is associated with a worse prognosis7. New chemotherapeutic agents, targeted at the HER2 receptor and its action pathway, have revolutionized the treatment of this type of cancer8. Trastuzumab, a humanized monoclonal antibody, was the first targeted therapy against the HER2 pathway and its use has changed the natural history of HER2+ breast cancer, resulting in improved survival similar to HER2- breast cancers. Thus, trastuzumab has become the key point in the treatment of HER2 + breast cancer. However, despite the outstanding benefits in survival related to anti-HER2 treatment, a significant increase in drug-related cardiac toxicity has been observed9, with several cardiac dysfunction events reported in clinical studies with the use of trastuzumab. Although cardiac toxicity induced by anti-HER2 therapy is not completely understood, preclinical studies have demonstrated an important role of HER2 signaling pathway in cardiac physiology, since both HER2 receptors and its ligands are expressed in cardiomyocytes. Despite the benefits offered by anti-HER therapy, there is justified concern about the potential adverse cardiac events and studies are needed to assess ways of early detection of this toxicity, as well as the best way of handling it, as the pathways of toxicity and therapeutics10 may be superimposed. It is believed that diastolic dysfunction may precede the onset of left ventricular systolic dysfunction11. In this issue, Dores et al12 studied 51 women with HER2 + breast cancer for five months to assess the occurrence of early cardiotoxicity. Although they found no symptomatic heart failure, the authors showed that as early as the third month of treatment, there were differences in diastolic parameters after the use of trastuzumab. The authors found a statistically significant difference in the E/e' ratio from the beginning to the third month of follow-up related to a reduction in myocardial velocity, as assessed by tissue Doppler. More than half of patients (57.9%) showed a decrease in ejection fraction, but only one had a decrease below 55%. With the development of cardio-oncology and the constant advent of new chemotherapeutic agents, surveillance studies and the search for early markers of cardiac abnormalities in cancer patients is of great importance for the adequate management of these patients. Editorial under the responsibility of Cardiosource in Portuguese. http://cientifico.cardiol.br/cardiosource2/default.asp

Comparative study of NT-proBNP and BNP assays for heart failure diagnosis in patients complicated with acute cerebral infarction

Objective To compare the capabilities of NT-proBNP and BNP in diagnosis of heart failure when complicated with acute cerebral infarction. Methods EP15-A2 document, was employed to verify the precision and accuracy of NT-proBNP and BNP assays on chemiluminescence analyzer Cobas E601 and ADVIA Centaur respectively for 363 samples from patients with chronic heart failure, cerebral hemorrhage and acute cerebral infarction, cerebral infarction complicated with heart failure and normal controls were collected and analyzed by Cobas E601 and ADVIA Centaur, and then determined the changing trends of NT-proBNP and BNP.Moreover, ROC curve was employed in diagnostic value comparison of NT-proBNP and BNP in heart failure groups. Results Cobas E601 and ADVIA Centaur showed good repeatability and accuracy in the detection of NT-proBNP and BNP that both total non-precision were below 3.5% and the deviations to calibrator were below 3.91%.The level of NT-proBNP an BNP didn′t elevate in normal people and cerebral hemorrhage patients.However, they significant elevated in heart failure, acute cerebral infarction and cerebral infarction complicated with heart failure patients(P<0.01).Their levels were heart failure grade dependent.The levels of NT-proBNP in cerebral infarction complicated with grade Ⅰ to Ⅲ heart failure patients were significantly higher than those in chronic heart failure patients, with same heart failure(P<0.05).However, compared to chronic heart failure patients, the level of BNP in cerebral infarction complicated with heart failure patients didn′t elevate significantly until grade Ⅲ heart failure happened.Areas under the ROC curve （AUCs） of NT-proBNP and BNP were both above 93% in the diagnosis of chronic heart failure.But for patients who suffered cerebral infarction complicated with heart failure, the diagnostic value of NT-proBNP and BNP were decreased due to cerebral infarction interference.However, the ROC area of BNP was larger than that of NT-proBNP(P<0.05). Conclusion In the diagnosis of cerebral infarction complicated with heart failure, BNP could be a better choice to determine the degree of heart failure.（Chin J Lab Med，2012,35：890-893） Key words: Brain infarction; Heart failure; Natriuretic peptide; brain