Evaluación de los niveles de NT-proBNP en los derrames pleurales de origen cardíaco / Evaluation of NT-proBNP levels in pleural effusions of cardiac origin

Objetivo: Evaluar el rendimiento diagnóstico del fragmento amino-terminal del péptido natriurético (NT-proBNP) en líquido pleural (LP) y suero (S) en pacientes con insuficiencia cardíaca congestiva (ICC) y valorar su utilidad en la identificación de derrames pleurales (DPs) de origen cardiogénico, frente a los criterios de Light y gradiente de proteínas (PT). Material y métodos: Se analizaron 21 DPs (42,85% trasudados) de los cuales, siete fueron secundarios a ICC. La precisión diagnóstica del NT-proBNP en LP y S y de los criterios de Light se obtuvo mediante el área bajo la curva (AUC). Resultados: NT-proBNP en S presenta mejor rentabilidad diagnóstica (AUC:0,889) que su determinación en LP, criterios de Light y gradiente de PT. Valores por encima de 1.053 pg/ml identifican la etiología cardíaca del derrame con una sensibilidad del 83% y una especificidad del 100%. De los derrames cardiogénicos clasificados erróneamente por el criterio de Light LDH (LP/S), NT-proBNP en S identifica correctamente la totalidad de los derrames (100%). Conclusión: La determinación de NT-proBNP en LP para diferenciar la naturaleza trasudativa de los DPs de origen cardiogénico, no resulta de utilidad en la práctica clínica. En derrames cuya etiología sea dudosa, las concentraciones séricas de NT-proBNP pueden ser útiles para el diagnóstico de ICC

Objective: To evaluate the diagnostic performance of the N-terminal pro-natriuretic peptide (NT-proBNP) in pleural fluid (PF) and serum, in patients with congestive heart failure (CHF) and assess its usefulness in the identification of cardiogenic pleural effusions, against the Light's criteria and protein gradient (PT). Material and Methods: We analyzed 21 DP (42.85% transudates) of which seven were secondary to CHF. The diagnostic accuracy of NT-proBNP in LP and S and the Light's criteria was obtained using the area under the curve (AUC). Results: The serum determination of NT-proBNP presents the best diagnostic yield (AUC: 0.889) than its determination in PF, Light's criteria and protein gradient. Values above 1,053 pg/ml identify the cardiac etiology of the effusion with a sensitivity of 83% and a specificity of 100%. Of the patients misclassified by the Light LDH criteria (LP/S), NT-proBNP in S correctly identifies all of the effusions (100%). Conclusion: The determination of NT-proBNP in pleural fluid to differentiate the transudative nature of cardiogenic pleural effusions, is not useful in clinical practice. In effusions whose etiology is doubtful, seric concentrations of NT-proBNP may be useful for the diagnosis of CHF

Documento de consenso y recomendaciones sobre el uso de los péptidos natriuréticos en la práctica clínica / Consensus document and recommendations on the use of natriuretic peptides in clinical practice

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 (AU)

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 specialised 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 (AU)

Aminoterminal proBrain Natriuretic Peptide en sangre como marcador de isquemia miocárdica en la evaluación de pacientes con dolor torácico y probabilidad intermedia para síndrome coronario agudo / Natriuretic peptide amino proBrain blood as a marker of myocardial ischemia in the evaluation of patients with chest pain and intermediate risk for acute coronary syndrome

Introducción: lo péptidos natruréticos son una familia de hormonas polipeptídicas sistetizadas, acumuladas en gránulos de reserva y secretadas por los cardiocitos auriculares y ventriculares; ellas regulan el tono vascular y mecanismos renales y metabólicos. Aminoterminal proBrain Natriuretic Peptide (NT.proBNP), es un fragmento inactivo que resulta del clivaje del proBrain Natriuretic Peptide y es un biomarcador de disfunción cardíaca. Los niveles plasmáticos de los péptidos natriuréticos pueden elevarse ante estímulos diversos como insuficiencia cardíaca, isquemia o inflamción. En los síndromes coronarios agudos son marcadores de riesgo y permiten una adecuada estratificación. Hipótesis: los niveles plasmáticos de NT-proBNP medidos antes de una prueba de esfuerzo en pacientes con probabilidad intermedia de síndrome coronario agudo, e inmediatamente después de maximo esfuerzo, detectarán isquemia miocárdica y predecirán eventos cardiovasculares a 30 días y 6 meses.

Introduction: natriuretic peptides are a family of polypeptide hormones synthesized, stored and secreted by atrial and ventricular cardiocytes; they regulate the vascular tone, and renal and metabolic mechanisms. Aminoterminal proBrain Natriuretic Peptide (NT-proBNP) is an inactive fragment thas is cleaved from the proBrain Natriuretic Peptide and it is a biomarker of different stimuli sch as heart failure, ischemia or inflammation. In acute coronary syndromes they are risk markers enabling adequate risk stratification. Hypothesis: plasma levels of NT-proBNP measured before a stress test in patients with an intermediate probability of acute coronary syndrome, and immediately after maximum stress will detect myocardial ischemia and will predict cardiovascular events at 30 days and 6 months.

Aminoterminal proBrain Natriuretic Peptide en sangre como marcador de isquemia miocárdica en la evaluación de pacientes con dolor torácico y probabilidad intermedia para síndrome coronario agudo / Natriuretic peptide amino proBrain blood as a marker of myocardial ischemia in the evaluation of patients with chest pain and intermediate risk for acute coronary syndrome

Introducción: lo péptidos natruréticos son una familia de hormonas polipeptídicas sistetizadas, acumuladas en gránulos de reserva y secretadas por los cardiocitos auriculares y ventriculares; ellas regulan el tono vascular y mecanismos renales y metabólicos. Aminoterminal proBrain Natriuretic Peptide (NT.proBNP), es un fragmento inactivo que resulta del clivaje del proBrain Natriuretic Peptide y es un biomarcador de disfunción cardíaca. Los niveles plasmáticos de los péptidos natriuréticos pueden elevarse ante estímulos diversos como insuficiencia cardíaca, isquemia o inflamción. En los síndromes coronarios agudos son marcadores de riesgo y permiten una adecuada estratificación. Hipótesis: los niveles plasmáticos de NT-proBNP medidos antes de una prueba de esfuerzo en pacientes con probabilidad intermedia de síndrome coronario agudo, e inmediatamente después de maximo esfuerzo, detectarán isquemia miocárdica y predecirán eventos cardiovasculares a 30 días y 6 meses.(AU)

Introduction: natriuretic peptides are a family of polypeptide hormones synthesized, stored and secreted by atrial and ventricular cardiocytes; they regulate the vascular tone, and renal and metabolic mechanisms. Aminoterminal proBrain Natriuretic Peptide (NT-proBNP) is an inactive fragment thas is cleaved from the proBrain Natriuretic Peptide and it is a biomarker of different stimuli sch as heart failure, ischemia or inflammation. In acute coronary syndromes they are risk markers enabling adequate risk stratification. Hypothesis: plasma levels of NT-proBNP measured before a stress test in patients with an intermediate probability of acute coronary syndrome, and immediately after maximum stress will detect myocardial ischemia and will predict cardiovascular events at 30 days and 6 months.(AU)

Causes of repeated remodeling of left ventricle after Dor procedure.

OBJECTIVES: To reveal morphological factors causing unfavorable follow-up outcome of surgical treatment of patients with ischemic cardiomyopathy (ICMP) and with left ventricle (LV) aneurysm according to the data of intraoperative biopsies of LV myocardium and right atrium (RA) auricle. METHODS: The object of the study was to examine biopsy material of LV myocardium and RA auricle from 36 patients with ICMP. Clinical criteria of patients' inclusion into the study were: ESI LV >80 ml/m(2), EDP LV >30 mmHg, LV EF <40%, presence of akinetic and dyskinetic areas in LV, angina of II-IV class CCS, heart failure of II-IV class NYHA. The following morphometrical parameters were estimated for revelation of postoperative remodeling risk factors: parenchymal-stromal ratio (PSR), trophic index (TI), pericapillar diffusion zone (PDZ), Kernogan index (KI) and specific volume of granules of natriuretic factor (NUF) in atrial cardiomyocytes. RESULTS: In all the patients LV EF increased significantly (from 36.4+/-4.1% to 46.3+/-4.2%) (P<0.05) in the early postoperative period; LV EDI decreased (from 139.3+/-11.2 ml/m(2) to 108.4+/-8.9 ml/m(2)) (P<0.05). In the follow-up period (one year) all the patients were divided into two groups: in 28 patients (the 1st group) volume of the cavity, contractile function of LV remained satisfactory. In the other eight patients (the 2nd group) there was significant decrease of LV EF (up to 33.9+/-10.2%) due to increase of LV EDI [up to 129.2+/-10.1 ml/m(2) (P<0.05)]. Grade of MR preoperatively was 1.21+/-0.5 and 1.47+/-0.9, correspondingly, for the patients with positive and negative changes in the follow-up postoperative period. Drawing morphological parallels of postoperative heart remodeling in patients with ICMP showed that diffusive, lymphocytic-macrophage inflammatory infiltration of myocardial stroma in combination with severe fibrosis (PSR<1.5), low TI (<0.015) and greater value of PDZ (>1000 microm) and KI (>1.6) of LV myocardium are the factors connected with unfavorable follow-up results of surgical treatment. Moreover, we showed an inverse correlative relationship between content of NUF granules in the cardiomyocytes of RA auricle and the outcomes of the Dor procedure. CONCLUSIONS: Thus, a combination of the foregoing features is a morphological predictor of postoperative heart remodeling in patients with ICMP.

[Brain natriuretic peptide in acute coronary syndromes: utility of NT-pro BNP assay]. / Peptide natriurétique B et syndromes coronariens aigus: utilité du dosage du fragment NT-pro BNP.

Better risk stratification strategies are required for patients with acute coronary syndromes. Plasma myocardial troponin is a specific but poorly sensitive marker. Levels of B natriuretic peptide, a 32-amino-acid peptide synthesized and released by left ventricular myocytes, correlate strongly both with the presence of acute myocardial lesions and with vital outcome. To address the possible influence of the sampling time, we measured NT-pro BNP plasma concentrations on emergency admission and 8 and 24 hours later in 64 patients with acute coronary syndromes. Troponin levels were abnormal in respectively 44%, 51% and 52% of patients, while NT-pro BNP levels were abnormal in 75%, 83% and 79% of patients (p < 10(-4)). Both troponin and NT-pro BNP levels were abnormal in patients with ST elevation MI (n = 15; 93% and 87%, NS) and in patients with non ST elevation MI (n = 19; 73% and 68%). In contrast, among 30 patients with unstable angina, troponin levels were always normal whereas NT-pro BNP levels were elevated in 73% of cases (p < 10(-4)). This suggests that more than 50% patients with acute coronary syndromes who have normal troponin levels 8 hours after admission--and would therefore be discharged--would qualify for further investigations on the basis of natriuretic peptide levels. NT-pro BNP is thus more sensitive than troponin as a marker of myocardial damage. In addition, its clinical significance is not influenced by the precise sampling time within 24 hours following emergency admission. NT-pro BNP therefore adds important information for patient stratification.

Effects of the order of running and cycling of similar intensity and duration on pulmonary diffusing capacity in triathletes.

To study the pathophysiological mechanisms involved in the decrease of post-triathlon diffusing capacity (DLco), blood rheologic properties (blood viscosity: eta(b); changes in plasma volume: deltaPV) and atrial natriuretic factor (ANF) were assessed in ten triathletes during cycle-run (CR) and run-cycle (RC) trials at a metabolic intensity of 75% of maximal oxygen consumption ( VO(2max)). The DLco was measured before and 10 min after trials. ANF and deltaPV were measured at rest, after the cycle and run of CR and RC trials, and at the end of and 10 min after exercise. RC led to a greater deltaDLco decrease, a lower ANF concentration and a lower deltaPV than did CR, whereas for both CR and RC eta(b) was increased throughout exercise and 10 min after. In addition, after CR the deltaDLco decrease was inversely correlated ( r=-0.764; P<0.01) with deltaPV. The association of decreased plasma volume, increased eta(b), and lower ANF concentrations after RC suggested that lower blood pulmonary volume may have caused the greater decrease in Dlco as compared with CR. The inverse correlation between deltaPV and deltaDLco reinforces the hypothesis that fluid shifts limit the post-exercise DLco decrease after the CR succession in triathletes. Lastly, cycling in the crouched position might increase intra-thoracic pressure, decrease thorax volume due to the forearm position on the handlebars, and weaken peripheral muscular pump efficacy, all of which would limit venous return to the heart, and thus result in low pulmonary blood volume. Compared with cycling, running appeared to induce the opposite effects.

[Prognostic value of neurohormones in heart failure in clinical practice]. / Valeur pronostique des neuro-hormones dans l'insuffisance cardiaque en pratique clinique.

The decisive therapeutic advances achieved in cardiac insufficiency in recent years have been thanks to drugs affecting the different neurohormonal systems in operation. Neurohormonal activation plays a major role in cardiac insufficiency. Several neuro-endocrine mechanisms exert vasoconstrictor effects: the sympathetic system, the renin-angiotensin-aldosterone system and the endothelins. In cardiac insufficiency these effects are counterbalanced, but insufficiently, by vasodilatory agents, mainly the natiuretic peptides, EDRF (endothelium derived relaxing factor), vasodilatory prostaglandins, bradykinin and adrenomedulin. Neurohormonal activation is an excellent marker of not only the severity but also the prognosis of cardiac insufficiency. Standardisation of dosage is desirable in order to allow the use of neurohormonal drugs in a very large number of centres.

[Study and treatment of heart failure require new approaches. Natriuretic peptides can be safe and simple diagnostic and outcome measures]. / Utredning och behandling av hjärtsvikt söker nya vägar. Natriuretiska peptider kan bli säkert och enkelt mått i diagnostik och behandling.

Analysis of plasma natriuretic peptides and related propeptide fragments may be a cost-effective aid to diagnostic evaluation and treatment follow-up in cases of heart failure. In diagnostic potential such variables may constitute first-line measures of high negative predictive value, allowing further examination, e.g. by echocardiography, in cases where values are above the respective cut-off levels. However, in many cases evaluation of published reports is rendered difficult by their omission of information on such pre-analytical variables as blood sampling and storage, and drug therapy. Moreover, different analytical methods may yield widely divergent results. Thus, before such assays are introduced in general use, their long-term validity needs to be ensured, for instance by consistency in calibration, and measurements need to be made in representative series of unselected patients for the determination of appropriate cut-off levels.

Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury.

PURPOSE: This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury. MATERIALS AND METHODS: We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years (with acute lung injury and compared those with hemodynamic parameters and pulmonary functions. RESULTS: Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = .608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days). CONCLUSION: These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.

Natriuretic peptide immunoreactivity in nerve structures and Purkinje fibres of human, pig and sheep hearts.

Atrial natriuretic peptide is a well-described peptide in cardiac Purkinje fibres and has been shown to interfere with the autonomic regulation in the heart of various species, including man. Recently, we detected immunoreactivity for the peptide in intracardial ganglionic cells and nerve fibre varicosities of bovine hearts, by the use of a modified immunostaining technique that induced an improved detection of natriuretic peptides. These findings raised the question as to whether natriuretic peptides are detectable in these tissues in man and other species. The conduction system from human, pig and sheep hearts was dissected processed with antisera against atrial natriuretic peptide and the closely related brain natriuretic peptide. Immunostaining for the brain natriuretic peptide was detected in some Purkinje fibres in all of these species. Interestingly, in pig, sheep and human hearts, some ganglionic cells and nerve fibres showed atrial natriuretic peptide immunoreactivity, particularly in the soma of human ganglionic cells. This is the first study showing immunoreactivity for the atrial natriuretic peptide in nerve structures and for the brain natriuretic peptide in Purkinje fibres of the human heart. The results give a morphological correlate for the documented effects of atrial natriuretic peptide on the heart autonomic nervous system and for the presumable effects of brain natriuretic peptide in the conduction system of man.

[The role of the natriuretic hormone in the action of nifedipine and verapamil on the kidneys]. / Rol' natriiureticheskogo gormona v deistvii nifedifina i verapamila na pochki.

It was demonstrated in experiments on albino rats that under the effect of nifedipine and verapamil the increase in the excretion of electrolytes and water by the kidneys is accompanied with a rise in the natriuretic hormone (NUH) content in blood plasma and urine. This causes the renal effects of the drugs under study. The sensitivity of the kidneys to NUH increases in this case.

Pituitary adenylate-cyclase activating polypeptide (PACAP) evokes long-lasting secretion and de novo biosynthesis of bovine adrenal medullary neuropeptides.

Recently, the pituitary adenylate-cyclase activating polypeptide (PACAP) has emerged as a potential noncholinergic neuromodulator of adrenal medullary function. In support of this hypothesis, we documented PACAP's effects on the secretion and biosynthesis of neuropeptides by cultured bovine chromaffin cells. Data presented in this study indicate that PACAP is a potent and efficacious secretagogue of leucine-enkephalin which was coreleased with catecholamines with identical profiles. In comparison to nicotinic activation, however, rates of PACAP-induced secretion were substantially slower but persisted for several hours causing a prolonged increase in the tonic release of both transmitters and peptides. Interestingly, renewal of intracellular pools of neuropeptides was also stimulated by PACAP but not the vasoactive intestinal peptide (VIP). Indeed, the higher incorporation of [35S]-labeled amino acids into atrial and brain natriuretic peptides (ANP, BNP) provided strong evidence that PACAP directly activated de novo biosynthesis. Of particular importance was PACAP's net preferential stimulation of the biosynthesis of BNP, similar to the differential regulation by protein kinase A (PK-A) and protein kinase C (PK-C) activators we have previously the differential regulation by protein kinase A (PK-A) and protein kinase C (PK-C) activators we have previously reported. PACAP-induced secretion and biosynthesis appeared to be mediated by the PACAP-specific type I receptors known to activate adenylate cyclase and phospholipase C. We verified that PACAP did indeed stimulate the production of cyclic AMP and inositol phosphates in our cell system. These findings suggest that the dual signaling properties of type I receptors may be important for PACAP's differential effect on the biosynthesis of natriuretic peptides. We conclude that PACAP might assume important noncholinergic trans-synaptic regulation of the adrenal medulla by releasing and modifying intragranular catecholamine and neuropeptide contents.

Is there an intestinal natriuretic factor?

Intestinal tissue from cats was homogenized and fractionated by ultrafiltration to a molecular range of about 500-10,000 and separated by gel chromatography. The fractions from the gel filtrations were tested with regard to their ability to inhibit Na,K-ATPase as assayed with p-nitrophenylphosphate. The fractions that inhibited Na,K-ATPase were pooled and named pooled fraction 2. Pooled fraction 1 contained molecules larger, and pooled fraction 3 and 4 the molecules smaller, than pooled fraction 2. The four fractions were assayed for natriuretic 'activity' on anaesthetized rats. Administering pooled fraction 3 (no Na,K-ATPase-inhibiting activity) i.v. augmented renal excretion of sodium and water, whereas the other pooled fractions did not exhibit any consistent natriuretic effect. Cardiac ventricular tissue from cats was fractionated in the same manner as was done for the intestine. None of the cardiac fractions contained any natriuretic material. It is proposed that the cat small intestine contains a natriuretic factor.

Cardiac content of brain natriuretic peptide in DOCA salt-hypertensive rats.

The cardiac content of immunoreactive rat brain natriuretic peptide (ir-rBNP) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats was measured by radioimmunoassay (RIA). The atrial content of ir-rBNP was significantly lower in the DOCA-salt group than in the control group (p less than 0.01). However, the ventricular content of ir-rBNP was markedly increased in the DOCA-salt group as compared to the other groups. Ir-rBNP level in the atria was negatively correlated with other groups. Ir-rBNP level in the atria was negatively correlated with blood pressure (r = -0.49, p less than 0.01), while that in the ventricle was positively correlated with blood pressure (r = 0.79, p less than 0.001). A significant correlation was observed between tissue levels of ir-rBNP and ir-rat atrial natriuretic peptide (rANP) both in atrium and ventricle (atrium, r = 0.63, p less than 0.001; ventricle, r = 0.95, p less than 0.001). These results raise the possibility that rBNP as well as rANP functions as a cardiac hormone, the production of which probably changes in response to increased of body fluid and blood pressure.