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. 

Corrigendum: Impact of COVID-19 in-hospital mortality in chagas disease patients.

[This corrects the article DOI: 10.3389/fmed.2022.880796.].

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.

Prevalence of metabolic syndrome and associated factors among patients with chronic Chagas disease.

The increase in life expectancy and the migration of individuals with Chagas disease (ChD) from rural to urban centers exposes them to the development of chronic-degenerative abnormalities that may increase the prevalence of metabolic syndrome (MetS). The present study aimed to identify the prevalence of MetS and its components in individuals with chronic ChD. This is a cross-sectional study with 361 patients of both sexes, aging >18 years, followed at a national reference center (Rio de Janeiro, Brazil). MetS diagnosis followed the International Diabetes Federation 2005 criteria. The association between the variables was determined through logistic regression models. The mean age was and 60.7±10.8 years. About half (56.2%) were female and the majority self-reported their race as mulatto (59.8%). The percentage of individuals with MetS was 40.4%. The variables independently associated with MetS were age (OR 1.06; 95%CI 1.04-1.09), high education levels (OR 0.36; 95%CI 0.17-0.79) and cardiac form with heart failure (OR 0.34; 95%CI 0.17-0.68). Therefore, a high prevalence of MetS was found in this Brazilian chronic ChD cohort. The identification of the associated factors can facilitate the development of effective approaches for preventing and managing MetS in ChD patients.

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.

Impact of pharmaceutical care on the quality of life of patients with heart failure due to chronic Chagas disease: Randomized clinical trial.

AIMS: Chronic Chagas disease (ChD) has high morbimortality and loss in quality of life due to heart failure (HF). Pharmaceutical care (PC) optimizes clinical treatment and can improve quality of life in HF. We evaluated if PC improves quality of life of patients with ChD and HF. METHODS: Single-blinded, randomized, controlled trial that assigned adult patients with ChD and HF (81 patients; 61 ± 11 years; 48% male) to PC (n = 40) or standard care (n = 41). Quality of life according to SF-36 and Minnesota living with HF questionnaires, incidence of drug-related problems (DRPs), and adherence to medical treatment were determined at baseline and at every 3 months for 1 year. Intention-to-treat analyses were performed by mixed linear model to verify the treatment effect on the changes of these variables throughout the intervention period. RESULTS: Relative changes from baseline to 1 year of follow-up of the domains physical functioning (+16.6 vs -8.5; P < .001), role-physical (+34.0 vs +5.2; P = .01), general health (+19.4 vs -6.1; P < .001), vitality (+11.5 vs. -5.8; P = .003), social functioning (+7.5 vs -13.3; P = .002), and mental health (+9.0 vs -3.7; P = .006) of the SF-36 questionnaire and the Minnesota living with HF questionnaire score (-12.7 vs +4.8; P < .001) were superior in the PC group than in the standard care group. Adherence to medical treatment increased as early as after 3 months of follow-up and DRPs incidence decreased after 6 months of follow-up only in the PC group. CONCLUSIONS: Patients with ChD and HF who received PC presented improved quality of life, decrease in DRP frequency, and increase in medication adherence.

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.

Effect of physical exercise training in patients with Chagas heart disease: study protocol for a randomized controlled trial (PEACH study).

BACKGROUND: The effects of exercise training on Chagas heart disease are still unclear. This study aimed to evaluate the effect of exercise training over functional capacity, cardiac function, quality of life, and biomarkers in Chagas heart disease. METHODS: The PEACH study is a superiority randomized clinical trial which will include subjects who meet the following criteria: Chagas heart disease with a left ventricular ejection fraction below 45 % with or without heart failure symptoms; clinical stability in the last 3 months; adherence to clinical treatment; and age above 18 years. The exclusion criteria are: pregnancy; neuromuscular limitations; smoking; evidence of non-chagasic heart disease; systemic conditions that limit exercise practice or cardiopulmonary exercise test; unavailability to attend the center three times a week during the intervention period; and practitioners of regular exercise. The intervention group will perform an exercise training intervention three times per week during 6 months and will be compared to the control group without exercise. Both groups will undergo the same monthly pharmaceutical and nutritional counseling as well as standard medical treatment according to the Brazilian consensus on Chagas disease. The primary outcome is functional capacity based on peak exercise oxygen consumption during cardiopulmonary exercise testing. Secondary outcomes are: cardiac function; body composition; muscle respiratory strength; microvascular reactivity; cardiac rhythm abnormalities; autonomic function; biochemical; oxidative stress and inflammatory biomarkers; and quality of life. Subjects will be evaluated at baseline, and at 3 and 6 months after randomization. Thirty patients will be randomly assigned into exercise or control groups at a ratio of 1:1. DISCUSSION: Findings of the present study will be useful to determine if physical exercise programs should be included as an important additional therapy in the treatment of patients with Chagas heart disease. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02517632 (registered on 6 August 2015).

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.

The association between nursing diagnoses and the occurrence of falls observed among elderly individuals assisted in an outpatient facility.

This is an exploratory descriptive study with a quantitative approach, in which variables associated to the occurrence of falls observed in elderly assisted in an outpatient clinic are delineated from the nursing diagnoses. Data from the files of 490 elderly with age between 60 and 98 years old were investigated. Univariate and bivariate statistical analyses were performed (p <0,05). The dependent variable, occurrence of falls, was prevalent in 30% of the cases and occurred with more frequency among females. A positive and independent association with the following diagnoses of Nursing was found: loss of balance (p <0,001), high blood pressure (p <0,001), weakness (p <0,025) and urinary incontinence (p <0,025). No association was observed for: altered vision, altered audition, joints pain, altered march and postural hypotension. The study shows the importance of working issues related to the variables that presented positive association with the occurrence of falls in the nursing practice.

The association between nursing diagnoses and the occurrence of falls observed among eldery individuals assisted in an outpatient facility

This is an exploratory descriptive study with a quantitative approach, in which variables associated to the occurrence of falls observed in elderly assisted in an outpatient clinic are delineated from the nursing diagnoses. Data from the files of 490 elderly with age between 60 and 98 years old were investigated. Univariate and bivariate statistical analyses were performed (p <0,05). The dependent variable, occurrence of falls, was prevalent in 30 percent of the cases and occurred with more frequency among females. A positive and independent association with the following diagnoses of Nursing was found: loss of balance (p <0,001), high blood pressure (p <0,001), weakness (p <0,025) and urinary incontinence (p <0,025). No association was observed for: altered vision, altered audition, joints pain, altered march and postural hypotension. The study shows the importance of working issues related to the variables that presented positive association with the occurrence of falls in the nursing practice.

Estudio descriptivo - exploratorio con enfoque cuantitativo, en el cual son mencionadas variables asociadas con caídas de ancianos atendidos ambulatoriamente, en base a los diagnósticos de Enfermería. Fueron investigados los registros de informaciones de las historias clínicas de 490 personas ancianas a partir de 60 años. Fue utilizado el análisis estadístico univariado y bivariado (p <0,05). La variable dependiente - ocurrencia de caídas - tuvo una prevalencia de 30 por ciento, siendo mayor en el sexo femenino. Se encontró una asociación positiva e independiente con los siguientes diagnósticos de enfermería: pérdida de equilíbrio (p <0,001), presión arterial alta (p <0,001), debilidad (p <0,025) e incontinencia urinaria (p <0,025). No se observó asociación entre las caídas y los siguientes diagnósticos: visión alterada, audición alterada, dolores osteo-articulares, marcha alterada e hipotensión postural. El estudio demuestra la importancia de ser trabajados por enfermería aspectos relacionados con las variables que presentan asociación directa con las caídas.

Trata-se de estudo descritivo exploratório com abordagem quantitativa, no qual são delineadas variáveis associadas à ocorrência de quedas nos idosos atendidos ambulatorialmente, a partir dos diagnósticos de enfermagem. Foram investigados os registros de dados dos prontuários de 490 idosos a partir de 60 anos. As variáveis sofreram análise univariada e bivariada (p<0,05). A variável dependente - ocorrência de quedas - obteve prevalência de 30 por cento com maior proporção no sexo feminino. Foi encontrada associação positiva e independente com os seguintes diagnósticos de enfermagem: perda de equilíbrio (p<0,001), pressão arterial elevada (p<0,001), fraqueza (p<0,025) e incontinência urinária (p<0,025). Não se observou associação entre quedas e os diagnósticos: visão alterada, audição alterada, dores osteoarticulares, marcha alterada e hipotensão postural. O estudo demonstra a importância de se trabalhar melhor as questões relativas às variáveis que apresentaram associação positiva com a ocorrência de quedas, na abordagem de enfermagem.