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1.
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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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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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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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.
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[The heart as an endocrine organ].
Mezősi, E, Bajnok, L, Tóth, K
Orvosi hetilap. 2012;(51):2041-7
Abstract
The discovery of cardiac hormone production significantly changed the evaluation of the function of the heart, which is rather regarded as a determining factor of the electrolyte and hemodynamic homeostasis cooperating with other organ systems instead of a mechanical pump. The most important hormones produced by the heart are the natriuretic peptides that have the primary role of protection against volume overload through natriuretic, diuretic, vasodilator and antiproliferative effects. They are integrative markers of the cardiac, vascular and renal functions and marking cardiorenal distress. Brain natriuretic peptide and the N-terminal pro-hormone (NT-proBNP) became generally accepted markers of heart failure exceeding traditional pathophysiological significance of those. They are useful in the diagnosis, estimation of prognosis and therapy guidance and their therapeutic administration is also available. Although the detection of extraadrenal aldosterone production is an exciting new discovery, intracardial aldosterone production is not significant in human beings. The intracardial thyroid hormone production is regulated by deiodinase activity. The role of elevated T3 concentration was suggested in the development of cardiac hypertrophy, while low T3 is assumed to be important in adaptation to hypoxia. An unexpected, complex relation can be determined between epicardial adipose tissue and coronary artery diseases, cytokine and adipokine production of adipocytes might be a part of the self-enhancing process of atherosclerosis.
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Bioimpedance and brain natriuretic peptide in peritoneal dialysis patients.
Crepaldi, C, Lamas, EI, Martino, FK, Rodighiero, MP, Scalzotto, E, Wojewodzka-Zelezniakowicz, M, Rosner, MH, Ronco, C
Contributions to nephrology. 2012;:174-181
Abstract
Assessment of ideal body weight in peritoneal dialysis (PD) patients is important for clinical practice. Fluid overload may produce hypertension, reduced arterial distensibility, left ventricular hypertrophy. All these are risk factors for mortality in PD patients: cardio- and cerebrovascular events are the main causes of morbidity and mortality in PD population. Nowadays, a clear and widely accepted definition of ideal body weight in PD patients does not exist. Probably the ideal body weight is the weight at which the extra cellular volume is normal. Many different tools have been used to assess the hydration status in dialysis patients. Ultrasonic evaluation of inferior vena cava diameter only assesses intravascular volume, and is also influenced by diastolic dysfunction and is thus a reflection of preload and not of tissue hydration. Direct measurement of extra cellular and total body water by dilution methods is considered as the golden standard, but these techniques are laborious and expensive. Parameters, such as brain natriuretic peptide (BNP) or NT-proBNP can reflect changes in hydration status and may help the nephrologist to estimate it. Natriuretic peptides are influenced both by preload and ventricular abnormalities and in patients with renal failure accumulation can occur. Bioimpedance is an accurate, reproducible, not expensive and not invasive technique that permits a good evaluation of hydration status in PD and can drive the nephrologist in his clinical choices. Clinical evaluation, strict control of body weight, diuresis, sodium and fluids intakes, bioimpedance monitoring and serum levels of natriuretic peptides may all together help us to maintain the PD patient euvolemic.
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An evidence-based algorithm for the use of B-type natriuretic testing in acute coronary syndromes.
McCullough, PA, Peacock, WF, O'Neil, B, de Lemos, JA, Lepor, NE, Berkowitz, R
Reviews in cardiovascular medicine. 2010;:S51-65
Abstract
Measurable B-type natriuretic peptides (BNPs), which are largely produced by the left ventricle, include BNP and N-terminal prohormone BNP (NT-proBNP). These proteins are released by cardiomyocytes in response to wall tension and neurohumoral signals, and are established tools in the diagnosis and prognosis of heart failure (HF). We identified 32 articles for entry into evidence tables that presented original data on BNP and/or NT-proBNP in more than 100 patients with acute coronary syndromes (ACS) presenting with chest discomfort with or without dyspnea. Natriuretic peptide (NP) elevation was associated with older age, female sex, hypertension, diabetes, prior HF, prior ischemic heart disease, and reduced renal function. Clinical correlates of elevated blood NP levels included left main or 3-vessel coronary disease, lipid-rich plaques with large necrotic cores in proximal locations, large zones of myocardial ischemia or infarction, no-reflow and impaired perfusion after percutaneous intervention, reduced left ventricular ejection fraction, higher Killip classification, and the development of cardiogenic shock. All studies indicated that after adjustment for baseline predictors and clinical risk scores, elevated NP concentrations were independently predictive of the development of HF and all-cause mortality. In contrast, studies did not consistently demonstrate that NPs were predictive of myocardial infarction and rehospitalization for ACS. In addition to baseline measurement, there is consensus that repeat testing at 4 to 12 weeks and 6 to 12 months in follow-up is helpful in the anticipation of late cardiac sequelae and may assist in assessing prognosis and guiding management.