Chagas Disease – ABC CARDIOL

IJCS

Editorial

Chagas Disease and Maternal Mortality: An Overlooked Link in a Neglected Disease in Brazil

Maria Alayde Mendonça Rivera et al. Ivan Romero Rivera Glaucia Maria Moraes de Oliveira Ana G. Múnera Echeverri Walkiria Avila

Maternal mortality (MM), defined as the death of a woman during pregnancy, childbirth, or within 42 days postpartum, is a key indicator of maternal health and the quality of care provided by the health care system to prevent and manage complications during this period.

In 2020, there were 287,000 maternal deaths worldwide, resulting in a maternal mortality ratio (MMR) of 223 deaths per 100,000 live births. According to the World Health Organization (WHO), 95% of these deaths will occur in low- and middle-income countries, and 90% will be preventable.

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IJCS

Review Article

Multimodality Imaging of Chagas Heart Disease: Review and Case Presentation

Amalia Peix et al. Raul Araujo Veronica Gomez Aylen Perez Barreda … Maurizio Dondi Anita Brink Erika Minoshima Diana Paez

Abstract

Chagas disease (CD) is a neglected tropical disease (NTD) caused by Trypanosoma cruzi, a hemoflagellate protozoa. CD is diagnosed by epidemiologic history and two positive serological tests. The infection has two main clinical phases: acute, early after acquiring the infection, and chronic. The electrocardiogram (ECG) is the first tool to diagnose chronic Chagas heart disease after CD serological diagnosis. In addition, the different cardiac imaging modalities, including chest X-ray, echocardiography, single photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance, play a crucial role in detecting the cardiac involvement, establishing the prognosis, stratifying patient risk, and addressing the management of CD patients. In this review of the current literature, we summarize the epidemiology, pathophysiology, and clinical presentation of CD. We also discuss the indications, advantages, and limitations of the different cardiac imaging modalities. We also present some case examples, where cardiac imaging proved helpful in cardiac CD (CCD). The early mortality and substantial disability caused by CD represents a health, social and economic burden, particularly in the Latin America. To harness the full potential of medical imaging for the effective management of patients with CD, a comprehensive approach is essential. This involves a concerted effort to invest in the education of medical providers and to facilitate widespread access to diagnostic tools. Accessible and timely diagnosis is crucial for initiating prompt and targeted interventions. Finally, continuous investment in research is vital to advance our understanding of CD and develop innovative solutions for improved patient care.

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IJCS

Review Article

Maternal Deaths by Chagas’ Disease in Brazil

Danielle Kaiser de Souza et al. Vinicius Medina Lopes Ana Luiza Cafe-Lopes Maria das Dores Medina-Lopes

Abstract

Introduction

Chagas’ Disease is responsible for a high rate of morbimortality in Brazil however its real relevance on the maternal mortality is unknown.

Objective

The aim of this study is to review the literature on the impact of Chagas’ Disease on the Brazilian maternal mortality during the pregnancy-puerperal cycle.

Method

A review of literature was conducted to identify publications about maternal mortality and Chagas’ Disease. Documents were also searched in the websites of the Brazilian Ministry of Health, World Health Organization (WHO), System of Information about Mortality (SIM) and Brazilian Society of Cardiology (SBC). Manuscripts, master’s degree and PhD thesis, consensus, epidemiologic bulletins and manuals were analyzed.

Results

Initially were found 1326 paper, however just 14 answered the objective. Five epidemiologic bulletins, 4 manuals of Ministry of Health, 3 consensuses of SBC, 1 book and 3 master’s degree thesis were also used. There is no description of the number of deaths of pregnant women per year caused by complications of Chagas’ Disease in the data of the Ministry of Health and in the SIM. According to the data found, one third of pregnant women with Chagas’ Disease are cardiac patients and the mortality among them is 3.5%, therefore is expected a mortality of about 1% in the pregnant-puerperal cycle. There is evidence of underreporting of maternal mortality among chagasic pregnant women.

Conclusion

The maternal mortality caused by Chagas’ Disease is not known, therefore more studies about it are necessary, in all clinical forms of the disease.

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IJCS

Editorial

Achievements, Challenges and Opportunities in MicroRNAs and Chagas Disease

Giovani Carlo Veríssimo da Costa

MicroRNAs (miRNAs) were discovered in 1993 in studies of the nematode Caenorhabditis elegans and since then, these molecules have been of considerable importance in clinical practice for their use as potential biomarkers of different health and disease conditions.

In cell biology, the miRNAs play an important role in the physiological and pathological regulation of various biological processes and act as post-transcriptional regulators by binding to messenger RNA and preventing its translation or promoting molecular cleavage.^–miRNAs regulate different degenerative processes, cancer and immunological diseases. The increase and extracellular circulation reinforce the importance of these molecules as molecular biomarkers for prognosis, diagnosis, evolution, monitoring and therapy.^–

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IJCS

Viewpoint

The Role of MicroRNAs in the Pathogenesis of Chagas Disease

Cristiane Tefe-Silva et al. Laura de Oliveira Teixeira Laura Ramos Durigan Maria Clara Silva Cardoso … Maria Laura de Castro Davi Paula Altieri Pin Stephanie Milanez Veronica Cestari Lourenço Thálita Cristina de Sousa Beine Eloisa Yara Araujo Clemente

Abstract

Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi and affects about six to seven million individuals worldwide. The distribution of cases is concentrated mainly throughout Latin America, especially in rural areas. This study aims to evaluate microRNAs (miRNAs) as indicators in CD diagnosis for possible contributions to its management. This is a literature review study, carried out in the PubMed, SciELO, Bireme Library, NCBI, Science Direct, and Embase databases, through which a total of 12 articles were included for qualitative analysis. The discussion of this review was based on the thematic axes regarding the modulation of T. cruzi in the immune system and the expression of miRNAs, their production and action, the modulation mechanism of host gene expression, how they act as biomarkers, the importance of miRNAs in the diagnosis of CD, and how their regulation occurs in Chronic Chagas Cardiomyopathy (CCC). Moreover, T. cruzi infection is associated with the downregulation of several miRNAs, which directly related to the findings of hypertrophy and fibrosis. When quantified, these could be used as consistent indicators for CD to support the diagnosis of patients with CD complications, as well as a possible therapeutic target. However, the need for clinical studies that evaluate the usefulness of this biomarker in humans is emphasized, considering that in the present study, only experimental in vitro studies were evaluated, reflecting a lack of studies with practical applicability.

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IJCS

Original Article

Dysautonomia Evaluation by Holter in Chagas Heart Disease

Michele Alves Rocha de Oliveira et al. Thais Aguiar Nascimento Gilson Soares Feitosa-Filho Luiz Eduardo Fonteles Ritt … Constança Margarida Sampaio Cruz Mário de Seixas Rocha

Abstract

Background

Sudden cardiac death is the main lethal mechanism associated with Chagas cardiomyopathy. Studies suggest that dysautonomia may represent a relevant, intense, independent, and early phenomenon in the natural history of the disease, even when ventricular systolic function is preserved, and may also be the mechanism that triggers malignant ventricular arrhythmias.

Objective

To evaluate the degree of dysautonomia and its possible association with ventricular arrhythmias in patients with Chagas cardiomyopathy, according to different categories of mortality risk, as defined by the score proposed by Rassi, used as a surrogate outcome for death.

Methods

A cross-sectional study involving 43 patients with Chagas cardiomyopathy stratified into risk categories based on the Rassi score, with 23 being classified as low risk and 20 as intermediate-to-high risk. Heart rate variability (HRV) was assessed using Holter monitoring for long-term recordings of 24 hours (time domain) and for short-term recordings of 5 minutes (frequency domain) at rest and after autonomic tests: deep breathing and Valsalva maneuver. The HRV variables were compared between the groups using the Student’s t-test and α=0.05.

Results

Comparison of the results between the risk stratification groups showed no differences in HRV indexes, either in the time or frequency domain. However, results showed a significant increase in the number of arrhythmias as a function of increased risk (p=0.02).

Conclusion

There was no association between the degree of dysautonomia, evaluated by Holter monitoring, and the categories of mortality risk, despite a direct association between the rate of arrhythmias and the higher risk group.

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IJCS

Case Report

ST-Elevation in a Patient with Acute Chagas Disease

Guilherme Dantas Campos Pinto et al. José Henrique Martins Pimentel Maria das Neves Dantas da Silveira Barros Carolina de Araújo Medeiros … Cristina de Fátima Velloso Carrazzone Silvia Marinho Matins Wilson Alves de Oliveira Júnior

Introduction

Chagas disease (CD) is classically reported as a neglected disease of vectorial transmission and is endemic in 21 Latin America countries. While it has long been stigmatized as a mere tropical pathology, CD has recently gained prominence, since new means of infection have become more common, including blood transmission and consumption of food contaminated with feces from a given vector. Taking immigration into account, the disease is currently spreading beyond the limits of endemic areas and has become a global issue.

Many acute CD (ACD) outbreaks have been reported since 1965, by oral accidental routes, in Brazil and in other Latin American countries.^, That phase of the disease is, in general, asymptomatic or presents unspecific symptoms, such as fever, fatigue, myalgia, facial and lower limb edema, abdominal pain, diarrhea, vomiting, and dyspnea. One to five percent of the patients develop severe disease, most commonly perimyocarditis, acute heart failure, and/or meningoencephalitis, with a mortality rate of around 5%.^,

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IJCS

Review Article

Heart Transplantation for Chagas Cardiomyopathy

Maria da Consolação Moreira et al. Fabio Morato Castilho Renato Braulio Guilherme Ferraz Messina de Pádua Andrade José Renan da Cunha Melo

Abstract

Heart transplantation (HT) is an established treatment for patients with advanced heart failure (HF). Chagas disease (CD), caused by the Trypanosoma cruzi (T.cruzi) is an important cause of HF in Latin America. Considering CD is a chronic infectious disease, the use of immunosuppressive therapy after HT can reactivate T. cruzi infection and compromise outcomes. Early diagnosis and treatment of this complication is extremely important, which requires knowledge, experience, and a high degree of suspicion by transplant physicians. Furthermore, with the international immigration of people, CD is no longer exclusive to Latin America, since a large number of immigrants with T. cruzi infection are living in non-endemic countries. This phenomenon represents not only a new global epidemiological problem, but also a challenge for transplant teams. This review aims to discuss the peculiarities of HT in the context of CD, with a focus on reactivation of the infection, clinical manifestations, etiological treatment of T. cruzi and differential diagnosis with allograft rejection, among HT recipients.

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IJCS

Review Article

Nuclear Medicine Methods for Assessment of Chronic Chagas Heart Disease

Marcus Vinicius Simões et al. Denise Mayumi Tanaka José Antonio Marin-Neto

Abstract

Several different imaging methods can be used to evaluate patients with Chagas heart disease (CHD) for diagnostic and prognostic purposes, including plain chest radiography; echocardiography; myocardial perfusion scintigraphy, for detection of ischemia and fibrosis; radionuclide gated-angiography, for evaluation of biventricular function; ¹²³I-MIBG labeling of sympathetic myocardial innervation; MRI, for detection and quantitation of myocardial fibrosis; and coronary angiography. This study aims to review the contributions of these nuclear medicine methods to understanding of the pathophysiology of chronic Chagas cardiomyopathy (CCC). Careful analysis and integration of findings provided by these imaging methods in patients with CCC at different stages has contributed significantly to improving understanding of several peculiarities of the disease. Clinical and experimental studies in animal models show that perfusion abnormalities detected in association with dysfunctional but viable myocardium are a common finding in CCC patients and correspond to areas of cardiac sympathetic denervation, as assessed by ¹²³I-MIBG imaging. Furthermore, recent reports have demonstrated a close relationship between coronary microvascular disturbances and myocardial inflammation. Thus, ongoing research, mainly focused on refinements of ¹⁸F-FDF -PET techniques and further exploration of nuclear methods, such as SPECT, have the potential to contribute to detection and monitoring of early subclinical myocardial damage thereby enabling evaluation of therapeutic strategies targeting inflammation and microvascular ischemia that could result in better prognostic stratification of patients with CHD.

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Viewpoint

Dysautonomic Arrhythmogenesis: A Working Hypothesis in Chronic Chagas Cardiomyopathy

Roberto Coury Pedrosa

Abstract

Sudden cardiac arrest (SCA) represents the most dramatic course of chronic Chagas cardiomyopathy (CCC) and is closely related to the presence of ventricular arrhythmias and heart disease. Although several aspects of ventricular arrhythmias in CCC have been elucidated in the last decades, such as the role of impaired cardiac autonomic modulation reported in pre-clinical studies, important questions remain unresolved regarding these cardiac problems and SCA. The aim of this article is to discuss recent developments in the understanding of the role played by the autonomic nervous system on arrhythmic events in CCC. We draw attention to the neurogenic theory of CCC (“catecholamine-induced cardiomyopathy”) and its autoimmune regulation. Finally, we contextualize treatment strategies for Chagas disease considering the prevention of malignant ventricular arrhythmias. The most clinically relevant message from this article may be the high negative predictive value of dysautonomia for SCA in CCC. Nevertheless, there is a long journey from the identification of a potential marker for SCA to its actual use, which will require a common effort by the entire Chagas community.

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Original Article

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Lorena dos Santos Marreto Rimolo et al. Roberto Magalhães Saraiva Ademir Batista da Cunha

Abstract

Background

The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized.

Objective

To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease.

Methods

The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded.

Results

A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia.

Conclusions

The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas’ disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

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Original Article

Influence of ACE Polymorphism on Echocardiographic Data of Patients with Heart Failure

Silene Jacinto da Silva et al. Salvador Rassi Alexandre da Costa Pereira

Abstract

Background:

Angiotensin converting enzyme (ACE) polymorphism has been associated with different clinical and echocardiographic parameters in patients with heart failure (HF). However, no studies have been investigated such association with HF caused by Chagas disease.

Objectives:

To perform a genetic study to evaluate the frequency of ACE polymorphism in patients with HF caused by Chagas disease attending a university hospital in the central-west region and its association with echocardiographic findings.

Methods:

Descriptive study of ACE polymorphism (I/D) and echocardiographic data of 103 patients with HF caused by Chagas disease. Echocardiographic parameters were compared between the genotypes using the ANOVA test.

Results:

Genotypic distribution of the ACE polymorphism was 16.5% DD, 57.3% DI and 26.2% II. There was no statistically significant difference in the distribution of genotypes between men and women. The echocardiographic findings were: left ventricular ejection fraction: 43.8 ± 14.8 (DD) vs. 42.3 ± 11.6 (ID) vs. 44.9 ± 13.0 (II), p = 0.664; left ventricular diastolic diameter: 59.2 ± 9.7 (DD) vs. 60.3 ± 7.6 (ID) vs. 59.7 ± 78.1 (II), p = 0.879; left ventricular systolic diameter: 48.6 ± 12.8 (DD) vs. 50.6 ± 9.7 (ID) vs. 49.3 ± 11.9 (II), p = 0.753; and left atrial volume: 44.9 ± 10.1 (DD) vs. 40.9 ± 9.6 (ID) vs. 38.2 ± 7.8 (II), p = 0.068. Significant correlation coefficients were found for gender, age, ethnicity, heart rate and dyslipidemia.

Conclusion:

ACE polymorphism was not associated with echocardiographic findings in patients with HF caused by Chagas disease.

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Original Article

Effect of Mild Aerobic Exercise in Atrial Granules of Mice with Chronic Chagas Disease

Roberto Ferraboli et al. Elisabete De Marco Ornelas Fernando Luiz Affonso Fonseca Glaucia Luciano da Veiga … Clever Gomes Cardoso Mara Rubia Marques Laura Beatriz Mesiano Maifrino

Abstract

Background:

Chagas disease presents in different clinical forms, ranging from asymptomatic to acute, with destruction of heart cells and a possibility of death. In the chronic phase, the parasites can cause serious injuries to different tissues.

Objectives:

Our objective was to study the effects of physical exercise (swimming) in atrial granules and components of cardiomyocytes in mice with chronic Chagas disease.

Methods:

In total, 20 male mice were divided into four different groups: untrained control (UC), trained control (TC), untrained infected (UI), and trained infected (TI). In the UI and TI groups, 1,000 forms of Trypanosoma cruzi (Y strain) were inoculated intraperitoneally. After 40 days of infection and proof of chronic phase, the exercise protocol began. The UC and UI groups performed exercise for 10 min/day, and the TC and TI groups followed a training protocol five times a week for 30 minutes during 8 weeks. Ultrathin sections were subjected to morphometric and stereological analyses using electron photomicrographs (x15000) obtained by transmission electron microscopy.

Results:

The TI group showed the lowest percentage of small granules (58%), while the UI group presented 80% of these granules. The volume density of the Golgi complex and myofibrils in the TI group were reduced compared with those in the UI group, while the parameters of atrial granules and mitochondria increased.

Conclusion:

Our results suggest that mild physical exercise changes the morphological and morphometric parameters of granules and organelles in the cardiac atrium of mice infected with T. cruzi, and produces moderate beneficial effects on the cardiovascular system.

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ABC

Original Article

Cerebral infarction in autopsies of chagasic patients with heart failure

Roque Aras et al. José Alberto M. da Matta Gildo Mota Irênio Gomes Ailton Melo

OBJECTIVE: To determine the frequency of encephalic infarction and its contribution to lethality in patients with Chagas’ disease and heart failure. METHODS: Medical records and autopsy reports of patients with Chagas’ disease complicated by heart failure, who died at the Professor Edgar Santos Hospital of the Federal University of Bahia in the past 45 years were retrospectively analyzed. Data comprised information regarding the clinical history on hospital admission, complementary and anatomicopathological examinations, including the presence of encephalic infarction, the impaired region, and the cause of death. RESULTS: Of the 5,447 autopsies performed, 524 were in patients with heart failure due to Chagas’ disease. The mean age was 45.7 years, and 51 (63%) patients were of the male sex. The frequency of encephalic infarction was 17.5%, corresponding to 92 events in 92 individuals, 82 (15.8%) of which involved the brain, 8 (1.5%) involved the cerebellum, and 2 (0.4%) involved the hypophysis. CONCLUSION: Cerebral infarction has been a frequent finding in autopsies of chagasic patients with heart failure, and it has been an important cause of death in our region. The presence of cerebral infarction and its complications have been associated with death in 52% of the cases studied.

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Original Article

Value of the radiological study of the thorax for diagnosing left ventricular dysfunction in Chagas' disease

Amanda Arantes Perez et al. Antonio Luiz Pinho Ribeiro Márcio Vinícius Lins Barros Marcos Roberto de Sousa … Roberto José Bittencourt Fernando Santana Machado Manoel Otávio Costa Rocha

OBJECTIVE: To determine the value of the radiological study of the thorax for diagnosing left ventricular dilation and left ventricular systolic dysfunction in patients with Chagas’ disease. METHODS: A cross-sectional study of 166 consecutive patients with Chagas’ disease and no other associated diseases. The patients underwent cardiac assessment with chest radiography and Doppler echocardiography. Sensitivity, specificity, and positive and negative predictive values of chest radiography were calculated to detect left ventricular dysfunction and the accuracy of the cardiothoracic ratio in the diagnosis of left ventricular dysfunction with the area below the ROC curve. The cardiothoracic ratio was correlated with the left ventricular ejection fraction and the left ventricular diastolic diameter. RESULTS: The abnormal chest radiogram had a sensitivity of 50%, specificity of 80.5%, and positive and negative predictive values of 51.2% and 79.8%, respectively, in the diagnosis of left ventricular dysfunction. The cardiothoracic ratio showed a weak correlation with left ventricular ejection fraction (r=-0.23) and left ventricular diastolic diameter (r=0.30). The area calculated under the ROC curve was 0.734. CONCLUSION: The radiological study of the thorax is not an accurate indicator of left ventricular dysfunction; its use as a screening method to initially approach the patient with Chagas’ disease should be reevaluated.

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Original Article

Prevalence of Chagas' Disease in Mulungu do Morro Northeastern Brazil

Roque Aras et al. Marielza Veiga Irênio Gomes Gildo Mota … Bernardo Rodrigues Rosângela Rabelo Carmen Guzman-Bracho Ailton Melo

OBJECTIVE – The aim of this paper is to describe the prevalence of T. Cruzi infection in patients of from Mulungu do Morro, a rural tropical region of Northeastern Brazil. METHODS – A cross-sectional study was performed. After randomly selecting samples of the population, and obtaining their consents , patients completed pretested epidemiological and clinical questionnaires. Serum samples from all patients were collected and screened for the presence of T. cruzi antibodies. RESULTS – Of 694 patients examined, 174 patients (25.1%) tested had a positive serology for Chagas’ disease. Of the study population, 341 patients were male with 27% Chagas’ disease prevalence, without a statistical difference. Illiteracy was the only variable related to T. cruzi infection in our population. CONCLUSION – In conclusion, our study points to the high prevalence of Chagas’ disease among patients in Mulungu do Morro, suggesting that this region has a high frequency of infection and probably active vectorial transmission.

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