Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.  Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities.   Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.  The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.  The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.     Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.    Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz.&nbsp

Avaliação da acurácia do strain pelo speckle tracking para detecção de fibrose miocárdica na ressonância magnética em portadores de doença de Chagas

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-02-04T11:32:50Z No. of bitstreams: 1 Carolina Thé Macedo Avaliação da acuracia...2015.pdf: 2036804 bytes, checksum: 926f70b1e7ec1709b317e04842607c6a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-02-04T11:33:56Z (GMT) No. of bitstreams: 1 Carolina Thé Macedo Avaliação da acuracia...2015.pdf: 2036804 bytes, checksum: 926f70b1e7ec1709b317e04842607c6a (MD5)Made available in DSpace on 2016-02-04T11:33:56Z (GMT). No. of bitstreams: 1 Carolina Thé Macedo Avaliação da acuracia...2015.pdf: 2036804 bytes, checksum: 926f70b1e7ec1709b317e04842607c6a (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUm dos principais desafios na miocardiopatia chagásica é a detecção de alterações precoces na função ventricular esquerda. A avaliação do strain pelo speckle tracking na ecocardiografia bidimensional (2-D ST) é um novo método com aplicações em diversas doenças cardíacas, tendo sido validado para pacientes com infarto do miocárdio em comparação à ressonância magnética cardíaca (RMC). Neste estudo, avaliamos a hipótese de que o strain global longitudinal (SGL) possui um valor incremental à fração de ejeção (FE) pelo método de Simpson para predição de fibrose miocárdica na RMC, em pacientes portadores de doença de Chagas (DC). Métodos: Estudo observacional, com um total de 58 pacientes portadores de DC. Todos os pacientes foram submetidos à realização de ecocardiograma convencional e com strain pelo speckle tracking, além de RMC. Resultados: A análise da curva ROC mostrou que tanto a SGL (área sob a curva: 0,78, p = 0,001) quanto a fração de ejeção (área sob a curva: 0,82, p < 0,001) tiveram significância estatística na detecção de fibrose. Em relação á porcentagem de fibrose, uma alta correlação foi observada tanto com a FE pela ecocardiografia (r = - 0,70, p < 0,001) quanto com o SGL (r = 0,64, p < 0,001). Contudo, quando ajustado pela regressão linear múltipla, o SGL perdeu a significância estatística como preditor independente de fibrose miocárdica (p = 0.111). Conclusões: SGL não possui valor incremental em relação à FE na predição de fibrose miocárdica em pacientes portadores de DC.One of the most challenging issues of chronic Chagas disease is to provide earlier detection of heart involvement. Two-dimensional speckle tracking (2-D ST) echocardiography, a new imaging modality with useful applications in several cardiac diseases, has been validated for subjects with myocardial infarction against cardiac magnetic resonance (CMR). Here we hypothesize that the longitudinal global strain (LGS) has an incremental value to ejection fraction for predicting myocardial fibrosis in subjects with Chagas disease. Methods: This observational study comprised 58 subjects with Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogram plus speckle tracking strain, and cardiac magnetic resonance. Results: The ROC curve analysis revealed that both LGS (Area under the curve: 0.78, p = 0.001) and ejection fraction (Area under the curve: 0.82, p < 0.001) were significant predictors of myocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r = - 0.70, p < 0.001) and LGS (r = 0.64, p < 0.001). However, when adjusted through multiple linear regression, the LGS lost statistical significance as a predictor of myocardial fibrosis (p = 0.111). Conclusions: LGS has no incremental value to conventional ejection fraction measurement in the prediction of myocardial fibrosis in subjects with Chagas disease

Assessment of speckle tracking strain predictive value for myocardial fibrosis in subjects with Chagas disease

One of the most challenging issues of chronic Chagas disease is to provide earlier detection of heart involvement. Two-dimensional speckle tracking (2-D ST) echocardiography, a new imaging modality with useful applications in several cardiac diseases, has been validated for subjects with myocardial infarction against cardiac magnetic resonance (CMR). Here we hypothesize that the longitudinal global strain (LGS) has an incremental value to ejection fraction for predicting myocardial fibrosis in subjects with Chagas disease. This observational study comprised 58 subjects with Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogram plus speckle tracking strain, and cardiac magnetic resonance. The ROC curve analysis revealed that both LGS (area under the curve: 0.78, p = 0.001) and ejection fraction (area under the curve: 0.82, p < 0.001) were significant predictors of myocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r = 0.70, p < 0.001) and LGS (r = 0.64, p < 0.001). However, when adjusted through multiple linear regression, the LGS lost statistical significance as a predictor of myocardial fibrosis (p = 0.111). LGS has no incremental value to conventional ejection fraction measurement in the prediction of myocardial fibrosis in subjects with Chagas disease

Assessment of speckle tracking strain predictive value for myocardial fibrosis in subjects with Chagas disease

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T12:36:51Z No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T12:51:06Z (GMT) No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5)Made available in DSpace on 2016-05-12T12:51:06Z (GMT). No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5) Previous issue date: 2015Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilBackground: One of the most challenging issues of chronic Chagas disease is to provide earlier detection of heart involvement. Two-dimensional speckle tracking (2-D ST) echocardiography, a new imagingmodalitywith useful applications in several cardiac diseases, has been validated for subjects with myocardial infarction against cardiac magnetic resonance (CMR). Here we hypothesize that the longitudinal global strain (LGS) has an incremental value to ejection fraction for predicting myocardial fibrosis in subjects with Chagas disease. Methods: This observational study comprised 58 subjectswith Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogramplus speckle tracking strain, and cardiacmagnetic resonance. Results: The ROC curve analysis revealed that both LGS (area under the curve: 0.78, p=0.001) and ejection fraction (area under the curve: 0.82, p b 0.001)were significant predictors ofmyocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r =0.70, p b 0.001) and LGS (r = 0.64, p b 0.001). However, when adjusted through multiple linear regression, the LGS lost statistical significance as a predictor of myocardial fibrosis (p = 0.111). Conclusions: LGS has no incremental value to conventional ejection fractionmeasurement in the prediction ofmyocardial fibrosis in subjects with Chagas disease

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-23T13:16:57Z No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-23T13:35:11Z (GMT) No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5)Made available in DSpace on 2016-03-23T13:35:11Z (GMT). No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5) Previous issue date: 2015Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilBACKGROUND: Galectin-3, a ß-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated. OBJECTIVE: The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease. METHODS: Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene. RESULTS: For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease. CONCLUSION: Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease

Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGFβ1) and T. cruzi stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC