Research Progress of Immune Checkpoint Inhibitor-associated Myocarditis / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) is a negative regulatory factor antibody, which activates T cells to play an anti-tumor effect in immunotherapy, and can also cause immune-related adverse responses, thereby inducing a series of immune related adverse events (irAEs). Among these irAEs, although the incidence of ICIs-related myocarditis is very low, the fatality rate is significantly higher than other adverse reactions, close to 50%. Clinicians should be vigilant when applying ICIs, but the pathogenesis of ICIs-related myocarditis is still unclear. This article combines the recent research results of ICIs to summarize the mechanism and clinical manifestations of ICIs-related myocarditis, so as to improve clinicians' understanding of the adverse reactions.
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Evolutive study of rheumatic carditis cases treated with corticosteroids in a Public Hospital / Estudo evolutivo de casos de cardite reumática tratados com corticosteróides em um hospital público

Background: Rheumatic carditis is a challenge for treatment and secondary prophylaxis, due to severe valve sequelae. Objective: To evaluate the cases of rheumatic carditis in patients under 18 years old treated with corticosteroids.Methods: An observational, longitudinal and retrospective study was carried out on the profile of patients, in the period of 2000-2015. We selected those who received corticosteroid therapy at immunosuppressive doses, for the treatment of carditis and were aged 5 to 18 years. Data were extracted from medical records. Calculations of: averages, standard deviations, medians and interquartile ranges, ratios and 95% confidence intervals were obtained. Chi-square and Wilcoxon tests were applied for comparisons. The level of significance was 5%. Results: Of the 93 cases, 93.53% developed moderate or severe carditis. Mitral regurgitation was detected in 100% of the sample. Pulse therapy was administered in 11.83%. Surgery was performed in 23.69% of patients: mitral, aortic and/or tricuspid valve repair or replacement. The evolution of the cases was favorable in 70.96%. There was a good response among those who received only clinical treatment and those who belonged to the surgical group. The comparison of the initial and posterior valve lesions to the corticoid use was statistically significant (p < 0.001). A difference between the ejection fraction medians was observed (p = 0.048). Hospitalization was required twice or more for 45.16% of the patients. The mortality rate was 5.38%.Conclusions: The patients showed significant clinical improvement. The treatment was effective, reducing trivalvular impairment

Efficacy of echocardiographic criteria for diagnosis of carditis in acute rheumatic fever.

Background: There is a great need forECHOcriteria for accurate diagnosis of carditis in acute rheumatic fever. Aim: To propose and test the efficacy of ECHO criteria for accurate diagnosis of carditis. Material and Methods: The 333 cases underwent detailed clinical examination, laboratory tests and meticulous Echocardiographic study.Vijay’s ECHO criteria for the diagnosis of carditis / subclinical valvulitis was used. 220 (66.06%) cases were both Jones’ positive and ECHO positive [True +ve], 52 cases (15.61%), probably had subclinical carditis as murmur was not heard (Jones’-ve) but ECHO was positive [False - ve]. Four cases, clinically diagnosed as carditis were Jones’+ve ,but ECHO showed congenital heart disease [False +ve]. 57 cases (17.11%) were clinically , echocardiographically and Jones’ negative were taken as control (True –ve). Sensitivity is81%and specificity is 93%. Conclusions: Precise diagnosis of both carditis /subclinical valvulitis is possible with Vijay’s ECHO criteria. ECHO should be included as a major criterion in Jones’criteria.

Compromiso miocárdico en infección grave por virus influenza H1N1 / Myocardial involvement in severe H1N1 influenza infection

Introduction: During the winter of 2009, some patients infected with Influenza virus H1N1 presented a severe disease. Some isolated reports of myocarditis were described. Objective: To describe severe cases of H1N1 with myocardial involvement. Patients and Methods: Chart review of children between 0-15 y.o. diagnosed as presenting Influenza A H1N1 through Polimerase Chain Reaction, who were admitted to the PICU at Hospital Roberto del Río and Clínica Dávila between June and July of 2009. Myocardial involvement was considered positive if the clinical picture showed such signs, and/or there was an altered echocardiogram. Results: Twenty one patients were hospitalized with the diagnosis of severe Infection by Influenza A H1N1 (+), of which 8 patients (38 percent) presented myocardial involvement. All required mechanical ventilation. Echocardiogram performed in the first 24 hours post admission showed shortening of the left ventricle on average 21,8 percent, with a range of 19 to 38 percent. In 7 patients (87.5 percent) a systodyastolic dysfunction was shown. Myocardial involvement lasted from 2 to 10 days (median 4). One patient died. Conclusions: Involvement of myocardium is frequent in this series. It must be sought to treat it adequately.

Introducción: Durante el invierno 2009 algunos paciente con infección por virus Influenza A H1N1, evolucionaron en forma grave. Se han descrito reportes aislados de miocarditis secundaria a Influenza A H1N1. Objetivo: Descripción de los casos graves de H1N1 que presentaron compromiso miocárdico. Material y Métodos: Revisión de los casos diagnosticados como Influenza A H1N1 por Reacción Polimerasa en Cadena, en niños entre 0-15 años, hospitalizados en la Unidad de Paciente Crítico del Hospital Roberto del Río y de Clínica Dávila, durante el período Junio - Julio del 2009. Se consideró criterio de compromiso miocárdico el cuadro clínico y/o una ecocardiografía alterada. Resultados: : 21 pacientes fueron hospitalizados con diagnóstico de infección grave por Influenza A H1N1 (+), de éstos 8 pacientes ( 38 por ciento) presentaron compromiso miocárdico. Todos requirieron ventilación mecánica. La ecocardiografia en las primeras 24 horas postingreso, evidenció una fracción de acortamiento del ventrículo izquierdo promedio de 21,8 por ciento, con un rango de 19 a 38 por ciento. En 7 pacientes (87.5 por ciento) se constató una disfunción sistodiastólica. La duración promedio del compromiso miocárdico osciló entre 2 a 10 días ( mediana 4).Hubo 1 fallecido en esta serie. Conclusiones: La frecuencia de compromiso miocárdico en esta serie es importante, debiendo buscarse dirigidamente para adecuar plan terapéutico.

Absence of Fas-L aggravates renal injury in acute Trypanosoma cruzi infection

Trypanosoma cruzi infection induces diverse alterations in immunocompetent cells and organs, myocarditis and congestive heart failure. However, the physiological network of disturbances imposed by the infection has not been addressed thoroughly. Regarding myocarditis induced by the infection, we observed in our previous work that Fas-L-/- mice (gld/gld) have very mild inflammatory infiltration when compared to BALB/c mice. However, all mice from both lineages die in the early acute phase. Therefore, in this work we studied the physiological connection relating arterial pressure, renal function/damage and cardiac insufficiency as causes of death. Our results show that a broader set of dysfunctions that could be classified as a cardio/anaemic/renal syndrome is more likely responsible for cardiac failure and death in both lineages. However, gld/gld mice had very early glomerular deposition of IgM and a more intense renal inflammatory response with reduced renal filtration, which is probably responsible for the premature death in the absence of significant myocarditis in gld/gld.

Curso de atualização em cardiologia: aula 10. Miocardite como modelo de doença imunológica: aspectos clínicos e diagnósticos / Cardiology updating course: class 10. Miocardite as model of disease imunológica: clinical aspects and diagnoses

Miocardites são um grupo de doenças heterogêneas que podem ser compreendidas com uma fisiopatologia imunológica. Os autores discutem aspectos históricos e a imunologia dessas doenças, correlacionando o trabalho de cientistas como Carlos Chagas, Noel Rose e Nelson Vaz. Levam em consideração a evolução histórica do conhecimento científico e a mudança de paradigma em andamento na imunologia. Também analisam as principais manifestações clínicas e estratégias para o diagnóstico e abordam novas propostas para investigação clínica dessas síndromes.

Atualização em miocardites / Myocarditides update

As miocardites (inflamações do músculo cardíaco, podendo envolver os miócitos, o interstício, estruturas vasculares e/ou o pericárdio) são importantes causas de morte súbita e inesperada em adultos com menos de 40 anos de idade e atletas jovens. Têm etiologia diversa, incluindo vírus, bactérias, protozoários, drogas e doenças sistêmicas. Sua fisiopatologia envolve a ativação prolongada das imunidades celular e humoral. Seu curso geralmente é assintomático ou insidioso, havendo considerável dificuldade no estabelecimento do diagnóstico, devido à inespecificidade de seu quadro clínico e à baixa sensibilidade dos exames complementares. O tratamento é basicamente suportivo e direcionado às possíveis complicações ou às causas de base. Possuem prognóstico variável, dependendo da causa-base, sendo pior nas doenças sistêmicas e na infecção pelo HIV.

Myocarditis are defined as inflammation of the cardiac muscle, which may involve the myocite, the interstitium, the vascular structures and/or the pericardium. They are important causes of sudden and unexpected death in adults and in young athletes. There are many known etiologies for myocarditis, including virus, bacteria, protozoan, drugs and systemic diseases. Its pathophysiology involves the continuum activation of humoral and cellular immunity. The course of the disease usually is assymptomatic or insidious, clinical manifestations are quite non-specific and complementary, exams show poor sensibility and specificity, making diagnosis difficult. Treatment is basically supportive and addressed to the possible complications or its causes. The prognosis is somewhat variable, depending on the underlying cause, being worse in systemic diseases and in HIV infections.

Miocardite aguda, uma apresentação típica e uma abordagem nova / Acute myocarditis - a typical case report with a new approach

Relato de caso que tem o objetivo de mostrar alguns aspectos da abordagem diagnóstica da miocardite aguda. Será discutido rapidamente o diagnóstico atual da miocardite e de forma mais abrangente sobre a abordagem diagnóstica pela ressonância magnética cardíaca

Frequency of myocarditis in cases of fatal meningococcal infection in children: observations on 31 cases studied at autopsy

A freqüência de miocardite associada à infcecçäo meningocócica em crianças foi descrita apenas em duas series de casos autopsiados (Estados Unidos e Africa do Sul). Nessa comunicaçäo relataremos a freqüência de miocardite em 31 crianças falecidas com doença meningocócica no Hospital Infantil N.S. da Glória em Vitória, E. Santo. O diagnóstico foi confirmado pelo isolamento da Neisseria meningitidis. Três secçöes ou mais, dos átrios e ventrículos, foram estudadas utilizando os critérios de Dallas para o diagnóstico morfológico de miocardite. A média de idade foi de 47,6 ñ 39,8 meses e o tempo médio de sobrevida após o início dos sintomas foi de 46,1 ñ 26,5 horas (12-112h). Miocardite foi identificada em 13 (41,9 por cento) casos sendo de intensidade mínima em 11 e de intensidade moderada em dois casos. Nenhum paciente apresentou quadro morfológico de miocardite grave, difusa. A freqüência de miocardite näo foi influenciada pelo sexo, presença de meningite, tempo de sobrevida após o início dos sintomas ou pelo uso de drogas vasoativas. A freqüência de miocardite aqui apresentada é intermediária entre as únicas duas séries relatadas na literatura (57 por cento nos Estados Unidos e 27 por cento na Africa do Sul). Embora confirme a alta freqüência de miocardite na doença meningocócica, investigaçöes säo necessárias para elucidar a contribuiçäo da miocardite para a disfunçäo miocárdica observada em casos de infecçäo meningocócica em crianças

Miocarditis viral asociada a bronquiolitis por virus sincitial respiratorio

La bronquiolitis por virus sincitial respiratorio (USR) es una enfermedad de las vías aéreas pequeñas, caracterizada por inflamación y obstrucción de los bronquiolos. El VSR fue aislado por primera vez en 1995, pertenece a la familia de los paramixovirus. Es clara la presentación epidérmica anual que compromete especialmente a lactantes pequeños. La tasa de infección por VSR durante el primer año de vida alcanza el 69 por ciento y el 83 por ciento durante el segundo. La mortalidad en niños previamente sanos es del 0.005 por ciento al 0.002 por ciento; en pacientes hospitalizados es del 1 al 3 por ciento. Aunque se ha descrito que la infección por VSR no altera la función cardíaca en pacientes con corazón sano, se encuentra en la literatura informes aislados al respecto; a continuación presentamos un caso de un paciente con bronquiolitis por VSR, en el que se documentó miocarditis por este mismo germen.

Experimental autoimmune myocarditis: a suitable model to study neuroimmune crosstalk

This review regards the main functional characteristics of hearts subjected to an autoimmune response focusinf especially on the role of T lymphocytes and autoantibodies in the development of cardiac dysfunction. Evidence of a strong association in the onset and time-course of immune response and cardiac dysfunction is presented and the results are viewed comparatively with myocarditis models induced by heart, parasite or virus inoculation. Cardiac damage is evaluated regarding various aspects, namely histologic, immunologic, biochemical, pharmacologic, physiologic. Finally, the model, for its characteristics of resulting from an autoimmune response against the heart with functional consequences, has proved its usefulness to study neuroimmune interaction, mainly the immune to nervous direction, as autoantibodies and T cell-derived factors have a role in cardiac failure.

Blood lymphocytes energy metabolism in myocardial inflammatory injuries

Cytochemical analysis and bioenergetics of blood lymphocytes have been studied in 68 patients of Infectious Allergical Myocarditis [IAM] and 44 patients of Myocardiosclerosis [MC]. Regarding cellular metabolism, the activity of Glucose-6-PO4 Dehydrogenase [G-6-PD] [E.C. I.I.I.49] was found to be high according to the Nitrobluetetrazolium Reduction Test [I] due to the disturbance of NAD and NADP diaphorase [E.C.I.6.4.3]. The activity of L-glycerophosphate Dehydrogenase [E.C.I.1.1.8, 1.1.99.5] and cytochrome C content of the cells was found to be reduced. Thus, study of energy metabolism of blood lymphocytes provides an additional differential characteristics of inflammatory injuries of myocardium

Convulsiones y paro cardíaco: forma inhabitual de presentación de miocarditis asociada a virus de Epstein Barr / Convulsions and heart arrest: atypical presentation of myocarditis associated with Epstein Barr virus

La incidencia de compromiso cardíaco en la mononucleosis infecciosa es baja. El espectro de manifestaciones incluye cambios electrocardiográficos en 6% y síntomas cardíacos en 0,7% de los casos. Se describe el caso de un paciente de 9 años que ingresó al hospital por convulsiones tónicas generalizadas, que se repitieron a pesar del empleo de fenobarbital y diazepam. Fue admitido a tratamiento intensivo, en coma, grado 3 de Glasgow, con bradicardia irregular y apneas, bloqueo auriculoventricular completo, frecuencia auricular 150/min y ventricular 53/min. Poco después de ingresar sufrió cinco paros cardíacos, requiriendo reanimación cardiopulmonar, ventilación mecánica, infusión de isoproterenol, dopamina y prednisona. Su evolución fue crítica con hipotensión y persistencia del bloqueo atrio ventricular. A las 24 horas de su ingreso se repitió la asistolía, por lo que se le instaló marcapaso externo. Los exámenes mostraron cardiomegalia en la radiografía de tórax; dilatación de la aurícula y ventrículo derecho, edema de pared y disminución de la contractilidad ventricular izquierda en la ultrasonografía cardíaca, concentraciones séricas de creatina fosfokinasa de 196 U/I con fracción MB de 53 U/I. La serología y los cultivos para virus Echo y Coxsackie fueron negativos. La IgM anticápside de virus de Epstein Barr al ingreso y 10 días después fue positiva en título máximo de dilución (1/40), proteína C reactiva 6 mg/l, velocidad de sedimentación de los eritrocitos 10 mm/h, factor reumatoídeo negativo. El bloqueo cedió progresivamente, el isoproterenol pudo ser suspendido al tercer día, la dopamina al noveno y el marcapaso al décimo séptimo día, siendo dado de alta 18 días después de ingresar con ritmo sinusal, extrasístoles ventriculares aislados, buena contractilidad ventricular y tasas normales de enzimas séricas