Consensus document and recommendations on the use of natriuretic peptides in clinical practice

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ANP: péptido natriurético tipo A o auricular; BNP: péptido natriurético tipo B o cerebral (brain); CNP: péptido natriurético tipo C; GMP: guanosín monofosfato; GTP: guanosín trifosfato; NPR: receptores de péptidos natriuréticos." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D.A. Pascual-Figal, J. Casademont, J.M. Lobos, P. Piñera, A. Bayés-Genis, J. Ordóñez-Llanos, J.R. González-Juanatey" "autores" => array:7 [ 0 => array:2 [ "nombre" => "D.A." "apellidos" => "Pascual-Figal" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Casademont" ] 2 => array:2 [ "nombre" => "J.M." "apellidos" => "Lobos" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Piñera" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Bayés-Genis" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Ordóñez-Llanos" ] 6 => array:2 [ "nombre" => "J.R." 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Pascual-Figal, J. Casademont, J.M. Lobos, P. Piñera, A. Bayés-Genis, J. Ordóñez-Llanos, J.R. González-Juanatey" "autores" => array:7 [ 0 => array:3 [ "nombre" => "D.A." "apellidos" => "Pascual-Figal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "J." "apellidos" => "Casademont" "email" => array:1 [ 0 => "jcasademont@santpau.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "J.M." "apellidos" => "Lobos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Piñera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "A." 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"apellidos" => "González-Juanatey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Sociedad Española de Cardiología (SEC), Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sociedad Española de Medicina Interna (SEMI), Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sociedad Española de Medicina Familiar y Comunitaria (SEMFyC), Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Sociedad Española de Medicina de Urgencias (SEMES), Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Documento de consenso y recomendaciones sobre el uso de los péptidos natriuréticos en la práctica clínica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4137 "Ancho" => 2616 "Tamanyo" => 749281 ] ] "descripcion" => array:1 [ "en" => "Diagram of the BNP production mechanism and natriuretic peptide receptor function. Abbreviations: ANP, A or atrial natriuretic peptide; BNP, B or brain natriuretic peptide; CNP, C natriuretic peptide; GMP, guanosine monophosphate; GTP: guanosine triphosphate; NPR, natriuretic peptide receptor." ] ] ] "textoCompleto" => "BackgroundThe present document emerged from the scientific societies that signed it as a set of evidence-based consensus recommendations on the use of natriuretic peptides (NPs) in heart failure (HF). The document's objective is to improve the medical care of patients with HF and to more efficiently use resources in healthcare activities.NPs have become a laboratory tool with significant implications in the diagnosis, prognosis and treatment of patients with suspected or confirmed HF. The use of NPs affects various healthcare settings (outpatient consultations, emergency department, hospitalization and laboratory) and by various primary care and specialized professionals. The proper use of NPs has implications for patients and for the healthcare system, especially considering the epidemic nature of HF. For this reason, a scientific consensus is needed as a guide and to establish specific recommendations on the appropriate use of NPs in clinical practice.Although there are various types of NPs, this document focuses on those that have shown their usefulness in clinical studies: B-type natriuretic peptides and related metabolites.Current situation in SpainThe current recommendations on the use of NPs in clinical practice are based on international guidelines from scientific societies. NPs are included in the diagnostic algorithm for patients with HF in the 2001 clinical practice guidelines.<a class="elsevierStyleCrossRef" href="#bib0185">1</a> Reference values for the diagnosis of acute HF were first published in 2005.<a class="elsevierStyleCrossRef" href="#bib0190">2</a> Since then, the incorporation of NPs in subsequent clinical practice guidelines has been progressive. The most recent guidelines of 2012 and 2013 published for the first time the reference concentrations for use in the outpatient and emergency diagnosis. A recommendation of IA was established for the use of NPs in the diagnosis and prognostic assessment of patients.<a class="elsevierStyleCrossRefs" href="#bib0195">3,4</a> Therefore, more than 10 years were needed for its definitive incorporation into the guidelines of scientific societies.In healthcare practice, the incorporation of NPs has been even slower and with significant disparity, which, although it has been improving, does not reflect the guidelines’ current recommendations. In fact, in a survey by the Spanish Society of Cardiology conducted in January 2015 among 107 public hospitals covering a treated population of more than 31 million inhabitants, the emergency reading of NPs was available in 65% of the emergency departments (which would equal only 66% of the population treated by this set of departments).<a class="elsevierStyleCrossRef" href="#bib0205">5</a> In a survey of 96 emergency departments a year earlier, the Spanish Society of Emergency Medicine reported that 59% of centers had NPs.<a class="elsevierStyleCrossRef" href="#bib0210">6</a>Definitions and prior knowledgeAn appropriate use and interpretation of NPs in clinical practice is possible only if the physician has knowledge of its pathophysiology and measurement methodology. The items related to their pathophysiology and methodology are listed below. Their reading and understanding are required for any physician who seeks to interpret NP concentrations in their patients.A. Pathophysiology<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.NPs are bioactive peptides with numerous biological effects.<a class="elsevierStyleCrossRef" href="#bib0215">7</a> There are 3 families of NPs: ANPs (type A, atrial NPs), BNPs (type B, brain NPs) and CNPs (C-type NPs). A and B-type NPs have systemic effects and are produced mainly in cardiomyocytes. CNPs are mainly produced in endothelial cells and act as an autocrine and paracrine factor.</li><li class="elsevierStyleListItem" id="lsti0010">2.The effects of NPs are mediated by its binding to 3 types of receptors, 2 of which are functional and 1 of which is clearing.<a class="elsevierStyleCrossRef" href="#bib0220">8</a> The 2 functional receptors (natriuretic peptide receptor [NPR]) have been characterized as A-type (NPR-A) and B-type (NPR-B) and are expressed in the cardiovascular system and numerous organs (lungs, kidneys, skin and brain). Binding to these receptors stimulates the production of cyclic guanosine-monophosphate (cGMP).</li><li class="elsevierStyleListItem" id="lsti0015">3.NPs are antagonists of the renin-angiotensin-aldosterone system. Their main actions are reducing peripheral vascular resistance and increasing natriuresis and diuresis. The antifibrotic and antihypertrophic effects of NPs in the myocardium have recently been identified.</li><li class="elsevierStyleListItem" id="lsti0020">4.B-type NPs are of greatest interest due to their proven clinical utility. The responsible gene is located in chromosome 1. The molecule is synthesized as a preprohormone (pre-proBNP), which undergoes cleavage of a signal peptide for conversion into the prohormone (proBNP). Most of the proBNP is then cleaved intracellularly or during its secretion to the circulation, resulting in the amino-terminal portion of the proBNP (NT-proBNP) and in the BNP (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0025">5.There are 3 major forms of B-type NPs in the circulation: The biologically inactive NT-proBNP of 76 amino acids; the biologically active BNP of 32 amino acids; and the compound precursor, proBNP, of 108 amino acids, whose biological activity is approximately 10% that of the BNP. Truncated fragments and modified forms of the 3 B-type NPs have also been detected.</li><li class="elsevierStyleListItem" id="lsti0030">6.B-type NPs are produced in atria and ventricles. The left ventricle is the main source, but production by the atria is significant.</li><li class="elsevierStyleListItem" id="lsti0035">7.The production of B-type NPs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) is governed mechanically and proportionally to the increase in tension in the cardiomyocytes. Their synthesis is rapid after the stimulation, with no significant intracellular deposits. After synthesis, the BNPs are secreted into the circulation. Myocardial damage also entails their secretion. In practice, HF is the main cause (although not the only one) of increased concentrations of circulating NPs. This increase occurs in the presence of both systolic and diastolic dysfunction.</li><li class="elsevierStyleListItem" id="lsti0040">8.Although the release of BNP and NT-proBNP is equimolecular, their half-lives are different. The half-lives of BNP and NT-proBNP are 21min and approximately 70min, respectively. NT-proBNP concentrations are therefore greater than those of BNP.</li><li class="elsevierStyleListItem" id="lsti0045">9.The clearance of circulating BNP is produced actively by its binding to the natriuretic peptide receptor C (NPR-C) and by the action of neprilysin. Neprilysin is a membrane neutral endopeptidase, which degrades the existing ring structure in BNP, proBNP and pre-proBNP but not in NT-proBNP and causes proteolysis of these molecules. In conditions of homeostasis, clearance through binding to NPR-C predominates. In volume overload or pressure conditions (e.g., in HF), clearance by neprilysin predominates (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</li></ul>B. Biochemistry and measurement methods<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0050">1.There are immunoassays for measuring the various A-type NPs (ANP, NT-proANP, MR-proANP) and B-type NPs (BNP, NT-proBNP, proBNP). The immunoassays can be totally automated or partially manual such as the point-of-care methods. <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> show the main characteristics of the methods available for measuring BNP and NT-proBNP.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0055">2.The existing immunoassays for measuring BNP use antibodies that recognize not only circulating BNP but also variably recognize BNP fragments and proBNP. This situation creates significant differences among the various immunoassays and hinders the comparison of values between the immunoassays (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</li><li class="elsevierStyleListItem" id="lsti0060">3.The existing immunoassays for measuring NT-proBNP use the same or similar antibodies and mostly detect NT-proBNP and residually detect proBNP (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</li><li class="elsevierStyleListItem" id="lsti0065">4.Due to the fact that the immunoassays detect molecular forms of BNP and NT-proBNP with different molecular weights, their concentrations cannot be expressed in molar units (e.g., mmol/L). The common unit for expressing their concentration is pg/mL (equivalent to ng/L).</li><li class="elsevierStyleListItem" id="lsti0070">5.Immunoassays for measuring BNP and NT-proBNP have low analytical variability, which is greater in the point-of-care type than in the automated type. This low variability helps detect differences between successive measurements attributable to changes in the clinical condition and not to analytical variability.<a class="elsevierStyleCrossRef" href="#bib0225">9</a></li><li class="elsevierStyleListItem" id="lsti0075">6.Circulating concentrations of B-type NPs have biological variability in healthy individuals and in stable patients. This variability is greater for BNP than for NT-proBNP and increases as the serial interval and NP concentration decrease. For example, for weekly measurements in patients with stable HF, the biological variability can reach 50% for BNP and 25% for NT-proBNP.<a class="elsevierStyleCrossRef" href="#bib0230">10</a></li><li class="elsevierStyleListItem" id="lsti0080">7.The BNP and NT-proBNP concentrations increase with age and are higher in women than in men. Reference values stratified by age have been published for both NPs. Obesity decreases the concentrations of BNP and NT-proBNP.<a class="elsevierStyleCrossRef" href="#bib0225">9</a></li><li class="elsevierStyleListItem" id="lsti0085">8.There are extracardiac causes for the increase in circulating concentrations of B-type NPs, either through cardiac stress or an increase in circulating blood volume, which should be interpreted in each clinical context. Among them, renal failure and pulmonary hypertension are the most clinically relevant.<a class="elsevierStyleCrossRef" href="#bib0235">11</a></li><li class="elsevierStyleListItem" id="lsti0090">9.BNP and NT-proBNP concentrations are increased in renal dysfunction and are higher the more severe the dysfunction. The use of reference values stratified by age minimizes the effect of renal dysfunction on NT-proBNPvalues.<a class="elsevierStyleCrossRef" href="#bib0240">12</a></li><li class="elsevierStyleListItem" id="lsti0095">10.When interpreting NP concentrations, clinicians should consider the effect of particular drugs (currently, neprilysin inhibitors and recombinant BNP) on the concentrations.</li></ul>Recommendations for using B-type NPsAs general criteria for the use of NPs in the various clinical scenarios, the recommendations are as follows:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0100">-Prior training in prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration with the symptoms) terms.</li><li class="elsevierStyleListItem" id="lsti0105">-Reasoned use based on the expected usefulness for improving decision making, the diagnosis or the treatment of patients.</li><li class="elsevierStyleListItem" id="lsti0110">-Use of consensus protocols, in which all departments involved in the use of NPs should participate.</li></ul>A. DiagnosisThe measurement of NPs for diagnostic purposes represents the main clinical application, the most extensively studied application and the one with the most scientific evidence.<a class="elsevierStyleCrossRefs" href="#bib0195">3,4</a>The following general recommendations have been established (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>):<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0115">-Their measurement coupled with clinical judgment improves diagnostic accuracy compared with clinical diagnosis alone, particularly in cases of uncertainty.<a class="elsevierStyleCrossRefs" href="#bib0245">13–15</a></li><li class="elsevierStyleListItem" id="lsti0120">-Their usefulness in the diagnosis has been studied in patients in whom dyspnea is the main symptom.<a class="elsevierStyleCrossRefs" href="#bib0240">12,16</a></li><li class="elsevierStyleListItem" id="lsti0125">-Their usefulness is mainly a result of their high negative predictive value for excluding HF, especially in patients with no prior diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0265">17,18</a></li></ul><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The diagnostic use of NPs in 2 settings (emergency department or hospital setting and the outpatient or doctor's office setting) is discussed below.A.1. The measurement of B-type NP concentrations should be performed for all patients who go to the emergency department for dyspnea and for those with suspected de novo HF (with no prior established diagnosis).<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0130">-The use of B-type NPs has been shown to be cost-effective in this scenario and to have an effect on patient diagnosis and treatment.<a class="elsevierStyleCrossRef" href="#bib0275">19</a></li><li class="elsevierStyleListItem" id="lsti0135">-Their usefulness is greater in conditions of clinical uncertainty, prior to the initial assessment that has to include the case history, physical examination, electrocardiogram and chest radiology.<a class="elsevierStyleCrossRefs" href="#bib0280">20,21</a></li><li class="elsevierStyleListItem" id="lsti0140">-Their measurement should be performed with the patient's first blood sample upon their arrival at the emergency department. The early availability of results facilitates a better diagnosis and treatment.</li><li class="elsevierStyleListItem" id="lsti0145">-A low value (NT-proBNP<300pg/mL or BNP<100pg/mL) helps rule out the presence of HF regardless of age, with a negative predictive value of 98% for NT-proBNP and 90% for BNP.<a class="elsevierStyleCrossRefs" href="#bib0240">12,13,16,22</a></li><li class="elsevierStyleListItem" id="lsti0150">-For NT-proBNP, the use of age-adjusted values helps improve the ability to identify the presence of HF: >450pg/mL (<50 years), >900pg/mL (50–75 years) and >1800pg/mL (>75 years).<a class="elsevierStyleCrossRefs" href="#bib0240">12,23</a> Overall, the positive predictive value of these values is 88%.<a class="elsevierStyleCrossRef" href="#bib0240">12</a></li><li class="elsevierStyleListItem" id="lsti0155">-A high BNP value (>400pg/mL), regardless of age, should lead clinicians to consider the diagnosis of HF as probable, with a positive predictive value of 86%.<a class="elsevierStyleCrossRef" href="#bib0290">22</a></li><li class="elsevierStyleListItem" id="lsti0160">-To interpret intermediate values of NT-proBNP or BNP, the clinical judgment for the likelihood of HF should predominate, taking into consideration other conditions that could influence the concentrations of both peptides.</li><li class="elsevierStyleListItem" id="lsti0165">-For patients who already have a prior diagnosis of HF, NPs should not be routinely measured on arrival at the emergency department or during hospitalization. Nevertheless, their measurement should be considered for patients who have a prior reading in a stable clinical condition (outpatient or at the time of discharge for a prior decompensation) and for whom there are questions about current acute decompensation of the HF. Only in these cases, individually and within a scenario of diagnostic uncertainty as to the role of HF in the current event, is their measurement recommended.</li></ul>A.2. The measurement of NP concentrations should be accessible in outpatient consultations at the physician's discretion for patients with clinically suspected de novo HF (with no prior established diagnosis). This criterion should take in account the following:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0170">-NP measurements should be requested for patients with diagnostic uncertainty, after the initial clinical assessment.<a class="elsevierStyleCrossRef" href="#bib0300">24</a></li><li class="elsevierStyleListItem" id="lsti0175">-It is recommended that the result be made available, ideally, within 48h of obtaining the sample.</li><li class="elsevierStyleListItem" id="lsti0180">-The result should provide data for ruling out HF, with reference values of 125pg/mL (NT-proBNP) and 35pg/mL (BNP). Lower concentrations have a negative predictive value of 96–99%.<a class="elsevierStyleCrossRefs" href="#bib0255">15,25</a></li><li class="elsevierStyleListItem" id="lsti0185">-Their initial request is preferable to echocardiography (due to accessibility and financial cost), especially if the latter is delayed by more than 7 days.</li><li class="elsevierStyleListItem" id="lsti0190">-A value higher than the upper limit means that treatment for HF should start and that echocardiography should be performed to define the presence of heart disease</li></ul>B. PrognosisAlthough the prognostic utility of NPs in HF has been firmly established, their use for this purpose should be tied to a number of specific conditions.The following general recommendations have been established:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0195">-All increases in NP levels should be interpreted, not only as support for the diagnosis but also as an “alarm signal” that provides short to medium-term risk information, supplementing clinical judgment.<a class="elsevierStyleCrossRefs" href="#bib0195">3,4,26</a></li><li class="elsevierStyleListItem" id="lsti0200">-In any clinical scenario, the greater the NP concentration, the greater the risk of complications and poorer the clinical outcome.</li><li class="elsevierStyleListItem" id="lsti0205">-The usefulness of NPs for assessing the prognosis is mainly applied to patients with HF. However, it should be noted that the presence of high concentrations in other diseases, as a marker of stress and cardiac damage, also identifies a greater cardiovascular risk.</li><li class="elsevierStyleListItem" id="lsti0210">-The measurement of NPs as a risk assessment tool should not be performed routinely but rather as support for clinical judgment, restricted to patients for whom the information provided affects the making of decisions regarding therapy.</li></ul>B.1. For patients in emergency departments or who are hospitalized, the same criteria of the previous section are applicable. The following conditions can also justify the use of NPs:<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0215">-Patients with questions regarding the decision to hospitalize.</li><li class="elsevierStyleListItem" id="lsti0220">-Patients with questions concerning the degree of care and hospital unit.</li><li class="elsevierStyleListItem" id="lsti0225">-Patients with questions as to the use or withdrawal of devices or circulatory support therapies.</li></ul>The following should be considered when interpreting the results:<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0230">-Absolute values of NT-proBNP greater than 5000pg/mL are associated with a greater risk of severe complications. The higher the NP concentration, the poorer the prognosis.<a class="elsevierStyleCrossRefs" href="#bib0240">12,27,28</a></li><li class="elsevierStyleListItem" id="lsti0235">-In the presence of very high NP concentrations but lacking signs of HF, the possibility should always be considered of a severe cardiovascular stress condition not attributable to HF (e.g., sepsis and pulmonary thromboembolism).</li></ul>B.2. For patients in outpatient consultations, the following conditions could justify measuring NPs:<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0240">-Patients with chronic HF with questions concerning the criteria for referral to specialists, emergency department or hospitalization.</li><li class="elsevierStyleListItem" id="lsti0245">-Patients seen in advanced HF consultations for the decision-making process for therapy, especially regarding the indication for heart transplantation and device implantation.</li></ul>The following should be considered when interpreting the results:<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0250">-Values above 1000pg/mL for NT-proBNP indicate an increased risk of death or hospitalization.<a class="elsevierStyleCrossRef" href="#bib0325">29</a> The increase in risk is linear; the higher the concentration, the higher the risk.</li><li class="elsevierStyleListItem" id="lsti0255">-Any value should be interpreted in the clinical context, taking into account modifiers such as age and comorbidity.</li></ul>C. Follow-up and treatmentThe use of NPs as a tool for guiding medical treatment has been evaluated primarily in the outpatient setting and following hospitalization. The results have been conflicting, although the meta-analyses suggest its usefulness for optimizing drug treatment and reducing adverse events.<a class="elsevierStyleCrossRefs" href="#bib0330">30,31</a>The following items are proposed as general recommendations for its use as a treatment guideline:<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0260">-The usefulness of NPs has been mainly demonstrated in patients younger than 75 years with systolic dysfunction. Given that these studies were performed in HF units, this use should only be considered in this context and by trained personnel.<a class="elsevierStyleCrossRefs" href="#bib0330">30,31</a></li><li class="elsevierStyleListItem" id="lsti0265">-Repeated NP measurements may also be assessed in specific circumstances, for decision making within protocols and as support for the clinical judgment.</li></ul>The measurement of NP concentrations should not be requested routinely as a follow-up tool and treatment guideline. This use should instead be performed under specific clinical considerations and scenarios.C.1. The following recommendations have been established for patients hospitalized for exacerbated HF:<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0270">-For the serial use of NPs, a value at admission needs to be obtained (during the first 24h of hospitalization) because their changes should be interpreted in terms of a relative reduction compared to the initial value.</li><li class="elsevierStyleListItem" id="lsti0275">-The reduction in NP levels in relative terms has greater usefulness than in absolute terms; a 30% reduction represents the threshold that has been associated with a better outcome.<a class="elsevierStyleCrossRef" href="#bib0340">32</a></li><li class="elsevierStyleListItem" id="lsti0280">-Their measurement as a therapy guideline, at intermediate times between admission and discharge, is not justified and should be restricted to specific conditions, such as diuretic adjustment to resolve congestion.</li><li class="elsevierStyleListItem" id="lsti0285">-Their serial measurement should not be performed to determine when the patient should be discharged. However, they can support the clinical judgment of discharge, when the progress of the concentrations is considered.</li></ul>C.2. In the follow-up of outpatients with HF, NP measurement is recommended within specialized HF units or consultations to…<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0290">-Confirm the decompensations. NPs can help confirm the presence of decompensation in cases that have reasonable clinical uncertainty.<a class="elsevierStyleCrossRef" href="#bib0345">33</a></li><li class="elsevierStyleListItem" id="lsti0295">-Optimize medical treatment. NPs can help optimize drug treatment, based on the objective of achieving an NT-proBNP level less than 1000pg/mL.<a class="elsevierStyleCrossRef" href="#bib0350">34</a> There are no BNP data for this use.</li><li class="elsevierStyleListItem" id="lsti0300">-In nonspecialized consultations, their use should be limited to confirming decompensations in patients who have a value measured in a stable clinical situation.</li></ul>D. Continuity of careNPs offer relevant information for the various professionals involved in caring for patients with HF during their progression, which can vary. The chronic character and complexity of HF entails the involvement of multidisciplinary teams, thus the importance of contextualizing the NP concentrations of each patient at each developmental stage. It is therefore recommended that…<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0305">-the medical history and medical reports reflect how many NP values are obtained at all points of the disease progression.</li><li class="elsevierStyleListItem" id="lsti0310">-the discharge report includes all values obtained during hospitalization.</li></ul>Conclusions and final recommendations<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0315">(1)NPs are diagnostic and prognostic tools with demonstrated usefulness and should therefore be available in all healthcare settings, both in primary care and specialized care, for use based on medical criteria.</li><li class="elsevierStyleListItem" id="lsti0320">(2)Their proper use requires that medical professionals receive sufficient training in the prelaboratory (pathophysiology), laboratory (measurement methods) and postlaboratory (interpretation in the clinical context) phases.</li><li class="elsevierStyleListItem" id="lsti0325">(3)Their efficient use requires their inclusion in consensus clinical protocols by all involved medical professionals (emergency department, specialized care, primary care and laboratory).</li><li class="elsevierStyleListItem" id="lsti0330">(4)Their measurement is recommended for diagnosing HF in all patients with dyspnea who are admitted to the emergency department and who have no prior diagnosis of HF.</li><li class="elsevierStyleListItem" id="lsti0335">(5)Their measurement is recommended in outpatient consultations at the physician's discretion, as an aid in the diagnosis of HF when there are questions concerning the diagnosis or when there is no prior diagnosis. The evidence for this recommendation is greater if echocardiography is not available early on.</li><li class="elsevierStyleListItem" id="lsti0340">(6)Whenever the concentrations are measured, they should be interpreted as a quantitative risk marker of death and unfavorable outcomes. This information should be used in risk stratification as a supplement to the clinical assessment.</li><li class="elsevierStyleListItem" id="lsti0345">(7)In patients previously diagnosed with HF, the request for NP measurement for the diagnosis of decompensation or as a prognostic marker per se is only recommended in those conditions in which the results help the clinical or therapeutic decision-making process.</li><li class="elsevierStyleListItem" id="lsti0350">(8)Their serial measurement or as a therapeutic guideline for patients with an established diagnosis of HF should not be performed routinely but instead should follow consensus clinical protocols or be restricted to specific HF units.</li><li class="elsevierStyleListItem" id="lsti0355">(9)Their usefulness in the continuity of care is unquestionable. The results of the measurements should therefore always be reflected in the medical history, the discharge report and the patient follow-up.</li><li class="elsevierStyleListItem" id="lsti0360">(10)Interaction between all involved professionals, clinicians and laboratory staff is recommended, which will result in joint training activities and improvements in the healthcare organization for the use of NPs.</li></ul>Conflicts of interestJordi Ordoñez-Llanos declares having received support for research and attendance at conferences and payments as a speaker and member of the advisory committees of the major companies that market tests for measuring natriuretic peptides.Antoni Bayés-Genis declares having received support for research and attendance at conferences and payments as a speaker by Roche Diagnostics.D. Pascual-Figal declares having received support for research from Roche Diagnostics and bioMerieux.The other authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres707935" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec717564" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres707934" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec717565" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Current situation in Spain" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Definitions and prior knowledge" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "A. Pathophysiology" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "B. Biochemistry and measurement methods" ] ] ] 7 => array:3 [ "identificador" => "sec0030" "titulo" => "Recommendations for using B-type NPs" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "A. Diagnosis" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "B. Prognosis" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "C. Follow-up and treatment" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "D. Continuity of care" ] ] ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions and final recommendations" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-01-14" "fechaAceptado" => "2016-02-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec717564" "palabras" => array:4 [ 0 => "Natriuretic peptides" 1 => "B-type natriuretic peptide" 2 => "Aminoterminal pro-B-type natriuretic peptide" 3 => "Heart failure" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec717565" "palabras" => array:4 [ 0 => "Péptidos natriuréticos" 1 => "Péptido natiurético de tipo B" 2 => "Fracción N-terminal del pro-péptido natiurético de tipo B" 3 => "Insuficiencia cardiaca" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialized professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Los péptidos natriuréticos son una herramienta de laboratorio útil en el diagnóstico, pronóstico y tratamiento de los pacientes con insuficiencia cardiaca. Su uso involucra a diferentes ámbitos sanitarios (consultas, urgencias, hospitalización, laboratorio) y a muy diferentes profesionales de la Atención Primaria o especializada. Sin embargo, su incorporación a la práctica asistencial aún es escasa y desigual. Para un correcto uso e interpretación en la práctica clínica se necesita un mínimo de conocimientos preanalíticos (fisiopatología), analíticos (métodos) y postanalíticos (interpretación e integración con los datos clínicos). Este documento de consenso elaborado por varias sociedades científicas tiene como objetivo actualizar los conceptos y conocimientos necesarios sobre los péptidos natriuréticos que permitan su aplicación para el diagnóstico, pronóstico y tratamiento de la insuficiencia cardiaca, en los diferentes ámbitos sanitarios." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Pascual-Figal DA, Casademont J, Lobos JM, Piñera P, Bayés-Genis A, Ordóñez-Llanos J, et al. Documento de consenso y recomendaciones sobre el uso de los péptidos natriuréticos en la práctica clínica. Rev Clin Esp. 2016;216:313–322." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "Consensus meeting held in Madrid on the 6th of October, 2015." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4137 "Ancho" => 2616 "Tamanyo" => 749281 ] ] "descripcion" => array:1 [ "en" => "Diagram of the BNP production mechanism and natriuretic peptide receptor function. Abbreviations: ANP, A or atrial natriuretic peptide; BNP, B or brain natriuretic peptide; CNP, C natriuretic peptide; GMP, guanosine monophosphate; GTP: guanosine triphosphate; NPR, natriuretic peptide receptor." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "The BNP values in the second column correspond with those observed in the same population of individuals evaluated with the various methods.<a class="elsevierStyleCrossRefs" href="#bib0355">35,36</a> The results are expressed as median (interquartile range)<a class="elsevierStyleCrossRef" href="#bib0355">35</a> or mean±standard deviation.<a class="elsevierStyleCrossRef" href="#bib0360">36</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BNP Instrumentation company \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">BNP (pg/mL)<a class="elsevierStyleCrossRefs" href="#bib0355">35,36</a></th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Capture antibody (aa of the epitope) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Detection antibody (aa of the epitope) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard employed to calibrate the method \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alere<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> Triage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">413 (5–2.170) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">133±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (5–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Omniclonal, uncharacterized epitope \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recombinant BNP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abbott Architect AxSYM iSTAT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">526 (13–3.065) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (5–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (26–32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic BNP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Beckman Coulter Access, Access 2 DxL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">464 (18–2.166) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Omniclonal, uncharacterized epitope \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (5–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recombinant BNP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens ACS 180 Advia Centaur Advia Centaur CP Advia Centaur XP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">315 (11–1.884) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">114±2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (14–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic BNP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens Dimension VISTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108±1.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (14–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic BNP \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1167742.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "This method is taken as a reference because it was employed to obtain the clinical decision limits in the BNP study.<a class="elsevierStyleCrossRef" href="#bib0260">16</a>" ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the methods for measuring BNP, including the antibodies used, the compound's epitopes recognized by the antibodies and the standard employed to calibrate the method." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "The NT-proBNP values in the second column correspond to the mean and 2 standard deviations of the same serum for quality control of the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC) assayed repeatedly by the various methods in various clinical laboratories. The methods with no NT-proBNP values were not used in any participating laboratory (n=123) in the Quality Control Program." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP Instrumentation company \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Capture antibody (aa of the epitope) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Detection antibody (aa of the epitope) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard employed to calibrate the method \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roche Diagnostics<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a>; Modular E170, Cobas e601, e602 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">116±6.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (42–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alere; Triage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (42–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">bioMerieux; VIDAS, MiniVIDAS, VIDAS 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86.5±11.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (42–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mitsubishi Chemical; PATHFAST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (1–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (39–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nanogen LifeSign; DXpress Reader \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal+polyclonal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ortho Clinical Diagnostics; Vitros ECi 3600, 5600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">226±8.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (1–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (39–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Radiometer; AQT90 FLEX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">224±7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (1–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (39–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Response Biomedical; RAMP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (39–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roche Diagnostics; Elecsys 2010, Cobas e411 Cobas e601, e602 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">91±7.1 118±9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (27–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (42–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens Dimension RxL, Xpand Dimension VISTA, Dimension EXL Stratus CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58±9.9 110±3.3 75±6.2 220±4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (22–28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal (42–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens Immulite 1000, 2000, 2500 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">401.5±7.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (1–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyclonal (39–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Synthetic NT-proBNP aa 1–76 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1167743.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "This method is taken as the reference because it was the most widely used by the laboratories that participated in the SEQC Quality Control Program." ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the Methods for Measuring NT-proBNP, including the antibodies used, the compound's epitopes recognized by the antibodies and the standard employed to calibrate the method." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP pg/mL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BNP pg/mL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Emergency Department</td><td class="td" title="table-entry " align="left" valign="top"><300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HF very unlikely \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><50 years: 300–450 50–75 years: 300–900 >75 years: 300–1800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100–400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not determinative. The clinical criterion of probability should predominate, taking into account other situations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><50 years: >450 50–75 years: >900 >75 years: >1800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HF with high probability \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outpatient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><125 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HF very unlikely \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1167741.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Reference NT-proBNP and BNP values for the diagnosis of heart failure." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0185" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the diagnosis and treatment of chronic heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.J. 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Consensus document and recommendations on the use of natriuretic peptides in clinical practice

Documento de consenso y recomendaciones sobre el uso de los péptidos natriuréticos en la práctica clínica

D.A. Pascual-Figala, J. Casademontb,

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jcasademont@santpau.cat

Corresponding author.

, J.M. Lobosc, P. Piñerad, A. Bayés-Genisa, J. Ordóñez-Llanosa, J.R. González-Juanateya

a Sociedad Española de Cardiología (SEC), Spain

b Sociedad Española de Medicina Interna (SEMI), Spain

c Sociedad Española de Medicina Familiar y Comunitaria (SEMFyC), Spain

d Sociedad Española de Medicina de Urgencias (SEMES), Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Diagram of the BNP production mechanism and natriuretic peptide receptor function&#46; <span class="elsevierStyleItalic">Abbreviations</span>&#58; ANP&#44; A or atrial natriuretic peptide&#59; BNP&#44; B or brain natriuretic peptide&#59; CNP&#44; C natriuretic peptide&#59; GMP&#44; guanosine monophosphate&#59; GTP&#58; guanosine triphosphate&#59; NPR&#44; natriuretic peptide receptor&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">The present document emerged from the scientific societies that signed it as a set of evidence-based consensus recommendations on the use of natriuretic peptides &#40;NPs&#41; in heart failure &#40;HF&#41;&#46; The document&#39;s objective is to improve the medical care of patients with HF and to more efficiently use resources in healthcare activities&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">NPs have become a laboratory tool with significant implications in the diagnosis&#44; prognosis and treatment of patients with suspected or confirmed HF&#46; The use of NPs affects various healthcare settings &#40;outpatient consultations&#44; emergency department&#44; hospitalization and laboratory&#41; and by various primary care and specialized professionals&#46; The proper use of NPs has implications for patients and for the healthcare system&#44; especially considering the epidemic nature of HF&#46; For this reason&#44; a scientific consensus is needed as a guide and to establish specific recommendations on the appropriate use of NPs in clinical practice&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Although there are various types of NPs&#44; this document focuses on those that have shown their usefulness in clinical studies&#58; B-type natriuretic peptides and related metabolites&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Current situation in Spain</span><p id="par0020" class="elsevierStylePara elsevierViewall">The current recommendations on the use of NPs in clinical practice are based on international guidelines from scientific societies&#46; NPs are included in the diagnostic algorithm for patients with HF in the 2001 clinical practice guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a> Reference values for the diagnosis of acute HF were first published in 2005&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a> Since then&#44; the incorporation of NPs in subsequent clinical practice guidelines has been progressive&#46; The most recent guidelines of 2012 and 2013 published for the first time the reference concentrations for use in the outpatient and emergency diagnosis&#46; A recommendation of IA was established for the use of NPs in the diagnosis and prognostic assessment of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3&#44;4</span></a> Therefore&#44; more than 10 years were needed for its definitive incorporation into the guidelines of scientific societies&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In healthcare practice&#44; the incorporation of NPs has been even slower and with significant disparity&#44; which&#44; although it has been improving&#44; does not reflect the guidelines&#8217; current recommendations&#46; In fact&#44; in a survey by the Spanish Society of Cardiology conducted in January 2015 among 107 public hospitals covering a treated population of more than 31 million inhabitants&#44; the emergency reading of NPs was available in 65&#37; of the emergency departments &#40;which would equal only 66&#37; of the population treated by this set of departments&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">5</span></a> In a survey of 96 emergency departments a year earlier&#44; the Spanish Society of Emergency Medicine reported that 59&#37; of centers had NPs&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Definitions and prior knowledge</span><p id="par0030" class="elsevierStylePara elsevierViewall">An appropriate use and interpretation of NPs in clinical practice is possible only if the physician has knowledge of its pathophysiology and measurement methodology&#46; The items related to their pathophysiology and methodology are listed below&#46; Their reading and understanding are required for any physician who seeks to interpret NP concentrations in their patients&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">A&#46; Pathophysiology</span><p id="par0035" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">NPs are bioactive peptides with numerous biological effects&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">7</span></a> There are 3 families of NPs&#58; ANPs &#40;type A&#44; atrial NPs&#41;&#44; BNPs &#40;type B&#44; brain NPs&#41; and CNPs &#40;C-type NPs&#41;&#46; A and B-type NPs have systemic effects and are produced mainly in cardiomyocytes&#46; CNPs are mainly produced in endothelial cells and act as an autocrine and paracrine factor&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">The effects of NPs are mediated by its binding to 3 types of receptors&#44; 2 of which are functional and 1 of which is clearing&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">8</span></a> The 2 functional receptors &#40;natriuretic peptide receptor &#91;NPR&#93;&#41; have been characterized as A-type &#40;NPR-A&#41; and B-type &#40;NPR-B&#41; and are expressed in the cardiovascular system and numerous organs &#40;lungs&#44; kidneys&#44; skin and brain&#41;&#46; Binding to these receptors stimulates the production of cyclic guanosine-monophosphate &#40;cGMP&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">NPs are antagonists of the renin-angiotensin-aldosterone system&#46; Their main actions are reducing peripheral vascular resistance and increasing natriuresis and diuresis&#46; The antifibrotic and antihypertrophic effects of NPs in the myocardium have recently been identified&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">B-type NPs are of greatest interest due to their proven clinical utility&#46; The responsible gene is located in chromosome 1&#46; The molecule is synthesized as a preprohormone &#40;pre-proBNP&#41;&#44; which undergoes cleavage of a signal peptide for conversion into the prohormone &#40;proBNP&#41;&#46; Most of the proBNP is then cleaved intracellularly or during its secretion to the circulation&#44; resulting in the amino-terminal portion of the proBNP &#40;NT-proBNP&#41; and in the BNP &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">There are 3 major forms of B-type NPs in the circulation&#58; The biologically inactive NT-proBNP of 76 amino acids&#59; the biologically active BNP of 32 amino acids&#59; and the compound precursor&#44; proBNP&#44; of 108 amino acids&#44; whose biological activity is approximately 10&#37; that of the BNP&#46; Truncated fragments and modified forms of the 3 B-type NPs have also been detected&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">B-type NPs are produced in atria and ventricles&#46; The left ventricle is the main source&#44; but production by the atria is significant&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall">The production of B-type NPs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; is governed mechanically and proportionally to the increase in tension in the cardiomyocytes&#46; Their synthesis is rapid after the stimulation&#44; with no significant intracellular deposits&#46; After synthesis&#44; the BNPs are secreted into the circulation&#46; Myocardial damage also entails their secretion&#46; In practice&#44; HF is the main cause &#40;although not the only one&#41; of increased concentrations of circulating NPs&#46; This increase occurs in the presence of both systolic and diastolic dysfunction&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Although the release of BNP and NT-proBNP is equimolecular&#44; their half-lives are different&#46; The half-lives of BNP and NT-proBNP are 21<span class="elsevierStyleHsp" style=""></span>min and approximately 70<span class="elsevierStyleHsp" style=""></span>min&#44; respectively&#46; NT-proBNP concentrations are therefore greater than those of BNP&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">The clearance of circulating BNP is produced actively by its binding to the natriuretic peptide receptor C &#40;NPR-C&#41; and by the action of neprilysin&#46; Neprilysin is a membrane neutral endopeptidase&#44; which degrades the existing ring structure in BNP&#44; proBNP and pre-proBNP but not in NT-proBNP and causes proteolysis of these molecules&#46; In conditions of homeostasis&#44; clearance through binding to NPR-C predominates&#46; In volume overload or pressure conditions &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; in HF&#41;&#44; clearance by neprilysin predominates &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">B&#46; Biochemistry and measurement methods</span><p id="par0085" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">1&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">There are immunoassays for measuring the various A-type NPs &#40;ANP&#44; NT-proANP&#44; MR-proANP&#41; and B-type NPs &#40;BNP&#44; NT-proBNP&#44; proBNP&#41;&#46; The immunoassays can be totally automated or partially manual such as the point-of-care methods&#46; <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> show the main characteristics of the methods available for measuring BNP and NT-proBNP&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">2&#46;</span><p id="par0095" class="elsevierStylePara elsevierViewall">The existing immunoassays for measuring BNP use antibodies that recognize not only circulating BNP but also variably recognize BNP fragments and proBNP&#46; This situation creates significant differences among the various immunoassays and hinders the comparison of values between the immunoassays &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">3&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">The existing immunoassays for measuring NT-proBNP use the same or similar antibodies and mostly detect NT-proBNP and residually detect proBNP &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">4&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Due to the fact that the immunoassays detect molecular forms of BNP and NT-proBNP with different molecular weights&#44; their concentrations cannot be expressed in molar units &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; mmol&#47;L&#41;&#46; The common unit for expressing their concentration is pg&#47;mL &#40;equivalent to ng&#47;L&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">5&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Immunoassays for measuring BNP and NT-proBNP have low analytical variability&#44; which is greater in the point-of-care type than in the automated type&#46; This low variability helps detect differences between successive measurements attributable to changes in the clinical condition and not to analytical variability&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">6&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Circulating concentrations of B-type NPs have biological variability in healthy individuals and in stable patients&#46; This variability is greater for BNP than for NT-proBNP and increases as the serial interval and NP concentration decrease&#46; For example&#44; for weekly measurements in patients with stable HF&#44; the biological variability can reach 50&#37; for BNP and 25&#37; for NT-proBNP&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">7&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall">The BNP and NT-proBNP concentrations increase with age and are higher in women than in men&#46; Reference values stratified by age have been published for both NPs&#46; Obesity decreases the concentrations of BNP and NT-proBNP&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a></p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">8&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall">There are extracardiac causes for the increase in circulating concentrations of B-type NPs&#44; either through cardiac stress or an increase in circulating blood volume&#44; which should be interpreted in each clinical context&#46; Among them&#44; renal failure and pulmonary hypertension are the most clinically relevant&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">11</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">9&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall">BNP and NT-proBNP concentrations are increased in renal dysfunction and are higher the more severe the dysfunction&#46; The use of reference values stratified by age minimizes the effect of renal dysfunction on NT-proBNPvalues&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">12</span></a></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">10&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">When interpreting NP concentrations&#44; clinicians should consider the effect of particular drugs &#40;currently&#44; neprilysin inhibitors and recombinant BNP&#41; on the concentrations&#46;</p></li></ul></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Recommendations for using B-type NPs</span><p id="par0140" class="elsevierStylePara elsevierViewall">As general criteria for the use of NPs in the various clinical scenarios&#44; the recommendations are as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0145" class="elsevierStylePara elsevierViewall">Prior training in prelaboratory &#40;pathophysiology&#41;&#44; laboratory &#40;methods&#41; and postlaboratory &#40;interpretation and integration with the symptoms&#41; terms&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">Reasoned use based on the expected usefulness for improving decision making&#44; the diagnosis or the treatment of patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">Use of consensus protocols&#44; in which all departments involved in the use of NPs should participate&#46;</p></li></ul></p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">A&#46; Diagnosis</span><p id="par0160" class="elsevierStylePara elsevierViewall">The measurement of NPs for diagnostic purposes represents the main clinical application&#44; the most extensively studied application and the one with the most scientific evidence&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The following general recommendations have been established &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">Their measurement coupled with clinical judgment improves diagnostic accuracy compared with clinical diagnosis alone&#44; particularly in cases of uncertainty&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">13&#8211;15</span></a></p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">Their usefulness in the diagnosis has been studied in patients in whom dyspnea is the main symptom&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12&#44;16</span></a></p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">Their usefulness is mainly a result of their high negative predictive value for excluding HF&#44; especially in patients with no prior diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">17&#44;18</span></a></p></li></ul></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">The diagnostic use of NPs in 2 settings &#40;emergency department or hospital setting and the outpatient or doctor&#39;s office setting&#41; is discussed below&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A&#46;1&#46;</span> The measurement of B-type NP concentrations should be performed for all patients who go to the emergency department for dyspnea and for those with suspected <span class="elsevierStyleItalic">de novo</span> HF &#40;with no prior established diagnosis&#41;&#46;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">The use of B-type NPs has been shown to be cost-effective in this scenario and to have an effect on patient diagnosis and treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">19</span></a></p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Their usefulness is greater in conditions of clinical uncertainty&#44; prior to the initial assessment that has to include the case history&#44; physical examination&#44; electrocardiogram and chest radiology&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">20&#44;21</span></a></p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Their measurement should be performed with the patient&#39;s first blood sample upon their arrival at the emergency department&#46; The early availability of results facilitates a better diagnosis and treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">A low value &#40;NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#60;300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL or BNP<span class="elsevierStyleHsp" style=""></span>&#60;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; helps rule out the presence of HF regardless of age&#44; with a negative predictive value of 98&#37; for NT-proBNP and 90&#37; for BNP&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12&#44;13&#44;16&#44;22</span></a></p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">For NT-proBNP&#44; the use of age-adjusted values helps improve the ability to identify the presence of HF&#58; &#62;450<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;&#60;50 years&#41;&#44; &#62;900<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;50&#8211;75 years&#41; and &#62;1800<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;&#62;75 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12&#44;23</span></a> Overall&#44; the positive predictive value of these values is 88&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">12</span></a></p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">A high BNP value &#40;&#62;400<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; regardless of age&#44; should lead clinicians to consider the diagnosis of HF as probable&#44; with a positive predictive value of 86&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a></p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">To interpret intermediate values of NT-proBNP or BNP&#44; the clinical judgment for the likelihood of HF should predominate&#44; taking into consideration other conditions that could influence the concentrations of both peptides&#46;</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">For patients who already have a prior diagnosis of HF&#44; NPs should not be routinely measured on arrival at the emergency department or during hospitalization&#46; Nevertheless&#44; their measurement should be considered for patients who have a prior reading in a stable clinical condition &#40;outpatient or at the time of discharge for a prior decompensation&#41; and for whom there are questions about current acute decompensation of the HF&#46; Only in these cases&#44; individually and within a scenario of diagnostic uncertainty as to the role of HF in the current event&#44; is their measurement recommended&#46;</p></li></ul></p><p id="par0235" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A&#46;2&#46;</span> The measurement of NP concentrations should be accessible in outpatient consultations at the physician&#39;s discretion for patients with clinically suspected <span class="elsevierStyleItalic">de novo</span> HF &#40;with no prior established diagnosis&#41;&#46; This criterion should take in account the following&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">NP measurements should be requested for patients with diagnostic uncertainty&#44; after the initial clinical assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">24</span></a></p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">It is recommended that the result be made available&#44; ideally&#44; within 48<span class="elsevierStyleHsp" style=""></span>h of obtaining the sample&#46;</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">-</span><p id="par0250" class="elsevierStylePara elsevierViewall">The result should provide data for ruling out HF&#44; with reference values of 125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;NT-proBNP&#41; and 35<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;BNP&#41;&#46; Lower concentrations have a negative predictive value of 96&#8211;99&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">15&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">-</span><p id="par0255" class="elsevierStylePara elsevierViewall">Their initial request is preferable to echocardiography &#40;due to accessibility and financial cost&#41;&#44; especially if the latter is delayed by more than 7 days&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">-</span><p id="par0260" class="elsevierStylePara elsevierViewall">A value higher than the upper limit means that treatment for HF should start and that echocardiography should be performed to define the presence of heart disease</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">B&#46; Prognosis</span><p id="par0265" class="elsevierStylePara elsevierViewall">Although the prognostic utility of NPs in HF has been firmly established&#44; their use for this purpose should be tied to a number of specific conditions&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The following general recommendations have been established&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">-</span><p id="par0275" class="elsevierStylePara elsevierViewall">All increases in NP levels should be interpreted&#44; not only as support for the diagnosis but also as an &#8220;alarm signal&#8221; that provides short to medium-term risk information&#44; supplementing clinical judgment&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3&#44;4&#44;26</span></a></p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">-</span><p id="par0280" class="elsevierStylePara elsevierViewall">In any clinical scenario&#44; the greater the NP concentration&#44; the greater the risk of complications and poorer the clinical outcome&#46;</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">-</span><p id="par0285" class="elsevierStylePara elsevierViewall">The usefulness of NPs for assessing the prognosis is mainly applied to patients with HF&#46; However&#44; it should be noted that the presence of high concentrations in other diseases&#44; as a marker of stress and cardiac damage&#44; also identifies a greater cardiovascular risk&#46;</p></li><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">-</span><p id="par0290" class="elsevierStylePara elsevierViewall">The measurement of NPs as a risk assessment tool should not be performed routinely but rather as support for clinical judgment&#44; restricted to patients for whom the information provided affects the making of decisions regarding therapy&#46;</p></li></ul></p><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">B&#46;1&#46;</span> For patients in emergency departments or who are hospitalized&#44; the same criteria of the previous section are applicable&#46; The following conditions can also justify the use of NPs&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">-</span><p id="par0300" class="elsevierStylePara elsevierViewall">Patients with questions regarding the decision to hospitalize&#46;</p></li><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">-</span><p id="par0305" class="elsevierStylePara elsevierViewall">Patients with questions concerning the degree of care and hospital unit&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">-</span><p id="par0310" class="elsevierStylePara elsevierViewall">Patients with questions as to the use or withdrawal of devices or circulatory support therapies&#46;</p></li></ul></p><p id="par0315" class="elsevierStylePara elsevierViewall">The following should be considered when interpreting the results&#58;<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">-</span><p id="par0320" class="elsevierStylePara elsevierViewall">Absolute values of NT-proBNP greater than 5000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL are associated with a greater risk of severe complications&#46; The higher the NP concentration&#44; the poorer the prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12&#44;27&#44;28</span></a></p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">-</span><p id="par0325" class="elsevierStylePara elsevierViewall">In the presence of very high NP concentrations but lacking signs of HF&#44; the possibility should always be considered of a severe cardiovascular stress condition not attributable to HF &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; sepsis and pulmonary thromboembolism&#41;&#46;</p></li></ul></p><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">B&#46;2</span>&#46; For patients in outpatient consultations&#44; the following conditions could justify measuring NPs&#58;<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">-</span><p id="par0335" class="elsevierStylePara elsevierViewall">Patients with chronic HF with questions concerning the criteria for referral to specialists&#44; emergency department or hospitalization&#46;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">-</span><p id="par0340" class="elsevierStylePara elsevierViewall">Patients seen in advanced HF consultations for the decision-making process for therapy&#44; especially regarding the indication for heart transplantation and device implantation&#46;</p></li></ul></p><p id="par0345" class="elsevierStylePara elsevierViewall">The following should be considered when interpreting the results&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">-</span><p id="par0350" class="elsevierStylePara elsevierViewall">Values above 1000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for NT-proBNP indicate an increased risk of death or hospitalization&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">29</span></a> The increase in risk is linear&#59; the higher the concentration&#44; the higher the risk&#46;</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">-</span><p id="par0355" class="elsevierStylePara elsevierViewall">Any value should be interpreted in the clinical context&#44; taking into account modifiers such as age and comorbidity&#46;</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">C&#46; Follow-up and treatment</span><p id="par0360" class="elsevierStylePara elsevierViewall">The use of NPs as a tool for guiding medical treatment has been evaluated primarily in the outpatient setting and following hospitalization&#46; The results have been conflicting&#44; although the meta-analyses suggest its usefulness for optimizing drug treatment and reducing adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">The following items are proposed as general recommendations for its use as a treatment guideline&#58;<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">-</span><p id="par0370" class="elsevierStylePara elsevierViewall">The usefulness of NPs has been mainly demonstrated in patients younger than 75 years with systolic dysfunction&#46; Given that these studies were performed in HF units&#44; this use should only be considered in this context and by trained personnel&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">30&#44;31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">-</span><p id="par0375" class="elsevierStylePara elsevierViewall">Repeated NP measurements may also be assessed in specific circumstances&#44; for decision making within protocols and as support for the clinical judgment&#46;</p></li></ul></p><p id="par0380" class="elsevierStylePara elsevierViewall">The measurement of NP concentrations should not be requested routinely as a follow-up tool and treatment guideline&#46; This use should instead be performed under specific clinical considerations and scenarios&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C&#46;1&#46;</span> The following recommendations have been established for patients hospitalized for exacerbated HF&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">-</span><p id="par0390" class="elsevierStylePara elsevierViewall">For the serial use of NPs&#44; a value at admission needs to be obtained &#40;during the first 24<span class="elsevierStyleHsp" style=""></span>h of hospitalization&#41; because their changes should be interpreted in terms of a relative reduction compared to the initial value&#46;</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">-</span><p id="par0395" class="elsevierStylePara elsevierViewall">The reduction in NP levels in relative terms has greater usefulness than in absolute terms&#59; a 30&#37; reduction represents the threshold that has been associated with a better outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">-</span><p id="par0400" class="elsevierStylePara elsevierViewall">Their measurement as a therapy guideline&#44; at intermediate times between admission and discharge&#44; is not justified and should be restricted to specific conditions&#44; such as diuretic adjustment to resolve congestion&#46;</p></li><li class="elsevierStyleListItem" id="lsti0285"><span class="elsevierStyleLabel">-</span><p id="par0405" class="elsevierStylePara elsevierViewall">Their serial measurement should not be performed to determine when the patient should be discharged&#46; However&#44; they can support the clinical judgment of discharge&#44; when the progress of the concentrations is considered&#46;</p></li></ul></p><p id="par0410" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C&#46;2&#46;</span> In the follow-up of outpatients with HF&#44; NP measurement is recommended within specialized HF units or consultations to&#8230;<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0290"><span class="elsevierStyleLabel">-</span><p id="par0415" class="elsevierStylePara elsevierViewall">Confirm the decompensations&#46; NPs can help confirm the presence of decompensation in cases that have reasonable clinical uncertainty&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0295"><span class="elsevierStyleLabel">-</span><p id="par0420" class="elsevierStylePara elsevierViewall">Optimize medical treatment&#46; NPs can help optimize drug treatment&#44; based on the objective of achieving an NT-proBNP level less than 1000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">34</span></a> There are no BNP data for this use&#46;</p></li><li class="elsevierStyleListItem" id="lsti0300"><span class="elsevierStyleLabel">-</span><p id="par0425" class="elsevierStylePara elsevierViewall">In nonspecialized consultations&#44; their use should be limited to confirming decompensations in patients who have a value measured in a stable clinical situation&#46;</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">D&#46; Continuity of care</span><p id="par0430" class="elsevierStylePara elsevierViewall">NPs offer relevant information for the various professionals involved in caring for patients with HF during their progression&#44; which can vary&#46; The chronic character and complexity of HF entails the involvement of multidisciplinary teams&#44; thus the importance of contextualizing the NP concentrations of each patient at each developmental stage&#46; It is therefore recommended that&#8230;<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0305"><span class="elsevierStyleLabel">-</span><p id="par0435" class="elsevierStylePara elsevierViewall">the medical history and medical reports reflect how many NP values are obtained at all points of the disease progression&#46;</p></li><li class="elsevierStyleListItem" id="lsti0310"><span class="elsevierStyleLabel">-</span><p id="par0440" class="elsevierStylePara elsevierViewall">the discharge report includes all values obtained during hospitalization&#46;</p></li></ul></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions and final recommendations</span><p id="par0445" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0315"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0450" class="elsevierStylePara elsevierViewall">NPs are diagnostic and prognostic tools with demonstrated usefulness and should therefore be available in all healthcare settings&#44; both in primary care and specialized care&#44; for use based on medical criteria&#46;</p></li><li class="elsevierStyleListItem" id="lsti0320"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0455" class="elsevierStylePara elsevierViewall">Their proper use requires that medical professionals receive sufficient training in the prelaboratory &#40;pathophysiology&#41;&#44; laboratory &#40;measurement methods&#41; and postlaboratory &#40;interpretation in the clinical context&#41; phases&#46;</p></li><li class="elsevierStyleListItem" id="lsti0325"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0460" class="elsevierStylePara elsevierViewall">Their efficient use requires their inclusion in consensus clinical protocols by all involved medical professionals &#40;emergency department&#44; specialized care&#44; primary care and laboratory&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0330"><span class="elsevierStyleLabel">&#40;4&#41;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Their measurement is recommended for diagnosing HF in all patients with dyspnea who are admitted to the emergency department and who have no prior diagnosis of HF&#46;</p></li><li class="elsevierStyleListItem" id="lsti0335"><span class="elsevierStyleLabel">&#40;5&#41;</span><p id="par0470" class="elsevierStylePara elsevierViewall">Their measurement is recommended in outpatient consultations at the physician&#39;s discretion&#44; as an aid in the diagnosis of HF when there are questions concerning the diagnosis or when there is no prior diagnosis&#46; The evidence for this recommendation is greater if echocardiography is not available early on&#46;</p></li><li class="elsevierStyleListItem" id="lsti0340"><span class="elsevierStyleLabel">&#40;6&#41;</span><p id="par0475" class="elsevierStylePara elsevierViewall">Whenever the concentrations are measured&#44; they should be interpreted as a quantitative risk marker of death and unfavorable outcomes&#46; This information should be used in risk stratification as a supplement to the clinical assessment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0345"><span class="elsevierStyleLabel">&#40;7&#41;</span><p id="par0480" class="elsevierStylePara elsevierViewall">In patients previously diagnosed with HF&#44; the request for NP measurement for the diagnosis of decompensation or as a prognostic marker <span class="elsevierStyleItalic">per se</span> is only recommended in those conditions in which the results help the clinical or therapeutic decision-making process&#46;</p></li><li class="elsevierStyleListItem" id="lsti0350"><span class="elsevierStyleLabel">&#40;8&#41;</span><p id="par0485" class="elsevierStylePara elsevierViewall">Their serial measurement or as a therapeutic guideline for patients with an established diagnosis of HF should not be performed routinely but instead should follow consensus clinical protocols or be restricted to specific HF units&#46;</p></li><li class="elsevierStyleListItem" id="lsti0355"><span class="elsevierStyleLabel">&#40;9&#41;</span><p id="par0490" class="elsevierStylePara elsevierViewall">Their usefulness in the continuity of care is unquestionable&#46; The results of the measurements should therefore always be reflected in the medical history&#44; the discharge report and the patient follow-up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0360"><span class="elsevierStyleLabel">&#40;10&#41;</span><p id="par0495" class="elsevierStylePara elsevierViewall">Interaction between all involved professionals&#44; clinicians and laboratory staff is recommended&#44; which will result in joint training activities and improvements in the healthcare organization for the use of NPs&#46;</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0500" class="elsevierStylePara elsevierViewall">Jordi Ordo&#241;ez-Llanos declares having received support for research and attendance at conferences and payments as a speaker and member of the advisory committees of the major companies that market tests for measuring natriuretic peptides&#46;</p><p id="par0505" class="elsevierStylePara elsevierViewall">Antoni Bay&#233;s-Genis declares having received support for research and attendance at conferences and payments as a speaker by Roche Diagnostics&#46;</p><p id="par0510" class="elsevierStylePara elsevierViewall">D&#46; Pascual-Figal declares having received support for research from Roche Diagnostics and bioMerieux&#46;</p><p id="par0515" class="elsevierStylePara elsevierViewall">The other authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Current situation in Spain"
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          "titulo" => "Recommendations for using B-type NPs"
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              "titulo" => "A&#46; Diagnosis"
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              "titulo" => "C&#46; Follow-up and treatment"
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              "titulo" => "D&#46; Continuity of care"
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    "fechaRecibido" => "2016-01-14"
    "fechaAceptado" => "2016-02-22"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Natriuretic peptides"
            1 => "B-type natriuretic peptide"
            2 => "Aminoterminal pro-B-type natriuretic peptide"
            3 => "Heart failure"
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        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec717565"
          "palabras" => array:4 [
            0 => "P&#233;ptidos natriur&#233;ticos"
            1 => "P&#233;ptido natiur&#233;tico de tipo B"
            2 => "Fracci&#243;n N-terminal del pro-p&#233;ptido natiur&#233;tico de tipo B"
            3 => "Insuficiencia cardiaca"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Natriuretic peptides are a useful laboratory tool for the diagnosis&#44; prognosis and treatment of patients with heart failure&#46; Natriuretic peptides are used in various healthcare settings &#40;consultations&#44; emergency department&#44; hospitalization&#44; laboratory&#41; and by various primary care and specialized professionals&#46; However&#44; their use in clinical practice is still scare and uneven&#46; Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory &#40;pathophysiology&#41;&#44; laboratory &#40;methods&#41; and postlaboratory &#40;interpretation and integration of clinical data&#41; expertise&#46; The objective of this consensus document&#44; developed by several scientific societies&#44; is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis&#44; prognosis and treatment of heart failure&#44; in various healthcare environments&#46;</p></span>"
      ]
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los p&#233;ptidos natriur&#233;ticos son una herramienta de laboratorio &#250;til en el diagn&#243;stico&#44; pron&#243;stico y tratamiento de los pacientes con insuficiencia cardiaca&#46; Su uso involucra a diferentes &#225;mbitos sanitarios &#40;consultas&#44; urgencias&#44; hospitalizaci&#243;n&#44; laboratorio&#41; y a muy diferentes profesionales de la Atenci&#243;n Primaria o especializada&#46; Sin embargo&#44; su incorporaci&#243;n a la pr&#225;ctica asistencial a&#250;n es escasa y desigual&#46; Para un correcto uso e interpretaci&#243;n en la pr&#225;ctica cl&#237;nica se necesita un m&#237;nimo de conocimientos preanal&#237;ticos &#40;fisiopatolog&#237;a&#41;&#44; anal&#237;ticos &#40;m&#233;todos&#41; y postanal&#237;ticos &#40;interpretaci&#243;n e integraci&#243;n con los datos cl&#237;nicos&#41;&#46; Este documento de consenso elaborado por varias sociedades cient&#237;ficas tiene como objetivo actualizar los conceptos y conocimientos necesarios sobre los p&#233;ptidos natriur&#233;ticos que permitan su aplicaci&#243;n para el diagn&#243;stico&#44; pron&#243;stico y tratamiento de la insuficiencia cardiaca&#44; en los diferentes &#225;mbitos sanitarios&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Pascual-Figal DA&#44; Casademont J&#44; Lobos JM&#44; Pi&#241;era P&#44; Bay&#233;s-Genis A&#44; Ord&#243;&#241;ez-Llanos J&#44; et al&#46; Documento de consenso y recomendaciones sobre el uso de los p&#233;ptidos natriur&#233;ticos en la pr&#225;ctica cl&#237;nica&#46; Rev Clin Esp&#46; 2016&#59;216&#58;313&#8211;322&#46;</p>"
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        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Consensus meeting held in Madrid on the 6th of October&#44; 2015&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Diagram of the BNP production mechanism and natriuretic peptide receptor function&#46; <span class="elsevierStyleItalic">Abbreviations</span>&#58; ANP&#44; A or atrial natriuretic peptide&#59; BNP&#44; B or brain natriuretic peptide&#59; CNP&#44; C natriuretic peptide&#59; GMP&#44; guanosine monophosphate&#59; GTP&#58; guanosine triphosphate&#59; NPR&#44; natriuretic peptide receptor&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The BNP values in the second column correspond with those observed in the same population of individuals evaluated with the various methods&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">35&#44;36</span></a> The results are expressed as median &#40;interquartile range&#41;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">35</span></a> or mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BNP<br>Instrumentation company&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">BNP &#40;pg&#47;mL&#41;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">35&#44;36</span></a></th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Capture antibody &#40;aa of the epitope&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Detection antibody &#40;aa of the epitope&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard employed to calibrate the method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alere<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><br>Triage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">413 &#40;5&#8211;2&#46;170&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">133<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;5&#8211;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Omniclonal&#44; uncharacterized epitope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recombinant BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abbott<br>Architect<br>AxSYM<br>iSTAT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">526 &#40;13&#8211;3&#46;065&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;5&#8211;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;26&#8211;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Beckman Coulter<br>Access&#44; Access 2<br>DxL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">464 &#40;18&#8211;2&#46;166&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Omniclonal&#44; uncharacterized epitope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;5&#8211;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recombinant BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens<br>ACS 180<br>Advia Centaur<br>Advia Centaur CP<br>Advia Centaur XP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">315 &#40;11&#8211;1&#46;884&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">114<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal &#40;27&#8211;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;14&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Siemens<br>Dimension VISTA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;14&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">This method is taken as a reference because it was employed to obtain the clinical decision limits in the BNP study&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">16</span></a></p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the methods for measuring BNP&#44; including the antibodies used&#44; the compound&#39;s epitopes recognized by the antibodies and the standard employed to calibrate the method&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The NT-proBNP values in the second column correspond to the mean and 2 standard deviations of the same serum for quality control of the Spanish Society of Clinical Chemistry and Molecular Pathology &#40;SEQC&#41; assayed repeatedly by the various methods in various clinical laboratories&#46; The methods with no NT-proBNP values were not used in any participating laboratory &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>123&#41; in the Quality Control Program&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP<br>Instrumentation company&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Capture antibody &#40;aa of the epitope&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Detection antibody &#40;aa of the epitope&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard employed to calibrate the method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Roche Diagnostics</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&#59; Modular E170&#44; Cobas e601&#44; e602&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">116<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;42&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Alere</span>&#59; Triage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;42&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">bioMerieux</span>&#59; VIDAS&#44; MiniVIDAS&#44; VIDAS 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">86&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;42&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mitsubishi Chemical</span>&#59; PATHFAST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;1&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;39&#8211;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Nanogen LifeSign</span>&#59; DXpress Reader&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>polyclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ortho Clinical Diagnostics</span>&#59; Vitros ECi 3600&#44; 5600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">226<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;1&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;39&#8211;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Radiometer</span>&#59; AQT90 FLEX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">224<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;1&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;39&#8211;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Response Biomedical</span>&#59; RAMP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;39&#8211;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Roche Diagnostics</span>&#59;<br>Elecsys 2010&#44; Cobas e411<br>Cobas e601&#44; e602&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;1<br>118<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;27&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;42&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Siemens</span><br>Dimension RxL&#44; Xpand Dimension VISTA&#44; Dimension EXL<br>Stratus CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;9<br>110<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3<br>75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;2<br>220<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal &#40;22&#8211;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monoclonal<br>&#40;42&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Siemens</span><br>Immulite 1000&#44; 2000&#44; 2500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">401&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;1&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polyclonal<br>&#40;39&#8211;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Synthetic NT-proBNP aa 1&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0010"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This method is taken as the reference because it was the most widely used by the laboratories that participated in the SEQC Quality Control Program&#46;</p>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the Methods for Measuring NT-proBNP&#44; including the antibodies used&#44; the compound&#39;s epitopes recognized by the antibodies and the standard employed to calibrate the method&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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            "detalle" => "Table "
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NT-proBNP<br>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BNP<br>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Emergency Department</td><td class="td" title="table-entry  " align="left" valign="top">&#60;300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HF very unlikely&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;50 years&#58; 300&#8211;450<br>50&#8211;75 years&#58; 300&#8211;900<br>&#62;75 years&#58; 300&#8211;1800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&#8211;400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not determinative&#46; The clinical criterion of probability should predominate&#44; taking into account other situations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;50 years&#58; &#62;450<br>50&#8211;75 years&#58; &#62;900<br>&#62;75 years&#58; &#62;1800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HF with high probability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outpatient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HF very unlikely&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1167741.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Reference NT-proBNP and BNP values for the diagnosis of heart failure&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
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                      "titulo" => "ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012&#58; the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology&#46; Developed in collaboration with the Heart Failure Association &#40;HFA&#41; of the ESC"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "S&#46; Adamopoulos"
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                      "doi" => "10.1093/eurheartj/ehs104"
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                      "titulo" => "2013 ACCF&#47;AHA Guideline for the management of heart failure a report of the American College of Cardiology Foundation&#47;American Heart Association Task Force on Practice Guidelines"
                      "autores" => array:1 [
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                            0 => "C&#46;W&#46; Yancy"
                            1 => "M&#46; Jessup"
                            2 => "B&#46; Bozkurt"
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                      "doi" => "10.1016/j.jacc.2013.05.019"
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                      "titulo" => "Resultados preliminares de una encuesta sobre manejo de la insuficiencia cardiaca aguda en Espa&#241;a"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46;A&#46; Pascual Figal"
                            1 => "J&#46;F&#46; Delgado Jim&#233;nez"
                            2 => "N&#46; Manito Lorite"
                            3 => "J&#46;L&#46; Lambert Rodriguez"
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                        "tituloSerie" => "Rev Esp Cardiol"
                        "fecha" => "2015"
                        "volumen" => "68"
                        "numero" => "Suppl&#46; 1"
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            5 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "6"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Encuesta de recursos asistenciales y manejo de la exacerbaci&#243;n"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;J&#46; Soler"
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2016.04.001

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