Valor pronóstico de biomarcadores cardíacos en la enfermedad por COVID-19 / value of cardiac biomarkers in COVID-19 disease

Resumen Introducción: En la enfermedad por COVID-19 se ha establecido que los pacientes con enfermedad cardiometabólica de base tienen mayor riesgo de presentar desenlaces adversos. Esto ha incrementado el interés en estudiar variables cardiovasculares relevantes, para plantear su correlación con los desenlaces clínicos en esta población. Objetivo: Describir el valor pronóstico de los biomarcadores cardíacos en la enfermedad por COVID-19. Métodos: Revisión no sistemática de la literatura en bases de datos como PubMed, Google Scholar, Clinical Key, SciELO, entre otras, utilizando palabras clave, términos planos y términos MeSh. Resultados: Se eligieron 22 bibliografías, entre ellas artículos de revisión de tema, revisiones sistemáticas, metaanálisis, estudios observacionales y artículos originales publicados hasta la fecha (mayo 13 de 2020), que en su mayoría describen la alteración de biomarcadores cardiacos y su relación con la evolución clínica de los pacientes con COVID-19. Discusión: Se encontró que la troponina y el péptido natriurético se comportan como factores de riesgo independientes para compromiso clínico severo, requerimiento de soporte ventilatorio o hemodinámico, estancia en la UCI, y aumento de la mortalidad. Conclusiones: Es razonable plantear el uso de estos biomarcadores en la estratificación del riesgo en pacientes con COVID-19 y enfermedad cardiovascular establecida.

Abstract Introduction: It has been established that patients with an underlying cardiometabolic disease and COVID-19 infections, have a higher risk of an adverse outcome. This has led to an increase in the interest of studying relevant cardiovascular variables, in order to establish their association with clinical outcomes in this population. Objective: To describe the prognostic value of cardiac biomarkers in disease caused by COVID-19. Methods: A non-systematic review of the literature was carried out in data bases that included PubMed, Google Scholar, Clinical Key, SciELO, using the key words, plain terms, and MeSH terms. Results: A total of 22 articles were chosen. They consisted of review articles on the subject, systematic reviews, meta-analyses, observational studies, and original articles published up until 13 May 2020. The majority of them described the changes in cardiac biomarkers and their relationship with the clinical outcome of patients COVID-19. Discussion: It was found that Troponin and Natriuretic Peptide behaved as independent risk factors for severe clinical compromise, requiring ventilatory or haemodynamic support, admission to ICU, and an increase in mortality. Conclusions: It is reasonable to recommend the use of these biomarkers in the risk stratification in patients with COVID-19 and an established cardiovascular disease.

Diagnostic and Prognostic Role of Liver Elastography in Heart Failure

Abstract Background: Hepatic congestion is a frequent finding in patients with heart failure (HF). Physical examination has limitations in quantifying systemic congestion and requires correlation with echocardiographic and laboratory data (usually B-type natriuretic peptide, BNP, or N-terminal pro-B type natriuretic peptide, NT-proBNP). Hepatic elastography evaluates liver stiffness using a transducer that transmits low-frequency vibrations (50 Hz), and the speed of shear waves propagating through the tissues is measured by ultrasound. The faster the vibrations propagate in the hepatic parenchyma, the stiffer the liver, which, in case of HF, can be correlated with hepatic congestion. Objective: In this systematic review, case-controls, cohort studies, and randomized clinical trials were searched in MEDLINE, LILACS and Cochrane Database of Systematic Review, to evaluate the use of elastography in the detection of hepatic congestion in patients with HF. Methods: From the 49 articles retrieved, seven were selected for review, according to the inclusion and exclusion criteria. The most used methods for the diagnosis and evaluation of HF were echocardiography combined with BNP and NT-proBNP measurements. Results: Elastography performed at bedside was able to establish a significant correlation between increased liver stiffness and increased venous capillary pressure. In addition, liver elastography performed at hospital discharge was able to predict rehospitalization and mortality. Conclusion: Liver elastography is a non-invasive method that can be useful in predicting prognosis and mortality of individuals with HF, contributing to the clinical management of these patients.

Resection of the atrial appendages and its impact in the natriuretic homeostasis: development and validation of an animal model in an academic medical center

ABSTRACT Background: The left atrial appendage (LAAp) resection is an effective treatment approach to reduce the risk of thromboembolism in patients with atrial fibrillation. Objective: To study was to study the impact of removing atrial appendages in the production of natriuretic peptides (NPs) in conditions of volume overload and to develop an experimental model of LAAp resection. Materials and Methods: In a swine model of ischemic heart failure (HF), serum NP levels were measured before (Basal-1A) and after (Basal-1B) a fluid overload. Animals were grouped as follows: (0) preserved appendages, (1) resected LAAp, and (2) both atrial appendages resected. Levels of NP were measured before (2A) and after a fluid overload (2B). Results: Furin levels were higher in Group 0-2A than in Group 2-2A, and a significant increase was found in Group 0-2B compared to Groups 1-2B and 2-2B. Corin levels increased in Basal-1B versus Basal-1A. Atrial NP (ANP) decreased in Basal-1B compared to Basal-1A. After HF induction, ANP increased in Groups 2-2A and 2-2B. Conclusions: Resection of atrial appendages drastically modifies the natriuretic mechanisms of cardiac homeostasis, especially after a fluid overload challenge. Herein, we describe the face and predictive validation of an animal model of atrial appendage resection useful to investigations in translational medicine.

Actualización en el uso de inhibidores de la neprilisina y del receptor de angiotensina II: onda expansiva en el beneficio sobre distintas entidades / Update on the use of neprilysin inhibitors and angiotensin II receptor: shock wave for the benefit of different entities

Resumen La insuficiencia cardiaca es una de las principales enfermedades a nivel cardiaco debido a su mayor riesgo de mortalidad y de hospitalizaciones por descompensaciones agudas o por presencia de novo de falla cardiaca, por eso en los últimos años se desarrollaron a partir de estudios clínicos randomizados, medicamentos que mejoraran estos eventos, a partir del estudio PARADIGM-HF. Con el surgimiento de sacubitril/valsartan se evaluó su efecto en diferentes escenarios, así el enfoque de este artículo se basa en la revisión de artículos con el objetivo de analizar la importancia de los efectos be neficiosos del sacubitril/valsartan en comparación con enalapril en diferentes análisis y subestudios basado en el estudio PARADIGM-HF, en los cuales se evaluó el impacto del sacubitril/valsartan en diabetes mellitus tipo 2, en la función renal, hipertensión arterial, a nivel de mortalidad y seguridad, a nivel de edad, de hiperkalemia e hiperkalemia severa, en los factores asociados con la falta de cumplimiento durante el período de ejecución antes de la aleatorización y la influen cia en el beneficio estimado de sacubitril/valsartan en el ensayo PARADIGM-HF, eficacia de sacubitril/valsartan con dosis metas bajas, tolerabilidad y seguridad en el inicio de sacubitril/valsartan en insuficiencia cardiaca, efectos de sacubitril/ valsartan asociado a antagonistas de receptores de mineralocorticoides en la reducción de hiperkalemia, implicaciones en el pronóstico de los pacientes con insuficiencia cardiaca con fracción de eyección reducida con los cambios de pépti dos natriuréticos, eficacia y seguridad de sacubitril/valsartan en distintos rangos de edades, efecto del fármaco sobre la terapia de fondo utilizada en insuficiencia cardiaca y eficacia e influencia de sacubitril/valsartan en la fracción de eyección y desenlace primario.

Abstract Descriptores: sacubitril/valsartan, enalapril, insuficiencia cardiaca, péptidos natriureticos Heart failure is one of the main diseases at the cardiac level due to its higher risk of mortality and hospitalizations due to acute decompensation or de novo heart failure, which is why in recent years they were developed from randomized clinical trials. medicines that will improve these events, from there and from the PARADIGM-HF study. From the emergence of sacubitril / valsartan its effect was evaluated in different scenarios, hence the focus of this article was based on the review of articles and with the aim of analyzing the importance of the beneficial effects of sacubitril / valsartan compared to enalapril in different analyzes and substudies from the PARADIGM-HF study, which will evaluate the impact of sacubitril / valsartan in type 2 diabetes mellitus, in renal function, arterial hypertension, in terms of mortality and safety, in terms of age, hyperkalemia and severe hyperkalemia, in the factors associated with non-compliance during the execution period before randomization and the influence on the estimated benefit of sacubitril / valsartan in the PARADIGM-HF trial, efficacy of sacubitril / valsartan with low target doses , tolerability and safety at the onset of sacubitril / valsartan in heart failure, effects of sacubitril / valsartan associated with antag of mineralocorticoid receptors in the reduction of hyperkalemia, implications in the prognosis of patients with heart failure with reduced ejection fraction with changes in natriuretic peptides, efficacy and safety of sacubitril / valsartan in different age ranges, effect of the drug on the background therapy used in heart failure and the efficacy and influence of sacubitril / valsartan on the ejection fraction and primary outcome.

Effectiveness of natriuretic peptide-guided treatmen of chronic heart failure. A meta-analysis / Efectividad del tratamiento guiado por el péptido natriurético para la insuficiencia cardiaca crónica. Meta-análisis

Abstract Objective: To evaluate the efficacy of natriuretic peptide (NP)-guided therapy compared to clinically-guided therapy in reducing mortality and hospital admissions in chronic heart failure (HF) patients. Methods: Randomised clinical trials (RCT) were selected through a systematic review. Four meta-analyses were conducted for the outcomes of overall mortality, HF-related mortality, overall hospital admissions, and HF-related hospital admissions. Heterogeneity between studies and publication bias were also assessed. Results: Nine RCTs were found with a total of 1914 patients. NP-guided therapy significantly reduced overall mortality and HF-related hospital admissions. No significant results were found for HF-related mortality and overall hospital admissions. Some clinical heterogeneity regarding interventions performed was found between studies. Publication bias was found for HF-related and overall hospital admissions. Conclusions: NP-guided therapy seems to improve outcomes compared to clinically-guided therapy. However, heterogeneity found between interventions might reduce the generalisation of these results. Specific interventions of the clinical trials should be examined when making recommendations regarding NP-guided therapy. © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Resumen Objetivo: Evaluar la eficacia de la terapia guiada por el péptido natriurético (PN) en comparación con la terapia guiada clínicamente para reducir la mortalidad y la hospitalización de la insuficiencia cardiaca (IC) crónica. Métodos: Los ensayos clínicos aleatorizados fueron seleccionados a través de una revisión sistemática. Cuatro metaanálisis se realizaron para los resultados de mortalidad general, mortalidad por IC, hospitalización general y la hospitalización por IC. Se evaluó la heterogeneidad entre los estudios y el sesgo de publicación. Resultados: Nueve ensayos clínicos aleatorizados se encontraron con un total de 1,914 pacientes. La terapia guiada con el PN reduce significativamente la mortalidad general y la hospitalización por IC. No se encontraron resultados significativos para la mortalidad por IC y la hospitalización general. El sesgo de publicación se encontró para las hospitalizaciones por IC y globales. Conclusiones: La terapia guiada por PN parece mejorar los resultados en comparación con la terapia guiada clínicamente. Sin embargo, la heterogeneidad encontrada entre las intervenciones podría reducir la generalización de estos resultados. Las intervenciones específicas de los ensayos clínicos deben ser analizadas al hacer recomendaciones con respecto a la terapia de guiada por PN. © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Actualización en insuficiencia cardiáca: nuevas gías terapéuticas / Update in Hearth Failure: New Treatment Guidelines

Antecedentes: En los últimos dos años se han publicado recientes Guias europeas y americanas para el diagnóstico y manejo de Insuiciencia cardiaca, destaca la evidencia a favor de marcadores séricos (péptidos natriureticos) y se publica un nuevo fármaco con acción dual en receptores de neprilisina y angiotensina que ha mostrado beneicio en morbilidad y mortalidad. Fuente: Se realizó una revisión de las Guias 2016 de la ESC (European Society of Cardiology), las Guias 2017 de la ACC/AHA (American College of Cardiology/American Hearth Asociation) y el Consenso de Centro América y el Caribe (2015) sobre Insuiciencia cardíaca; se complementó información en revisiones sistemáticas, metaanálisis y artículos de revisión en bases de revistas PUBMED, EMBASE e Hinari entre 2001 y 2017. Desarrollo: Se presenta al lector una síntesis de la actualidad en cuanto al uso de métodos convencionales y marcadores séricos en el diagnóstico y pronóstico de falla cardíaca; se exponen los fármacos e intervenciones indicados con mayor evidencia para su tratamiento. Conclusiones: La medición de Peptido Natriuretico B es útil para establecer el pronóstico y severidad de la IC crónica; se recomienda la inhibición del sistema renina angiotensina aldosterona mediante los IECAs, ARAII, ARNI en conjunto con betabloqueadores y mineralocorticoides en pacientes con IC con FE reducida para reducción de morbilidad y mortalidad. En pacientes con IC crónica clase funcional II o III que toleran los IECA o ARAII se recomienda cambio a ARNI para mayor beneicio...(AU)

Insuficiência cardíaca - fisiopatologia atual e implicações terapêuticas / Heart failure - current pathophysiology and terapeutic implications

Conhecer a fisiopatologia da insuficiência cardíaca propiciou uma evolução terapêutica em seu manejo, que se traduziu em melhora de desfechos clínicos relevantes, incluindo redução da mortalidade. O conceito do remodelamento ventricular, associado à ativação neuro-humoral descrita inicialmente, via ativação do sistema renina-angiotensina-aldosterona, e posteriormente via ativação simpática, levou ao uso de inibidores da ECA e de betabloqueadores, respectivamente, que mudaram o curso da história da insuficiência cardíaca. Ainda na categoria farmacológica, mais recentemente a modulação da rota da neprilisina, através do uso do composto sacubitril/valsartan, trouxe impacto adicional de redução de mortalidade em pacientes com insuficiência cardíaca. Por fim, dispositivos que também interfiram no processo de remodelamento ventricular, como marcapassos de ressincronização biventricular, demonstraram benefícios clínicos significativos. Novos alvos moleculares, microRNAs ou moléculas de sinalização intracelular, devem crescer como potenciais áreas de investigação na progressão da doença e, potencialmente, se transformarem em alvos terapêuticos

Knowledge of the pathophysiology of heart failure has led to a therapeutic evolution in its management that has resulted in improved clinical outcomes, including a reduction in mortality. The concept of ventricular remodeling associated with neurohumoral activation, initially described via activation of the renin-angiotensin-aldosterone system and later, via sympathetic activation, led to the use of ACE inhibitors and beta blockers, respectively, altering the course of history of heart failure. Also in the pharmacological category, more recently, modulation of the neprilysin route, through the use of the compound sacubitril/valsartan, brought additional impacts in reducing mortality in patients with heart failure. Finally, devices that also interfere in the process of ventricular remodeling, such as biventricular resynchronization pacemakers, have demonstrated significant clinical benefits. New molecular targets, microRNAs, or intracellular signaling molecules should increase as potential areas of research on disease progression, and could potentially become therapeutic targets

Avaliação dos níveis plasmáticos do peptídeo natriurético NT-proBNP em cães da raça Poodle em diferentes estágios da doença valvar crônica mitral / Evaluation of plasma levels of NT-proBNP natriuretic peptide in Poodle dogs at different stages of chronic mitral valve disease

A doença valvar crônica mitral (DVCM) é comum em cães e pode não causar sintomas clínicos da insuficiência cardíaca (IC) durante anos. O peptídeo natriurético tipo B (BNP) é armazenado nos miócitos ventriculares e secretado para circulação com seu fragmento NT-proBNP, quando ocorre aumento. Este estudo avaliou os níveis plasmáticos do peptídeo natriurético NT-proBNP em cães da raça Poodle em diferentes estágios da DVCM, seguindo as diretrizes do American College of Veterinary Internal Medicine (ACVIM, 2009). Amostras de sangue foram coletadas para determinação do biomarcador NT-proBNP para comparação entre grupos. As medianas do NT-proBNP nos grupos estudados foram: 551pmol/L (controle), 302pmol/L (grupo B1), 1.033pmol/L (grupo B2), 954pmol/L (grupo C) e 5.541pmol/L (grupo D). Mediante o uso de um ponto de corte ideal de >709pmol/L, foi possível identificar os cães com aumento cardíaco verdadeiro daqueles sem aumento cardíaco, com sensibilidade de 75% e especificidade de 100%. O NT-proBNP aumentou de acordo com o avanço dos estágios da DVCM, sendo os estágios B2, C e D aqueles com valores mais elevados desse biomarcador. Para o estágio B2, a mensuração do NT-proBNP mostrou ser uma excelente ferramenta para diagnosticar precocemente o aumento cardíaco em cães da raça Poodle.(AU)

Chronic mitral valve disease (CMVD) is common in dogs, it may not cause clinical symptoms of heart failure (HF) for years. The type B natriuretic peptide (BNP) is stored in the ventricular myocytes and secreted for circulation with its NT-proBNP fragment, when an increase occurs. This study evaluated the plasma levels of the NT-proBNP natriuretic peptide in Poodles at different stages of CMVD, following the guidelines of the American College of Veterinary Internal Medicine (ACVIM, 2009). Blood samples were collected for determination of NT-proBNP biomarker for comparison between groups. This median NT-proBNP in the studied groups were: 551pmol/L (Control), 302pmol/L (Group B1), 1,033pmol/L (Group B2), 954pmol/L (Group C) and 5,541pmol/L (Group D). Using an ideal cutoff of > 709pmol/L it was possible to identify dogs with true heart enlargement of those without a cardiac increase with sensitivity of 75% and specificity of 100%. NT-proBNP increased according to the progress of the stages of CMVD, being that stages B2, C and D, with the highest values of the biomarker. To stage B2, the NT-proBNP measurement proved to be an excellent tool for early diagnosis of cardiac enlargement in Poodles.(AU)

Avaliação de peptídeo natriurético em cães doentes renais crônicos / Natriuretic peptide assessment in dogs with chronic kidney disease

Na doença renal crônica (DRC), a hipertensão arterial é uma das complicações mais comuns, que pode estar associada a liberação dos peptídeos natriuréticos e a hipertrofia ventricular no homem. Em cães os peptídeos natriuréticos são estudados como biomarcadores cardíacos, mas ainda se desconhece sua função em cães com DRC. Desta forma, este estudo teve como objetivo relacionar a concentração sérica de peptídeo natriurético B aos achados de pressão arterial, eletrocardiográficos, eletrolíticos, hematológicos e bioquímicos séricos e urinários em cães nos distintos estágios da DRC. Foram constatadas diferenças significativas na relação de proteína creatinina urinária (UPC, p=0,006), anemia, creatinina e uréia sérica (p<0,001) nos grupos de doentes renais comparado com saudáveis. Apesar das variações de pressão arterial, amplitude e intervalo QRS e fósforo não serem significativas, foi observada tendência de alteração desses valores com o avanço da doença. Não foi observado correlação entre BNP (peptídeo natriurético cerebral) e DRC.(AU)

In chronic kidney disease (CKD) hypertension is one of the most common complications that may be associated with the release of natriuretic peptides and ventricular hypertrophy in humans. In dogs the natriuretic peptides are studied as cardiac biomarkers, but still unaware their function in dogs with CKD. Thus, this study aimed to relate the serum natriuretic peptide B with blood pressure findings, electrocardiographic, electrolyte, blood and serum and urinary biochemistry in dogs in different stages of CKD. Significant differences were found in urinary protein to creatinine ratio (UPC, p=0.006), anemia, serum creatinine and urea (p<0.001) in the group of patients with renal disease compared with the healthy group. Despite the variation in blood pressure, amplitude and QRS interval and phosphorus are not significant, a tendency for alterations of these values was observed with the advance of the disease. There was no correlation between BNP and CKD.(AU)

Natriuretic peptide precursor C coding gene contributes to zebrafish angiogenesis / 生理学报

This study aimed to investigate the expression of the natriuretic peptide precursor C coding gene nppc and its role in angiogenesis during embryonic period of the zebrafish. Whole mount in situ hybridization was performed to detect the expression pattern of nppc. nppc specific morpholino and nppc mRNA were injected respectively into the one-cell stage embryo to specifically knock-down and rescue the expression of nppc in Tg (flk1:GFP) and Tg (fli1a:nGFP) transgenic lines. The morphology and endothelial cell number of intersegmental vessel (ISV) were analyzed after imaging using the laser scanning confocal microscope. The results revealed that nppc was expressed in the brain, heart and vasculature of zebrafish larvae at 24 and 48 hours post-fertilization (hpf). Knock-down of nppc affected the development of ISV. Endothelial cell number was reduced after the knock-down of nppc. These results suggest that nppc controls zebrafish angiogenesis by affecting the endothelial cell proliferation and migration.

Inhibición dual de la neprilisina y del receptor de la angiotensina (ARNI): una alternativa en los pacientes con falla cardiaca / Dual angiotensin receptor and neprilysin inhibition (ARNI): an alternative for patients with cardiac failure

La falla cardiaca (FC) es la causa más común de admisión hospitalaria en adultos en el mundo. Además, de su importante prevalencia la FC tiene un alta tasa de mortalidad, se estima que aproximadamente el 50% de los pacientes con FC mueren a los 5 años posterior al egreso hospitalario. Esto ha motivado el desarrollo de nuevas terapias seguras y efectivas para el manejo de esta entidad. El LCZ696 es un inhibidor dual de la neprilisina y del receptor de angiotensina II que demostró en estudios de fase III disminuir el desenlace primario de muerte cardiovascular y hospitalización por empeoramiento de la FC y muerte global. Probablemente el LCZ696 se convertirá en la piedra angular del manejo en pacientes con FC con fracción de eyección deprimida.

Cardiac failure (CF) is the most common cause of hospital admission in adults all over the world. In addition to its important prevalence, CF presents a high mortality rate. It is estimated that approximately 59% of patients with CF die within 5 years after the admission. This has been the motivation for the development of new, safe and effective therapies aimed at the management of this disease. LCZ696 is an angiotensin II receptor-neprilysin inhibitor; phase III studies have shown it decreases the primary outcome of cardiovascular death and admission due to worsening of the CF and global death. LCZ696 could probably become the cornerstone of the management of patients with CF with depressed ejection fraction.

Marcadores cardiacos y riesgo cardiovascular / Cardiac markers and cardiovascular risk

La identificación del riesgo que un individuo o una población tienen de presentar un evento cardiovascular y la posibilidad de intervenir oportunamente para evitarlo, constituye el fundamento que ha propiciado la investigación de marcadores cardiacos y su potencial de predicción de riesgo cardiovascular. La mortalidad por causa cardiovascular es la primera causa de muerte en el mundo desarrollado y tambièc)n en Chile, por lo que los esfuerzos de identificación acuciosa y de correcta clasificación de riesgo de los individuos o población permiten una eficiente focalización de los esfuerzos por disminuir los eventos cardiovasculares. En este artículo se revisan distintos marcadores cardiacos (proteína C reactiva ultra sensible, score calcio coronario, pèc)ptido natriurèc)tico y troponina ultrasensible) y las evidencias que apoyan o desalientan su uso para una adecuada evaluación de riesgo cardiovascular.

The identification of the risk that an individual or populations have of developing a cardiovascular event, and the opportunity for an early intervention to avoid it, is the foundation that has motivated the research in cardiac markers and their potential in cardiovascular risk prediction. Cardiovascular disease is the leading cause of mortality in Chile and the developed world, therefore, a precise identification and a correct risk classification of the individuals or a population allow a more focalized and efficient effort to decrease cardiovascular events. In this paper, different cardiac markers are reviewed, high sensitive C reactive protein, coronary calcium score, brain natriuretic peptide and high sensitive troponin among others, and the evidence to support or discourage their use for an adequate assessment of cardiovascular risk.

Base of the skull morphology and Class III malocclusion in patients with unilateral cleft lip and palate

OBJECTIVE: The aim of the present study was to determine the morphological differences in the base of the skull of individuals with cleft lip and palate and Class III malocclusion in comparison to control groups with Class I and Class III malocclusion. METHODS: A total of 89 individuals (males and females) aged between 5 and 27 years old (Class I, n = 32; Class III, n = 29; and Class III individuals with unilateral cleft lip and palate, n = 28) attending PUC-MG Dental Center and Cleft Lip/Palate Care Center of Baleia Hospital and PUC-MG (CENTRARE) were selected. Linear and angular measurements of the base of the skull, maxilla and mandible were performed and assessed by a single calibrated examiner by means of cephalometric radiographs. Statistical analysis involved ANCOVA and Bonferroni correction. RESULTS: No significant differences with regard to the base of the skull were found between the control group (Class I) and individuals with cleft lip and palate (P > 0.017). The cleft lip/palate group differed from the Class III group only with regard to CI.Sp.Ba (P = 0.015). Individuals with cleft lip and palate had a significantly shorter maxillary length (Co-A) in comparison to the control group (P < 0.001). No significant differences were found in the mandible (Co-Gn) of the control group and individuals with cleft lip and palate (P = 1.000). CONCLUSION: The present findings suggest that there are no significant differences in the base of the skull of individuals Class I or Class III and individuals with cleft lip and palate and Class III malocclusion. .

OBJETIVO: o objetivo do presente estudo foi determinar diferenças morfológicas da base do crânio de indivíduos portadores de fissura de lábio e palato e de má oclusão de Classe III, comparado-os com indivíduos controle com má oclusão de Classes I ou III. MÉTODOS: oitenta e nove indivíduos, de ambos os sexos, com idade variando entre 5 e 27 anos, Classe I (n = 32), Classe III não fissurados (n = 29) e Classe III com fissura labiopalatina unilateral (n = 28), oriundos do Centro de Odontologia e Pesquisa da PUC-MG e do Centro de Atendimento de Fissurados do Hospital da Baleia e da PUC-MG (CENTRARE), foram selecionados. Medições lineares e angulares da base do crânio, maxila e mandíbula foram realizadas e avaliadas por um único examinador calibrado, por meio de radiografias cefalométricas. Foram utilizados os testes ANCOVA e correção de Bonferroni para a análise estatística dos dados. RESULTADOS: com relação à base do crânio, os resultados não indicaram diferença estatística entre indivíduos controle (Classe I) e os indivíduos com fissuras (p > 0,017). O grupo com fissura foi diferente do grupo Classe III somente em relação à medida CI.Sp.Ba (p = 0,015). O comprimento maxilar (Co-A) apresentou diferença estatisticamente significativa na comparação entre o grupo controle (Classe I) e o grupo com fissuras (p < 0,001), sendo que os fissurados apresentaram uma maxila menor. Não foram encontradas diferenças na mandíbula (Co-Gn) entre indivíduos do grupo controle (Classe I) e indivíduos fissurados (p = 1,000). CONCLUSÃO: os resultados sugerem que não houve diferença estatisticamente significativa na base do crânio entre indivíduos Classe I e III e indivíduos com fissuras de lábio e palato com má oclusão de Classe III. .

Natriuretic peptides, obesity and cardiovascular diseases / Peptídeos natriuréticos, obesidade e doenças cardiovasculares

Obesity, hypertension and heart failure are conditions commonly associated with each other. Recent investigations have demonstrated that low plasmatic levels of natriuretic peptides are linked with obesity. Thus, knowing the actions of these hormones in water and salt homeostasis, it is possible to establish that low levels of natriuretic peptides may be the common denominator among obesity, hypertension and heart failure. Knowledge on this topic is crucial to develop further investigation for definitive conclusions.

EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes, by Activating AMPK-Dependent Pathway

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

Factores asociados a mortalidad en pacientes con falla cardiaca descompensada / Factors associated with mortality in patients with decompensated heart failure

Introducción: la falla cardiaca (FC) es una de las principales causas de morbimortalidad a nivel mundial, la cual ha experimentado aumento gradual de su incidencia sin variación importante en su desenlace en las dos últimas décadas. En Colombia muy pocos estudios evalúan factores asociados a mortalidad por falla cardiaca. Métodos: estudio de cohorte prospectivo en el que se incluyeron pacientes con diagnóstico de falla cardiaca descompensada al momento del ingreso a urgencias, entre febrero de 2010 y marzo de 2013. Se calculó el tamaño de muestra y se realizó un análisis multivariado para la evaluación de los factores de riesgo asociados a mortalidad intrahospitalaria y a 30 días. Resultados: se incluyeron 462 pacientes. La mortalidad hospitalaria fue de 8.9% y a 30 días de 13.8%, en el modelo multivariado para el desenlace mortalidad intrahospitalaria se observó que la única variable con significancia estadística fue el BUN ≥43 mg/dL (OR, 3.45 [IC 95% 1.54-7.74], p= 0.003). Para la mortalidad a 30 días, la estancia hospitalaria >5 días (OR, 2.23 [IC 95% 1.20-4.12], p= 0.011), el BUN ≥43 mg/dL (OR, 2.55 [IC 95% 1.31-4.94], p= 0.005) y el NT-proBNP ≥ 4630 pg/dL (OR, 2.47 [IC 95% 1.30-4.70], p= 0.006). Conclusiones: la mortalidad intrahospitalaria de los pacientes con falla cardiaca descompensada en la población evaluada fue alta. En los análisis multivariados, se encontró que el BUN ≥ 43 mg/dL fue el único factor de riesgo independiente asociado a mortalidad intrahospitalaria; mientras que la mortalidad a 30 días se relacionó además con el NT-proBNP y la estancia hospitalaria superior a cinco días.

Introduction: heart failure is one of the main causes of morbidity and mortality worldwide; it has experienced a gradual increase in incidence with no significant variation in outcome in the last two decades. In Colombia there are no studies to evaluate risk factors for mortality, which is the subject of this study. Methods: prospective cohort study in which patients with diagnosis of decompensated heart failure on admission to the emergency department between February 2010 and March 2013 were included. The sample size was calculated and a multivariate analysis was performed to evaluate the risk factors associated with in-hospital and 30-day mortality. Results: 462 patients were included. Hospital mortality was 8.9% and 30-day mortality 13.8%; in the multivariate model for hospital mortality outcome was observed that the only variable with statistic significance was BUN ≥ 43 mg/dL (OR, 3.45 [95% CI 1.54- 7.74], p = 0.003). For 30 day mortality, hospital stay > 5 days (OR, 2.23 [95% CI 1.20-4.12], p = 0.011), BUN ≥43 mg/dL (OR, 2.55 [95% CI 1.31-4.94] , p = 0.005) and NT-proBNP ≥ 4630 pg/dL (OR, 2.47 [95% CI 1.30-4.70], p = 0.006). Conclusions: in-hospital mortality in patients with decompensated heart failure in the study population was high. In multivariate analysis, it was found that BUN ≥ 43 mg/dL was the only independent risk factor associated with hospital mortality, while the 30-day mortality was also associated with NT-proBNP and hospital stay greater than five days.

The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery / O valor preditivo do peptídeo natriurético tipo-B em resultados de crianças com hipertensão pulmonar submetidas à cirurgia cardíaca congênita / El valor predictivo del plasma en niveles de péptido natriurético tipo B, y los resultados en niños con hipertensión pulmonar en proceso de cirugía de cardiopatía congénita

Background and objectives: In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. Methods: In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48 h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72 h, (2) intensive care unit stay >7days, and (3) mortality. Results: The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n = 35, n = 16, respectively) showed significant differences in repeated measurement time points (p = 0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5 pg mL−1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r = 0.67, p = 0.0001). Conclusions: In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5 pg mL−1 ...

Justificativa e objetivo: Em crianças submetidas à cirurgia cardíaca congênita, os níveis plasmáticos de peptídeo natriurético cerebral (PNC) podem ter um papel no desenvolvimento da síndrome de baixo débito cardíaco (SBDC), definida como uma combinação de achados clínicos e intervenções para aumentar o débito cardíaco em crianças com hipertensão pulmonar. Métodos: Em um estudo prospectivo observacional, foram inscritas 51 crianças submetidas à cirurgia cardíaca congênita, com avaliação ecocardiográfica pré-operatória que mostrava hipertensão pulmonar. Os níveis plasmáticos de PNC foram avaliados antes e 12, 24 e 48 h após a operação. Os pacientes incluídos no estudo foram divididos em dois grupos em função de: (1) desenvolvimento de SBDC; (2) determinação dos valores de corte de PNC no pré-operatório pela análise da curva de funcionamento do receptor para SBDC. Os desfechos secundários foram: (1) duração da ventilação mecânica ≥ 72 h, (2) permanência em unidade de terapia intensiva > 7 dias e (3) mortalidade. Resultados: Os níveis de PNC nos períodos pré- e pós-operatório dos pacientes com ou sem SBDC (n = 35, n = 16, respectivamente) apresentaram diferenças significantes nos tempos de mensuração repetidos (p = 0,0001). O valor de corte de PNC de 125,5 pg mL−1 no pré-operatório obteve a maior sensibilidade de 88,9% e especificidade de 96,9% para prever a SBDC em pacientes com hipertensão pulmonar. Uma boa correlação foi descoberta entre o nível plasmático de PNC no pré-operatório e duração a ventilação mecânica (r = 0,67, p = 0,0001). Conclusões: Em ...

Justificación y objetivo: En niños sometidos a cirugía de cardiopatía congénita, los niveles plasmáticos de péptido natriurético cerebral pueden tener un papel en el desarrollo del síndrome de bajo gasto cardíaco, definido como una combinación de hallazgos clínicos e intervenciones para aumentar el gasto cardíaco en niños con hipertensión pulmonar. Métodos: En un estudio prospectivo observacional, se inscribieron 51 niños sometidos a cirugía de cardiopatía congénita, y cuya evaluación ecocardiográfica preoperatoria mostró hipertensión pulmonar. Los niveles plasmáticos de péptido natriurético cerebral fueron evaluados antes de la operación, y 12, 24 y 48 h después de la operación. Los pacientes incluidos en el estudio fueron divididos en 2 grupos en función de: (1) desarrollo de síndrome de bajo gasto cardíaco, definido como una combinación de hallazgos clínicos o de intervenciones para aumentar el gasto cardíaco en el postoperatorio; (2) determinación de los valores de corte de péptido natriurético cerebral en el preoperatorio por el análisis de la curva de funcionamiento del receptor para el síndrome de bajo gasto cardíaco. Los resultados secundarios fueron: (1) duración de la ventilación mecánica ≥ 72 h, (2) permanencia en unidad de cuidados intensivos (UCI) > 7 días, y (3) mortalidad. Resultados: Los niveles de péptido natriurético cerebral en los períodos pre y postoperatorio de los pacientes con o sin síndrome de bajo gasto cardíaco (n = 35 y n = 16, respectivamente) tuvieron diferencias significativas en los tiempos de medida repetidos (p = 0,0001). El valor de corte de péptido natriurético cerebral de 125,5 pg/mL−1 en el preoperatorio obtuvo la mayor ...

Biomarcadores de lesión miocárdica y edema pulmonar de las alturas / Biological markers of myocardial damage and high-altitude pulmonary edema

El edema pulmonar de las alturas es una entidad potencialmente fatal que se presenta en individuos que ascienden rápidamente por encima de 2.500 msnm. La hipoxia, el deterioro de la clase funcional y la dificultad respiratoria son el resultado de un edema pulmonar no cardiogénico. En este caso clínico de edema pulmonar de las alturas se encontró elevación de biomarcadores de lesión miocárdica y de sobrecarga de presión, sin compromiso estructural cardiaco o coronario, hallazgo que no ha sido ampliamente documentado. En observaciones recientes se ha evidenciado la elevación del péptido natriurético cerebral (BNP por su sigla en Inglés) en pacientes con enfermedad de las alturas y edema pulmonar de las alturas, con solo un caso clínico publicado que reportó elevación de la troponina asociado a edema pulmonar de las alturas.

The high-altitude pulmonary edema is a potentially fatal condition that occurs in people who rapidly ascend above 2,500 m. Hypoxia, functional class deterioration, and breathing difficulty are due to a non-carcinogenic pulmonary edema. In this case report of high-altitude pulmonary edema, we found an elevation of biomarkers of myocardial damage without myocardial or coronary compromise. This finding has not been widely documented. Recent observations have shown the elevation of brain natriuretic peptide, and even a case with positive troponin associated with high-altitude pulmonary edema has been found.