Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study / Troponina y Tropomiosina de Músculo Esquelético como Fuente Alimentaria de Péptidos Bioactivos Antidiabéticos y Antihipertensivos: Estudio In Silico

Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods:In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and ASparameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders

Antecedentes: Las propiedades nutracéuticas de los hidrolizados de alimentos dependen de múltiples interacciones bioquímicos que involucran la modulación de enzimas y receptores celulares. Se han identificado numerosos péptidos bioactivos liberados de la digestión de troponina y tropomiosina, pero su caracterización se ha llevado a cabo principalmente por hidrólisis catalizada por proteasas ajenas al sistema digestivo humano. Objetivo: Este estudio tuvo como objetivo determinar el perfil bioactivo de la carne de res, cerdo y pollo mediante el análisis de la frecuencia y farmacocinética de los biopéptidos liberados de la troponina y la tropomiosina. Métodos: Se estudió la digestión in silico y la frecuencia de liberación de biopéptidos mediante dos parámetros; frecuencia de liberación de fragmentos bioactivos (AE), frecuencia porcentual (W) y ocurrencia media (AS), ambos indicados en la plataforma BIOPEP-UWM. Más adelante, los productos finales de la hidrólisis se examinaron en función de la probabilidad de absorción gastrointestinal y el perfil farmacocinético realizado en las herramientas bioinformáticas SwissADME, SwissTargetPrediction y ADME/Tlab. El análisis estadístico se llevó a cabo mediante una prueba ANOVA de una vía. Resultados: Los biopéptidos inhibidores de la dipeptidil peptidasa IV (DPP-IV) y la enzima convertidora de angiotensina (ECA) exhibieron la mayor frecuencia de liberación. Además, los parámetros W y ASno mostraron diferencias significativas (p> 0.05) entre las isoformas miofibrilares evaluadas. Siete biopéptidos se clasificaron como altamente absorbibles e informaron un cumplimiento óptimo de similitud con el fármaco. Aunque los biopéptidos tienen propiedades farmacocinéticas adecuadas, su potencia terapéutica demostró ser menor que la de los fármacos inhibidores de la DPP-IV y la ACE. Conclusiones: La troponina y la tropomiosina son una fuente dietética rica en péptidos bioactivos, principalmente DPP-IV e inhibidores de la ACE. Los productos finales de la digestión son principalmente dipéptidos con propiedades farmacocinéticas óptimas y similares a la de los fármacos, lo que sugiere una aplicación terapéutica factible en trastornos hipertensivos e hiperglicémicos

Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway

Purpose: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2 S, TNF-α and mitoKATP in melatoninmediated effects in RIPC. Methods: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. Results: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2 S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). Conclusion: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels.

Principais complicações cardíacas em idosos infectados pelo SARS-CoV-2: uma revisão sistemática / Principales complicaciones cardíacas en ancianos infectados por SARS-CoV-2: una revisión sistemática / Main cardiac complications in elderly infected by SARS-CoV-2: a systematic review

Objetivo: compreender as principais complicações ocasionadas pelo vírus SARS-CoV-2 no sistema cardíaco do público idoso. Métodos: trata-se de uma revisão sistemática da literatura de abordagem qualitativa e característica descritivo-exploratória realizada no ano de 2020. Resultados: as complicações cardíacas mais prevalentes na população idosa foram miocardite, arritmias, insuficiência cardíaca, infarto agudo, choque cardiogênico, lesão miocárdica aguda e parada cardiorrespiratória. O principal biomarcador cardíaco foi a troponina, apresentando elevação superior ao percentil 99°, evidenciando a necessidade de tratamento em Unidade de Terapia Intensiva. Considerações Finais: o aparecimento desse vírus causou grande prejuízo no campo da saúde, especialmente a população idosa, que apresenta risco elevado de óbito ao contrair essa doença. Destarte, é de extrema importância se ater a mensuração da troponina sérica no público alvo e realizar monitorização longitudinal, utilizando para tal a telecardiologia, uma vez que diminuem as chances de contaminação entre infectado e profissional de saúde

Objective: to understand the main complications of SARS-CoV-2 in the elderly cardiac system. Methods: systematic literature review conducted in 2020. Results: the most prevalent cardiac complications in the elderly population were myocarditis, arrhythmias, heart failure, acute infarction, cardiogenic shock, acute myocardial injury and cardiorespiratory arrest. The main cardiac biomarker was troponin, showing an elevation above the 99th percentile, evidencing the need for treatment in the Intensive Care Unit. Final Considerations: the appearance of this virus has caused great damage in the health field, especially the elderly population, who is at high risk of death when contracting this disease. Therefore, it is important to stick to the measurement of serum troponin in the target audience and perform longitudinal monitoring, using telecardiology for this purpose, since they reduce the chances of contamination between infected and health professionals

Objetivo: comprender las principales complicaciones del SARS-CoV-2 en el sistema cardíaco anciano. Métodos: revisión sistemática de la literatura realizada en 2020. Resultados: las complicaciones cardíacas más prevalentes en la población anciana fueron miocarditis, arritmias, insuficiencia cardíaca, infarto agudo, shock cardiogénico, lesión miocárdica aguda y parada cardiorrespiratoria. El principal biomarcador cardíaco fue la troponina, mostrando una elevación por encima del percentil 99, evidenciando la necesidad de tratamiento en la Unidad de Cuidados Intensivos. Consideraciones finales: la aparición de este virus ha provocado un gran daño en el campo de la salud, especialmente en la población anciana, que se encuentra en alto riesgo de muerte al contraer esta enfermedad. Por tanto, es importante ceñirse a la medición de troponina sérica en el público objetivo y realizar un seguimiento longitudinal, utilizando para ello la telecardiología, ya que reducen las posibilidades de contaminación entre los infectados y los profesionales sanitarios

Associação entre Parâmetros Plasmático de Tiol e Níveis de Troponina em Pacientes com Síndrome Coronariana Aguda e Predição de Arritmia Ventricular Hospitalar / Association between Plasma Thiol Parameters and Troponin Levels in Patients with Acute Coronary Syndrome and Prediction of In-Hospital Ventricular Arrhythmia

Resumo Fundamento As arritmias ventriculares (AVs) são a principal causa de mortalidade e morbidade hospitalar em pacientes com síndrome coronariana aguda (SCA) e sua relação com o tiol é desconhecida. Objetivo Investigar a relação entre os níveis plasmáticos de tióis e os níveis de troponina em pacientes com SCA e estimar o desenvolvimento de AV intra-hospitalar durante a internação. Método O estudo incluiu 231 pacientes consecutivos com SCA com supradesnivelamento do segmento ST (SCA-SDST) e pacientes com SCA sem supradesnivelamento do segmento ST (SCA-SSDST). Após a aplicação dos critérios de exclusão, 191 pacientes foram incluídos na análise estatística. Os pacientes foram classificados em dois grupos: grupo SCA-SDST (n=94) e grupo SCA-SSDST (n=97). Os níveis plasmáticos de tiol, dissulfeto e troponina foram medidos e a razão de troponina para tiol nativo (RTTN) foi calculada. Considerou-se estatisticamente significativo um valor de p bilateral inferior a 0,05. Resultados Tiol nativo plasmático, tiol total, dissulfeto e suas razões foram semelhantes entre os grupos. A RTTN se mostrou significativamente maior no grupo SCA-SDST em comparação com o grupo SCA-SSDST. Houve correlação negativa significativa entre os níveis de troponina e tiol. Verificou-se que o tiol nativo é preditor independente do desenvolvimento de AV em pacientes com SCA-SDST e em todos os pacientes com SCA. Verificou-se que o RTTN é preditor independente do desenvolvimento de AV em pacientes com SCA-SSDST e em todos os pacientes com SCA. Conclusão Os níveis plasmáticos de tiol podem ser usados para identificar pacientes com alto risco de desenvolvimento de AV intra-hospitalar em pacientes com SCA. A correlação entre os níveis de troponina e tiol pode sugerir que os tióis possam ser marcadores importantes para o diagnóstico e prognóstico da SCA com a ajuda de estudos futuros.

Abstract Background Ventricular arrhythmias (VAs) are the main cause of in-hospital mortality and morbidity in acute coronary syndrome (ACS) patients and its relationship with thiol is not known. Objective To investigate the relationship between plasma thiol levels and troponin levels in patients with ACS and to estimate in-hospital VA development during hospital stay. Method The study included 231 consecutive ST-segment elevation ACS (STE-ACS) and non-ST-segment elevation ACS (NSTE-ACS) patients. After application of exclusion criteria, 191 patients were included in the statistical analysis. Patients were classified into two groups: STE-ACS group (n=94) and NSTE-ACS group (n=97). Plasma thiol, disulphide and troponin levels were measured and troponin-to-native thiol ratio (TNTR) was calculated. A two-sided p value of less than 0.05 was considered to be statistically significant. Results Plasma native thiol, total thiol, disulphide and their ratios were similar between the groups. TNTR was significantly higher in the STE-ACS group compared to the NSTE-ACS group. Troponin and thiol levels correlated negatively and significantly. Native thiol was found to be an independent predictor of VA development in STE-ACS patients and in all ACS patients. TNTR was found to be an independent predictor of VA development in NSTE-ACS patients and in all ACS patients. Conclusion Plasma thiol levels can be used to identify ACS patients at high risk for in-hospital VA development. Correlation between troponin and thiol levels may suggest that thiols may be an important marker for diagnosis and prognosis of ACS with the help of future studies.

Lesão Miocárdica após Cirurgia Não Cardíaca - Estado da Arte / Myocardial Injury after Non-cardiac Surgery - State of the Art

Resumo Aproximadamente 300 milhões de cirurgias não cardíacas são realizadas anualmente no mundo, e eventos cardiovasculares adversos são as principais causas de morbimortalidade no período perioperatório e pós-operatório. A lesão miocárdica após cirurgia não cardíaca (MINS, do inglês myocardial injury after non-cardiac surgery) é uma nova entidade clínica associada com desfechos cardiovasculares adversos. MINS é definida como uma lesão miocárdica que pode resultar em necrose secundária à isquemia, com elevação dos biomarcadores. A lesão tem importância prognóstica e ocorre em até 30 dias após a cirurgia não cardíaca. Os critérios diagnósticos para MINS são: níveis elevados de troponina durante ou em até 30 dias após a cirurgia não cardíaca, sem evidência de etiologia não isquêmica, sem que haja necessariamente sintomas isquêmicos ou achados eletrocardiográficos de isquemia. Recentemente, pacientes com maior risco para MINS têm sido identificados por variáveis clínicas e biomarcadores, bem como por protocolos de vigilância quanto ao monitoramento eletrocardiográfico e dosagem de troponina cardíaca. Pacientes idosos com doença aterosclerótica prévia necessitam medir troponina diariamente no período pós-operatório. O objetivo deste trabalho é descrever este novo problema de saúde pública, seu impacto clínico e a abordagem terapêutica contemporânea.

Abstract Approximately 300 million non-cardiac surgeries are performed annually worldwide and adverse cardiovascular events are the main cause of morbidity and mortality in the peri- and postoperative period. Myocardial injury after non-cardiac surgery (MINS) is a new clinical entity associated with adverse cardiovascular outcomes. MINS is defined as myocardial injury that can result in necrosis due to ischemia, marked by increase in biomarker levels. It has prognostic relevance and occurs within up to 30 days after non-cardiac surgery. The diagnostic criteria for MINS are an elevated postoperative measure of troponin judged as secondary to myocardial ischemia, i.e., with no evidence of a non-ischemic etiology, during or within 30 days after non-cardiac surgery, and without the requirement of an ischemic symptom or electrocardiographic finding of ischemia. Recently, patients at higher risk for MINS have been recognized using clinical variables and biomarkers and established protocols for greater surveillance in relation to electrocardiographic monitoring and cardiac troponin dosage. Elderly patients with previous atherosclerotic disease need to measure troponin daily in the postoperative period. The aim of the present work is to describe this new public health problem, its clinical impact and contemporary therapeutic approach.

Practical Approach to Acute Coronary Syndrome in Patients with COVID-19

Abstract Acute cardiac injury is associated with higher mortality in patients with the novel coronavirus disease-2019 (COVID-19) and the exact etiology can be challenging to diagnose in the emergency setting during the pandemic. From a pathophysiological perspective, SARS-CoV-2 infection is characterized by an overproduction of inflammatory cytokines (IL-6, TNF-alpha) that leads to systemic inflammation and consequent increased risk of acute myocardial infarction (AMI) caused by atheromatous plaque rupture and significant myocardial oxygen supply-demand imbalance. Moreover, SARS-CoV-2 tropism to the renin-angiotensin-aldosterone system through the ACE2 receptor induces myocarditis that may rapidly progress to left ventricular dysfunction and hemodynamic instability. Myocardial inflammation with pericardial involvement, i.e. , myopericarditis, can progress to cardiac tamponade and obstructive shock. These cardiovascular complications, which are associated with a worse prognosis and higher mortality, can be associated with clinical manifestations, electrocardiographic changes, and troponin values similar to AMI. Thus, the diagnosis and treatment of patients with acute chest pain and dyspnea admitted to the emergency department is a significant challenge during the COVID-19 pandemic. Here, we provide a review of the literature focusing on a practical approach to acute coronary syndrome patients with confirmed or suspected COVID-19.

C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant

OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not.

Clinical-pathological and immunohistochemical evaluations of cardiac lesions in cats with chronic kidney disease / Avaliações clínico-patológica e imuno-histoquímica de lesões cardíacas em gatos com doença renal crônica

Chronic kidney disease (CKD) is characterized by irreversible morphostructural lesions that can progressively evolve to chronic renal insufficiency and kidney failure. It is known that the heart and kidneys are closely related, and that communication between these organs occurs through a variety of pathways; subtle physiological changes in one of them are compensated by the other. Histopathological cardiac evaluation through routine staining presents a limitation to identify specific or discreet lesions in the cardiomyocytes. This study aimed to evaluate serum troponin levels in cats with CKD, associated with clinical and pathological findings, as well as to correlate the morphostructural cardiac lesions to determine their distribution through macroscopic and histological assessments and anti-cardiac troponin C (cTnC) immunohistochemistry (IHC). To this end, 20 cats (18 diagnosed with CKD and two controls) were selected. Anti-human cTnC IHC was conducted after necropsy and separation in eight regions of each collected heart. Heart fragments from two cats without CKD were used as controls. The anti-human cTnC antibody is useful in detecting cardiac lesions and has shown decreased expression in cardiomyocytes of cats with CKD. Serum troponin was above the reference values in 11/18 (61.11%) animals and decreased expression for the cTnC antibody was observed in individual cardiomyocytes in 9/18 (50%) animals. It was verified that the number of regions with decreased expression for the cTnC antibody in cardiomyocytes is significantly correlated with serum troponin. The anti-human cTnC antibody has been found effective in detecting cardiac lesions and has shown decreased expression in the cardiomyocytes of cats with CKD. Correlation was observed between increased serum cTnI and loss of immunoreactivity at anti-cTnC antibody IHC in cats with CKD, which proves damage to cardiomyocytes secondary to kidney disease.(AU)

A doença renal crônica (DRC) é caracterizada por lesões morfoestruturais irreversíveis, que podem evoluir progressivamente para insuficiência renal crônica e falência renal. Sabe-se que o coração e os rins mantêm estreita relação e a comunicação entre esses órgãos ocorre por uma variedade de vias; alterações fisiológicas sutis em um desses órgãos são compensadas pelo outro. A avaliação histopatológica cardíaca mediante a colorações rotineiras são limitadas para identificar lesões específicas ou discretas em cardiomiócitos. O presente trabalho teve como objetivos avaliar os níveis séricos de troponina em gatos com DRC, associados aos achados clínico-patológicos, bem como correlacionar as lesões cardíacas morfoestruturais, a fim de determinar a distribuição destas, por meio da avaliação macroscópica, histológica e imuno-histoquímica com anti-cTnC. Neste estudo foram selecionados 20 gatos (18 diagnosticados com DRC e 2 animais controle). Para a aplicação da técnica de imuno-histoquímica anti-troponina C humana, necropsias foram realizadas e cada coração coletado separadamente em 8 regiões. Fragmentos do coração de 2 gatos sem lesão cardíaca foram utilizados como controle. O anticorpo anti-TnC humano é útil na detecção de lesões cardíacas e apresentou expressão diminuída em cardiomiócitos de gatos com DRC. Em 11/18 animais (61,11%) a troponina sérica encontrava-se acima dos valores de referência e foram observadas diminuição da expressão para anticorpo-cTnC em cardiomiócitos individuais em 9/18 (50%). Notou-se que o número de regiões com diminuição da expressão para anticorpo-cTnC em cardiomiócitos está significativamente correlacionado com a troponina sérica. O anticorpo anti-TnC humano se mostrou eficaz para detectar lesões cardíacas e demonstrou diminuição da expressão nos cardiomiócitos de gatos com DRC. Houve correlação entre o aumento da CTnI sérica e perda da imunorretividade na avaliação imuno-histoquímica com anticorpo anti-TnC em gatos com DRC o que comprova danos em cardiomiócitos secundários a doença renal.(AU)

Dor torácica na emergência: quando pensar em síndrome de Takotsubo? / Emergency chest pain: when to think about Takotsubo syndrome?

A síndrome de Takotsubo é uma cardiomiopatia induzida por estresse, caracterizada por disfunção transitória do ventrículo esquerdo. Essa disfunção pode ser confundida com infarto agudo miocárdio na sala de emergência por ter características clínicas semelhantes ­ principalmente a dor torácica. A fisiopatologia ainda não é bem definida, mas está associada à deficiência de estrogênio e ao aumento de catecolaminas que estimulam o acoplamento dos receptores beta-2 do coração, o que resulta em atividade inotrópica negativa, levando à disfunção contrátil do ventrículo esquerdo. As enzimas cardíacas alteradas dificultam ainda mais o diagnóstico da síndrome de Takotsubo. O exame padrão-ouro, que diferencia a síndrome de Takotsubo do infarto agudo do miocárdio, é a angiografia coronariana. Uma das opções na emergência é o ecocardiograma na beira do leito. Além disso, os critérios de Mayo devem ser usados para diagnosticar a síndrome de Takotsubo. É importante, para o profissional que trabalha no pronto-socorro, ter a síndrome de Takotsubo como diagnóstico diferencial na dor torácica.

Takotsubo syndrome is a stress-induced cardiomyopathy characterized by a transient left ventricular dysfunction. This dysfunction can be confused with acute myocardial infarction in the emergency room as it has similar clinical characteristics, especially chest pain. Its pathophysiology is not yet well defined, but is associated with estrogen deficiency and increased catecholamines that stimulate the coupling of cardiac beta-2 receptors, resulting in negative inotropic activity and leading to contractile dysfunction of the left ventricle. Altered cardiac enzymes make the diagnosis of Takotsubo syndrome even more difficult. The gold standard exam that will differentiate Takotsubo syndrome from acute myocardial infarction is coronary angiography. One of the options in the emergency room is bedside echocardiography. In addition, Mayo criteria should be used to diagnose Takotsubo syndrome. Professionals working in the emergency room shall have Takotsubo syndrome as a differential diagnosis in chest pain.

Valor Prognóstico da Troponina T e do Peptídeo Natriurético Tipo B em Pacientes Internados por COVID-19 / Prognostic Value of Troponin-T and B-Type Natriuretic Peptide in Patients Hospitalized for COVID-19

Resumo Fundamento: A COVID-19 causa grave acometimento pulmonar, porém o sistema cardiovascular também pode ser afetado por miocardite, insuficiência cardíaca e choque. A elevação de biomarcadores cardíacos tem sido associada a um pior prognóstico. Objetivos: Avaliar o valor prognóstico da Troponina T (TnT) e do peptídeo natriurético tipo B (BNP) em pacientes internados por Covid-19. Métodos: Amostra de conveniência de pacientes hospitalizados por COVID-19. Foram coletados dados dos prontuários com o objetivo de avaliar a relação da TnT e o BNP medidos nas primeiras 24h de admissão com o desfecho combinado (DC) óbito ou necessidade de ventilação mecânica. Análise univariada comparou os grupos com e sem DC. Modelo multivariado de Cox foi utilizada para determinar preditores independentes do DC. Resultados: Avaliamos 183 pacientes (idade=66,8±17 anos, sendo 65,6% do sexo masculino). Tempo de acompanhamento foi de 7 dias (1 a 39 dias). O DC ocorreu em 24% dos pacientes. As medianas de TnT e BNP foram 0,011 e 0,041 ng/dl (p<0,001); 64 e 198 pg/dl (p<0,001) respectivamente para os grupos sem e com DC. Na análise univariada, além de TnT e BNP, idade, presença de doença coronariana, saturação de oxigênio, linfócitos, dímero-D, proteína C reativa titulada (PCR-t) e creatinina, foram diferentes entre os grupos com e sem desfechos. Na análise multivariada boostraped apenas TnT (1,12[IC95%1,03-1,47]) e PCR-t (1,04[IC95%1,00-1,10]) foram preditores independentes do DC. Conclusão: Nas primeiras 24h de admissão, TnT, mas não o BNP, foi marcador independente de mortalidade ou necessidade de ventilação mecânica invasiva. Este dado reforça ainda mais a importância clínica do acometimento cardíaco da COVID-19. (AArq Bras Cardiol. 2020; 115(4):660-666)

Abstract Background: COVID-19 causes severe pulmonary involvement, but the cardiovascular system can also be affected by myocarditis, heart failure and shock. The increase in cardiac biomarkers has been associated with a worse prognosis. Objectives: To evaluate the prognostic value of Troponin-T (TNT) and natriuretic peptide (BNP) in patients hospitalized for Covid-19. Methods: This was a convenience sample of patients hospitalized for COVID-19. Data were collected from medical records to assess the association of TnT and BNP measured in the first 24 hours of hospital admission with the combined outcome (CO) of death or need for mechanical ventilation. Univariate analysis was used to compare the groups with and without the CO. Cox's multivariate model was used to determine independent predictors of the CO. Results: We evaluated 183 patients (age = 66.8±17 years, 65.6% of which were males). The time of follow-up was 7 days (range 1 to 39 days). The CO occurred in 24% of the patients. The median troponin-T and BNP levels were 0.011 and 0.041ng/dL (p <0.001); 64 and 198 pg/dL (p <0.001), respectively, for the groups without and with the CO. In the univariate analysis, in addition to TnT and BNP, age, presence of coronary disease, oxygen saturation, lymphocytes, D-dimer, t-CRP and creatinine, were different between groups with and without outcomes. In the bootstrap multivariate analysis, only TnT (1.12 [95% CI 1.03-1.47]) and t-CRP (1.04 [95% CI 1.00-1.10]) were independent predictors of the CO. Conclusion: In the first 24h of admission, TnT, but not BNP, was an independent marker of mortality or need for invasive mechanical ventilation. This finding further reinforces the clinical importance of cardiac involvement in COVID-19. (Arq Bras Cardiol. 2020; 115(4):660-666)

Injuria miocárdica luego de cirugía no cardíaca / Myocardial injury after non-cardiac surgery

Resumen Las complicaciones cardiovasculares mayores en el postoperatorio son frecuentes y el principal factor contribuyente es la injuria miocárdica o infarto (MINS, Myocardial Injury after Noncardiac Surgery) asociado a cirugía no cardíaca. El riesgo de mortalidad a 30 días de los pacientes con injuria miocárdica es 4-5 veces mayor que los pacientes que no lo presentan. Se estima que 85% de los pacientes con MINS no presentan síntomas, por lo que la única manera de detectarlos es mediante screening sistemático de troponinas. Si bien no existen intervenciones de aplicación sistemática que permitan prevenir esta complicación, existen alternativas de tratamiento y manejo, por lo que la pesquisa activa es costo-efectiva y relevante desde el punto de visto clínico.

Major cardiovascular complications in the postoperative period are frequent and the main contributing factor is myocardial injury or infarction (MINS, Myocardial Injury after Noncardiac Surgery) associated with non-cardiac surgery. The 30-day mortality risk in patients with myocardial injury is 4-5 times higher than in patients without this complication. It is estimated that 85% of patients with MINS/infarction are asymptomatic, hence the only way to detect them is through systematic screening of troponins. Although there are no systematic interventions to prevent this complication, there are treatment and management alternatives, so the active early diagnosis is cost effective and relevant from a clinical point of view.

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.

Os Escores HEART, TIMI e GRACE para Predição de Eventos Cardiovasculares Adversos Maiores no Período de 30 Dias na Era de Troponina I de Alta Sensibilidade / HEART, TIMI, and GRACE Scores for Prediction of 30-Day Major Adverse Cardiovascular Events in the Era of High-Sensitivity Troponin

Resumo Fundamento Múltiplos sistemas de pontuação têm sido elaborados para calcular o risco de eventos cardiovasculares adversos maiores (MACE) em pacientes com dor no peito. Não há dados que avaliem se o escore HEART tem um desempenho superior a TIMI e GRACE para a predição de MACE, especialmente na era de troponina I de alta sensibilidade e em uma população exclusivamente latino-americana. Objetivo Comparar o desempenho dos escores HEART, TIMI e GRACE para a predição de MACE em 30 dias de acompanhamento, em pacientes atendidos com dor no peito no departamento de emergência. Métodos Os escores HEART, TIMI e GRACE foram analisados em 519 pacientes com dor no peito no departamento de emergência. O desfecho primário foi a ocorrência de MACE no período de 30 dias. O desempenho do escore HEART foi comparado com o dos escores TIMI e GRACE utilizando o teste de DeLong, considerando estatisticamente significativos os valores de p de 0,05. Resultados Um total de 224 pacientes (43%) apresentaram MACE no período de 30 dias. A estatística C para os escores HEART, TIMI e GRACE foi de 0,937, 0,844 e 0,797 respectivamente (p < 0,0001). Uma pontuação de 3 ou menos no escore HEART apresentou uma sensibilidade de 99,5% e um valor preditivo negativo de 99% para classificar pacientes de baixo risco de maneira correta; ambos os valores foram mais elevados do que aqueles obtidos pelos outros escores. Conclusão O escore HEART, em um período de 30 dias, prediz eventos cardiovasculares, mais eficazmente, em comparação com os outros escores. Troponinas de alta sensibilidade mantêm a superioridade previamente demonstrada deste escore. Este escore oferece uma identificação mais precisa dos pacientes de baixo risco. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Multiple scoring systems have been designed to calculate the risk of major adverse cardiovascular events (MACE) in patients with chest pain. There is no data on whether the HEART score outperforms TIMI and GRACE in the prediction of MACE, especially in the era of high-sensitivity troponin assay and in an exclusively Latin-American population. Objective To compare the performance of the HEART, TIMI, and GRACE scores for predicting major cardiovascular events at 30 days of follow-up, in patients who consult for chest pain in the emergency department. Methods HEART, TIMI, and GRACE scores were analyzed in 519 patients with chest pain at the emergency department. The primary endpoint was the occurrence of MACE within 30 days. The performance of the HEART score was compared with the TIMI and GRACE scores using the DeLong test with p values of 0.05 considered statistically significant. Results A total of 224 patients (43%) had MACE at 30 days. The C statistic for the HEART, TIMI, and GRACE score was 0.937, 0.844, and 0.797 respectively (p < 0.0001). A HEART score of 3 or less had a sensitivity of 99.5% and a negative predictive value of 99% to classify low risk patients correctly; both values were higher than those obtained by the other scores. Conclusion The HEART score more effectively predicts cardiovascular events at 30 days of follow-up compared to the other scores. High-sensitivity troponins maintain this score's previously demonstrated superiority. This score offers more precise identification of low-risk patients. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Asociación entre troponina y perfil lipídico Niveles en pacientes con insuficiencia cardíaca crónica / Association between Troponin and Lipid Profile Levels in Patients with Chronic Heart Failure

Background: Older women have a high chance of suffering from coronary heart diseases and heart failure. Possessing high-sensitive tests will permit early detection of cardiac troponin and lipid proteins (HDL, LDL, VLDL, & Triglyceride) I in levels that are below the diagnostic endpoint for the acute coronary syndrome. Aim of the study: The intent in this study is to analyze the association among the 3 ranks taking into consideration any future cardiac happening within the community setting and involving elderly women who are aged seventy years and above. Patients and Methods: 212 women were grouped for this study, and this lot was lacking any CHD within the set baseline or the troponin and lipid proteins (HDL, LDL, VLDL, & Triglyceride) established above the analytical limits for the disease to be studied (acute coronary syndrome). These elderly women had a 15-year continuation of hospitalization and mortality measures. Results: The analysis showed 22 percent of the study group to be suffering from CHD, there was 15 percent of myocardial infarction or death brought about by CHD, and 10 percent of the heart failure. The 99 percent of assessed serum illustrations, troponin, and lipid proteins (HDL, LDL, VLDL, & Triglyceride) levels were above recognition. Taking into consideration of the Framingham risk features, the correction done for each SD normal linear changed troponin and lipid proteins (HDL, LDL, VLDL, & Triglyceride) upsurge was connected to an upsurge uncertainty for the coronary heart disease. Conclusions: conclusively, the troponin and lipid profile (HDL, LDL, VLDL, & Triglyceride) I am autonomously linked with the foreseeable cardiac happenings in older women across Iraq without seeming clinical indicators. Adding cardiac troponin and lipid proteins (HDL, LDL, VLDL, & Triglyceride) 1 to the conventional risk factor can greatly enhance the risk prediction in this background.

Fisiopatología, perfil epidemiológico y manejo terapéutico en el síndrome coronario agudo / Pathophysiology, epidemiological profile and therapeutic management in acute coronary syndrome

Las enfermedades cardiovasculares siguen siendo ampliamente la primera causa de muerte en el mundo actual. La cardiopatía isquémica conlleva a una importante carga de gastos de Salud Pública, por lo cual es importante conocer la prevalencia, epidemiología, fisiopatología y el manejo diagnóstico y terapéutico adecuado del síndrome coronario agudo (SCA). Los hallazgos recientes indican que los primeros pasos en la aterosclerosis son esencialmente inflamatorios. Una respuesta inflamatoria sistémica a menudo acompaña al SCA, y la documentación de su presencia ha sido ampliamente reconocida como un indicador de eventos coronarios a repetición. La medicina basada en la evidencia sugiere fuertemente la importancia de la etiología inflamatoria en el SCA. Los factores tradicionales de riesgo coronario terminan en un pasaje final común que desarrolla un proceso inflamatorio en la pared arterial. El entendimiento mejorado y la comprensión adecuada de la influencia de los procesos inflamatorios en el SCA pueden llevar no solo a una mejor utilización de la terapéutica actualmente disponible sino también al desarrollo de nuevas herramientas terapéuticas. Sin duda alguna los refinamientos constantes en las diferentes estrategias terapéuticas del SCA, sumados a la combinación del entendimiento científico en el uso adecuado de los marcadores inflamatorios, los nuevos agentes farmacológicos y las nuevas técnicas de intervención coronaria percutánea con los nuevos stents y otros dispositivos intracoronarios van a aclarar nuestras dudas y mejorar nuestro manejo diagnóstico y terapéutico del síndrome coronario agudo basado en la evidencia científica

Cardiovascular diseases are still widely the leading cause of death in the world today. Ischemic heart disease leads to a significant burden of public health expenses, which is why it is important to know the prevalence, epidemiology, pathophysiology and the adequate diagnostic and therapeutic management of acute coronary syndrome (ACS). Recent findings indicate that the first steps in atherosclerosis are essentially inflammatory. A systemic inflammatory response often accompanies ACS, and the documentation of its presence has been widely recognized as an indicator of recurrent coronary events. Evidence based medicine strongly suggests the importance of the inflammatory etiology in ACS. The traditional coronary risk factors end in a common final passage that develops an inflammatory process in the arterial wall. Improved and adequate understanding of the influence of inflammatory processes in ACS can lead not only to a better use of currently available therapeutics but also to the development of new therapeutic tools. Undoubtedly the constant refinements in the different therapeutic strategies of the ACS, combined with the addition of scientific understanding in the proper use of inflammatory markers, new pharmacological agents and new techniques of percutaneous coronary intervention with newer stents and other intracoronary devices will clarify our doubts and improve our diagnostic and therapeutic management of acute coronary syndrome based on scientific evidence

Interferencia analítica en la determinación de troponina por anticuerpos heterófilos / Interference in the determination of Troponin due to heterophile antibodies

Resumen Por su elevada especificidad y sensibilidad, y a raíz de la tercera definición universal de infarto estas isoformas cardiacas han sido aceptadas en el ámbito internacional como los biomarcadaores de elección en la práctica clínica para el diagnóstico de síndrome coronario agudo, preferibles a la determinación de las enzimas creatina quinasa y su isoforma MB. Se presenta el caso de un varón de ochenta años, quien, de manera persistente, tuvo valores elevados de troponinas, pese a evolución clínica no compatible con síndrome coronario agudo ni otras causas de elevación de este biomarcador.

Abstract Due to its elevated specificity and sensitivity, and on being the third universal definition of myocardial infarction, these cardiac isoforms have been accepted internationally as the biomarkers of choice in clinical practice for the diagnosis of acute coronary syndrome, and are preferable to the determinations of creatine kinase and its MB isoform. A case is presented on an eighty year-old man, who persistently had elevated Troponin values, despite a clinical course that was incompatible with an acute coronary syndrome or any other causes of elevation of this biomarker.

Risk of late appearance of acute myocardial infartion after carbon monoxide (CO) intoxication / Riesgo de aparición de infarto agudo de miocardio en el largo plazo después de una intoxicación por monóxido de carbono (CO)

ABSTRACT Background: After acute carbon monoxide intoxication, there may be a higher risk for late adverse cardiac events. However, these patients are usually not followed to monitor the appearance of these effects. Aim: To follow patients seen at an emergency department for carbon monoxide intoxication, monitoring the appearance of myocardial infarction. To assess the predictive value for such complication of serum troponin, carboxyhemoglobin, and procalcitonin levels at the moment of intoxication. Material and Methods: We followed 237 patients receiving emergency care for carbon monoxide intoxication, with a serum carboxyhemoglobin of 5% or more, between 2010 and 2012. Levels of procalcitonin and troponin I were measured. Patients were followed for five years after the intoxication. Results: During the follow up period, 35 patients had a myocardial infarction. These patients had significantly higher carboxyhemoglobin, procalcitonin and troponin I levels at the moment of the intoxication than their counterparts who did not had a myocardial infarction in the follow up. A logistic regression analysis showed that age, carboxyhemoglobin levels, procalcitonin, troponin 1 and length of CO exposure were associated with a higher risk of myocardial infarction. Procalcitonin, troponin and carboxyhemoglobin levels had a high sensitivity and specificity to predict the appearance of myocardial infarction, with high areas under the receiver operating characteristic (ROC) curves. Conclusions: In patients with CO intoxication, carboxyhemoglobin, troponin and procalcitonin levels at the moment of the intoxication are significant predictors of the late appearance of myocardial infarction.

Antecedentes: Después de una intoxicación con monóxido de carbono, hay un mayor riesgo de desarrollar problemas cardiovasculares a largo plazo. Sin embargo, estos pacientes no son seguidos habitualmente para evaluar la aparición de estos eventos. Objetivo: Efectuar un seguimiento de pacientes que han sufrido una intoxicación con CO, evaluando la aparición de infarto del miocardio. Evaluar el valor de los niveles de troponina, carboxihemoglobina y procalcitonina para predecir la aparición de estos eventos. Material y Métodos: Seguimos 237 pacientes que fueron atendidos de urgencia por una intoxicación con CO, con niveles de carboxihemoglobina de 5% o más, entre 2010 y 2012. Se midieron los niveles de procalcitonina, troponina 1 y carboxihemoglobina y los pacientes fueron seguidos por cinco años después de la intoxicación. Resultados: Durante el seguimiento, 35 pacientes tuvieron un infarto al miocardio. Estos pacientes tenían niveles significativamente más altos de procalcitonina, troponina 1 y carboxihemoglobina al momento de la intoxicación, que los pacientes que no tuvieron un infarto durante el seguimiento. Una regresión logística mostró que la edad, carboxihemoglobina, procalcitonina, troponina y la duración de exposición a CO se asociaron a un mayor riesgo de infarto. Procalcitonina, troponina 1 y carboxihemoglobina tuvieron una alta sensibilidad y especificidad para predecir la aparición de infarto, con áreas bajo la curva ROC (receiver operating characteristic) elevadas. Conclusiones: En pacientes con intoxicación por CO, la carboxihemoglobina, procalcitonina y troponina son predictores significativos de la aparición de infarto agudo de miocardio en el largo plazo.

Comparative analysis of myocardial protection with htk solution and hypothermic hyperkalemic blood solution in the correction of acyanogenic congenital cardiopathies - a randomized study

Abstract Objective: The goal of the present study was to compare the myocardial protection obtained with histidine-tryptophan-ketoglutarate (HTK) cardioplegic solution (Custodiol®) and with intermittent hypothermic blood solution. Methods: Two homogenous groups of 25 children with acyanotic congenital heart disease who underwent total correction with mean aortic clamping time of 60 minutes were evaluated in this randomized study. Troponin and creatine kinase-MB curves, vasoactive-inotropic score, and left ventricular function were obtained by echocardiogram in each group. The values were correlated and presented through graphs and tables after adequate statistical treatment. Results: It was observed that values of all the studied variables varied over time, but there was no difference between the groups. Conclusion: We conclude that in patients with acyanotic congenital cardiopathies submitted to total surgical correction, mean aortic clamping time around one hour, and cardiopulmonary bypass with moderate hypothermia, the HTK crystalloid cardioplegic solution offers the same myocardial protection as the cold-blood hyperkalemic cardioplegic solution analyzed, according to the variables considered in our study model.

Diagnóstico diferencial de pericardite aguda no infarto agudo do miocárdio com supradesnivelamento de segmento ST: relato de caso / Differential diagnosis of acute pericarditis in ST-segment elevation acute myocardial infarction: case report

A pericardite é um processo inflamatório do pericárdio de múltiplas causas, sendo a infecção viral a mais comum. O infarto agudo do miocárdio é um dos principais diagnósticos diferenciais. O objetivo deste artigo foi relatar um caso de pericardite aguda com supradesnivelamento de segmento ST. Os dados foram coletados em um hospital de ensino do Estado de Minas Gerais. O paciente era do sexo masculino, tinha 24 anos e era negro. Foi encaminhado ao serviço médico terciário devido à hipótese de síndrome coronariana aguda com supradesnivelamento do segmento ST. Nos exames do serviço médico de origem, apresentava supradesnivelamento do segmento ST de caráter difuso simultaneamente em paredes inferior e anterior, e alteração da isoenzima MB da creatina quinase de 100ng/mL e troponina I de 21ng/mL. No momento da admissão, encontrava-se em bom estado geral, afebril, estável hemodinamicamente e sem queixa de dor. Referiu que 4 dias antes da admissão, apresentou febre, mal-estar geral, odinofagia e tratamento de amigdalite. Os exames da admissão demonstravam ritmo sinusal, frequência cardíaca de 75bpm, supradesnivelamento de ST em D2, D3, aVF, V1 a V6, isoenzima MB da creatina quinase de 152ng/mL, troponina I de 1,28ng/mL, hemograma normal; ecocardiograma mostrou pericárdio de aspecto anatômico normal e fração de ejeção de 64%. O diagnóstico foi de pericardite aguda de provável etiologia infecciosa. O tratamento foi realizado com ibuprofeno por 7 dias e colchicina por 3 meses. Paciente evoluiu com alta hospitalar após 5 dias. O diagnóstico correto proporcionou a condução adequada do caso, permitindo a redução dos custos hospitalares e eliminando riscos de procedimentos desnecessários. (AU)

Pericarditis is an inflammatory process of the pericardium of multiple causes, being the most common viral infection. Acute myocardial infarction is one of the main differential diagnoses. The objective of this article was to report a case of acute pericarditis with ST-segment elevation. Data were collected at a teaching hospital in the state of Minas Gerais. The patient was a man of 24 years, black. He was referred to the tertiary medical service due to the hypothesis of Acute Coronary Syndrome with ST-segment elevation. In the tests from the medical service of origin, there was diffuse ST-segment elevation, simultaneously on lower and anterior walls, and a change in the Creatinine Kinase MB Isoenzyme of 100ng/ml, and troponin I of 21ng/ml. At the time of admission, he was in good general condition, afebrile, hemodynamically stable, with no complaint of pain. He said that 4 days before admission he had fever, malaise, odynophagia, and treatment for tonsillitis. The admission tests showed sinus rhythm, heart rate of 75bpm, ST-elevation in D2, D3, aVF, V1 to V6, MB isoenzyme of creatine kinase of 152ng/ml, troponin I of 1.28ng/ml, normal complete blood count; echocardiogram showed pericardium of normal anatomical aspect and ejection fraction of 64%. The diagnosis was acute pericarditis of probable infectious etiology. Treatment was performed with ibuprofen for seven days, and colchicine for three months. The patient was discharged from hospital after 5 days. The correct diagnosis provided adequate case management, allowing for reduced hospital costs, and eliminating risks of unnecessary procedures. (AU)