PPAR Alpha Activation by Clofibrate Alleviates Ischemia/Reperfusion Injury in Metabolic Syndrome Rats by Decreasing Cardiac Inflammation and Remodeling and by Regulating the Atrial Natriuretic Peptide Compensatory Response.

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.

Peptídeos Natriuréticos tipo B (BNP e NT-ProBNP) para pacientes de 18 a 44 anos com insuficiência cardíaca / Type B Natriuretic Peptides (BNP and NT-ProBNP) for patients 18 to 44 years old with heart failure

INTRODUÇÃO: A dosagem dos níveis séricos de peptídeos natriuréticos cerebrais (BNP e o Nterminal do pró-hormônio do peptídeo natriurético do tipo B - NT-proBNP) é frequentemente utilizada em pacientes elegíveis para estabelecer o diagnóstico e a gravidade da insuficiência cardíaca. Na Diretriz do Ministério da Saúde preconiza-se a dosagem de peptídeos natriuréticos tipo B (BNP ou NT-proBNP) em duas situações: 1. Diagnóstico de IC de forma complementar à ecocardiografia nos casos com risco baixo a moderado e suspeita da doença; 2. Critério para a utilização de sacubitril/valsartana. O procedimento de dosagem de peptídeos natriuréticos tipo B (NBP e NT-proBNP) foi incorporado ao Sistema Único de Saúde em 2020 por meio da Portaria (retificação) n°296 de 03/04/2020 da Secretaria de Atenção Especializada à Saúde (SAES). Neste momento estabeleceu-se como idade mínima para acesso ao procedimento a de 45 anos. Entretanto, em 2021, por meio da Portaria n° 78 de 27/01/21 da SAES incorporou-se o medicamento sacubitril/valsartana para o tratamento de insuficiência cardíaca com fração de ejeção reduzida em pacientes classificados, segundo a New York Heart Association (NYHA), na classe II, com idade inferior a 75 anos e com elevação dos peptídeos cerebrais natriuréticos. Segundo a Portaria n° 78 de 2021, estabeleceu-se um limite inferior de idade de 18 anos para ter acesso ao medicamento. Dessa forma, faz-se necessário expandir a faixa etária elegível para ter acesso ao procedimento de dosagem de peptídeos natriuréticos para incluir o segmento de 18 a 44 anos. EVIDÊNCIAS CLÍNICAS: A Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) tornou pública, por meio da publicação da Portaria nº 40, de 8 de agosto de 2019, a decisão de incorporar o sacubitril/valsartana para o tratamento de insuficiência cardíaca crônica em pacientes com classe funcional NYHA II e BNP > 150 (ou NTProBNP > 600), com fração de ejeção reduzida (FEVE < ou = 35%), idade menor ou igual a 75 anos e refratários ao melhor tratamento disponível, no âmbito do Sistema Único de Saúde ­ SUS. Dessa forma, a recomendação da Comissão acatada pela SCTIE já previa a utilização da dosagem de peptídeos natriuréticos do tipo B em adultos diagnosticados com insuficiência cardíaca e com indicação inicial de tratamento com sacubitril/valsartana. Entende-se, portanto, que seja dispensável uma nova análise de evidências clínicas sobre a utilização da dosagem desses peptídeos na faixa etária de 18 a 44 anos. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Elaborou-se uma análise de impacto orçamentário na perspectiva do Sistema Único de Saúde no horizonte temporal de cinco anos a partir da série histórica da produção ambulatorial do procedimento de dosagem de peptídeos natriuréticos tipo B no SUS. Por meio de regressão linear estimou-se a provável produção do exame para o período de 2023 a 2024 para indivíduos na faixa etária acima de 45 anos. Em seguida, por proporcionalidade, utilizando como balizador a incidência da doença nas diferentes faixas etárias (maiores que 45 anos e entre 18 e 44 anos) derivou-se o número de exames esperados para a população mais jovem. O impacto orçamentário incremental estimado para a ampliação do procedimento de dosagem de peptídeo a natriuréticos para a faixa etária de 18 a 44 anos variou entre R$ 96.876 e R$ R$ 97.864, para os anos de 2023 e 2027, respectivamente, somando no período de cinco anos aproximadamente R$ 500.000,00. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Após buscas nas bases ClinicalTrials e Cortelis foram encontradas cinco tecnologias já com registro na Anvisa que são compatíveis com a realização da dosagem de peptídeos natriuréticos tipo B. CONSIDERAÇÕES FINAIS: Este relatório sofreu uma ampla modificação em relação à versão incialmente submetida para a Conitec. Isso ocorreu porque a primeira versão fora elaborada em momento anterior à possibilidade de acessar os dados consolidados sobre a produção ambulatorial dos procedimentos de dosagem dos peptídeos natriuréticos e também sobre a utilização de sacubitril/valsartana. No momento em que esses dados consolidados foram avaliados, como explicou-se no relatório, identificou-se que uma análise de impacto orçamentário baseada em demanda epidemiológica causaria uma grande distorção em relação à real projeção de exames que seriam realizados entre 2023 e 2027. Essa percepção se formou pela análise dos dados referentes ao número de serviços no SUS que vem ofertando o serviço de dosagem dos peptídeos natriuréticos no período de 2020 a 2022, ainda reduzido e em ampliação. Isso significa que o serviço vem se estruturando para que possam ofertar esse serviço e seria de fato o fator determinante do número de procedimentos realizados no SUS. Desta forma, optouse por refazer a análise com dados de demanda aferida. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Durante a 115ª reunião ordinária da Conitec em 1º de dezembro de 2022 o plenário emitiu por unanimidade recomendação favorável à ampliação de uso do procedimento de dosagem de peptídeos natriuréticos tipo B (BNP e NT-ProBNP) para a fixa etária de 18 a 44 anos. RECOMENDAÇÃO FINAL DA CONITEC: Pelo exposto, os membros do Comitê de Produtos e Procedimentos presentes na 116ª Reunião Ordinária, realizada no dia 15 de março de 2023, deliberaram, por unanimidade, recomendar a ampliação de uso da dosagem de peptídeos natriuréticos tipo B (BNP e NT-ProBNP) para o diagnóstico da insuficiência cardíaca em pacientes de 18 a 44 anos no SUS, conforme as Diretrizes Brasileiras para Diagnóstico e Tratamento da Insuficiência Cardíaca com Fração de Ejeção Reduzida. Por fim, foi assinado o Registro de Deliberação nº 802/2023. DECISÃO: Ampliar o uso do procedimento de dosagem de peptídeos natriuréticos tipo B (BNP e NT-ProBNP) para a fixa etária de 18 a 44 anos, conforme as Diretrizes Brasileiras para Diagnóstico e Tratamento da Insuficiência Cardíaca com Fração de Ejeção Reduzida, no âmbito do Sistema Único de Saúde - SUS, publicada no Diário Oficial da União nº 89, seção 1, página 222, em 11 de maio de 2023.

Xanthomonas natriuretic peptide is recognized by the Arabidopsis natriuretic peptide receptor 1 and through this interaction triggers similar plant responses to its plant counterpart.

Plant natriuretic peptides (PNPs) are hormone peptides that participate in the regulation of ions and water homeostasis in plants. Xanthomonas citri subsp. citri (Xcc) the causal agent of citrus canker disease also possesses a PNP-like peptide (XacPNP). This peptide, similarly to AtPNP-A, the most studied PNP from Arabidopsis thaliana, causes stomatal aperture and enhances photosynthetic efficiency in plant leaves. Thus, the function that has been attributed to XacPNP is to contribute to maintain photosynthetic efficiency and water homeostasis in plant tissue during the infection process, to create favorable conditions for biotrophic pathogens survival. A PNP receptor (AtPNP-R1) for AtPNP-A has been identified and the AtPNP-A activity in regulation of water homeostasis has been observed to depend on the presence of AtPNP-R1. Here, we demonstrated that both AtPNP-A and XacPNP require the presence of AtPNP-R1 to induce plant stomatal aperture. Also, less necrotic tissue was found in infections with pathogens expressing XacPNP and this was dependent on the presence of AtPNP-R1, suggesting that XacPNP interacts with this receptor to exert its function. Finally, we confirmed that AtPNP-A and XacPNP interact with AtPNP-R1 in planta, which support the idea that XacPNP triggers similar plant responses to its plant counterpart.

Alerta monitoramento do horizonte tecnológico: Vosoritida para o tratamento de Acondroplasia / Technological horizon monitoring alert: Vosoritida for the treatment of Achondroplasia

A TECNOLOGIA: Descrição da tecnologia: A vosoritida é uma molécula análoga ao peptídeo natriurético do tipo C (CNP ­ do inglês: C-type natriuretic peptide), um hormônio natural que regula o crescimento linear dos ossos. Esse medicamento inibe a via da proteína quinase, que ativa a jusante do receptor do fator de crescimento de fibroblastos 3 (FGFR3). Como resultado, a vosoritida atua como um regulador positivo da ossificação endocondral, uma vez que promove a proliferação e diferenciação dos condrócitos. Condição clínica: A acondroplasia é uma doença genética rara descrita como a displasia esquelética primária mais comum em humanos. Essa forma de displasia é responsável por mais de 90% dos casos de baixa estatura desproporcional, também conhecida como nanismo. Etimologicamente, o termo acondroplasia significa "sem formação de cartilagem" e é categorizada como uma displasia fisária (da placa de crescimento). A acondroplasia ocorre em aproximadamente 1:20.000 a 1:30.000 nascidos vivos por ano. Por difícil que seja determinar a prevalência global dessa condição, estima-se que ela afete aproximadamente 1 a 9 indivíduos por 100.000 da população geral. Um extenso estudo epidemiológico de base populacional europeu calculou a prevalência em 3,72 por 100.000 nascimentos (8). Esse estudo demonstrou que a prevalência foi estável ao longo do tempo, contudo, foram observadas diferenças regionais. INFORMAÇÕES REGULATÓRIAS: Informações sobre registro: A vosoritida foi registrada em 29/11/2021 na Agência Nacional de Vigilância Sanitária (Anvisa) como um produto novo, cumprindo com o disposto na RDC nº 55/2010 para o registro de produtos biológicos novos. Por se tratar de uma necessidade médica não atendida atualmente, este produto foi priorizado de acordo com os critérios da RDC nº 204/2017 e nas agências reguladoras internacionais para as seguintes indicações clínicas: Agência Nacional de Vigilância Sanitária (Anvisa): indicado para o tratamento de acondroplasia (ACH) em pacientes a partir de 2 anos de idade e cujas epífises não estão fechadas. O diagnóstico de acondroplasia deve ser confirmado por teste genético apropriado. U.S. Food and Drug Administration (FDA): é indicado para aumentar o crescimento linear em pacientes pediátricos com acondroplasia com 5 anos de idade ou mais com epífises abertas. Essa é uma autorização contingente, o que significa que para ser mantida, os benefícios clínicos deverão ser confirmados por ensaio clínico. European Medicines Agency (EMA): é indicado para o tratamento da acondroplasia em crianças a partir dos dois anos de idade até o fechamento das placas de crescimento. Pharmaceuticals and Medical Devices Agency (PMDA): é indicado para o tratamento de crianças de todas as idades que ainda não tiveram o fechamento das placas de crescimento. PANORAMA DE DESENVOLVIMENTO: Estratégia de busca: A estratégia de busca foi composta por duas etapas. A primeira objetivou identificar os registros de estudos clínicos do vosoritida para o tratamento de acondroplasia no ClinicalTrials.gov e no Cortellis. A busca no Cortellis foi realizada em 17 de agosto de 2022 com o termo 'vosoritide'. Já a busca no ClinicalTrials foi realizada em 19 de agosto de 2022 com os termos 'vosoritide' e 'achondroplasia'. Foram incluídos ensaios clínicos, randomizados ou não, a partir da fase 2, em que o vosoritida tenha sido utilizado para o tratamento da acondroplasia. Não houve restrição quanto ao idioma. Não foram incluídas análises post hocs, pool analysis. Na segunda etapa, foi realizada busca nas bases Medline e PMC (via PubMed) e Embase (via Portal Periódicos Capes) com o objetivo de localizar estudos publicados e não publicados referentes aos ensaios clínicos conduzidos que utilizaram o vosoritida no tratamento da acondroplasia. Desta forma, foram construídas estratégias de busca utilizando termos controlados e seus respectivos sinônimos (Apêndice 1). Estas buscas foram realizadas em 5 de setembro de 2022. CONSIDERAÇÕES FINAIS: A acondroplasia é causada por mutações no gene do receptor 3 do fator de crescimento de fibroblastos, que levam à ossificação endocondral prejudicada. O medicamento vosoritida é um análogo do peptídeo natriurético tipo C, que foi desenvolvido para o tratamento de crianças portadoras dessa doença. Os resultados disponíveis, até a última atualização deste alerta, foram promissores e subsidiaram o registro da vosoritida em vários países, inclusive no Brasil. Mas é importante destacar que devido à variabilidade do crescimento e ao menor pico de crescimento durante a puberdade, em crianças com acondroplaisa, os efeitos a longo prazo da vosoritida só serão conhecidos quando as crianças atingirem a altura adulta final.

New insights into plant natriuretic peptide evolution: From the lysogenic conversion in Xanthomonas to the lateral transfer to the whitefly Bemisia tabaci.

Plant natriuretic peptide-like (PNP) are signaling molecules related to adaptive responses to stress. The Arabidopsis thaliana PNP (AtPNP-A) is capable of modulating catalase 2 (CAT2) and rubisco activase (RCA) activity in some circumstances. Interestingly, many plant-pathogens co-opted PNP-like molecules to their benefit. For instance, the citrus pathogen Xanthomonas citri carries a PNP-like (XacPNP) that can mimic and regulate plant homeostasis, and many phytopathogenic fungi carry effectors (e.g., Ave1 and AvrLm6) that are indeed PNP-like homologs. This work investigates the PNP-like evolution across the tree of life, revealing many parallel gains and duplications in plant and fungi kingdoms. All PNP-like proteins in the final dataset are structurally similar, containing the AtPNP-A active domains modulating CAT2 activity and RCA interaction. Comparative genomics evinced that XacPNP is a lysogenic conversion factor associated with a Myoviridae-like prophage identified in many Xanthomonas species. Surprisingly, a PNP-like homolog was identified in Bemisia tabaci, an important agricultural pest, being to date the second example of lateral gene transfer (LGT) from plant to the whitefly. Moreover, the Bemisia PNP-like homolog can also be considered a potential new effector of this phloem-feeding insect. Noteworthy, the whiteflies infest many plants carrying PNP-like copies and interact with some of their bacterial and fungal pathogens, strongly suggesting complex recipient/donor traits of PNP by LGT and bringing new insights into the evolution of host-pathogen arms race across the tree of life.

Natriuretic peptides to differentiate constrictive pericarditis and restrictive cardiomyopathy: A systematic review and meta-analysis.

Previous studies have shown that natriuretic peptide levels are increased in patients with restrictive cardiomyopathy (RCM) but not in constrictive pericarditis (CP). We performed a systematic review and meta-analysis to evaluate the diagnostic utility of B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) to differentiate CP and RCM. We searched electronic databases from inception to January 07, 2021. Studies involving adult patients that assessed the utility of natriuretic peptides to differentiate CP and RCM were included. All meta-analyses were performed using a random-effects model. Seven studies (four case-control and three cohorts) involving 204 patients were included. The mean age ranged between 25.7 and 64.1 years and 77% of patients were men. BNP levels were significantly lower (standardized median difference [SMD], -1.48; 95% confidence interval [CI], -2.33 to -0.63) in patients with CP compared to RCM. The pooled area under the curve (AUC) of the BNP level was 0.81 (95% CI, 0.70-0.92). NT-proBNP (SMD, -0.86; 95% CI, -1.38 to -0.33) and log NT-proBNP (SMD, -1.89; 95% CI, -2.59 to -1.20) levels were significantly lower in patients with CP compared to RCM. Our review shows that BNP and NT-proBNP levels were significantly lower in patients with CP compared to RCM. The pooled AUC of BNP level showed a good diagnostic accuracy to differentiate both conditions.

Role of natriuretic peptides in the cardiovascular-adipose communication: a tale of two organs.

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in the energy metabolism of several substrates in humans and animals, thus interrelating the heart, as an endocrine organ, with various insulin-sensitive tissues and organs such as adipose tissue, muscle skeletal, and liver. Adipose tissue dysfunction is associated with altered regulation of the natriuretic peptide system, also indicated as a natriuretic disability. Evidence points to a contribution of this natriuretic disability to the development of obesity, type 2 diabetes mellitus, and cardiometabolic complications; although the causal relationship is not fully understood at present. However, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on the current literature on the metabolic functions of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Natriuretic peptide system alterations could be proposed as one of the linking mechanisms between adipose tissue dysfunction and cardiovascular disease.

NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats.

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx). Adult male Wistar rats following a 5/6 Nx were treated with enalapril (NxE group, 10 mg/kg/day, n = 9) or vehicle (Nx group, n = 8) for two weeks. On the 15th day after Nx, rats were anaesthetized and submitted to mean arterial pressure (MAP) determination before and after receiving two intravenous injections of saline (vehicle, n = 9) or NPCdc (0.3 µg/kg dissolved in saline, n = 18) separated by a 20-min interval. The kidneys were submitted to oxidative stress analysis. The basal MAP of the NxE group was nearly 20% lower (P < 0.05) than non-treated rats. NPCdc administration decreased the MAP in both groups; however, in the NxE group, the effects were observed only in the second injection. The peptide also decreased the NADPH oxidase activity in the renal cortex. Additionally, the hydrolysis of NPCdc by recombinant neprilysin (NEP) was monitored by mass spectrometry. NPCdc was cleaved by NEP at different peptides with an inhibition constant (Ki) of 1.5 µM, determined by a competitive assay using the NEP fluorescence resonance energy transfer (FRET) peptide substrate Abz-(d)Arg-Gly-Leu-EDDnp. Docking experiments confirmed the high affinity of NPCdc toward NEP. These findings provide new insights into the antihypertensive and antioxidant mechanism of action of NPCdc. Altogether, the results presented here suggest that NPCdc must be further studied as a potential therapy for cardiorenal syndromes.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

Effects of different stimulators of cGMP synthesis on lipid content in bovine oocytes matured in vitro

Bovine oocytes and blastocysts produced in vitro are frequently of lower quality and less cryotolerant than those produced in vivo, and greater accumulation of lipids in the cytoplasm has been pointed out as one of the reasons. In human adipocytes cGMP signaling through the activation of PKG appears to be involved in lipid metabolism, and components of this pathway have been detected in bovine cumulus-oocyte complexes (COCs). The aim of this study was to investigate the influence of this pathway on the lipid content in oocytes and expression of PLIN2 (a lipid metabolism-related gene) in cumulus cells. COCs were matured in vitro for 24 h with different stimulators of cGMP synthesis. The activation of soluble guanylyl cyclase (sGC) by Protoporphyrin IX reduced lipid content (22.7 FI) compared to control oocytes (36.45 FI; P <0.05). Stimulation of membrane guanylyl cyclase (mGC) with natriuretic peptides precursors A and C (NPPA and NPPC) had no effect (36.5 FI; P>0.05). When the PKG inhibitor KT5823 was associated with Protoporphyrin IX, its effect was reversed and lipid contents increased (52.71 FI; P<0.05). None of the stimulators of cGMP synthesis affected the expression of PLIN2 in cumulus cells. In conclusion, stimulation of sGC for cGMP synthesis promotes lipolytic activities in bovine oocytes matured in vitro and such effect is mediated by PKG. However, such effect may vary depending on the stimulus received and/or which synthesis enzyme was activated, as stimulation of mGC had no effects.(AU)

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

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.

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.

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.

Biomarkers in cardiovascular medicine: towards precision medicine.

Biomarkers are noninvasive, inexpensive, highly reproducible tools that allow clinicians to quantify pathophysiological processes relevant to a specific disease. Although the concept of biomarker-guided precision medicine is still in its infancy once a specific cardiovascular diagnosis is established, biomarker guidance has become the standard of care in the early diagnosis of acute cardiovascular disease in patients presenting to the emergency department with common symptoms such as acute chest pain or acute dyspnoea. This review highlights recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers, namely high-sensitivity cardiac troponin and natriuretic peptides in established indications such as the early diagnosis of acute myocardial infarction and heart failure. In addition, we address emerging indications such as the screening for perioperative myocardial infarction.

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.