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A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.
Gachpazan, M, Mohammadinejad, A, Saeidinia, A, Rahimi, HR, Ghayour-Mobarhan, M, Vakilian, F, Rezayi, M
Analytical and bioanalytical chemistry. 2021;(24):5949-5967
Abstract
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.
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Risk of heart failure progression in patients with reduced ejection fraction: mechanisms and therapeutic options.
Gronda, E, Vanoli, E, Sacchi, S, Grassi, G, Ambrosio, G, Napoli, C
Heart failure reviews. 2020;(2):295-303
Abstract
Transition from stage C to stage D of heart failure (HF) represents an irreversible process toward end-stage disease. Crucial interventions to be adopted in the attempt to interfere with this process are represented by the identification of patients at high risk to develop HF progression and by an effective and prompt management. Markers of worse prognosis and disease progression are well established and include recurrence of HF decompensation, intolerance to the neurohormonal standard pharmacological treatment, and resistance to loop diuretics. In addition, both NT-proBNP and sympathetic nervous system (SNS) overdrive are strong predictors of adverse clinical outcome and allow to identify high-risk HF patients even in the presence of mild symptoms. To counteract the deleterious effects of the SNS activation, new strategies such as a new drug combining angiotensin receptor and neprilysin inhibition and baroreceptor stimulation therapy (BAT) have been investigated. Inability to properly counteract the SNS overdrive leads to acute HF decompensation by different mechanisms. The leading ones are represented by the progressive sodium and water retention with fluid overload and by the blood volume redistribution between splanchnic and non-splanchnic regions. The correct understanding of these mechanisms, together with the availability of new therapeutic options such as peritoneal ultrafiltration, represent the rationale but not infrequently overlooked therapeutic options to improve congestion management in HF patients.
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B-type natriuretic peptide and its role in altering Ca2+-regulatory proteins in heart failure-mechanistic insights.
Zhao, J, Xu, T, Zhou, Y, Zhou, Y, Xia, Y, Li, D
Heart failure reviews. 2020;(5):861-871
Abstract
Heart failure (HF) is a worldwide disease with high levels of morbidity and mortality. The pathogenesis of HF is complicated and involves imbalances in hormone and electrolyte. B-type natriuretic peptide (BNP) has served as a biomarker of HF severity, and in recent years, it has been used to treat the disease, thanks to its cardio-protective effects, such as diuresis, natriuresis, and vasodilatation. In stage C/D HF, symptoms are severe despite elevated BNP. Disturbances in Ca2+ homeostasis are often a dominating feature of the disease, causing Ca2+-regulatory protein dysfunction, including reduced expression and activity of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a), impaired ryanodine receptors (RYRs) function, intensive Na+-Ca2+ exchanger (NCX), and downregulation of S100A1. The relationship between natriuretic peptides (NPs) and Ca2+-regulatory proteins has been widely studied and represents important mechanisms in the etiology of HF. In this review, we present evidence that BNP may regulate Ca2+-regulatory proteins, in particular, suppressing SERCA2a and S100A1 expression. However, relationships between BNP and other Ca2+-regulatory proteins remain vague.
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Analytical barriers in clinical B-type natriuretic peptide measurement and the promising analytical methods based on mass spectrometry technology.
Xiao, P, Li, H, Li, X, Song, D
Clinical chemistry and laboratory medicine. 2019;(7):954-966
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Abstract
B-type natriuretic peptide (BNP) is a circulating biomarker that is mainly applied in heart failure (HF) diagnosis and to monitor disease progression. Because some identical amino acid sequences occur in the precursor and metabolites of BNP, undesirable cross-reactions are common in immunoassays. This review first summarizes current analytical methods, such as immunoassay- and mass spectrometry (MS)-based approaches, including the accuracy of measurement and the inconsistency of the results. Second, the review presents some promising approaches to resolve the current barriers in clinical BNP measurement, such as how to decrease cross-reactions and increase the measurement consistency. Specific approaches include research on novel BNP assays with higher-specificity chemical antibodies, the development of International System of Units (SI)-traceable reference materials, and the development of structure characterization methods based on state-of-the-art ambient and ion mobility MS technologies. The factors that could affect MS analysis are also discussed, such as biological sample cleanup and peptide ionization efficiency. The purpose of this review is to explore and identify the main problems in BNP clinical measurement and to present three types of approaches to resolve these problems, namely, materials, methods and instruments. Although novel approaches are proposed here, in practice, it is worth noting that the BNP-related peptides including unprocessed proBNP were all measured in clinical BNP assays. Therefore, approaches that aimed to measure a specific BNP or proBNP might be an effective way for the standardization of a particular BNP form measurement, instead of the standardization of "total" immunoreactive BNP assays in clinical at present.
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New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides.
Zhai, Y, Luo, Y, Wu, P, Li, D
Journal of medical genetics. 2018;(5):287-296
Abstract
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial. Moreover, BNP was shown to inhibit SERCA2a expression. Therefore, it is possible that high BNP levels interact with treatment effects of SERCA2a gene transfer and accordingly lead to negative results of CUPID 2 trial. From this point of view, effects of SERCA2a gene therapy should be explored in heart failure with preserved ejection fraction, which is characterised by lower BNP levels compared with HFrEF. In this review, we summarise the current knowledge of SERCA2a gene therapy for heart failure, analyse potential interaction between BNP levels and therapeutic effects of SERCA2a gene transfer and provide directions for future research to solve the identified problems.
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A review of pediatric pulmonary hypertension with new guidelines.
Kula, S, Pektaş, A
Turkish journal of medical sciences. 2017;(2):375-380
Abstract
This study aims to review pediatric pulmonary hypertension (PH) by comparing the guidelines of the European Society of Cardiology (ESC)/European Respiratory Society (ERS), the American Heart Association (AHA)/American Thoracic Society (ATS), and the European Pediatric Pulmonary Vascular Disease Network (EPPVDN). All three sets of guidelines define PH as having a mean pulmonary artery pressure of ≥25 mmHg and accept the validity of the World Health Organization (WHO) classification system. Every child with a high index of suspicion for PH should undergo an initial work-up of chest X-rays, electrocardiography, and echocardiography. The AHA/ATS guidelines emphasize the necessity of cardiac catheterization and hemodynamic studies. As mentioned in the AHA/ATS guidelines, the symptoms and tests that can detect PH include right ventricle failure, WHO functional class, syncope, echocardiography findings, hemodynamic data, brain natriuretic peptide (BNP)/N-terminal pro-BNP, the 6-min walk test, and cardiopulmonary exercise tests. The EPPVDN guidelines refer to positive acute vasoreactivity test results and growth as risk factors. All three guidelines highlight the importance of treating and following affected children in specialized centers and recommend calcium channel blockers as a first-line treatment in children (aged >12 months) who have a positive acute vasoreactivity test. Children with PH have distinct clinical features. In order to overcome the controversies related to the optimal management of pediatric PH, well-designed clinical studies should be carried out on a large cohort of affected children.
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Brain Natriuretic Peptide Counteracting the Renin-angiotensin-aldosterone System in Accelerated Malignant Hypertension.
Nakagawa, H, Mizuno, Y, Harada, E, Morikawa, Y, Kuwahara, K, Saito, Y, Yasue, H
The American journal of the medical sciences. 2016;(5):534-539
Abstract
We describe 2 patients, a 52-year-old woman and a 57-year-old man, with rapidly progressive hypertension and marked elevation of brain natriuretic peptide who exhibited polyuria, natriuresis, hypokalemia, posterior reversible encephalopathy syndrome and left ventricular dysfunction together with retinopathy and nephropathy, which were attenuated in a short time span of 1-2 months with normalization of blood pressure after the antihypertensive treatment. The possible role of brain natriuretic peptide in the pathophysiology of accelerated malignant hypertension was discussed and a review of the literature was completed.
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Cardiovascular disease screening.
Duffy, JY, Hameed, AB
Seminars in perinatology. 2015;(4):264-7
Abstract
Cardiovascular disease is the leading cause of death amongst women worldwide. Cardiovascular risk assessment and primary prevention are important strategies to improve morbidity and mortality. In additional to the traditional risk factors, pregnancy complications such as pre-eclampsia and gestational diabetes increment future risk of developing cardiovascular complications. Additionally, several serum biomarkers are valuable measures for both risk assessment and predictors of clinical outcomes in women. The purpose of this review is to describe current risk stratification schemes as well as outline the role of obstetric history and serum biomarkers in adjusting risk stratification in women.
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Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD.
Colbert, G, Jain, N, de Lemos, JA, Hedayati, SS
Clinical journal of the American Society of Nephrology : CJASN. 2015;(3):515-29
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Abstract
Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.
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Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis.
Troughton, RW, Frampton, CM, Brunner-La Rocca, HP, Pfisterer, M, Eurlings, LW, Erntell, H, Persson, H, O'Connor, CM, Moertl, D, Karlström, P, et al
European heart journal. 2014;(23):1559-67
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Abstract
AIMS: Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality. METHODS AND RESULTS Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF. CONCLUSION Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.