Preditores de fibrilação atrial de novo em unidade de cuidados intensivos não cardíaca / Predictors of de novo atrial fibrillation in a non-cardiac intensive care unit

RESUMO Objetivo: Avaliar quais os preditores de fibrilação atrial de novo em doentes de uma unidade de cuidados intensivos não cardíaca. Métodos: Foram analisados 418 doentes internados entre janeiro e setembro de 2016 em uma unidade de cuidados intensivos não cardíaca. Registaram-se as características clínicas, as intervenções efetuadas e os marcadores bioquímicos durante a internação. Avaliaram-se ainda a mortalidade hospitalar e o tempo de internação hospitalar e na unidade de cuidados intensivos. Resultados: Foram incluídos 310 doentes, com média de idades de 61,0 ± 18,3 anos, 49,4% do sexo masculino, 23,5% com fibrilação atrial de novo. O modelo multivariável identificou acidente vascular cerebral prévio (OR de 10,09; p = 0,016) e valores aumentados de proBNP (OR de 1,28 por cada aumento em 1.000pg/mL; p = 0,004) como preditores independentes de fibrilação atrial de novo. A análise por curva Característica de Operação do Receptor do proBNP para predição de fibrilação atrial de novo revelou área sob a curva de 0,816 (p < 0,001), com sensibilidade de 65,2% e especificidade de 82% para proBNP > 5.666pg/mL. Não se verificaram diferenças na mortalidade (p = 0,370), porém a duração da internação hospitalar (p = 0,002) e na unidade de cuidados intensivos (p = 0,031) foi superior nos doentes com fibrilação atrial de novo. Conclusões: História de acidente vascular cerebral prévio e proBNP elevado em internação constituíram preditores independentes de fibrilação atrial de novo na unidade de cuidados intensivos polivalente. O proBNP pode constituir ferramenta útil, de fácil e rápido acesso na estratificação do risco de fibrilação atrial.

ABSTRACT Objective: To assess the predictors of de novo atrial fibrillation in patients in a non-cardiac intensive care unit. Methods: A total of 418 hospitalized patients were analyzed between January and September 2016 in a non-cardiac intensive care unit. Clinical characteristics, interventions, and biochemical markers were recorded during hospitalization. In-hospital mortality and length of hospital stay in the intensive care unit were also evaluated. Results: A total of 310 patients were included. The mean age of the patients was 61.0 ± 18.3 years, 49.4% were male, and 23.5% presented de novo atrial fibrillation. The multivariate model identified previous stroke (OR = 10.09; p = 0.016) and elevated levels of pro-B type natriuretic peptide (proBNP, OR = 1.28 for each 1,000pg/mL increment; p = 0.004) as independent predictors of de novo atrial fibrillation. Analysis of the proBNP receiver operating characteristic curve for prediction of de novo atrial fibrillation revealed an area under the curve of 0.816 (p < 0.001), with a sensitivity of 65.2% and a specificity of 82% for proBNP > 5,666pg/mL. There were no differences in mortality (p = 0.370), but the lengths of hospital stay (p = 0.002) and stay in the intensive care unit (p = 0.031) were higher in patients with de novo atrial fibrillation. Conclusions: A history of previous stroke and elevated proBNP during hospitalization were independent predictors of de novo atrial fibrillation in the polyvalent intensive care unit. The proBNP is a useful and easy- and quick-access tool in the stratification of atrial fibrillation risk.

Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.

Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.

Expressions of Mast Cell Tryptase and Brain Natriuretic Peptide in Myocardium of Sudden Death due to Hypersensitivity and Coronary Atherosclerotic Heart Disease / 法医学杂志

OBJECTIVES@#To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.@*METHODS@#Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting.@*RESULTS@#Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （P<0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （P<0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （P>0.05）.@*CONCLUSIONS@#The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.

Influence of Spironolactone on Matrix Metalloproteinase-2 in Acute Decompensated Heart Failure / Influência da Espironolactona na Metaloproteinase de Matriz 2 na Insuficiência Cadíaca Aguda Descompensada

Background: Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment. Objective: Our aim was to test the influence of spironolactone in MMP2 levels. Methods: Secondary analysis of a prospective, interventional study including 100 patients with ADHF. Fifty patients were non-randomly assigned to spironolactone (100 mg/day) plus standard ADHF therapy (spironolactone group) or standard ADHF therapy alone (control group). Results: Spironolactone group patients were younger and had lower creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight did not differ between spironolactone and control groups. A trend towards a more pronounced decrease in MMP2 from baseline to day 3 was observed in the spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro BNP and weight also had a greater decrease in the spironolactone group. The proportion of patients with a decrease in MMP2 levels from baseline to day 3 was also likely to be greater in the spironolactone group (50% vs 66.7%), but without statistical significance. Correlations between MMP2, NT-pro BNP and weight variation were not statistically significant. Conclusion: MMP2 levels are increased in ADHF. Patients treated with spironolactone may have a greater reduction in MMP2 levels. .

Fundamento: As metaloproteinases de matriz (MMPs) constituem uma família de enzimas importantes para a reabsorção da matriz extracelular e controle do remodelamento e da reparação vasculares. Demonstrou-se aumento da atividade de MMP2 na insuficiência cardíaca, e, na insuficiência cardíaca agudamente descompensada (ICAD), demonstrou-se uma diminuição nas MMPs circulantes juntamente com o tratamento bem-sucedido. Objetivos: Testar a influência da espironolactona nos níveis de MMP2. Métodos: Análise secundária de estudo prospectivo, intervencionista, incluindo 100 pacientes com ICAD, 50 designados não aleatoriamente para o uso de espironolactona (100 mg/dia) mais terapia padrão para ICAD (grupo espironolactona) e 50 para terapia padrão para ICAD apenas (grupo controle). Resultados: Os pacientes do grupo espironolactona eram mais jovens e tinham níveis mais baixos de creatinina e ureia (todos p < 0,05). Os valores basais de MMP2, NT-pro BNP e peso não diferiram entre os grupos espironolactona e controle. Observou-se tendência para uma redução mais pronunciada na MMP2 do basal para o dia 3 no grupo espironolactona (-21 [-50 a 19] vs 1,5 [-26 a 38] ng/ml, p = 0,06). Os valores de NT-pro BNP e peso também apresentaram maior diminuição no grupo espironolactona. A proporção de pacientes com redução nos níveis de MMP2 do basal para o dia 3 também foi maior no grupo espironolactona (50% vs 66,7%), embora sem significado estatístico. As correlações entre as variações de MMP2, NT-pro BNP e peso não apresentaram significado estatístico. Conclusões: Os níveis de MMP2 acham-se aumentados na ICAD. Pacientes tratados com espironolactona podem apresentar maior redução nos níveis de MMP2. .

El corazón endocrino y el proceso inflamatorio / [The endocrine heart and inflammation].

The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor (ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions of these hormones the heart contributes to the regulation of the cardiac preload and afterload. More recently, new functions for these hormones have been described including the modulation of the immune response. Plasma levels of BNP but not those of ANF, increase following an acute rejection episode of a cardiac allotransplant but return to levels pre-rejection with successful treatment. This observation constitutes the first observation leading to characterizing the interactions of BNP with the immune response. Several other pathologies with an inflammatory component are now known to be associated with an increase in the production of BNP. Such an increase is due to an increase in the transcriptional activity of the BNP gene induced by cytokines and related substances. In vitro investigations have shown that an increase in BNP directly modulates immunological activity. Inflammation and hemodynamic changes co-exist in several cardiovascular diseases and therefore it may be beneficial to measure circulating levels of both ANF and BNP as biomarkers of changes in intravascular volume and of changes in intravascular volume plus inflammation, respectively. Changes in plasma ANF, that are relatively larger than those of BNP, might be an indication of hemodynamic deterioration while important changes in circulating BNP could indicate a worsening of the inflammatory process.

Expression of BNP in rat myocardial tissue after acute cardiac dysfunction / 法医学杂志

OBJECTIVE@#To investigate the expression of brain natriuretic peptide (BNP) in rat myocardial tissue after acute cardiac dysfunction and to explore the role of BNP in diagnosis of cardiac dysfunction in forensic practice.@*METHODS@#Rat models of acute cardiac dysfunction were established. The expression of BNP protein and BNP mRNA in myocardial tissue after cardiac dysfunction were detected by immunohistochemistry, Western blotting and real-time RT-PCR.@*RESULTS@#The extent of positive staining of BNP increased over the time course during cardiac dysfunction. The expression of BNP showed mild positive in cardiomyocytes from 1 h to 2 h. From 4 h to 6 h, the expression was moderate positive. From 10 h to 12 h, the BNP showed a strongest positive expression. The expression of BNP presented a significant raise with the increasing time of cardiac dysfunction by Western blotting and real-time RT-PCR. The expression of BNP mRNA increased significantly 1 h after cardiac dysfunction.@*CONCLUSION@#Investigating the expression of BNP protein and BNP mRNA in myocardial tissue may provide a new approach to evaluate the cardiac function for forensic pathologists.

Application of brain natriuretic peptide in evaluation of cardiac function in forensic medicine / 法医学杂志

Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.

Cardiac biomarkers in the diagnosis, prognosis and management of coronary artery disease: A primer for internists.

Initially coined in 1989, biomarkers have become a cornerstone of modern cardiovascular medicine. The past decade has borne witness to the rapid transition of cardiac biomarkers from bench to bedside in the management of patients with coronary artery disease. The implementation of cardiac biomarkers has transformed the internists' approach to cardiovascular patients. This article reviews several cardiac biomarkers in the context of diagnosis, prognosis, risk-assessment and management of patients at risk of adverse cardiovascular outcomes. Biomarkers are presented according to their relevant role in the atherosclerotic cascade, a pathologic classification of particular value for internists, as it defines the role of these agents in the pathogenesis of heart disease. Where pertinent, limitations of cardiac biomarkers are discussed, thus allowing the discerning practitioner to remain cognizant of situations that may lead to spurious marker elevation or suppression. The review concludes with highlights on novel avenues of biomarker research that promise an exciting future for these entities.

The analysis of pericardial fluid in forensic practice / 法医学杂志

Pericardial fluid is a kind of serous fluid in pericardial cavity. Because blood undergoes postmortem changes such as autolysis and putrefaction, vitreous humor is limited,cerebrospinal fluid is easily mixed with blood, pericardial fluid, on the other hand, exists in a closed cavity and can be hardly contaminated by postmortem changes, and also is easily obtained. Pericardial fluid not only plays an important role in clinic practice, but also is widely applicable in forensic practice. This paper briefly presented the properties of pericardial fluid and its clinical significance. It reviewed biochemical changes in decedents died of heart diseases, drowning and asphyxia, and explored the significance in medico-legal investigation. Moreover, application of pericardial fluid in forensic serology, forensic toxicological analysis and other fields were also discussed. Pericardial fluid analysis may provide important information for determination of the cause of death with further investigation concerning forensic applicability of pericardial fluid.

The application of biochemical indexes detecting in sudden cardiac death in forensic autopsy / 法医学杂志

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.

Expression of brain natriuretic peptide and c-fos gene in rat after acute myocardial ischemia and its medicolegal significance / 法医学杂志

OBJECTIVE@#To study the mRNA expression of BNP and c-fos gene in rat heart after acute myocardial ischemia (AMI) and to provide a marker for its medicolegal diagnosis.@*METHODS@#AMI animal model of rat was made by ligating LAD. mRNA expression of BNP and c-fos gene were studied with RT-qPCR and ordinary PCR at 10 min, 30 min, 60 min and 3h after the successful ligation. The H&E staining was also used. Changes of the mRNA expression in different time groups were compared.@*RESULTS@#There was significant difference in BNP mRNA expression of the 3 h group by RT-qPCR compared with normal control group, 10 min, 30 min, and 60 min groups (P < 0.05). There were dramatic differences in c-fos mRNA expression between every two groups (P < 0.05) except between the normal group and the 10 min group, between the 30 min group and the 3 h group. The peak of c-fos expression was in 60 min group. No difference was shown between groups by the ordinary PCR. Myocardial fiber acidophilia staining and wavy changes could be seen occasionally at 3 h experimental group by H&E staining.@*CONCLUSIONS@#C-fos gene probably be used as an auxiliary test for myocardial ischemia of duration of 30 minutes or longer. RT-qPCR may be suitable for diagnosis of early AMI.

Revisión clínica: depresión miocárdica en sepsis y shock séptico / Clinical revision: myocardial depression in sepsis and septic shock

La sepsis y el shock séptico son patologías de gran mortalidad, cuyo evento final es la hipotensión refractaria, colapso cardiocirculatorio y falla multiorgánica. En los últimos años se han realizado importantes esfuerzos para entender la disfunción cardiaca asociada a este cuadro, que puede objetivarse hasta en el 50 por ciento de los pacientes con sepsis severa y shock séptico. A pesar de que hoy se acepta que la disfunción miocárdica juega un importante rol en la sepsis, aún no existe consenso respecto a la manera de evaluar la función cardiaca en este contexto, surgiendo nuevas propuestas como el uso de marcadores séricos. Por otra parte, el tratamiento más utilizado hasta hoy han sido los inótropos como la dobutamina, sin embargo con los nuevos estudios sobre la etiología de la disfunción miocárdica, se ha logrado el desarrollo de nuevas líneas experimentales de tratamiento.

The sepsis and the septic shock are pathologies of the great mortality, whose final event is the refractory hypotension, circulatory collapse and multiorganic failure. In the last years important efforts have been made to understand the associate cardiac dysfunction to this picture, which can appear until in 50 percent of the patients with severe sepsis and septic shock. Although today it is accepted that the myocardial dysfunction plays an important role in the sepsis. It does not yet exist consensus with respect to the way to evaluate the function cardiac. New proposals arising as the use from seric markers. On the other hand, the more used treatment until today has been the inotropic agent like the dobutamine. But with the new studies on the etiology of the myocardial dysfunction, has been obtained the development of experimental new line of treatment.

El NT-proBNP predice mal pronóstico en pacientes con síndromes coronarios agudos sin elevación del segmento ST y función ventricular conservada / NT-proBNP predicts clinical outcomes in patients with NSTE-ACS and preserved left ventricular function

Antecedentes: El NT-proBNP se asocia con disfunción ventricular y mala evolución en síndromes coronarios agudos sin elevación del ST (SCA-SEST). La evidencia sobre su valor pronóstico en pacientes con SCA-SEST y función sistólica conservada es escasa. Objetivos: Explorar el valor pronóstico del NT-proBNP en pacientes con SCA-SEST sin disfunción ventricular. Material y métodos: De una cohorte de pacientes con SCA-SEST sometidos a angiografía se seleccionaron 393 con fracción de eyección del ventrículo izquierdo menor igual 40 por ciento. Laboratorios centrales independientes analizaron las angiografías y las determinaciones de NT-proBNP, troponina T, mioglobina y proteína C reactiva. Se empleó un punto de corte de NT-proBNP de 586 pg/ml. El punto final primario fue la incidencia de muerte o infarto a los 180 días. Resultados: Ochenta y tres pacientes (21 por ciento) tuvieron NT-proBNP mayor igual 586 pg/ml y 310 (79 por ciento) niveles < 586 pg/ml. Los pacientes con NT-proBNP elevado eran más añosos, con mayor frecuencia de sexo femenino; tuvieron una proporción mayor de marcadores séricos elevados y una proporción mayor de enfermedad coronaria extensa y de lesiones coronarias complejas. Estos pacientes, comparados con aquellos con NT-proBNP < 586 pg/ml, tuvieron una incidencia mayor de muerte (9,6 por ciento versus 2,3 por ciento; p = 0,002), infarto (9,6 por ciento versus 3,2 por ciento; p = 0,01) y muerte o infarto (16,9 por ciento versus 5,5 por ciento; p = 0,001) a los 180 días. Ajustando por variables clínicas, electrocardiográficas y angiográficas, el NT-proBNP resultó ser un predictor independiente del punto final combinado de muerte o infarto a los 6 meses y de muerte por cualquier causa. Conclusiones: El NT-proBNP es un predictor independiente de muerte e infarto y de muerte global a los 6 meses en pacientes con SCA-SEST sin disfunción ventricular.

Síndrome cerebral perdedor de sal / Cerebral salt losing syndrome

Se presenta escolar de 9 años, sexo masculino con una hemorragia subaracnoida secundario a malformación vascular dorsolumbar: Evoluciona con hipovolemia severa, natriuveris y tendencia a la hiponatremia lo que hace plantear Síndrome Cerebral Perdedor de Sal (SCPS). Se manejó con aporte extra de sodio y fármaco con propiedades mineralocorticoides (Fluorhidrocortisona) con lo cual se observa mejoría. Alrededor de 1988 se plantea por primera vez este síndrome, presentándose entre el 9 y el 33 por ciento de los pacientes con hemorragia subaracnoídea. Dado lo difícil que resulta precisar la causa de la hiponetremia en estos pacientes se expone las características clínicas, fisiopatológicas y manejode esta afección