Guideline of the Brazilian Society of Cardiology on Diagnosis and Treatment of Patients with Chagas Disease Cardiomyopathy / 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. 

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience.

BACKGROUND: We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. METHODS: This was an observational retrospective study with clinical data retrieved from medical records. RESULTS: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. CONCLUSIONS: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil.

INTRODUCTION: We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS: This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS: A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS: The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil

Abstract INTRODUCTION We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. METHODS: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. RESULTS: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 4 8 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). CONCLUSION: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Cardiosphere-derived cells do not improve cardiac function in rats with cardiac failure.

BACKGROUND: Heart failure represents an important public health issue due to its high costs and growing incidence worldwide. Evidence showing the regenerative potential of postmitotic heart tissue has suggested the existence of endogenous cardiac stem cells in adult hearts. Cardiosphere-derived cells (CDC) constitute a candidate pool of such cardiac stem cells. Previous studies using acute myocardial infarction (MI) models in rodents demonstrated an improvement in cardiac function after cell therapy with CDC. We evaluated the therapeutic potential of CDC 60 days after MI in a rat model. METHODS: CDC were obtained from human discarded myocardial tissue and rat hearts by enzymatic digestion with collagenase II. At 10-15 days after isolation, small, round, phase-bright cells (PBCs) appeared on top of the adherent fibroblast-like cells. The PBCs were collected and placed on a nonadherent plate for 2 days, where they formed cardiospheres which were then transferred to adherent plates, giving rise to CDC. These CDC were characterized by flow cytometry. Wistar rats were submitted to MI through permanent occlusion of the anterior descending coronary artery. After 60 days, they were immunosuppressed with cyclosporine A during 10 days. On the third day, infarcted animals were treated with 5 × 105 human CDC (hCDC) or placebo through intramyocardial injection guided by echocardiogram. Another group of animals was treated with rat CDC (rCDC) without immunosuppression. hCDC and rCDC were stably transduced with a viral construct expressing luciferase under control of a constitutive promoter. CDC were then used in a bioluminescence assay. Functional parameters were evaluated by echocardiogram 90 and 120 days after MI and by Langendorff at 120 days. RESULTS: CDC had a predominantly mesenchymal phenotype. Cell tracking by bioluminescence demonstrated over 85% decrease in signal at 5-7 days after cell therapy. Cardiac function evaluation by echocardiography showed no differences in ejection fraction, end-diastolic volume, or end-systolic volume between groups receiving human cells, rat cells, or placebo. Hemodynamic analyses and infarct area quantification confirmed that there was no improvement in cardiac remodeling after cell therapy with CDC. CONCLUSION: Our study challenges the effectiveness of CDC in post-ischemic heart failure.

Torção do ventrículo esquerdo é reduzido e sua dinâmica alterada em estágios avançados da forma cardíaca da doença de Chagas / Decreased left ventricular torsion with distorted dynamics at advanced stages of Chagas'heart disease

Fundamentos: A expressão mais grave da doença de Chagas é a insuficiência cardíaca (IC). A torção do ventrículo esquerdo (VE) é reduzida na IC de outras etiologias e pode ser importante para avaliação do desempenho cardíaco na doença de Chagas. Objetivo: Avaliar a torção do VE em diferentes estágios dadoença de Chagas. Métodos: Foi realizado estudo longitudinal entre março e outubro de 2010 avaliando ecocardiogramas de 17 controles e 139 pacientes sendo 44 da forma indeterminada (sem cardiopatia aparente), 27 pacientes no estágio A da forma cardíaca (alterações limitadas ao eletrocardiograma), 31 no estágio B (sem clínica de IC com alteração da função sistólica global ou segmentar do VE), 26 no estágio C (IC compensável) e 11 no estágio D (IC refratária).Resultados: A torção do VE foi similar entre controles (12,7±3,9º), indeterminados (11,7±5,5º) e pacientes no estágio A (9,9±4,6º), mas foi progressivamente menor nospacientes do estágio B ao D (B:8,6±6,3º; C:4,7±4,1º; D:0,1±3,1º;p<0,0001). Enquanto os controles apresentaram padrão normal de torção do VE com rotação apical anti-horária erotação basal no sentido horário, o padrão de torção foi anormal em 15 dos pacientes indeterminados e noestágio A; 37 dos pacientes no estágio B; 35 dos pacientes no estágio C; e 82 dos pacientes no estágio D.Conclusões: A torção do VE é reduzida e sua dinâmica progressivamente mais alterada conforme a doença de Chagas atinge estágios mais avançados de acometimento cardíaco. A contribuição desses eventos para o prognósticoda doença de Chagas ainda deve ser estabelecida.